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Complex Manner (complex + manner)
Selected AbstractsInterferon-, differentially modulates the release of cytokines and chemokines in lipopolysaccharide- and pneumococcal cell wall-stimulated mouse microglia and macrophagesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Karl Georg Häusler Abstract During bacterial infections of the CNS, activated microglia could support leucocyte recruitment to the brain through the synthesis of cyto- and chemokines. In turn, invading leucocytes may feedback on microglial cells to influence their chemokine release pattern. Here, we analyzed the capacity of interferon-, (IFN,) to serve as such a leucocyte-to-microglia signal. Production of cyto- and chemokines was stimulated in mouse microglia cultures by treatments with lipopolysaccharide (LPS) from Gram-negative Escherichia coli or cell walls from Gram-positive Streptococcus pneumoniae (PCW). IFN, presence during the stimulation (0.1,100 ng/mL) modulated the patterns of LPS- and PCW-induced cyto- and chemokine release in a dose-dependent, potent and complex manner. While amounts of TNF, and IL-6 remained nearly unchanged, IFN, enhanced the production of IL-12, MCP-1 and RANTES, but attenuated that of KC, MIP-1, and MIP-2. Release modulation was obtained with IFN, preincubation (treatment of cells before LPS or PCW administration), coincubation and even delayed addition to an ongoing LPS or PCW stimulation. Together the changes observed for the microglial chemokine release under IFN, would shift the chemoattractive profile from favouring neutrophils to a preferential attraction of monocytes and T lymphocyte populations , as actually seen during the course of bacterial meningitis. The findings support the view of activated microglia as a major intrinsic source for an instant production of a variety of chemokines and suggest that leucocyte-derived IFN, could potentially regulate the microglial chemokine release pattern. [source] GEOGRAPHIC VARIATION IN THE EVOLUTION AND COEVOLUTION OF A TRITROPHIC INTERACTIONEVOLUTION, Issue 5 2007Timothy P. Craig The geographic mosaic theory of coevolution predicts that geographic variation in species interactions will lead to differing selective pressures on interacting species, producing geographic variation in the traits of interacting species (Thompson 2005). We supported this hypothesis in a study of the geographic variation in the interactions among Eurosta solidaginis and its natural enemies. Eurosta solidaginis is a fly (Diptera: Tephritidae) that induces galls on subspecies of tall goldenrod, Solidago altissima altissima and S. a. gilvocanescens. We measured selection on E. solidaginis gall size and shape in the prairie and forest biomes in Minnesota and North Dakota over an 11-year period. Galls were larger and more spherical in the prairie than in the forest. We supported the hypothesis that the divergence in gall morphology in the two biomes is due to different selection regimes exerted by natural enemies of E. solidaginis. Each natural enemy exerted similar selection on gall diameter in both biomes, but differences in the frequency of natural enemy attack created strong differences in overall selection between the prairie and forest. Bird predation increased with gall diameter, creating selection for smaller-diameter galls. A parasitic wasp, Eurytoma gigantea, and Mordellistena convicta, an inquiline beetle, both caused higher E. solidaginis mortality in smaller galls, exerting selection for increased gall diameter. In the forest there was stabilizing selection on gall diameter due to a combination of bird predation on larvae in large galls, and M. convicta - and E. gigantea- induced mortality on larvae in small galls. In the prairie there was directional selection for larger galls due to M. convicta and E. gigantea mortality on larvae in small galls. Mordellistena convicta- induced mortality was consistently higher in the prairie than in the forest, whereas there was no significant difference in E. gigantea- induced mortality between biomes. Bird predation was nonexistent in the prairie so the selection against large galls found in the forest was absent. We supported the hypothesis that natural enemies of E. solidaginis exerted selection for spherical galls in both biomes. In the prairie M. convicta exerts stabilizing selection to maintain spherical galls. In the forest there was directional selection for more spherical galls. Eurytoma gigantea exerted selection on gall shape in the forest in a complex manner that varied among years. We also supported the hypothesis that E. gigantea is coevolving with E. solidaginis. The parasitoid had significantly longer ovipositors in the prairie than in the forest, indicating the possibility that it has evolved in response to selection to reach larvae in the larger-diameter prairie galls. [source] New developments in our understanding of acne pathogenesis and treatmentEXPERIMENTAL DERMATOLOGY, Issue 10 2009Ichiro Kurokawa Abstract:, Interest in sebaceous gland physiology and its diseases is rapidly increasing. We provide a summarized update of the current knowledge of the pathobiology of acne vulgaris and new treatment concepts that have emerged in the last 3 years (2005,2008). We have tried to answer questions arising from the exploration of sebaceous gland biology, hormonal factors, hyperkeratinization, role of bacteria, sebum, nutrition, cytokines and toll-like receptors (TLRs). Sebaceous glands play an important role as active participants in the innate immunity of the skin. They produce neuropeptides, excrete antimicrobial peptides and exhibit characteristics of stem cells. Androgens affect sebocytes and infundibular keratinocytes in a complex manner influencing cellular differentiation, proliferation, lipogenesis and comedogenesis. Retention hyperkeratosis in closed comedones and inflammatory papules is attributable to a disorder of terminal keratinocyte differentiation. Propionibacterium acnes, by acting on TLR-2, may stimulate the secretion of cytokines, such as interleukin (IL)-6 and IL-8 by follicular keratinocytes and IL-8 and -12 in macrophages, giving rise to inflammation. Certain P. acnes species may induce an immunological reaction by stimulating the production of sebocyte and keratinocyte antimicrobial peptides, which play an important role in the innate immunity of the follicle. Qualitative changes of sebum lipids induce alteration of keratinocyte differentiation and induce IL-1 secretion, contributing to the development of follicular hyperkeratosis. High glycemic load food and milk may induce increased tissue levels of 5,-dihydrotestosterone. These new aspects of acne pathogenesis lead to the considerations of possible customized therapeutic regimens. Current research is expected to lead to innovative treatments in the near future. [source] Ordered Mesoporous Silica Derived from Layered SilicatesADVANCED FUNCTIONAL MATERIALS, Issue 4 2009Tatsuo Kimura Abstract Here, the development of ordered mesoporous silica prepared by the reaction of layered silicates with organoammonium surfactants is reviewed. The specific features of mesoporous silica are discussed with relation to the probable formation mechanisms. The recent understanding of the unusual structural changes from the 2D structure to periodic 3D mesostructures is presented. The formation of mesophase silicates from layered silicates with single silicate sheets depends on combined factors including the reactivity of layered silicates, the presence of layered intermediates, the variation of the silicate sheets, and the assemblies of surfactant molecules in the interlayer spaces. FSM-16-type (p6mm) mesoporous silica is formed via layered intermediates composed of fragmented silicate sheets and alkyltrimethylammonium (CnTMA) cations. KSW-2-type (c2mm) mesoporous silica can be prepared through the bending of the individual silicate sheets with intralayer and interlayer condensation. Although the structure of the silicate sheets changes during the reactions with CnTMA cations in a complex manner, the structural units caused by kanemite in the frameworks are retained. Recent development of the structural design in the silicate framework is very important for obtaining KSW-2-based mesoporous silica with molecularly ordered frameworks. The structural units originating from layered silicates are chemically designed and structurally stabilized by direct silylation of as-synthesized KSW-2. Some proposed applications using these mesoporous silica are also summarized with some remarks on the uniqueness of the use of layered silicates by comparison with MCM-type mesoporous silica. [source] Diagnostic osteology and analysis of the Mid- to Late Holocene dynamics of shags and cormorants in Tierra del FuegoINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 2 2007D. Causey Abstract We present here illustrated characteristics and anatomical descriptions of features that can be used to discriminate between four common skeletal elements (i.e. humerus, coracoid, femur, tarsometatarsus) of the five species of shags and cormorants known to occur in southern South America. We also present a detailed study of their distribution and abundance from about 6000 years before present to historical times as revealed by identification of faunal material excavated earlier and by re-analysis of material published previously. Our results present a high-resolution examination of the avian resource base used by early human hunters, and provide a foundation for future studies on the palaeoavifauna of Tierra del Fuego during the Mid- to Late Holocene. On the broadest scales, species diversity of the Phalacrocoracidae is qualitatively stable over space and time, a pattern that is also reflected in the larger marine bird community. On a finer scale, however, our results indicate that the abundance and distribution of cormorants and shags in Mid- and Late Holocene zooarchaeological deposits varied in a complex manner through time. These patterns do not appear to be related to proximity effects of hunters to colonies, but to other factors possibly associated with environmental change. Copyright © 2006 John Wiley & Sons, Ltd. [source] Differential Contribution of Osteoclast- and Osteoblast-Lineage Cells to CpG-Oligodeoxynucleotide (CpG-ODN) Modulation of Osteoclastogenesis,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Alla Amcheslavsky Abstract CpG-ODNs modulate osteoclast differentiation through Toll-like receptor 9 (TLR9). Using TLR9-deficient mice, we found that activation of TLR9 on both osteoclast precursors and osteoblasts mediate the osteoclastogenic effect of CpG-ODN. Osteoclastic TLR9 is more important for this activity. Introduction: Bacterial infections cause pathological bone loss by accelerating differentiation and activation of the osteoclast. A variety of bacteria-derived molecules have been shown to enhance osteoclast differentiation through activation of Toll-like receptors (TLRs). We have shown that CpG-oligodeoxynucleotides (CpG-ODNs), mimicking bacterial DNA and exerting their cellular activities through TLR9, modulate osteoclast differentiation in a complex manner: the ODNs inhibit the activity of the physiological osteoclast differentiation factor RANKL in early osteoclast precursors (OCPs) but markedly stimulate osteoclastogenesis in cells primed by RANKL. Materials and Methods: Osteoclast precursors and osteoblasts from TLR9-deficient (TLR9,/,) and wildtype (TLR9+/+) mice were used for in vitro analyses of osteoclast differentiation and modulation of signal transduction and gene expression. Results: As expected CpG-ODN did not exert any activity in cells derived from TLR9,/,mice; these cells, however, responded in a normal manner to other stimuli. Using bone marrow/osteoblasts co-cultures from all possible combinations of TLR9,/, and TLR9+/+ mice-derived cells, we showed that TLR9 in the two lineages is required for CpG-ODN induction of osteoclastogenesis. Conclusions: CpG-ODN modulates osteoclastogenesis in a TLR9-dependent manner. Activation of TLR9 in bone marrow-derived osteoclasts precursors is more crucial to induction of osteoclastogenesis than activation of the osteoblastic TLR9. [source] Predicting Treatment Seekers' Readiness to Change Their Drinking Behavior in the COMBINE StudyALCOHOLISM, Issue 5 2009Carlo C. DiClemente Background:, Initial motivation and readiness to change (RTC) are complex constructs and have been important but inconsistent predictors of treatment attendance and drinking outcomes in studies of alcoholism treatment. Motivation can be described in multiple ways as simply the accumulation of consequences that push change, a shift in intentions, or engagement in various tasks that are part of a larger process of change. Method:, Using baseline data from participants in the COMBINE Study, this study reevaluated the psychometric properties of a 24-item measure of motivation derived from the University of Rhode Island Change Assessment Scale that yielded 4 subscales representing attitudes and experiences related to tasks of stages of Precontemplation, Contemplation, Action, and Maintenance Striving as well as a second-order factor score representing a multidimensional view of RTC drinking. A variety of hypothesized predictors of readiness and the stage subscales were examined using multiple regression analyses to better understand the nature of this measure of motivation. Results:, Findings supported the basic subscale structure and the overall motivational readiness score derived from this measure. RTC drinking behavior was predicted by baseline measures of perceived stress, drinking severity, psychiatric comorbidity, self-efficacy, craving, and positive treatment outcome expectancies. However, absolute values were small, indicating that readiness for change is not explained simply by demographic, drinking severity, treatment, change process, or contextual variables. Conclusion:, This measure demonstrated good psychometric properties and results supported the independence as well as convergent and divergent validity of the measured constructs. Predictors of overall readiness and subscale scores indicate that a variety of personal and contextual factors contribute to treatment seekers' motivation to change in an understandable but complex manner. [source] Effect of hindered piperidine light stabilizer molecular structure and UV-absorber addition on the oxidation of HDPE.JOURNAL OF VINYL & ADDITIVE TECHNOLOGY, Issue 2 2004Part 1: Long-term thermal, photo-oxidation studies This series of papers explores the effect of structural characteristics of 2,2,6,6-tetramethylpiperidine-based hindered amine light stabilizers (HALS) on the long-term (40 months) thermal (110°C in air) and photo-stabilization (Microscal unit wavelength >300 nm) performance characteristics of high-density polyethylene formulations. Possible synergism with a triazine functional UV absorber is also explored. Under thermal degradation (measured by carbonyl index) the polymeric HALS performed best, mainly because of reduced volatilization. Additionally, >N-methyl HALS generally showed superior performance under thermal degradation. There was no synergism between an N-CH3 polymeric HALS and the UV1164 triazine additive. However, the equivalent N-H polymeric HALS interacted in a complex manner with UV1164, giving synergism and antagonism, depending on HALS/UV1164 ratio. Strong synergism was evident with the monomeric HALS when the total stabilizer level was 0.2% w/w. Reduction in the overall stabilizer level to 0.05% w/w eliminated the synergism. The UV1164 alone led to rapid and intense yellowing; however, the rate and intensity of yellowing reduced dramatically upon combination with HALS, particularly when the UV1164 level was above 0.1% w/w. When the formulation was under UV attack, the molar mass and the type of N-substitution had no influence on stabilization performance because of the relatively low temperature of testing (leading to reduced volatilization), and the similarly effective UV-stabilization routes for N-methyl HALS and N-H HALS. Under UV attack, yellowing reached a maximum and then decreased to approximately the initial level, while HALS/UV1164 combinations generally showed weak antagonism. J. Vinyl Addit. Technol. 10:79,87, 2004. © 2004 Society of Plastics Engineers. [source] Rad51 overexpression rescues radiation resistance in BRCA2-defective cancer cellsMOLECULAR CARCINOGENESIS, Issue 2 2009Erika T. Brown Abstract Breast cancers with BRCA2 mutations exhibit DNA repair defects and are particularly sensitive to radiation. BRCA2 interacts with Rad51 in a complex manner involving internal BRC and C-terminal TR2 domains which play a key role in homologous recombination. BRCA2 expression also modulates Rad51 protein levels such that Rad51 protein is relatively decreased in BRCA2-defective cancer cells. This is mediated in part through BRCA2's capacity to protect Rad51 from caspase-3 proteolytic degradation. In order to distinguish between functional and expression related roles for BRCA2 we studied the results of Rad51 overexpression in mouse and human cells with inactivating BRCA2 mutations. The results show that overexpression of wild-type Rad51 partially rescues BRCA2 deficiency but that overexpression of a caspase-3 resistant Rad51 completely complements the BRCA2 defect in radiation responsiveness. These results indicate that Rad51 can compensate for some aspects of a BRCA2 gene defect and suggest that Rad51 expression levels may be an important modifier of the BRCA2 defective genotype. © 2008 Wiley-Liss, Inc. [source] Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of Protochlamydia amoebophilaMOLECULAR MICROBIOLOGY, Issue 6 2006Ilka Haferkamp Summary Protochlamydia amoebophila UWE25 is related to the Chlamydiaceae comprising major pathogens of humans, but thrives as obligate intracellular symbiont in the protozoan host Acanthamoeba sp. The genome of P. amoebophila encodes five paralogous carrier proteins belonging to the nucleotide transporter (NTT) family. Here we report on three P. amoebophila NTT isoforms, PamNTT2, PamNTT3 and PamNTT5, which possess several conserved amino acid residues known to be critical for nucleotide transport. We demonstrated that these carrier proteins are able to transport nucleotides, although substrate specificities and mode of transport differ in an unexpected manner and are unique among known NTTs. PamNTT2 is a counter exchange transporter exhibiting submillimolar apparent affinities for all four RNA nucleotides, PamNTT3 catalyses an unidirectional proton-coupled transport confined to UTP, whereas PamNTT5 mediates a proton-energized GTP and ATP import. All NTT genes of P. amoebophila are transcribed during intracellular multiplication in acanthamoebae. The biochemical characterization of all five NTT proteins from P. amoebophila in this and previous studies uncovered that these metabolically impaired bacteria are intimately connected with their host cell's metabolism in a surprisingly complex manner. [source] Involvement of trichothecenes in fusarioses of wheat, barley and maize evaluated by gene disruption of the trichodiene synthase (Tri5) gene in three field isolates of different chemotype and virulenceMOLECULAR PLANT PATHOLOGY, Issue 6 2006FRANK J. MAIER SUMMARY Fusarium graminearum is the main causative agent of Fusarium head blight on small grain cereals and of ear rot on maize. The disease leads to dramatic yield losses and to an accumulation of mycotoxins. The most dominant F. graminearum mycotoxins are the trichothecenes, with deoxynivalenol and nivalenol being the most prevalent derivatives. To investigate the involvement of trichothecenes in the virulence of the pathogen, the gene coding for the initial enzyme of the trichothecene pathway was disrupted in three field isolates, differing in chemotype and in virulence. From each isolate three individual disruption mutants were tested for their virulence on wheat, barley and maize. Despite the different initial virulence of the three wild-type progenitor strains on wheat, all disruption mutants caused disease symptoms on the inoculated spikelet, but the symptoms did not spread into other spikelets. On barley, the trichothecene deficient mutants showed no significant difference compared to the wild-type strains: all were equally aggressive. On maize, mutants derived from the NIV-producing strain caused less disease than their wild-type progenitor strain, while mutants derived from DON-producing strains caused the same level of disease as their progenitor strains. These data demonstrate that trichothecenes influence the virulence of F. graminearum in a highly complex manner, which is strongly host as well as moderately chemotype specific. [source] Multiple minute carcinoids in type A gastritis: Attempt at 3-D reconstructionPATHOLOGY INTERNATIONAL, Issue 7 2001Takuya Nojiri In type A gastritis, the numbers of endocrine cell micronests (ECM) and carcinoids increase through the trophic action of gastrin. This study examined the characteristics and growth of carcinoids in type A gastritis. A total of 395 lesions in five surgically removed stomachs with type A gastritis were investigated, in terms of number, size, distribution and histological appearance, to clarify the tumorigenesis and progression of carcinoids. 3-D reconstruction using serial paraffin sections was used to study carcinoid progression. Our findings suggest that in type A gastritis, carcinoids arise in areas where minute carcinoids are present at a high density. They also suggest that early stage carcinoids not only become large expansively, but also develop in a very complex manner, by maintaining contact with surrounding minute carcinoids. [source] Genome-wide Examination of the Natural Solar Radiation Response in Shewanella oneidensis MR-1PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2005Xiaoyun Qiu ABSTRACT We previously reported that Shewanella oneidensis MR-1 is extremely sensitive to natural solar radiation (NSR). Here we analyzed the global transcriptional profile of MR-1 during a 1-h recovering period after exposure to ambient solar light at a dose that yields about 20% survival rate on a Luria-Bertani (LB) plate. We observed the induction of DNA damage-repair genes, the SOS response as well as detoxification strategies that we previously observed in MR-1 following artificial UV-A irradiation. Few prophage-related genes were induced by natural solar UV radiation, however, in contrast to what was observed following artificial UV-B irradiation. Overall, the cellular response to NSR in MR-1 was more similar to that of UV-A than that of UV-B, but additional genes involved in detoxification were induced compared with induction by either UV-B or UV-A or their sum. Thus, oxidative stress appeared to contribute greatly to the NSR-induced cytotoxic effects in MR-1. A total of 29.1% of genome showed differential expression following NSR exposure, which is much greater than following exposure by UV-B (4.0%), UV-A (8.2%) or their sum (10.7%). Our data suggest that NSR may impact biological processes in a much more complex manner than previously thought. [source] Effects of Combined Photodynamic Therapy and Ionizing Radiationon Human Glioma Spheroids,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2002Steen J. Madsen ABSTRACT The effects of combined photodynamic therapy (PDT) and ionizing radiation are studied in a human glioma spheroid model. The degree of interaction between the two modalities depends in a complex manner on factors such as PDT irradiation fluence, fluence rate and dose of ionizing radiation. It is shown that gamma radiation and PDT interact in a synergistic manner only if both light fluence and gamma radiation dose exceed approximately 25 J cm,2 and 8 Gy, respectively. Synergistic interactions are observed only for the lower fluence rate (25 mW cm,2) investigated. The degree of interaction appears to be independent of both sequence and the PDT or ionizing radiation time intervals investigated (1 and 24 h). Terminal deoxynucleotidyl transferase,mediated deoxyuridine triphosphate nick-end labeling assays show that low-fluence rate PDT is very efficient at inducing apoptotic cell death, whereas neither high-fluence rate PDT nor ionizing radiation produces significant apoptosis. Although the mechanisms remain to be elucidated, the data imply that the observed synergism is likely not due to gamma-induced cell cycle arrest or to PDT-induced inhibition of DNA repair. [source] Input,output organization of jaw movement-related areas in monkey frontal cortexTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2005Nobuhiko Hatanaka Abstract The brain mechanisms underlying mastication are not fully understood. To address this issue, we analyzed the distribution patterns of cortico,striatal and cortico,brainstem axon terminals and the origin of thalamocortical and intracortical fibers by injecting anterograde/retrograde tracers into physiologically and morphologically defined jaw movement-related cortical areas. Four areas were identified in the macaque monkey: the primary and supplementary orofacial motor areas (MIoro and SMAoro) and the principal and deep parts of the cortical masticatory area (CMaAp and CMaAd), where intracortical microstimulation produced single twitch-like or rhythmic jaw movements, respectively. Tracer injections into these areas labeled terminals in the ipsilateral putamen in a topographic fashion (MIoro vs. SMAoro and CMaAp vs. CMaAd), in the lateral reticular formation and trigeminal sensory nuclei contralaterally (MIoro and CMaAp) or bilaterally (SMAoro) in a complex manner of segregation vs. overlap, and in the medial parabranchial and Kölliker-Fuse nuclei contralaterally (CMaAd). The MIoro and CMaAp received thalamic projections from the ventrolateral and ventroposterolateral nuclei, the SMAoro from the ventroanterior and ventrolateral nuclei, and the CMaAd from the ventroposteromedial nucleus. The MIoro, SMAoro, CMaAp, and CMaAd received intracortical projections from the ventral premotor cortex and primary somatosensory cortex, the ventral premotor cortex and rostral cingulate motor area, the ventral premotor cortex and area 7b, and various sensory areas. In addition, the MIoro and CMaAp received projections from the three other jaw movement-related areas. Our results suggest that the four jaw movement-related cortical areas may play important roles in the formation of distinctive masticatory patterns. J. Comp. Neurol. 492:401,425, 2005. © 2005 Wiley-Liss, Inc. [source] Structure of intraglomerular dendritic tufts of mitral cells and their contacts with olfactory nerve terminals and calbindin-immunoreactive type 2 periglomerular neuronsTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 3 2001Katsuko Kosaka Abstract Intraglomerular dendritic tufts of Golgi-impregnated and biotinylated dextran amine (BDA)-labeled mitral cells in the rat main olfactory bulb were analyzed in detail. In particular, the relationships of BDA-labeled tufts with olfactory nerve (ON) terminals and processes of calbindin D-28K-immunoreactive (CB-IR) cells were investigated with confocal laser-scanning light microscopic (CLSM) and electron microscopic (EM) analyses. CB-IR cells were type 2 periglomerular cells that restricted their processes in the ON-free (non-ON) zone of the glomerulus and received few synapses from ON terminals. The mitral tufts varied in complexity, but individual branches were rather simple, smooth processes that bore some branchlets and spines and extended more or less in a straight line or a gentle curve rather than winding tortuously within glomeruli as though they did not consider the compartmental organization, which consisted of ON and non-ON zones that interdigitated in a complex manner with one another. Conventional EM analysis revealed that both thin and thick, presumed proximal branches of mitral/tufted cell dendritic tufts received asymmetrical synapses from ON terminals. Correlated CLSM-EM analysis confirmed direct contacts between the BDA- and CB-labeled processes detected in the CLSM examinations, and synapses were recognized at some of those sites. Furthermore, ON terminals and CB-IR processes were distributed on both proximal and distal dendritic branches in a more or less mosaic pattern. These findings revealed that, on the mitral dendritic tufts, ON terminals and processes of type 2 periglomerular neurons were not clearly segregated proximodistally but, rather, were arranged in a mosaic pattern, which may be important in fine tuning the output from individual glomeruli. J. Comp. Neurol. 440:219,235, 2001. © 2001 Wiley-Liss, Inc. [source] Inhibition of slow Ca2+ -activated K+ current by 4-aminopyridine in rat hippocampal CA1 pyramidal neuronesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002Mogens Andreasen The effect of 4-aminopyridine (4-AP) on the slow afterhyperpolarization (sAHP) seen after high frequency dendritic or somatic firing was investigated in rat hippocampal CA1 pyramidal neurones (PC). Intracellular recordings were obtained from the distal apical dendrites and somata and suprathreshold depolarizing current pulses were used to evoke a sAHP. The sAHP was blocked by low concentrations of carbacholine (Cch) but insensitive to high concentrations of apamin. In the presence of extracellular 4-AP, the first dendritic sAHP evoked was reduced compared to a maximal sAHP evoked in the absence of 4-AP. The reduction was evident at submillimolar concentration and increased to about 80% with 4 mM 4-AP. The stability of the 4-AP-induced block was affected by the type of anion used in the electrode solution. With K+ acetate (KAc) or K+ methylsulphate (KMeSO4) containing electrodes, the block was progressively removed during the initial 300 , 400 s of recordings. With KCl containing electrodes, the block remained stable and was 10% larger than that obtained with acetate. Detailed investigations showed that intracellular acetate promotes the removal of the 4-AP-induced block in an activity-dependent manner. Intracellularly applied 4-AP also induced an acetate-sensitive block of the dendritic sAHP. 4-AP also blocked the somatic sAHP and the stability of the block showed the same sensitivity towards anions as the dendritic sAHP. Thus 4-AP appears to block the slow Ca2+ -activated K+ current underlying the sAHP in a complex manner which is sensitive to certain types of anions. British Journal of Pharmacology (2002) 135, 1013,1025; doi:10.1038/sj.bjp.0704533 [source] Regulation of cell death during infection by the severe acute respiratory syndrome coronavirus and other coronavirusesCELLULAR MICROBIOLOGY, Issue 11 2007Yee-Joo Tan Summary Both apoptosis and necrosis have been observed in cells infected by various coronaviruses, suggesting that the regulation of cell death is important for viral replication and/or pathogenesis. Expeditious research on the severe acute respiratory syndrome (SARS) coronavirus, one of the latest discovered coronaviruses that infect humans, has provided valuable insights into the molecular aspects of cell-death regulation during infection. Apoptosis was observed in vitro, while both apoptosis and necrosis were observed in tissues obtained from SARS patients. Viral proteins that can regulate apoptosis have been identified, and many of these also have the abilities to interfere with cellular functions. Occurrence of cell death in host cells during infection by other coronaviruses, such as the mouse hepatitis virus and transmissible porcine gastroenteritis virus, has also being extensively studied. The diverse cellular responses to infection revealed the complex manner by which coronaviruses affect cellular homeostasis and modulate cell death. As a result of the complex interplay between virus and host, infection of different cell types by the same virus does not necessarily activate the same cell-death pathway. Continuing research will lead to a better understanding of the regulation of cell death during viral infection and the identification of novel antiviral targets. [source] | ||||||||||||||||