bluuebunny/crossref_metadata_2025_split huggingface dataset:
An emerging view of presynaptic structure from electron microscopic studies
Authors: Siksou Léa , Triller Antoine , Marty Serge 
Published: January 2009

AbstractIn response to calcium influx, some of the synaptic vesicles in presynaptic terminals fuse rapidly with the presynaptic membrane, allowing fast synaptic transmission. The regulated recycling of synaptic vesicles at the terminals is required for a sustained release of neurotransmitters. Localization of ‘ready to be released’ vesicles in close vicinities to voltage‐gated calcium channels enables the rapid release of neurotransmitters. Thus, recycling vesicles must translocate from the sites of endocytosis to these release sites. However, the sub‐cellular organization that supports this local vesicular traffic remains poorly understood. We will review the results of various electron microscopy studies, which have begun to unveil the structure of presynaptic terminals.
Spatial congruence between ecotones and range‐restricted species: implications for conservation biogeography at the sub‐continental scale
Authors: Van Rensburg Berndt J. , Levin Noam , Kark Salit 
Published: January 2009

ABSTRACTAim  To examine whether at a sub‐continental scale range‐limited species tend to occur close to areas of transition between vegetation boundaries more often than expected by chance.Location  South Africa and Lesotho.Methods  We examined the relationship between the distance of a grid square to ecological transition areas between vegetation types and both avian and frog range‐limited species richness in the quadrat. We used quadrats at a spatial resolution of quarter degree (15′ × 15′≈ 676 km2). Spatial congruence between areas representing range‐restricted species and those representing ecological transition zones was assessed using a random draw technique.Results  Species richness and range size rarity are generally negatively correlated with distance to transition areas between vegetation communities when analysed for the whole region for both groups. Although this relationship becomes weaker after controlling for environmental energy and topographical heterogeneity, the explanatory power of distance to transition areas remains significant, and compared to the different biomes examined, accounts for most of the variation in bird richness (20%), frog richness (18%), range‐restricted bird species (17%) and range‐restricted frog species (16%) in the savanna biome. The random draw technique indicated that areas representing range‐restricted species were situated significantly closer in space to those areas representing transition areas between vegetation communities than expected by chance.Main conclusions  We find that at the sub‐continental scale, when examined for South Africa, areas of transition between vegetation communities hold concentrations of range‐limited species in both birds and frogs. We find that South African endemic/range‐limited birds and frogs are located closer to ecological transition zones than endemics and non‐endemics combined. This has important implications for ongoing conservation planning in a biogeographical context.
Detection of a colonizing, aquatic, non‐indigenous species
Authors: Harvey Chad T. , Qureshi Samir A. , MacIsaac Hugh J. 
Published: January 2009

ABSTRACTDetecting the presence of rare species has interested ecologists and conservation biologists for many years. A particularly daunting application of this problem pertains to the detection of non‐indigenous species (NIS) as they colonize new ecosystems. Ethical issues prevent experimental additions of NIS to most natural systems to explore the relationship between sampling intensity and the detection probability of a colonizing NIS. Here we examine this question using a recently introduced water flea, Cercopagis pengoi, in Lake Ontario. The species has biphasic population development, with sexually‐produced ‘spring morphs’ developing prior to parthenogenetically‐produced ‘typical’ morphs. Thus, this biphasic morphology allows distinction between new colonists (spring morphs) from subsequent generations. We repeatedly sampled Hamilton Harbour, Lake Ontario for the presence of both spring and typical morphs. Probability of detection was positively related to both the number of samples taken and animal density in the lake; however, even highly intensive sampling (100 samples) failed to detect the species in early spring when densities were very low. Spatial variation was greatest when densities of Cercopagis were intermediate to low. Sub‐sampling, which increased space between adjacent samples, significantly decreased the number of samples required to reach greater, calculated detection probabilities on these dates. Typical sampling protocols for zooplankton have a low probability (< 0.2) of detecting the species unless population density is high. Results of this study suggest that early detection of colonizing, aquatic NIS may be optimized through use of a risk‐based sampling design, combined with high sampling intensity in areas deemed most vulnerable to invasion, rather than less intensive sampling at a wider array of sites.
Habitat heterogeneity as a driver of ungulate diversity and distribution patterns: interaction of body mass and digestive strategy
Authors: Cromsigt Joris P. G. M. , Prins Herbert H. T. , Olff Han 
Published: January 2009

ABSTRACTAim Classic island biogeographical theory predicts that reserves have to be large to conserve high biodiversity. Recent literature, however, suggests that habitat heterogeneity can counterbalance the effect of small reserve size. For savanna ungulates, body mass is said to drive habitat selection and facilitate species coexistence, where large species use a higher proportion of the landscape than smaller species, because a wider food quality tolerance allows them to use a higher diversity of habitat types. In this case, high habitat heterogeneity would facilitate diverse assemblages of different‐sized ungulates. Digestive physiology should further modify this relationship, because non‐ruminants have a wider diet tolerance than ruminants. We tested this hypothesis with an empirical dataset on distribution and habitat preference of different‐sized African grazers.Location Hluhluwe‐iMfolozi Park, Republic of South Africa.Methods We recorded herbivore dung and habitat type on 24 line transects varying between 4 and 11 km with a total length of 190 km to determine habitat selection and landscape distribution of six grazer species, three ruminants and three non‐ruminants.Results Larger ruminant grazers were more evenly distributed than smaller ruminants, had a more diverse use of habitats and used more low quality habitat. In contrast, non‐ruminant grazers were more evenly distributed than similar‐sized ruminants and body mass did not clearly influence diversity of habitat use and use of low quality habitat.Main conclusions  We confirm that body mass influences diversity of habitat use of large herbivores but digestive strategy potentially modifies this relationship. Hence, habitat heterogeneity might facilitate herbivore diversity in savanna ecosystems and high heterogeneity might counterbalance the effects of fragmentation and declining reserve size. Concluding, processes that homogenize the landscape, such as fire (mis)management and artificial waterholes, might be as threatening to biodiversity as landscape fragmentation, especially for smaller ruminant herbivores.
Effect of nebivolol on blood oxygen transport indices and endothelial dysfunction in patients with arterial hypertension
Authors: Pronko T. P. , Zinchuk V. V. 
Published: January 2009

SummaryEndothelial dysfunction, which is characterized by impairment of nitric oxide (NO) bioavailability, plays an important role in the development of arterial hypertension. The L‐arginine‐NO pathway is closely related to oxygen transport to tissue. Endothelial dysfunction in patients with arterial hypertension can affect haemoglobin‐oxygen affinity and tissue oxygen supply. Alterations in blood oxygen transport indices may play role in the pathogenesis of arterial hypertension. The aim of the present study was to investigate the effect of the beta‐selective adrenoblocker nebilet (nebivolol) on blood oxygen transport indices and on endothelial dysfunction in patients with arterial hypertension. The study population included 52 patients with grade II and grade III arterial hypertension. The results of our studies indicate that endothelial dysfunction in hypertensive patients significantly changes blood oxygen indices. The endothelium can be involved in formation of these impairments because only NO synthesized in sufficient amounts can maintain normal blood flow and oxygen transport to tissues. Endothelial dysfunction impairs formation of different haemoglobin NO‐derivatives, that influence not only on the release of NO at different sites of the vascular bed, but also on haemoglobin‐oxygen affinity, and accordingly, on optimal blood oxygenation in capillaries of pulmonary circulation and its deoxygenation in capillaries of systemic circulation. Treatment of hypertensive patients with nebivolol corrects the blood oxygen transport indices, stimulates NO production and improves endothelium‐dependent dilatation. Normalization of blood oxygen transport indices may regulate the activity of the L‐arginine‐NO pathway. Thus, nebivolol may improve efficiency of the treatment of hypertension.
Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild‐type and W/Wv mice
Authors: McCloskey KD , Anderson UA , Davidson RA , Bayguinov YR , Sanders KM , Ward SM 
Published: January 2009

Background and purpose:  W/Wv and wild‐type murine bladders were studied to determine whether the W/Wv phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).Experimental approach:  Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild‐type and mutant bladders.Key results:  Wild‐type and W/Wv detrusors contained c‐Kit‐ and vimentin‐immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin‐sensitive contractions in wild‐type and W/Wv detrusor strips. Atropine reduced wild‐type responses by 50% whereas a 25% reduction occurred in W/Wv strips. The atropine‐insensitive component was blocked by pyridoxal‐5‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid in both tissue types. Wild‐type and W/Wv detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine‐sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild‐type tissues but not in W/Wv preparations. The atropine‐insensitive component was abolished by pyridoxal‐5‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid in both preparations.Conclusions and implications:  Bladders from W/Wv mice contain c‐Kit‐ and vimentin‐immunopositive ICC. There are similarities in the electrical and contractile properties of W/Wv and wild‐type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up‐regulation of the purinergic component. These findings indicate that the W/Wv strain may not be the best model to study ICC function in the bladder.
Selective desensitization of the 5‐HT4receptor‐mediated response in pig atrium but not in stomach
Authors: De Maeyer JH , Schuurkes JAJ , Lefebvre RA 
Published: January 2009

Background and purpose: The time dependency of the effect of 5‐HT4receptor agonists depends on many specific regulatory mechanisms, which vary between tissues. This has important implications with regard to the effects of endogenous 5‐HT, as well as to the clinical use of 5‐HT4receptor agonists, and might contribute to tissue selectivity of agonists.Experimental approach: The progression and desensitization of 5‐HT4receptor‐mediated responses were evaluated in an organ bath set‐up using two, clinically relevant, porcinein vitromodels: gastric cholinergic neurotransmission and atrial contractility.Key results: Exposure of gastric tissue to 5‐HT or to the selective 5‐HT4receptor agonists prucalopride and M0003 results in a sustained non‐transient effect during exposure; after washout, the response to a subsequent challenge with 5‐HT shows no clear desensitization. Incubation of left atrial tissue with 5‐HT resulted in a transient response, leading after washout to a marked desensitization of the subsequent response to 5‐HT. The selective 5‐HT4receptor agonists prucalopride and M0003 induce only very weak atrial responses whereas they are very effective in desensitizing the atrial response to 5‐HT. The observations also suggest that the properties of prucalopride and M0003 to bind to and/or activate the 5‐HT4receptor differ from those of 5‐HT. This difference might have contributed to the observed desensitization.Conclusions and implications: The high potency of prucalopride and M0003 in desensitizing the response to 5‐HT together with their low efficacy in the atrium emphasizes the cardiac safety of this class of 5‐HT4receptor agonists.
Inhibitory actions of the phosphatidylinositol 3‐kinase inhibitor LY294002 on the human Kv1.5 channel
Authors: Wu J , Ding W‐G , Matsuura H , Tsuji K , Zang W‐J , Horie M 
Published: January 2009

Background and purpose: Kv1.5 channels conduct the ultra‐rapid delayed rectifier potassium current (IKur), and in humans, Kv1.5 channels are highly expressed in cardiac atria but are scarce in ventricles. Pharmacological blockade of human Kv1.5 (hKv1.5) has been regarded as effective for prevention and treatment of re‐entry‐based atrial tachyarrhythmias. Here we examined blockade of hKv1.5 channels by LY294002, a well‐known inhibitor of phosphatidylinositol 3‐kinase (PI3K).Experimental approach: hKv1.5 channels were heterologously expressed in Chinese hamster ovary cells. Effects of LY294002 on wild‐type and mutant (T462C, H463C, T480A, R487V, A501V, I502A, I508A, L510A and V516A) hKv1.5 channels were examined by using the whole‐cell patch‐clamp method.Key results: LY294002 rapidly and reversibly inhibited hKv1.5 current in a concentration‐dependent manner (IC50of 7.9 µmol·L−1). In contrast, wortmannin, a structurally distinct inhibitor of PI3K, had little inhibitory effect on hKv1.5 current. LY294002 block of hKv1.5 current developed with time during depolarizing voltage‐clamp steps, and this blockade was also voltage‐dependent with a steep increase over the voltage range for channel openings. The apparent binding (k+1) and unbinding (k−1) rate constants were calculated to be 1.6 µmol·L−1−1·s−1and 5.7 s−1respectively. Inhibition by LY294002 was significantly reduced in several hKv1.5 mutant channels: T480A, R487V, I502A, I508A, L510A and V516A.Conclusions and implications: LY294002 acts directly on hKv1.5 currents as an open channel blocker, independently of its effects on PI3K activity. Amino acid residues located in the pore region (Thr480, Arg487) and the S6 segment (Ile502, Ile508, Leu510, Val516) appear to constitute potential binding sites for LY294002.
Roflumilast, a phosphodiesterase 4 inhibitor, alleviates bleomycin‐induced lung injury
Authors: Cortijo J , Iranzo A , Milara X , Mata M , Cerdá‐Nicolás M , Ruiz‐Saurí A , Tenor H , Hatzelmann A , Morcillo EJ 
Published: January 2009

Mandarin translation of abstractBackground and purpose: The effects of a phosphodiesterase 4 (PDE4) inhibitor, roflumilast, on bleomycin‐induced lung injury were explored in ‘preventive’ and ‘therapeutic’ protocols and compared with glucocorticoids.Experimental approach: Roflumilast (1 and 5 mg·kg−1·d−1, p.o.) or dexamethasone (2.5 mg·kg−1·d−1, p.o.) was given to C57Bl/6J mice from day 1 to 14 (preventive) or day 7 to 21 (therapeutic) after intratracheal bleomycin (3.75 U·kg−1). In Wistar rats, roflumilast (1 mg·kg−1·d−1, p.o.) was compared with methylprednisolone (10 mg·kg−1·d−1, p.o.) from day 1 to 21 (preventive) or from day 10 to 21 (therapeutic), following intratracheal instillation of bleomycin (7.5 U·kg−1). Analyses were performed at the end of the treatment periods.Key results: Preventive. Roflumilast reduced bleomycin‐induced lung hydroxyproline, lung fibrosis and right ventricular hypertrophy; muscularization of intraacinar pulmonary vessels was also attenuated. The PDE4 inhibitor diminished bleomycin‐induced transcripts for tumour necrosis factor (TNFα), transforming growth factor (TGFβ), connective tissue growth factor, αI(I)collagen, endothelin‐1 and the mucin, Muc5ac, in lung, and reduced bronchoalveolar lavage fluid levels of TNFα, interleukin‐13, TGFβ, Muc5ac, lipid hydroperoxides and inflammatory cell counts.Therapeutic. In mice, roflumilast but not dexamethasone reduced bleomycin‐induced lung αI(I)collagen transcripts, fibrosis and right ventricular hypertrophy. Similar results were found in the rat.Conclusions and implications: Roflumilast prevented the development of bleomycin‐induced lung injury, and alleviated the lung fibrotic and vascular remodeling response to bleomycin in atherapeuticprotocol, the latter being resistant to glucocorticoids.Mandarin translation of abstract
Complex adrenergic and inflammatory mechanisms contribute to phase 2 ventricular arrhythmias in anaesthetized rats
Authors: Clements‐Jewery Hugh , Andrag Ellen , Hearse David J , Curtis Michael J 
Published: January 2009

Mandarin translation of abstractBackground and purpose: The mechanisms responsible for phase 2 (infarct‐related) ventricular arrhythmias remain unclear. We have investigated the role of α1and β1adrenoceptor activation and the interaction of this with infarct neutrophil accumulation, in anaesthetized rats.Experimental approach: Neutrophil‐replete Sprague‐Dawley rats (n = 8–9 per group) were anaesthetized and randomized to receive vehicle, prazosin (0.5 mg·kg−1i.v.), atenolol (4 mg·kg−1i.v.) or their combination prior to left main coronary artery occlusion. A further group was depleted of neutrophils and received both atenolol and prazosin. Coronary ligation in all groups was maintained for 240 min.Key results: Atenolol and prazosin treatment lowered heart rates and blood pressures respectively, but neither agent given alone affected the incidence of phase 2 ventricular tachycardia or fibrillation. However, co‐administration of atenolol with prazosin reduced phase 2 ventricular premature beats (log10‐transformed totals were 1.25 ± 0.26 vs. 2.43 ± 0.18 in controls;P < 0.05). Neutrophil depletion attenuated this antiarrhythmic effect (log10‐transformed total ventricular premature beats were 1.66 ± 0.35;P > 0.05 vs. controls).Conclusions and implications: Phase 2 arrhythmias appear to depend in part on a complex interaction between catecholamines and neutrophils. A model of this interaction is proposed.Mandarin translation of abstract
Relative contribution of ecto‐ATPase and ecto‐ATPDase pathways to the biphasic effect of ATP on acetylcholine release from myenteric motoneurons
Authors: Duarte‐Araújo M , Nascimento C , Timóteo MA , Magalhães‐Cardoso MT , Correia‐de‐Sá P 
Published: January 2009

Mandarin translation of abstractBackground and purpose: The relative contribution of distinct ecto‐nucleotidases to the modulation of purinergic signalling may depend on differential tissue distribution and substrate preference.Experimental approach: Extracellular ATP catabolism (assessed by high‐performance liquid chromatography) and its influence on [3H]acetylcholine ([3H]ACh) release were investigated in the myenteric plexus of rat ileumin vitro.Key results: ATP was primarily metabolized via ecto‐ATPDase (adenosine 5′‐triphosphate diphosphohydrolase) into AMP, which was then dephosphorylated into adenosine by ecto‐5′‐nucleotidase. Alternative conversion of ATP into ADP by ecto‐ATPase (adenosine 5′‐triphosphatase) was more relevant at high ATP concentrations. ATP transiently increased basal [3H]ACh outflow in a 2′,3′‐O‐(2,4,6‐trinitrophenyl)adenosine‐5′‐triphosphate (TNP‐ATP)‐dependent, tetrodotoxin‐independent manner. ATP and ATPγS (adenosine 5′‐[γ‐thio]triphosphate), but not α,β‐methyleneATP, decreased [3H]ACh release induced by electrical stimulation. ADP and ADPβS (adenosine 5′[β‐thio]diphosphate) only decreased evoked [3H]ACh release. Inhibition by ADPβS was prevented by MRS 2179 (2′‐deoxy‐N6‐methyl adenosine 3′,5′‐diphosphate diammonium salt, a selective P2Y1antagonist); blockade of ADP inhibition required co‐application of MRS 2179 plus adenosine deaminase (which inactivates endogenous adenosine). Blockade of adenosine A1receptors with 1,3‐dipropyl‐8‐cyclopentyl xanthine enhanced ADPβS inhibition, indicating that P2Y1stimulation is cut short by tonic adenosine A1receptor activation. MRS 2179 facilitated evoked [3H]ACh release, an effect reversed by the ecto‐ATPase inhibitor, ARL67156, which delayed ATP conversion into ADP without affecting adenosine levels.Conclusions and implications: ATP transiently facilitated [3H]ACh release from non‐stimulated nerve terminals via prejunctional P2X (probably P2X2) receptors. Hydrolysis of ATP directly into AMP by ecto‐ATPDase and subsequent formation of adenosine by ecto‐5′‐nucleotidase reduced [3H]ACh release via inhibitory adenosine A1receptors. Stimulation of inhibitory P2Y1receptors by ADP generated alternatively via ecto‐ATPase might be relevant in restraining ACh exocytosis when ATP saturates ecto‐ATPDase activity.Mandarin translation of abstract
Eicosapentaenoic acid inhibits voltage‐gated sodium channels and invasiveness in prostate cancer cells
Authors: Nakajima T , Kubota N , Tsutsumi T , Oguri A , Imuta H , Jo T , Oonuma H , Soma M , Meguro K , Takano H , Nagase T , Nagata T 
Published: January 2009

Mandarin translation of abstractBackground and purpose:  The voltage‐gated Na+ channels (Nav) and their corresponding current (INa) are involved in several cellular processes, crucial to metastasis of cancer cells. We investigated the effects of eicosapentaenoic (EPA), an omega‐3 polyunsaturated fatty acid, on INa and metastatic functions (cell proliferation, endocytosis and invasion) in human and rat prostate cancer cell lines (PC‐3 and Mat‐LyLu cells).Experimental approach:  The whole‐cell voltage clamp technique and conventional/quantitative real‐time reverse transcriptase polymerase chain reaction analysis were used. The presence of Nav proteins was shown by immunohistochemical methods. Alterations in the fatty acid composition of phospholipids after treatment with EPA and metastatic functions were also examined.Key results:  A transient inward Na+ current (INa), highly sensitive to tetrodotoxin, and NaV proteins were found in these cells. Expression of NaV1.6 and NaV1.7 transcripts (SCN8A and SCN9A) was predominant in PC‐3 cells, while NaV1.7 transcript (SCN9A) was the major component in Mat‐LyLu cells. Tetrodotoxin or synthetic small interfering RNA targeted for SCN8A and SCN9A inhibited metastatic functions (endocytosis and invasion), but failed to inhibit proliferation in PC‐3 cells. Exposure to EPA produced a rapid and concentration‐dependent suppression of INa. In cells chronically treated (up to 72h) with EPA, the EPA content of cell lipids increased time‐dependently, while arachidonic acid content decreased. Treatment of PC‐3 cells with EPA decreased levels of mRNA for SCN9A and SCN8A, cell proliferation, invasion and endocytosis.Conclusion and implications:  Treatment with EPA inhibited INa directly and also indirectly, by down‐regulation of Nav mRNA expression in prostate cancer cells, thus inhibiting their metastatic potential. Mandarin translation of abstract