bluuebunny/crossref_metadata_2025 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

Although 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

A 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

General 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

The 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

Sustained 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

In 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

We 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

Future 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

Glucagon-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

Tropical 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

Rhodnius 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

Peatlands 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

Becker 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

Chronic 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

Advanced 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.
Distinctive Clinical Effects of Haemorrhagic Markers in Cerebral Amyloid Angiopathy
Authors: Jang Young Kyoung , Kim Hee Jin , Lee Jin San , Kim Yeo Jin , Kim Ko Woon , Kim Yeshin , Jang Hyemin , Lee Juyoun , Lee Jong Min , Kim Seung-Joo , Yu Kyung-Ho , Charidimou Andreas , Werring David J. , Kim Sung Tae , Na Duk L. , Seo Sang Won
Published: November 2017

Restricted lobar cerebral microbleeds (CMBs) and cortical superficial siderosis (CSS) are the characteristic markers of cerebral amyloid angiopathy (CAA). However, their effects on clinical features has not been evaluated well. The purpose of this study is to investigate the clinical implication of these markers in clinical-radiologically diagnosed CAA. A total of 372 patients with possible or probable CAA who met the modified Boston criteria were recruited in a memory clinic setting. Cortical thickness was measured using surface based methods. Presence of restricted multiple lobar CMBs were independently associated with cortical thinning across the entire cortical regions while presence of CSS was independently associated with cortical thinning primarily in the bilateral frontal region. Presence of restricted multiple lobar CMBs was associated with impairment in all cognitive domains such as attention, language, visuospatial, memory and frontal executive functions while presence of CSS was associated with attention and frontal dysfunction. The relationships of restricted multiple lobar CMBs or CSS with cognitive impairment were partially mediated by thinning in the corresponding cortical regions. Our findings suggested that restricted multiple lobar CMBs and CSS affect distinctive clinical features, providing new insights into potential mechanisms in CAA.
Insights into the species-specific metabolic engineering of glucosinolates in radish (Raphanus sativus L.) based on comparative genomic analysis
Authors: Wang Jinglei , Qiu Yang , Wang Xiaowu , Yue Zhen , Yang Xinhua , Chen Xiaohua , Zhang Xiaohui , Shen Di , Wang Haiping , Song Jiangping , He Hongju , Li Xixiang
Published: November 2017

Glucosinolates (GSLs) and their hydrolysis products present in Brassicales play important roles in plants against herbivores and pathogens as well as in the protection of human health. To elucidate the molecular mechanisms underlying the formation of species-specific GSLs and their hydrolysed products in Raphanus sativus L., we performed a comparative genomics analysis between R. sativus and Arabidopsis thaliana. In total, 144 GSL metabolism genes were identified, and most of these GSL genes have expanded through whole-genome and tandem duplication in R. sativus. Crucially, the differential expression of FMOGS-OX2 in the root and silique correlates with the differential distribution of major aliphatic GSL components in these organs. Moreover, MYB118 expression specifically in the silique suggests that aliphatic GSL accumulation occurs predominantly in seeds. Furthermore, the absence of the expression of a putative non-functional epithiospecifier (ESP) gene in any tissue and the nitrile-specifier (NSP) gene in roots facilitates the accumulation of distinctive beneficial isothiocyanates in R. sativus. Elucidating the evolution of the GSL metabolic pathway in R. sativus is important for fully understanding GSL metabolic engineering and the precise genetic improvement of GSL components and their catabolites in R. sativus and other Brassicaceae crops.
A Novel Multiplex HRM Assay to Detect Clopidogrel Resistance
Authors: Zhang Lichen , Ma Xiaowei , You Guoling , Zhang Xiaoqing , Fu Qihua
Published: November 2017

Clopidogrel is an antiplatelet medicine used to prevent blood clots in patients who have had a heart attack, stroke, or other symptoms. Variability in the clinical response to clopidogrel treatment has been attributed to genetic factors. In particular, five SNPs of rs4244285, rs4986893, rs12248560, rs662 and rs1045642 have been associated with resistance to clopidogrel therapy in Chinese population. This work involves the development of a multiplex high-resolution melting (HRM) assay to genotype all five of these loci in 2 tubes. Amplicons corresponding to distinct SNPs in a common tube were designed with the aid of uMelt prediction software to have different melting temperatures Tm by addition of a GC-rich tail to the 5′ end of the certain primers. Two kinds of commercial methods, Digital Fluorescence Molecular Hybridization (DFMH) and Sanger sequencing, were used as a control. Three hundred sixteen DFMH pretested samples from consecutive acute coronary syndrome patients were used for a blinded study of multiplex HRM. The sensitivity of HRM was 100% and the specificity was 99.93% reflecting detection of variants other than the known resistance SNPs. Multiplex HRM is an effective closed-tube, highly accurate, fast, and inexpensive method for genotyping the 5 clopidogrel resistance associated SNPs.
The directed evolution of ligand specificity in a GPCR and the unequal contributions of efficacy and affinity
Authors: Di Roberto Raphaël B. , Chang Belinda , Peisajovich Sergio G.
Published: November 2017

G protein-coupled receptors (GPCRs) must discriminate between hundreds of related signal molecules. In order to better understand how GPCR specificity can arise from a common promiscuous ancestor, we used laboratory evolution to invert the specificity of the Saccharomyces cerevisiae mating receptor Ste2. This GPCR normally responds weakly to the pheromone of the related species Kluyveromyces lactis, though we previously showed that mutation N216S is sufficient to make this receptor promiscuous. Here, we found that three additional substitutions, A265T, Y266F and P290Q, can act together to confer a novel specificity for K. lactis pheromone. Unlike wild-type Ste2, this new variant does not rely on differences in binding affinity to discriminate against its non-preferred ligand. Instead, the mutation P290Q is critical for suppressing the efficacy of the native pheromone. These two alternative methods of ligand discrimination were mapped to specific amino acid positions on the peptide pheromones. Our work demonstrates that changes in ligand efficacy can drive changes in GPCR specificity, thus obviating the need for extensive binding pocket re-modeling.
High corrosion resistance and weak corrosion anisotropy of an as-rolled Mg-3Al-1Zn (in wt.%) alloy with strong crystallographic texture
Authors: Wang B. J. , Xu D. K. , Xin Y. C. , Sheng L. Y. , Han E. H.
Published: November 2017

Combining with electrochemical corrosion measurements, immersion and hydrogen evolution testing performed in 0.9 wt.% NaCl solution at 37 °C, the corrosion resistance of an as-rolled Mg-3%Al-1%Zn alloy before and after a 3% compressive strain along the rolling direction was investigated. Results revealed that the corrosion behavior of differently oriented surfaces of the as-rolled samples with a strong basal texture was obviously different. Among them, the corrosion rate of sample surface with the orientation parallel to the normal direction (ND) of the plate was the fastest, the corrosion rate of sample surface with the orientation parallel to the rolling direction (RD) of the plate took the second place and the corrosion rate of sample surface with the orientation parallel to the transverse direction (TD) was the slowest. After being pre-strained, the activation of a high density of {10–12} twins could remarkably reduce the corrosion rate of surrounding α-Mg matrix and simultaneously weaken the corrosion anisotropy between differently oriented samples. The main reason was that similar to grain boundaries, twin boundaries acted as physical barriers to the corrosion attack. Moreover, the activated twins increased the protectiveness of surface films and then suppressed the micro corrosion couples occurred in twinned grains.
Efficacy and safety of low dose alteplase for intravenous thrombolysis in Asian stroke patients: a meta-analysis
Authors: Tan Ge , Wang Haijiao , Chen Sihan , Chen Deng , Zhu Lina , Xu Da , Zhang Yu , Liu Ling
Published: November 2017

Whether low dose alteplase is comparable to standard dose in efficacy and safety for intravenous thrombolysis (IVT) in Asian stroke patients remains unverified. PubMed, EMBASE, and Cochrane Library Database from the beginning to June 30, 2017 were searched. IVT efficacy was measured by favorable outcome (modified Rankin Scale scores of 0–1) at 3 months, and safety measured by mortality within 3 months and symptomatic intracerebral hemorrhage (SICH). Pooled estimates were conducted using fixed- or random-effects model depending on heterogeneity. For SICH, studies were pooled separately according to different definitions. Twelve studies involving 7,905 participants were included. No association was found between alteplase dose and favorable outcome (OR = 0.94, 95% CI 0.78–1.14, P = 0.5; heterogeneity: P
hetero
 = 0.01, I2 = 57.3%) and mortality (OR = 0.87, 95% CI 0.74–1.02, P = 0.08; P
hetero
 = 0.83, I2 = 0) using random- and fixed-effects models, respectively. Low dose alteplase was associated with lower SICH as defined by the National Institute of Neurological Disorders and Stroke study (OR = 0.79, 95% CI 0.64–0.99, P = 0.04; P
hetero
 = 0.57, I2 = 0) using fixed-effects model. Subgroup and sensitivity analysis could change the results significantly. Current limited evidence was insufficient to support the speculation that low dose alteplase was comparable to standard dose in thrombolytic efficacy and safety in Asian stroke patients.
Comparative Genomics of Color Morphs In the Coral Montastraea cavernosa
Authors: Jarett Jessica K. , MacManes Matthew D. , Morrow Kathleen M. , Pankey M. Sabrina , Lesser Michael P.
Published: November 2017

Montastraea cavernosa is a common coral in the Caribbean basin found in several color morphs. To investigate the causes for brown and orange morphs we undertook a genomics approach on corals collected at the same time and depth in the Bahamas. The coral holobiont includes the host, symbiotic dinoflagellates (Symbiodinium spp.), and a diverse microbiome. While the coral host showed significant genetic differentiation between color morphs both the composition of the Symbiodinium spp. communities and the prokaryotic communities did not. Both targeted and global gene expression differences in the transcriptome of the host show no difference in fluorescent proteins while the metatranscriptome of the microbiome shows that pigments such as phycoerythrin and orange carotenoid protein of cyanobacterial origin are significantly greater in orange morphs, which is also consistent with the significantly greater number of cyanobacteria quantified by 16S rRNA reads and flow cytometry. The microbiome of orange color morphs expressed significantly more nitrogenase (nifH) transcripts consistent with their known ability to fix nitrogen. Both coral and Symbiodinium spp. transcriptomes from orange morphs had significantly increased expression of genes related to immune response and apoptosis, which may potentially be involved in maintaining and regulating the unique symbiont population in orange morphs.
Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury
Authors: Sharif-Paghaleh Ehsan , Yap May Lin , Puhl Sarah-Lena , Badar Adam , Torres Julia Baguña , Chuamsaamarkkee Krisanat , Kampmeier Florian , Smith Richard A. , Clark James , Blower Philip J. , Sacks Steven , Mullen Gregory E.
Published: November 2017

Complement activation is a recognised mediator of myocardial ischaemia-reperfusion-injury (IRI) and cardiomyocytes are a known source of complement proteins including the central component C3, whose activation products can mediate tissue inflammation, cell death and profibrotic signalling. We investigated the potential to detect and quantify the stable covalently bound product C3d by external body imaging, as a marker of complement activation in heart muscle in a murine model of myocardial IRI. We used single-photon-emission-computed-tomography (SPECT) in conjunction with99mTechnecium-labelled recombinant complement receptor 2 (99mTc-rCR2), which specifically detects C3d at the site of complement activation. Compared to control imaging with an inactive CR2 mutant (99mTc-K41E CR2) or an irrelevant protein (99mTc-PSMA) or using99mTc-rCR2 in C3-deficient mice, the use of99mTc-rCR2 in complement-intact mice gave specific uptake in the reperfused myocardium. The heart to skeletal muscle ratio of99mTc-rCR2 was significantly higher than in the three control groups. Histological analysis confirmed specific uptake of99mTc-rCR2. Following therapeutic inhibition of complement C3 activation, we found reduced myocardial uptake of99mTc-rCR2. We conclude, therefore that99mTc-rCR2 imaging can be used for non-invasive detection of activated complement and in future could be exploited to quantify the severity of myocardial damage due to complement activation.
Au19M (M=Cr, Mn, and Fe) as magnetic copies of the golden pyramid
Authors: Tam Nguyen Minh , Cuong Ngo Tuan , Pham Hung Tan , Tung Nguyen Thanh
Published: November 2017

An investigation on structure, stability, and magnetic properties of singly doped Au19M (M=Cr, Mn, and Fe) clusters is carried out by means of density functional theory calculations. The studied clusters prefer forming magnetic versions of the unique tetrahedral Au20. Stable sextet Au19Cr is identified as the least reactive species and can be qualified as a magnetic superatom. Analysis on cluster electronic structures shows that the competition between localized and delocalized electronic states governs the stability and magnetic properties of Au19M clusters.
Isolation and functional identification of three cuticle protein genes during metamorphosis of the beet armyworm, Spodoptera exigua
Authors: jan Saad , Liu Sisi , Hafeez Muhammad , Zhang Xiangmei , Dawar Farman Ullah , Guo Jiyun , Gao Chao , Wang Mo
Published: November 2017

The beet armyworm, Spodoptera exigua (Hubner), is one of the major crop pests and is a target for current pest control approaches using insecticides. In this study three cuticular protein genes CPG316, CPG860 and CPG4855 have been cloned from 0 h pupal integument of S. exigua through race PCR Strategy. The deduced amino acid sequences were found to contain the RR-2 consensus region of other insect cuticular proteins and construct phylogenetic trees for each protein. Using quantitative RT-PCR, the developmental expression of the three genes through several larval and the early pupal stages was studied. All three genes contribute to the endocuticle although CPG316 may have a different role from the other two genes. All three newly isolated genes were analyzed and their functions were determined by using direct injection of the dsRNA into early 5th instar larvae. All genes are expressed in the larvae and early pupae but in different patterns. Furthermore, phenotypic results show that these genes have differing effects on the development of cuticle, its flexibility and a big role in metamorphosis in both larval and pupal stages.
Nanoparticle core stability and surface functionalization drive the mTOR signaling pathway in hepatocellular cell lines
Authors: Lunova Mariia , Prokhorov Andrey , Jirsa Milan , Hof Martin , Olżyńska Agnieszka , Jurkiewicz Piotr , Kubinová Šárka , Lunov Oleg , Dejneka Alexandr
Published: November 2017

Specifically designed and functionalized nanoparticles hold great promise for biomedical applications. Yet, the applicability of nanoparticles is critically predetermined by their surface functionalization and biodegradability. Here we demonstrate that amino-functionalized polystyrene nanoparticles (PS-NH2), but not amino- or hydroxyl-functionalized silica particles, trigger cell death in hepatocellular carcinoma Huh7 cells. Importantly, biodegradability of nanoparticles plays a crucial role in regulation of essential cellular processes. Thus, biodegradable silica nanoparticles having the same shape, size and surface functionalization showed opposite cellular effects in comparison with similar polystyrene nanoparticles. At the molecular level, PS-NH2 obstruct and amino-functionalized silica nanoparticles (Si-NH2) activate the mTOR signalling in Huh7 and HepG2 cells. PS-NH2 induced time-dependent lysosomal destabilization associated with damage of the mitochondrial membrane. Solely in PS-NH2-treated cells, permeabilization of lysosomes preceded cell death. Contrary, Si-NH2 nanoparticles enhanced proliferation of HuH7 and HepG2 cells. Our findings demonstrate complex cellular responses to functionalized nanoparticles and suggest that nanoparticles can be used to control activation of mTOR signaling with subsequent influence on proliferation and viability of HuH7 cells. The data provide fundamental knowledge which could help in developing safe and efficient nano-therapeutics.
Development of fluorescence polarization immunoassays for parallel detection of pesticides carbaryl and triazophos in wheat grains
Authors: Boroduleva Anna Yu , Wu Jing , Yang Qingqing , Li Hui , Zhang Qi , Li Peiwu , Eremin Sergei A.
Published: November 2017

Fluorescence polarization immunoassays (FPIA) were developed for the determination of pesticides triazophos and carbaryl in wheat grains using the portable FPIA device Sentry 200 (Ellie).
Correction: Synthesis by free radical polymerization and properties of BN-polystyrene and BN-poly(vinylbiphenyl)
Authors: Wan Wen-Ming , Baggett Andrew W. , Cheng Fei , Lin Huina , Lamm Ashley N. , Liu Shih-Yuan , Jäkle Frieder
Published: November 2017

Correction for ‘Synthesis by free radical polymerization and properties of BN-polystyrene and BN-poly(vinylbiphenyl)’ by Wen-Ming Wan et al., Chem. Commun., 2016, 52, 13616–13619.
Chalcogenide substitution in the [2Fe] cluster of [FeFe]-hydrogenases conserves high enzymatic activity
Authors: Kertess L. , Wittkamp F. , Sommer C. , Esselborn J. , Rüdiger O. , Reijerse E. J. , Hofmann E. , Lubitz W. , Winkler M. , Happe T. , Apfel U.-P.
Published: November 2017

Combination of biological and chemical methods allow for creation of [FeFe]-hydrogenases with an artificial synthetic cofactor.
The mechanism of reduced IgG/IgE-binding of β-lactoglobulin by pulsed electric field pretreatment combined with glycation revealed by ECD/FTICR-MS
Authors: Yang Wenhua , Tu Zongcai , Wang Hui , Zhang Lu , Kaltashov Igor A. , Zhao Yunlong , Niu Chendi , Yao Honglin , Ye Wenfeng
Published: November 2017

PEF pretreatment significantly reduced the IgG/IgE-binding ability of β-Lg by the modification of linear epitopes and destruction of conformational epitopes.
Surface coatings of silver nanowires lead to effective, high conductivity, high-strain, ultrathin sensors
Authors: Boland Conor S. , Khan Umar , Benameur Hanane , Coleman Jonathan N.
Published: November 2017

Integrated sensors for bodily measurements require a sensing material that is highly conductive, flexible, thin and sensitive.
In situ/operando characterization techniques for rechargeable lithium–sulfur batteries: a review
Authors: Tan Jian , Liu Dongna , Xu Xu , Mai Liqiang
Published: November 2017

This review summarizes and classifies the recent progress of in situ/operando characterization techniques for Li–S batteries.
Graphene integrated circuits: new prospects towards receiver realisation
Authors: Saeed Mohamed , Hamed Ahmed , Wang Zhenxing , Shaygan Mehrdad , Neumaier Daniel , Negra Renato
Published: November 2017

This work demonstrates a design approach which enables the fabrication of fully integrated radio frequency (RF) and millimetre-wave frequency direct-conversion graphene receivers by adapting the frontend architecture to exploit the state-of-the-art performance of the recently reported wafer-scale CVD metal–insulator–graphene (MIG) diodes.
An extremely low Pt loading cathode for a highly efficient proton exchange membrane water electrolyzer
Authors: Kim Hoyoung , Choe Seunghoe , Park Hyanjoo , Jang Jong Hyun , Ahn Sang Hyun , Kim Soo-Kil
Published: November 2017

The self-terminated electrodeposition (SED) of a Pt cathode with enhanced mass transfer demonstrates high performance of PEMWEs at high current density.
Non-invasive detection of gastric cancer relevantd-amino acids with luminescent DNA/silver nanoclusters
Authors: Zhang Zhikun , Liu Yang , Liu Peifeng , Yang Lu , Jiang Xingyu , Luo Dan , Yang Dayong
Published: November 2017

Gastric cancer relevantd-amino acids were non-invasively detected with luminescent DNA/silver nanoclusters.
Fabrication of carbon quantum dots with nano-defined position and pattern in one stepviasugar-electron-beam writing
Authors: Weng Yuyan , Li Zhiyun , Peng Lun , Zhang Weidong , Chen Gaojian
Published: November 2017

Combining an electron beam with PMAG enables thein situproduction of CQDs with a nano-defined position and pattern.
Correction: Key role of surface oxidation and reduction processes in the coarsening of Pt nanoparticles
Authors: Solano Eduardo , Dendooven Jolien , Minjauw Matthias M. , Ramachandran Ranjith K. , Van de Kerckhove Kevin , Dobbelaere Thomas , Hermida-Merino Daniel , Detavernier Christophe
Published: November 2017

Correction for ‘Key role of surface oxidation and reduction processes in the coarsening of Pt nanoparticles’ by Eduardo Solano et al., Nanoscale, 2017, 9, 13159–13170.
A fluorescent combinatorial logic gate with Na+, H+-enabled OR and H+-driven low-medium-high ternary logic functions
Authors: Spiteri Jasmine M. A. , Mallia Carl J. , Scerri Glenn J. , Magri David C.
Published: November 2017

A fluorescent combinatorial Na+, H+logic gate is demonstrated that could represent a class of probes for investigating antiporters in biological systems.
Investigating the lithium ion battery electrolyte additive tris (2,2,2-trifluoroethyl) phosphite by gas chromatography with a flame ionization detector (GC-FID)
Authors: Dagger Tim , Henschel Jonas , Rad Babak , Lürenbaum Constantin , Schappacher Falko M. , Winter Martin , Nowak Sascha
Published: November 2017

The quantification of lithium ion battery electrolyte additives like flame retardants is both important and challenging. Here, different analytical methods were applied to investigate detection phenomena when applying GC-FID for the quantification.
Efficient interface and bulk passivation of PbS quantum dot infrared photodetectors by PbI2incorporation
Authors: Qiao Keke , Cao Yulin , Yang Xiaokun , Khan Jahangeer , Deng Hui , Zhang Jian , Farooq Umar , Yuan Shengjie , Song Haisheng
Published: November 2017

A simple passivation method based on PbI2was developed, which can effectively suppress the heterojunction interface and PbS QD surface defects by interface and ligand passivation.
Chiral carbon dots and their effect on the optical properties of photosensitizers
Authors: Deka Manash Jyoti , Chowdhury Devasish
Published: November 2017

In this work, we have successfully prepared intrinsically chiral carbon dots from chiral precursors. We have also demonstrated that the chirality of these carbon dots can affect the optical properties of photosensitizer molecules like azobenzene.
Combinatorial experimental and DFT theoretical investigation over the formation mechanism of a binuclear phthalocyanine dimer
Authors: Wang Chiming , Chen Xin , Liu Qingyun , Qi Dongdong , Wang Kang , Jiang Jianzhuang
Published: November 2017

Herein, a density functional calculation method was used to explore the formation mechanism of a metal-free, homobinuclear phthalocyanine dimer.
Correction: Mesoporous Ag1(NH4)2PW12O40 heteropolyacids as effective catalysts for the esterification of oleic acid to biodiesel
Authors: Zhang Qiu-yun , Wei Fang-fang , Li Qian , Huang Jin-shu , Feng Yun-mei , Zhang Yu-tao
Published: November 2017

Correction for ‘Mesoporous Ag1(NH4)2PW12O40 heteropolyacids as effective catalysts for the esterification of oleic acid to biodiesel’ by Qiu-yun Zhang et al., RSC Adv., 2017, 7, 51090–51095.
Non-Gaussian elasticity and charge density-dependent swelling of strong polyelectrolyte poly(N-isopropylacrylamide-co-sodium acrylate) hydrogels
Authors: Orakdogen Nermin , Boyacı Talin
Published: November 2017

The charge density dependence of swelling and volume dependence of the elastic modulus were investigated with a predicted course of non-Gaussian elasticity ofN-isopropylacrylamide-based hydrogels.