bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drift-dependent changes in iceberg size-frequency distributions
Authors: Kirkham James D. , Rosser Nick J. , Wainwright John , Vann Jones Emma C. , Dunning Stuart A. , Lane Victoria S. , Hawthorn David E. , Strzelecki Mateusz C. , Szczuciński Witold 
Published: November 2017

AbstractAlthough the size-frequency distributions of icebergs can provide insight into how they disintegrate, our understanding of this process is incomplete. Fundamentally, there is a discrepancy between iceberg power-law size-frequency distributions observed at glacial calving fronts and lognormal size-frequency distributions observed globally within open waters that remains unexplained. Here we use passive seismic monitoring to examine mechanisms of iceberg disintegration as a function of drift. Our results indicate that the shift in the size-frequency distribution of iceberg sizes observed is a product of fracture-driven iceberg disintegration and dimensional reductions through melting. We suggest that changes in the characteristic size-frequency scaling of icebergs can be explained by the emergence of a dominant set of driving processes of iceberg degradation towards the open ocean. Consequently, the size-frequency distribution required to model iceberg distributions accurately must vary according to distance from the calving front.
Simultaneous quarter-wave plate and half-mirror operation through a highly flexible single layer anisotropic metasurface
Authors: Khan M. Ismail , Tahir Farooq A. 
Published: November 2017

AbstractA highly flexible single-layer metasurface manifesting quarter-wave plate as well as half-mirror (1:1 beam-splitter) operation in the microwave frequency regime is being presented in this research. The designed metasurface reflects half power of the impinging linearly polarized electromagnetic wave as circularly polarized wave while the remaining half power is transmitted as circularly polarized wave at resonance frequency. Similarly, a circularly polarized incident wave is reflected and transmitted as linearly polarized wave with equal half powers. Moreover, the response of the metasurface is quite stable against the variations in the incidence angle up to 45°. The measurements performed on the fabricated prototype exhibit a good agreement with the simulation results. The compact size, flexible structure, angular stability and two in one operation (operating as a quarter-wave plate and beam-splitter at the same time) are the main characteristics of the subject metasurface that makes it a potential candidate for numerous applications in communication and miniaturized and conformal polarization control devices.
Intelligence is associated with the modular structure of intrinsic brain networks
Authors: Hilger Kirsten , Ekman Matthias , Fiebach Christian J. , Basten Ulrike 
Published: November 2017

AbstractGeneral intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain’s modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.
Systematic Screening of Chemokines to Identify Candidates to Model and Create Ectopic Lymph Node Structures for Cancer Immunotherapy
Authors: Yagawa Yohsuke , Robertson-Tessi Mark , Zhou Susan L. , Anderson Alexander R. A. , Mulé James J. , Mailloux Adam W. 
Published: November 2017

AbstractThe induction of ectopic lymph node structures (ELNs) holds great promise to augment immunotherapy against multiple cancers including metastatic melanoma, in which ELN formation has been associated with a unique immune-related gene expression signature composed of distinct chemokines. To investigate the therapeutic potential of ELNs induction, preclinical models of ELNs are needed for interrogation of these chemokines. Computational models provide a non-invasive, cost-effective method to investigate leukocyte trafficking in the tumor microenvironment, but parameterizing such models is difficult due to differing assay conditions and contexts among the literature. To better achieve this, we systematically performed microchemotaxis assays on purified immune subsets including human pan-T cells, CD4+ T cells, CD8+ T cells, B cells, and NK cells, with 49 recombinant chemokines using a singular technique, and standardized conditions resulting in a dataset representing 238 assays. We then outline a groundwork computational model that can simulate cellular migration in the tumor microenvironment in response to a chemoattractant gradient created from stromal, lymphoid, or antigen presenting cell interactions. The resulting model can then be parameterized with standardized data, such as the dataset presented here, and demonstrates how a computational approach can help elucidate developing ELNs and their impact on tumor progression.
Baseline and Breakthrough Resistance Mutations in HCV Patients Failing DAAs
Authors: Paolucci Stefania , Premoli Marta , Novati Stefano , Gulminetti Roberto , Maserati Renato , Barbarini Giorgio , Sacchi Paolo , Piralla Antonio , Sassera Davide , De Marco Leone , Girello Alessia , Mondelli Mario U. , Baldanti Fausto 
Published: November 2017

AbstractSustained virologic response rates have increased dramatically following direct acting antiviral (DAA) therapy in chronic HCV infection. However, resistance-associated substitutions (RASs) may occur either prior to DAA or following drug exposure. The aim of this study was to determine RASs in DAA treatment-failing patients and the role of RASs in failure treatment. Six hundred and twenty HCV patients were evaluated. Direct sequencing of HCV genes was performed at breakthrough in all 31 patients failing DAAs, and in 19 baseline patients. Deep sequencing analysis was performed in 15/19 baseline patients. RASs were detected at breakthrough in 17/31 patients and at baseline in 11/19 patients, although, only 8/19 patients carried RASs associated with the prescribed regimen. Deep sequencing analysis showed RASs at baseline in 10/15 treatment-failing patients. No significant difference was observed with the Sanger sequencing. Treatment failure in the 14/31 patients without RASs was associated with suboptimal treatment. In 54.8% of treatment-failing patients one of the causes of failure might be the presence of RASs. In the majority of patients with RASs, mutations were present at baseline. Direct resistance test is advocated before treatment and at breakthrough in order to optimize retreatment regimens.
Characterization of the early molecular changes in the glomeruli of Cd151
−/− mice highlights induction of mindin and MMP-10
Authors: Naudin Crystal , Smith Brian , Bond Danielle R. , Dun Matthew D. , Scott Rodney J. , Ashman Leonie K. , Weidenhofer Judith , Roselli Séverine 
Published: November 2017

AbstractIn humans and FVB/N mice, loss of functional tetraspanin CD151 is associated with glomerular disease characterised by early onset proteinuria and ultrastructural thickening and splitting of the glomerular basement membrane (GBM). To gain insight into the molecular mechanisms associated with disease development, we characterised the glomerular gene expression profile at an early stage of disease progression in FVB/N Cd151−/− mice compared to Cd151+/+ controls. This study identified 72 up-regulated and 183 down-regulated genes in FVB/N Cd151−/− compared to Cd151+/+ glomeruli (p < 0.05). Further analysis highlighted induction of the matrix metalloprotease MMP-10 and the extracellular matrix protein mindin (encoded by Spon2) in the diseased FVB/N Cd151−/− GBM that did not occur in the C57BL/6 diseased-resistant strain. Interestingly, mindin was also detected in urinary samples of FVB/N Cd151−/− mice, underlining its potential value as a biomarker for glomerular diseases associated with GBM alterations. Gene set enrichment and pathway analysis of the microarray dataset showed enrichment in axon guidance and actin cytoskeleton signalling pathways as well as activation of inflammatory pathways. Given the known function of mindin, its early expression in the diseased GBM could represent a trigger of both further podocyte cytoskeletal changes and inflammation, thereby playing a key role in the mechanisms of disease progression.
Dynamical Binding Modes Determine Agonistic and Antagonistic Ligand Effects in the Prostate-Specific G-Protein Coupled Receptor (PSGR)
Authors: Wolf Steffen , Jovancevic Nikolina , Gelis Lian , Pietsch Sebastian , Hatt Hanns , Gerwert Klaus 
Published: November 2017

AbstractWe analysed the ligand-based activation mechanism of the prostate-specific G-protein coupled receptor (PSGR), which is an olfactory receptor that mediates cellular growth in prostate cancer cells. Furthermore, it is an olfactory receptor with a known chemically near identic antagonist/agonist pair, α- and β-ionone. Using a combined theoretical and experimental approach, we propose that this receptor is activated by a ligand-induced rearrangement of a protein-internal hydrogen bond network. Surprisingly, this rearrangement is not induced by interaction of the ligand with the network, but by dynamic van der Waals contacts of the ligand with the involved amino acid side chains, altering their conformations and intraprotein connectivity. Ligand recognition in this GPCR is therefore highly stereo selective, but seemingly lacks any ligand recognition via polar contacts. A putative olfactory receptor-based drug design scheme will have to take this unique mode of protein/ligand action into account.
Warming, shading and a moth outbreak reduce tundra carbon sink strength dramatically by changing plant cover and soil microbial activity
Authors: Dahl Mathilde Borg , Priemé Anders , Brejnrod Asker , Brusvang Peter , Lund Magnus , Nymand Josephine , Kramshøj Magnus , Ro-Poulsen Helge , Haugwitz Merian Skouw 
Published: November 2017

AbstractFuture increases in temperature and cloud cover will alter plant growth and decomposition of the large carbon pools stored in Arctic soils. A better understanding of interactions between above- and belowground processes and communities of plants and microorganisms is essential for predicting Arctic ecosystem responses to climate change. We measured ecosystem CO2 fluxes during the growing season for seven years in a dwarf-shrub tundra in West Greenland manipulated with warming and shading and experiencing a natural larvae outbreak. Vegetation composition, soil fungal community composition, microbial activity, and nutrient availability were analyzed after six years of treatment. Warming and shading altered the plant community, reduced plant CO2 uptake, and changed fungal community composition. Ecosystem carbon accumulation decreased during the growing season by 61% in shaded plots and 51% in warmed plots. Also, plant recovery was reduced in both manipulations following the larvae outbreak during the fifth treatment year. The reduced plant recovery in manipulated plots following the larvae outbreak suggests that climate change may increase tundra ecosystem sensitivity to disturbances. Also, plant community changes mediated via reduced light and reduced water availability due to increased temperature can strongly lower the carbon sink strength of tundra ecosystems.
Glucagon-like peptide-1 mimetics, optimal for Asian type 2 diabetes patients with and without overweight/obesity: meta-analysis of randomized controlled trials
Authors: Zhang Fang , Tang Lizhi , Zhang Yuwei , Lü Qingguo , Tong Nanwei 
Published: November 2017

AbstractGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are desirable for diabetes, especially in patients with overweight/obesity. We aimed to determine whether GLP-1RAs exhibit different glucose-lowering efficacies between Asian type 2 diabetes (T2D) patients with and without overweight/obesity. Randomized controlled trials were searched in EMBASE, MEDLINE, CENTRAL, and ClinicalTrials.gov. Studies published in English with treatment duration ≥12 weeks and information on HbA1c changes were included. The studies were divided into normal body mass index (BMI) and overweight/obese groups according to baseline BMI. Among 3190 searched studies, 20 trials were included in the meta-analysis. The standardized mean differences in HbA1c change, fasting glucose change, and postprandial glucose change were equivalent between normal BMI and overweight/obese studies (p > 0.05). The relative risk of HbA1c < 6.5% target achievement in normal BMI trials (7.93; 95% confidence interval: 3.27, 19.20) was superior to that in overweight/obesity trials (2.23; 1.67, 2.97), with a significant difference (p = 0.020). Body weight loss (p = 0.572) and hypoglycemic risk(p = 0.920) were similar in the two groups. The glucose-lowering effects of GLP-1RAs were equivalent among Asian T2D patients. With their advantages for weight-loss or weight-maintenance, GLP-1RAs are optimal medicines for Asian T2D patients with and without overweight/obesity.
Elevation in tropical sky islands as the common driver in structuring genes and communities of freshwater organisms
Authors: Gueuning Morgan , Suchan Tomasz , Rutschmann Sereina , Gattolliat Jean-Luc , Jamsari Jamsari , Kamil Al Ihsan , Pitteloud Camille , Buerki Sven , Balke Michael , Sartori Michel , Alvarez Nadir 
Published: November 2017

AbstractTropical mountains are usually characterized by a vertically-arranged sequence of ecological belts, which, in contrast to temperate habitats, have remained relatively stable in space across the Quaternary. Such long-lasting patterning of habitats makes them ideal to test the role of environmental pressure in driving ecological and evolutionary processes. Using Sumatran freshwater mayfly communities, we test whether elevation, rather than other spatial factors (i.e. volcanoes, watersheds) structures both species within communities and genes within species. Based on the analysis of 31 mayfly (Ephemeroptera) communities and restriction-site-associated-DNA sequencing in the four most ubiquitous species, we found elevation as the major spatial component structuring both species and genes in the landscape. In other words, similar elevations across different mountains or watersheds harbor more similar species and genes than different elevations within the same mountain or watershed. Tropical elevation gradients characterized by environmental conditions that are both steep and relatively stable seasonally and over geological time scales, are thus responsible for both ecological and genetic differentiation. Our results demonstrate howin situecological diversification at the micro-evolutionary level might fuel alpha- and beta- components of diversity in tropical sky islands.
Functional aspects of salivary nitric oxide synthase of Rhodnius prolixus (Hemiptera, Reduviidae) and nitric oxide trafficking at the vector-host interface
Authors: Paim Rafaela M. M. , Nascimento Bruno W. L. , Nascimento Ana Mércia D. , Pacheco Dimitri E. , Soares Adriana C. , Araujo Ricardo N. , Sant’Anna Mauricio R. V. , Pessoa Grasielle C. D. , Gontijo Nelder F. , Pereira Marcos H. 
Published: November 2017

AbstractRhodnius prolixus expresses nitric oxide synthase (NOS) in the cytosol of the salivary gland (SG) cells. The NO produced is stored in the SG lumen bound to NO-carrier haemeproteins called nitrophorins (NPs). NPs bind tightly to NO in the acidic SG lumen, but release NO when the pH becomes high, e.g., at the host skin (pH~7.4). NO elicits potent and transient relaxation of vascular smooth muscle. Here, we investigated the role of salivary NO in the R. prolixus feeding behaviour and the salivary vasodilator activity of the host microcirculation. NOS knockdown in R. prolixus changed the SG colour, decreased the number of NO-loaded NPs and caused impairment of feeding performance. When salivary gland extracts (SGEs) were obtained from NOS- and NPs-knockdown insects and prepared in pH 5.0 solution and injected (i.v.) into mice via the tail vein, no vasodilation was observed, whereas SGEs from control insects caused long-term venodilation in the mouse skin. SGs disrupted directly in PBS (pH 7.4) containing BSA produced long-term vasodilation compared to the controls without BSA due to the possible formation of nitroso-albumin, suggesting that host serum albumin extends the NO half-life when NO is injected into the host skin by triatomine during their blood-feeding.
Mercury evasion from a boreal peatland shortens the timeline for recovery from legacy pollution
Authors: Osterwalder Stefan , Bishop Kevin , Alewell Christine , Fritsche Johannes , Laudon Hjalmar , Åkerblom Staffan , Nilsson Mats B. 
Published: November 2017

AbstractPeatlands are a major source of methylmercury that contaminates downstream aquatic food webs. The large store of mercury (Hg) in peatlands could be a source of Hg for over a century even if deposition is dramatically reduced. However, the reliability of Hg mass balances can be questioned due to missing long-term land-atmosphere flux measurements. We used a novel micrometeorological system for continuous measurement of Hg peatland-atmosphere exchange to derive the first annual Hg budget for a peatland. The evasion of Hg (9.4 µg m−2 yr−1) over the course of a year was seven times greater than stream Hg export, and over two times greater than wet bulk deposition to the boreal peatland. Measurements of dissolved gaseous Hg in the peat pore water also indicate Hg evasion. The net efflux may result from recent declines in atmospheric Hg concentrations that have turned the peatland from a net sink into a source of atmospheric Hg. This net Hg loss suggests that open boreal peatlands and downstream ecosystems can recover more rapidly from past atmospheric Hg deposition than previously assumed. This has important implications for future levels of methylmercury in boreal freshwater fish and the estimation of historical Hg accumulation rates from peat profiles.
Muscle MRI and functional outcome measures in Becker muscular dystrophy
Authors: Barp Andrea , Bello Luca , Caumo Luca , Campadello Paola , Semplicini Claudio , Lazzarotto Annalisa , Sorarù Gianni , Calore Chiara , Rampado Alessandro , Motta Raffaella , Stramare Roberto , Pegoraro Elena 
Published: November 2017

AbstractBecker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene, and characterized by a clinical progression that is both milder and more heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed as biomarker of disease progression in dystrophinopathies. Correlation with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this study, 51 molecularly confirmed BMD patients (aged 7–69 years) underwent muscle MRI and were evaluated with functional measures (NSAA and 6MWT) at the time of the MRI, and subsequently after one year. We confirmed a pattern of fatty substitution involving mainly the hip extensors and most thigh muscles. Severity of muscle fatty substitution was significantly correlated with specific DMD mutations: in particular, patients with an isolated deletion of exon 48, or deletions bordering exon 51, showed milder involvement. Fat infiltration scores correlated with baseline functional measures, and predicted changes after 1 year. We conclude that in BMD, skeletal muscle MRI not only strongly correlates with motor function, but also helps in predicting functional deterioration within a 12-month time frame.
Levodopa-induced abnormal involuntary movements correlate with altered permeability of the blood-brain-barrier in the basal ganglia
Authors: Lerner Renata P. , Francardo Veronica , Fujita Koji , Bimpisidis Zisis , Jourdain Vincent A. , Tang Chris C. , Dewey Stephen L. , Chaly Thomas , Cenci M. Angela , Eidelberg David 
Published: November 2017

AbstractChronic levodopa treatment leads to the appearance of dyskinesia in the majority of Parkinson’s disease patients. Neurovascular dysregulation in putaminal and pallidal regions is thought to be an underlying feature of this complication of treatment. We used microPET to study unilaterally lesioned 6-hydroxydopamine rats that developed levodopa-induced abnormal involuntary movements (AIMs) after three weeks of drug treatment. Animals were scanned with [15O]-labeled water and [18F]-fluorodeoxyglucose, to map regional cerebral blood flow and glucose metabolism, and with [11C]-isoaminobutyric acid (AIB), to assess blood-brain-barrier (BBB) permeability, following separate injections of levodopa or saline. Multitracer scan data were acquired in each animal before initiating levodopa treatment, and again following the period of daily drug administration. Significant dissociation of vasomotor and metabolic levodopa responses was seen in the striatum/globus pallidus (GP) of the lesioned hemisphere. These changes were accompanied by nearby increases in [11C]-AIB uptake in the ipsilateral GP, which correlated with AIMs scores. Histopathological analysis revealed high levels of microvascular nestin immunoreactivity in the same region. The findings demonstrate that regional flow-metabolism dissociation and increased BBB permeability are simultaneously induced by levodopa within areas of active microvascular remodeling, and that such changes correlate with the severity of dyskinesia.
Pyridoxamine improves survival and limits cardiac dysfunction after MI
Authors: Deluyker Dorien , Ferferieva Vesselina , Driesen Ronald B. , Verboven Maxim , Lambrichts Ivo , Bito Virginie 
Published: November 2017

AbstractAdvanced glycation end products (AGEs) play a key role in the progression of heart failure. Whether treatments limiting AGEs formation would prevent adverse left ventricular remodeling after myocardial infarction (MI) remain unknown. We investigated whether pyridoxamine (PM) could limit adverse cardiac outcome in MI. Rats were divided into MI, MI + PM and Sham. Echocardiography and hemodynamic parameters were used to assess cardiac function 8 weeks post-surgery. Total interstitial collagen, collagen I and collagen III were quantified using Sirius Red and polarized light microscopy. PM improved survival following LAD occlusion. Pre-treatment with PM significantly decreased the plasma AGEs levels. MI rats treated with PM displayed reduced left ventricular end-diastolic pressure and tau compared to untreated MI rats. Deformation parameters were also improved with PM. The preserved diastolic function was related to the reduced collagen content, in particular in the highly cross-linked collagen type I, mainly in the peri-infarct region, although not via TGF-β1 pathway. Our data indicate that PM treatment prevents the increase in AGEs levels and reduces collagen levels in a rat model of MI, resulting in an improved cardiac phenotype. As such, therapies targeting formation of AGEs might be beneficial in the prevention and/or treatment of maladaptive remodeling following MI.