bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structures of highly simplified BPTIs provide insights into hydration-driven increase of unfolding enthalpy
Authors: Islam Mohammad Monirul , Yohda Masafumi , Kidokoro Shun-ichi , Kuroda Yutaka
Published: March 2017

We report a thermodynamic and structural analysis of six extensively simplified bovine pancreatic trypsin inhibitor (BPTI) variants containing 19–24 alanines out of 58 residues. Differential scanning calorimetry indicated a two-state thermal unfolding, typical of a native protein with densely packed interior. Surprisingly, increasing the number of alanines induced enthalpy stabilization, which was however over-compensated by entropy destabilization. X-ray crystallography indicated that the alanine substitutions caused the recruitment of novel water molecules facilitating the formation of protein–water hydrogen bonds and improving the hydration shells around the alanine’s methyl groups, both of which presumably contributed to enthalpy stabilization. There was a strong correlation between the number of water molecules and the thermodynamic parameters. Overall, our results demonstrate that, in contrast to our initial expectation, a protein sequence in which over 40% of the residues are alanines can retain a densely packed structure and undergo thermal denaturation with a large enthalpy change, mainly contributed by hydration.
Design of a k-space spectrometer for ultra-broad waveband spectral domain optical coherence tomography
Authors: Lan Gongpu , Li Guoqiang
Published: March 2017

Nonlinear sampling of the interferograms in wavenumber (k) space degrades the depth-dependent signal sensitivity in conventional spectral domain optical coherence tomography (SD-OCT). Here we report a linear-in-wavenumber (k-space) spectrometer for an ultra-broad bandwidth (760 nm–920 nm) SD-OCT, whereby a combination of a grating and a prism serves as the dispersion group. Quantitative ray tracing is applied to optimize the linearity and minimize the optical path differences for the dispersed wavenumbers. Zemax simulation is used to fit the point spread functions to the rectangular shape of the pixels of the line-scan camera and to improve the pixel sampling rates. An experimental SD-OCT is built to test and compare the performance of the k-space spectrometer with that of a conventional one. Design results demonstrate that this k-space spectrometer can reduce the nonlinearity error in k-space from 14.86% to 0.47% (by approximately 30 times) compared to the conventional spectrometer. The 95% confidence interval for RMS diameters is 5.48 ± 1.76 μm—significantly smaller than both the pixel size (14 μm × 28 μm) and the Airy disc (25.82 μm in diameter, calculated at the wavenumber of 7.548 μm−1). Test results demonstrate that the fall-off curve from the k-space spectrometer exhibits much less decay (maximum as −5.20 dB) than the conventional spectrometer (maximum as –16.84 dB) over the whole imaging depth (2.2 mm).
Formation and evolution of a pair of collisionless shocks in counter-streaming flows
Authors: Yuan Dawei , Li Yutong , Liu Meng , Zhong Jiayong , Zhu Baojun , Li Yanfei , Wei Huigang , Han Bo , Pei Xiaoxing , Zhao Jiarui , Li Fang , Zhang Zhe , Liang Guiyun , Wang Feilu , Weng Suming , Li Yingjun , Jiang Shaoen , Du Kai , Ding Yongkun , Zhu Baoqiang , Zhu Jianqiang , Zhao Gang , Zhang Jie
Published: March 2017

A pair of collisionless shocks that propagate in the opposite directions are firstly observed in the interactions of laser-produced counter-streaming flows. The flows are generated by irradiating a pair of opposing copper foils with eight laser beams at the Shenguang-II (SG-II) laser facility. The experimental results indicate that the excited shocks are collisionless and electrostatic, in good agreement with the theoretical model of electrostatic shock. The particle-in-cell (PIC) simulations verify that a strong electrostatic field growing from the interaction region contributes to the shocks formation. The evolution is driven by the thermal pressure gradient between the upstream and the downstream. Theoretical analysis indicates that the strength of the shocks is enhanced with the decreasing density ratio during both flows interpenetration. The positive feedback can offset the shock decay process. This is probable the main reason why the electrostatic shocks can keep stable for a longer time in our experiment.
Nkx2.1 regulates the generation of telencephalic astrocytes during embryonic development
Authors: Minocha Shilpi , Valloton Delphine , Arsenijevic Yvan , Cardinaux Jean-René , Guidi Raffaella , Hornung Jean-Pierre , Lebrand Cécile
Published: March 2017

The homeodomain transcription factor Nkx2.1 (NK2 homeobox 1) controls cell differentiation of telencephalic GABAergic interneurons and oligodendrocytes. Here we show that Nkx2.1 also regulates astrogliogenesis of the telencephalon from embryonic day (E) 14.5 to E16.5. Moreover we identify the different mechanisms by which Nkx2.1 controls the telencephalic astrogliogenesis. In Nkx2.1 knockout (Nkx2.1−/−) mice a drastic loss of astrocytes is observed that is not related to cell death. Further, in vivo analysis using BrdU incorporation reveals that Nkx2.1 affects the proliferation of the ventral neural stem cells that generate early astrocytes. Also, in vitro neurosphere assays showed reduced generation of astroglia upon loss of Nkx2.1, which could be due to decreased precursor proliferation and possibly defects in glial specification/differentiation. Chromatin immunoprecipitation analysis and in vitro co-transfection studies with an Nkx2.1-expressing plasmid indicate that Nkx2.1 binds to the promoter of glial fibrillary acidic protein (GFAP), primarily expressed in astrocytes, to regulate its expression. Hence, Nkx2.1 controls astroglial production spatiotemporally in embryos by regulating proliferation of the contributing Nkx2.1-positive precursors.
Quantification of free-living activity patterns using accelerometry in adults with mental illness
Authors: Chapman Justin J. , Roberts James A. , Nguyen Vinh T. , Breakspear Michael
Published: March 2017

Physical activity is disrupted in many psychiatric disorders. Advances in everyday technologies – such as accelerometers in smart phones – opens exciting possibilities for non-intrusive acquisition of activity data. Successful exploitation of this opportunity requires the validation of analytical methods that can capture the full movement spectrum. The study aim was to demonstrate an analytical approach to characterise accelerometer-derived activity patterns. Here, we use statistical methods to characterize accelerometer-derived activity patterns from a heterogeneous sample of 99 community-based adults with mental illnesses. Diagnoses were screened using the Mini International Neuropsychiatric Interview, and participants wore accelerometers for one week. We studied the relative ability of simple (exponential), complex (heavy-tailed), and composite models to explain patterns of activity and inactivity. Activity during wakefulness was a composite of brief random (exponential) movements and complex (heavy-tailed) processes, whereas movement during sleep lacked the heavy-tailed component. In contrast, inactivity followed a heavy-tailed process, lacking the random component. Activity patterns differed in nature between those with a diagnosis of bipolar disorder and a primary psychotic disorder. These results show the potential of complex models to quantify the rich nature of human movement captured by accelerometry during wake and sleep, and the interaction with diagnosis and health.
High-throughput search of ternary chalcogenides for p-type transparent electrodes
Authors: Shi Jingming , Cerqueira Tiago F. T. , Cui Wenwen , Nogueira Fernando , Botti Silvana , Marques Miguel A. L.
Published: March 2017

Delafossite crystals are fascinating ternary oxides that have demonstrated transparent conductivity and ambipolar doping. Here we use a high-throughput approach based on density functional theory to find delafossite and related layered phases of composition ABX2, where A and B are elements of the periodic table, and X is a chalcogen (O, S, Se, and Te). From the 15 624 compounds studied in the trigonal delafossite prototype structure, 285 are within 50 meV/atom from the convex hull of stability. These compounds are further investigated using global structural prediction methods to obtain their lowest-energy crystal structure. We find 79 systems not present in the materials project database that are thermodynamically stable and crystallize in the delafossite or in closely related structures. These novel phases are then characterized by calculating their band gaps and hole effective masses. This characterization unveils a large diversity of properties, ranging from normal metals, magnetic metals, and some candidate compounds for p-type transparent electrodes.
Commensal gut bacteria modulate phosphorylation-dependent PPARγ transcriptional activity in human intestinal epithelial cells
Authors: Nepelska Malgorzata , de Wouters Tomas , Jacouton Elsa , Béguet-Crespel Fabienne , Lapaque Nicolas , Doré Joël , Arulampalam Velmurugesan , Blottière Hervé M.
Published: March 2017

In healthy subjects, the intestinal microbiota interacts with the host’s epithelium, regulating gene expression to the benefit of both, host and microbiota. The underlying mechanisms remain poorly understood, however. Although many gut bacteria are not yet cultured, constantly growing culture collections have been established. We selected 57 representative commensal bacterial strains to study bacteria-host interactions, focusing on PPARγ, a key nuclear receptor in colonocytes linking metabolism and inflammation to the microbiota. Conditioned media (CM) were harvested from anaerobic cultures and assessed for their ability to modulate PPARγ using a reporter cell line. Activation of PPARγ transcriptional activity was linked to the presence of butyrate and propionate, two of the main metabolites of intestinal bacteria. Interestingly, some stimulatory CMs were devoid of these metabolites. A Prevotella and an Atopobium strain were chosen for further study, and shown to up-regulate two PPARγ-target genes, ANGPTL4 and ADRP. The molecular mechanisms of these activations involved the phosphorylation of PPARγ through ERK1/2. The responsible metabolites were shown to be heat sensitive but markedly diverged in size, emphasizing the diversity of bioactive compounds found in the intestine. Here we describe different mechanisms by which single intestinal bacteria can directly impact their host’s health through transcriptional regulation.
Abnormalities in A-to-I RNA editing patterns in CNS injuries correlate with dynamic changes in cell type composition
Authors: Gal-Mark Nurit , Shallev Lea , Sweetat Sahar , Barak Michal , Billy Li Jin , Levanon Erez Y. , Eisenberg Eli , Behar Oded
Published: March 2017

Adenosine to Inosine (A-to-I) RNA editing is a co- or post-transcriptional mechanism that modifies genomically encoded nucleotides at the RNA level. A-to-I RNA editing is abundant in the brain, and altered editing levels have been reported in various neurological pathologies and following spinal cord injury (SCI). The prevailing concept is that the RNA editing process itself is dysregulated by brain pathologies. Here we analyzed recent RNA-seq data, and found that, except for few mammalian conserved editing sites, editing is significantly higher in neurons than in other cell populations of the brain. We studied A-to-I RNA editing in stab wound injury (SWI) and SCI models and showed that the apparent under-editing observed after injury correlates with an approximately 20% reduction in the relative density of neurons, due to cell death and immune cell infiltration that may account for the observed under-editing. Studies of neuronal and astrocyte cultures and a computational analysis of SCI RNA-seq data further supported the possibility that a reduction in neuronal density is responsible for alterations in the tissue-wide editing patterns upon injury. Thus, our data suggest that the case for a mechanistic linkage between A-to-I RNA editing and brain pathologies should be revisited.
Hydrogen peroxide in deep waters from the Mediterranean Sea, South Atlantic and South Pacific Oceans
Authors: Hopwood Mark J. , Rapp Insa , Schlosser Christian , Achterberg Eric P.
Published: March 2017

Hydrogen peroxide (H2O2) is present ubiquitously in marine surface waters where it is a reactive intermediate in the cycling of many trace elements. Photochemical processes are considered the dominant natural H2O2source, yet cannot explain nanomolar H2O2concentrations below the photic zone. Here, we determined the concentration of H2O2in full depth profiles across three ocean basins (Mediterranean Sea, South Atlantic and South Pacific Oceans). To determine the accuracy of H2O2measurements in the deep ocean we also re-assessed the contribution of interfering species to ‘apparent H2O2’, as analysed by the luminol based chemiluminescence technique. Within the vicinity of coastal oxygen minimum zones, accurate measurement of H2O2was not possible due to interference from Fe(II). Offshore, in deep (>1000 m) waters H2O2concentrations ranged from 0.25 ± 0.27 nM (Mediterranean, Balearics-Algeria) to 2.9 ± 2.2 nM (Mediterranean, Corsica-France). Our results indicate that a dark, pelagic H2O2production mechanism must occur throughout the deep ocean. A bacterial source of H2O2is the most likely origin and we show that this source is likely sufficient to account for all of the observed H2O2in the deep ocean.
Parasitism perturbs the mucosal microbiome of Atlantic Salmon
Authors: Llewellyn M. S. , Leadbeater S. , Garcia C. , Sylvain F.-E. , Custodio M. , Ang K. P. , Powell F. , Carvalho G. R. , Creer S. , Elliot J. , Derome N.
Published: March 2017

Interactions between parasite, host and host-associated microbiota are increasingly understood as important determinants of disease progression and morbidity. Salmon lice, including the parasitic copepod Lepeophtheirus salmonis and related species, are perhaps the most important problem facing Atlantic Salmon aquaculture after feed sustainability. Salmon lice parasitize the surface of the fish, feeding off mucus, scales and underlying tissue. Secondary bacterial infections are a major source of associated morbidity. In this study we tracked the diversity and composition of Salmo salar skin surface microbiota throughout a complete L. salmonis infection cycle among 800 post-smolts as compared to healthy controls. Among infected fish we observed a significant reduction in microbial richness (Chao1, P = 0.0136), raised diversity (Shannon, P < 7.86e-06) as well as highly significant destabilisation of microbial community composition (Pairwise Unifrac, beta-diversity, P < 1.86e-05; P = 0.0132) by comparison to controls. While undetectable on an individual level, network analysis of microbial taxa on infected fish revealed the association of multiple pathogenic genera (Vibrio, Flavobacterium, Tenacibaculum, Pseudomonas) with high louse burdens. We discuss our findings in the context of ecological theory and colonisation resistance, in addition to the role microbiota in driving primary and secondary pathology in the host.
Identifying ionic interactions within a membrane using BLaTM, a genetic tool to measure homo- and heterotypic transmembrane helix-helix interactions
Authors: Schanzenbach Christoph , Schmidt Fabian C. , Breckner Patrick , Teese Mark G. , Langosch Dieter
Published: March 2017

The assembly of integral membrane protein complexes is frequently supported by transmembrane domain (TMD) interactions. Here, we present the BLaTM assay that measures homotypic as well as heterotypic TMD-TMD interactions in a bacterial membrane. The system is based on complementation of β-lactamase fragments genetically fused to interacting TMDs, which confers ampicillin resistance to expressing cells. We validated BLaTM by showing that the assay faithfully reports known sequence-specific interactions of both types. In a practical application, we used BLaTM to screen a focussed combinatorial library for heterotypic interactions driven by electrostatic forces. The results reveal novel patterns of ionizable amino acids within the isolated TMD pairs. Those patterns indicate that formation of heterotypic TMD pairs is most efficiently supported by closely spaced ionizable residues of opposite charge. In addition, TMD heteromerization can apparently be driven by hydrogen bonding between basic or between acidic residues.
Nitrification inhibitors can increase post-harvest nitrous oxide emissions in an intensive vegetable production system
Authors: Scheer Clemens , Rowlings David , Firrell Mary , Deuter Peter , Morris Stephen , Riches David , Porter Ian , Grace Peter
Published: March 2017

To investigate the effect of nitrification inhibitors (NIs) 3,4-dimethylpyrazole phosphate (DMPP) and 3-methylpyrazole 1,2,4-triazole (3MP + TZ), on N2O emissions and yield from a typical vegetable rotation in sub-tropical Australia we monitored soil N2O fluxes continuously over an entire year using an automated greenhouse gas measurement system. The temporal variation of N2O fluxes showed only low emissions over the vegetable cropping phases, but significantly higher emissions were observed post-harvest accounting for 50–70% of the annual emissions. NIs reduced N2O emissions by 20–60% over the vegetable cropping phases; however, this mitigation was offset by elevated N2O emissions from the NIs treatments over the post-harvest fallow period. Annual N2O emissions from the conventional fertiliser, the DMPP treatment, and the 3MP + TZ treatment were 1.3, 1.1 and 1.6 (sem = 0.2) kg-N ha−1 year−1, respectively. This study highlights that the use of NIs in vegetable systems can lead to elevated N2O emissions by storing N in the soil profile that is available to soil microbes during the decomposition of the vegetable residues. Hence the use of NIs in vegetable systems has to be treated carefully and fertiliser rates need to be adjusted to avoid an oversupply of N during the post-harvest phase.
Effects of biophysical constraints, climate and phylogeny on forest shrub allometries along an altitudinal gradient in Northeast China
Authors: Sun Han , Wang Xiangping , Fan Yanwen , Liu Chao , Wu Peng , Li Qiaoyan , Yin Weilun
Published: March 2017

Whether there is a general allometry law across plant species with different sizes and under different environment has long been controversial and shrubs are particularly useful to examine these questions. Here we sampled 939 individuals from 50 forest shrub species along a large altitudinal gradient. We tested several allometry models with four relationships simultaneously (between stem diameter, height, leaf, stem and aboveground biomass), including geometric, elastic and stress similarity, and metabolic scaling theory’s predictions on small plants (MSTs) and trees (MSTt). We also tested if allometric exponents change markedly with climate and phylogeny. The predicted exponents of MSTt, elastic similarity and stress similarity (models for trees) were not supported by our data, while MSTs and geometric similarity gained more support, suggesting the finite size effect is more important for shrub allometries than being a woody plant. The influence of climate and phylogeny on allometric exponents were not significant or very weak, again suggesting strong biophysical constraints on shrub allometries. Our results reveal clear differences of shrub allometries from previous findings on trees (e.g. much weaker climatic and phylogenic control). Comparisons of herbs, shrubs and trees along a same climatic gradient are needed for better understanding of plant allometries.
Microbiota alteration is associated with the development of stress-induced despair behavior
Authors: Marin Ioana A. , Goertz Jennifer E. , Ren Tiantian , Rich Stephen S. , Onengut-Gumuscu Suna , Farber Emily , Wu Martin , Overall Christopher C. , Kipnis Jonathan , Gaultier Alban
Published: March 2017

Depressive disorders often run in families, which, in addition to the genetic component, may point to the microbiome as a causative agent. Here, we employed a combination of behavioral, molecular and computational techniques to test the role of the microbiota in mediating despair behavior. In chronically stressed mice displaying despair behavior, we found that the microbiota composition and the metabolic signature dramatically change. Specifically, we observed reduced Lactobacillus and increased circulating kynurenine levels as the most prominent changes in stressed mice. Restoring intestinal Lactobacillus levels was sufficient to improve the metabolic alterations and behavioral abnormalities. Mechanistically, we identified that Lactobacillus-derived reactive oxygen species may suppress host kynurenine metabolism, by inhibiting the expression of the metabolizing enzyme, IDO1, in the intestine. Moreover, maintaining elevated kynurenine levels during Lactobacillus supplementation diminished the treatment benefits. Collectively, our data provide a mechanistic scenario for how a microbiota player (Lactobacillus) may contribute to regulating metabolism and resilience during stress.
Actual fusion efficiency in the lipid mixing assay - Comparison between nanodiscs and liposomes
Authors: François-Martin Claire , Pincet Frédéric
Published: March 2017

Lipid exchange occurs between membranes during fusion or active lipid transfer. These processes are necessary in vivo for the homeostasis of the cell at the level of the membranes, the organelles and the cell itself. They are also used by the cell to interact with the surrounding medium. Several assays have been developed to characterize in vitro these processes on model systems. The most common one, relying on fluorescence dequenching, measures lipid mixing between small membranes such as liposomes or nanodiscs in bulk. Usually, relative comparisons of the rate of lipid exchange are made between measurements performed in parallel. Here, we establish a quantitative standardization of this assay to avoid any bias resulting from the temperatures, the chosen fluorescent lipid fractions and from the various detergents used to normalize the measurements. We used this standardization to quantitatively compare the efficiency of SNARE-induced fusion in liposome-liposome and liposome-nanodisc configurations having similar collision frequency. We found that the initial yield of fusion is comparable in both cases, 1 per 2–3 million collisions in spite of a much larger dequenching signal with nanodiscs. Also, the long-term actual fusion rate is slightly lower with nanodiscs than in the liposome-liposome assay.
Ultrathin (<1 μm) Substrate-Free Flexible Photodetector on Quantum Dot-Nanocellulose Paper
Authors: Wu Jingda , Lin Lih Y.
Published: March 2017

Conventional approaches to flexible optoelectronic devices typically require depositing the active materials on external substrates. This is mostly due to the weak bonding between individual molecules or nanocrystals in the active materials, which prevents sustaining a freestanding thin film. Herein we demonstrate an ultrathin freestanding ZnO quantum dot (QD) active layer with nanocellulose structuring, and its corresponding device fabrication method to achieve substrate-free flexible optoelectronic devices. The ultrathin ZnO QD-nanocellulose composite is obtained by hydrogel transfer printing and solvent-exchange processes to overcome the water capillary force which is detrimental to achieving freestanding thin films. We achieved an active nanocellulose paper with ~550 nm thickness, and >91% transparency in the visible wavelength range. The film retains the photoconductive and photoluminescent properties of ZnO QDs and is applied towards substrate-free Schottky photodetector applications. The device has an overall thickness of ~670 nm, which is the thinnest freestanding optoelectronic device to date, to the best of our knowledge, and functions as a self-powered visible-blind ultraviolet photodetector. This platform can be readily applied to other nano materials as well as other optoelectronic device applications.
D-Glutamate is metabolized in the heart mitochondria
Authors: Ariyoshi Makoto , Katane Masumi , Hamase Kenji , Miyoshi Yurika , Nakane Maiko , Hoshino Atsushi , Okawa Yoshifumi , Mita Yuichiro , Kaimoto Satoshi , Uchihashi Motoki , Fukai Kuniyoshi , Ono Kazunori , Tateishi Syuhei , Hato Daichi , Yamanaka Ryoetsu , Honda Sakiko , Fushimura Yohei , Iwai-Kanai Eri , Ishihara Naotada , Mita Masashi , Homma Hiroshi , Matoba Satoaki
Published: March 2017

D-Amino acids are enantiomers of L-amino acids and have recently been recognized as biomarkers and bioactive substances in mammals, including humans. In the present study, we investigated functions of the novel mammalian mitochondrial protein 9030617O03Rik and showed decreased expression under conditions of heart failure. Genomic sequence analyses showed partial homology with a bacterial aspartate/glutamate/hydantoin racemase. Subsequent determinations of all free amino acid concentrations in 9030617O03Rik-deficient mice showed high accumulations of D-glutamate in heart tissues. This is the first time that a significant amount of D-glutamate was detected in mammalian tissue. Further analysis of D-glutamate metabolism indicated that 9030617O03Rik is a D-glutamate cyclase that converts D-glutamate to 5-oxo-D-proline. Hence, this protein is the first identified enzyme responsible for mammalian D-glutamate metabolism, as confirmed in cloning analyses. These findings suggest that D-glutamate and 5-oxo-D-proline have bioactivities in mammals through the metabolism by D-glutamate cyclase.
Mirolydidae, a new family of Jurassic pamphilioid sawfly (Hymenoptera) highlighting mosaic evolution of lower Hymenoptera
Authors: Wang Mei , Rasnitsyn Alexandr P. , Yang Zhongqi , Shih Chungkun , Wang Hongbin , Ren Dong
Published: March 2017

We describe Pamphilioidea: Mirolydidae Wang, Rasnitsyn et Ren, fam. n., containing Mirolyda hirta Wang, Rasnitsyn et Ren, gen. et sp. n., from the late Middle Jurassic Jiulongshan Formation of Daohugou, Inner Mongolia, China. The new taxon is characterized by unique forewing venation with the presence of forewing SC, 1-RS almost as long as 1-M, M + Cu straight, 2r-rs strongly reclival, and antenna with homonomous flagellum, revealing new and important details in antennal evolutionary transformations. Thus, M. hirta with a combination of primitive and more derived characters highlights its transitional state in the Pamphilioidea and complex mosaic evolution within Pamphilioidea in the late Middle Jurassic. The body of this species is densely covered with thin and long setae, suggesting its possible habit of visiting gymnosperm reproductive organs for pollen feeding and/or pollination during the late Middle Jurassic, much earlier than the appearance of angiosperm flowers.
Anomalous shear band characteristics and extra-deep shock-affected zone in Zr-based bulk metallic glass treated with nanosecond laser peening
Authors: Wei Yanpeng , Xu Guangyue , Zhang Kun , Yang Zhe , Guo Yacong , Huang Chenguang , Wei Bingchen
Published: March 2017

The effects of nanosecond laser peening on Zr41Ti14Cu12.5Ni10Be22.5 metallic glass were investigated in this study. The peening treatment produced an extra-deep shock-affected zone compared to crystal metal. As opposed to the conventional shear bands, numerous arc shear bands appeared and aggregated in the vertical direction of the laser beam, forming basic units for accommodating plastic deformation. The arc shear bands exhibited short and discrete features near the surface of the material, then grew longer and fewer at deeper peened layer depths, which was closely related to the laser shock wave attenuation. An energy dissipation model was established based on Hugoniot Elastic Limit and shear band characteristics to represent the formation of an extra-deep shock-affected zone. The results presented here suggest that the bulk modification of metallic glass with a considerable affected depth is feasible. Further, they reveal that nanosecond laser peening is promising as an effective approach to tuning shear bands for improved MGs ductility.
Cluster analysis: a new approach for identification of underlying risk factors for coronary artery disease in essential hypertensive patients
Authors: Guo Qi , Lu Xiaoni , Gao Ya , Zhang Jingjing , Yan Bin , Su Dan , Song Anqi , Zhao Xi , Wang Gang
Published: March 2017

Grading of essential hypertension according to blood pressure (BP) level may not adequately reflect clinical heterogeneity of hypertensive patients. This study was carried out to explore clinical phenotypes in essential hypertensive patients using cluster analysis. This study recruited 513 hypertensive patients and evaluated BP variations with ambulatory blood pressure monitoring. Four distinct hypertension groups were identified using cluster analysis: (1) younger male smokers with relatively high BP had the most severe carotid plaque thickness but no coronary artery disease (CAD); (2) older women with relatively low diastolic BP had more diabetes; (3) non-smokers with a low systolic BP level had neither diabetes nor CAD; (4) hypertensive patients with BP reverse dipping were most likely to have CAD but had least severe carotid plaque thickness. In binary logistic analysis, reverse dipping was significantly associated with prevalence of CAD. Cluster analysis was shown to be a feasible approach for investigating the heterogeneity of essential hypertension in clinical studies. BP reverse dipping might be valuable for prediction of CAD in hypertensive patients when compared with carotid plaque thickness. However, large-scale prospective trials with more information of plaque morphology are necessary to further compare the predicative power between BP dipping pattern and carotid plaque.
Physics of chewing in terrestrial mammals
Authors: Virot Emmanuel , Ma Grace , Clanet Christophe , Jung Sunghwan
Published: March 2017

Previous studies on chewing frequency across animal species have focused on finding a single universal scaling law. Controversy between the different models has been aroused without elucidating the variations in chewing frequency. In the present study we show that vigorous chewing is limited by the maximum force of muscle, so that the upper chewing frequency scales as the −1/3 power of body mass for large animals and as a constant frequency for small animals. On the other hand, gentle chewing to mix food uniformly without excess of saliva describes the lower limit of chewing frequency, scaling approximately as the −1/6 power of body mass. These physical constraints frame the −1/4 power law classically inferred from allometry of animal metabolic rates. All of our experimental data stay within these physical boundaries over six orders of magnitude of body mass regardless of food types.
Incidence and risk factors of retreatment after three-monthly aflibercept therapy for exudative age-related macular degeneration
Authors: Kikushima Wataru , Sakurada Yoichi , Yoneyama Seigo , Sugiyama Atsushi , Tanabe Naohiko , Kume Atsuki , Mabuchi Fumihiko , Iijima Hiroyuki
Published: March 2017

Though anti-vascular endothelial growth factor therapy has become the standard treatment for exudative age-related macular degeneration (AMD), retreatment after the initial loading injection is inevitable in most eyes with residual or recurrent exudative changes. In the present study, we studied 140 treatment naïve eyes with typical neovascular AMD (n = 71) or polypoidal choroidal vasculopathy (PCV) (n = 69) and investigated the incidence and risk factors of retreatment after 3-monthly intravitreal aflibercept injection for exudative AMD during the 12-month period. At 12 months, best-corrected visual acuity (BCVA) improved significantly from 0.45 ± 0.39 to 0.26 ± 0.33 (P = 4.1 × 10−11). Multiple regression analysis revealed that better baseline BCVA (P = 3.6 × 10−14) and thicker subfoveal choroidal thickness (P = 0.039) were associated with better BCVA at 12-months. Retreatment was required in 94 out of 140 (67.1%) eyes. Multivariate logistic regression analysis revealed that older age (P = 7.2 × 10−3) and T-allele of ARMS2 A69S (rs10490924) variants (P = 1.9 × 10−3) were associated with retreatment. Cox-regression analysis revealed that older age (P = 1.0 × 10−2) and T-allele of the ARMS2 gene (P = 6.0 × 10−3) were associated with retreatment-free period. The number of retreatment episodes was significantly different among the ARMS2 genotypes (P = 8.1 × 10−4). These findings might be helpful for physicians when considering the optimal treatment regimen for exudative AMD.
Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner
Authors: Jašarević Eldin , Howard Christopher D. , Misic Ana M. , Beiting Daniel P. , Bale Tracy L.
Published: March 2017

The microbiome is a regulator of host immunity, metabolism, neurodevelopment, and behavior. During early life, bacterial communities within maternal gut and vaginal compartments can have an impact on directing these processes. Maternal stress experience during pregnancy may impact offspring development by altering the temporal and spatial dynamics of the maternal microbiome during pregnancy. To examine the hypothesis that maternal stress disrupts gut and vaginal microbial dynamics during critical prenatal and postnatal windows, we used high-resolution 16S rRNA marker gene sequencing to examine outcomes in our mouse model of early prenatal stress. Consistent with predictions, maternal fecal communities shift across pregnancy, a process that is disrupted by stress. Vaginal bacterial community structure and composition exhibit lasting disruption following stress exposure. Comparison of maternal and offspring microbiota revealed that similarities in bacterial community composition was predicted by a complex interaction between maternal body niche and offspring age and sex. Importantly, early prenatal stress influenced offspring bacterial community assembly in a temporal and sex-specific manner. Taken together, our results demonstrate that early prenatal stress may influence offspring development through converging modifications to gut microbial composition during pregnancy and transmission of dysbiotic vaginal microbiome at birth.
Molecular outcomes, clinical consequences, and genetic diagnosis of Oculocutaneous Albinism in Pakistani population
Authors: Shahzad Mohsin , Yousaf Sairah , Waryah Yar M. , Gul Hadia , Kausar Tasleem , Tariq Nabeela , Mahmood Umair , Ali Muhammad , Khan Muzammil A. , Waryah Ali M. , Shaikh Rehan S. , Riazuddin Saima , Ahmed Zubair M. ,   University of Washington Center for Mendelian Genomics (UW CMG) Consortium, Bamshad Michael J. , Shendure Jay , Nickerson Deborah A. , Abecasis Gonçalo R. , Anderson Peter , Marchani Blue Elizabeth , Annable Marcus , Browning Brian L. , Buckingham Kati J. , Chen Christina , Chin Jennifer , Chong Jessica X. , Cooper Gregory M. , Davis Colleen P. , Frazar Christopher , Harrell Tanya M. , He Zongxiao , Jain Preti , Jarvik Gail P. , Jimenez Guillaume , Johanson Eric , Jun Goo , Kircher Martin , Kolar Tom , Krauter Stephanie A. , Krumm Niklas , Leal Suzanne M. , Luksic Daniel , Marvin Colby T. , McGee Sean , Patterson Karynne , Perez Marcos , Phillips Sam W. , Pijoan Jessica , Poel Christa , Ragan Seamus , Reinier Frederic , Robertson Peggy D. , Santos-Cortez Regie , Shankar Aditi , Slattery Krystal , Shephard Cindy , Shively Kathryn M. , Siegel Deborah L. , Smith Joshua D. , Tabor Holly K. , Tackett Monica , Wegener Marc , Wang Gao , Wheeler Marsha M. , Wright Amber , Yi Qian
Published: March 2017

Nonsyndromic oculocutaneous Albinism (nsOCA) is clinically characterized by the loss of pigmentation in the skin, hair, and iris. OCA is amongst the most common causes of vision impairment in children. To date, pathogenic variants in six genes have been identified in individuals with nsOCA. Here, we determined the identities, frequencies, and clinical consequences of OCA alleles in 94 previously unreported Pakistani families. Combination of Sanger and Exome sequencing revealed 38 alleles, including 22 novel variants, segregating with nsOCA phenotype in 80 families. Variants of TYR and OCA2 genes were the most common cause of nsOCA, occurring in 43 and 30 families, respectively. Twenty-two novel variants include nine missense, four splice site, two non-sense, one insertion and six gross deletions. In vitro studies revealed retention of OCA proteins harboring novel missense alleles in the endoplasmic reticulum (ER) of transfected cells. Exon-trapping assays with constructs containing splice site alleles revealed errors in splicing. As eight alleles account for approximately 56% (95% CI: 46.52–65.24%) of nsOCA cases, primarily enrolled from Punjab province of Pakistan, hierarchical strategies for variant detection would be feasible and cost-efficient genetic tests for OCA in families with similar origin. Thus, we developed Tetra-primer ARMS assays for rapid, reliable, reproducible and economical screening of most of these common alleles.
Superior Pre-Osteoblast Cell Response of Etched Ultrafine-Grained Titanium with a Controlled Crystallographic Orientation
Authors: Baek Seung Mi , Shin Myeong Hwan , Moon Jongun , Jung Ho Sang , Lee See Am , Hwang WoonBong , Yeom Jong Taek , Hahn Sei Kwang , Kim Hyoung Seop
Published: March 2017

Ultrafine-grained (UFG) Ti for improved mechanical performance as well as its surface modification enhancing biofunctions has attracted much attention in medical industries. Most of the studies on the surface etching of metallic biomaterials have focused on surface topography and wettability but not crystallographic orientation, i.e., texture, which influences the chemical as well as the physical properties. In this paper, the influences of texture and grain size on roughness, wettability, and pre-osteoblast cell response were investigated in vitro after HF etching treatment. The surface characteristics and cell behaviors of ultrafine, fine, and coarse-grained Ti were examined after the HF etching. The surface roughness during the etching treatment was significantly increased as the orientation angle from the basal pole was increased. The cell adhesion tendency of the rough surface was promoted. The UFG Ti substrate exhibited a higher texture energy state, rougher surface, enhanced hydrophilic wettability, and better cell adhesion and proliferation behaviors after etching than those of the coarse- and fine-grained Ti substrates. These results provide a new route for enhancing both mechanical and biological performances using etching after grain refinement of Ti.
Influence of the Valsalva maneuver on cardiac hemodynamics and right to left shunt in patients with patent foramen ovale
Authors: Zhao Enfa , Zhang Yafei , Kang Chunmiao , Niu Hua , Zhao Jing , Sun Lei , Liu Baomin
Published: March 2017

The purpose of this study was to investigate the influence of the Valsalva maneuver (VM) on cardiac hemodynamics in patients with patent foramen ovale (PFO). Sixty-five patients who were highly suspected to have PFO were included. The changes in E, A, E/A ratio of mitral valve blood flow, E, A, E/A ratio of tricuspid valve blood flow, left ventricular end-diastolic volume, area and right atrial area during the resting state and the strain phase of the Valsalva maneuver were observed by transthoracic echocardiography (TTE). Statistical analyses were performed using SPSS Version18.0. Compared to the resting state, mitral valve diastolic velocity E and A peaks at the strain phase of the Valsalva maneuver significantly decreased (P < 0.05), left ventricular end diastolic volume(LVEDV) and area(LVEDA) decreased significantly (P < 0.05), while E/A ratio of mitral valve, tricuspid valve systolic velocity E and A peaks and E/A ratio remained unchanged (P > 0.05). PFO hemodynamic changes mainly occurred in the left ventricle when the Valsalva maneuver was performed. The Valsalva maneuver increased pressure in the chest, then pulmonary venous return was impeded, which resulted in left ventricular limited filling, and E and A peaks decreased. The pressure of the left ventricle and atrium was lower than that of the right side, which resulted in right-to-left shunt (RLS) through PFO.
Preparation of Pt(iv)-crosslinked polymer nanoparticles with an anti-detoxifying effect for enhanced anticancer therapy
Authors: Zhang Zihao , Li Yongjing , Wan Jiaxun , Long Peihua , Guo Jia , Chen Guosong , Wang Changchun
Published: March 2017

A new kind of Pt(iv)-crosslinked polymer nanoparticle with small, uniform size and high loading of cisplatin has been prepared for greatly attenuating the detoxifying effect of Pt(ii) species.
Correction: Quantifying and understanding the steric properties of N-heterocyclic carbenes
Authors: Gómez-Suárez Adrián , Nelson David J. , Nolan Steven P.
Published: March 2017

Correction for ‘Quantifying and understanding the steric properties of N-heterocyclic carbenes’ by Adrián Gómez-Suárez et al., Chem. Commun., 2017, 53, 2650–2660.
Liquid metal droplets with high elasticity, mobility and mechanical robustness
Authors: Chen Yuzhen , Liu Zhou , Zhu Deyong , Handschuh-Wang Stephan , Liang Suqing , Yang Jinbin , Kong Tiantian , Zhou Xiaohu , Liu Yizhen , Zhou Xuechang
Published: March 2017

Non-stick, ultra-elastic liquid metal droplets were fabricated by coating PTFE particles onto the surface of NaOH-treated liquid metal droplets.
Poly(fluoroacrylate)s with tunable surface hydrophobicity via radical copolymerization of 2,2,2-trifluoroethyl α-fluoroacrylate and 2-(trifluoromethyl)acrylic acid
Authors: Banerjee Sanjib , Tawade Bhausaheb V. , Ladmiral Vincent , Dupuy Lionel X. , MacDonald Michael P. , Améduri Bruno
Published: March 2017

Fluorinated polyacrylates with tunable surface hydrophobicity are preparedviaradical copolymerization of an α-fluoroacrylate and 2-(trifluoromethyl)acrylic acid.
Advanced signal processing techniques for multiclass disturbance detection and classification in microgrids
Authors: Chakravorti Tatiana , Patnaik Rajesh Kumar , Dash Praditpta Kishor
Published: March 2017

This study proposes the application of fuzzy assessment tree (FAT)‐based short‐time modified Hilbert transform (STMHT) as a new multiclass detection and classification technique, for a distributed generation (DG)‐based microgrid. The time varying non‐stationary power signal samples extracted near the target DG are initially de‐noised by passing through the morphological median filter and then processed through the proposed STMHT technique for disturbance detection. Further based on the overlapping in the target attribute values, an FAT has been incorporated, which significantly classifies the different multiclass disturbances on a standard IEC microgrid model simulated in MATLAB/Simulink environment with highest precision in accuracy.
Hyperphosphatasia with Mental Retardation Syndrome Due to a Novel Mutation in PGAP3
Authors: Nampoothiri Sheela , Hebbar Malavika , Roy Arun , Kochumon Sheena , Bielas Stephanie , Shukla Anju , Girisha Katta
Published: March 2017

Hyperphosphatasia with mental retardation syndrome is a heterogeneous genetic condition. Two siblings aged 5 years and 3 years were evaluated for global development delay and facial dysmorphism. A novel missense variant, c.851A>G (p.H284R, NM_033419.3), in PGAP3 was identified using whole-exome sequencing. Assays for elevated alkaline phosphatase and exome sequencing can be useful for the diagnosis of hyperphosphatasia with mental retardation syndrome.
Wolf-Hirschhorn Syndrome: Clinical and Genetic Data from a First Case Diagnosed in Central Africa
Authors: Mbuyi-Musanzayi Sébastien , Lumaka Aimé , Kasole Toni , Ilunga Erick , Asani Bienvenu , Tshilobo Prosper , Muenze Prosper , Reychler Hervé , Katombe François , Devriendt Koenraad
Published: March 2017

Wolf-Hirschhorn syndrome (WHS) is a multiple congenital anomaly-intellectual disability syndrome caused by a deletion involving chromosome 4p16.3. We report clinical and genetic findings of the first WHS patient diagnosed in central Africa. This boy who presented with cleft palate, microcephaly, severe growth delay, and intellectual disability was 12 years old. Typical craniofacial features were present, though the characteristic “Greek helmet” appearance of the nose was less evident, probably reflecting a variable expression related to the genetic background. The clinical diagnosis of WHS was confirmed by array CGH, which revealed a terminal 4p16.3 deletion of 3.47 Mb, typically associated with a milder phenotype, contributing to the long survival of this child in a developing country.
Stochasticity induced mixed-mode oscillations and distribution of recurrent outbreaks in an ecosystem
Authors: Sadhu Susmita
Published: March 2017

The effect of stochasticity, in the form of Gaussian white noise, in a predator–prey model with two distinct time-scales is presented. A supercritical singular Hopf bifurcation yields a Type II excitability in the deterministic model. We explore the effect of stochasticity in the excitable regime, leading to dynamics that are not anticipated by its deterministic counterpart. The stochastic model admits several kinds of noise-driven mixed-mode oscillations which capture the intermediate dynamics between two cycles of population outbreaks. Depending on the strength of noise, the prey population exhibits intermediate to high-amplitude fluctuations (related to moderate or severe outbreaks respectively). We classify these fluctuations as isolated or intermittent or as clusters depending on their recurrences. We study the distribution of the random variable N, representing the number of small oscillations between successive spikes, as a function of the noise intensity and the distance to the Hopf bifurcation. The distribution of N is “asymptotically geometric” with the corresponding parameter related to the principal eigenvalue of a substochastic Markov chain. Finally, the stochastic model is transformed into its “normal form” which is used to obtain an estimate of the probability of repeated outbreaks.
Outdoor gyms and older adults – acceptability, enablers and barriers: a survey of park users
Authors: Stride Vicki , Cranney Leonie , Scott Ashleigh , Hua Myna
Published: March 2017

Issue addressed

Increasing the proportion of older adults meeting current recommendations for physical activity is important. This study aimed to determine the acceptability of outdoor gym use among older adults by assessing their outdoor gym use, intention to use, motivators, frequency and preference for use, and barriers and enablers to use.

Methods

Interviews were conducted with 438 consenting English speaking park users ≥ 50 years after installation and promotion of an outdoor gym.

Results

Forty‐two percent of older adults interviewed had used the outdoor gym. Outdoor gym users had a significantly higher proportion of local residents (χ2 = 10.43; P < 0.01), were more frequent park users (χ2 = 8.75; P < 0.01) and spoke a language other than English (χ2 = 15.44; P < 0.0001) compared with general park users. Shade and different equipment types were the most cited enablers.

Conclusions

Outdoor gyms may be an acceptable form of physical activity for older adult park users. Installations should offer a variety of equipment types and shade.

So what?

Outdoor gyms are a potential equitable approach to engaging older adults in a variety of physical activity types. Social and physical benefits of outdoor gym use in high risk groups for physical inactivity should be explored.