bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tree hollows are of conservation importance for a Near‐Threatened python species
Authors: Bryant G. L. , Dundas S. J. , Fleming P. A. 
Published: September 2011

AbstractUnderstanding microhabitat requirements for species vulnerable to anthropogenic threats can provide important information to conservation managers. This may be particularly true for ectotherms, where behaviour and physiology (e.g. digestion, responsiveness and activity patterns) are strongly influenced by thermal conditions of microhabitat retreat sites. Retreat sites selected by south‐west carpet pythons (Morelia spilota imbricata) were identified through radiotracking 46 pythons over 3 years. Tree hollows appear to be a very important resource for pythons: 61% (22 of 36 individuals tracked over winter) used tree hollows as retreat sites (56% of all observations in winter), and remained in hollows for an average of 124 ± 49 (range 34 to 210) days. If pythons did not use tree hollows over winter, they found refuge in one of four alternative microhabitats: low vegetation cover (26% of winter observations), ground cover (10%), on tree branches (6%) or in hollow logs on the ground (2%). We tested whether tree hollows provide a thermally distinct environment compared with alternative microhabitats, but found no difference in minimum, average, maximum or range of temperatures recorded between microhabitats. When within tree hollows over winter, pythons had colder daily average and maximum body temperatures (cf. pythons that used other microhabitats), but this did not give them an energy saving (in terms of body condition scores). Pythons ate very little over winter and we predict that animals sequestered within tree hollows do not access prey at this time. Tree hollows provide a critical refuge over winter when python body temperature is low, and their responsiveness is limited, rendering individuals vulnerable to predation by terrestrial predators (e.g. introduced red fox). Destruction of hollows through fire, land clearing, competition with other fauna species and the significant age required for hollows to form in trees all contribute to the decline in availability of this important microhabitat.
Phylogeography and cryptic diversity of the solitary‐dwelling silvery mole‐rat, genus Heliophobius (family: Bathyergidae)
Authors: Faulkes C. G. , Bennett N. C. , Cotterill F. P. D. , Stanley W. , Mgode G. F. , Verheyen E. 
Published: September 2011

AbstractAlongside the eusocial naked mole‐rat, Heterocephalus glaber, Heliophobius argenteocinereus represents the second oldest lineage within the African mole‐rat family Bathyergidae, and phylogenetically intermediate between the East African Het. glaber and the South African genera Bathyergus and Georychus. Across its geographic range, Hel.. argenteocinereus is widely distributed on both sides of the East African Rift System (EARS), and is a key taxon for understanding the phylogeographic patterns of divergence of the family as a whole. Phylogenetic analysis of 62 mitochondrial cyt b sequences, representing 48 distinct haplotypes from 26 geographic locations across the range of Heliophobius, consistently and robustly resolved six genetically divergent clades that we recognize as distinct evolutionary species. Early species descriptions of Heliophobius were synonymized into a monotypic taxonomy that recognized only Hel. argentocinereus. These synonyms constitute available names for these rediscovered cryptic lineages, for which combined morphological and genetic evidence for topotypical populations endorses the recognition of six to eight distinct taxa. Bayesian estimates of divergence times using the fossil Proheliophobius as a calibration for the molecular clock suggest that the adaptive radiation of the genus began in the early Miocene, and that cladogenesis, represented in the extant species, reflects a strident signature of tectonic activity that forged the principal graben in the EARS.
Nonrandom spatial structuring of orchids in a hybrid zone of three Orchis species
Authors: Jacquemyn Hans , Brys Rein , Honnay Olivier , Roldán‐Ruiz Isabel , Lievens Bart , Wiegand Thorsten 
Published: September 2011

Summary
Nonrandom  species–species associations may arise from a range of factors, including localized dispersal, intra‐ and interspecific interactions and heterogeneous environmental conditions. Because seed germination and establishment in orchids are critically dependent upon the availability of suitable mycorrhizal fungi, species–species associations in orchids may reflect associations with mycorrhizal fungi.
To test this hypothesis, we examined spatial association patterns, mycorrhizal associations and germination success in a hybrid zone containing three species of the genus Orchis (Orchis anthropophora, Orchis militaris and Orchis purpurea).
Hybridization occurred predominantly between O. purpurea and O. militaris. The spatial distribution patterns of most pure species and hybrids were independent from each other, except that of O. purpurea and its hybrids. The fungal community composition of established individuals differed significantly between pure species, but not between hybrids and O. purpurea. Seed germination experiments using pure seeds showed that the highest number of protocorms were found in regions where adult individuals were most abundant. In the case of hybrid seeds, germination was restricted to areas where the mother plant was most abundant.
Overall, these results suggest that the observed nonrandom spatial distribution of both pure and hybrid plants is dependent on the contingencies of the spatial distribution of suitable mycorrhizal fungi.
Landscape‐scale effects of fire on bird assemblages: does pyrodiversity beget biodiversity?
Authors: Taylor Rick S. , Watson Simon J. , Nimmo Dale G. , Kelly Luke T. , Bennett Andrew F. , Clarke Michael F. 
Published: September 2011

AbstractAim A common strategy for conserving biodiversity in fire‐prone environments is to maintain a diversity of post‐fire age classes at the landscape scale, under the assumption that ‘pyrodiversity begets biodiversity’. Another strategy is to maintain extensive areas of a particular seral state regarded as vital for the persistence of threatened species, under the assumption that this will also cater for the habitat needs of other species. We investigated the likely effects of these strategies on bird assemblages in tree mallee vegetation, characterized by multi‐stemmedEucalyptusspecies, where both strategies are currently employed.Location The semi‐arid Murray Mallee region of south‐eastern Australia.Methods We systematically surveyed birds in 26 landscapes (each 4‐km diameter), selected to represent gradients in the diversity of fire age classes and the proportion of older vegetation (> 35 years since fire). Additional variables were measured to represent underlying vegetation‐ or fire‐mediated properties of the landscape, as well as its biogeographic context. We used an information‐theoretic approach to investigate the relationships between these predictor variables and the species richness of birds (total species, threatened species and rare species).Results Species richness of birds was not strongly associated with fire‐mediated heterogeneity. Species richness was associated with increasing amounts of older vegetation in landscapes, but not with the proportion of recently burned vegetation in landscapes.Main conclusions The preference of many mallee birds for older vegetation highlights the risk of a blanket application of the ‘pyrodiversity begets biodiversity’ paradigm. If application of this paradigm involved converting large areas from long unburned to recently burned vegetation to increase fire‐mediated heterogeneity in tree mallee landscapes, our findings suggest that this could threaten birds. This research highlights the value of adopting a landscape‐scale perspective when evaluating the utility of fire‐management strategies intended to benefit biodiversity.
Effects of P2Y1 receptor antagonism on the reactivity of platelets from patients with stable coronary artery disease using aspirin and clopidogrel
Authors: Labarthe B , Babin J , Bryckaert M , Théroux P , Bonnefoy A 
Published: September 2011

BACKGROUND AND PURPOSE P2Y1 is a purine receptor that triggers platelet aggregation. Its inhibition was studied in patients with stable coronary artery disease (CAD) receiving standard anti‐platelet therapy.EXPERIMENTAL APPROACH Blood samples from 10 patients on aspirin therapy (ASA, 80 mg·day−1) were withdrawn before and 24 h after the administration of 450 mg clopidogrel (ASA/C) and were anti‐coagulated with citrate or hirudin/PPACK in the presence or absence of the P2Y1 inhibitor MRS2179 (M, 100 µM). Platelet responses to ADP (2.5 µM) and TRAP (2.5 µM), and collagen‐induced thrombosis under flow conditions were analysed.KEY RESULTS Compared with ASA, ASA + M strongly inhibited ADP‐induced peak platelet aggregation (88%), late aggregation (84%), P‐selectin expression (85%) and αIIbβ3 activation (62%) (28%, 65%, 70% and 51% inhibition, respectively, for ASA/C vs. ASA). ASA + M also inhibited platelet/monocyte and platelet/neutrophil conjugate formation by 69% and 71% (57% and 59% for ASA/C vs. ASA). In TRAP‐activated blood, ASA + M unexpectedly inhibited αIIbb3 activation by 30%. In blood perfused in collagen‐coated glass capillaries (shear rate of 1500 s−1), ASA/C prevented thrombus growth beyond 5 min in relation to thrombus fragments embolization. ASA + M with or without clopidogrel completely prevented thrombus formation. Finally, ex vivo addition of MRS2179 and ASA to the blood of healthy donors markedly blocked thrombus formation on collagen in flow conditions, in contrast to ASA plus the P2Y12 inhibitor 2‐MeSAMP.CONCLUSIONS AND IMPLICATIONS Through particularly efficient complementarities with ASA to inhibit platelet activation and thrombus formation, the inhibition of P2Y1 in the blood of patients with CAD appears to play a more important role than previously anticipated.
High potency inhibition of hERG potassium channels by the sodium–calcium exchange inhibitor KB‐R7943
Authors: Cheng Hongwei , Zhang Yihong , Du Chunyun , Dempsey Christopher E , Hancox Jules C 
Published: September 2011

BACKGROUND AND PURPOSE KB‐R7943 is an isothiourea derivative that is used widely as a pharmacological inhibitor of sodium–calcium exchange (NCX) in experiments on cardiac and other tissue types. This study investigated KB‐R7943 inhibition of hERG (human ether‐à‐go‐go‐related gene) K+ channels that underpin the cardiac rapid delayed rectifier potassium current, IKr.EXPERIMENTAL APPROACH Whole‐cell patch‐clamp measurements were made of hERG current (IhERG) carried by wild‐type or mutant hERG channels and of native rabbit ventricular IKr. Docking simulations utilized a hERG homology model built on a MthK‐based template.KEY RESULTS KB‐R7943 inhibited both IhERG and native IKr rapidly on membrane depolarization with IC50 values of ∼89 and ∼120 nM, respectively, for current tails at −40 mV following depolarizing voltage commands to +20 mV. Marked IhERG inhibition also occurred under ventricular action potential voltage clamp. IhERG inhibition by KB‐R7943 exhibited both time‐ and voltage‐dependence but showed no preference for inactivated over activated channels. Results of alanine mutagenesis and docking simulations indicate that KB‐R7943 can bind to a pocket formed of the side chains of aromatic residues Y652 and F656, with the compound's nitrobenzyl group orientated towards the cytoplasmic side of the channel pore. The structurally related NCX inhibitor SN‐6 also inhibited IhERG, but with a markedly reduced potency.CONCLUSIONS AND IMPLICATIONS KB‐R7943 inhibits IhERG/IKr with a potency that exceeds that reported previously for acute cardiac NCX inhibition. Our results also support the feasibility of benzyloxyphenyl‐containing NCX inhibitors with reduced potential, in comparison with KB‐R7943, to inhibit hERG.
The metabolism and pharmacokinetics of phospho‐sulindac (OXT‐328) and the effect of difluoromethylornithine
Authors: Xie G , Nie T , Mackenzie GG , Sun Y , Huang L , Ouyang N , Alston N , Zhu C , Murray OT , Constantinides PP , Kopelovich L , Rigas B 
Published: September 2011

BACKGROUND AND PURPOSE Phospho‐sulindac (PS; OXT‐328) prevents colon cancer in mice, especially when combined with difluoromethylornithine (DFMO). Here, we explored its metabolism and pharmacokinetics.EXPERIMENTAL APPROACH PS metabolism was studied in cultured cells, liver microsomes and cytosol, intestinal microsomes and in mice. Pharmacokinetics and biodistribution of PS were studied in mice.KEY RESULTS PS undergoes reduction and oxidation yielding PS sulphide and PS sulphone; is hydrolysed releasing sulindac, which generates sulindac sulphide (SSide) and sulindac sulphone (SSone), all of which are glucuronidated. Liver and intestinal microsomes metabolized PS extensively but cultured cells converted only 10% of it to PS sulphide and PS sulphone. In mice, oral PS is rapidly absorbed, metabolized and distributed to the blood and other tissues. PS survives only partially intact in blood; of its three major metabolites (sulindac, SSide and SSone), sulindac has the highest Cmax and SSone the highest t1/2; their AUC0–24h are similar. Compared with conventional sulindac, PS generated more SSone but less SSide, which may contribute to the safety of PS. In the gastroduodenal wall of mice, 71% of PS was intact; sulindac, SSide and SSone together accounted for <30% of the total. This finding may explain the lack of gastrointestinal toxicity by PS. DFMO had no effect on PS metabolism but significantly reduced drug level in mouse plasma and other tissues.CONCLUSIONS AND IMPLICATIONS Our findings establish the metabolism of PS define its pharmacokinetics and biodistribution, describe its interactions with DFMO and largely explain its gastrointestinal safety.
Molecular pharmacological profile of a novel thiazolinone‐based direct and selective 5‐lipoxygenase inhibitor
Authors: Hofmann B , Rödl CB , Kahnt AS , Maier TJ , Michel AA , Hoffmann M , Rau O , Awwad K , Pellowska M , Wurglics M , Wacker M , Živković A , Fleming I , Schubert‐Zsilavecz M , Stark H , Schneider G , Steinhilber D 
Published: September 2011

BACKGROUND AND PURPOSE The potency of many 5‐lipoxygenase (5‐LOX) inhibitors depends on the cellular peroxide tone and the mechanism of 5‐LOX enzyme activation. Therefore, new inhibitors that act regardless of the mode of enzyme activation need to be developed. Recently, we identified a novel class of thiazolinone‐based compounds as potent 5‐LOX inhibitors. Here, we present the molecular pharmacological profile of (Z)‐5‐(4‐methoxybenzylidene)‐2‐(p‐tolyl)‐5H‐thiazol‐4‐one, compound C06.EXPERIMENTAL APPROACH Inhibition of 5‐LOX product formation was determined in intact cells [polymorphonuclear leukocytes (PMNL), rat basophilic leukaemia‐1, RAW264.7] and in cell‐free assays [homogenates, 100 000×g supernatant (S100), partially purified 5‐LOX] applying different stimuli for 5‐LOX activation. Inhibition of peroxisome proliferator‐activated receptor (PPAR), cytosolic phospholipase A2 (cPLA2), 12‐LOX, 15‐LOX‐1 and 15‐LOX‐2 as well as cyclooxygenase‐2 (COX‐2) were measured in vitro.KEY RESULTS C06 induced non‐cytotoxic, direct 5‐LOX inhibition with IC50 values about 0.66 µM (intact PMNL, PMNL homogenates) and approximately 0.3 µM (cell‐free PMNL S100, partially purified 5‐LOX). Action of C06 was independent of the stimulus used for 5‐LOX activation and cellular redox tone and was selective for 5‐LOX compared with other arachidonic acid binding proteins (PPAR, cPLA2, 12‐LOX, 15‐LOX‐1, 15‐LOX‐2, COX‐2). Experimental results suggest an allosteric binding distinct from the active site and the C2‐like domain of 5‐LOX.CONCLUSIONS AND IMPLICATIONS C06 was identified as a potent selective direct 5‐LOX inhibitor exhibiting a novel and unique mode of action, different from other established 5‐LOX inhibitors. This thiazolinone may possess potential for intervention with inflammatory and allergic diseases and certain types of cancer.
Preexisting Mitral Valve Prosthesis in Patients Undergoing Left Ventricular Assist Device Implantation
Authors: Schweiger Martin , Stepanenko Alexander , Vierecke Juliane , Drews Thorsten , Potapov Evgenij , Hetzer Roland , Krabatsch Thomas 
Published: September 2011

AbstractExperience with patients undergoing left ventricular assist device (LVAD) implantation with preexisting mitral valve prostheses is limited. Patients with mechanical heart valves might have an increased risk of thromboembolism; in patients with biologic valves, there might be a risk of structural deterioration of the leaflets. Out of 597 patients supported with a LVAD system between 2000 and 2009, 18 patients had mitral valve surgery prior to implantation. We excluded all patients below 18 years of age, those with postcardiotomy failure, and patients who had had mitral valve reconstruction. Only 1% of the studied patient population (n= 6) had mitral valve replacement. The mitral valve implantation has been performed 7.4 ± 9.4 years prior to LVAD insertion. None of the valves (one biologic, five mechanical) were exchanged or explanted. LVAD implantation was done either with left lateral thoracotomy (n= 5) or with midline resternotomy (n= 1). Temporary right ventricular assist device support was necessary in one case (16.6%); 30‐day mortality was 16.6% (n= 1). Median support time was 14 ± 15 months. Two patients received heart transplantation after 6 and 26 months on the device; four patients died on mechanical circulatory support after 1, 2, 5, and 40 months. No valve or pump thrombosis or other clinically relevant thromboembolic events were observed. Only a small number of patients (1%) had a preexisting mitral valve prosthesis prior to LVAD implantation. No severe adverse events were observed when the prosthesis was left in place. Attention should be paid to the anticoagulation regime.
A Double‐Blind, Placebo‐Controlled Trial to Assess the Efficacy of Quetiapine Fumarate XR in Very Heavy‐Drinking Alcohol‐Dependent Patients
Authors: Litten Raye Z. , Fertig Joanne B. , Falk Daniel E. , Ryan Megan L. , Mattson Margaret E. , Collins Joseph F. , Murtaugh Cristin , Ciraulo Domenic , Green Alan I. , Johnson Bankole , Pettinati Helen , Swift Robert , Afshar Maryam , Brunette Mary F. , Tiouririne Nassima A.‐D. , Kampman Kyle , Stout Robert ,   the NCIG 001 Study Group
Published: September 2011

Background:  Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol‐dependent population of very heavy drinkers.
Methods:  In this double‐blind, placebo‐controlled trial, 224 alcohol‐dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization.
Results:  No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy‐drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%).
Conclusions:  This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy‐drinking alcohol‐dependent patients.
Predictors of Duloxetine versus Other Treatments among Veterans with Diabetic Peripheral Neuropathic Pain: A Retrospective Study
Authors: Zhao Yingnan , Liu Jinan , Zhao Yang , Thethi Tina , Fonseca Vivian , Shi Lizheng 
Published: September 2011

AbstractObjective:  This study used medical and pharmacy records from the Veterans Affairs (VA) health system to explore the predictors of duloxetine versus other treatments for patients with diabetic peripheral neuropathic pain (DPNP).Methods:  The electronic medical and pharmacy records from January 2004 to December 2008 were requested from the Veterans Integrated Service Network 16 data warehouse. All select patients received either duloxetine or other treatments [tricyclic antidepressants (TCAs), venlafaxine, gabapentin, and pregabalin] over the study period, with the first dispense date of the index agent as the index date. All patients must have 1+ prior DPNP diagnosis (ICD‐9‐CM: 250.6x or 357.2), but no diagnoses of prior depression (ICD‐9‐CM: 296.2, 296.3, 300.4, 309.1, or 311.0), fibromyalgia (ICD‐9‐CM: 729.1), or neuralgia (ICD‐9‐CM: 729.2). Logistic regression was used to examine the predictors of receiving duloxetine versus other treatments, controlling for demographics, comorbidities, prior pain level, prior use of other medications, and opioid use.Results:  The analytical sample included 2,694 patients (duloxetine cohort, n = 216; other‐treatment cohort, n = 2,478). Prior uses of gabapentin (odds ratio [OR] = 13.66, 95% confidence interval [CI]: 9.70–19.24), TCAs (OR = 5.40, 95% CI: 3.73–7.82), or venlafaxine (OR = 3.67, 95% CI: 1.67–8.06) were strong predictors of duloxetine. Other comorbidities associated with duloxetine were anxiety (OR = 2.08, 95% CI: 1.40–3.08), cerebrovascular disease (OR = 1.44, 95% CI: 1.01–2.07), and substance abuse (OR = 2.11, 95% CI: 1.10–4.03). Prior opioid users were 1.47 (95% CI: 1.02–2.12) times as likely to receive duloxetine as those without prior opioid use. Patients with self‐reported severe pain were 1.66 (95% CI: 1.11–2.50) times as likely to receive duloxetine as those with no pain reported.Conclusion:  DPNP patients in the VA healthcare system with prior other treatment use, select comorbid conditions, prior substance abuse, prior opioid use, and higher pain level were more likely to receive duloxetine.
Variant screening of the RHD gene in a large cohort of subjects with D phenotype ambiguity: report of 17 novel rare alleles
Authors: Fichou Yann , Le Maréchal Cédric , Bryckaert Laurence , Guerry Christine , Bénech Caroline , Dupont Isabelle , Jamet Déborah , Férec Claude , Chen Jian‐Min 
Published: September 2011

BACKGROUND: A considerable number of RHD alleles responsible for weak and partial D phenotypes have been identified over the past decade. Two particular concerns, namely, 1) that red blood cells of these phenotypes may cause anti‐D immunization when transfused to D– recipients and 2) that serologic determination of these phenotypes is often doubtful, make genetic analysis of the RHD gene highly desirable.STUDY DESIGN AND METHODS: Blood samples that displayed D phenotype ambiguity (as determined by serologic analyses) were collected from several sites of the Etablissement Français du Sang and subjected to RHD variant screening by means of a previously established denaturing high‐performance liquid chromatography method followed by direct sequencing.RESULTS: Systematic screening of the RHD coding sequences as well as the exon‐intron boundaries identified DNA variants in 755 of the 806 samples analyzed. In particular, this resulted in the identification of 10 novel single‐nucleotide substitutions and seven novel complex alleles.CONCLUSION: This study further increased the already large repertoire of RHD allelic variants. Whereas most of the newly found variants are putative weak or partial D alleles, most of the complex alleles are readily understandable in the present phylogenetic model of RHD.