bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of TROY‐expressing cells in the developing and postnatal CNS: the possible role in neuronal and glial cell development
Authors: Hisaoka Tomoko , Morikawa Yoshihiro , Komori Tadasuke , Sugiyama Takuya , Kitamura Toshio , Senba Emiko 
Published: June 2006

AbstractA member of the tumor necrosis factor receptor superfamily, TROY, is expressed in the CNS of embryonic and adult mice. In the present study, we characterized TROY‐expressing cells in the embryonic and postnatal forebrain. In the early embryonic forebrain, TROY was highly expressed in nestin‐positive neuroepithelial cells and radial glial cells, but not in microtubule‐associated protein 2‐positive postmitotic neurons. During the late embryonic and postnatal development, expression of TROY was observed in radial glial cells and astrocytes, whereas its expression was not detected in neuronal lineage cells. In addition, TROY was exclusively expressed in Musashi‐1‐positive multipotent/glial progenitors in the postnatal subventricular zone. To investigate the functions of TROY in neural development, we overexpressed TROY in PC12 cells and established stably expressing cell clones. As expected, the signals from overexpressed TROY were constitutively transduced via the activation of the nuclear factor‐κB and the c‐Jun N‐terminal kinase pathways in such clones. In addition, upregulation of negative basic helix–loop–helix transcription factors, HES‐5 and Id2 proteins, was observed in the TROY‐overexpressing clones. Interestingly, the overexpression of TROY in PC12 cells strongly inhibited nerve growth factor‐induced neurite outgrowth with reduction of some markers of differentiated neurons, such as neurofilament 150 kDa and neuron‐specific β‐tubulin. These findings suggest that the signaling from TROY regulates neuronal differentiation at least in part.
Cochlear damage induces GAP‐43 expression in cholinergic synapses of the cochlear nucleus in the adult rat: a light and electron microscopic study
Authors: Meidinger Markus A. , Hildebrandt‐Schoenfeld Heika , Illing Robert‐Benjamin 
Published: June 2006

AbstractRecent studies suggest a potential for activity‐dependent reconstruction in the adult mammalian brainstem that exceeds previous expectations. We found that a unilateral cochlear lesion led within 1 week to a rise of choline acetyltransferase (ChAT) immunoreactivity in the ventral cochlear nucleus of the affected side, matching the lesion‐induced expression of growth‐associated protein 43 (GAP‐43) previously described. The rise of both ChAT and GAP‐43 immunoreactivity was reflected in the average density of the staining. Moreover, the number of light‐microscopically identifiable boutons increased in both stains. GAP‐43‐positive boutons could, by distinct ultrastructural features, regularly be identified as presynaptic endings. However, GAP‐43 immunoreactivity was not only found in presynaptic endings with a classical morphology, but also in profiles that suggest morphological dynamic structures by showing filopodia, assemblages of pleomorphic vesicles, large vesicles (diameter up to 200 nm) fusing with the presynaptic plasma membrane close to synaptic contacts, small dense‐core vesicles (diameter about 80 nm) and presynaptic ribosomes. Moreover, we observed perforated synapses as well as GAP‐43 immunoreactivity condensed in rafts, both indicative of growing or changing neuronal connections. Classical and untypical ultrastructural profiles that contained GAP‐43 also contained ChAT. We conclude that there is extensive deafness‐induced GAP‐43‐mediated synaptic plasticity in the cochlear nucleus, and that this plasticity is predominantly, if not exclusively, based on cholinergic afferents.
Signalling mechanisms mediated by the phosphoinositide 3‐kinase/Akt cascade in synaptic plasticity and memory in the rat
Authors: Horwood Jennifer M. , Dufour Franck , Laroche Serge , Davis Sabrina 
Published: June 2006

AbstractThe phosphoinositide 3‐kinase (PI3K)/Akt signalling cascade has classically been implicated in promoting cell survival but more recently has been shown to regulate a number of other cellular functions. In particular, studies have suggested that PI3K contributes to mechanisms associated with synaptic plasticity and memory processes but the function of this cascade in forms of synaptic plasticity, such as long‐term potentiation, remains controversial and the PI3K substrates which mediate these effects are poorly understood. Here we report that the PI3K inhibitor LY294002 infused i.c.v. in vivo blocked maintenance of long‐term potentiation induced in the dentate gyrus with a single tetanus to the perforant path but not with repeated tetani. This pattern of stimulation led to rapid and transient phosphorylation of the PI3K substrate Akt at Ser473 but not at Thr308. Functional readout of partial activation of Akt was demonstrated by an increase in phosphorylation of two downstream substrates, Forkhead (FKHR) and mammalian target of rapamycin (mTOR), in a delayed and prolonged manner at Akt‐specific phosphorylation sites. LY294002 blocked phosphorylation of Akt and the prolonged phosphorylation of FKHR and mTOR but did not impair long‐term potentiation‐induced phosphorylation of extracellular receptor kinase. In addition, the same i.c.v. concentration of LY294002 impaired long‐term consolidation of recognition memory but not short‐term recognition memory or spatial learning and repeated training in the recognition memory task overcame the deficit in consolidation. These results suggest that activation of the PI3K/Akt pathway may contribute to the mechanisms of synaptic plasticity and memory consolidation by promoting cell survival via FKHR and protein synthesis via mTOR. Importantly, only partial activation of Akt at its Ser473 residue was necessary to mediate these effects.
Pheromonal recognition memory induced by TRPC2‐independent vomeronasal sensing
Authors: Kelliher Kevin R. , Spehr Marc , Li Xiao‐Hong , Zufall Frank , Leinders‐Zufall Trese 
Published: June 2006

AbstractDetection and transduction of pheromonal signals by the mouse vomeronasal organ (VNO) is critical for the formation of a persistent memory required for mate recognition in the context of selective pregnancy failure (the Bruce effect). This pregnancy block can be mediated by peptide ligands of disparate major histocompatibility complex (MHC) molecules, but little is known about the molecular mechanisms underlying this effect. Given the proposed key role of the transient receptor potential channel, TRPC2, in VNO signal transduction, we tested whether TRPC2 is essential for memory formation in the context of the Bruce effect. Surprisingly, the loss of the TRPC2 channel did not significantly influence memory formation, whereas surgical lesions of the VNO caused a profound deficit. Furthermore, field potential and single‐cell patch‐clamp recordings showed that TRPC2 is dispensable for the transduction of MHC peptide ligands by sensory neurons in the basal zone of the VNO. This indicates that a previously unrecognized TRPC2‐independent signal transduction mechanism in the VNO underlies the sensing of cues required for the formation of this pheromonal recognition memory.
The dynamic developmental localization of the full‐length corticotropin‐releasing factor receptor type 2 in rat cerebellum
Authors: Gounko Natalia V. , Kalicharan Dharamdajal , Rybakin Vasily , Gramsbergen Albert , Van Der Want Johannes J. L. 
Published: June 2006

AbstractCorticotropin releasing factor receptor 2 (CRF‐R2) is strongly expressed in the cerebellum and plays an important role in the development of the cerebellar circuitry, particularly in the development of the dendritic trees and afferent input to Purkinje cells. However, the mechanisms responsible for the distribution and stabilization of CRF‐R2 in the cerebellum are not well understood. Here, we provide the first detailed analysis of the cellular localization of the full‐length form of CRF‐R2 in rat cerebellum during early postnatal development. We document unique and developmentally regulated subcellular distributions of CRF‐R2 in cerebellar cell types, e.g. granule cells after postnatal day 15. The presence of one or both receptor isoforms in the same cell may provide a molecular basis for distinct developmental processes. The full‐length form of CRF‐R2 may be involved in the regulation of the first stage of dendritic growth and at later stages in the controlling of the structural arrangement of immature cerebellar circuits and in the autoregulatory pathway of the cerebellum.
Power law relationships among hierarchical taxonomic categories in algae reveal a new paradox of the plankton
Authors: Passy Sophia I. , Legendre Pierre 
Published: June 2006

ABSTRACTAim  In this continental‐scale study, the biodiversity of benthic and planktonic algal communities was explored. A recent analysis of extinct and extant tree communities by Enquist et al. (2002) showed that richness of higher taxa was a power function of species richness, invariant across temporal and spatial scales. Here we examined whether the relationships between algal richness at hierarchical taxonomic levels conform to power laws as seen for trees, and if these relationships differ between benthic and planktonic habitats.Location  Streams from more than 50 major watersheds in the United States.Method  A total of 3698 samples were collected from 1277 locations by the National Water‐Quality Assessment Program. Three types of stream habitat were sampled: richest targeted habitats, depositional targeted habitats, and phytoplankton. The relationships between taxonomic richness at the species level vs. all higher categories from genus to phylum across the three habitats were examined by ordinary least squares (OLS) regressions after ln‐transformation of all variables. The slopes, b, of these regressions represent the exponents of the power functions that scaled the richness of higher taxonomic levels (T) to species richness (S) in the form: T∝Sb.Results  Algal richness at hierarchical taxonomic categories (genus to phylum) is a power function of species richness. The scaling exponent of this function, which captures the diversification of higher taxa, i.e. the rate of increase of their richness with the increase of species richness, is significantly different across environments.Main conclusions  The differential algal diversification in the three studied habitats emphasizes the fundamental role of the environment in structuring the communities of simple organisms such as algae. The finding that the diversification of higher taxa is greater in the seemingly homogeneous planktonic environment, when compared to benthic habitats, encompassing an array of ecological niches, poses a new paradox of the plankton.
Oxidative stress and neurodegeneration: where are we now?
Authors: Halliwell Barry 
Published: June 2006

AbstractThe brain and nervous system are prone to oxidative stress, and are inadequately equipped with antioxidant defense systems to prevent ‘ongoing’ oxidative damage, let alone the extra oxidative damage imposed by the neurodegenerative diseases. Indeed, increased oxidative damage, mitochondrial dysfunction, accumulation of oxidized aggregated proteins, inflammation, and defects in protein clearance constitute complex intertwined pathologies that conspire to kill neurons. After a long lag period, therapeutic and other interventions based on a knowledge of redox biology are on the horizon for at least some of the neurodegenerative diseases.
Prion diseases of humans and farm animals: epidemiology, genetics, and pathogenesis
Authors: Aguzzi Adriano 
Published: June 2006

AbstractNeuronal vacuolation (spongiosis), neuronal death, and pronounced glial reactions are the hallmarks of transmissible spongiform encephalopathies (TSEs), or prion diseases. A wealth of physical, biochemical, and immunological evidence indicates that the TSE agent, termed prion, does not contain agent‐specific nucleic acid encoding its own constituents, as is the case for all other infectious pathogens. Also, no adaptive immune responses are elicited upon infection. A defining feature of TSEs is the deposition, mainly in the brain and lymphoreticular tissues, of an aggregated and structurally abnormal protein, designated PrPSc or PrP‐res, which represents a conformational isomer of the ubiquitous surface protein PrPC. Biochemical and genetic evidence link PrP and its gene to the disease. Although TSEs are by definition transmissible, a growing number of Prnp‐associated non‐infectious neurodegenerative proteinopathies are now being recognized.
The glutamate/GABA‐glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer
Authors: Bak Lasse K. , Schousboe Arne , Waagepetersen Helle S. 
Published: June 2006

AbstractNeurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and γ‐aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA‐glutamine cycle describes the release of neurotransmitter glutamate or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA‐glutamine cycle will be discussed, including aspects of transport and metabolism. Discussions of stoichiometry, the relative role of glutamate vs. GABA and pathological conditions affecting the glutamate/GABA‐glutamine cycling are presented. Furthermore, a section is devoted to the accompanying ammonia homeostasis of the glutamate/GABA‐glutamine cycle, examining the possible means of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA‐glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA‐glutamine cycle must be seen as a bi‐directional transfer of not only carbon units but also nitrogen units.
Agonist and antagonist sensitivity of non‐selective cation channel currents evoked by muscarinic receptor stimulation in bovine ciliary muscle cells
Authors: Sugawara R. , Takai Y. , Miyazu M. , Ohinata H. , Yoshida A. , Takai A. 
Published: June 2006

Summary1 In the bovine ciliary muscle, stimulation of muscarinic receptors with carbachol (CCh) opens two types of non‐selective cation channels (NSCCS and NSCCL) with widely different unitary conductances (100 fS and 35 pS). Here we examined the dependence of the activity of NSCCS on the agonist (CCh) concentration by whole‐cell voltage clamp in freshly isolated bovine ciliary muscle cells. We also examined the sensitivity of CCh‐evoked NSCCS currents to several muscarinic receptor antagonists.2 The voltage clamp experiments were carried out using Ba2+as the charge carrier, as this divalent cation is the most permeant for NSCCS of the alkali and alkaline earth metal ions hitherto examined, whereas it is relatively impermeant to NSCCL. For the dose–activation relationship obtained, the apparent dissociation constantKwas estimated to be 0.5 ± 0.2 μm(n = 31), a value of an order of magnitude smaller than the one reported for CCh‐evoked NSCCL currents in our previous experiments.3 In the dose‐inhibition experiments we observed that the CCh‐evoked NSCCS currents were inhibited by the muscarinic antagonists with the following potency sequence: atropine ≈ 4‐DAMP >> pirenzepine > AF‐DX116, indicating that the activation of NSCCS by CCh is mediated by an M3muscarinic receptor.4 We have previously shown by reverse transcriptase‐polymerase chain reaction that the bovine ciliary muscle contains mRNAs for several transient receptor potential channel homologues (TRPC1, TRPC3, TRPC4 and TRPC6) which are attracting attention as molecular candidates for receptor‐operated NSCCs. In the present experiments, we succeeded in visually identifying these TRPCs in the plasma membrane of cultured bovine ciliary muscle cells by immunofluorescence microscopy.
Muscarinic stimulation of the rat isolated whole bladder: pathophysiological models of detrusor overactivity
Authors: Drake M. , Gillespie J. , Hedlund P. , Harvey I. , Lagou M. , Andersson K.‐E. 
Published: June 2006

Summary 1 Hypotheses as to the pathophysiological basis of bladder detrusor muscle overactivity (DO) have identified both central nervous and peripheral mechanisms as likely contributory factors. In this paper, we describe peripheral autonomous bladder activity in two animal models of DO and discuss how the differences observed between the two models support the likelihood that clinical DO has a multifactorial basis. 2 A total of 12 adult female Sprague–Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Six adult female spontaneously hypertensive rats (SHR) were compared with normal Wistar controls. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure in response to the muscarinic receptor agonist arecaidine were performed under standardized conditions. 3 In the partially obstructed rat bladder, the amplitude of pressure fluctuations elicited by the muscarinic agonist arecaidine was significantly increased compared with sham‐operated animals. The tonic component of the response was no different for the two groups. No difference from controls was apparent in the SHR. 4 We conclude that alterations in autonomous bladder activity in the obstructed rat model suggest that peripheral functional changes contribute to the pathophysiological abnormality. In contrast, the fundamental abnormality in the SHR appears to be at a more central level. The observations support the supposition that lesions at widely separate sites can give rise to apparently similar abnormalities of lower urinary tract function.
Muscarinic receptor function, density and G‐protein coupling in the overactive diabetic rat bladder
Authors: Stevens L. A. , Sellers D. J. , McKay N. G. , Chapple C. R. , Chess‐Williams R. 
Published: June 2006

Summary 1 Bladder smooth muscle sensitivity to muscarinic agonists is increased in the overactive bladder. Treatment of rats with streptozotocin induces a diabetic state in which the bladder muscle is overactive and also supersensitive to muscarinic agonists. This study has examined bladder contraction, muscarinic receptor density and receptor/G‐protein coupling in the streptozotocin‐induced overactive bladder of the rat. 2 Diabetes was induced by a single intraperitoneal dose of streptozotocin. Seven days later contraction of isolated detrusor muscle strips was assessed in tissue bath experiments, while receptor density was assayed in saturation experiments with [3H]‐QNB (quinuclidinyl benzilate, l‐[benzilic‐4,4′‐3H]) and receptor/G‐protein coupling was determined in agonist displacement experiments with this radioligand. 3 Isolated detrusor strips from diabetic animals displayed an enhanced degree of spontaneous activity (0.060 ± 0.016 g mg−1, compared with 0.015 ± 0.004 g mg−1, P < 0.05). Carbachol produced contractile responses in tissues from both control and diabetic rats, but the diabetic tissues were more sensitive to this agonist, the pEC50 being 6.52 ± 0.17 compared with 5.93 ± 0.06 in controls (P < 0.001). Maximum responses to carbachol were similar in both groups of animals. The increase in carbachol potency was accompanied by a 40% increase in receptor density from 158 ± 5 to 221 ± 22 fmol mg−1 protein (P < 0.05), but this was not enough to fully account for the change in tissue sensitivity. 4 In the absence of GTP‐γ‐S, carbachol displaced [3H]‐QNB from two binding sites, the high‐affinity site (pKi = 7.06 ± 0.26) which represents the receptors coupled to G‐proteins made up 43.1 ± 5.9% of the total binding sites in control tissues and this value was similar (41.0 ± 4.0%) in the diabetic tissues (pKi = 6.64 ± 0.31). In the presence of GTP‐γ‐S, carbachol displaced [3H]‐QNB from a single binding site which had a low‐affinity, similar to the low‐affinity site observed in the absence of GTP‐γ‐S. 5 These data demonstrate that detrusor supersensitivity is observed after only 1 week of untreated diabetes in the rat. The overactivity is associated with an enhanced sensitivity to carbachol, which is partly explained by an increase in receptor density, but there appears to be no change in receptor/G‐protein coupling.
Measurement of expired carbon dioxide, oxygen and volume in conjunction with pretest probability estimation as a method to diagnose and exclude pulmonary venous thromboembolism
Authors: Kline Jeffrey A. , Hogg Melanie 
Published: June 2006

SummaryBackground:  The classical alveolar pCO2–pO2 relationship predicts that pulmonary embolism (PE) causes a low ratio of pCO2/pO2 at end expiration. Our purpose was to define a simple protocol to collect expired pCO2/pO2 to diagnose PE. Emergency department patients with suspected PE were enrolled. Clinical pretest probabilities for PE were estimated prior to diagnostic testing using the Canadian score and clinicians’ unstructured estimate. Patients provided three 30‐s periods of tidal breathing, separated by three deep exhalations. Expired pCO2, pO2 and breath volume were measured. All patients underwent standardized objective testing for PE including 90‐day follow‐up. Diagnosis (PE+) required anticoagulation for image‐proven PE within 90 days.Results:  Of 200 patients enrolled, 178 were included in final analysis (24 PE+). The mean coefficient of variability for the deep‐exhaled and end‐tidal pCO2/pO2 ratios were 6·8 ± 6·7 and 7·5 ± 6·8%, respectively. Mean pCO2/pO2 ratios were stable throughout the collection periods in both methods. When compared with the deep‐exhaled ratio, the end‐tidal mean ratio demonstrated slightly better diagnostic utility by the area under the receiver operating characteristic curve. The end‐tidal ratios were divided into four interval likelihood ratios and coupled with pretest probability from the two methods to generate three sets of posttest probabilities. Receiver operating characteristic analysis demonstrated good overall diagnostic performance (areas under the curves >0·88) for both posttest probability sets.Conclusion:  This preliminary work demonstrates that the end‐tidal pCO2/pO2 averaged from 30 s of breathing can produce clinically relevant likelihood ratios for the diagnosis and exclusion of PE.