bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vesicular glutamate transporter 2 is required for the respiratory and parasympathetic activation produced by optogenetic stimulation of catecholaminergic neurons in the rostral ventrolateral medulla of mice in vivo
Authors: Abbott Stephen B. G. , Holloway Benjamin B. , Viar Kenneth E. , Guyenet Patrice G. 
Published: November 2013

AbstractCatecholaminergic neurons of the rostral ventrolateral medulla (RVLM‐CA neurons; C1 neurons) contribute to the sympathetic, parasympathetic and neuroendocrine responses elicited by physical stressors such as hypotension, hypoxia, hypoglycemia, and infection. Most RVLM‐CA neurons express vesicular glutamate transporter (VGLUT)2, and may use glutamate as a ionotropic transmitter, but the importance of this mode of transmission in vivo is uncertain. To address this question, we genetically deleted VGLUT2 from dopamine‐β‐hydroxylase‐expressing neurons in mice [DβHCre/0;VGLUT2flox/flox mice (cKO mice)]. We compared the in vivo effects of selectively stimulating RVLM‐CA neurons in cKO vs. control mice (DβHCre/0), using channelrhodopsin‐2 (ChR2–mCherry) optogenetics. ChR2–mCherry was expressed by similar numbers of rostral ventrolateral medulla (RVLM) neurons in each strain (~400 neurons), with identical selectivity for catecholaminergic neurons (90–99% colocalisation with tyrosine hydroxylase). RVLM‐CA neurons had similar morphology and axonal projections in DβHCre/0 and cKO mice. Under urethane anesthesia, photostimulation produced a similar pattern of activation of presumptive ChR2‐positive RVLM‐CA neurons in DβHCre/0 and cKO mice. Photostimulation in conscious mice produced frequency‐dependent respiratory activation in DβHCre/0 mice but no effect in cKO mice. Similarly, photostimulation under urethane anesthesia strongly activated efferent vagal nerve activity in DβHCre/0 mice only. Vagal responses were unaffected by α1‐adrenoreceptor blockade. In conclusion, two responses evoked by RVLM‐CA neuron stimulation in vivo require the expression of VGLUT2 by these neurons, suggesting that the acute autonomic responses driven by RVLM‐CA neurons are mediated by glutamate.
Related flavonoids cause cooperative inhibition of the sarcoplasmic reticulum Ca2+ ATPase by multimode mechanisms
Authors: Ogunbayo Oluseye A. , Michelangeli Francesco 
Published: November 2013

Flavonoids are group of plant‐derived hydroxylated polycyclic molecules found in fruit and vegetables. They are known to bio‐accumulate within humans and are considered to have beneficial health effects, including cancer chemoprotection. One mechanism proposed to explain this is that they are able to induce apoptosis in cancer cells by inhibiting a variety of kinases and also the Ca2+ ATPase. An investigation was undertaken with respect to the mechanism of inhibition for three flavonoids: quercetin, galangin and 3,6 dihydroxyflavone (3,6‐DHF). Each inhibited the Ca2+ ATPase with Ki values of 8.7, 10.3 and 5.4 μm, respectively, showing cooperative inhibition with n ~ 2. Given their similar structures, the flavonoids showed several differences in their mechanisms of inhibition. All three flavonoids stabilized the ATPase in the E1 conformation and reduced [32P]‐ATP binding. However, both galangin and 3,6‐DHF increased the affinity of Ca2+ for the ATPase by decreasing the Ca2+‐dissociation rate constant, whereas quercetin had little effect. Ca2+‐induced changes in tryptophan fluorescence levels were reduced in the presence of 3,6‐DHF and galangin (but not with quercetin), indicating that Ca2+‐associated changes within the transmembrane helices are altered. Both galangin and quercetin reduced the rates of ATP‐dependent phosphorylation and dephosphorylation, whereas 3,6‐DHF did not. Modelling studies suggest that flavonoids could potentially bind to two sites: one directly where nucleotides bind within ATP binding site and the other at a site close by. We hypothesize that interactions of these two neighbouring sites may account for both the cooperative inhibition and the multimode mechanisms of action seen with related flavonoids.
Foliar senescence is the most sensitive response to ozone in Bromus hordeaceus and is modulated by nitrogen input
Authors: Sanz J. , Calvete‐Sogo H. , González‐Fernández I. , Lin J. , García‐Gómez H. , Muntifering R. , Alonso R. , Bermejo‐Bermejo V. 
Published: November 2013

AbstractA study was conducted on the effect of tropospheric ozone (O3) on soft brome (Bromus hordeaceus) and the modulation of its response by nitrogen (N). Two assays were conducted using open‐top chambers (OTCs). Three O3 treatments were considered: filtered air, with concentrations below background levels (charcoal‐filtered air), non‐filtered air (NFA) that simulates ambient O3 concentrations, and unfiltered air to which 40 nL L−1 O3 above‐ambient concentrations was added (NFA+), simulating elevated values recorded in natural areas of annual pastures in the Iberian Peninsula. Three N rates were used, simulating the increase in soil N through atmospheric deposition and excreta from livestock grazing. Ozone caused an augmentation in foliar senescence, whereas green biomass was not altered; consequently, an increased senescent/green biomass ratio was produced. A stronger O3 effect was detected in the second assay compared with the first. This was related to the estimated absorbed O3 fluxes, which were double the value calculated in the former. Increasing N input enhanced biomass production, but its effectiveness was greater in the first assay, under less‐favourable weather conditions and lower plant growth. In the first assay, the O3 response was modulated by N availability, which mitigated the effects of O3 to medium concentration values. In the first assay, O3 reduced the aerial/subterranean biomass ratio, caused by a positive‐trend effect on roots. Foliar concentration of lignin was increased by O3, and in vitro digestibility of aerial biomass and the plant cell wall fraction tended to decrease with increasing O3.
Positive selection drives accelerated evolution of mosquito salivary genes associated with blood‐feeding
Authors: Arcà B. , Struchiner C. J. , Pham V. M. , Sferra G. , Lombardo F. , Pombi M. , Ribeiro J. M. C. 
Published: November 2013

AbstractThe saliva of bloodsucking animals contains dozens to hundreds of proteins that counteract their hosts’ haemostasis, inflammation and immunity. It was previously observed that salivary proteins involved in haematophagy are much more divergent in their primary sequence than those of housekeeping function, when comparisons were made between closely related organisms. While this pattern of evolution could result from relaxed selection or drift, it could alternatively be the result of positive selection driven by the intense pressure of the host immune system. We investigated the polymorphism of five different genes associated with blood‐feeding in the mosquito Anopheles gambiae and obtained evidence in four genes for sites with signatures of positive selection. These results add salivary gland genes from bloodsucking arthropods to the small list of genes driven by positive selection.
The concept of shared mental models in healthcare collaboration
Authors: McComb Sara , Simpson Vicki 
Published: November 2013

AbstractAimTo report an analysis of the concept of shared mental models in health care.BackgroundShared mental models have been described as facilitators of effective teamwork. The complexity and criticality of the current healthcare system requires shared mental models to enhance safe and effective patient/client care. Yet, the current concept definition in the healthcare literature is vague and, therefore, difficult to apply consistently in research and practice.DesignConcept analysis.Data sourcesLiterature for this concept analysis was retrieved from several databases, including CINAHL, PubMed and MEDLINE (EBSCO Interface), for the years 1997–2013.MethodsWalker and Avant's approach to concept analysis was employed and, following Paley's guidance, embedded in extant theory from the team literature.ResultsAlthough teamwork and collaboration are discussed frequently in healthcare literature, the concept of shared mental models in that context is not as commonly found but is increasing in appearance. Our concept analysis defines shared mental models as individually held knowledge structures that help team members function collaboratively in their environments and are comprised of the attributes of content, similarity, accuracy and dynamics.ConclusionThis theoretically grounded concept analysis provides a foundation for a middle‐range descriptive theory of shared mental models in nursing and health care. Further research concerning the impact of shared mental models in the healthcare setting can result in development and refinement of shared mental models to support effective teamwork and collaboration.
Co‐targeting the PI3K/mTOR and JAK2 signalling pathways produces synergistic activity against myeloproliferative neoplasms
Authors: Bartalucci Niccolò , Tozzi Lorenzo , Bogani Costanza , Martinelli Serena , Rotunno Giada , Villeval Jean‐Luc , Vannucchi Alessandro M. 
Published: November 2013

AbstractAberrant JAK2 signalling plays a central role in myeloproliferative neoplasms (MPN). JAK2 inhibitors have proven to be clinically efficacious, however, they are not mutation‐specific and competent enough to suppress neoplastic clonal haematopoiesis. We hypothesized that, by simultaneously targeting multiple activated signalling pathways, MPN could be more effectively treated. To this end we investigated the efficacy of BEZ235, a dual PI3K/mTOR inhibitor, alone and in combination with the JAK1/JAK2 inhibitor ruxolitinib, in different preclinical models of MPN. Single‐agent BEZ235 inhibited the proliferation and induced cell cycle arrest and apoptosis of mouse and human JAK2V617F mutated cell lines at concentrations significantly lower than those required to inhibit the wild‐type counterpart, and preferentially prevented colony formation from JAK2V617F knock‐in mice and patients' progenitor cells compared with normal ones. Co‐treatment of BEZ235 and ruxolitinib produced significant synergism in all these in‐vitro models. Co‐treatment was also more effective than single drugs in reducing the extent of disease and prolonging survival of immunodeficient mice injected with JAK2V617F‐mutated Ba/F3‐EPOR cells and in reducing spleen size, decreasing reticulocyte count and improving spleen histopathology in conditional JAK2V617F knock‐in mice. In conclusion, combined inhibition of PI3K/mTOR and JAK2 signalling may represent a novel therapeutic strategy in MPN.
Using Neural Data to Test a Theory of Investor Behavior: An Application to Realization Utility
Authors: FRYDMAN CARY , BARBERIS NICHOLAS , CAMERER COLIN , BOSSAERTS PETER , RANGEL ANTONIO 
Published: November 2013

ABSTRACTWe conduct a study in which subjects trade stocks in an experimental market while we measure their brain activity using functional magnetic resonance imaging. All of the subjects trade in a suboptimal way. We use the neural data to test a “realization utility” explanation for their behavior. We find that activity in two areas of the brain that are important for economic decision‐making exhibit activity consistent with the predictions of realization utility. These results provide support for the realization utility model. More generally, they demonstrate that neural data can be helpful in testing models of investor behavior.
Gastroprotective effects (in rodents) of a flavonoid rich fraction obtained from Syngonanthus macrolepsis
Authors: Batista Leônia Maria , de Almeida Ana Beatriz Albino , de Morais Lima Gedson Rodrigues , de Sousa Falcão Heloina , de Pietro Magri Luciana , Luiz-Ferreira Anderson , dos Santos Lourdes Campaner , Hiruma-Lima Clélia Akiko , Vilegas Wagner , Souza Brito Alba Regina Monteiro 
Published: November 2013

Abstract

Objectives
Syngonanthus macrolepis, popularly known in Brazil as ‘sempre-vivas’, is a plant from the family Eriocaulaceae, it is found in the states of Minas Gerais and Bahia. The species contains a variety of constituents, including flavonoids with gastroprotective effect. In this work, a flavonoid-rich fraction (Sm-FRF) obtained from scapes of S. macrolepis was investigated for preventing gastric ulceration in mice and rats.

Methods
The activity was evaluated in models of induced gastric ulcer (absolute ethanol, stress, non-steroidal anti-inflammatory drugs and pylorus ligation). The cytoprotective mechanisms of the Sm-FRF in relation to sulfhydryl (SH) groups, nitric oxide (NO) and antioxidant enzymes were also evaluated.

Key findings
The Sm-FRF (100 mg/kg, p.o.) significantly reduced gastric injury in all models, and did not alter gastric juice parameters after pylorus ligation.

Conclusions
The results indicate significant gastroprotective activity for the Sm-FRF, which probably involves the participation of both SH groups and the antioxidant system. Both are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors.
Effect of disease states on α1-adrenoceptor binding and signal transduction parameters in isolated perfused heart: quantification by pharmacokinetic-pharmacodynamic modelling
Authors: Weiss Michael , Arendt Petra , Hassna Rana 
Published: November 2013

Abstract

Objectives
To employ a pharmacokinetic-pharmacodynamic modelling approach for analysing the effect of experimental endotoxemia and mild hypoxia on α1-adrenoceptor (α1AR) binding and signal transduction.

Methods
In Langendorff-perfused rat hearts, phenylephrine was continuously infused, and [3H]-prazosin was injected as single dose (infused over 1 min). Simultaneous analysis of the time courses of prazosin outflow concentration and inotropic response (left ventricular developed pressure) using an agonist-antagonist interaction model and nonlinear regression allowed to estimate receptor affinity, as well as the parameters of the operational model of agonism.

Key findings
Both endotoxemia and hypoxia, significantly reduced the maximum response achievable in the system to 67% and 49% of the control group mean, respectively. In addition, endotoxemia decreased the efficiency of stimulus-response coupling and increased the steepness of the stimulus-response curve. In both disease models, no change in receptor affinity and density were found.

Conclusions
The results revealed the causes of reduced α1AR-mediated inotropic responsiveness in endotoxemia and hypoxia. In contrast with traditional dose-response studies, it was possible to quantify separately the underlying changes in α1AR binding and signal transduction.
Use of Withdrawal (Coitus Interruptus) for Both Pregnancy and HIV Prevention among Young Adults in Rakai, Uganda
Authors: Higgins Jenny A. , Gregor Laura , Mathur Sanyukta , Nakyanjo Neema , Nalugoda Fred , Santelli John S. 
Published: November 2013

Abstract

Introduction
Although understudied in the context of AIDS, use of withdrawal (coitus interruptus) with or in place of other prevention methods affects exposure to both pregnancy and human immunodeficiency virus (HIV).

Aim
We used mixed methods to assess use of withdrawal among 15–24-year-olds in a rural Ugandan setting with considerable HIV prevalence.

Methods
We measured withdrawal reporting among (i) sexually active 15–24-year-olds enrolled in a quantitative community survey (n = 6,722) and (ii) in-depth qualitative interview participants systematically selected from the latest round of the community survey (N = 60). Respondents were asked about family planning and HIV prevention practices, including a direct question about withdrawal in the in-depth interviews.

Main Outcome Measures
The main outcome measures were reports of current use of withdrawal on the quantitative survey (general question about family planning methods) and reports of current or recent use withdrawal in qualitative interviews (specific question about withdrawal). Qualitative interviews also probed for factors associated with withdrawal use.

Results
Although less than 1% of quantitative survey participants spontaneously named withdrawal as their current family planning method, 48% of qualitative interview respondents reported current or lifetime use of withdrawal. Withdrawal was often used as a pleasurable alternative to condoms, when condoms were not available, and/or as a “placeholder” method before obtaining injectable contraception. A few respondents described using withdrawal to reduce HIV risk.

Conclusion
Qualitative findings revealed widespread withdrawal use among young adults in Rakai, mainly as a condom alternative. Thus, withdrawal may shape exposure to both pregnancy and HIV. Future behavioral surveys should assess withdrawal practices directly—and separately from other contraceptives and HIV prevention methods. Further clinical research should further document withdrawal's association with HIV risk.
Bioavailability of morphine, methadone, hydromorphone, and oxymorphone following buccal administration in cats
Authors: Pypendop B. H. , Ilkiw J. E. , Shilo‐Benjamini Y. 
Published: November 2013

Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time–concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7–49.5), 44.2 ± 7.9 (18.7–70.5), 22.4 ± 6.9 (6.4–43.4), and 18.8 ± 2.0 (12.9–23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone.
Characterizing the plasticity of nitrogen metabolism by the host and symbionts of the hydrothermal vent chemoautotrophic symbioses Ridgeia piscesae
Authors: Liao Li , Wankel Scott D. , Wu Min , Cavanaugh Colleen M. , Girguis Peter R. 
Published: November 2013

AbstractChemoautotrophic symbionts of deep sea hydrothermal vent tubeworms are known to provide their hosts with all their primary nutrition. While studies have examined how chemoautotrophic symbionts provide the association with nitrogen, fewer have examined if symbiont nitrogen metabolism varies as a function of environmental conditions. Ridgeia piscesae tubeworms flourish at Northeastern Pacific vents, occupy a range of microhabitats, and exhibit a high degree of morphological plasticity [e.g. long‐skinny (LS) and short‐fat (SF) phenotypes] that may relate to environmental conditions. This plasticity affords an opportunity to examine whether symbiont nitrogen metabolism varies among host phenotypes. LS and SF R. piscesae were recovered from the Axial and Main Endeavour Field hydrothermal vents. Nitrate and ammonium were quantified in Ridgeia blood, and the expression of key nitrogen metabolism genes, as well as stable nitrogen isotope ratios, was quantified in host branchial plume and symbiont‐containing tissues. Nitrate and ammonium were abundant in the blood of both phenotypes though environmental ammonium concentrations were, paradoxically, lowest among individuals with the highest blood ammonium. Assimilatory nitrate reductase transcripts were always below detection, though in both LS and SF R. piscesae symbionts, we observed elevated expression of dissimilatory nitrate reductase genes, as well as symbiont and host ammonium assimilation genes. Site‐specific differences in expression, along with tissue stable isotope analyses, suggest that LS and SF Ridgeia symbionts are engaged in both dissimilatory nitrate reduction and ammonia assimilation to varying degrees. As such, it appears that environmental conditions –not host phenotype—primarily dictates symbiont nitrogen metabolism.
Hybridization and adaptation to introduced balloon vines in anAustralian soapberry bug
Authors: Andres J. A. , Thampy P. R. , Mathieson M. T. , Loye J. , Zalucki M. P. , Dingle H. , Carroll S. P. 
Published: November 2013

AbstractContemporary adaptation of plant feeding insects to introduced hosts provides clear cases of ecologically based population divergence. In most cases the mechanisms permitting rapid differentiation are not well known. Here we study morphological and genetic variation associated with recent shifts by the Australian soapberry bugLeptocoris tagalicusonto two naturalized Neotropical balloon vines,Cardiospermum halicacabumandC. grandiflorumthat differ in time since introduction. Our results show that these vines have much larger fruits than the native hosts (Whitewood tree –Atalaya hemiglauca– and Woolly Rambutan –Alectryon tomentosus–) and that bugs living on them have evolved significantly longer beaks and new allometries. Genetic analyses of mitochondrial haplotypes and amplified fragment length polymorphic (AFLP) markers indicate that the lineage of bugs on the annual vineC. halicacabum, the older introduction, is intermediate between the two subspecies ofL. tagalicusfound on native hosts. Moreover, where the annual vine and Whitewood tree co‐occur, the morphology and genomic composition of the bugs are similar to those occurring in allopatry. These results show that hybridization provided the genetic elements underlying the strongly differentiated ‘Halicacabumbugs’. In contrast, the bugs feeding on the recently introduced perennial balloon vine (C. grandiflorum) showed no evidence of admixture, and are genetically indistinguishable from the nearby populations on a native host.
Progress towards an interdisciplinary science of plant phenology: building predictions across space, time and species diversity
Authors: Wolkovich Elizabeth M. , Cook Benjamin I. , Davies T. Jonathan 
Published: November 2013

SummaryClimate change has brought renewed interest in the study of plant phenology – the timing of life history events. Data on shifting phenologies with warming have accumulated rapidly, yet research has been comparatively slow to explain the diversity of phenological responses observed across latitudes, growing seasons and species. Here, we outline recent efforts to synthesize perspectives on plant phenology across the fields of ecology, climate science and evolution. We highlight three major axes that vary among these disciplines: relative focus on abiotic versus biotic drivers of phenology, on plastic versus genetic drivers of intraspecific variation, and on cross‐species versus autecological approaches. Recent interdisciplinary efforts, building on data covering diverse species and climate space, have found a greater role of temperature in controlling phenology at higher latitudes and for early‐flowering species in temperate systems. These efforts have also made progress in understanding the tremendous diversity of responses across species by incorporating evolutionary relatedness, and linking phenological flexibility to invasions and plant performance. Future research with a focus on data collection in areas outside the temperate mid‐latitudes and across species' ranges, alongside better integration of how risk and investment shape plant phenology, offers promise for further progress.