bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring genetic origins and phenotypic traits of George Bähr, the architect of the Dresden Frauenkirche
Authors: Peltzer Alexander , Mittnik Alissa , Wang Chuan-Chao , Begg Tristan , Posth Cosimo , Nieselt Kay , Krause Johannes
Published: January 2018

For historic individuals, the outward appearance and other phenotypic characteristics remain often non-resolved. Unfortunately, images or detailed written sources are only scarcely available in many cases. Attempts to study historic individuals with genetic data so far focused on hypervariable regions of mitochondrial DNA and to some extent on complete mitochondrial genomes. To elucidate the potential of in-solution based genome-wide SNP capture methods - as now widely applied in population genetics - we extracted DNA from the 17th century remains of George Bähr, the architect of the Dresdner Frauenkirche. We were able to identify the remains to be of male origin, showing sufficient DNA damage, deriving from a single person and being thus likely authentic. Furthermore, we were able to show that George Bähr had light skin pigmentation and most likely brown eyes. His genomic DNA furthermore points to a Central European origin. We see this analysis as an example to demonstrate the prospects that new in-solution SNP capture methods can provide for historic cases of forensic interest, using methods well established in ancient DNA (aDNA) research and population genetics.
Elevated particulate organic carbon export flux induced by internal waves in the oligotrophic northern South China Sea
Authors: Li Dewang , Chou Wen-Chen , Shih Yung-Yen , Chen Guan-Yu , Chang Yi , Chow Chun Hoe , Lin Tsang-Yuh , Hung Chin-Chang
Published: January 2018

To understand the biogeochemical response to internal waves in the deep basin of the northern South China Sea (NSCS), particulate organic carbon (POC) export fluxes were quantified for the first time during the passage of large internal waves using drifting sediment traps attached with hydrographic sensors. Results revealed large variations in temperature, nitrate and chlorophyll a (Chl a) concentrations during and after internal waves, suggesting that cold nutrient-replete waters may be brought to the euphotic zone in the dissipation zone during and after the passage of internal wave packets, resulted in phytoplankton flourished. Most importantly, POC export fluxes (110.9 ± 10.7 mg C m−2 d−1) were significantly enhanced after internal waves compared to non-internal wave area (32.6–73.0 mg C m−2 d−1) in the NSCS. Such elevated POC fluxes may be induced by downward flourished biogenic particles, particle aggregation or converged particles from mixed layer triggered by internal waves.
‘Photonic Hook’ based optomechanical nanoparticle manipulator
Authors: Ang Angeleene S. , Karabchevsky Alina , Minin Igor V. , Minin Oleg V. , Sukhov Sergey V. , Shalin Alexander S.
Published: January 2018

Specialized electromagnetic fields can be used for nanoparticle manipulation along a specific path, allowing enhanced transport and control over the particle’s motion. In this paper, we investigate the optical forces produced by a curved photonic jet, otherwise known as the “photonic hook”, created using an asymmetric cuboid. In our case, this cuboid is formed by appending a triangular prism to one side of a cube. A gold nanoparticle immersed in the cuboid’s transmitted field moves in a curved trajectory. This result could be used for moving nanoparticles around obstacles; hence we also consider the changes in the photonic hook’s forces when relatively large glass and gold obstacles are introduced at the region where the curved photonic jet is created. We show, that despite the obstacles, perturbing the field distribution, a particle can move around glass obstacles of a certain thickness. For larger glass slabs, the particle will be trapped stably near it. Moreover, we noticed that a partial obstruction of the photonic jet’s field using the gold obstacle results in a complete disruption of the particle’s trajectory.
Link between the causative genes of holoprosencephaly: Zic2 directly regulates Tgif1 expression
Authors: Ishiguro Akira , Hatayama Minoru , Otsuka Maky I. , Aruga Jun
Published: January 2018

One of the causal genes for holoprosencephaly (HPE) is ZIC2 (HPE5). It belongs to the zinc finger protein of the cerebellum (Zic) family of genes that share a C2H2-type zinc finger domain, similar to the GLI family of genes. In order to clarify the role of Zic2 in gene regulation, we searched for its direct target genes using chromatin immunoprecipitation (ChIP). We identified TGIF1 (HPE4), another holoprosencephaly-causative gene in humans. We identified Zic2-binding sites (ZBS) on the 5′ flanking region of Tgif1 by in vitro DNA binding assays. ZBS were essential for Zic2-dependent transcriptional activation in reporter gene assays. Zic2 showed a higher affinity to ZBS than GLI-binding sequences. Zic2-binding to the cis-regulatory element near the Tgif1 promoter may be involved in the mechanism underlying forebrain development and incidences of HPE.
Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP)
Authors: Huff Matthew , da Silveira Willian A. , Carnevali Oliana , Renaud Ludivine , Hardiman Gary
Published: January 2018

The organic compound diethylhexyl phthalate (DEHP) represents a high production volume chemical found in cosmetics, personal care products, laundry detergents, and household items. DEHP, along with other phthalates causes endocrine disruption in males. Exposure to endocrine disrupting chemicals has been linked to the development of several adverse health outcomes with apical end points including Non-Alcoholic Fatty Liver Disease (NAFLD). This study examined the adult male zebrafish (Danio rerio) transcriptome after exposure to environmental levels of DEHP and 17α-ethinylestradiol (EE2) using both DNA microarray and RNA-sequencing technologies. Our results show that exposure to DEHP is associated with differentially expressed (DE) transcripts associated with the disruption of metabolic processes in the liver, including perturbation of five biological pathways: ‘FOXA2 and FOXA3 transcription factor networks’, ‘Metabolic pathways’, ‘metabolism of amino acids and derivatives’, ‘metabolism of lipids and lipoproteins’, and ‘fatty acid, triacylglycerol, and ketone body metabolism’. DE transcripts unique to DEHP exposure, not observed with EE2 (i.e. non-estrogenic effects) exhibited a signature related to the regulation of transcription and translation, and ruffle assembly and organization. Collectively our results indicate that exposure to low DEHP levels modulates the expression of liver genes related to fatty acid metabolism and the development of NAFLD.
Identification of coffee bean varieties using hyperspectral imaging: influence of preprocessing methods and pixel-wise spectra analysis
Authors: Zhang Chu , Liu Fei , He Yong
Published: January 2018

Hyperspectral imaging was used to identify and to visualize the coffee bean varieties. Spectral preprocessing of pixel-wise spectra was conducted by different methods, including moving average smoothing (MA), wavelet transform (WT) and empirical mode decomposition (EMD). Meanwhile, spatial preprocessing of the gray-scale image at each wavelength was conducted by median filter (MF). Support vector machine (SVM) models using full sample average spectra and pixel-wise spectra, and the selected optimal wavelengths by second derivative spectra all achieved classification accuracy over 80%. Primarily, the SVM models using pixel-wise spectra were used to predict the sample average spectra, and these models obtained over 80% of the classification accuracy. Secondly, the SVM models using sample average spectra were used to predict pixel-wise spectra, but achieved with lower than 50% of classification accuracy. The results indicated that WT and EMD were suitable for pixel-wise spectra preprocessing. The use of pixel-wise spectra could extend the calibration set, and resulted in the good prediction results for pixel-wise spectra and sample average spectra. The overall results indicated the effectiveness of using spectral preprocessing and the adoption of pixel-wise spectra. The results provided an alternative way of data processing for applications of hyperspectral imaging in food industry.
The activity of the C4-dicarboxylic acid chemoreceptor of Pseudomonas aeruginosa is controlled by chemoattractants and antagonists
Authors: Martín-Mora David , Ortega Álvaro , Pérez-Maldonado Francisco J. , Krell Tino , Matilla Miguel A.
Published: January 2018

Chemotaxis toward organic acids has been associated with colonization fitness and virulence and the opportunistic pathogen Pseudomonas aeruginosa exhibits taxis toward several tricarboxylic acid intermediates. In this study, we used high-throughput ligand screening and isothermal titration calorimetry to demonstrate that the ligand binding domain (LBD) of the chemoreceptor PA2652 directly recognizes five C4-dicarboxylic acids with KD values ranging from 23 µM to 1.24 mM. In vivo experimentation showed that three of the identified ligands act as chemoattractants whereas two of them behave as antagonists by inhibiting the downstream chemotaxis signalling cascade. In vitro and in vivo competition assays showed that antagonists compete with chemoattractants for binding to PA2652-LBD, thereby decreasing the affinity for chemoattractants and the subsequent chemotactic response. Two chemosensory pathways encoded in the genome of P. aeruginosa, che and che2, have been associated to chemotaxis but we found that only the che pathway is involved in PA2652-mediated taxis. The receptor PA2652 is predicted to contain a sCACHE LBD and analytical ultracentrifugation analyses showed that PA2652-LBD is dimeric in the presence and the absence of ligands. Our results indicate the feasibility of using antagonists to interfere specifically with chemotaxis, which may be an alternative strategy to fight bacterial pathogens.
Strain-engineered two-dimensional MoS2 as anode material for performance enhancement of Li/Na-ion batteries
Authors: Hao Jiongyue , Zheng Junfeng , Ling Faling , Chen Yankun , Jing Huirong , Zhou Tingwei , Fang Liang , Zhou Miao
Published: January 2018

Recent years have witnessed a surge of research in two-dimensional (2D) nanostructures for development of new rechargeable Li/Na-ion battery systems. Herein,viafirst-principles calculations we demonstrate strain-engineered Li/Na adsorption and storage in 2D MoS2as anode material, aiming to enhance the operating performance of Li/Na-ion batteries. Our results show that tensile strain greatly increases the adsorption of Li/Na atoms on MoS2, and a modest strain of 6% increases Li (Na) adsorption energy by over 70%, which originates from the strain-induced upshift of Modstates towards Fermi level that interact strongly with Li/Nasstates, in analogy with thed-band model in metal catalyst. Significant narrowing of the n-doped semiconducting gap of MoS2suggests the improved electric conductivity that may benefit charge carrier transport. By mapping out the potential energy surfaces, we show shallow energy barriers of ion diffusion with ~0.2 eV for Li and 0.1 eV for Na. Furthermore, the strain-steered competition between chemical bonding and coulomb repulsion results in high Li/Na storage capability and relatively low average operating voltage. We believe that the fundamental principle underlying the use of strain to enhance performance of renewable ion battery is applicable to other stretchable low-dimensional nanomaterials.
Effects of the floral phytochemical eugenol on parasite evolution and bumble bee infection and preference
Authors: Palmer-Young Evan C. , Calhoun Austin C. , Mirzayeva Anastasiya , Sadd Ben M.
Published: January 2018

Ecological and evolutionary pressures on hosts and parasites jointly determine infection success. In pollinators, parasite exposure to floral phytochemicals may influence between-host transmission and within-host replication. In the bumble bee parasiteCrithidia bombi, strains vary in phytochemical resistance, and resistance increases underin vitroselection, implying that resistance/infectivity trade-offs could maintain intraspecific variation in resistance. We assessed costs and benefits ofin vitroselection for resistance to the floral phytochemical eugenol onC. bombiinfection inBombus impatiensfed eugenol-rich and eugenol-free diets. We also assessed infection-induced changes in host preferences for eugenol.In vitro, eugenol-exposed cells initially increased in size, but normalized during adaptation. Selection for eugenol resistance resulted in considerable (55%) but non-significant reductions in infection intensity; bee colony and body size were the strongest predictors of infection. Dietary eugenol did not alter infection, and infected bees preferred eugenol-free over eugenol-containing solutions. Although direct effects of eugenol exposure could influence between-host transmission at flowers, dietary eugenol did not ameliorate infection in bees. Limited within-host benefits of resistance, and possible trade-offs between resistance and infectivity, may relax selection for eugenol resistance and promote inter-strain variation in resistance. However, infection-induced dietary shifts could influence pollinator-mediated selection on floral traits.
Precipitation of string-shaped morphologies consisting of aligned α phase in a metastable β titanium alloy
Authors: Zhan Hongyi , Ceguerra Anna , Wang Gui , Cairney Julie , Dargusch Matthew
Published: January 2018

String-shaped morphologies consisting of preferentially aligned lath-shaped α precipitates were observed in the metastable β Ti-6Cr-5Mo-5V-4Al alloy after deformations at high strain rates and elevated temperatures. The morphology and 3-dimentional arrangement of this feature have been elaborated based on the characterizations via a combination of transmission electron microscopy, transmission kikuchi diffraction and atom probe tomography. The 2D projected morphology of the coalescent α laths observed in the etched samples by SEM depends on the metallographic section. All the microstructural observations indicate that dislocation structures are most likely the nucleation sites for the aligned α laths. In addition, an appropriate testing temperature, which can ensure a relatively high diffusion rate of solutes without inducing strong recovery of dislocation structures, is necessary for the occurrence of the string-shaped morphologies.
Small Molecule Analogues of the parasitic worm product ES-62 interact with the TIR domain of MyD88 to inhibit pro-inflammatory signalling
Authors: Suckling Colin J. , Alam Shahabuddin , Olson Mark A. , Saikh Kamal U. , Harnett Margaret M. , Harnett William
Published: January 2018

ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is anti-inflammatory by virtue of covalently attached phosphorylcholine. Previously we have reported that drug-like Small Molecule Analogues (SMAs) of its phosphorylcholine moiety can mimic ES-62 in protecting against disease development in certain mouse models of autoimmune and allergic conditions, due to them causing partial degradation of the TLR/IL-1R adaptor MyD88. We have now taken a molecular modelling approach to investigating the mechanism underlying this effect and this predicts that the SMAs interact directly with the MyD88 TIR domain. Further support for this is provided by assay of LPS-induced MyD88/NF-κB-driven secreted alkaline phosphatase (SEAP) reporter activity in commercially-available stably transfected (TLR4-MD2-NF-κB-SEAP) HEK293 cells, as SMA12b-mediated inhibition of such SEAP activity is blocked by its pre-incubation with recombinant MyD88-TIR domain. Direct binding of SMA12b to the TIR domain is also shown to inhibit homo-dimerization of the adaptor, an event that can explain the observed degradation of the adaptor and inhibition of subsequent downstream signalling. Thus, these new data identify initial events by which drug-like ES-62 SMAs, which we also demonstrate are able to inhibit cytokine production by human cells, homeostatically maintain “safe” levels of MyD88 signalling.
VOC emissions influence intra- and interspecific interactions among stored-product Coleoptera in paddy rice
Authors: Giunti Giulia , Palmeri Vincenzo , Algeri Giuseppe Massimo , Campolo Orlando
Published: January 2018

Olfaction is a pivotal sense for insects and granivorous pests may exploit grain volatiles for food selection.Tribolium confusum, is a secondary pest of stored cereals that benefits from primary pests’ infestation, as other secondary feeders, triggering competition. This study aimed to evaluate the preferences ofT. confusumfemales toward different-infested paddy rice, highlighting the impact of intra- and interspecific competition.Tribolium confusumshowed positive chemotaxis toward rice infested by larvae of a primary pest (Sitophilus zeamais), but not for grain attacked by adults alone. Furthermore, kernels concurrently infested by a primary (S. zeamais) and a secondary pest (T. confusumorCryptolestes ferrugineus) were evaluated in Y-tube bioassays, highlighting that both food-sources were innately attractive forT. confusumfemales. Moreover, females positively oriented toward rice infested by conspecifics, while they avoided grain infested byC. ferrugineus, averting an extremely competitive habitat. Behavioural responses ofT. confusumfemales and volatile emissions of different-infested rice highlighted the occurrence of plant-mediated interactions among insects from the same trophic guild. Seventy volatiles were identified and significant differences among the tested food-sources were recorded, emphasizing the presence of 6 putative attractants and 6 repellents, which may be useful biocontrol tools.
miR-539 acts as a tumor suppressor by targeting epidermal growth factor receptor in breast cancer
Authors: Guo Jilong , Gong Guohua , Zhang Bin
Published: January 2018

Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancer-associated death in women worldwide. microRNAs (miRNAs) play critical roles in the cellular processes of breast cancer. However, the crucial roles and underlying mechanisms of miR-539 in breast cancer remain unclear. By RT-qPCR, we found that expression of miR-539 was markedly down-regulated in breast cancer tissues and cell lines compared with that in paired adjacent normal tissues and normal cell lines. The low level of miR-539 expression was positively associated with lymph node metastasis. Furthermore, forced expression of miR-539 inhibited proliferation and migration of breast cancer MDA-MB-231 and MCF7 cells in vitro and suppressed tumor growth in vivo. Moreover, bioinformatics analysis and luciferase reporter assays indicated that epidermal growth factor receptor (EGFR) was a direct target of miR-539. Over-expression of miR-539 decreased the EGFR mRNA and protein levels in MDA-MB-231 and MCF7 cells. In addition, ectopic over-expression of EGFR partly reversed miR-539-inhibited proliferation as well as migration of MDA-MB-231 and MCF7 cells. Taken together, our results demonstrate that miR-539 functions as a tumor suppressor in breast cancer by downregulating EGFR, supporting the targeting of the novel miR-539/EGFR axis as a potentially effective therapeutic approach for breast cancer.
The fossil teeth of the Peking Man
Authors: Xing Song , Martinón-Torres María , Bermúdez de Castro José María
Published: January 2018

This study provides new original data, including the endostructure of most Zhoukoudian H. erectus teeth preserved to date, since the publication of Black in 1927 and Weidenreich in 1937. The new evidence ratifies the similarities of Zhoukoudian with other East Asian mid-Middle Pleistocene hominins such as Hexian and Yiyuan, and allows defining a dental pattern potentially characteristic of this population commonly referred to as classic H. erectus. Given the possible chronological overlaps of classic H. erectus with other archaic Homo, the characterization of this group becomes a key issue when deciphering the taxonomy and evolutionary scenario of the Middle Pleistocene hominins in East Asia. Internally, the most remarkable feature of Zhoukoudian teeth is the highly crenulated enamel-dentine junction (EDJ) and its imprint on the roof of the pulp cavity. So far, this “dendrite-like” EDJ has been found only in East Asia Middle Pleistocene hominins although a large group of samples were assessed, and it could be useful to dentally define classic H. erectus in China. The crenulated EDJ surface, together with the stout roots and the taurodontism could be a mechanism to withstand high biomechanical demand despite a general dentognathic reduction, particularly of the crowns, in these populations.
Recent intensification of winter haze in China linked to foreign emissions and meteorology
Authors: Yang Yang , Wang Hailong , Smith Steven J. , Zhang Rudong , Lou Sijia , Qian Yun , Ma Po-Lun , Rasch Philip J.
Published: January 2018

Wintertime aerosol pollution in the North China Plain has increased over the past several decades as anthropogenic emissions in China have increased, and has dramatically escalated since the beginning of the 21st century, but the causes and their quantitative attributions remain unclear. Here we use an aerosol source tagging capability implemented in a global aerosol-climate model to assess long-term trends of PM2.5 (particulate matter less than 2.5 μm in diameter) in the North China Plain. Our analysis suggests that the impact of China’s increasing domestic emissions on PM2.5 concentrations over the last two decades of 20th century was partially offset (13%) by decreasing foreign emission over this period. As foreign emissions stabilized after 2000, their counteracting effect almost disappeared, uncovering the impact of China’s increasing domestic emissions that had been partially offset in previous years by reductions in foreign emissions. A slowdown in the impact from foreign emission reductions together with weakening winds explain 25% of the increased PM2.5 trend over 2000–2014 as compared to 1980–2000. Further reductions in foreign emissions are not expected to relieve China’s pollution in the future. Reducing local emissions is the most certain way to improve future air quality in the North China Plain.
SMARCA2-regulated host cell factors are required for MxA restriction of influenza A viruses
Authors: Dornfeld Dominik , Dudek Alexandra H. , Vausselin Thibaut , Günther Sira C. , Hultquist Judd F. , Giese Sebastian , Khokhlova-Cubberley Daria , Chew Yap C. , Pache Lars , Krogan Nevan J. , Garcia-Sastre Adolfo , Schwemmle Martin , Shaw Megan L.
Published: January 2018

The human interferon (IFN)-induced MxA protein is a key antiviral host restriction factor exhibiting broad antiviral activity against many RNA viruses, including highly pathogenic avian influenza A viruses (IAV) of the H5N1 and H7N7 subtype. To date the mechanism for how MxA exerts its antiviral activity is unclear, however, additional cellular factors are believed to be essential for this activity. To identify MxA cofactors we performed a genome-wide siRNA-based screen in human airway epithelial cells (A549) constitutively expressing MxA using an H5N1 reporter virus. These data were complemented with a proteomic screen to identify MxA-interacting proteins. The combined data identified SMARCA2, the ATPase subunit of the BAF chromatin remodeling complex, as a crucial factor required for the antiviral activity of MxA against IAV. Intriguingly, our data demonstrate that although SMARCA2 is essential for expression of some IFN-stimulated genes (ISGs), and the establishment of an antiviral state, it is not required for expression of MxA, suggesting an indirect effect on MxA activity. Transcriptome analysis of SMARCA2-depleted A549-MxA cells identified a small set of SMARCA2-regulated factors required for activity of MxA, in particular IFITM2 and IGFBP3. These findings reveal that several virus-inducible factors work in concert to enable MxA restriction of IAV.
IGFBPL1 Regulates Axon Growth through IGF-1-mediated Signaling Cascades
Authors: Guo Chenying , Cho Kin-Sang , Li Yingqian , Tchedre Kissauo , Antolik Christian , Ma Jie , Chew Justin , Utheim Tor Paaske , Huang Xizhong A. , Yu Honghua , Malik Muhammad Taimur A. , Anzak Nada , Chen Dong Feng
Published: January 2018

Activation of axonal growth program is a critical step in successful optic nerve regeneration following injury. Yet the molecular mechanisms that orchestrate this developmental transition are not fully understood. Here we identified a novel regulator, insulin-like growth factor binding protein-like 1 (IGFBPL1), for the growth of retinal ganglion cell (RGC) axons. Expression of IGFBPL1 correlates with RGC axon growth in development, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. In contrast, administration of IGFBPL1 promoted axon growth. Moreover, IGFBPL1 bound to insulin-like growth factor 1 (IGF-1) and subsequently induced calcium signaling and mammalian target of rapamycin (mTOR) phosphorylation to stimulate axon elongation. Blockage of IGF-1 signaling abolished IGFBPL1-mediated axon growth, and vice versa, IGF-1 required the presence of IGFBPL1 to promote RGC axon growth. These data reveal a novel element in the control of RGC axon growth and suggest an unknown signaling loop in the regulation of the pleiotropic functions of IGF-1. They suggest new therapeutic target for promoting optic nerve and axon regeneration and repair of the central nervous system.
Substitutions of the S4DIV R2 residue (R1451) in NaV1.4 lead to complex forms of paramyotonia congenita and periodic paralyses
Authors: Poulin Hugo , Gosselin-Badaroudine Pascal , Vicart Savine , Habbout Karima , Sternberg Damien , Giuliano Serena , Fontaine Bertrand , Bendahhou Saïd , Nicole Sophie , Chahine Mohamed
Published: January 2018

Mutations in NaV1.4, the skeletal muscle voltage-gated Na+ channel, underlie several skeletal muscle channelopathies. We report here the functional characterization of two substitutions targeting the R1451 residue and resulting in 3 distinct clinical phenotypes. The R1451L is a novel pathogenic substitution found in two unrelated individuals. The first individual was diagnosed with non-dystrophic myotonia, whereas the second suffered from an unusual phenotype combining hyperkalemic and hypokalemic episodes of periodic paralysis (PP). The R1451C substitution was found in one individual with a single attack of hypoPP induced by glucocorticoids. To elucidate the biophysical mechanism underlying the phenotypes, we used the patch-clamp technique to study tsA201 cells expressing WT or R1451C/L channels. Our results showed that both substitutions shifted the inactivation to hyperpolarized potentials, slowed the kinetics of inactivation, slowed the recovery from slow inactivation and reduced the current density. Cooling further enhanced these abnormalities. Homology modeling revealed a disruption of hydrogen bonds in the voltage sensor domain caused by R1451C/L. We concluded that the altered biophysical properties of R1451C/L well account for the PMC-hyperPP cluster and that additional factors likely play a critical role in the inter-individual differences of clinical expression resulting from R1451C/L.
Expression analysis of candidate genes for fatty acid composition in adipose tissue and identification of regulatory regions
Authors: Revilla Manuel , Puig-Oliveras Anna , Crespo-Piazuelo Daniel , Criado-Mesas Lourdes , Castelló Anna , Fernández Ana I. , Ballester Maria , Folch Josep M.
Published: January 2018

The aim of this work was to study the genetic basis of the backfat expression of lipid-related genes associated with meat quality traits in pigs. We performed a genome-wide association study with the backfat gene expression measured in 44 genes by qPCR and thePorcineSNP60 BeadChipgenotypes in 115 Iberian x Landrace backcross animals. A total of 193 expression-associated SNPs located in 19 chromosomal regions were associated with expression levels ofACSM5,ELOVL6,FABP4,FADS2, andSLC27A4genes. Three expression quantitative trail loci (eQTLs) corresponding toACSM5,FABP4, andFADS2were classified ascis-acting eQTLs, whereas the remaining 16 eQTLs havetrans-regulatory effects. Remarkably, a SNP in theACSM5promoter region and a SNP in the 3′UTR region ofFABP4were the most associated polymorphisms with theACSM5andFABP4expression levels, respectively. Moreover, relevant lipid-related genes mapped in thetrans-eQTLs regions associated with theACSM5,FABP4,FADS2, andSLC27A4genes. Interestingly, atrans-eQTL hotspot on SSC13 regulating the gene expression ofELOVL6,ELOLV5, andSCD, three important genes implicated in the elongation and desaturation of fatty acids, was identified. These findings provide new data to further understand the functional regulatory mechanisms implicated in the variation of fatty acid composition in pigs.
Chaos and dynamical complexity in the quantum to classical transition
Authors: Pokharel Bibek , Misplon Moses Z. R. , Lynn Walter , Duggins Peter , Hallman Kevin , Anderson Dustin , Kapulkin Arie , Pattanayak Arjendu K.
Published: January 2018

We study the largest Lyapunov exponents λ and dynamical complexity for an open quantum driven double-well oscillator, mapping its dependence on coupling to the environment Γ as well as effective Planck’s constant β2. We show that in general λ increases with effective Hilbert space size (as β decreases, or the system becomes larger and closer to the classical limit). However, if the classical limit is regular, there is always a quantum system with λ greater than the classical λ, with several examples where the quantum system is chaotic even though the classical system is regular. While the quantum chaotic attractors are generally of the same family as the classical attractors, we also find quantum attractors with no classical counterpart. Contrary to the standard wisdom, the correspondence limit can thus be the most difficult to achieve for certain classically chaotic systems. These phenomena occur in experimentally accessible regimes.
KIBRA is associated with accelerated cognitive decline and hippocampal atrophy in APOE ε4-positive cognitively normal adults with high Aβ-amyloid burden
Authors: Porter Tenielle , Burnham Samantha C. , Doré Vincent , Savage Greg , Bourgeat Pierrick , Begemann Kimberly , Milicic Lidija , Ames David , Bush Ashley I. , Maruff Paul , Masters Colin L. , Rowe Christopher C. , Rainey-Smith Stephanie , Martins Ralph N. , Groth David , Verdile Giuseppe , Villemagne Victor L. , Laws Simon M.
Published: January 2018

A single nucleotide polymorphism, rs17070145, in the KIdney and BRAin expressed protein (KIBRA) gene has been associated with cognition and hippocampal volume in cognitively normal (CN) individuals. However, the impact of rs17070145 on longitudinal cognitive decline and hippocampal atrophy in CN adults at greatest risk of developing Alzheimer’s disease is unknown. We investigated the impact rs17070145 has on the rate of cognitive decline and hippocampal atrophy over six years in 602 CN adults, with known brain Aβ-amyloid levels and whether there is an interactive effect with APOE genotype. We reveal that whilst limited independent effects of KIBRA genotype were observed, there was an interaction with APOE in CN adults who presented with high Aβ-amyloid levels across study duration. In comparison to APOE ε4-ve individuals carrying the rs17070145-T allele, significantly faster rates of cognitive decline (global, p = 0.006; verbal episodic memory, p = 0.004), and hippocampal atrophy (p = 0.04) were observed in individuals who were APOE ε4 + ve and did not carry the rs17070145-T allele. The observation of APOE effects in only non-carriers of the rs17070145-T allele, in the presence of high Aβ-amyloid suggest that carriers of the rs17070145-T allele are conferred a level of resilience to the detrimental effects of high Aβ-amyloid and APOE ε4.
Heterologous pathway assembly reveals molecular steps of fungal terreic acid biosynthesis
Authors: Kong Chuixing , Huang Hezhou , Xue Ying , Liu Yiqi , Peng Qiangqiang , Liu Qi , Xu Qin , Zhu Qiaoyun , Yin Ying , Zhou Xiangshan , Zhang Yuanxing , Cai Menghao
Published: January 2018

Terreic acid is a potential anticancer drug as it inhibits Bruton’s tyrosine kinase; however, its biosynthetic molecular steps remain unclear. In this work, the individual reactions of terreic acid biosynthesis were determined by stepwise pathway assembly in a heterologous host, Pichia pastoris, on the basis of previous knockout studies in a native host, Aspergillus terreus. Polyketide synthase AtX was found to catalyze the formation of partially reduced polyketide 6-methylsalicylic acid, followed by 3-methylcatechol synthesis by salicylate 1-monooxygenase AtA-mediated decarboxylative hydroxylation of 6-methylsalicylic acid. Our results show that cytochrome P450 monooxygenase AtE hydroxylates 3-methylcatechol, thus producing the next product, 3-methyl-1,2,4-benzenetriol. A smaller putative cytochrome P450 monooxygenase, AtG, assists with this step. Then, AtD causes epoxidation and hydroxyl oxidation of 3-methyl-1,2,4-benzenetriol and produces a compound terremutin, via which the previously unknown function of AtD was identified as cyclooxygenation. The final step involves an oxidation reaction of a hydroxyl group by a glucose-methanol-choline oxidoreductase, AtC, which leads to the final product: terreic acid. Functions of AtD and AtG were determined for the first time. All the genes were reanalyzed and all intermediates and final products were isolated and identified. Our model fully defines the molecular steps and corrects previous results from the literature.
Dual-functional tunable coding metasurface based on saline water substrate
Authors: Chen Lei , Ma He Liang , Song Xiao Jun , Ruan Ying , Cui Hao Yang
Published: January 2018

In this paper, a dual-functional tunable coding metasurface is presented at X band based on water substrate, which can realize two different functions of specific scattering pattern and absorption at two different frequency ranges. Besides, by changing the salinity of the saline water substrate, the absorption performance in high frequency can be tuned, while the scattering pattern in low frequency remains unchanged. A coding element is designed with small water cavity in it. Three coding sequences with different radiation patterns are designed to verify these functions, and one of them is fabricated and measured. Experimental results have good accordance with our simulations, which demonstrates our schemes. We believe this work can not only broaden our design manner of metasurfaces, but also have plenty potential applications in biological and medical detection domain.
Association of estimated glomerular filtration rate and proteinuria with all-cause mortality in community-based population in China: A Result from Kailuan Study
Authors: Wu Jianwei , Jia Jiaokun , Li Zhaoxia , Pan Hua , Wang Anxin , Guo Xiuhua , Wu Shouling , Zhao Xingquan
Published: January 2018

This study was based on 95391 participants (18–98 years old) from the Kailuan study, which assessed all-cause mortality in a community-based population in northern China according to estimated glomerular filtration rate (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and proteinuria estimated from urine dipstick results. Data were analysed based on Cox proportional hazards models with adjustment for relevant confounders, and the results were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). During eight years of follow-up, a total of 6024 participants died. The two indicators, eGFR < 45 ml/min/1.73 m2 and the presence of proteinuria, were independently associated with all-cause mortality. Compared with eGFR ≥45 ml/min/1.73 m2 with negative proteinuria, HRs of all-cause mortality were 1.26 (95% CI 1.10–1.44) for eGFR < 45 ml/min/1.73 m2 without proteinuria, 1.95 (1.78–2.14) for eGFR ≥45 ml/min/1.73 m2 with proteinuria, and 2.63 (2.14–3.23) for eGFR < 45 ml/min/1.73 m2 with proteinuria. The all-cause mortality risk of eGFR and/or proteinuria was much higher in females than in males (P for interaction < 0.01). In conclusion, both severely decreased eGFR and proteinuria are independent predictors of all-cause mortality in the general northern Chinese population. A combination of severely decreased eGFR and proteinuria increases the risk of all-cause mortality, which is even over 5-fold higher in females.
Therapeutic effects of anti-CD154 antibody in cynomolgus monkeys with advanced rheumatoid arthritis
Authors: Choi Eun Wha , Lee Kyo Won , Park Hyojun , Kim Hwajung , Lee Jong Hyun , Song Ji Woo , Yang Jehoon , Kwon Yeongbeen , Kim Tae Min , Park Jae Berm , Kim Sungjoo
Published: January 2018

Rheumatoid arthritis is one major chronic inflammatory systemic autoimmune disease. The CD154-CD40 interactions play a critical role in the regulation of immune responses and the maintenance of autoimmunity. Therefore, we aimed to determine whether anti-CD154 antibody treatment show positive effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in cynomolgus monkeys. Arthritis was induced using chicken type II collagen (CII) and arthritic monkey were divided into control and anti-CD154 treatment groups based on their concentrations of anti-CII antibodies on week 7 post-immunization. Blood and tissue samples were collected on week 16 post-immunization. Anti-CD154 antibody treatment improved arthritis and movement, and significantly decreased the numbers of proliferating B cells and the serum levels of anti-type II collagen antibody and sCD154 compared with non-treatment group. Further anti-CD154 antibody treatment significantly decreased the percentage of CD4+ cells and the ratio of CD4+ to CD8+ T cells and significantly increased the percentage of CD8+ cells and effector memory CD8+ cells in peripheral blood. We have shown for the first time in a nonhuman primate model of RA that CD154 blockade has beneficial effects. This study might be valuable as preclinical data of CD154 blockade in nonhuman primate models of severe rheumatoid arthritis.
A Wearable High-Resolution Facial Electromyography for Long Term Recordings in Freely Behaving Humans
Authors: Inzelberg Lilah , Rand David , Steinberg Stanislav , David-Pur Moshe , Hanein Yael
Published: January 2018

Human facial expressions are a complex capacity, carrying important psychological and neurological information. Facial expressions typically involve the co-activation of several muscles; they vary between individuals, between voluntary versus spontaneous expressions, and depend strongly on personal interpretation. Accordingly, while high-resolution recording of muscle activation in a non-laboratory setting offers exciting opportunities, it remains a major challenge. This paper describes a wearable and non-invasive method for objective mapping of facial muscle activation and demonstrates its application in a natural setting. We focus on muscle activation associated with “enjoyment”, “social” and “masked” smiles; three categories with distinct social meanings. We use an innovative, dry, soft electrode array designed specifically for facial surface electromyography recording, a customized independent component analysis algorithm, and a short training procedure to achieve the desired mapping. First, identification of the orbicularis oculi and the levator labii superioris was demonstrated from voluntary expressions. Second, the zygomaticus major was identified from voluntary and spontaneous Duchenne and non-Duchenne smiles. Finally, using a wireless device in an unmodified work environment revealed expressions of diverse emotions in face-to-face interaction. Our high-resolution and crosstalk-free mapping, along with excellent user-convenience, opens new opportunities in gaming, virtual-reality, bio-feedback and objective psychological and neurological assessment.
Kisspeptin-10 (KP-10) stimulates osteoblast differentiation through GPR54-mediated regulation of BMP2 expression and activation
Authors: Son Hyo-Eun , Kim Kyeong-Min , Kim Eun-Jung , Jang Won-Gu
Published: January 2018

Kisspeptin-10 (KP-10) acts as a tumor metastasis suppressor via its receptor, G-protein-coupled receptor 54 (GPR54). The KP-10-GPR54 system plays an important role in embryonic kidney development. However, its function in osteoblast differentiation is unknown. Osteoblast differentiation is controlled by a range of hormones and cytokines, such as bone morphogenetic protein (BMPs), and multiple transcription factors, such as Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and Distal-less homeobox 5 (Dlx5). In the present study, KP-10-treatment significantly increased the expression of osteogenic genes, including mRNA and protein levels of BMP2, in C3H10T1/2 cells. Moreover, KP-10 induced BMP2-luc activity and increased phosphorylation of Smad1/5/9. In addition, NFATc4 specifically mediated KP-10-induced BMP2 gene expression. However, KP-10 treatment did not induce expression of the BMP2 and Runx2 genes in GPR54−/− cells. To examine whether KP-10 induced secretion of BMP2 to the culture medium, we used the conditioned-medium (C.M) of KP-10 treated medium on C3H10T1/2 cells. Dlx5 and Runx2 expressions were higher in GPR54−/− cells treated with C.M than in those treated with KP-10. These results demonstrate that BMP2 protein has an autocrine effect upon KP-10 treatment. Taken together, these findings suggest that KP-10/GPR54 signaling induces osteoblast differentiation via NFATc4-mediated BMP2 expression.
Panton-Valentine Leukocidin associated with S. aureus osteomyelitis activates platelets via neutrophil secretion products
Authors: Niemann Silke , Bertling Anne , Brodde Martin F. , Fender Anke C. , Van de Vyver Hélène , Hussain Muzaffar , Holzinger Dirk , Reinhardt Dirk , Peters Georg , Heilmann Christine , Löffler Bettina , Kehrel Beate E.
Published: January 2018

Globalization and migration promote the spread of Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus strains. The toxin PVL is linked to the development of thrombosis in association with osteomyelitis. The mechanisms by which PVL drives thrombosis development are however still unknown. We demonstrate that PVL-damaged neutrophils activate platelets via neutrophil secretion products, such as α-defensins and the myeloperoxidase product HOCl, as well as the formation of HOCl-modified proteins. Neutrophil damage by PVL is blocked by anti-PVL-antibodies, explaining why especially young osteomyelitis patients with a low antibody titre against PVL suffer from thrombotic complications. Platelet activation in the presence of PVL-damaged neutrophils is prevented by α-defensin inhibitors and by glutathione and resveratrol, which are both inhibitors of HOCl-modified protein-induced platelet activation. Remarkably, intravenously infused glutathione also prevents activation of human platelets in an ex vivo assay. We here describe a new mechanism of PVL-neutrophil-platelet interactions, which might be extrapolated to other toxins that act on neutrophils. Our observations may make us think about new approaches to treat and/or prevent thrombotic complications in the course of infections with PVL-producing S. aureus strains.
Resistance Switching and Memristive Hysteresis in Visible-Light-Activated Adsorbed ZnO Thin Films
Authors: Barnes Benjamin Kerr , Das Kausik S.
Published: January 2018

The discovery of resistance switching memristors marks a paradigm shift in the search for alternative non-volatile memory components in the semiconductor industry. Normally a dielectric in these bistable memory cells changes its resistance with an applied electric field or current, albeit retaining the resistive state based on the history of the applied field. Despite showing immense potential, sustainable growth of this new memory technology is bogged down by several factors including cost, intricacies of design, lack of efficient tunability, and issues with scalability and eco-friendliness. Here, we demonstrate a simple arrangement wherein an ethanol-adsorbed ZnO thin film exhibits orders of magnitude change in resistance when activated by visible light. We show that there exists two stable ohmic states, one in the dark and the other in the illuminated regime, as well as a significant delay in the transition between these saturated states. We also demonstrate that visible light acts as a non-invasive tuning parameter for the bistable resistive states. Furthermore, a pinched hysteresis I-V response observed in these devices indicate what seems to be a new type of memristive behaviour.
Chitosan nanoparticles functionalized with β-cyclodextrin: a promising carrier for botanical pesticides
Authors: Campos Estefânia V. R. , Proença Patrícia L. F. , Oliveira Jhones L. , Melville Cirano C. , Della Vechia Jaqueline F. , de Andrade Daniel J. , Fraceto Leonardo F.
Published: January 2018

Carvacrol and linalool are natural compounds extracted from plants and are known for their insecticidal and repellent activities, respectively. However, their low aqueous solubility, high photosensitivity, and high volatility restrict their application in the control of agricultural pests. The encapsulation of volatile compounds can be an effective way of overcoming such problems. Inclusion complexes between beta-cyclodextrin (β-CD) and carvacrol (CVC) or linalool (LNL) were investigated. Inclusion complexes were prepared by the kneading method. Both complexes presented 1:1 host:guest stoichiometry and the highest affinity constants were observed at 20 °C for both molecules. The nanoparticles containing carvacrol and linalool had mean diameters of 175.2 and 245.8 nm, respectively and high encapsulation efficiencies (<90%) were achieved for both compounds. Biological assays with mites (Tetranychus urticae) showed that the nanoparticles possessed repellency, acaricidal, and oviposition activities against this organism. Nanoencapsulated carvacrol and linalool were significantly more effective in terms of acaricidal and oviposition activities, while the unencapsulated compounds showed better repellency activity. The nanoformulations prepared in this study are good candidates for the sustainable and effective use of botanical compounds in agriculture, contributing to the reduction of environmental contamination, as well as promoting the effective control of pests in agriculture.
Double MgO-based Perpendicular Magnetic-Tunnel-Junction Spin-valve Structure with a Top Co2Fe6B2 Free Layer using a Single SyAF [Co/Pt]n Layer
Authors: Choi Jin-Young , Lee Dong-gi , Baek Jong-Ung , Park Jea-Gun
Published: January 2018

A new perpendicular spin-transfer-torque magnetic-tunnel-junction (p-MTJ) spin-valve was developed to achieve a high tunneling magnetoresistance (TMR) ratio. It had a double MgO-based spin-valve structure with a top Co2Fe6B2 free layer and incorporated a single SyAF [Co(0.4 nm)/Pt(0.3 nm)]3 layer and a new buffer layer of Co(0.6)/Pt(0.3)/Co(0.4). It had a TMR ratio of 180% and anisotropy exchange field (H
ex
) of 3.44 kOe after ex-situ annealing of 350 °C for 30 min under a vacuum below 10−6 torr and a perpendicular magnetic field of 3 tesla, thereby ensuring a memory margin and avoiding read disturbance failures. Its high level of performance was due to the face-center-cubic crystallinity of the MgO tunneling barrier being significantly improved by decreasing its surface roughness (i.e., peak-to-valley length of 1.4 nm).