bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic signatures of invasive status in populations of marine invertebrates
Authors: Ardura Alba , Zaiko Anastasija , Morán Paloma , Planes Serge , Garcia-Vazquez Eva
Published: February 2017

Epigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced. Decreased methylation was interpreted as a rapid way of increasing phenotypic plasticity that would help invasive populations to thrive. This epigenetic signature of early invasion was stronger than the expected environmental signature of environmental stress in younger populations sampled from ports, otherwise detected in a much older population (>90 year old) of the also invasive tubewormFicopomatus enigmaticusestablished in similar locations. Higher epigenetic than genetic diversity found inX. securiswas confirmed fromF. enigmaticussamples. As reported for introduced plants and vertebrates, epigenetic variation could compensate for relatively lower genetic variation caused by founder effects. These phenomena were compared with epigenetic mechanisms involved in metastasis, as parallel processes of community (biological invasion) and organism (cancer) invasions.
Genome editing reveals dmrt1 as an essential male sex-determining gene in Chinese tongue sole (Cynoglossus semilaevis)
Authors: Cui Zhongkai , Liu Yun , Wang Wenwen , Wang Qian , Zhang Ning , Lin Fan , Wang Na , Shao Changwei , Dong Zhongdian , Li Yangzhen , Yang Yingming , Hu Mengzhu , Li Hailong , Gao Fengtao , Wei Zhanfei , Meng Liang , Liu Yang , Wei Min , Zhu Ying , Guo Hua , Cheng Christopher H. K. , Schartl Manfred , Chen Songlin
Published: February 2017

Chinese tongue sole is a marine fish with ZW sex determination. Genome sequencing suggested that the Z-linked dmrt1 is a putative male determination gene, but direct genetic evidence is still lacking. Here we show that TALEN of dmrt1 efficiently induced mutations of this gene. The ZZ dmrt1 mutant fish developed ovary-like testis, and the spermatogenesis was disrupted. The female-related genes foxl2 and cyp19a1a were significantly increased in the gonad of the ZZ dmrt1 mutant. Conversely, the male-related genes Sox9a and Amh were significantly decreased. The dmrt1 deficient ZZ fish grew much faster than ZZ male control. Notably, we obtained an intersex ZW fish with a testis on one side and an ovary on the other side. This fish was chimeric for a dmrt1 mutation in the ovary, and wild-type dmrt1 in the testis. Our data provide the first functional evidence that dmrt1 is a male determining gene in tongue sole.
Hypoxia-induced angiotensin II by the lactate-chymase-dependent mechanism mediates radioresistance of hypoxic tumor cells
Authors: Xie Guozhu , Liu Ying , Yao Qiwei , Zheng Rong , Zhang Lanfang , Lin Jie , Guo Zhaoze , Du Shasha , Ren Chen , Yuan Quan , Yuan Yawei
Published: February 2017

The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism. We further demonstrate in nasopharyngeal carcinoma CNE2 and 5–8F cells that this chymase-dependent effect is mediated by increased levels of lactate, a by-product of glycolytic metabolism. Finally, we show that the enhanced angiotensin II plays an important role in the intracellular accumulation of HIF-1α of hypoxic nasopharyngeal carcinoma cells and mediates the radiation-resistant phenotype of these nasopharyngeal carcinoma cells. Thus, our findings reveal the critical role of hypoxia in producing local angiotensin II by a lactate-chymase-dependent mechanism and highlight the importance of local angiotensin II in regulating radioresistance of hypoxic tumor cells.
Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins
Authors: Vale Filipa F. , Nunes Alexandra , Oleastro Mónica , Gomes João P. , Sampaio Daniel A. , Rocha Raquel , Vítor Jorge M. B. , Engstrand Lars , Pascoe Ben , Berthenet Elvire , Sheppard Samuel K. , Hitchings Matthew D. , Mégraud Francis , Vadivelu Jamuna , Lehours Philippe
Published: February 2017

Helicobacter pylorigenetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements ofH. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found inH. pyloriisolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6–33.0 Kbp, consisting of 27–39 open reading frames. A 36.6% GC was found in prophages in contrast to 39% inH. pylorigenome. Remarkably a conserved integration site was found in over 50% of the cases. Nearly 40% of the prophages harbored insertion sequences (IS) previously described inH. pylori. Tandem repeats were frequently found in the intergenic region between the prophage at the 3′ end and the bacterial gene. Furthermore, prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. Evidence of recombination was detected within the genome of some prophages, resulting in genome mosaics composed by different populations, which may yield additionalH. pyloriphenotypes.
A data-driven approach for evaluating multi-modal therapy in traumatic brain injury
Authors: Haefeli Jenny , Ferguson Adam R. , Bingham Deborah , Orr Adrienne , Won Seok Joon , Lam Tina I. , Shi Jian , Hawley Sarah , Liu Jialing , Swanson Raymond A. , Massa Stephen M.
Published: February 2017

Combination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint. Data was curated and analyzed in a linked workflow involving non-linear principal component analysis followed by hypothesis testing with a linear mixed model. Results revealed significant benefits of the neurotrophic agent LM11A-31 on learning and memory outcomes after traumatic brain injury. In addition, modulations of LM11A-31 effects by co-administration of minocycline and by the type of physical therapy applied reached statistical significance. These results suggest a combinatorial effect of drug and physical therapy interventions that was not evident by univariate analysis. The study designs and analytic techniques applied here form a structured, unbiased, internally validated workflow that may be applied to other combinatorial studies, both in animals and humans.
Retinal Structure and Function in Eyes with Optic Nerve Hypoplasia
Authors: Katagiri Satoshi , Nishina Sachiko , Yokoi Tadashi , Mikami Masashi , Nakayama Yuri , Tanaka Michiko , Azuma Noriyuki
Published: February 2017

We investigated retinal structure and function in eyes with optic nerve hypoplasia (ONH). Twenty-nine eyes of 18 patients with ONH and 21 eyes of 21 control patients were analyzed. Spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (FF-ERG), and focal macular ERG (FM-ERG) were performed. SD-OCT analysis of the macular region showed significant ganglion cells complex (GCC) thinning nasally and temporally (P < 0.05), but the thickness from the inner nuclear layer (INL) to the retinal pigment epithelium (RPE) became thinner only nasally (P < 0.05). SD-OCT analysis of the circumpapillary region showed significant thinning in the retinal nerve fiber layer and from the INL to the RPE (P < 0.05). The horizontal SD-OCT images showed variable foveal abnormalities. FF-ERG analysis showed significantly reduced amplitudes (P < 0.05) and preserved implicit time in the photopic negative response. The amplitudes and implicit times of the other FF-ERG components did not differ significantly. FM-ERG analysis showed significantly reduced amplitudes (P < 0.05) but preserved implicit times in all components. The current study showed the change of retinal structure and function in eyes with ONH compared with those with control, representing by decreased retinal ganglion cells (RGCs) and their axons, foveal abnormalities, and preserved peripheral retina except for the RGCs and their axons.
Wnt5a is a crucial regulator of neurogenesis during cerebellum development
Authors: Subashini Chandramohan , Dhanesh Sivadasan Bindu , Chen Chih-Ming , Riya Paul Ann , Meera Vadakkath , Divya Thulasi Sheela , Kuruvilla Rejji , Buttler Kerstin , James Jackson
Published: February 2017

The role of Wnt5a has been extensively explored in various aspects of development but its role in cerebellar development remains elusive. Here, for the first time we unravel the expression pattern and functional significance of Wnt5a in cerebellar development using Wnt5a−/− and Nestin-Cre mediated conditional knockout mouse models. We demonstrate that loss of Wnt5a results in cerebellar hypoplasia and depletion of GABAergic and glutamatergic neurons. Besides, Purkinje cells of the mutants displayed stunted, poorly branched dendritic arbors. Furthermore, we show that the overall reduction is due to decreased radial glial and granule neuron progenitor cell proliferation. At molecular level we provide evidence for non-canonical mode of action of Wnt5a and its regulation over genes associated with progenitor proliferation. Altogether our findings imply that Wnt5a signaling is a crucial regulator of cerebellar development and would aid in better understanding of cerebellar disease pathogenesis caused due to deregulation of Wnt signaling.
Biological motion distorts size perception
Authors: Veto Peter , Einhäuser Wolfgang , Troje Nikolaus F.
Published: February 2017

Visual illusions explore the limits of sensory processing and provide an ideal testbed to study perception. Size illusions – stimuli whose size is consistently misperceived – do not only result from sensory cues, but can also be induced by cognitive factors, such as social status. Here we investigate, whether the ecological relevance of biological motion can also distort perceived size. We asked observers to judge the size of point-light walkers (PLWs), configurations of dots whose movements induce the perception of human movement, and visually matched control stimuli (inverted PLWs). We find that upright PLWs are consistently judged as larger than inverted PLWs, while static point-light figures do not elicit the same effect. We also show the phenomenon using an indirect paradigm: observers judged the relative size of a disc that followed an inverted PLW larger than a disc following an upright PLW. We interpret this as a contrast effect: The upright PLW is perceived larger and thus the subsequent disc is judged smaller. Together, these results demonstrate that ecologically relevant biological-motion stimuli are perceived larger than visually matched control stimuli. Our findings present a novel case of illusory size perception, where ecological importance leads to a distorted perception of size.
Non-reliance of metazoans on stromatolite-forming microbial mats as a food resource
Authors: Rishworth Gavin M. , Perissinotto Renzo , Bird Matthew S. , Strydom Nadine A. , Peer Nasreen , Miranda Nelson A. F. , Raw Jacqueline L.
Published: February 2017

Grazing and burrowing organisms usually homogenise microalgal mats that form on benthic sediments of many aquatic ecosystems. In the absence of this disruption, microalgal mats can accrete laminated deposits (stromatolites). Stromatolites are rare in modern coastal ecosystems, but persist at locations where metazoans are largely excluded. This study aimed to assess the trophic structure at stromatolite locations where metazoans co-occur, to determine the grazing influence exerted by the metazoans on the stromatolite-forming microalgae (cyanobacteria and diatoms). Stable isotope signatures (δ13C and δ15N) were used as food-web tracers and dietary composition of consumers was calculated using source mixing models. Results clearly demonstrate that the dominant macrofaunal grazers do not utilise stromatolite material as a food resource, but rather subsist on autochthonous macroalgae. For instance, the mean (±SD) dietary composition of two of the most abundant grazers, Melita zeylanica (Amphipoda) and Composetia cf. keiskama (Polychaeta), consisted of 80 ± 11% and 91 ± 7% macroalgae, respectively. This suggests that the stromatolite-forming benthic microalgae are not disrupted significantly by grazing pressures, allowing for the layered mineralisation process to perpetuate. Additionally, grazers likely have a restrictive influence on pool macroalgae, maintaining the competitive balance between micro- and macroalgal groups.
DNA analysis of a 30,000-year-old Urocitellus glacialis from northeastern Siberia reveals phylogenetic relationships between ancient and present-day arctic ground squirrels
Authors: Faerman Marina , Bar-Gal Gila Kahila , Boaretto Elisabetta , Boeskorov Gennady G. , Dokuchaev Nikolai E. , Ermakov Oleg A. , Golenishchev Fedor N. , Gubin Stanislav V. , Mintz Eugenia , Simonov Evgeniy , Surin Vadim L. , Titov Sergei V. , Zanina Oksana G. , Formozov Nikolai A.
Published: February 2017

In contrast to the abundant fossil record of arctic ground squirrels, Urocitellus parryii, from eastern Beringia, only a limited number of fossils is known from its western part. In 1946, unnamed GULAG prisoners discovered a nest with three mummified carcasses of arctic ground squirrels in the permafrost sediments of the El’ga river, Yakutia, Russia, that were later attributed to a new species, Citellus (Urocitellus) glacialis Vinogr. To verify this assignment and to explore phylogenetic relationships between ancient and present-day arctic ground squirrels, we performed 14C dating and ancient DNA analyses of one of the El’ga mummies and four contemporaneous fossils from Duvanny Yar, northeastern Yakutia. Phylogenetic reconstructions, based on complete cytochrome b gene sequences of five Late Pleistocene arctic ground squirrels and those of modern U. parryii from 21 locations across western Beringia, provided no support for earlier proposals that ancient arctic ground squirrels from Siberia constitute a distinct species. In fact, we observed genetic continuity of the glacialis mitochondrial DNA lineage in modern U. parryii of the Kamchatka peninsula. When viewed in a broader geographic perspective, our findings provide new insights into the genetic history of U. parryii in Late Pleistocene Beringia.
Genome-wide DNA-(de)methylation is associated with Noninfectious Bud-failure exhibition in Almond (Prunus dulcis [Mill.] D.A.Webb)
Authors: Fresnedo-Ramírez Jonathan , Chan Helen M. , Parfitt Dan E. , Crisosto Carlos H. , Gradziel Thomas M.
Published: February 2017

Noninfectious bud-failure (BF) remains a major threat to almond production in California, particularly with the recent rapid expansion of acreage and as more intensive cultural practices and modern cultivars are adopted. BF has been shown to be inherited in both vegetative and sexual progeny, with exhibition related to the age and propagation history of scion clonal sources. These characteristics suggest an epigenetic influence, such as the loss of juvenility mediated by DNA-(de)methylation. Various degrees of BF have been reported among cultivars as well as within sources of clonal propagation of the same cultivar. Genome-wide methylation profiles for different clones within almond genotypes were developed to examine their association with BF levels and association with the chronological time from initial propagation. The degree of BF exhibition was found to be associated with DNA-(de)methylation and clonal age, which suggests that epigenetic changes associated with ageing may be involved in the differential exhibition of BF within and among almond clones. Research is needed to investigate the potential of DNA-(de)methylation status as a predictor for BF as well as for effective strategies to improve clonal selection against age related deterioration. This is the first report of an epigenetic-related disorder threatening a major tree crop.
Identification of a substrate domain that determines system specificity in mycobacterial type VII secretion systems
Authors: Phan Trang H. , Ummels Roy , Bitter Wilbert , Houben Edith N. G.
Published: February 2017

Type VII secretion (T7S) systems are specialized machineries used by mycobacterial pathogens to transport important virulence factors across their highly hydrophobic cell envelope. There are up to five mycobacterial T7S systems, named ESX-1 to ESX-5, at least three of which specifically secrete a different subset of substrates. The T7S substrates or substrate complexes are defined by the general secretion motif YxxxD/E. However this motif does not determine system specificity. Here, we show that the substrate domain recognized by the EspG chaperone is the determinant factor for this specificity. We first show that the introduction of point mutations into the EspG1-binding domain of the ESX-1 substrate pair PE35/PPE68_1 affects their secretion. Subsequently, we demonstrate that replacing this domain by the EspG5-binding domain of the ESX-5 substrate PPE18 resulted in EspG5 dependence and exclusive rerouting to the ESX-5 system. This rerouting of PE35/PPE68_1 to the ESX-5 system had a negative effect on the secretion of endogenous ESX-5 substrates.
Complement component 5 promotes lethal thrombosis
Authors: Mizuno Tomohiro , Yoshioka Kengo , Mizuno Masashi , Shimizu Mie , Nagano Fumihiko , Okuda Tomoyuki , Tsuboi Naotake , Maruyama Shoichi , Nagamatsu Tadashi , Imai Masaki
Published: February 2017

Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45–75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis.
Mitochondrial behaviour throughout the lytic cycle of Toxoplasma gondii
Authors: Ovciarikova Jana , Lemgruber Leandro , Stilger Krista L. , Sullivan William J. , Sheiner Lilach
Published: February 2017

Mitochondria distribution in cells controls cellular physiology in health and disease. Here we describe the mitochondrial morphology and positioning found in the different stages of the lytic cycle of the eukaryotic single-cell parasite Toxoplasma gondii. The lytic cycle, driven by the tachyzoite life stage, is responsible for acute toxoplasmosis. It is known that whilst inside a host cell the tachyzoite maintains its single mitochondrion at its periphery. We found that upon parasite transition from the host cell to the extracellular matrix, mitochondrion morphology radically changes, resulting in a reduction in peripheral proximity. This change is reversible upon return to the host, indicating that an active mechanism maintains the peripheral positioning found in the intracellular stages. Comparison between the two states by electron microscopy identified regions of coupling between the mitochondrion outer membrane and the parasite pellicle, whose features suggest the presence of membrane contact sites, and whose abundance changes during the transition between intra- and extra-cellular states. These novel observations pave the way for future research to identify molecular mechanisms involved in mitochondrial distribution in Toxoplasma and the consequences of these mitochondrion changes on parasite physiology.
From Initial Nucleation to Cassie-Baxter State of Condensed Droplets on Nanotextured Superhydrophobic Surfaces
Authors: Lv Cunjing , Zhang Xiwen , Niu Fenglei , He Feng , Hao Pengfei
Published: February 2017

Understanding how droplet condensation happens plays an essential role for our fundamental insights of wetting behaviors in nature and numerous applications. Since there is a lack of study of the initial formation and growing processes of condensed droplets down to nano-/submicroscale, relevant underlying mechanisms remain to be explored. We report an in situ observation of vapor condensation on nano-/microtextured superhydrophobic surfaces using optical microscopy. An interesting picture of the vapor condensation, from the initial appearance of individual small droplets (≤1 μm) to a Cassie-Baxter wetting state (>30 μm), are exhibited. It is found that individual droplets preferentially nucleate at the top and the edge of single micropillars with very high apparent contact angles on the nanotextures. Scenarios of two distinguished growing modes are reported statistically and the underlying mechanisms are discussed in the view of thermodynamics. We particularly reveal that the formation of the Cassie-Baxter wetting state is a result of a continuous coalescence of individual small droplets, in which the nanotexture-enhanced superhydrophobicity plays a crucial role. We envision that these fundamental findings can deepen our understanding of the nucleation and development of condensed droplets in nanoscale, so as to optimize design strategies of superhydrophobic materials for a broad range of water-harvesting and heat-transfer systems.
Removal of silver nanoparticles by mussel-inspired Fe3O4@ polydopamine core-shell microspheres and its use as efficient catalyst for methylene blue reduction
Authors: Wu Maoling , Li Yinying , Yue Rui , Zhang Xiaodan , Huang Yuming
Published: February 2017

The removal of silver nanoparticles (AgNPs) from water is highly needed because of their increasing use and potential risk to the environment due to their toxic effects. Catalysis over AgNPs has received significant attention because of their highly catalytic performance. However, their use in practical applications is limited due to high cost and limited resources. Here, we present for the first time that the mussel-inspired Fe3O4@polydopamine (Fe3O4@PDA) nanocomposite can be used for efficient removal and recovery of AgNPs. Adsorption of AgNPs over Fe3O4@PDA was confirmed by TEM, FT-IR, XRD, TGA and magnetic property. The adsorption efficiency of AgNPs by Fe3O4@PDA was investigated as a function of pH, contact time, ionic strength and concentration of AgNPs. The kinetic data were well fitted to a pseudo-second order kinetic model. The isotherm data were well described by Langmuir model with a maximum adsorption capacity of 169.5 mg/g, which was higher than those by other adsorbents. Notably, the obtained AgNPs-Fe3O4@PDA exhibited highly catalytic activity for methylene blue reduction by NaBH4 with a rate constant of 1.44 × 10−3/s, which was much higher than those by other AgNPs catalysts. The AgNPs-Fe3O4@PDA promised good recyclability for at least 8 cycles and acid resistant with good stability.
Calpain-1 deletion impairs mGluR-dependent LTD and fear memory extinction
Authors: Zhu Guoqi , Briz Victor , Seinfeld Jeff , Liu Yan , Bi Xiaoning , Baudry Michel
Published: February 2017

Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α. This signaling pathway was required for both the early and late phase of Arc translation during mGluR-LTD, through a mechanism involving mTOR and ribosomal protein S6 activation. In contrast, in hippocampal slices from calpain-1 knock-out (KO) mice, application of the mGluR agonist, DHPG, did not result in B56α truncation, increased Arc synthesis and reduced levels of membrane GluA1-containing AMPA receptors. Consistently, mGluR-LTD was impaired in calpain-1 KO mice, and the impairment could be rescued by phosphatase inhibitors, which also restored Arc translation in response to DHPG. Furthermore, calpain-1 KO mice exhibited impairment in fear memory extinction to tone presentation. These results indicate that calpain-1 plays a critical role in mGluR-LTD and is involved in many forms of synaptic plasticity and learning and memory.
BAR502, a dual FXR and GPBAR1 agonist, promotes browning of white adipose tissue and reverses liver steatosis and fibrosis
Authors: Carino Adriana , Cipriani Sabrina , Marchianò Silvia , Biagioli Michele , Santorelli Chiara , Donini Annibale , Zampella Angela , Monti Maria Chiara , Fiorucci Stefano
Published: February 2017

Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease. Here, we have investigated whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs. Treatment with BAR502 caused a ≈10% reduction of b.w., increased insulin sensitivity and circulating levels of HDL, while reduced steatosis, inflammatory and fibrosis scores and liver expression of SREPB1c, FAS, PPARγ, CD36 and CYP7A1 mRNA. BAR502 increased the expression of SHP and ABCG5 in the liver and SHP, FGF15 and GLP1 in intestine. BAR502 promoted the browning of epWAT and reduced liver fibrosis induced by CCl4. In summary, BAR502, a dual FXR and GPBAR1 agonist, protects against liver damage caused by HFD by promoting the browning of adipose tissue.
Deciphering the distance to antibiotic resistance for the pneumococcus using genome sequencing data
Authors: Mobegi Fredrick M. , Cremers Amelieke J. H. , de Jonge Marien I. , Bentley Stephen D. , van Hijum Sacha A. F. T. , Zomer Aldert
Published: February 2017

Advances in genome sequencing technologies and genome-wide association studies (GWAS) have provided unprecedented insights into the molecular basis of microbial phenotypes and enabled the identification of the underlying genetic variants in real populations. However, utilization of genome sequencing in clinical phenotyping of bacteria is challenging due to the lack of reliable and accurate approaches. Here, we report a method for predicting microbial resistance patterns using genome sequencing data. We analyzed whole genome sequences of 1,680 Streptococcus pneumoniae isolates from four independent populations using GWAS and identified probable hotspots of genetic variation which correlate with phenotypes of resistance to essential classes of antibiotics. With the premise that accumulation of putative resistance-conferring SNPs, potentially in combination with specific resistance genes, precedes full resistance, we retrogressively surveyed the hotspot loci and quantified the number of SNPs and/or genes, which if accumulated would confer full resistance to an otherwise susceptible strain. We name this approach the ‘distance to resistance’. It can be used to identify the creep towards complete antibiotics resistance in bacteria using genome sequencing. This approach serves as a basis for the development of future sequencing-based methods for predicting resistance profiles of bacterial strains in hospital microbiology and public health settings.
Exposure to tobacco smoke and childhood rhinitis: a population-based study
Authors: Yao Tsung-Chieh , Chang Su-Wei , Chang Wei-Chiao , Tsai Ming-Han , Liao Sui-Ling , Hua Man-Chin , Lai Shen-Hao , Yeh Kuo-Wei , Tseng Yu-Lun , Lin Wan-Chen , Tsai Hui-Ju , Huang Jing-Long
Published: February 2017

Exposure to tobacco smoke has been associated with harmful effects on child health. The association between tobacco smoke exposure and childhood rhinitis has not been established in developed or developing countries. We investigated the association between serum cotinine levels and rhinitis in a population sample of 1,315 Asian children. Serum cotinine levels were positively associated with rhinitis ever (adjusted odds ratio [AOR] = 2.95; 95% confidence interval [CI]: 1.15–7.60) and current rhinitis (AOR = 2.71; 95% CI: 1.07–6.89), while the association for physician-diagnosed rhinitis approaching borderline significance (AOR = 2.26; 95% CI: 0.88–5.83). Stratified analyses demonstrated significant association of serum cotinine levels with current rhinitis among children without allergic sensitization (AOR = 6.76; 95% CI: 1.21–37.74), but not among those with allergic sensitization. Serum cotinine levels were positively associated with rhinitis ever (AOR = 3.34; 95% CI: 1.05–10.61) and current rhinitis (AOR = 4.23; 95% CI: 1.28–13.97) among adolescents but not in children aged less than 10 years. This population-based study demonstrates supportive evidence for positive association of tobacco smoke exposure with rhinitis, while the effect is mainly confined to non-allergic rhinitis and more pronounced in adolescents than in young children, highlighting the need for raising public health awareness about the detrimental effects of tobacco smoke exposure on children’s respiratory health.
Evaporation of inclined water droplets
Authors: Kim Jin Young , Hwang In Gyu , Weon Byung Mook
Published: February 2017

When a drop is placed on a flat substrate tilted at an inclined angle, it can be deformed by gravity and its initial contact angle divides into front and rear contact angles by inclination. Here we study on evaporation dynamics of a pure water droplet on a flat solid substrate by controlling substrate inclination and measuring mass and volume changes of an evaporating droplet with time. We find that complete evaporation time of an inclined droplet becomes longer as gravitational influence by inclination becomes stronger. The gravity itself does not change the evaporation dynamics directly, whereas the gravity-induced droplet deformation increases the difference between front and rear angles, which quickens the onset of depinning and consequently reduces the contact radius. This result makes the evaporation rate of an inclined droplet to be slow. This finding would be important to improve understanding on evaporation dynamics of inclined droplets.
Cryogel-supported stem cell factory for customized sustained release of bispecific antibodies for cancer immunotherapy
Authors: Aliperta Roberta , Welzel Petra B. , Bergmann Ralf , Freudenberg Uwe , Berndt Nicole , Feldmann Anja , Arndt Claudia , Koristka Stefanie , Stanzione Marcello , Cartellieri Marc , Ehninger Armin , Ehninger Gerhard , Werner Carsten , Pietzsch Jens , Steinbach Jörg , Bornhäuser Martin , Bachmann Michael P.
Published: February 2017

Combining stem cells with biomaterial scaffolds provides a promising strategy for the development of drug delivery systems. Here we propose an innovative immunotherapeutic organoid by housing human mesenchymal stromal cells (MSCs), gene-modified for the secretion of an anti-CD33-anti-CD3 bispecific antibody (bsAb), in a small biocompatible star-shaped poly(ethylene glycol)-heparin cryogel scaffold as a transplantable and low invasive therapeutic machinery for the treatment of acute myeloid leukemia (AML). The macroporous biohybrid cryogel platform displays effectiveness in supporting proliferation and survival of bsAb-releasing-MSCs overtime in vitro and in vivo, avoiding cell loss and ensuring a constant release of sustained and detectable levels of bsAb capable of triggering T-cell-mediated anti-tumor responses and a rapid regression of CD33+ AML blasts. This therapeutic device results as a promising and safe alternative to the continuous administration of short-lived immunoagents and paves the way for effective bsAb-based therapeutic strategies for future tumor treatments.
β-globin gene cluster haplotypes in ethnic minority populations of southwest China
Authors: Sun Hao , Liu Hongxian , Huang Kai , Lin Keqin , Huang Xiaoqin , Chu Jiayou , Ma Shaohui , Yang Zhaoqing
Published: February 2017

The genetic diversity and relationships among ethnic minority populations of southwest China were investigated using seven polymorphic restriction enzyme sites in the β-globin gene cluster. The haplotypes of 1392 chromosomes from ten ethnic populations living in southwest China were determined. Linkage equilibrium and recombination hotspot were found between the 5′ sites and 3′ sites of the β-globin gene cluster. 5′ haplotypes 2 (+−−−), 6 (−++−+), 9 (−++++) and 3′ haplotype FW3 (−+) were the predominant haplotypes. Notably, haplotype 9 frequency was significantly high in the southwest populations, indicating their difference with other Chinese. The interpopulation differentiation of southwest Chinese minority populations is less than those in populations of northern China and other continents. Phylogenetic analysis shows that populations sharing same ethnic origin or language clustered to each other, indicating current β-globin cluster diversity in the Chinese populations reflects their ethnic origin and linguistic affiliations to a great extent. This study characterizes β-globin gene cluster haplotypes in southwest Chinese minorities for the first time, and reveals the genetic variability and affinity of these populations using β-globin cluster haplotype frequencies. The results suggest that ethnic origin plays an important role in shaping variations of the β-globin gene cluster in the southwestern ethnic populations of China.
Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease
Authors: Faccini Julien , Ruidavets Jean-Bernard , Cordelier Pierre , Martins Frédéric , Maoret Jean-José , Bongard Vanina , Ferrières Jean , Roncalli Jérôme , Elbaz Meyer , Vindis Cécile
Published: February 2017

Coronary artery disease (CAD) is the most prevalent cause of mortality and morbidity worldwide and the number of individuals at risk is increasing. To better manage cardiovascular diseases, improved tools for risk prediction including the identification of novel accurate biomarkers are needed. MicroRNA (miRNA) are essential post-transcriptional modulators of gene expression leading to mRNA suppression or translational repression. Specific expression profiles of circulating miRNA have emerged as potential noninvasive diagnostic biomarkers of diseases. The aim of this study was to identify the potential diagnostic value of circulating miRNA with CAD. Circulating miR-145, miR-155, miR-92a and let-7c were selected and validated by quantitative PCR in 69 patients with CAD and 30 control subjects from the cross-sectional study GENES. The expression of miR-145, miR-155 and let-7c showed significantly reduced expression in patients with CAD compared to controls. Multivariate logistic regression analysis revealed that low levels of circulating let-7c, miR-145 and miR-155 were associated with CAD. Receiver operating curves analysis showed that let-7c, miR-145 or miR-155 were powerful markers for detecting CAD. Furthermore, we demonstrated that the combination of the three circulating miRNA managed to deliver a specific signature for diagnosing CAD.
Activation performance and mechanism of a novel heterogeneous persulfate catalyst: metal–organic framework MIL-53(Fe) with FeII/FeIII mixed-valence coordinatively unsaturated iron center
Authors: Pu Mengjie , Ma Yongwen , Wan Jinquan , Wang Yan , Wang Jiumei , Brusseau Mark L.
Published: February 2017

In this work, a novel and effective heterogeneous catalyst, the metal–organic framework MIL-53(Fe), has been synthesized for the purpose of activating persulfate (PS).
Influence of the organic linker substituent on the catalytic activity of MIL-101(Cr) for the oxidative coupling of benzylamines to imines
Authors: Santiago-Portillo Andrea , Blandez Juan F. , Navalón Sergio , Álvaro Mercedes , García Hermenegildo
Published: February 2017

MIL-101(Cr) having substituents at the terephthalate linker (X = H, NO2, SO3H, Cl, CH3 and NH2) promotes the aerobic oxidation of benzylamines to the corresponding N-benzylidene benzylamines at different rates.
Borocation catalysis
Authors: Eisenberger P. , Crudden C. M.
Published: February 2017

The synthesis, stability and catalytic reactivity of borocations are described in the context of their reaction in frustrated Lewis pair-type processes.
Interactions of TiO2nanoparticles and the freshwater nematode Plectus aquatilis: particle properties, kinetic parameters and bioconcentration factors
Authors: Isaacson C. W. , Sigg L. , Ammann A. A. , Stadnicka-Michalak J. , Schirmer K.
Published: February 2017

Principles for determining uptake kinetics and bioconcentration factors for nanoparticles and test organisms are explored.
Real-time dark-field light scattering imaging to monitor the coupling reaction with gold nanorods as an optical probe
Authors: Zhang Hong Zhi , Li Rong Sheng , Gao Peng Fei , Wang Ni , Lei Gang , Huang Cheng Zhi , Wang Jian
Published: February 2017

The coupling reaction between Au, ferric chloride and thiourea was monitored with gold nanorods using dark-field light scattering microscopy.
Phytic acid-derivative transition metal phosphides encapsulated in N,P-codoped carbon: an efficient and durable hydrogen evolution electrocatalyst in a wide pH range
Authors: Pu Zonghua , Amiinu Ibrahim Saana , Zhang Chengtian , Wang Min , Kou Zongkui , Mu Shichun
Published: February 2017

TMPs wrapped in NPC show excellent catalytic activities and stabilities towards hydrogen evolution reaction in a wide pH range.
A nanoplasmonic label-free surface-enhanced Raman scattering strategy for non-invasive cancer genetic subtyping in patient samples
Authors: Wang Jing , Koo Kevin M. , Wee Eugene J. H. , Wang Yuling , Trau Matt
Published: February 2017

Our method enables label-free SERS detection of multiple low-abundance RNA biomarkers in patient urinary samples.
Recyclable palladium–graphene nanocomposite catalysts containing ionic polymers: efficient Suzuki coupling reactions
Authors: Kwon Tae Hui , Cho Kie Yong , Baek Kyung-Youl , Yoon Ho Gyu , Kim B. Moon
Published: February 2017

Palladium nanoparticles on ionic polymer-doped graphene (Pd–IPG) nanocomposite catalysts exhibited efficient catalytic performance in Suzuki coupling reactions.
Strong enhancement of spin–orbit splitting induced by σ–π coupling in Pb-decorated silicene
Authors: Li Tongwei , Su Xiangying , Li Haisheng , Ju Weiwei
Published: February 2017

Electronic properties and spin–orbit (SO) splitting of silicene adsorbed with Cu, Ag, Au and Pb atoms at different coverages are investigated by means of first-principles calculations.
A cyclodextrin-core star copolymer with Y-shaped ABC miktoarms and its unimolecular micelles
Authors: Wang Yan , Liu Yuyang , Liang Jianghu , Zou Minhao
Published: February 2017

A β-cyclodextrin-core star copolymer with Y-shaped ABC miktoarms was designed which exhibits unimolecular micelles in aqueous solution. It is a good platform for unimolecular container encapsulating hydrophobic molecules with release of the payload exhibiting pH-sensitivity.
68Ga-Chelation and comparative evaluation of N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) conjugated NGR and RGD peptides as tumor targeted molecular imaging probes
Authors: Satpati Drishty , Sharma Rohit , Kumar Chandan , Sarma Haladhar Dev , Dash Ashutosh
Published: February 2017

Radiosynthesis and bioevaluation of HBED-CC conjugated RGD and NGR peptides,68Ga-HBED-CC-c(NGR) and68Ga-HBED-CC-c(RGD) is described.
Hydrophilicities of amylose and natural cellulose are regulated by the linkage between sugar rings
Authors: Bao Yu , Xu Duo , Qian Lu , Zhao Li , Lu Zhong-yuan , Cui Shuxun
Published: February 2017

Amylose is more hydrophilic than natural cellulose, even though their molecular structures are very similar.
Sn–Co nanoalloys embedded in porous N-doped carbon microboxes as a stable anode material for lithium-ion batteries
Authors: Shi Xiao , Song Huaihe , Li Ang , Chen Xiaohong , Zhou Jisheng , Ma Zhaokun
Published: February 2017

A tin source was introduced into ZIF-67, and after carbonization Sn–Co nanoalloys were in situ formed in N-doped carbon.
Structural interface between LRRK2 and 14-3-3 protein
Authors: Stevers Loes M. , de Vries Rens M.J.M. , Doveston Richard G. , Milroy Lech-Gustav , Brunsveld Luc , Ottmann Christian
Published: February 2017

Binding of 14-3-3 proteins to leucine-rich repeat protein kinase 2 (LRRK2) is known to be impaired by many Parkinson's disease (PD)-relevant mutations. Abrogation of this interaction is connected to enhanced LRRK2 kinase activity, which in turn is implicated in increased ubiquitination of LRRK2, accumulation of LRRK2 into inclusion bodies and reduction in neurite length. Hence, the interaction between 14-3-3 and LRRK2 is of significant interest as a possible drug target for the treatment of PD. However, LRRK2 possesses multiple sites that, upon phosphorylation, can bind to 14-3-3, thus rendering the interaction relatively complex. Using biochemical assays and crystal structures, we characterize the multivalent interaction between these two proteins.
Simvastatin pre-treatment improves survival and mitochondrial function in a 3-day fluid-resuscitated rat model of sepsis
Authors: Morel Jerome , Hargreaves Iain , Brealey David , Neergheen Viruna , Backman Janne T. , Lindig Sandro , Bläss Marcus , Bauer Michael , McAuley Daniel F. , Singer Mervyn
Published: February 2017

Statins may offer protective effects in sepsis through anti-inflammatory, mitochondrial protection and other actions. We thus evaluated the effects of simvastatin on survival, organ and mitochondrial function, tissue and plasma ubiquinone levels and liver transcriptomics in a 3-day rat model of sepsis. Comparisons of rat plasma simvastatin and ubiquinone levels were made against levels sampled in blood from patients with acute lung injury (ALI) enrolled into a trial of statin therapy. Animals received simvastatin by gavage either pre- or post-induction of faecal peritonitis. Control septic animals received vehicle alone. Seventy-two-hour survival was significantly greater in statin pre-treated animals (43.7%) compared with their statin post-treated (12.5%) and control septic (25%) counterparts (P<0.05). Sepsis-induced biochemical derangements in liver and kidney improved with statin therapy, particularly when given pre-insult. Both simvastatin pre- and post-treatment prevented the fall in mitochondrial oxygen consumption in muscle fibres taken from septic animals at 24 h. This beneficial effect was paralleled by recovery of genes related to fatty acid metabolism. Simvastatin pre-treatment resulted in a significant decrease in myocardial ubiquinone. Patients with ALI had a marked variation in plasma simvastatin acid levels; however, their ubiquinone/low-density lipoprotein (LDL) cholesterol ratio did not differ regardless of whether they were receiving statin or placebo. In summary, despite protective effects seen with statin treatment given both pre- and post-insult, survival benefit was only seen with pre-treatment, reflecting experiences in patient studies.
Preoperative Embolization for Skull Base Meningiomas
Authors: Nagaishi Masaya , Matsumoto Yoshiyuki , Fujii Yoshiko , Inoue Yuki , Sugiura Yoshiki , Hirata Koji , Suzuki Ryotaro , Kawamura Yosuke , Nakae Ryuta , Tanaka Yoshihiro , Hyodo Akio , Suzuki Kensuke
Published: February 2017

The results of preoperative embolization for skull base meningiomas were retrospectively evaluated to confirm the efficacy of this procedure. Skull base meningiomas that were treated with preoperative embolization were evaluated in 20 patients. The occluded arteries, embolic materials, treatment time, excision rate, neurologic manifestations, and complications were analyzed. The embolic material was 80% liquid, 30% coils, and 15% particles. The surgery was normally completed within 3 to 5 hours. Blood loss was normally approximately 250 mL, excluding four patients having the following conditions: malignant meningioma, a large tumor located on the medial side of the sphenoidal ridge, the petroclival tumor, and infiltrated tumor into the sigmoid sinus. The mean excision rate was 90%, achieving a Simpson grade III, but 10% were graded as Simpson grade IV. No permanent complications due to the preoperative embolization occurred. No neurologic symptoms occurred after excision. Current cerebral endovascular treatment is sophisticated, and the complication rate has markedly decreased. Although it was impossible to compare directly with or without operative embolization, preoperative embolization should be actively used as part of the treatment for this benign tumor, with better understanding of dangerous anastomosis.