bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise in pregnancy: 1-year and 7-year follow-ups of mothers and offspring after a randomized controlled trial
Authors: Chiavaroli Valentina , Hopkins Sarah A. , Derraik José G. B. , Biggs Janene B. , Rodrigues Raquel O. , Brennan Christine H. , Seneviratne Sumudu N. , Higgins Chelsea , Baldi James C. , McCowan Lesley M. E. , Cutfield Wayne S. , Hofman Paul L.
Published: August 2018

There are limited data on long-term outcomes of mothers or their offspring following exercise interventions during pregnancy. We assessed long-term effects of an exercise intervention (home-based stationary cycling) between 20–36 weeks of gestation on anthropometry and body composition in mothers and offspring after 1 and 7 years. 84 women were randomised to intervention or usual activity, with follow-up data available for 61 mother-child pairs (38 exercisers) at 1 year and 57 (33 exercisers) at 7 years. At 1 year, there were no observed differences in measured outcomes between mothers and offspring in the two groups. At the 7-year follow-up, mothers were mostly similar, except that exercisers had lower systolic blood pressure (−6.2 mmHg; p = 0.049). However, offspring of mothers who exercised during pregnancy had increased total body fat (+3.2%; p = 0.034) and greater abdominal (+4.1% android fat; p = 0.040) and gynoid (+3.5% gynoid fat; p = 0.042) adiposity compared with controls. Exercise interventions beginning during pregnancy may be beneficial to long-term maternal health. However, the initiation of exercise during pregnancy amongst sedentary mothers may be associated with adverse effects in the offspring during childhood. Larger follow-up studies are required to investigate long-term effects of exercise in pregnancy.
Experimental evidence for the preservation of U-Pb isotope ratios in mantle-recycled crustal zircon grains
Authors: Bea Fernando , Montero Pilar , Palma Jose Francisco Molina
Published: August 2018

Zircon of crustal origin found in mantle-derived rocks is of great interest because of the information it may provide about crust recycling and mantle dynamics. Consideration of this requires understanding of how mantle temperatures, notably higher than zircon crystallization temperatures, affected the recycled zircon grains, particularly their isotopic clocks. Since Pb2+ diffuses faster than U4+ and Th+4, it is generally believed that recycled zircon grains lose all radiogenic Pb after a few million years, thus limiting the time range over which they can be detected. Nonetheless, this might not be the case for zircon included in mantle minerals with low Pb2+ diffusivity and partitioning such as olivine and orthopyroxene because these may act as zircon sealants. Annealing experiments with natural zircon embedded in cristobalite (an effective zircon sealant) show that zircon grains do not lose Pb to their surroundings, although they may lose some Pb to molten inclusions. Diffusion tends to homogenize the Pb concentration in each grain changing the U-Pb and Th-Pb isotope ratios proportionally to the initial 206Pb, 207Pb and 208Pb concentration gradients (no gradient-no change) but in most cases the original age is still recognizable. It seems, therefore, that recycled crustal zircon grains can be detected, and even accurately dated, no matter how long they have dwelled in the mantle.
Removal of choroidal vasculature using concurrently applied ultrasound bursts and nanosecond laser pulses
Authors: Zhang Haonan , Xie Xinyi , Li Jia , Qin Yu , Zhang Wei , Cheng Qian , Yuan Songtao , Liu Qinghuai , Paulus Yannis M. , Wang Xueding , Yang Xinmai
Published: August 2018

Pathologic microvasculature plays a crucial role in innumerable diseases causing death and major organ impairment. A major clinical challenge is the development of selective therapies to remove these diseased microvessels without damaging surrounding tissue. This report describes our development of novel photo-mediated ultrasound therapy (PUT) technology for precisely removing choroidal blood vessels in the eye. PUT selectively removes microvessels by concurrently applying nanosecond laser pulses with ultrasound bursts. In PUT experiments on rabbit eyes in vivo, we applied 55–75 mJ/cm2 of light fluence at the retinochoroidal surface at 532-nm and 0.5 MPa of ultrasound pressure at 0.5 MHz. PUT resulted in significantly reduced blood perfusion in the choroidal layer which persisted to four weeks without causing collateral tissue damage, demonstrating that PUT is capable of removing choroidal microvasculature safely and effectively. With its unique advantages, PUT holds potential for the clinical management of eye diseases associated with microvessels and neovascularization.
Modeling of inhomogeneous electromagnetic fields in the nervous system: a novel paradigm in understanding cell interactions, disease etiology and therapy
Authors: Isakovic Jasmina , Dobbs-Dixon Ian , Chaudhury Dipesh , Mitrecic Dinko
Published: August 2018

All major processes in the nervous system depend on interactions between cells and nerve fibers. In this work we present a novel model of inhomogeneous electromagnetic fields originating from nerve fibers and delineate their influence on cells. By expanding Hodgkin-Huxley’s applied current into axial current, governed by$${J}_{i}^{j+1}=K\times {J}_{i}^{j}$$

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, we reveal that cell-with-neuron interactions are regulated by the strength of the electromagnetic fields, which are homogeneous up to 2.066 μm or 6.606 μm away from neurilemma and axolemma, respectively. At the nodes of Ranvier, these fields reach strengths of 3.0 × 10−12T, while at the myelinated segments they only peak at 2.3 × 10−12T. These are the same fields which are, due to inhomogeneity, detected as 1,000 times weaker by magnetoencephalography. Considering the widespread occurrence of neurodegenerative disorders, our model reveals that a 50% demyelination increases the field strength by 0.35 × 10−12T, while a complete demyelination increases it by 0.7 × 10−12T. Since this suggests that the inhomogeneous electromagnetic fields around neurons play a role in physiological and pathological processes, including cell-to-neuron and cell-to-cell communication, their improved understanding opens up new therapeutic strategies based on electromagnetic field modulation or cell’s surface charge alteration.
Transcriptional shifts account for divergent resource allocation in feed efficient broiler chickens
Authors: Reyer Henry , Metzler-Zebeli Barbara U. , Trakooljul Nares , Oster Michael , Muráni Eduard , Ponsuksili Siriluck , Hadlich Frieder , Wimmers Klaus
Published: August 2018

Considerable variation in feed efficiency (FE) has been observed in indigenous and selected meat-type chicken populations. Although this variation could be partially linked to extrinsic factors like diet, housing environment and microbiota, it further illustrates the existence of strong molecular mechanisms enabling the differential allocation of resources for various physiological processes. To further deepen the molecular basis of individual allocation capacity in male and female broilers, an RNA-seq experiment was conducted which based on a phenotyped chicken population divergent in FE. Transcriptional differences linked to FE were pronounced in intestinal and muscular tissue sites of male animals. Specifically, signalling pathways of farnesoid X receptor (FXR) and retinoid X receptor (RXR) might contribute to mediate individual FE. The transcriptional profiles suggested ACSBG2 (muscular lipid utilisation), ASBT (intestinal bile salt transport), CLEC2B (natural killer cell activation), HMGCS2 (jejunal, duodenal and muscular ketogenesis), and SCARB1 (jejunal lipid uptake) as potential mediators driving FE. Results indicate that improvements in FE exploit shifts in resource allocation which might occur at the expense of general immune responsiveness in high efficient male chickens. Consequently, to further improve FE traits and to explore causative molecular patterns, effects originating from sex-dimorphism in chickens need to be taken into consideration.
The splicing factor SRSF3 is functionally connected to the nuclear RNA exosome for intronless mRNA decay
Authors: Mure Fabrice , Corbin Antoine , Benbahouche Nour El Houda , Bertrand Edouard , Manet Evelyne , Gruffat Henri
Published: August 2018

The RNA exosome fulfills important functions in the processing and degradation of numerous RNAs species. However, the mechanisms of recruitment to its various nuclear substrates are poorly understood. Using Epstein-Barr virus mRNAs as a model, we have discovered a novel function for the splicing factor SRSF3 in the quality control of nuclear mRNAs. We have found that viral mRNAs generated from intronless genes are particularly unstable due to their degradation by the nuclear RNA exosome. This effect is counteracted by the viral RNA-binding protein EB2 which stabilizes these mRNAs in the nucleus and stimulates both their export to the cytoplasm and their translation. In the absence of EB2, SRSF3 participates in the destabilization of these viral RNAs by interacting with both the RNA exosome and its adaptor complex NEXT. Taken together, our results provide direct evidence for a connection between the splicing machinery and mRNA decay mediated by the RNA exosome. Our results suggest that SRSF3 aids the nuclear RNA exosome and the NEXT complex in the recognition and degradation of certain mRNAs.
Visualizing the hydrodynamics in sieve-based lateral displacement systems
Authors: Dijkshoorn J. P. , de Valença J. C. , Wagterveld R. M. , Boom R. M. , Schutyser M. A. I.
Published: August 2018

Deterministic lateral displacement (DLD) systems structure suspension flow in so called flow lanes. The width of these flow lanes is crucial for separation of particles and determines whether particles with certain size are displaced or not. In previous research, separation was observed in simplified DLD systems that did not meet the established DLD geometric design criteria, by adjusting the outflow conditions. We here investigated why these simplified DLD systems are able to displace particles, by experimentally investigating the hydrodynamics in the device. Flow lanes were visualized and the local flow velocities were measured using µPIV and compared with 2D fluid dynamics simulations. The size of the flow lanes strongly correlates with the local flow velocity (Vy and Vx), which depends on the hydrodynamics. Therefore, the geometric design criteria of DLD devices is in fact just one method to control the local hydrodynamics, which may also be influenced by other means. These findings give a new perspective on the separation principle, which makes the technique more flexible and easier to translate to industrial scale.
Colloidal nitrogen is an important and highly-mobile form of nitrogen discharging into the Great Barrier Reef lagoon
Authors: Judy Jonathan D. , Kirby Jason K. , Farrell Mark , McLaughlin Mike J. , Wilkinson Scott N. , Bartley Rebecca , Bertsch Paul M.
Published: August 2018

Soil-borne colloids have been linked to long-distance transport of radionuclides, metal(loid)s and nutrients. Colloid-associated nitrogen (N) will have different mechanisms of biogeochemical cycling and potential for water-borne transport over longer distances compared to dissolved N. The role that colloids play in the supply and mobility of N within catchments discharging into the Great Barrier Reef (GBR) lagoon is unexplored. Here, we examine water-dispersible clay (WDC) from soil samples collected from gullies and agricultural drains within three different land uses (sugarcane, non-agricultural land and grazing) within the Townsville area. The proportion of soil N associated with WDC was inversely correlated with total soil N, with up to 45% of the total soil N being colloid-associated in low N gully soils. Within the <0.45 µm fraction of the WDC, only 17–25% of the N was truly dissolved (<3 kDa) at the gully sites compared to 58% in the sugarcane sites. Our results demonstrate the importance of colloidal N and the inaccuracy of assuming N < 0.45 µm is dissolved in the sampled areas, as well as providing an alternate explanation for the large amounts of what has previously been defined as dissolved inorganic N in runoff from non-fertilized grazing land. In particular, they describe why non-fertilized land uses can contribute significant N < 0.45 µm, and why catchment models of nutrient export based on soil N concentrations can over-estimate loads of particulate nitrogen derived from monitoring data (N > 0.45 µm). The findings suggest that managing soil erosion may also contribute to managing N < 0.45 µm.
Defining the architecture of KPC-2 Carbapenemase: identifying allosteric networks to fight antibiotics resistance
Authors: Galdadas Ioannis , Lovera Silvia , Pérez-Hernández Guillermo , Barnes Melissa D. , Healy Jess , Afsharikho Hamidreza , Woodford Neil , Bonomo Robert A. , Gervasio Francesco L. , Haider Shozeb
Published: August 2018

The rise of multi-drug resistance in bacterial pathogens is one of the grand challenges facing medical science. A major concern is the speed of development of β-lactamase-mediated resistance in Gram-negative species, thus putting at risk the efficacy of the most recently approved antibiotics and inhibitors, including carbapenems and avibactam, respectively. New strategies to overcome resistance are urgently required, which will ultimately be facilitated by a deeper understanding of the mechanisms that regulate the function of β-lactamases such as the Klebsiella Pneumoniae carbapenemases (KPCs). Using enhanced sampling computational methods together with site-directed mutagenesis, we report the identification of two “hydrophobic networks” in the KPC-2 enzyme, the integrity of which has been found to be essential for protein stability and corresponding resistance. Present throughout the structure, these networks are responsible for the structural integrity and allosteric signaling. Disruption of the networks leads to a loss of the KPC-2 mediated resistance phenotype, resulting in restored susceptibility to different classes of β-lactam antibiotics including carbapenems and cephalosporins. The ”hydrophobic networks” were found to be highly conserved among class-A β-lactamases, which implies their suitability for exploitation as a potential target for therapeutic intervention.
A novel pathway for the photooxidation of catechin in relation to its prooxidative activity
Authors: Shishido Shunichi , Miyano Rei , Nakashima Takuji , Matsuo Hirotaka , Iwatsuki Masato , Nakamura Keisuke , Kanno Taro , Egusa Hiroshi , Niwano Yoshimi
Published: August 2018

In the present study, we evaluated the prooxidative mode of action of photoirradiated (+)-catechin at 400 nm in relation to reactive oxygen species generation and its possible application to disinfection. Photoirradiation of (+)-catechin at a concentration of 1 mg/mL yielded not only hydrogen peroxide (H2O2) but hydroxyl radical (·OH) in a total amount of approximately 20 μM in 10 min. As a result, photoirradiated catechin killed Staphylococcus aureus, and a > 5-log reduction in viable bacteria counts was observed within 20 min. Liquid chromatography-high-resolution-electrospray ionization-mass spectrometry showed that photoirradiation decreased the (+)-catechin peak (molecular formula C15H14O6) whilst it increased two peaks of a substance with the molecular formula C15H12O6 with increasing irradiation time. Nuclear magnetic resonance analysis revealed that the two C15H12O6 peaks were allocated to intramolecular cyclization products that are enantiomers of each other. These results suggest that photoirradiation induces oxidation of (+)-catechin resulting in the reduction of oxygen to generate H2O2. This H2O2 is then homolytically cleaved to ·OH, and alongside this process, (+)-catechin is finally converted to two intramolecular cyclization products that are different from the quinone structure of the B ring, as proposed previously for the autoxidation and enzymatic oxidation of catechins.
Detection of pathogenic microorganisms from bloodstream infection specimens using TaqMan array card technology
Authors: Zhang Chao , Zheng Xin , Zhao Chengna , Li Yan , Chen Shuiping , Liu Gang , Wang Chengbin , Lv Qingyu , Liu Peng , Zheng Yuling , Kong Decong , Jiang Hua , Jiang Yongqiang
Published: August 2018

Bloodstream infections (BSIs) are often life-threatening, and rapid identification is critical. Here, we developed a TaqMan array card (TAC) assay to detect pathogens in BSI specimens. The TAC included 30 primer/probe pairs targeting 27 species and 3 controls. Reverse transcription and 0.1% blue dextran 2000 increased the TAC assay efficiency. The primer/probe pairs had a limit of detection of 100–102 CFU/mL and a specificity of 100%. For whole blood specimens, the TAC assay showed a sensitivity and specificity of 79.4% and 99.69%, respectively. For blood culture samples, the TAC assay showed a sensitivity and specificity of 100% and 99.67%, respectively. The TAC assay could be a promising method for early detection of bloodstream infection.
Spontaneous light-induced Turing patterns in a dye-doped twisted nematic layer
Authors: Andrade-Silva Ignacio , Bortolozzo Umberto , Clerc Marcel G. , González-Cortés Gregorio , Residori Stefania , Wilson Mario
Published: August 2018

Optical pattern formation is usually due either to the combination of diffraction and nonlinearity in a Kerr medium or to the temporal modulation of light in a photosensitive chemical reaction. Here, we show a different mechanism by which light spontaneously induces stripe domains between nematic states in a twisted nematic liquid crystal layer doped with azo-dyes. Thanks to the photoisomerization process of the dopants, light in the absorption band of the dopants creates spontaneous patterns without the need of temporal modulation, diffraction, Kerr or other optical nonlinearity, but based on the different scales for dopant transport processes and nematic order parameter, which identifies a genuine Turing mechanism for this instability. Theoretically, the emergence of the stripe patterns is described on the basis of a model for the dopant concentration coupled with the nematic order parameter.
Projecting groundwater storage changes in California’s Central Valley
Authors: Massoud Elias C. , Purdy Adam J. , Miro Michelle E. , Famiglietti James S.
Published: August 2018

Accurate and detailed knowledge of California’s groundwater is of paramount importance for statewide water resources planning and management, and to sustain a multi-billion-dollar agriculture industry during prolonged droughts. In this study, we use water supply and demand information from California’s Department of Water Resources to develop an aggregate groundwater storage model for California’s Central Valley. The model is evaluated against 34 years of historic estimates of changes in groundwater storage derived from the United States Geological Survey’s Central Valley Hydrologic Model (USGS CVHM) and NASA’s Gravity Recovery and Climate Experiment (NASA GRACE) satellites. The calibrated model is then applied to predict future changes in groundwater storage for the years 2015–2050 under various precipitation scenarios from downscaled climate projections. We also discuss and project potential management strategies across different annual supply and demand variables and how they affect changes in groundwater storage. All simulations support the need for collective statewide management intervention to prevent continued depletion of groundwater availability.
Two-Dimensional MoxW1−xS2 Graded Alloys: Growth and Optical Properties
Authors: Bogaert Kevin , Liu Song , Liu Tao , Guo Na , Zhang Chun , Gradečak Silvija , Garaj Slaven
Published: August 2018

Two-dimensional (2D) transition metal dichalcogenides can be alloyed by substitution at the metal atom site with negligible effect on lattice strain, but with significant influence on optical and electrical properties. In this work, we establish the relationship between composition and optical properties of the MoxW1−xS2 alloy by investigating the effect of continuously-varying composition on photoluminescence intensity. We developed a new process for growth of two-dimensional MoxW1−xS2 alloys that span nearly the full composition range along a single crystal, thus avoiding any sample-related heterogeneities. The graded alloy crystals were grown using a diffusion-based chemical vapor deposition (CVD) method that starts by synthesizing a WS2 crystal with a graded point defect distribution, followed by Mo alloying in the second stage. We show that point defects promote the diffusion and alloying, as confirmed by Raman and photoluminescence measurements, density functional theory calculations of the reaction path, and observation that no alloying occurs in CVD-treated exfoliated crystals with low defect density. We observe a significant dependence of the optical quantum yield as a function of the alloy composition reaching the maximum intensity for the equicompositional Mo0.5W0.5S2 alloy. Furthermore, we map the growth-induced strain distribution within the alloyed crystals to decouple composition and strain effects on optical properties: at the same composition, we observe significant decrease in quantum yield with induced strain. Our approach is generally applicable to other 2D materials as well as the optimization of other composition-dependent properties within a single crystal.
Neural Evidence of Cross-domain Structural Interaction between Language and Arithmetic
Authors: Nakai Tomoya , Okanoya Kazuo
Published: August 2018

The presence of a shared neural system for the syntactic processing in language and arithmetic is controversial. Recent behavioral studies reported a cross-domain structural priming between language and arithmetic. Using functional magnetic resonance imaging, we examined whether the neural activation reflects the structural interaction between language and arithmetic. We prepared sentences and arithmetic expressions (A-expressions) with same and different syntactic structures and presented structurally congruent/incongruent pairs consecutively. By directly comparing activations in the congruent and incongruent conditions, we observed significant repetition suppression effect in the regions including the bilateral inferior frontal gyrus, i.e., neural activation with an A-expression decreased after a sentence with the same syntactic structure (and vice versa). The results strongly support the idea that arithmetic and language share the neural basis for processing syntactic structures.
A deep convolutional neural network approach for astrocyte detection
Authors: Suleymanova Ilida , Balassa Tamas , Tripathi Sushil , Molnar Csaba , Saarma Mart , Sidorova Yulia , Horvath Peter
Published: August 2018

Astrocytes are involved in various brain pathologies including trauma, stroke, neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases, or chronic pain. Determining cell density in a complex tissue environment in microscopy images and elucidating the temporal characteristics of morphological and biochemical changes is essential to understand the role of astrocytes in physiological and pathological conditions. Nowadays, manual stereological cell counting or semi-automatic segmentation techniques are widely used for the quantitative analysis of microscopy images. Detecting astrocytes automatically is a highly challenging computational task, for which we currently lack efficient image analysis tools. We have developed a fast and fully automated software that assesses the number of astrocytes using Deep Convolutional Neural Networks (DCNN). The method highly outperforms state-of-the-art image analysis and machine learning methods and provides precision comparable to those of human experts. Additionally, the runtime of cell detection is significantly less than that of other three computational methods analysed, and it is faster than human observers by orders of magnitude. We applied our DCNN-based method to examine the number of astrocytes in different brain regions of rats with opioid-induced hyperalgesia/tolerance (OIH/OIT), as morphine tolerance is believed to activate glia. We have demonstrated a strong positive correlation between manual and DCNN-based quantification of astrocytes in rat brain.
Role of solvent accessibility for aggregation-prone patches in protein folding
Authors: Mishra Avinash , Ranganathan Shoba , Jayaram B. , Sattar Abdul
Published: August 2018

The arrangement of amino acids in a protein sequence encodes its native folding. However, the same arrangement in aggregation-prone regions may cause misfolding as a result of local environmental stress. Under normal physiological conditions, such regions congregate in the protein’s interior to avoid aggregation and attain the native fold. We have used solvent accessibility of aggregation patches (SAAPp) to determine the packing of aggregation-prone residues. Our results showed that SAAPp has low values for native crystal structures, consistent with protein folding as a mechanism to minimize the solvent accessibility of aggregation-prone residues. SAAPp also shows an average correlation of 0.76 with the global distance test (GDT) score on CASP12 template-based protein models. Using SAAPp scores and five structural features, a random forest machine learning quality assessment tool, SAAP-QA, showed 2.32 average GDT loss between best model predicted and actual best based on GDT score on independent CASP test data, with the ability to discriminate native-like folds having an AUC of 0.94. Overall, the Pearson correlation coefficient (PCC) between true and predicted GDT scores on independent CASP data was 0.86 while on the external CAMEO dataset, comprising high quality protein structures, PCC and average GDT loss were 0.71 and 4.46 respectively. SAAP-QA can be used to detect the quality of models and iteratively improve them to native or near-native structures.
Na1−xSn2P2 as a new member of van der Waals-type layered tin pnictide superconductors
Authors: Goto Yosuke , Miura Akira , Moriyoshi Chikako , Kuroiwa Yoshihiro , Matsuda Tatsuma D. , Aoki Yuji , Mizuguchi Yoshikazu
Published: August 2018

Superconductors with a van der Waals (vdW) structure have attracted a considerable interest because of the possibility for truly two-dimensional (2D) superconducting systems. We recently reported NaSn2As2 as a novel vdW-type superconductor with transition temperature (Tc) of 1.3 K. Herein, we present the crystal structure and superconductivity of new material Na1−xSn2P2 with Tc = 2.0 K. Its crystal structure consists of two layers of a buckled honeycomb network of SnP, bound by the vdW forces and separated by Na ions, as similar to that of NaSn2As2. Amount of Na deficiency (x) was estimated to be 0.074(18) using synchrotron X-ray diffraction. Bulk nature of superconductivity was confirmed by the measurements of electrical resistivity, magnetic susceptibility, and specific heat. First-principles calculation using density functional theory shows that Na1−xSn2P2 and NaSn2As2 have comparable electronic structure, suggesting higher Tc of Na1−xSn2P2 resulted from increased density of states at the Fermi level due to Na deficiency. Because there are various structural analogues with tin-pnictide (SnPn) conducting layers, our results indicate that SnPn-based layered compounds can be categorized into a novel family of vdW-type superconductors, providing a new platform for studies on physics and chemistry of low-dimensional superconductors.
A Kelch domain-containing KLHDC7B and a long non-coding RNA ST8SIA6-AS1 act oppositely on breast cancer cell proliferation via the interferon signaling pathway
Authors: Jeong Gookjoo , Bae Hansol , Jeong Dawoon , Ham Juyeon , Park Sungbin , Kim Hyeon Woo , Kang Han-Sung , Kim Sun Jung
Published: August 2018

In our previous study, the Kelch domain-containing 7B (KLHDC7B) was revealed to be hypermethylated at the promoter but upregulated in breast cancer. In this study, we identified a long non-coding RNA, ST8SIA6-AS1 (STAR1), whose expression was significantly associated with KLHDC7B in breast cancer (R2 = 0.3466, P < 0.01). Involvement of the two genes in tumorigenesis was examined via monitoring their effect on cellular as well as molecular events after each gene dysregulation in cultured mammary cell lines. Apoptosis of MCF-7 decreased by 49.5% and increased by 33.1%, while proliferation noted increase and decrease by up- and downregulation of KLHDC7B, respectively, suggesting its oncogenic property. STAR1, however, suppressed cell migration and increased apoptosis. Network analysis identified many target genes that appeared to have similar regulation, especially in relation to the interferon signaling pathway. Concordantly, expression of genes such as IFITs, STATs, and IL-29 in that pathway was affected by KLHDC7B and STAR1. Taken together, KLHDC7B and STAR1 are both overexpressed in breast cancer and significantly associated with gene modulation activity in the interferon signaling pathway during breast tumorigenesis.
Identification of a Novel Clinical Phenotype of Severe Malaria using a Network-Based Clustering Approach
Authors: Cominetti Ornella , Smith David , Hoffman Fred , Jallow Muminatou , Thézénas Marie L. , Huang Honglei , Kwiatkowski Dominic , Maini Philip K. , Casals-Pascual Climent
Published: August 2018

The parasite Plasmodium falciparum is the main cause of severe malaria (SM). Despite treatment with antimalarial drugs, more than 400,000 deaths are reported every year, mainly in African children. The diversity of clinical presentations associated with SM highlights important differences in disease pathogenesis that often require specific therapeutic options. The clinical heterogeneity of SM is largely unresolved. Here we report a network-based analysis of clinical phenotypes associated with SM in 2,915 Gambian children admitted to hospital with Plasmodium falciparum malaria. We used a network-based clustering method which revealed a strong correlation between disease heterogeneity and mortality. The analysis identified four distinct clusters of SM and respiratory distress that departed from the WHO definition. Patients in these clusters characteristically presented with liver enlargement and high concentrations of brain natriuretic peptide (BNP), giving support to the potential role of circulatory overload and/or right-sided heart failure as a mechanism of disease. The role of heart failure is controversial in SM and our work suggests that standard clinical management may not be appropriate. We find that our clustering can be a powerful data exploration tool to identify novel disease phenotypes and therapeutic options to reduce malaria-associated mortality.
The Importance of Signal Strength in Quantitative Assessment of Retinal Vessel Density Using Optical Coherence Tomography Angiography
Authors: Lim Hyung Bin , Kim Yong Woo , Kim Ju Mi , Jo Young Joon , Kim Jung Yeul
Published: August 2018

The quality of the scan image is important in microvascular circulation analysis using optical coherence tomography (OCTA). We aimed to investigate the effect of signal strength (SS) on OCTA metrics and minimum SS level that could be considered optimal. Macular 6 × 6 mm angiography images were acquired, and all subjects were divided into four groups according to the SS (SS 7, SS 8, SS 9, and SS 10) of the OCTA image. Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) metrics of the superficial capillary plexus were compared. In total, 446 eyes from young healthy subjects were included. As the SS increased from 7 to 10, the VD and PD of the total area, and the FAZ area increased significantly (all, p < 0.001), but there were no significant difference between SS 9 and SS 10 in all metrics. Correlation analysis between the SS and each parameter showed a high correlation coefficient (VD, r = 0.668; PD, r = 0.671; FAZ area, r = 0.570; all, p < 0.001). The measurements of VD, PD, and FAZ using OCTA varied significantly with the SS, and at least 9 of SS is recommended. The physician should be careful in the analyses of OCTA measurements showing different values of the SS.
Anatomical features of the incisivus labii superioris muscle and its relationships with the upper mucolabial fold, labial glands, and modiolar area
Authors: Hur Mi-Sun
Published: August 2018

The current study examined the incisivus labii superioris muscle (ILS) and its morphologic and spatial relationships with the surrounding structures, especially focusing on the upper mucolabial fold, labial glands, and modiolar area. ILSs were investigated in 52 specimens obtained from formalin-fixed Korean adult cadavers (26 left sides, 26 right sides of the face; 15 men, 11 women; mean age, 70.8 years). ILSs were observed in all specimens (100%). The ILS has an oblique and linear origin from the incisive fossa of the maxilla to the point just medial to the origin of the levator anguli oris muscle (LAO). The arising fibers of the ILS arched and covered the prominent labial glands at the superior margin of the orbicularis oris muscle (OOr). After the ILS coursed laterally along the anterior part of the upper mucolabial fold, it divided into superficial and deep inserting fibers in 48 specimens (92.3%) and it did not divide in 4 specimens (7.7%). The superficial inserting ILS fibers and the ILS fibers that did not divide blended with the medial fibers of the LAO to converge toward the modiolus. The deep inserting fibers of the ILS blended with the lateral deep fibers of the OOr in the 48 specimens (92.3%), and the deep inserting fibers continued to descend to converge toward the modiolus in 20 of those specimens (38.5%). These observations indicate that the ILS may assist to compress the labial glands and the upper oral vestibule, controlling modiolar movements and thereby integrating the movements of the mouth and lips.
Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy in primary care offices
Authors: Abràmoff Michael D. , Lavin Philip T. , Birch Michele , Shah Nilay , Folk James C.
Published: August 2018

Artificial Intelligence (AI) has long promised to increase healthcare affordability, quality and accessibility but FDA, until recently, had never authorized an autonomous AI diagnostic system. This pivotal trial of an AI system to detect diabetic retinopathy (DR) in people with diabetes enrolled 900 subjects, with no history of DR at primary care clinics, by comparing to Wisconsin Fundus Photograph Reading Center (FPRC) widefield stereoscopic photography and macular Optical Coherence Tomography (OCT), by FPRC certified photographers, and FPRC grading of Early Treatment Diabetic Retinopathy Study Severity Scale (ETDRS) and Diabetic Macular Edema (DME). More than mild DR (mtmDR) was defined as ETDRS level 35 or higher, and/or DME, in at least one eye. AI system operators underwent a standardized training protocol before study start. Median age was 59 years (range, 22–84 years); among participants, 47.5% of participants were male; 16.1% were Hispanic, 83.3% not Hispanic; 28.6% African American and 63.4% were not; 198 (23.8%) had mtmDR. The AI system exceeded all pre-specified superiority endpoints at sensitivity of 87.2% (95% CI, 81.8–91.2%) (>85%), specificity of 90.7% (95% CI, 88.3–92.7%) (>82.5%), and imageability rate of 96.1% (95% CI, 94.6–97.3%), demonstrating AI’s ability to bring specialty-level diagnostics to primary care settings. Based on these results, FDA authorized the system for use by health care providers to detect more than mild DR and diabetic macular edema, making it, the first FDA authorized autonomous AI diagnostic system in any field of medicine, with the potential to help prevent vision loss in thousands of people with diabetes annually. ClinicalTrials.gov NCT02963441
In situ serial crystallography for rapid de novo membrane protein structure determination
Authors: Huang Chia-Ying , Olieric Vincent , Howe Nicole , Warshamanage Rangana , Weinert Tobias , Panepucci Ezequiel , Vogeley Lutz , Basu Shibom , Diederichs Kay , Caffrey Martin , Wang Meitian
Published: August 2018

De novo membrane protein structure determination is often limited by the availability of large crystals and the difficulties in obtaining accurate diffraction data for experimental phasing. Here we present a method that combines in situ serial crystallography with de novo phasing for fast, efficient membrane protein structure determination. The method enables systematic diffraction screening and rapid data collection from hundreds of microcrystals in in meso crystallization wells without the need for direct crystal harvesting. The requisite data quality for experimental phasing is achieved by accumulating diffraction signals from isomorphous crystals identified post-data collection. The method works in all experimental phasing scenarios and is particularly attractive with fragile, weakly diffracting microcrystals. The automated serial data collection approach can be readily adopted at most microfocus macromolecular crystallography beamlines.
Structural rearrangements in the C-terminal domain homolog of Orange Carotenoid Protein are crucial for carotenoid transfer
Authors: Harris Dvir , Wilson Adjele , Muzzopappa Fernando , Sluchanko Nikolai N. , Friedrich Thomas , Maksimov Eugene G. , Kirilovsky Diana , Adir Noam
Published: August 2018

A recently reported family of soluble cyanobacterial carotenoproteins, homologs of the C-terminal domain (CTDH) of the photoprotective Orange Carotenoid Protein, is suggested to mediate carotenoid transfer from the thylakoid membrane to the Helical Carotenoid Proteins, which are paralogs of the N-terminal domain of the OCP. Here we present the three-dimensional structure of a carotenoid-free CTDH variant from Anabaena (Nostoc) PCC 7120. This CTDH contains a cysteine residue at position 103. Two dimer-forming interfaces were identified, one stabilized by a disulfide bond between monomers and the second between each monomer’s β-sheets, both compatible with small-angle X-ray scattering data and likely representing intermediates of carotenoid transfer processes. The crystal structure revealed a major positional change of the C-terminal tail. Further mutational analysis revealed the importance of the C-terminal tail in both carotenoid uptake and delivery. These results have allowed us to suggest a detailed model for carotenoid transfer via these soluble proteins.
Comprehensive high-resolution multiple-reaction monitoring mass spectrometry for targeted eicosanoid assays
Authors: Sorgi Carlos Artério , Peti Ana Paula Ferranti , Petta Tania , Meirelles Alyne Fávero Galvão , Fontanari Caroline , Moraes Luiz Alberto Beraldo de , Faccioli Lúcia Helena
Published: August 2018

Eicosanoids comprise a class of bioactive lipids derived from a unique group of essential fatty acids that mediate a variety of important physiological functions. Owing to the structural diversity of these lipids, their analysis in biological samples is often a major challenge. Advancements in mass spectrometric have been helpful for the characterization and quantification of these molecular lipid species in complex matrices. However, there are technical limitations to this approach, including low-abundant and/or poorly ionizable lipids. Using high-resolution multiple-reaction monitoring (MRMHR), we were able to develop a targeted bioanalytical method for eicosanoid quantification. For this, we optimized the LC-MS/MS conditions and evaluated several parameters, including linearity, limits of quantification, matrix effects and recovery yields. For validation purposes, we looked at the method’s precision and accuracy. A library of high-resolution fragmentation spectra for eicosanoids was developed. Our comprehensive dataset meets benchmark standards for targeted analysis, having been derived using best-practice workflows and rigorous quality assessments. As such, our method has applications for determining complex eicosanoid profiles in the biomedical field.
Precursor ion survival energies of protonated N-glycopeptides and their weak dependencies on high mannose N-glycan composition in collision-induced dissociation
Authors: Aboufazeli Forouzan , Dodds Eric D.
Published: August 2018

This work demonstrates that optimum conditions for CID MS/MS of high mannose N-glycopeptides is relatively insensitive to the glycan composition.
Synthesis of five-membered cyclic nitrones based on the Lewis acid-catalysed [3+2]-annulation reaction of donor–acceptor cyclopropanes with 1,4,2-dioxazoles
Authors: Wang Zhe-Hao , Zhang Huan-Huan , Xu Peng-Fei , Luo Yong-Chun
Published: August 2018

A Lewis acid-catalysed reaction of D–A cyclopropanes with 1,4,2-dioxazoles has been developed for the synthesis of five-membered cyclic nitrones.
Optically-regulated thermal energy storage in diverse organic phase-change materials
Authors: Han Grace G. D. , Deru Joshua H. , Cho Eugene N. , Grossman Jeffrey C.
Published: August 2018

Optical regulation of heat storage in diverse sets of organic phase-change materials is demonstrated and compared.
Pharmaceutical cocrystallization: an effective approach to modulate the physicochemical properties of solid-state drugs
Authors: Dai Xia-Lin , Chen Jia-Mei , Lu Tong-Bu
Published: August 2018

This highlight presents an update on applications of cocrystallization to modify properties relevant to efficacy, safety, and manufacturability of drugs.
A facile and green template-engaged synthesis of PbSe nanotubes with the assistance of Vc
Authors: Fan Huaiyun , Gao Shiyong , Xu Zhikun , Jiao Shujie , Yu Qi , Zhang Yong , Wang Jinzhong , Zhang Xitian , Zhao Liancheng
Published: August 2018

PbSe nanotubes (NTs) were synthesized through a low cost, facile and green hydrothermal route in combination with the assistance of ascorbic acid.
Extreme electron transport suppression in siloxane ring-based molecular devices
Authors: Li Jie , Duan Yunrui , Li Tao , Li Hui
Published: August 2018

Siloxane ring-based molecular devices possess excessive transport suppression and size-dependent transport decay, based on an analysis of electronic coupling.
Phase transition in CaFeAsH: bridging 1111 and 122 iron-based superconductors
Authors: Muraba Yoshinori , Iimura Soshi , Matsuishi Satoru , Hiramatsu Hidenori , Honda Takashi , Ikeda Kazutaka , Otomo Toshiya , Hosono Hideo
Published: August 2018

CaFeAsH bridges a gap between 1111-type and other 11-, 111- and 122-type iron based superconductors.
Functionalized polyoxometalate-based metal–organic cuboctahedra for selective adsorption toward cationic dyes in aqueous solution
Authors: Gong Ya-Ru , Chen Wei-Chao , Zhao Liang , Shao Kui-Zhan , Wang Xin-Long , Su Zhong-Min
Published: August 2018

Two new VMOPs with cuboctahedral geometries were synthesized based on [V6O6(OCH3)9X] (X = VO4 or SO4) and the rigid tridentate carboxylate ligand H3TATB, which present selective adsorption toward cationic dyes in aqueous solution.
Mg–porphyrin complex doped divinylbenzene based porous organic polymers (POPs) as highly efficient heterogeneous catalysts for the conversion of CO2 to cyclic carbonates
Authors: Wang Wenlong , Li Cunyao , Jin Jutao , Yan Li , Ding Yunjie
Published: August 2018

Mg–porphyrin complex doped divinylbenzene based POPs were afforded as heterogeneous catalysts for the conversion of CO2 to cyclic carbonates.
Dehydropolymerisation of methylamine borane using a dinuclear 1,3-allenediyl bridged zirconocene complex
Authors: Trose M. , Reiß M. , Reiß F. , Anke F. , Spannenberg A. , Boye S. , Lederer A. , Arndt P. , Beweries T.
Published: August 2018

The dinuclear zirconocene chloride complex 1 is a highly active precatalyst for the dehydropolymerisation of methylamine borane.
Thermally stable, planar hybrid perovskite solar cells with high efficiency
Authors: Choi Kyoungwon , Lee Junwoo , Kim Hong Il , Park Cheol Woong , Kim Guan-Woo , Choi Hyuntae , Park Sungjin , Park Sang Ah , Park Taiho
Published: August 2018

We developed a novel interface engineering strategy for highly stable and efficient SnO2-based planar-perovskite solar cells.
Dibenzofuran and dibenzothiophene based palladium(ii)/NHC catalysts – synthesis and applications in C–C bond formation
Authors: Karthik Shanmugam , Gandhi Thirumanavelan
Published: August 2018

In the quest for a new ligand system for Pd(ii)/NHCs, we developed new dibenzofuran and dibenzothiophene based palladium N-heterocyclic carbene catalystsD1–D6in good yields and applied it in C–C bond formation.
Electrochemical oxygen evolution reaction efficiently boosted by thermal-driving core–shell structure formation in nanostructured FeNi/S, N-doped carbon hybrid catalyst
Authors: Liu Zong , Yu Huaguang , Dong Baoxia , Yu Xu , Feng Ligang
Published: August 2018

Thermal-driving core–shell structure formation in Fe–Ni alloy incorporated by S, N-doped carbon can greatly boost the catalytic performance for electrochemical oxygen evolution reaction.
Different hybridized oxygen atoms controlled chemoselective formation of oxocarbenium ions: synthesis of chiral heterocyclic compounds
Authors: Wu Xiao-Na , You Zhi-Hao , Liu Yan-Kai
Published: August 2018

The chemoselective formation of oxocarbenium ions was realized by the chemoselective protonation of different hybridized oxygen atoms.
Thioester functional polymers
Authors: Aksakal Suzan , Aksakal Resat , Becer C. Remzi
Published: August 2018

Inspired by the uniqueness and ubiquity of thioesters in nature, much attention has been paid to thioester functionalized materials, yielding applications ranging from responsive polymers to bioconjugates and (bio)degradable polymers.
Synthesis of 2D Zn–Co LDH nanosheets by a successive ionic layer deposition method as a material for electrodes of high-performance alkaline battery–supercapacitor hybrid devices
Authors: Lobinsky A. A. , Tolstoy V. P.
Published: August 2018

A novel synthetic route of Zn–Co LDH ultrathin nanosheets with hydrotalcite-like crystal structure by SILD method. The obtained layers demonstrated high values of capacity and good electrochemical stability as electrode material for the BSH devise.
β-Escin inhibits the proliferation of osteosarcoma cells via blocking the PI3K/Akt pathway
Authors: Zhu Minyu , Ying Jinwei , Lin Chaowei , Wang Yu , Huang Kelun , Zhou Yang , Teng Honglin
Published: August 2018

β-Escin exhibits anticancer effects on a panel of established cancer cells. However, the effects of β-escin on human osteosarcoma (OS) are still unknown.
A glucose modified filter paper for effective oil/water separation
Authors: Luo Zhonglin , Duan Cong , Li Yan , Wang Yanbin , Wang Biaobing
Published: August 2018

Toluene/water emulsion cannot be separated by the un-treated filter paper. In comparison, toluene/water emulsion could be efficiently separated by the glucose (GLC) treated filter paper.
Dynamic random lasing in silica aerogel doped with rhodamine 6G
Authors: Wetter Niklaus Ursus , Ramos de Miranda Adriana , Pecoraro Édison , Lima Ribeiro Sidney José , Jimenez-Villar Ernesto
Published: August 2018

We demonstrate dynamically adjustable resonant lasing in silica aerogel, which makes this a truly versatile photonics material.
Formation of Mn–Cr mixed oxide nanosheets with enhanced lithium storage properties
Authors: Li Liewu , Wang Liping , Zhang Mingyu , Huang Qizhong
Published: August 2018

Novel carbon-free Mn2O3/MnCr2O4 hybrid nanosheets are synthesized. As an anode for lithium-ion batteries, they deliver a wonderful electrochemical performance.
Cromoglycate mesogen forms isodesmic assemblies promoted by peptides and induces aggregation of a range of proteins
Authors: Ibanez Arizza Chiara S. , Marji Elaine , Luk Yan-Yeung
Published: August 2018

5′DSCG molecules form isodesmic assembly in the presence of peptides, and cause a wide range of proteins to aggregate.
A cross-linking strategy with moderated pre-polymerization of resin for stereolithography
Authors: Ni Rongping , Qian Bin , Liu Chang , Liu Xiaofeng , Qiu Jianrong
Published: August 2018

We demonstrate a cross-linking strategy with moderated pre-polymerization for stereolithography and variations of diluents to tailor the resin characteristics needed for applications.