bluuebunny/crossref_metadata_2025 huggingface dataset:
Health benefits of late-onset metformin treatment every other week in mice
Authors: Alfaras Irene , Mitchell Sarah J. , Mora Hector , Lugo Darisbeth Rosario , Warren Alessandra , Navas-Enamorado Ignacio , Hoffmann Vickie , Hine Christopher , Mitchell James R. , Le Couteur David G. , Cogger Victoria C. , Bernier Michel , de Cabo Rafael
Published: November 2017

Chronic 1% metformin treatment is nephrotoxic in mice, but this dose may nonetheless confer health benefits if given intermittently rather than continuously. Here, we examined the effects of 1% metformin given every-other week (EOW) or two consecutive weeks per month (2WM) on survival of 2-year-old male mice fed standard chow. EOW and 2WM mice had comparable life span compared with control mice. A significant reduction in body weight within the first few weeks of metformin treatment was observed without impact on food consumption and energy expenditure. Moreover, there were differences in the action of metformin on metabolic markers between the EOW and 2WM groups, with EOW metformin conferring greater benefits. Age-associated kidney lesions became more pronounced with metformin, although without pathological consequences. In the liver, metformin treatment led to an overall reduction in steatosis and was accompanied by distinct transcriptomic and metabolomic signatures in response to EOW versus 2WM regimens. Thus, the absence of adverse outcomes associated with chronic, intermittent use of 1% metformin in old mice has clinical translatability into the biology of aging in humans.
Krüpple-like-factor 4 Attenuates Lung Fibrosis via Inhibiting Epithelial-mesenchymal Transition
Authors: Lin Lianjun , Han Qian , Xiong Yan , Li Ting , Liu Zhonghui , Xu Huiying , Wu Yanping , Wang Nanping , Liu Xinmin
Published: November 2017

Epithelial-mesenchymal transition (EMT) plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Krüpple-like-factor 4 (KLF4), has been suggested to play an important role in the phenotype transition. However, its function in pulmonary fibrosis and EMT of human alveolar epithelial cells (AECs) remains unclear. This study aimed to examine the role of KLF4 in pulmonary fibrosis and EMT. Decreased expression of KLF4 was first observed in human IPF lung tissues and models of bleomycin-induced pulmonary fibrosis. Transgenic mice with overexpression of KLF4 were subjected to bleomycin-induced pulmonary fibrosis model and showed attenuated lung fibrosis and EMT compared to wild type group. Furthermore, the effects overexpression and knockdown of KLF4 on TGF-β1-induced EMT were examined in AECs. Adenovirus-mediated overexpression of KLF4 attenuated TGF-β1-induced EMT and activation of Smad2/3 and Dvl in AECs. Conversely, knockdown of KLF4 promoted the activation of pathways above mentioned and TGF-β1-induced EMT. Our results demonstrates that KLF4 plays an important role in bleomycin-induced lung fibrosis through suppressing TGFβ1-induced EMT. Thus, it may serve as a potential target for the treatment of pulmonary fibrosis.
miRDDCR: a miRNA-based method to comprehensively infer drug-disease causal relationships
Authors: Chen Hailin , Zhang Zuping , Peng Wei
Published: November 2017

Revealing the cause-and-effect mechanism behind drug-disease relationships remains a challenging task. Recent studies suggested that drugs can target microRNAs (miRNAs) and alter their expression levels. In the meanwhile, the inappropriate expression of miRNAs will lead to various diseases. Therefore, targeting specific miRNAs by small-molecule drugs to modulate their activities provides a promising approach to human disease treatment. However, few studies attempt to discover drug-disease causal relationships through the molecular level of miRNAs. Here, we developed a miRNA-based inference method miRDDCR to comprehensively predict drug-disease causal relationships. We first constructed a three-layer drug-miRNA-disease heterogeneous network by combining similarity measurements, existing drug-miRNA associations and miRNA-disease associations. Then, we extended the algorithm of Random Walk to the three-layer heterogeneous network and ranked the potential indications for drugs. Leave-one-out cross-validations and case studies demonstrated that our method miRDDCR can achieve excellent prediction power. Compared with related methods, our causality discovery-based algorithm showed superior prediction ability and highlighted the molecular basis miRNAs, which can be used to assist in the experimental design for drug development and disease treatment. Finally, comprehensively inferred drug-disease causal relationships were released for further studies.
Pulse frequency dependency of photobiomodulation on the bioenergetic functions of human dental pulp stem cells
Authors: Kim Hong Bae , Baik Ku Youn , Choung Pill-Hoon , Chung Jong Hoon
Published: November 2017

Photobiomodulation (PBM) therapy contributes to pain relief, wound healing, and tissue regeneration. The pulsed wave (PW) mode has been reported to be more effective than the continuous wave (CW) mode when applying PBM to many biological systems. However, the reason for the higher effectiveness of PW-PBM is poorly understood. Herein, we suggest using delayed luminescence (DL) as a reporter of mitochondrial activity after PBM treatment. DL originates mainly from mitochondrial electron transport chain systems, which produce reactive oxygen species (ROS) and adenosine triphosphate (ATP). The decay time of DL depends on the pulse frequencies of applied light, which correlate with the biological responses of human dental pulp stem cells (hDPSCs). Using a low-power light whose wavelength is 810 nm and energy density is 38 mJ/cm2, we find that a 300-Hz pulse frequency prolonged the DL pattern and enhanced alkaline phosphatase activity. In addition, we analyze mitochondrial morphological changes and their volume density and find evidence supporting mitochondrial physiological changes from PBM treatment. Our data suggest a new methodology for determining the effectiveness of PBM and the specific pulse frequency dependency of PBM in the differentiation of hDPSCs.
Allometric scaling of skin thickness, elasticity, viscoelasticity to mass for micro-medical device translation: from mice, rats, rabbits, pigs to humans
Authors: Wei Jonathan C. J. , Edwards Grant A. , Martin Darren J. , Huang Han , Crichton Michael L. , Kendall Mark A. F.
Published: November 2017

Emerging micro-scale medical devices are showing promise, whether in delivering drugs or extracting diagnostic biomarkers from skin. In progressing these devices through animal models towards clinical products, understanding the mechanical properties and skin tissue structure with which they interact will be important. Here, through measurement and analytical modelling, we advanced knowledge of these properties for commonly used laboratory animals and humans (~30 g to ~150 kg). We hypothesised that skin’s stiffness is a function of the thickness of its layers through allometric scaling, which could be estimated from knowing a species’ body mass. Results suggest that skin layer thicknesses are proportional to body mass with similar composition ratios, inter- and intra-species. Experimental trends showed elastic moduli increased with body mass, except for human skin. To interpret the relationship between species, we developed a simple analytical model for the bulk elastic moduli of skin, which correlated well with experimental data. Our model suggest that layer thicknesses may be a key driver of structural stiffness, as the skin layer constituents are physically and therefore mechanically similar between species. Our findings help advance the knowledge of mammalian skin mechanical properties, providing a route towards streamlined micro-device research and development onto clinical use.
An Evolutionary Game Theory Model of Spontaneous Brain Functioning
Authors: Madeo Dario , Talarico Agostino , Pascual-Leone Alvaro , Mocenni Chiara , Santarnecchi Emiliano
Published: November 2017

Our brain is a complex system of interconnected regions spontaneously organized into distinct networks. The integration of information between and within these networks is a continuous process that can be observed even when the brain is at rest, i.e. not engaged in any particular task. Moreover, such spontaneous dynamics show predictive value over individual cognitive profile and constitute a potential marker in neurological and psychiatric conditions, making its understanding of fundamental importance in modern neuroscience. Here we present a theoretical and mathematical model based on an extension of evolutionary game theory on networks (EGN), able to capture brain's interregional dynamics by balancing emulative and non-emulative attitudes among brain regions. This results in the net behavior of nodes composing resting-state networks identified using functional magnetic resonance imaging (fMRI), determining their moment-to-moment level of activation and inhibition as expressed by positive and negative shifts in BOLD fMRI signal. By spontaneously generating low-frequency oscillatory behaviors, the EGN model is able to mimic functional connectivity dynamics, approximate fMRI time series on the basis of initial subset of available data, as well as simulate the impact of network lesions and provide evidence of compensation mechanisms across networks. Results suggest evolutionary game theory on networks as a new potential framework for the understanding of human brain network dynamics.
The corepressor NCOR1 regulates the survival of single-positive thymocytes
Authors: Müller Lena , Hainberger Daniela , Stolz Valentina , Hamminger Patricia , Hassan Hammad , Preglej Teresa , Boucheron Nicole , Sakaguchi Shinya , Wiegers G. Jan , Villunger Andreas , Auwerx Johan , Ellmeier Wilfried
Published: November 2017

Nuclear receptor corepressor 1 (NCOR1) is a transcriptional regulator bridging repressive chromatin modifying enzymes with transcription factors. NCOR1 regulates many biological processes, however its role in T cells is not known. Here we show thatCd4-Cre-mediated deletion of NCOR1 (NCOR1 cKOCd4) resulted in a reduction of peripheral T cell numbers due to a decrease in single-positive (SP) thymocytes. In contrast, double-positive (DP) thymocyte numbers were not affected in the absence of NCOR1. The reduction in SP cells was due to diminished survival of NCOR1-null postselection TCRβhiCD69+and mature TCRβhiCD69−thymocytes. NCOR1-null thymocytes expressed elevated levels of the pro-apoptotic factor BIM and showed a higher fraction of cleaved caspase 3-positive cells upon TCR stimulationex vivo. However, staphylococcal enterotoxin B (SEB)-mediated deletion of Vβ8+CD4SP thymocytes was normal, suggesting that negative selection is not altered in the absence of NCOR1. Finally, transgenic expression of the pro-survival protein BCL2 restored the population of CD69+thymocytes in NCOR1 cKOCd4mice to a similar percentage as observed in WT mice. Together, these data identify NCOR1 as a crucial regulator of the survival of SP thymocytes and revealed that NCOR1 is essential for the proper generation of the peripheral T cell pool.
Three Dimensional Honeycomb Patterned Fibrinogen Based Nanofibers Induce Substantial Osteogenic Response of Mesenchymal Stem Cells
Authors: Nedjari Salima , Awaja Firas , Altankov George
Published: November 2017

Stem cells therapy offers a viable alternative for treatment of bone disorders to the conventional bone grafting. However clinical therapies are still hindered by the insufficient knowledge on the conditions that maximize stem cells differentiation. Hereby, we introduce a novel 3D honeycomb architecture scaffold that strongly support osteogenic differentiation of human adipose derived mesenchymal stem cells (ADMSCs). The scaffold is based on electrospun hybrid nanofibers consisting of poly (L-lactide ε-caprolactone) and fibrinogen (PLCL/FBG). Classical fibers orientations, random or aligned were also produced and studied for comparison. The overall morphology of ADMSC’s generally followed the nanofibers orientation and dimensionality developing regular focal adhesions and direction-dependent actin cytoskeleton bundles. However, there was an initial tendency for cells rounding on honeycomb scaffolds before ADMSCs formed a distinct bridging network. This specific cells organization appeared to have significant impact on the differentiation potential of ADMSCs towards osteogenic lineage, as indicated by the alkaline phosphatase production, calcium deposition and specific genes expression. Collectively, it was observed synergistic effect of nanofibers with honeycomb architecture on the behavior of ADMSCs entering osteogenic path of differentiation which outlines the potential benefits from insertion of such bioinspired geometrical cues within scaffolds for bone tissue engineering.
Protocadherin-αC2 is required for diffuse projections of serotonergic axons
Authors: Katori Shota , Noguchi-Katori Yukiko , Okayama Atsushi , Kawamura Yoshimi , Luo Wenshu , Sakimura Kenji , Hirabayashi Takahiro , Iwasato Takuji , Yagi Takeshi
Published: November 2017

Serotonergic axons extend diffuse projections throughout various brain areas, and serotonergic system disruption causes neuropsychiatric diseases. Loss of the cytoplasmic region of protocadherin-α (Pcdh-α) family proteins, products of the diverse clustered Pcdh genes, causes unbalanced distributions (densification and sparsification) of serotonergic axons in various target regions. However, which Pcdh-α member(s) are responsible for the phenotype is unknown. Here we demonstrated that Pcdh-αC2 (αC2), a Pcdh-α isoform, was highly expressed in serotonergic neurons, and was required for normal diffusion in single-axon-level analyses of serotonergic axons. The loss of αC2 from serotonergic neurons, but not from their target brain regions, led to unbalanced distributions of serotonergic axons. Our results suggest that αC2 expressed in serotonergic neurons is required for serotonergic axon diffusion in various brain areas. The αC2 extracellular domain displays homophilic binding activity, suggesting that its homophilic interaction between serotonergic axons regulates axonal density via αC2′s cytoplasmic domain.
MiR-30e inhibits tumor growth and chemoresistance via targeting IRS1 in Breast Cancer
Authors: Liu Min-min , Li Zhi , Han Xue-dong , Shi Jian-hua , Tu Dao-yuan , Song Wei , Zhang Jian , Qiu Xiao-lan , Ren Yi , Zhen Lin-lin
Published: November 2017

MicroRNA-30e (miR-30e) is downregulated in various tumor types. However, its mechanism in inhibiting tumor growth of breast cancer remains to be elucidated. In this study, we found that miR-30e was significantly downregulated in tumor tissues of breast cancer (BC) patients and cell lines, and overexpression of miR-30e inhibited cell proliferation, migration and invasion. To understand the potential mechanism of miR-30e in inhibiting tumor growth, we showed that miR-30e blocked the activation of AKT and ERK1/2 pathways, and the expression of HIF-1α and VEGF via directly targeting IRS1. Moreover, miR-30e regulates cell proliferation, migration, invasion and increases chemosensitivity of MDA-MB-231 cells to paclitaxel by inhibiting its target IRS1. MiR-30e also inhibited tumor growth and suppressed expression of IRS1, AKT, ERK1/2 and HIF-1α in mouse xenograft tumors. To test the clinical relevance of these results, we used 40 pairs of BC tissues and adjacent normal tissues, analyzed the levels of miR-30e and IRS1 expression in these tissues, and found that miR-30e levels were significantly inversely correlated with IRS1 levels in these BC tissues, suggesting the important implication of our findings in translational application for BC diagnostics and treatment in the future.
FSCN1 gene polymorphisms: biomarkers for the development and progression of breast cancer
Authors: Wang Chao-Qun , Tang Chih-Hsin , Wang Yan , Jin Lulu , Wang Qian , Li Xiaoni , Hu Gui-Nv , Huang Bi-Fei , Zhao Yong-Ming , Su Chen-Ming
Published: November 2017

Breast cancer is a major cause of cancer mortality worldwide. Fascin-1 (FSCN1) is an actin-binding protein found in mammalian cells, including endothelial, neuronal and mesenchymal cells. FSCN1 overexpression has been indicated in breast cancer patients. However, scant information is available regarding the association between FSCN1 single nucleotide polymorphisms (SNPs) and the risk or prognosis of breast cancer. We report on the association between 6 SNPs of the FSCN1 gene (rs56156320, rs8772, rs3801004, rs2966447, rs852479 and rs1640233) and breast cancer susceptibility as well as clinical outcomes in 316 patients with breast cancer and in 222 healthy controls. Carriers of the AC or AC + CC allele of the variant rs56156320 were at greater risk of breast cancer compared with wild-type (AA) carriers. Moreover, carriers of at least one G allele in rs3801004 were likely to progress to stage III/IV disease and lymph node metastasis. Individuals with at least one T allele at FSCN1 SNP rs2966447 were at higher risk of developing pathologic grade G3 disease. Furthermore, individuals bearing the C/C haplotype at SNPs rs56156320 and rs3801004 had nearly twice the risk of breast cancer. Our results indicate that genetic variations in the FSCN1 gene may serve as an important predictor of early-stage breast cancer.
Keratin-water-NMF interaction as a three layer model in the human stratum corneum using in vivo confocal Raman microscopy
Authors: Choe ChunSik , Schleusener Johannes , Lademann Jürgen , Darvin Maxim E.
Published: November 2017

The secondary and tertiary structure of keratin and natural moisturizing factor (NMF) are of great importance regarding the water regulating functions in the stratum corneum (SC). In this in vivo study, the depth-dependent keratin conformation and its relationship to the hydrogen bonding states of water and its content in the SC, are investigated using confocal Raman microscopy. Based on the obtained depth-profiles for the β-sheet/α-helix ratio, the stability of disulphide bonds, the amount of cysteine forming disulphide bonds, the buried/exposed tyrosine and the folding/unfolding states of keratin, a “three layer model” of the SC, regarding the keratin-water-NMF interaction is proposed. At the uppermost layers (30–0% SC depth), the keratin filaments are highly folded, entailing limited water binding sites, and NMF is mostly responsible for binding water. At the intermediate layers (70–30% SC depth), the keratin filaments are unfolded, have the most water binding sites and are prone to swelling. At the bottom layers (100–80% SC depth), the water binding sites are already occupied with water and cannot swell substantially. The hydrogen bonding states of water molecules can only be explained by considering both, the molecular structure of keratin and the contribution of NMF as a holistic system.
β-adrenergic stimulation augments transmural dispersion of repolarization via modulation of delayed rectifier currents IKs and IKr in the human ventricle
Authors: Kang C. , Badiceanu A. , Brennan J. A. , Gloschat C. , Qiao Y. , Trayanova N. A. , Efimov I. R.
Published: November 2017

Long QT syndrome (LQTS) is an inherited or drug induced condition associated with delayed repolarization and sudden cardiac death. The cardiac potassium channel, IKr, and the adrenergic-sensitive cardiac potassium current, IKs, are two primary contributors to cardiac repolarization. This study aimed to elucidate the role of β-adrenergic (β-AR) stimulation in mediating the contributions of IKr and IKs to repolarizing the human left ventricle (n = 18). Optical mapping was used to measure action potential durations (APDs) in the presence of the IKs blocker JNJ-303 and the IKr blocker E-4031. We found that JNJ-303 alone did not increase APD. However, under isoprenaline (ISO), both the application of JNJ-303 and additional E-4031 significantly increased APD. With JNJ-303, ISO decreased APD significantly more in the epicardium as compared to the endocardium, with subsequent application E-4031 increasing mid- and endocardial APD80 more significantly than in the epicardium. We found that β-AR stimulation significantly augmented the effect of IKs blocker JNJ-303, in contrast to the reduced effect of IKr blocker E-4031. We also observed synergistic augmentation of transmural repolarization gradient by the combination of ISO and E-4031. Our results suggest β-AR-mediated increase of transmural dispersion of repolarization, which could pose arrhythmogenic risk in LQTS patients.
Developmental evolution facilitates rapid adaptation
Authors: Lin Hui , Kazlauskas Romas J. , Travisano Michael
Published: November 2017

Developmental evolution has frequently been identified as a mode for rapid adaptation, but direct observations of the selective benefits and associated mechanisms of developmental evolution are necessarily challenging to obtain. Here we show rapid evolution of greatly increased rates of dispersal by developmental changes when populations experience stringent selection. Replicate populations of the filamentous fungus Trichoderma citrinoviride underwent 85 serial transfers, under conditions initially favoring growth but not dispersal. T. citrinoviride populations shifted away from multicellular growth toward increased dispersal by producing one thousand times more single-celled asexual conidial spores, three times sooner than the ancestral genotype. Conidia of selected lines also germinated fifty percent faster. Gene expression changed substantially between the ancestral and selected fungi, especially for spore production and growth, demonstrating rapid evolution of tight regulatory control for down-regulation of growth and up-regulation of conidia production between 18 and 24 hours of growth. These changes involved both developmentally fixed and plastic changes in gene expression, showing that complex developmental changes can serve as a mechanism for rapid adaptation.
Chemopreventive effects of Ku-jin tea against AOM-induced precancerous colorectal lesions in rats and metabolomic analysis
Authors: Bi Wu , Liu Haibo , Shen Jie , Zhang Ling-hua , Li Pei , Peng Bing , Cao Li , Zhang Pengfei , He Chunnian , Xiao Peigen
Published: November 2017

Ku-jin tea (KJT) is a health beverage prepared from the leaves of the plant Acer tataricum subsp. ginnala that has been consumed in some regions of China for thousands of years. KJT contains high levels of anti-inflammatory and antioxidative compounds such as ginnalins, but little is known about the chemopreventive effect of KJT on colon cancer. In this study, we investigated the preventive effects of KJT on colon carcinogenesis using the azoxymethane (AOM)-induced precancerous colorectal lesion model in rats. The results showed that the number of aberrant crypts, aberrant crypt foci (ACF) and crypts/focus in rats of the KJT + AOM group were significantly decreased compared with rats of the AOM group (p < 0.01). Further exploration of the prevention mechanism of KJT by UPLC-QTOF/MS-based urinary metabolomics showed that 5 metabolic pathways were modulated, including purine metabolism and amino acid metabolism, in the group with KJT. In addition, the levels of the immunomodulatory cytokines IL-1α and IL-10 were significantly decreased, and the levels of IL-2 in the serum of AOM rats increased after KJT treatment. Our present data suggest that KJT can inhibit AOM-induced colonic ACF formation and might be a useful chemopreventive agent against colorectal carcinogenesis.
Association of serum sodium and risk of all-cause mortality in patients with chronic kidney disease: A meta-analysis and sysematic review
Authors: Sun Liguang , Hou Yue , Xiao Qingfei , Du Yujun
Published: November 2017

Studies on the association of dysnatraemia with all-cause mortality risk in chronic kidney disease (CKD) patients have yielded inconsistent results. This meta-analysis aimed to evaluate the association of hyponatremia or hypernatremia with all-cause mortality risk in CKD patients. An electronic literature search was performed in Web of Science, Pubmed and Embase databases from inception to March 2017 for available observational studies evaluating the association of dysnatraemia with all-cause mortality risk in CKD patients. Pooled hazard risk (HR) with 95% confidence interval (CI) was calculated for hyponatremia or hypernatremia vs. normonatremia. Seven studies that enrolled 742,979 CKD patients were identified. Baseline hyponatremia (HR 1.34; 95% CI: 1.15–1.57), and not hypernatremia (HR 1.12; 95%: CI 0.93–1.34), was independently associated with increased risk of all-cause mortality, when compared than the normonatremia category. In time-dependent analyses, both time-averaged hyponatremia (HR 1.65; 95% CI: 1.27–2.15) and hypernatremia (HR 1.41; 95% CI: 1.20–1.65) had a higher independent risk of all-cause mortality. Furthermore, subgroup analyses by type of patients, study design, sample size and follow-up duration revealed similar results across most of these analyses. Baseline hyponatremia and time-dependent hyponatremia or hypernatremia were independently associated with increased all-cause mortality risk in CKD patients.
Sublethal effects of imidacloprid on targeting muscle and ribosomal protein related genes in the honey bee Apis mellifera L.
Authors: Wu Yan-Yan , Luo Qi-Hua , Hou Chun-Sheng , Wang Qiang , Dai Ping-Li , Gao Jing , Liu Yong-Jun , Diao Qing-Yun
Published: November 2017

A sublethal concentration of imidacloprid can cause chronic toxicity in bees and can impact the behavior of honey bees. The nectar- and water-collecting, and climbing abilities of bees are crucial to the survival of the bees and the execution of responsibilities in bee colonies. Besides behavioral impact, data on the molecular mechanisms underlying the toxicity of imidacloprid, especially by the way of RNA-seq at the transcriptomic level, are limited. We treated Apis mellifera L. with sublethal concentrations of imidacloprid (0.1, 1 and 10 ppb) and determined the effect on behaviors and the transcriptomic changes. The sublethal concentrations of imidacloprid had a limited impact on the survival and syrup consumption of bees, but caused a significant increase in water consumption. Moreover, the climbing ability was significantly impaired by 10 ppb imidacloprid at 8 d. In the RNA-seq analysis, gene ontology (GO) term enrichment indicated a significant down-regulation of muscle-related genes, which might contribute to the impairment in climbing ability of bees. The enriched GO terms were attributed to the up-regulated ribosomal protein genes. Considering the ribosomal and extra-ribosomal functions of the ribosomal proteins, we hypothesized that imidacloprid also causes cell dysfunction. Our findings further enhance the understanding of imidacloprid sublethal toxicity.
Trophic and tectonic limits to the global increase of marine invertebrate diversity
Authors: Cermeño Pedro , Benton Michael J. , Paz Óscar , Vérard Christian
Published: November 2017

The marine invertebrate fossil record provides the most comprehensive history of how the diversity of animal life has evolved through time. One of the main features of this record is a modest rise in diversity over nearly a half-billion years. The long-standing view is that ecological interactions such as resource competition and predation set upper limits to global diversity, which, in the absence of external perturbations, is maintained indefinitely at equilibrium. However, the effect of mechanisms associated with the history of the seafloor, and their influence on the creation and destruction of marine benthic habitats, has not been explored. Here we use statistical methods for causal inference to investigate the drivers of marine invertebrate diversity dynamics through the Phanerozoic. We find that diversity dynamics responded to secular variations in marine food supply, substantiating the idea that global species richness is regulated by resource availability. Once diversity was corrected for changes in food resource availability, its dynamics were causally linked to the age of the subducting oceanic crust. We suggest that the time elapsed between the formation (at mid-ocean ridges) and destruction (at subduction zones) of ocean basins influences the diversity dynamics of marine invertebrates and may have contributed to constrain their diversification.
CT dose reduction factors in the thousands using X-ray phase contrast
Authors: Kitchen Marcus J. , Buckley Genevieve A. , Gureyev Timur E. , Wallace Megan J. , Andres-Thio Nico , Uesugi Kentaro , Yagi Naoto , Hooper Stuart B.
Published: November 2017

Phase-contrast X-ray imaging can improve the visibility of weakly absorbing objects (e.g. soft tissues) by an order of magnitude or more compared to conventional radiographs. Combining phase retrieval with computed tomography (CT) can increase the signal-to-noise ratio (SNR) by up to two orders of magnitude over conventional CT at the same radiation dose, without loss of image quality. Our experiments reveal that as the radiation dose decreases, the relative improvement in SNR increases. We show that this enhancement can be traded for a reduction in dose greater than the square of the gain in SNR. Upon reducing the dose 300 fold, the phase-retrieved SNR was still up to 9.6 ± 0.2 times larger than the absorption contrast data with spatial resolution in the tens of microns. We show that this theoretically reveals the potential for dose reduction factors in the tens of thousands without loss in image quality, which would have a profound impact on medical and industrial imaging applications.
Dysbiosis of the microbiome in gastric carcinogenesis
Authors: Castaño-Rodríguez Natalia , Goh Khean-Lee , Fock Kwong Ming , Mitchell Hazel M. , Kaakoush Nadeem O.
Published: November 2017

The gastric microbiome has been proposed as an etiological factor in gastric carcinogenesis. We compared the gastric microbiota in subjects presenting with gastric cancer (GC, n = 12) and controls (functional dyspepsia (FD), n = 20) from a high GC risk population in Singapore and Malaysia. cDNA from 16S rRNA transcripts were amplified (515F-806R) and sequenced using Illumina MiSeq 2 × 250 bp chemistry. Increased richness and phylogenetic diversity but not Shannon’s diversity was found in GC as compared to controls. nMDS clustered GC and FD subjects separately, with PERMANOVA confirming a significant difference between the groups.H. pyloriserological status had a significant impact on gastric microbiome α-diversity and composition. Several bacterial taxa were enriched in GC, includingLactococcus,Veilonella, andFusobacteriaceae(FusobacteriumandLeptotrichia). Prediction of bacterial metabolic contribution indicated that serological status had a significant impact on metabolic function, while carbohydrate digestion and pathways were enriched in GC. Our findings highlight three mechanisms of interest in GC, including enrichment of pro-inflammatory oral bacterial species, increased abundance of lactic acid producing bacteria, and enrichment of short chain fatty acid production pathways.
RNA metabolism is the primary target of formamide in vivo
Authors: Hoyos-Manchado Rafael , Reyes-Martín Félix , Rallis Charalampos , Gamero-Estévez Enrique , Rodríguez-Gómez Pablo , Quintero-Blanco Juan , Bähler Jürg , Jiménez Juan , Tallada Víctor A.
Published: November 2017

The synthesis, processing and function of coding and non-coding RNA molecules and their interacting proteins has been the focus of a great deal of research that has boosted our understanding of key molecular pathways that underlie higher order events such as cell cycle control, development, innate immune response and the occurrence of genetic diseases. In this study, we have found that formamide preferentially weakens RNA related processes in vivo. Using a non-essential Schizosaccharomyces pombe gene deletion collection, we identify deleted loci that make cells sensitive to formamide. Sensitive deletions are significantly enriched in genes involved in RNA metabolism. Accordingly, we find that previously known temperature-sensitive splicing mutants become lethal in the presence of the drug under permissive temperature. Furthermore, in a wild type background, splicing efficiency is decreased and R-loop formation is increased in the presence of formamide. In addition, we have also isolated 35 formamide-sensitive mutants, many of which display remarkable morphology and cell cycle defects potentially unveiling new players in the regulation of these processes. We conclude that formamide preferentially targets RNA related processes in vivo, probably by relaxing RNA secondary structures and/or RNA-protein interactions, and can be used as an effective tool to characterize these processes.
Metabolomics biomarker analysis of threatened abortion in polycystic ovary syndrome: a clinical discovery study
Authors: Feng Xiaoling , Chen Lu , Li Na , Zhao Yan , Han Qimao , Wang Xiaolin , Wang Wei , Ma Liping , Zhao Xinjie
Published: November 2017

In this study, using an advanced metabolomics platform based on UPLC-QTOF-MS, we found that pregnancy significantly altered the profile of metabolites in the plasma of women with PCOS.
Combined determination of copper ions and β-amyloid peptide by a single ratiometric electrochemical biosensor
Authors: Yu Yanyan , Wang Peng , Zhu Xiaodan , Peng Qiwen , Zhou Yi , Yin Tianxiao , Liang Yixin , Yin Xiaoxing
Published: November 2017

A novel ratiometric electrochemical biosensor was developed for the combined determination of copper ion and β-amyloid peptide.
Highly sensitive detection of hesperidin using AuNPs/rGO modified glassy carbon electrode
Authors: Gao Yang , Wu Xiufeng , Wang Hui , Lu Wenbo , Guo Mandong
Published: November 2017

The highly sensitive and selective electrochemical sensor of hesperidin based on gold nanoparticles (AuNPs) and reduced graphene oxide (rGO) modified glassy carbon electrode (GCE) is reported.
Towards improved quantitative analysis using surface-enhanced Raman scattering incorporating internal isotope labelling
Authors: Subaihi Abdu , Xu Yun , Muhamadali Howbeer , Mutter Shaun T. , Blanch Ewan W. , Ellis David I. , Goodacre Royston
Published: November 2017

Surface-enhanced Raman scattering can be used for the molecular characterisation of different molecules and isotopologues can be used to generate highly quantitative data.
Exploring the science of thinking independently together: Faraday Discussion Volume 204 – Complex Molecular Surfaces and Interfaces, Sheffield, UK, July 2017
Authors: Samperi M. , Hirsch B. E. , Diaz Fernandez Y. A.
Published: November 2017

This Faraday Discussion meeting brought together theoreticians and experimentalists from both physical and chemical backgrounds to discuss the relevant applied and fundamental research topics within the broader field of chemical surface analysis and characterization.
The selective hydrogenation of furfural over supported palladium nanoparticle catalysts prepared by sol-immobilisation: effect of catalyst support and reaction conditions
Authors: Albilali Reem , Douthwaite Mark , He Qian , Taylor Stuart H.
Published: November 2017

Pd-TiO2 nanoparticles prepared by sol-immobilisation are very active for selective hydrogenation of furfural under mild conditions, and addition of Pt enhances performance to achieve a 95% yield of tetrahydrofurfuryl alcohol.
Near-infrared aza-BODIPY fluorescent probe for selective Cu2+detection and its potential in living cell imaging
Authors: Tachapermpon Yordkhuan , Thavornpradit Sopida , Charoenpanich Adisri , Sirirak Jitnapa , Burgess Kevin , Wanichacheva Nantanit
Published: November 2017

A near-infrared (NIR) fluorescent sensor1composed of an aza-boron-dipyrromethene (aza-BODIPY) core covalently bound to two di-2-picolylamine moieties was prepared for Cu2+detection in aqueous solutions.
A pilot study on clinical pharmacokinetics and preclinical pharmacodynamics of (+)-epicatechin on cardiometabolic endpoints
Authors: Moreno-Ulloa Aldo , Nájera-García Nayelli , Hernández Marcela , Ramírez-Sánchez Israel , Taub Pam R. , Su Yongxuan , Beltrán-Partida Ernesto , Ceballos Guillermo , Dugar Sundeep , Schreiner George , Best Brookie M. , Ciaraldi Theodore P. , Henry Robert R. , Villarreal Francisco
Published: November 2017

We reported that (−)-epicatechin can stimulate mitochondria biogenesis and improve metabolism.
Synthesis and antioxidant evaluation of lipophilic oleuropein aglycone derivatives
Authors: Nardi M. , Bonacci S. , Cariati L. , Costanzo P. , Oliverio M. , Sindona G. , Procopio A.
Published: November 2017

A set of oleuropein aglycone derivatives were synthesized by transacetalization under mild and environmental friendly conditions. The antioxidant activities of the obtained compounds exhibited a dependence on their level of lipophilicity thus demonstrating their potential application as a preservative in fatty foods.
Computational modelling of the redistribution of copper isotopes by proteins in the liver
Authors: Tennant Alexander , Rauk Arvi , Wieser Michael E.
Published: November 2017

The copper isotopic composition of blood serum as the mass balance of the copper isotopic composition of serum proteins.
Construction of hierarchical Ag@TiO2@ZnO nanowires with high photocatalytic activity
Authors: Xiang Xiao-Bo , Yu Yang , Wen Wei , Wu Jin-Ming
Published: November 2017

Appropriate combinations of Ag/TiO2 Schottky barriers and TiO2/ZnO heterojunctions afford hierarchical Ag@TiO2@ZnO nanowires with a high photocatalytic activity.
Electroconductive nanoscale topography for enhanced neuronal differentiation and electrophysiological maturation of human neural stem cells
Authors: Yang Kisuk , Yu Seung Jung , Lee Jong Seung , Lee Hak-Rae , Chang Gyeong-Eon , Seo Jungmok , Lee Taeyoon , Cheong Eunji , Im Sung Gap , Cho Seung-Woo
Published: November 2017

Electroconductive nanotopography for enhanced neurogenesis of neural stem cell.
Nicking enzyme-controlled toehold regulation for DNA logic circuits
Authors: Pan Linqiang , Wang Zhiyu , Li Yifan , Xu Fei , Zhang Qiang , Zhang Cheng
Published: November 2017

A toehold regulation mechanism in which toeholds can be precisely generated and removed responding to different nicking enzymes.
Probing magnetic coupling between LnPc2 (Ln = Tb, Er) molecules and the graphene/Ni (111) substrate with and without Au-intercalation: role of the dipolar field
Authors: Corradini V. , Candini A. , Klar D. , Biagi R. , De Renzi V. , Lodi Rizzini A. , Cavani N. , del Pennino U. , Klyatskaya S. , Ruben M. , Velez-Fort E. , Kummer K. , Brookes N. B. , Gargiani P. , Wende H. , Affronte M.
Published: November 2017

The dipolar field contribution is revealed to be significant in the magnetic coupling between LnPc2 and Ni(111) substrate.
Damage-free and rapid transfer of CVD-grown two-dimensional transition metal dichalcogenides by dissolving sacrificial water-soluble layers
Authors: Zhang Lili , Wang Chenyu , Liu Xue-Lu , Xu Tao , Long Mingsheng , Liu Erfu , Pan Chen , Su Guangxu , Zeng Junwen , Fu Yajun , Wang Yiping , Yan Zhendong , Gao Anyuan , Xu Kang , Tan Ping-Heng , Sun Litao , Wang Zhenlin , Cui Xinyi , Miao Feng
Published: November 2017

As one of the most important family members of two-dimensional (2D) materials, the growth and damage-free transfer of transition metal dichalcogenides (TMDs) play crucial roles in their future applications.
Polyethylene nano crystalsomes formed at a curved liquid/liquid interface
Authors: Wang Wenda , Staub Mark C. , Zhou Tian , Smith Derrick M. , Qi Hao , Laird Eric D. , Cheng Shan , Li Christopher Y.
Published: November 2017

We report the growth and structure of self-assembled, mechanically robust nanosized crystalsomes.
Complete tetraglycosylation of a calix[4]arene by a chemo-enzymatic approach
Authors: Bernardi Silvia , Yi Dong , He Ning , Casnati Alessandro , Fessner Wolf-Dieter , Sansone Francesco
Published: November 2017

It was demonstrated that a calixarene can be a substrate for glycosyltransferases and thanks to an exhaustive glycosylation a multivalent tetralactosaminyl calix[4]arene was obtained.
[18F]ODIBO: a prosthetic group for bioorthogonal radiolabeling of macromolecules via strain-promoted alkyne–azide cycloaddition
Authors: Boudjemeline Mehdi , McNitt Christopher D. , Singleton Thomas A. , Popik Vladimir V. , Kostikov Alexey P.
Published: November 2017

[18F]oxadibenzocyclooctyne ([18F]ODIBO) allows for efficient biorthogonal radiolabeling of macromolecules at low concentrations and room temperature via SPAAC.
Fe-Catalyzed radical-type difunctionalization of styrenes with aliphatic aldehydes and trimethylsilyl azide via a decarbonylative alkylation–azidation cascade
Authors: Li Wei-Yu , Wang Qi-Qiang , Yang Luo
Published: November 2017

A three-component oxidative decarbonylative alkylation–azidation cascade reaction of styrene derivatives with aliphatic aldehydes and TMSN3 to provide aliphatic azides is developed.
The application of blocked isocyanate chemistry in the development of tunable thermoresponsive crosslinkers
Authors: Rolph Marianne S. , Inam Maria , O'Reilly Rachel K.
Published: November 2017

The synthesis of a novel monomer, methacryloyl pyrazole, and its subsequent reaction with diisocyanates to produce thermoresponsive crosslinkers is reported.
Secondary structures of synthetic polypeptide polymers
Authors: Bonduelle Colin
Published: November 2017

Synthetic peptide-based polymers can fold into different secondary structures in the same way as do proteins. This review article presents how tuning the polypeptide secondary structure could be a key step to modulate various properties in advanced polymeric materials (size, rigidity, self-assembly,etc.).
New crown ether complex cation ionic liquids with N-heterocycle anions: preparation and application in CO2 fixation
Authors: Wang Jinyuan , Liang Yatao , Zhou Dagang , Ma Jiangping , Jing Huanwang
Published: November 2017

A series of CECILs have been devised, synthesized and characterized by NMR, IR, elemental analysis and TGA-DSC.
Thiazolium salt-catalyzed [3 + 2 + 1] cyclization for the synthesis of trisubstituted 2-pyrones using arylglyoxals as a carbonyl source
Authors: Xu Li-Chen , Zhou Peng , Li Jia-Zhuo , Hao Wen-Juan , Tu Shu-Jiang , Jiang Bo
Published: November 2017

A new thiazolium salt-catalyzed [3 + 2 + 1] cyclization of acetylenedicarboxylates with arylglyoxals has been developed, enabling organocatalytic umpolung to access trisubstituted 2-pyrones with good yields via C–C bond cleavage.
Formation of environmentally-persistent free radicals (EPFR) on α-Al2O3 clusters
Authors: Assaf Niveen W. , Altarawneh Mohammednoor , Radny Marian W. , Al-Nu'airat Jomana , Dlugogorski Bogdan Z.
Published: November 2017

This study explores the role of alumina clusters assume an important role in catalyzing formation of notorious environmental persistent free radicals (EPFRs).
Corrosion mechanism for local enrichment of acids and copper ions in copper-insulating paper contacts leading to the acceleration of copper sulfide formation induced by dibenzyl disulfide
Authors: Gao Sihang , Yang Lijun , Deng Bangfei , Zhang Jiang
Published: November 2017

Local enrichment of acids and copper ions in copper-insulating paper accelerates sulfur corrosion.
Strain-stiffening gels based on latent crosslinking
Authors: Tran Yen H. , Rasmuson Matthew J. , Emrick Todd , Klier John , Peyton Shelly R.
Published: November 2017

Strain-stiffening gels based on crosslinking moieties, initially hidden in the network then activated and accelerated to crosslink under strain.
Mussel-inspired surface functionalization of porous carbon nanosheets using polydopamine and Fe3+/tannic acid layers for high-performance electrochemical capacitors
Authors: Lee Yeong A. , Lee Jiyoung , Kim Dae Wook , Yoo Chung-Yul , Park Sang Hyun , Yoo Jung Joon , Kim Seungchul , Kim Bongsoo , Cho Woo Kyung , Yoon Hana
Published: November 2017

The mussel-inspired surface modification for high-performance electrochemical capacitors is demonstrated.
Photolithography-compatible conformal electrodes for high-performance bottom-contact organic single-crystal transistors
Authors: Zhao Xiaoli , Ding Xueyan , Tang Qingxin , Tong Yanhong , Liu Yichun
Published: November 2017

A novel photolithography-compatible conformal electrode was demonstrated for the fabrication of high-performance bottom-contact organic single-crystal transistors on planar and curved surfaces.
Chloroplast division protein ARC3 acts on FtsZ2 by preventing filament bundling and enhancing GTPase activity
Authors: Shaik Rahamthulla S. , Sung Min Woo , Vitha Stanislav , Holzenburg Andreas
Published: November 2017

Chloroplasts evolved from cyanobacterial endosymbiotic ancestors and their division is a complex process initiated by the assembly of cytoskeletal FtsZ (Filamentous temperature sensitive Z) proteins into a ring structure at the division site (Z-ring). The cyanobacterial Z-ring positioning system (MinCDE proteins) is also conserved in chloroplasts, except that MinC was lost and replaced by the eukaryotic ARC3 (accumulation and replication of chloroplasts). Both MinC and ARC3 act as negative regulators of FtsZ assembly, but ARC3 bears little sequence similarity with MinC. Here, light scattering assays, co-sedimentation, GTPase assay and transmission electron microscopy in conjunction with single-particle analysis have been used to elucidate the structure of ARC3 and its effect on its main target in chloroplast division, FtsZ2. Analysis of FtsZ2 in vitro assembly reactions in the presence and absence of GMPCPP showed that ARC3 promotes FtsZ2 debundling and disassembly of existing filaments in a concentration-dependent manner and requires GTP hydrolysis. Three-dimensional reconstruction of ARC3 revealed an almost circular molecule in which the FtsZ-binding N-terminus and the C-terminal PARC6 (paralog of ARC6)-binding MORN (Membrane Occupation and Recognition Nexus) domain are in close proximity and suggest a model for PARC6-enabled binding of ARC3 to FtsZ2. The latter is corroborated by in vivo data.
Analysis of single-cell genome sequences of bacteria and archaea
Authors: Bowers Robert M. , Doud Devin F.R. , Woyke Tanja
Published: November 2017

Single-cell genome sequencing of individual archaeal and bacterial cells is a vital approach to decipher the genetic makeup of uncultured microorganisms. With this review, we describe single-cell genome analysis with a focus on the unique properties of single-cell sequence data and with emphasis on quality assessment and assurance.
Low‐cost positioning with rotating antenna in constrained environment for global navigation satellite systems
Authors: Wang Jin , Zhang Kai
Published: November 2017

In high‐precision relative positioning applications of global navigation satellite systems, multipath and phase centre offset/variation remain as the major coupled error sources, as they cannot be eliminated by the differential operation. A circular rotating low‐cost antenna is introduced for the rover station in a constrained environment. The spatial diversity of multipath is explored by circular motion to aid the carrier‐phase ambiguity resolution and error elimination. The multipath and phase centre offset are separated and estimated. Field tests demonstrate that the proposed method with low‐cost antenna is able to achieve the survey‐grade precision.
Current vector control of wireless power transfer system with 2D transmitting coils
Authors: Seol W.‐K. , Chung S.‐K.
Published: November 2017

Current vector control of a resonant‐type wireless power transfer system with 2D transmitting (Tx) coils is presented. The equivalent circuit model between two Tx and one receiving coils is derived in d–q coordinates. The control method to obtain the maximum power transmission efficiency is proposed. The experimental results are provided to verify the proposed control method.