bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatio‐temporal dynamics of adaptation in the human visual system: a high‐density electrical mapping study
Authors: Andrade Gizely N. , Butler John S. , Mercier Manuel R. , Molholm Sophie , Foxe John J. 
Published: February 2015

AbstractWhen sensory inputs are presented serially, response amplitudes to stimulus repetitions generally decrease as a function of presentation rate, diminishing rapidly as inter‐stimulus intervals (ISIs) fall below 1 s. This ‘adaptation’ is believed to represent mechanisms by which sensory systems reduce responsivity to consistent environmental inputs, freeing resources to respond to potentially more relevant inputs. While auditory adaptation functions have been relatively well characterized, considerably less is known about visual adaptation in humans. Here, high‐density visual‐evoked potentials (VEPs) were recorded while two paradigms were used to interrogate visual adaptation. The first presented stimulus pairs with varying ISIs, comparing VEP amplitude to the second stimulus with that of the first (paired‐presentation). The second involved blocks of stimulation (N = 100) at various ISIs and comparison of VEP amplitude between blocks of differing ISIs (block‐presentation). Robust VEP modulations were evident as a function of presentation rate in the block‐paradigm, with strongest modulations in the 130–150 ms and 160–180 ms visual processing phases. In paired‐presentations, with ISIs of just 200–300 ms, an enhancement of VEP was evident when comparing S2 with S1, with no significant effect of presentation rate. Importantly, in block‐presentations, adaptation effects were statistically robust at the individual participant level. These data suggest that a more taxing block‐presentation paradigm is better suited to engage visual adaptation mechanisms than a paired‐presentation design. The increased sensitivity of the visual processing metric obtained in the block‐paradigm has implications for the examination of visual processing deficits in clinical populations.
On the ethical use of placebos
Authors: Rawlins Richard 
Published: February 2015

AbstractSham drugs, fake therapies and non‐effective treatments have long been used to placate patients and are often referred to as ‘placebos’. Placebos are used regularly as controls for clinical drug trials but their use as therapeutic modalities in their own right is controversial. This article combines my experience as a consultant surgeon with the insight of also being a magician, and member of The Magic Circle, UK, in viewing the world of deception and delusion in health care. This perspective endorses the use of placebos within the paradigm of ethical care based on patients giving fully informed consent. This means that unless and until there is generally accepted plausible evidence that a specific complementary or alternative medicine (CAM) or practice produces outcomes better than those produced by therapeutic encounters with attentive empathic practitioners alone, it should be accepted that the CAM therapy works through the mechanism of a placebo response – and that is what patients should be told. That may diminish the beneficial effects of the CAM/placebo therapy, but the placebo response will not be entirely negated – honesty and intellectual integrity should trump the convenience of the practitioner.
Oxygen limitations on marine animal distributions and the collapse of epibenthic community structure during shoaling hypoxia
Authors: Chu Jackson W. F. , Tunnicliffe Verena 
Published: February 2015

AbstractDeoxygenation in the global ocean is predicted to induce ecosystem‐wide changes. Analysis of multidecadal oxygen time‐series projects the northeast Pacific to be a current and future hot spot of oxygen loss. However, the response of marine communities to deoxygenation is unresolved due to the lack of applicable data on component species. We repeated the same benthic transect (n = 10, between 45 and 190 m depths) over 8 years in a seasonally hypoxic fjord using remotely operated vehicles equipped with oxygen sensors to establish the lower oxygen levels at which 26 common epibenthic species can occur in the wild. By timing our surveys to shoaling hypoxia events, we show that fish and crustacean populations persist even in severe hypoxia (<0.5 mL L−1) with no mortality effects but that migration of mobile species occurs. Consequently, the immediate response to hypoxia expansion is the collapse of community structure; normally partitioned distributions of resident species coalesced and localized densities increased. After oxygen renewal and formation of steep oxygen gradients, former ranges re‐established. High frequency data from the nearby VENUS subsea observatory show the average oxygen level at our site declined by ~0.05 mL L−1 year−1 over the period of our study. The increased annual duration of the hypoxic (<1.4 mL L−1) and severely hypoxic periods appears to reflect the oxygen dynamics demonstrated in offshore source waters and the adjacent Strait of Georgia. Should the current trajectory of oxygen loss continue, community homogenization and reduced suitable habitat may become the dominant state of epibenthic systems in the northeast Pacific. In situ oxygen occurrences were not congruent with lethal and sublethal hypoxia thresholds calculated across the literature for major taxonomic groups indicating that research biases toward laboratory studies on Atlantic species are not globally applicable. Region‐specific hypoxia thresholds are necessary to predict future impacts of deoxygenation on marine biodiversity.
Early glial activation precedes neurodegeneration in the cerebral cortex after SIV infection: A 3D, multivoxel proton magnetic resonance spectroscopy study
Authors: Wu WE , Babb JS , Tal A , Kirov II , George AE , Ratai E‐M , Gonzalez RG , Gonen O 
Published: February 2015

ObjectivesAs ∼40% of HIV‐infected individuals experience neurocognitive decline, we investigated whether proton magnetic resonance spectroscopic imaging (1H‐MRSI) detects early metabolic abnormalities in the cerebral cortex of a simian immunodeficiency virus (SIV)‐infected rhesus monkey model of neuroAIDS.MethodsThe brains of five rhesus monkeys before and 4 or 6 weeks after SIV infection (with CD8+ T‐cell depletion) were assessed with T2‐weighted quantitative magnetic resonance imaging (MRI) and 16×16×4 multivoxel 1H‐MRSI (echo time/repetition time = 33/1440 ms). Grey matter and white matter masks were segmented from the animal MRIs and used to produce cortical masks co‐registered to 1H‐MRSI data to yield cortical metabolite concentrations of the glial markers myo‐inositol (mI), creatine (Cr) and choline (Cho), and of the neuronal marker N‐acetylaspartate (NAA). The cortex volume within the large, 28 cm3 (∼35% of total monkey brain) volume of interest was also calculated for each animal pre‐ and post‐infection. Mean metabolite concentrations and cortex volumes were compared pre‐ and post‐infection using paired sample t‐tests.ResultsThe mean (± standard deviation) pre‐infection concentrations of the glial markers mI, Cr and Cho were 5.8 ± 0.9, 7.2 ± 0.4 and 0.9 ± 0.1 mM, respectively; these concentrations increased 28% (p ≈ 0.06), 15% and 10% (both p < 0.05), respectively, post‐infection. The mean concentration of neuronal marker NAA remained unchanged (7.0 ± 0.6 mM pre‐infection vs. 7.3 ± 0.8 mM post‐infection; p ≈ 0.37). The mean cortex volume was also unchanged (8.1 ± 1.1 cm3 pre‐infection vs. 8.3 ± 0.5 cm3 post‐infection; p ≈ 0.76).ConclusionsThese results support the hypothesis that early cortical glial activation occurs after SIV infection prior to the onset of neurodegeneration. This suggests HIV therapeutic interventions should potentially target early glial activation in the cerebral cortex.
The rapid test in Spanish pharmacies: a novel programme to reach heterosexual men?
Authors: Fernández‐Balbuena S , Marcos H , Pérez‐Rubio A , Hoyos J , Belza MJ , de la Fuente L 
Published: February 2015

ObjectivesSpain has been a pioneer in the implementation of rapid HIV testing programmes in pharmacies to increase access to testing. However, no formal evaluation of the effectiveness of these programmes has been carried out to date. Our aim was to evaluate the ability of a novel in‐pharmacy rapid HIV testing programme to promote diagnosis and reach vulnerable populations.MethodsBetween 2011 and 2012, 2168 people underwent testing in 16 urban pharmacies in 10 cities of a Spanish region with a low prevalence of HIV infection. The main outcomes of the programme were compared with those of the regional surveillance system for new HIV diagnoses (RHSS‐CyL).ResultsOverall, 52.8% of those tested were heterosexual men, 15.8% were men who have sex with men (MSM) and 25.3% were women. Nine per cent were immigrants and 41.9% were < 30 years old. In total, 59.5% of the heterosexual men, 44.6% of the MSM and 65.3% of the women were previously untested. There were 23 positive results, representing 6% of all new regional diagnoses in 2011. The global prevalence was 1.1% (95% confidence interval 0.6–1.5%) and the prevalence in MSM was 3.8%. Of the reactive results, 60.9% were in MSM, 34.8% in heterosexual men and only 4.3% in women, vs. 35.4%, 37.5% and 15.0%, respectively, reported by the RHSS‐CyL. The mean age of those testing positive was 32.7 years vs. 38.7 years in the RHSS‐CyL. Fifty per cent of MSM and 75% of heterosexual men testing positive were previously untested.ConclusionsIn Spain, this is the first programme not targeted at the most at‐risk populations, and has been shown to be effective in reaching and diagnosing heterosexual men, who are the group most affected by delayed diagnoses. Heterosexual men accounted for over half of those tested and a third of those diagnosed, and most of them were previously untested. Young and previously untested MSM also greatly benefitted from the programme.
A systematic review on the effects of air polishing devices on oral tissues
Authors: Bühler J , Amato M , Weiger R , Walter C 
Published: February 2015

AbstractObjectivesAir‐polishing devices are used for the instrumentation of the root surface. Their potential of harm to the hard and/or soft tissues needs to be considered during periodontal treatment. The objective of this systematic review was to analyse the effects of air polishing devices on oral tissues.MethodsThe electronic databases MEDLINE, EMBASE and the Cochrane Library were screened for studies published through 18 November 2013. The surface modifications on human cementum, dentine or gingiva after the instrumentation were considered as outcomes.ResultsOf the 1266 abstracts screened, 17 studies were included in the analysis. Different air polishing powders consisting of sodium bicarbonate, calcium carbonate, pumice or glycine were used in different ex vivo or in vitro settings. Thirteen publications reported data on the effects of air polishing devices on cementum and dentine. Hard tissue modifications, including defect depths and volume, caused by sodium bicarbonate or calcium carbonate powders were significantly greater compared to powders consisting of glycine. The soft tissue modifications using different modes of instrumentation were assessed in four publications. The data demonstrate less potential of harm to the gingiva after spraying with glycine powder compared to sodium bicarbonate powder or instrumentation with curettes.ConclusionGlycine powder air polishing may be safely applied to human root surfaces and gingivae.
Use of Atypical Antipsychotics in Nursing Homes and Pharmaceutical Marketing
Authors: Pimentel Camilla B. , Donovan Jennifer L. , Field Terry S. , Gurwitz Jerry H. , Harrold Leslie R. , Kanaan Abir O. , Lemay Celeste A. , Mazor Kathleen M. , Tjia Jennifer , Briesacher Becky A. 
Published: February 2015

ObjectivesTo describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs.DesignNested mixed‐methods, cross‐sectional study of NHs in a cluster randomized trial.SettingForty‐one NHs in Connecticut.ParticipantsNH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%).MeasurementsQuantitative data, including prescription drug dispensing data (September 2009–August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility‐level prevalence of atypical antipsychotic use, facility‐level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing.ResultsLeadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet‐based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader.ConclusionNH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear.
Apolipoprotein E, Carbon Dioxide Vasoreactivity, and Cognition in Older Adults: Effect of Hypertension
Authors: Hajjar Ihab , Sorond Farzaneh , Lipsitz Lewis A. 
Published: February 2015

ObjectivesTo investigate the associations between the apolipoprotein E (APOE) ε4 allele, carbon dioxide (CO2) vasoreactivity, and cognitive performance and to explore the effect of CO2 vasoreactivity and hypertension on the associations between APOE and cognition.DesignObservational.SettingCommunity.ParticipantsOlder adults (N = 625) enrolled in the Maintenance of Balance, Independent Living, Intellect and Zest in the Elderly of Boston Study.MeasurementsChange in cerebral blood flow velocity in response to CO2 challenge (CO2), measured using transcranial Doppler ultrasonography, Trail‐Making Test Part B – A (TMT), Hopkins Verbal Learning Test delayed recall (HVLT).ResultsAPOE‐ε4 was associated with lower CO2 vasoreactivity (P = .009) and poorer performance on the TMT (P < .001) and HVLT (P < .001). Having hypertension and APOE‐ε4 was associated with worse cognitive and CO2 vasoreactivity measures than having neither or either alone (P < .001 for TMT and HVLT, P = .01 for CO2 vasoreactivity). The association between APOE‐ε4 and cognition was only significant if it was present concurrent with low CO2 vasoreactivity, defined as below the median of the sample (APOE by CO2 vasoreactivity interaction: P = .04 for TMT, P = .04 for HVLT). In hypertension, the association between APOE‐ε4 and executive function was also only significant in participants with lower CO2 vasoreactivity (P = .005 for APOE by CO2 vasoreactivity).ConclusionIndividuals at risk of Alzheimer's disease (AD) because they have APOE‐ε4 may have lower CO2 vasoreactivity, which in turn may be contributing to the observed lower cognitive performance associated with this allele. The cognitive effect of APOE‐ε4 is magnified in hypertension and low CO2 vasoreactivity. This study offers evidence that APOE‐ε4 may be associated with microvascular brain injury even in the absence of clinical AD.
Global Human Appropriation of Net Primary Production for Biomass Consumption in the European Union, 1986–2007
Authors: Kastner Thomas , Erb Karl‐Heinz , Haberl Helmut 
Published: February 2015

SummaryThe ongoing globalization process strengthens the connections between different geographic regions through trade. Biomass products, such as food, fiber, or bioenergy, are increasingly traded globally, thereby leading to telecouplings between distant, seemingly unrelated regions. For example, restrictions for agricultural production or changes in bioenergy demand in Europe or the United States might contribute to deforestation in Latin America or Sub‐Saharan Africa. One approach to analyze trade‐related land‐use effects of the global socioeconomic biomass metabolism is the “embodied human appropriation of net primary production” or eHANPP. eHANPP accounts allocate to any product the entire amount of the human appropriation of net primary production (HANPP) that emerges throughout its supply chain. This allows consumption‐based accounts to move beyond simple area‐demand approaches by taking differences in natural productivity as well as in land‐use intensity into account, both across land‐use types as well as across world regions. In this article, we discuss the eHANPP related to the European Union's (EU) consumption of biomass products in the period 1986–2007, based on a consistent global trade data set derived from bilateral data. We find a considerable dependency of the EU on the appropriation of biological productivity outside its own boundaries, with increasing reliance on Latin America as a main supplier. By using the EU as an illustrative example, we demonstrate the usefulness of eHANPP for assessing land‐use impacts caused by nations’ socioeconomic activities and conclude that the eHANPP approach can provide useful information to better manage ecosystems globally in the face of an increasingly interconnected world.
Dynamic increases in AMPA receptor phosphorylation in the rat hippocampus in response to amphetamine
Authors: Mao Li‐Min , Xue Bing , Jin Dao‐Zhong , Wang John Q. 
Published: February 2015

AbstractIncreasing evidence supports the critical role of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) glutamate receptors in psychostimulant action. These receptors are regulated via a phosphorylation‐dependent mechanism in their trafficking, distribution, and function. The hippocampus is a brain structure important for learning and memory and is emerging as a critical site for processing psychostimulant effects. To determine whether the hippocampal pool of AMPA receptors is regulated by stimulants, we investigated and characterized the impact of amphetamine (AMPH) on phosphorylation of AMPA receptors in the adult rat hippocampus in vivo. We found that AMPH markedly increased phosphorylation of AMPA receptor GluA1 subunits at serine 845 (S845) in the hippocampus. The effect of AMPH was dose dependent. A single dose of AMPH induced a rapid and transient increase in S845 phosphorylation. Among different hippocampal subfields, AMPH primarily elevated S845 phosphorylation in the Cornu Ammonis area 1 and dentate gyrus. In contrast to S845, serine 831 phosphorylation of GluA1 and serine 880 phosphorylation of GluA2 were not altered by AMPH. In addition, surface expression of hippocampal GluA1 was up‐regulated, while the amount of intracellular GluA1 fraction was concurrently reduced in response to AMPH. GluA2 protein levels in either the surface or intracellular pool were insensitive to AMPH. These data demonstrate that the AMPA receptor in the hippocampus is sensitive to dopamine stimulation. Acute AMPH administration induces dose‐, time‐, site‐, and subunit‐dependent phosphorylation of AMPA receptors and facilitates surface trafficking of GluA1 AMPA receptors in hippocampal neurons in vivo.
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Acute injection of amphetamine increased phosphorylation of α‐Amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor GluA1 subunits at a protein kinase A (PKA)‐sensitive site (S845) in the rat hippocampus. This increase was dose‐ and time‐dependent and correlated with an increase in surface GluA1 expression. Thus, amphetamine can upregulate GluA1 phosphorylation and surface trafficking of GluA1 in hippocampal neurons in vivo.
Targeting cyclin D3/CDK6 activity for treatment of Parkinson's disease
Authors: Alquézar Carolina , Barrio Estíbaliz , Esteras Noemí , de la Encarnación Ana , Bartolomé Fernando , Molina José A. , Martín‐Requero Ángeles 
Published: February 2015

AbstractAt present, treatment for Parkinson's disease (PD) is only symptomatic; therefore, it is important to identify new targets tackling the molecular causes of the disease. We previously found that lymphoblasts from sporadic PD patients display increased activity of the cyclin D3/CDK6/pRb pathway and higher proliferation than control cells. These features were considered systemic manifestations of the disease, as aberrant activation of the cell cycle is involved in neuronal apoptosis. The main goal of this work was to elucidate whether the inhibition of cyclin D3/CDK6‐associated kinase activity could be useful in PD treatment. For this purpose, we investigated the effects of two histone deacetylase (HDAC) inhibitors, suberoylanilide hydroxamic (SAHA) acid and sodium butyrate (NaB), and the m‐TOR inhibitor rapamycin on cell viability and cyclin D3/CDK6 activity. Moreover, the potential neuroprotective action of these drugs was evaluated in 6‐hydroxy‐dopamine (6‐OHDA) treated dopaminergic SH‐SY5Y cells and primary rat mesencephalic cultures. Here, we report that both compounds normalized the proliferative activity of PD lymphoblasts and reduced the 6‐OHDA‐induced cell death in neuronal cells by preventing the over‐activation of the cyclin D3/CDK6/pRb cascade. Considering that these drugs are already used in clinic for treatment of other diseases with good tolerance, it is plausible that they may serve as novel therapeutic drugs for PD.
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We report here that peripheral cells from Parkinson's disease (PD) patients show an enhanced proliferative activity due to the activation of cyclin D3/CDK6‐mediated phosphorylation of retinoblastoma protein (pRb). Treatment of PD lymphoblasts with inhibitors of histone deacetylases like suberoylanilide hydroxamic acid (SAHA) and sodium butyrate (NaB), or with rapamycin, inhibitor of mechanistic target of rapamycin (mTOR) normalized the proliferation of PD lymphoblasts by preventing the over‐activation of the cyclin D3/CDK6/pRb cascade. These drugs were shown to have neuroprotective effects in both human neuroblastoma SH‐SY5Y cells and primary rat mid‐brain dopaminergic neuronal cultures toxicity induced by 6‐hidroxydopamine. Considering that these drugs are already used in clinic for treatment of other diseases with good tolerance, it seems reasonable to believe that the repositioning of these drugs toward PD holds promise as a novel therapeutic strategy.
Disruption of a CAROTENOID CLEAVAGE DIOXYGENASE 4 gene converts flower colour from white to yellow in Brassica species
Authors: Zhang Bao , Liu Chao , Wang Yaqin , Yao Xuan , Wang Fang , Wu Jiangsheng , King Graham J. , Liu Kede 
Published: February 2015

Summary

In Brassica napus, yellow petals had a much higher content of carotenoids than white petals present in a small number of lines, with violaxanthin identified as the major carotenoid compound in yellow petals of rapeseed lines.

Using positional cloning we identified a carotenoid cleavage dioxygenase 4 gene, BnaC3.CCD4, responsible for the formation of flower colour, with preferential expression in petals of white‐flowered B. napus lines. Insertion of a CACTA‐like transposable element 1 (TE1) into the coding region of BnaC3.CCD4 had disrupted its expression in yellow‐flowered rapeseed lines.

α‐Ionone was identified as the major volatile apocarotenoid released from white petals but not from yellow petals. We speculate that BnaC3.CCD4 may use δ‐ and/or α‐carotene as substrates.

Four variations, including two CACTA‐like TEs (alleles M1 and M4) and two insertion/deletions (INDELs, alleles M2 and M3), were identified in yellow‐flowered Brassica oleracea lines. The two CACTA‐like TEs were also identified in the coding region of BcaC3.CCD4 in Brassica carinata. However, the two INDELs were not detected in B. napus and B. carinata. We demonstrate that the insertions of TEs in BolC3.CCD4 predated the formation of the two allotetraploids.