bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zaprinast, an inhibitor of cGMP‐selective phosphodiesterases, enhances the secretion of TNF‐α and IL‐1β and the expression of iNOS and MHC class II molecules in rat microglial cells
Authors: Choi Sang‐Hyun , Choi Dong‐Hee , Song Kwang‐Seon , Shin Kyung‐Ho , Chun Boe‐Gwun 
Published: August 2002

AbstractProinflammatory cytokines produced by activated glial cells may in turn augment the immune/inflammatory reactions of glial cells through autocrine and paracrine routes. The NO/cGMP signaling represents one of the reactions of activated glial cells. We investigated whether the production of proinflammatory cytokines by glial cells is affected by NO‐dependent downstream cGMP signaling. In primary cultures of mixed astrocytes and microglial cells, zaprinast (0.1 mM), an inhibitor of cGMP‐selective phosphodiesterases, enhanced the basal and LPS (1.0 μg/ml)‐induced secretion of TNF‐α and IL‐1β. Zaprinast also enhanced NO production induced by LPS or IFN‐γ (100 U/ml), and in microglial cell cultures, but not in astrocyte cultures, zaprinast enhanced the basal and the IFN‐γ‐induced production of the cytokines, TNF‐α and IL‐1β, and of NO. This upregulation by zaprinast was partially inhibited by KT5823 (1.0 μM), an inhibitor of protein kinase G. The LPS‐induced production of TNF‐α, IL‐1β, and NO was inhibited by ODQ (50 μM), an inhibitor of soluble guanylyl cyclase, and by KT5823. Immunohistochemical analysis of mixed glial cell cultures showed that LPS/IFN‐γ‐induced iNOS expression and the enhanced expression of iNOS by zaprinast were restricted to microglial cells. Zaprinast enhanced the IFN‐γ (200 U/ml)‐induced expression of MHC Class II molecules in astrocytes and microglial cells in mixed cultures, but did not enhance this IFN‐γ‐induced expression in pure astrocytes, which lacked paracrine TNF‐α from microglial cells. Summarizing, zaprinast, which is associated with cGMP/protein kinase G signaling, may augment central immune/inflammatory reactions, possibly via the increased production of TNF‐α and IL‐1β by activated microglial cells. © 2002 Wiley‐Liss, Inc.
Cytoskeleton participation in subcellular trafficking of signal transduction proteins in rod photoreceptor cells
Authors: McGinnis James F. , Matsumoto Brian , Whelan James P. , Cao Wei 
Published: August 2002

AbstractLight sensitivity and adaptation, general characteristics of rod photoreceptor cell vision, allow rods to modulate their response depending on the lighting environment to which they are exposed. In dim light, rods are maximally sensitive, whereas, in bright light, rods are essentially inactive. In the retinas of dark‐adapted mice, arrestin (an inhibitory protein) is located in the rod inner segment (RIS), and transducin (an activating protein) is located in the rod outer segment (ROS). In light‐adapted retinas, the proteins have reciprocal localizations. In this study, our data demonstrate that the temporal and spatial changes in the subcellular localization of arrestin and β‐transducin are correlated with the amount of light to which the animals are exposed. By using the frog Xenopus laevis and immunofluorescence confocal microscopy, our results also show that in the dark‐adapted retina some arrestin remains in the ROS. The data most dramatically demonstrate that this residual arrestin is highly concentrated in the connecting cilium, the axoneme, and the microtubules associated with the disc incisures. These data suggest a structure–function relationship between the light‐dependent positional status of arrestin and the elements of the rod photoreceptor cytoskeleton. The massive, rapid, light‐induced reciprocal changes in the subcellular concentrations of these proteins must directly affect phototransduction and appear to be a general phenomenon by which photoreceptor cells rapidly and transiently regulate the trafficking and subcellular concentration of a variety of signal transduction proteins within the RIS and ROS. Hereditary mutations in the components of the movement mechanism should lead to defects in vision and possibly blindness. © 2002 Wiley‐Liss, Inc.
Down‐regulation of γ‐glutamylcysteine synthetase regulatory subunit gene expression in rat brain tissue during aging
Authors: Liu Rui‐Ming 
Published: August 2002

AbstractThe mechanism underlying age‐related neurodegenerative diseases is still an area of significant controversy. Increased evidence suggests that oxidative stress contributes importantly to neuronal damage observed in the brains of aged animals and in neurodegenerative diseases. Glutathione (GSH), the most abundant intracellular nonprotein thiol, plays an important role in antioxidant defense. The concentration of this important antioxidant decreases with age in the brain, which is accompanied by an increase in oxidative damage to macromolecules. The mechanism underlying the age‐associated decline in GSH content in the brain, however, is not clear. In this study, we demonstrate for the first time that the expression of the regulatory subunit of γ‐glutamylcysteine synthetase (GCS), the rate‐limiting enzyme in de novo GSH synthesis, decreases with age in cerebellum, cerebral cortex, and hippocampus of Fisher 344 rats. This was accompanied by a decline in GCS activity and GSH content. There were no significant differences in either the concentrations of cysteine and glutathione disulfide (GSSG) or the activities of glutathione synthetase (GS), γ‐glutamyl traspeptidase (GGT), and glutathione reductase (GR) in the brains from different age groups. Our results suggest that the age‐associated decrease in GSH in the brain may result from the down‐regulation of GCS regulatory subunit and consequently a decrease in the activity of GCS. © 2002 Wiley‐Liss, Inc.
Dual role for p75NTR signaling in survival and cell death: Can intracellular mediators provide an explanation?
Authors: Mamidipudi Vidya , Wooten Marie W. 
Published: August 2002

AbstractSeveral recent reports support a dual role of p75NTR in cell death, as well as survival, depending on the physiological or developmental stage of the cells. Coexpression of the TrkA receptor with p75NTR further enhances the complexity of nerve growth factor (NGF) signaling. Recent identification of serine/threonine kinases that interact with the p75NTR provides an explanation for the lack of an apparent kinase domain needed for signaling. In this report, we review the possible roles of the intracellular proteins that directly interact with the p75NTR, atypical protein kinase C (PKC) binding protein, p62 and second messengers in the functional antagonism exhibited by TrkA and p75NTR with an emphasis on the nuclear factor‐kappa B activation pathway. © 2002 Wiley‐Liss, Inc.
Neurite growth promotion by nerve growth factor and insulin‐like growth factor‐1 in cultured adult sensory neurons: Role of phosphoinositide 3‐kinase and mitogen activated protein kinase
Authors: Kimpinski Kurt , Mearow Karen 
Published: August 2002

AbstractAlthough neurons of the PNS no longer require neurotrophins such as Nerve Growth Factor (NGF) for their survival, such factors are involved in regulating axonal sprouting and regeneration after injury. In addition to the neurotrophin receptors, sensory neurons are reported to express IGF‐1, EGF and FGF receptors. To investigate the influence of growth factors in addition to NGF, we examined the effects of IGF‐1 EGF and FGF on neurite growth from adult rat dorsal root ganglion sensory neurons in both dissociated cultures and in compartmented cultures. As expected, NGF elicited robust neuritic growth in both the dissociated and compartmented cultures. The growth response to IGF‐1 was similar, although there was minimal neurite growth in response to EGF or FGF. In addition, IGF‐1 (but neither FGF nor EGF), when applied to cell bodies in compartmented cultures, potentiated the distal neurite growth into NGF‐containing side compartments. This potentiation was not seen when these factors were provided along with NGF in the side compartments of compartmented cultures, or in the dissociated cultures. To determine the contribution of signaling intermediates downstream of receptor activation, we used inhibitors of the potential effectors and Western blotting. The PI 3‐kinase inhibitor, LY294002 attenuated neurite growth evoked by NGF, IGF and EGF in dissociated cultures, although the MAP kinase kinase (MEK) inhibitor PD098059 diminished the growth in only IGF. Immunoprecipitation and Western blotting results demonstrated differential activation of MAPK, PI 3‐kinase, PLCγ1 and SNT by the different factors. Activation of PI 3‐kinase and SNT by both NGF and IGF‐1 correlated with their effects on neurite growth. These results support the hypothesis that the PI 3‐kinase pathway plays an important role in neuritogenesis. J. Neurosci. Res. 63:486–499, 2001. © 2001 Wiley‐Liss, Inc.
TNF‐α stimulates caspase‐3 activation and apoptotic cell death in primary septo‐hippocampal cultures
Authors: Zhao Xiurong , Bausano Brian , Pike Brian R. , Newcomb‐Fernandez Jennifer K. , Wang Kevin K.W. , Shohami Esther , Ringger N.C. , DeFord S.M. , Anderson Douglas K. , Hayes Ronald L. 
Published: August 2002

AbstractPrimary septo‐hippocampal cell cultures were incubated in varying concentrations of tumor necrosis factor (TNF‐α; 0.3–500 ng/ml) to examine proteolysis of the cytoskeletal protein α‐spectrin (240 kDa) to a signature 145 kDa fragment by calpain and to the apoptotic‐linked 120‐kDa fragment by caspase‐3. The effects of TNF‐α incubation on morphology and cell viability were assayed by fluorescein diacetate‐propidium iodide (FDA‐PI) staining, assays of lactate dehydrogenase (LDH) release, nuclear chromatin alterations (Hoechst 33258), and internucleosomal DNA fragmentation. Incubation with varying concentrations of TNF‐α produced rapid increases in LDH release and nuclear PI uptake that were sustained over 48 hr. Incubation with 30 ng/ml TNF‐α yielded maximal, 3‐fold, increase in LDH release and was associated with caspase‐specific 120‐kDa fragment but not calpain‐specific 145‐kDa fragment as early as 3.5 hr after injury. Incubation with the pan‐caspase inhibitor, carbobenzosy‐ Asp‐CH2‐OC (O)‐2‐6‐dichlorobenzene (Z‐D‐DCB, 50‐140 μM) significantly reduced LDH release produced by TNF‐α. Apoptotic‐associated oligonucleosomal‐sized DNA fragmentation on agarose gels was detected from 6 to 72 hr after exposure to TNF‐α. Histochemical changes included chromatin condensation, nuclear fragmentation, and formation of apoptotic bodies. Results of this study suggest TNF‐α may induce caspase‐3 activation but not calpain activation in septo‐hippocampal cultures and that this activation of caspase‐3 at least partially contributes to TNF‐α‐induced apoptosis. J. Neurosci. Res. 64:121–131, 2001. © 2001 Wiley‐Liss, Inc.
Local synthesis of nuclear‐encoded mitochondrial proteins in the presynaptic nerve terminal
Authors: Gioio Anthony E. , Eyman Maria , Zhang Hengshan , Lavina Zeno Scotto , Giuditta Antonio , Kaplan Barry B. 
Published: August 2002

AbstractOne of the central tenets in neuroscience has been that the protein constituents of distal compartments of the neuron (e.g., the axon and nerve terminal) are synthesized in the nerve cell body and are subsequently transported to their ultimate sites of function. In contrast to this postulate, we have established previously that a heterogeneous population of mRNAs and biologically active polyribosomes exist in the giant axon and presynaptic nerve terminals of the photoreceptor neurons in squid. We report that these mRNA populations contain mRNAs for nuclear‐encoded mitochondrial proteins to include: cytochrome oxidase subunit 17, propionyl‐CoA carboxylase (EC 6.4.1.3), dihydrolipoamide dehydrogenase (EC 1.8.1.4), and coenzyme Q subunit 7. The mRNA for heat shock protein 70, a chaperone protein known to be involved in the import of proteins into mitochondria, has also been identified. Electrophoretic gel analysis of newly synthesized proteins in the synaptosomal fraction isolated from the squid optic lobe revealed that the large presynaptic terminals of the photoreceptor neuron contain a cytoplasmic protein synthetic system. Importantly, a significant amount of the cycloheximide resistant proteins locally synthesized in the terminal becomes associated with mitochondria. PCR analysis of RNA from synaptosomal polysomes establishes that COX17 and CoQ7 mRNAs are being actively translated. Taken together, these findings indicate that proteins required for the maintenance of mitochondrial function are synthesized locally in the presynaptic nerve terminal, and call attention to the intimacy of the relationship between the terminal and its energy generating system. J. Neurosci. Res. 64:447–453, 2001. Published 2001 Wiley‐Liss, Inc.
Delayed induction of αB‐crystallin in activated glia cells of hippocampus in kainic acid‐treated mouse brain
Authors: Che Yongzhe , Piao Chun Shu , Han Pyung‐Lim , Lee Ja‐Kyeong 
Published: August 2002

AbstractSmall heat shock proteins have been implicated in playing a role in various cellular processes, including stress‐induced cell death. In kainic acid (KA)‐treated rat brain, the immunoreactivity of heat‐shock protein 27 (HSP27) was markedly increased in glia cells of the limbic system. In the present study, we demonstrated that αB‐crystallin, a member of the small heat‐shock protein family, was strongly induced in reactive astrocytes in hippocampus after KA‐induced seizure. The induction was localized mainly in the CA3 region of hippocampus, where massive neuronal loss occurred. We also demonstrated that the delayed induction of αB‐crystallin and HSP27 immunoreactivities in the hippocampus of epileptic animals was repressed to the levels seen in control animals with preadministration of the selective nNOS inhibitor 7‐nitroindazole (7‐NI). This repression was reversed by coinjection of L‐arginine, a substrate of NOS. Together, these data suggest a role for αB‐crystallin and HSP27 in reactive gliosis and/or in delayed neuronal death proceeded after KA‐induced seizure. J. Neurosci. Res. 65:425–431, 2001. © 2001 Wiley‐Liss, Inc.
Time course studies on the effectiveness of tetrodotoxin in reducing consequences of spinal cord contusion
Authors: Rosenberg Lisa J. , Wrathall Jean R. 
Published: August 2002

AbstractFocal injection of the sodium channel blocker tetrodotoxin (TTX) into the injury site at either 5 or 15 min after a standardized thoracic contusion spinal cord injury (SCI) reduces white matter pathology and loss of axons in the first 24 hr after injury. Focal injection of TTX at 15 min after SCI also reduces chronic white matter loss and hindlimb functional deficits. We have now tested the hypothesis that the reduction in chronic deficits with TTX treatment is associated with long‐term preservation of axons after SCI and compared both acute (24 hr) and chronic (6 weeks) effects of TTX administered at 15 min prior to and 5 min or 4 hr after SCI. Our results indicate a significant reduction of acute white matter pathology in rats treated with TTX at 15 min before and 5 min after injury but no effect when treatment was delayed until 4 hr after contusion. Compared with injury controls, groups treated with TTX at 5 min and 4 hr after injury did not show a significant deficit reduction, nor was there a significant sparing of white matter at 6 weeks compared with injury controls. In contrast, the group treated with TTX at 15 min before SCI demonstrated significantly reduced hindlimb functional deficits beginning at 1 week after injury and throughout the 6 weeks of the study. This was associated with a significantly higher axon density in the ventromedial white matter at 6 weeks. The results demonstrate that blockade of sodium channels preserves axons from loss after SCI and points to the importance of time of administration of such drugs for therapeutic effectiveness. J. Neurosci. Res. 66:191–202, 2001. © 2001 Wiley‐Liss, Inc.
Sunshine records from Ireland: cloud factors and possible links to solar activity and cosmic rays
Authors: Pallé E. , Butler C.J. 
Published: August 2002

AbstractThe records of sunshine hours obtained since the late 19th century from four stations distributed throughout Ireland were analysed. A gradual decrease in sunshine hours has occurred at all four sites since records began. Increasing cloud factors, resulting from enhanced evaporation rates over the Atlantic as sea surface temperatures have risen, is one possible explanation for the decline in sunshine.A strong negative correlation was confirmed between sunshine factors from ground‐based observations and satellite‐based cloud factors over Ireland. In addition, it was found that cloud factors over Ireland correlated well with cloud factors over large oceanic areas such as the North Atlantic and mid‐high latitudes generally. Thus cloud factors (and similarly sunshine factors) from regions on the boundaries of large oceans which lie in the direction of the prevailing wind could be useful in determining the long‐term changes in cloud factors over more extended areas. Knowledge of such long term variability in the Earth's cloud cover is important input information for modelling past climate change.The importance of cosmic rays as a link between solar activity and climate was assessed from a study of the ISCCP‐D2 satellite cloud factors and Irish sunshine data. Whilst these results confirmed the strong correlation between total cloud factor and cosmic rays over non‐tropical oceans between 1984 and 1991 previously reported, it was found that this correlation did not hold in the subsequent period 1991–1994. Other work has established a link through specifically low cloud.Indirect evidence of cloud formation by cosmic rays from a variation in the sunshine factor following Forbush decreases, and over the sunspot cycle, was mostly negative. Although a dip at seven years past sunspot minimum is evident in the sunshine factor for all four sites and in most seasons, it is of marginal statistical significance. Copyright © 2001 Royal Meteorological Society
Classification of rainfall variability by using artificial neural networks
Authors: Michaelides Silas Chr. , Pattichis Constantinos S. , Kleovoulou Georgia 
Published: August 2002

AbstractIn this paper, the usefulness of artificial neural networks (ANNs) as a suitable tool for the study of the medium and long‐term climatic variability is examined. A method for classifying the inherent variability of climatic data, as represented by the rainfall regime, is investigated. The rainfall recorded at a climatological station in Cyprus over a long time period has been used in this paper as the input for various ANN and cluster analysis models. The analysed rainfall data cover the time span 1917–1995. Using these values, two different procedures were followed for structuring the input vectors for training the ANN models: (a) each 1‐year subset consisting of the 12 monthly elements, and (b) each 2‐year subset consisting of the 24 monthly elements. Several ANN models with a varying number of output nodes have been trained, using an unsupervised learning paradigm, namely, the Kohonen's self‐organizing feature maps algorithm. For both the 1‐ and 2‐year subsets, 16 classes were empirically considered as the optimum for computing the prototype classes of weather variability for this meteorological parameter. The classification established by using the ANN methodology is subsequently compared with the classification generated by using cluster analysis, based on the agglomerative hierarchical clustering algorithm. To validate the classification results, the rainfall distributions for the more recent years 1996, 1997 and 1998 were utilized. The respective 1‐ and 2‐year distributions for these years were assigned to particular classes for both the ANN and cluster analysis procedures. Compared with cluster analysis, the ANN models were more capable of detecting even minor characteristics in the rainfall waveshapes investigated, and they also performed a more realistic categorization of the available data. It is suggested that the proposed ANN methodology can be applied to more climatological parameters, and with longer cycles. Copyright © 2001 Royal Meteorological Society
The intertropical convergence zone of the eastern Pacific revisited
Authors: Hastenrath Stefan 
Published: August 2002

AbstractThe Intertropical Convergence Zone (ITCZ) complex over the eastern Pacific is re‐examined from the NCEP–NCAR 40 year reanalysis and other data. Consistent with earlier work, the new analysis yields for July–August: a surface position of the near‐equatorial wind confluence at 12°N; the cross‐equatorial flow changing from divergent to convergent at the latitude of recurvature from southeasterly to southwesterly; strongest convergence in the surface layer to the south of the wind confluence, with this feeding vigorous ascending motion and compensating divergence in the upper troposphere; and the interface between cross‐equatorial flow and northeast trades sloping southward at 1 : 1500. An easterly speed maximum in the mid troposphere over the equator is consistent with the 4 year rawin record at Galapagos. The new coarse‐resolution dataset fails to capture a well‐developed Intertropical Divergence Zone. The annual cycle features for the wind confluence and the ITCZ a position closest to the equator in February, a northward migration to June, southward shift in July and August, and a northernmost location in September. This behaviour is paralleled by maxima in the frequency of the Temporal weather systems and rainfall on the Pacific side of Central America in June and September. Regarding the climatic variability, with an anomalously far southerly position of the wind confluence, Central American rainfall tends to be deficient, and such a combination of departures is common in the warm phase of the southern oscillation. The long‐term evolution is characterized by a warming trend of equatorial Pacific waters and weakening of cross‐equatorial wind, while trends in the latitude position of the wind confluence and in Central American rainfall are not significant. Copyright © 2002 Royal Meteorological Society.
Timing and significance of mid‐Holocene glacier advances in northern and central Iceland
Authors: Kirkbride Martin P. , Dugmore Andrew J. 
Published: August 2002

AbstractTephrochronology is used to date mid‐Holocene moraines in Iceland. In the Granavatn cirque (Tröllaskagi Peninsula) the H‐4 tephra (ca. 3830 yr BP) lies within sediment accumulated against the distal slope of a lateral moraine, providing a minimum age for glaciation, and the absence of H‐5 (ca. 5950 yr BP) provides a maximum age. By implication, the cirque was glaciated in the early Neoglacial period. A large rock glacier, the development of which post‐dates the moraine, probably formed within the ‘Little Ice Age’ (LIA) of the sixteenth to nineteenth centuries ad. At Eystri‐Loðmundarjökull in central Iceland, frozen colluvium containing the H‐3 (ca. 2900 yr BP) and H‐4 tephras provides a minimum age of ca. 3830 yr BP for two terminal moraines, and a maximum age of ca. 2900 yr BP for a third. The older moraines are correlated with the Vatnsdalur I/Drangagíl advances (ca. 4700 yr BP and ≥ 4500 yr BP respectively) and the Begisárdalur I advance (ca. 4200 yr BP). They imply that early Neoglacial advances throughout Iceland were locally more extensive than those of the LIA. The apparent LIA Holocene glacial maximum may reflect (i) selective sampling of large ice‐cap‐outlet glaciers, where the preservation potential of pre‐LIA deposits is low, and (ii) reliance on lichenometric dating, which has a restriced temporal range. Copyright © 2001 John Wiley & Sons, Ltd.