bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between copper and lipids and atherogenic indices soon after birth in Japanese preterm infants of 32–35 weeks
Authors: Shoji H. , Ikeda N. , Kojima C. , Kitamura T. , Suganuma H. , Hisata K. , Hirayama S. , Ueno T. , Miida T. , Shimizu T.
Published: December 2016

Several studies have reported association of altered levels of lipids and some trace elements with risk factors for cardiovascular disease development in adulthood. Accordingly, the present study aimed to determine the relationship among the serum levels of copper (Cu), zinc (Zn), lipids, lipoproteins and apolipoproteins in preterm infants through an assessment of atherogenic indices shortly after birth. Blood samples were collected within 20 min of birth from 45 preterm infants with gestational ages ranging from 32 to 35 weeks. Serum Cu, Zn, total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels were measured, and the TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were calculated. Upon determining the correlation between the levels of Cu, Zn and these indices of lipid metabolism, triglyceride (TG) and Cu were found to correlate negatively with birth weight (BW) and the standard deviation (s.d.) score for body weight. Furthermore, Cu levels correlated positively with the TG level and TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios and negatively with the HDLc level and HDLc/apoA1 ratios. However, a stepwise multiple regression analysis indicated that the s.d. score for BW and TG level were significant independent determinants of the Cu level. In contrast, Zn did not correlate with any of these indices. In conclusion, intrauterine growth restriction and the TG level at birth influence Cu levels in preterm infants, whereas atherogenic indices do not affect this parameter.
Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics in young adult horses
Authors: Valenzuela O. A. , Jellyman J. K. , Allen V. L. , Holdstock N. B. , Forhead A. J. , Fowden A. L.
Published: December 2016

In several species, adult metabolic phenotype is influenced by the intrauterine environment, often in a sex-linked manner. In horses, there is also a window of susceptibility to programming immediately after birth but whether adult glucose–insulin dynamics are altered by neonatal conditions remains unknown. Thus, this study investigated the effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics of young adult horses. For the first 5 days after birth, term foals were treated with saline as a control or ACTH to raise cortisol levels to those of stressed neonates. At 1 and 2 years of age, insulin secretion and sensitivity were measured by exogenous glucose administration and hyperinsulinaemic–euglycaemic clamp, respectively. Glucose-stimulated insulin secretion was less in males than females at both ages, although there were no sex-linked differences in glucose tolerance. Insulin sensitivity was greater in females than males at 1 year but not 2 years of age. Birth weight was inversely related to the area under the glucose curve and positively correlated to insulin sensitivity at 2 years but not 1 year of age. In contrast, neonatal glucocorticoid overexposure induced by adrenocorticotropic hormone (ACTH) treatment had no effect on whole body glucose tolerance, insulin secretion or insulin sensitivity at either age, although this treatment altered insulin receptor abundance in specific skeletal muscles of the 2-year-old horses. These findings show that glucose–insulin dynamics in young adult horses are sexually dimorphic and determined by a combination of genetic and environmental factors acting during early life.
Modeling of soil nitrification responses to temperature reveals thermodynamic differences between ammonia-oxidizing activity of archaea and bacteria
Authors: Taylor Anne E , Giguere Andrew T , Zoebelein Conor M , Myrold David D , Bottomley Peter J
Published: December 2016

Soil nitrification potential (NP) activities of ammonia-oxidizing archaea and bacteria (AOA and AOB, respectively) were evaluated across a temperature gradient (4–42 °C) imposed upon eight soils from four different sites in Oregon and modeled with both the macromolecular rate theory and the square root growth models to quantify the thermodynamic responses. There were significant differences in response by the dominant AOA and AOB contributing to the NPs. The optimal temperatures (Topt) for AOA- and AOB-supported NPs were significantly different (P<0.001), with AOA having Topt>12 °C greater than AOB. The change in heat capacity associated with the temperature dependence of nitrification (ΔCP‡) was correlated with Topt across the eight soils, and the ΔCP‡ of AOB activity was significantly more negative than that of AOA activity (P<0.01). Model results predicted, and confirmatory experiments showed, a significantly lower minimum temperature (Tmin) and different, albeit very similar, maximum temperature (Tmax) values for AOB than for AOA activity. The results also suggested that there may be different forms of AOA AMO that are active over different temperature ranges with different Tmin, but no evidence of multiple Tmin values within the AOB. Fundamental differences in temperature-influenced properties of nitrification driven by AOA and AOB provides support for the idea that the biochemical processes associated with NH3 oxidation in AOA and AOB differ thermodynamically from each other, and that also might account for the difficulties encountered in attempting to model the response of nitrification to temperature change in soil environments.
Experimental warming reveals positive feedbacks to climate change in the Eurasian Steppe
Authors: Zhang Ximei , Johnston Eric R , Li Linghao , Konstantinidis Konstantinos T , Han Xingguo
Published: December 2016

Identifying soil microbial feedbacks to increasing temperatures and moisture alterations is critical for predicting how terrestrial ecosystems will respond to climate change. We performed a 5-year field experiment manipulating warming, watering and their combination in a semiarid temperate steppe in northern China. Warming stimulated the abundance of genes responsible for degrading recalcitrant soil organic matter (SOM) and reduced SOM content by 13%. Watering, and warming plus watering also increased the abundance of recalcitrant SOM catabolism pathways, but concurrently promoted plant growth and increased labile SOM content, which somewhat offset SOM loss. The treatments also increased microbial biomass, community complexity and metabolic potential for nitrogen and sulfur assimilation. Both microbial and plant community composition shifted with the treatment conditions, and the sample-to-sample compositional variations of the two communities (pairwise β-diversity distances) were significantly correlated. In particular, microbial community composition was substantially correlated with the dominant plant species (~0.54 Spearman correlation coefficient), much more than with measured soil indices, affirming a tight coupling between both biological communities. Collectively, our study revealed the direction and underlying mechanisms of microbial feedbacks to warming and suggested that semiarid regions of northern steppes could act as a net carbon source under increased temperatures, unless precipitation increases concurrently.
Structural insights into ribosomal rescue by Dom34 and Hbs1 at near-atomic resolution
Authors: Hilal Tarek , Yamamoto Hiroshi , Loerke Justus , Bürger Jörg , Mielke Thorsten , Spahn Christian M.T.
Published: December 2016

The surveillance of mRNA translation is imperative for homeostasis. Monitoring the integrity of the message is essential, as the translation of aberrant mRNAs leads to stalling of the translational machinery. During ribosomal rescue, arrested ribosomes are specifically recognized by the conserved eukaryotic proteins Dom34 and Hbs1, to initiate their recycling. Here we solve the structure of Dom34 and Hbs1 bound to a yeast ribosome programmed with a nonstop mRNA at 3.3 Å resolution using cryo-electron microscopy. The structure shows that Domain N of Dom34 is inserted into the upstream mRNA-binding groove via direct stacking interactions with conserved nucleotides of 18S rRNA. It senses the absence of mRNA at the A-site and part of the mRNA entry channel by direct competition. Thus, our analysis establishes the structural foundation for the recognition of aberrantly stalled 80S ribosomes by the Dom34·Hbs1·GTP complex during Dom34-mediated mRNA surveillance pathways.
The biomechanical properties of an epithelial tissue determine the location of its vasculature
Authors: Kragl Martin , Schubert Rajib , Karsjens Haiko , Otter Silke , Bartosinska Barbara , Jeruschke Kay , Weiss Jürgen , Chen Chunguang , Alsteens David , Kuss Oliver , Speier Stephan , Eberhard Daniel , Müller Daniel J. , Lammert Eckhard
Published: December 2016

An important question is how growing tissues establish a blood vessel network. Here we study vascular network formation in pancreatic islets, endocrine tissues derived from pancreatic epithelium. We find that depletion of integrin-linked kinase (ILK) in the pancreatic epithelial cells of mice results in glucose intolerance due to a loss of the intra-islet vasculature. In turn, blood vessels accumulate at the islet periphery. Neither alterations in endothelial cell proliferation, apoptosis, morphology, Vegfa expression and VEGF-A secretion nor ‘empty sleeves’ of vascular basement membrane are found. Instead, biophysical experiments reveal that the biomechanical properties of pancreatic islet cells, such as their actomyosin-mediated cortex tension and adhesive forces to endothelial cells, are significantly changed. These results suggest that a sorting event is driving the segregation of endothelial and epithelial cells and indicate that the epithelial biomechanical properties determine whether the blood vasculature invades or envelops a growing epithelial tissue.
Rapid tuning shifts in human auditory cortex enhance speech intelligibility
Authors: Holdgraf Christopher R. , de Heer Wendy , Pasley Brian , Rieger Jochem , Crone Nathan , Lin Jack J. , Knight Robert T. , Theunissen Frédéric E.
Published: December 2016

Experience shapes our perception of the world on a moment-to-moment basis. This robust perceptual effect of experience parallels a change in the neural representation of stimulus features, though the nature of this representation and its plasticity are not well-understood. Spectrotemporal receptive field (STRF) mapping describes the neural response to acoustic features, and has been used to study contextual effects on auditory receptive fields in animal models. We performed a STRF plasticity analysis on electrophysiological data from recordings obtained directly from the human auditory cortex. Here, we report rapid, automatic plasticity of the spectrotemporal response of recorded neural ensembles, driven by previous experience with acoustic and linguistic information, and with a neurophysiological effect in the sub-second range. This plasticity reflects increased sensitivity to spectrotemporal features, enhancing the extraction of more speech-like features from a degraded stimulus and providing the physiological basis for the observed ‘perceptual enhancement’ in understanding speech.
Insect mimicry of plants dates back to the Permian
Authors: Garrouste Romain , Hugel Sylvain , Jacquelin Lauriane , Rostan Pierre , Steyer J.-Sébastien , Desutter-Grandcolas Laure , Nel André
Published: December 2016

In response to predation pressure, some insects have developed spectacular plant mimicry strategies (homomorphy), involving important changes in their morphology. The fossil record of plant mimicry provides clues to the importance of predation pressure in the deep past. Surprisingly, to date, the oldest confirmed records of insect leaf mimicry are Mesozoic. Here we document a crucial step in the story of adaptive responses to predation by describing a leaf-mimicking katydid from the Middle Permian. Our morphometric analysis demonstrates that leaf-mimicking wings of katydids can be morphologically characterized in a non-arbitrary manner and shows that the new genus and speciesPermotettigonia gallicadeveloped a mimicking pattern of forewings very similar to those of the modern leaf-like katydids. Our finding suggests that predation pressure was already high enough during the Permian to favour investment in leaf mimicry.
A genome-scale Escherichia coli kinetic metabolic model k-ecoli457 satisfying flux data for multiple mutant strains
Authors: Khodayari Ali , Maranas Costas D.
Published: December 2016

Kinetic models of metabolism at a genome scale that faithfully recapitulate the effect of multiple genetic interventions would be transformative in our ability to reliably design novel overproducing microbial strains. Here, we introduce k-ecoli457, a genome-scale kinetic model of Escherichia coli metabolism that satisfies fluxomic data for wild-type and 25 mutant strains under different substrates and growth conditions. The k-ecoli457 model contains 457 model reactions, 337 metabolites and 295 substrate-level regulatory interactions. Parameterization is carried out using a genetic algorithm by simultaneously imposing all available fluxomic data (about 30 measured fluxes per mutant). The Pearson correlation coefficient between experimental data and predicted product yields for 320 engineered strains spanning 24 product metabolites is 0.84. This is substantially higher than that using flux balance analysis, minimization of metabolic adjustment or maximization of product yield exhibiting systematic errors with correlation coefficients of, respectively, 0.18, 0.37 and 0.47 (k-ecoli457 is available for download at http://www.maranasgroup.com).
Tunable molecular separation by nanoporous membranes
Authors: Wang Zhengbang , Knebel Alexander , Grosjean Sylvain , Wagner Danny , Bräse Stefan , Wöll Christof , Caro Jürgen , Heinke Lars
Published: December 2016

Metal-organic frameworks offer tremendous potential for efficient separation of molecular mixtures. Different pore sizes and suitable functionalizations of the framework allow for an adjustment of the static selectivity. Here we report membranes which offer dynamic control of the selectivity by remote signals, thus enabling a continuous adjustment of the permeate flux. This is realized by assembling linkers containing photoresponsive azobenzene-side-groups into monolithic, crystalline membranes of metal-organic frameworks. The azobenzene moieties can be switched from the trans to the cis configuration and vice versa by irradiation with ultraviolet or visible light, resulting in a substantial modification of the membrane permeability and separation factor. The precise control of the cis:trans azobenzene ratio, for example, by controlled irradiation times or by simultaneous irradiation with ultraviolet and visible light, enables the continuous tuning of the separation. For hydrogen:carbon-dioxide, the separation factor of this smart membrane can be steplessly adjusted between 3 and 8.
MicroRNA-182 targets SMAD7 to potentiate TGFβ-induced epithelial-mesenchymal transition and metastasis of cancer cells
Authors: Yu Jingyi , Lei Rong , Zhuang Xueqian , Li Xiaoxun , Li Gang , Lev Sima , Segura Miguel F. , Zhang Xue , Hu Guohong
Published: December 2016

The transforming growth factor β (TGFβ) pathway plays critical roles during cancer cell epithelial-mesenchymal transition (EMT) and metastasis. SMAD7 is both a transcriptional target and a negative regulator of TGFβ signalling, thus mediating a negative feedback loop that may potentially restrain TGFβ responses of cancer cells. Here, however, we show that TGFβ treatment induces SMAD7 transcription but not its protein level in a panel of cancer cells. Mechanistic studies reveal that TGFβ activates the expression of microRNA-182 (miR-182), which suppresses SMAD7 protein. miR-182 silencing leads to SMAD7 upregulation on TGFβ treatment and prevents TGFβ-induced EMT and invasion of cancer cells. Overexpression of miR-182 promotes breast tumour invasion and TGFβ-induced osteoclastogenesis for bone metastasis. Furthermore, miR-182 expression inversely correlates with SMAD7 protein in human tumour samples. Therefore, our data reveal the miR-182-mediated disruption of TGFβ self-restraint and provide a mechanism to explain the unleashed TGFβ responses in metastatic cancer cells.
Disease surveillance based on Internet-based linear models: an Australian case study of previously unmodeled infection diseases
Authors: Rohart Florian , Milinovich Gabriel J. , Avril Simon M. R. , Lê Cao Kim-Anh , Tong Shilu , Hu Wenbiao
Published: December 2016

Effective disease surveillance is critical to the functioning of health systems. Traditional approaches are, however, limited in their ability to deliver timely information. Internet-based surveillance systems are a promising approach that may circumvent many of the limitations of traditional health surveillance systems and provide more intelligence on cases of infection, including cases from those that do not use the healthcare system. Infectious disease surveillance systems built on Internet search metrics have been shown to produce accurate estimates of disease weeks before traditional systems and are an economically attractive approach to surveillance; they are, however, also prone to error under certain circumstances. This study sought to explore previously unmodeled diseases by investigating the link between Google Trends search metrics and Australian weekly notification data. We propose using four alternative disease modelling strategies based on linear models that studied the length of the training period used for model construction, determined the most appropriate lag for search metrics, used wavelet transformation for denoising data and enabled the identification of key search queries for each disease. Out of the twenty-four diseases assessed with Australian data, our nowcasting results highlighted promise for two diseases of international concern, Ross River virus and pneumococcal disease.
The Quantum Biology of Reactive Oxygen Species Partitioning Impacts Cellular Bioenergetics
Authors: Usselman Robert J. , Chavarriaga Cristina , Castello Pablo R. , Procopio Maria , Ritz Thorsten , Dratz Edward A. , Singel David J. , Martino Carlos F.
Published: December 2016

Quantum biology is the study of quantum effects on biochemical mechanisms and biological function. We show that the biological production of reactive oxygen species (ROS) in live cells can be influenced by coherent electron spin dynamics, providing a new example of quantum biology in cellular regulation. ROS partitioning appears to be mediated during the activation of molecular oxygen (O2) by reduced flavoenzymes, forming spin-correlated radical pairs (RPs). We find that oscillating magnetic fields at Zeeman resonance alter relative yields of cellular superoxide (O2•−) and hydrogen peroxide (H2O2) ROS products, indicating coherent singlet-triplet mixing at the point of ROS formation. Furthermore, the orientation-dependence of magnetic stimulation, which leads to specific changes in ROS levels, increases either mitochondrial respiration and glycolysis rates. Our results reveal quantum effects in live cell cultures that bridge atomic and cellular levels by connecting ROS partitioning to cellular bioenergetics.
TIARP attenuates autoantibody-mediated arthritis via the suppression of neutrophil migration by reducing CXCL2/CXCR2 and IL-6 expression
Authors: Inoue Asuka , Matsumoto Isao , Tanaka Yuki , Umeda Naoto , Takai Chinatsu , Kawaguchi Hoshimi , Ebe Hiroshi , Yoshida Hiroto , Matsumoto Yoshihiro , Segawa Seiji , Takahashi Satoru , Sumida Takayuki
Published: December 2016

TNFα-induced adipose-related protein (TIARP) is a six-transmembrane protein expressed on macrophages, neutrophils and synoviocytes. We reported recently that mice deficient in TIARP (TIARP−/−) spontaneously develop arthritis and are highly susceptible to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effects of TIARP on neutrophils and fibroblast-like synoviocytes (FLS) have not been elucidated. We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP−/− mice. Arthritis in TIARP−/− mice transferred with K/BxN serum was significantly exacerbated compared with WT mice. We characterized the differences in neutrophils between wild-type (WT) and TIARP−/− mice by DNA microarray. Overexpression of CXCR1 and CXCR2 was noted in TIARP−/− neutrophils. Neutrophils of TIARP−/− mice showed strong migration activity, which was markedly facilitated by CXCL2 in vitro and in vivo. Moreover, enhanced production of CXCL2 and IL-6 and cell proliferation was noted in TIARP−/− TNFα-stimulated FLS. Blockade of IL-6R significantly attenuated serum-transferred TIARP−/− arthritis with diminished neutrophil recruitment in joints. Our findings suggested that TIARP independently down-regulated CXCL2 and IL-6 production by FLS, and the expression of chemokine receptors (CXCR1 and CXCR2) in neutrophils, with resultant reduction of neutrophil migration into arthritic joints.
Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis
Authors: Celestino-Soper Patricia B. S. , Simpson Edward , Tumbleson Brink Danika , Lynnes Ty C. , Dlouhy Stephen , Vatta Matteo , Yeley Jana , Brown Cynthia , Bai Shaochun
Published: December 2016

Cystic fibrosis (CF) is an autosomal recessive disorder characterized by the accumulation of sticky and heavy mucus that can damage several organs. CF shows variable expressivity in affected individuals, but it typically causes respiratory and digestive complications as well as congenital bilateral absence of the vas deferens in males. Individuals with classic CF usually have variants that produce a defective protein from both alleles of the CFTR gene. Individuals with other variants may present with classic, non-classic, or milder forms of CF due to lower levels of functional CFTR protein. This article reports the genetic analysis of a female with features of asthma and mild or non-classic CF. CFTR sequencing demonstrated that she is a carrier for a maternally derived 5T/12TG variant. Deletion/duplication analysis by multiplex ligation-dependent probe amplification (MLPA) showed the presence of an intragenic paternally derived duplication involving exons 7–11 of the CFTR gene. This duplication is predicted to result in the production of a truncated CFTR protein lacking the terminal part of the nucleotide-binding domain 1 (NBD1) and thus is likely to be a non-functioning allele. The combination of this large intragenic duplication and 5T/12TG is the probable cause of the mild or non-classic CF features in this individual.
Intelligence and eeg measures of information flow: efficiency and homeostatic neuroplasticity
Authors: Thatcher R. W. , Palmero-Soler E. , North D. M. , Biver C. J.
Published: December 2016

The purpose of this study was to explore the relationship between the magnitude of EEG information flow and intelligence. The electroencephalogram (EEG) was recorded from 19 scalp locations from 371 subjects ranging in age from 5 years to 17.6 years. The Wechler Intelligence Scale for Children (WISC-R) was administered for individuals between 5 years of age and 16 years and the Weschler Adult Intelligence Scale revised (WAIS-R) was administered to subjects older than 16 years to estimate I.Q. The phase slope index estimated the magnitude of information flow between all electrode combinations for difference frequency bands. Discriminant analyses were performed between high I.Q. (>120) and low I.Q. groups (<90). The magnitude of information flow was inversely related to I.Q. especially in the alpha and beta frequency bands. Long distance inter-electrode distances exhibited greater information flow than short inter-electrode distances. Frontal-parietal correlations were the most significant. It is concluded that higher I.Q. is related to increased efficiency of local information processing and reduced long distance compensatory dynamics that supports a small-world model of intelligence.
Identification of an evolutionary conserved structural loop that is required for the enzymatic and biological function of tryptophan 2,3-dioxygenase
Authors: Michels Helen , Seinstra Renée I. , Uitdehaag Joost C. M. , Koopman Mandy , van Faassen Martijn , Martineau Céline N. , Kema Ido P. , Buijsman Rogier , Nollen Ellen A. A.
Published: December 2016

The enzyme TDO (tryptophan 2,3-dioxygenase; TDO-2 in Caenorhabditis elegans) is a potential therapeutic target to cancer but is also thought to regulate proteotoxic events seen in the progression of neurodegenerative diseases. To better understand its function and develop specific compounds that target TDO we need to understand the structure of this molecule. In C. elegans we compared multiple different CRISPR/Cas9-induced tdo-2 deletion mutants and identified a motif of three amino acids (PLD) that is required for the enzymatic conversion of tryptophan to N-formylkynurenine. Loss of TDO-2’s enzymatic activity in PDL deletion mutants was accompanied by an increase in motility during aging and a prolonged lifespan, which is in line with the previously observed phenotypes induced by a knockdown of the full enzyme. Comparison of sequence structures suggests that blocking this motif might interfere with haem binding, which is essential for the enzyme’s activity. The fact that these three residues are situated in an evolutionary conserved structural loop of the enzyme suggests that the findings can be translated to humans. The identification of this specific loop region in TDO-2–essential for its catalytic function–will aid in the design of novel inhibitors to treat diseases in which the TDO enzyme is overexpressed or hyperactive.
A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers
Authors: Espinoza J. Luis , Nguyen Viet H. , Ichimura Hiroshi , Pham Trang T. T. , Nguyen Cuong H. , Pham Thuc V. , Elbadry Mahmoud I. , Yoshioka Katsuji , Tanaka Junji , Trung Ly Q. , Takami Akiyoshi , Nakao Shinji
Published: December 2016

Human papillomavirus (HPV) is the most common sexually transmitted agent worldwide and is etiologically linked to several cancers, including cervical and genital cancers. NKG2D, an activating receptor expressed by NK cells, plays an important role in cancer immune-surveillance. We analyzed the impact of a NKG2D gene variant, rs1049174, on the incidence of HPV-related cancers in Vietnamese patients and utilized various molecular approaches to elucidate the mechanisms of NKG2D receptor regulation by rs1049174. In a group of 123 patients with HPV+ anogenital cancers, the low cytotoxicity allele LNK was significantly associated with increased cancer susceptibility (p = 0.016). Similar results were also observed in a group of 153 women with cervical cancer (p = 0.05). In functional studies, NK cells from individuals with LNK genotype showed a lower NKG2D expression and displayed less efficient NKG2D-mediated functions than NK cells with HNK genotype. Notably, the rs1049174 variant occurs within a targeting site for miR-1245, a negative regulator of NKG2D expression. Compared with the higher cytotoxicity allele HNK, the LNK allele was more efficiently targeted by miR-1245 and thus determined lower NKG2D expression in NK cells with the LNK genotype. The NKG2D variants may influence cancer immunosurveillance and thus determine susceptibility to various malignancies, including HPV-induced cancers.
Evidences for Piperine inhibiting cancer by targeting human G-quadruplex DNA sequences
Authors: Tawani Arpita , Amanullah Ayeman , Mishra Amit , Kumar Amit
Published: December 2016

Piperine, a naturally occurring alkaloid, is well known as anti-oxidant, anti-mutagenic, anti-tumor and anti-proliferative agent. Piperine exerts such pharmacological activities by binding or interacting with various cellular targets. Recently, the first report for Piperine interaction with duplex DNA has been published last year but its interaction with G-quadruplex structures has not been studied yet. Herein, we report for the first time the interaction of Piperine with various DNA G-quadruplex structures. Comprehensive biophysical techniques were employed to determine the basis of interaction for the complex formed between Piperine and G-quadruplex DNA sequences. Piperine showed specificity for G-quadruplex DNA over double stranded DNA, with highest affinity for G-quadruplex structure formed at c-myc promoter region. Further, in-vitro studies show that Piperine causes apoptosis-mediated cell death that further emphasizes the potential of this natural product, Piperine, as a promising candidate for targeting G-quadruplex structure and thus, acts as a potent anti-cancer agent.
Biliary Phospholipids Sustain Enterocyte Proliferation and Intestinal Tumor Progression via Nuclear Receptor Lrh1 in mice
Authors: Petruzzelli Michele , Piccinin Elena , Pinto Claudio , Peres Claudia , Bellafante Elena , Moschetta Antonio
Published: December 2016

The proliferative-crypt compartment of the intestinal epithelium is enriched in phospholipids and accumulation of phospholipids has been described in colorectal tumors. Here we hypothesize that biliary phospholipid flow could directly contribute to the proliferative power of normal and dysplastic enterocytes. We used Abcb4−/− mice which lack biliary phospholipid secretion. We first show that Abcb4−/− mice are protected against intestinal tumorigenesis. At the molecular level, the transcriptional activity of the nuclear receptor Liver Receptor Homolog-1 (Lrh1) is reduced in Abcb4−/− mice and its re-activation re-establishes a tumor burden comparable to control mice. Feeding Abcb4−/− mice a diet supplemented with phospholipids completely overcomes the intestinal tumor protective phenotype, thus corroborating the hypothesis that the absence of biliary phospholipids and not lack of Abcb4 gene per se is responsible for the protection. In turn, phospholipids cannot re-establish intestinal tumorigenesis in Abcb4−/− mice crossed with mice with intestinal specific ablation of Lrh1, a nuclear hormone receptor that is activates by phospholipids. Our data identify the key role of biliary phospholipids in sustaining intestinal mucosa proliferation and tumor progression through the activation of nuclear receptor Lrh1.
Iron arsenides with three-dimensional FeAs layer networks: Can(n+1)/2(Fe1−xPtx)(2+3n)Ptn(n−1)/2As(n+1)(n+2)/2 (n = 2, 3)
Authors: Katayama Naoyuki , Onari Seiichiro , Matsubayashi Kazuyuki , Uwatoko Yoshiya , Sawa Hiroshi
Published: December 2016

We report the comprehensive studies between synchrotron X-ray diffraction, electrical resistivity and magnetic susceptibility experiments for the iron arsenides Can(n+1)/2(Fe1−xPtx)(2+3n)Ptn(n−1)/2As(n+1)(n+2)/2 for n = 2 and 3. Both structures crystallize in the monoclinic space group P21/m (#11) with three-dimensional FeAs structures. The horizontal FeAs layers are bridged by inclined FeAs planes through edge-sharing FeAs5 square pyramids, resulting in triangular tunneling structures rather than the simple layered structures found in conventional iron arsenides. n = 3 system shows a sign of superconductivity with a small volume fraction. Our first-principles calculations of these systems clearly indicate that the Fermi surfaces originate from strong Fe-3d characters and the three-dimensional nature of the electric structures for both systems, thus offering the playgrounds to study the effects of dimensionality on high Tc superconductivity.
Purified Lesser weever fish venom (Trachinus vipera) induces eryptosis, apoptosis and cell cycle arrest
Authors: Fezai Myriam , Slaymi Chaker , Ben-Attia Mossadok , Lang Florian , Jemaà Mohamed
Published: December 2016

Accidents caused by the sting of Trachinus vipera (known as Lesser weever fish) are relatively common in shallow waters of the Mediterranean. Symptoms after the sting vary from severe pain to edema or even tissue necrosis in some cases. Here we show that purified Lesser weever fish venom induces eryptosis, the suicidal erythrocyte death, and apoptosis of human colon carcinoma cells. The venom leads to erythrocyte shrinkage, phosphatidylserine translocation and increased intracellular Ca2+, events typical for eryptosis. According to mitochondrial staining cancer cells dyed after the activation of the intrinsic apoptotic pathway. Trachinus vipera venom further causes cell cycle arrest.
Polarization shaping of high-order harmonics in laser-aligned molecules
Authors: Skantzakis E. , Chatziathanasiou S. , Carpeggiani P. A. , Sansone G. , Nayak A. , Gray D. , Tzallas P. , Charalambidis D. , Hertz E. , Faucher O.
Published: December 2016

The present work reports on the generation of short-pulse coherent extreme ultraviolet radiation of controlled polarization. The proposed strategy is based on high-order harmonics generated in pre-aligned molecules. Field-free molecular alignment produced by a short linearly-polarized infrared laser pulse is used to break the isotropy of a gas medium. Driving the aligned molecules by a circularly-polarized infrared pulse allows to transfer the anisotropy of the medium to the polarization of the generated harmonic light. The ellipticity of the latter is controlled by adjusting the angular distribution of the molecules at the time they interact with the driving pulse. Extreme ultraviolet radiation produced with high degree of ellipticity (close to circular) is demonstrated.
Yields and Nutritional of Greenhouse Tomato in Response to Different Soil Aeration Volume at two depths of Subsurface drip irrigation
Authors: Li Yuan , Niu Wenquan , Dyck Miles , Wang Jingwei , Zou Xiaoyang
Published: December 2016

This study investigated the effects of 4 aeration levels (varied by injection of air to the soil through subsurface irrigation lines) at two subsurface irrigation line depths (15 and 40 cm) on plant growth, yield and nutritional quality of greenhouse tomato. In all experiments, fruit number, width and length, yield, vitamin C, lycopene and sugar/acid ratio of tomato markedly increased in response to the aeration treatments. Vitamin C, lycopene, and sugar/acid ratio increased by 41%, 2%, and 43%, respectively, in the 1.5 times standard aeration volume compared with the no-aeration treatment. An interaction between aeration level and depth of irrigation line was also observed with yield, fruit number, fruit length, vitamin C and sugar/acid ratio of greenhouse tomato increasing at each aeration level when irrigation lines were placed at 40 cm depth. However, when the irrigation lines were 15 cm deep, the trend of total fruit yields, fruit width, fruit length and sugar/acid ratio first increased and then decreased with increasing aeration level. Total soluble solids and titrable acid decreased with increasing aeration level both at 15 and 40 cm irrigation line placement. When all of the quality factors, yields and economic benefit are considered together, the combination of 40 cm line depth and “standard” aeration level was the optimum combination.
Specific arrangements of species dominance can be more influential than evenness in maintaining ecosystem process and function
Authors: Wohlgemuth Daniel , Solan Martin , Godbold Jasmin A.
Published: December 2016

The ecological consequences of species loss are widely studied, but represent an end point of environmental forcing that is not always realised. Changes in species evenness and the rank order of dominant species are more widespread responses to directional forcing. However, despite the repercussions for ecosystem functioning such changes have received little attention. Here, we experimentally assess how the rearrangement of species dominance structure within specific levels of evenness, rather than changes in species richness and composition, affect invertebrate particle reworking and burrow ventilation behaviour - important moderators of microbial-mediated remineralisation processes in benthic environments - and associated levels of sediment nutrient release. We find that the most dominant species exert a disproportionate influence on functioning at low levels of evenness, but that changes in biomass distribution and a change in emphasis in species-environmental interactions become more important in governing system functionality as evenness increases. Our study highlights the need to consider the functional significance of alterations to community attributes, rather than to solely focus on the attainment of particular levels of diversity when safeguarding biodiversity and ecosystems that provide essential services to society.
Targeting bacterial adherence inhibits multidrug-resistant Pseudomonas aeruginosa infection following burn injury
Authors: Huebinger Ryan M. , Stones Daniel H. , de Souza Santos Marcela , Carlson Deborah L. , Song Juquan , Vaz Diana Pereira , Keen Emma , Wolf Steven E. , Orth Kim , Krachler Anne Marie
Published: December 2016

Classical antimicrobial drugs target proliferation and therefore place microbes under extreme selective pressure to evolve resistance. Alternative drugs that target bacterial virulence without impacting survival directly offer an attractive solution to this problem, but to date few such molecules have been discovered. We previously discovered a widespread group of bacterial adhesins, termed Multivalent Adhesion Molecules (MAMs) that are essential for initial binding of bacteria to host tissues and virulence. Thus, targeting MAM-based adherence is a promising strategy for displacing pathogens from host tissues and inhibiting infection. Here, we show that topical application of polymeric microbeads functionalized with the adhesin MAM7 to a burn infected with multidrug-resistant Pseudomonas aeruginosa substantially decreased bacterial loads in the wound and prevented the spread of the infection into adjacent tissues. As a consequence, the application of this adhesion inhibitor allowed for vascularization and wound healing, and maintained local and systemic inflammatory responses to the burn. We propose that MAM7-functionalized microbeads can be used as a topical treatment, to reduce bacterial attachment and hence prevent bacterial colonization and infection of wounds. As adhesion is not required for microbial survival, this anti-infective strategy has the potential to treat multidrug-resistant infections and limit the emergence of drug-resistant pathogens.
SLINGER: large-scale learning for predicting gene expression
Authors: Vervier Kévin , Michaelson Jacob J.
Published: December 2016

Recent studies have established that single nucleotide polymorphisms are sufficient to build accurate predictive models of gene expression. Gamazon, et al., found that gene expression values predicted from cis neighborhood SNPs show statistical association with disease status. In this work, we remove the cis neighborhood constraint during the learning process, and propose a novel predictive approach called SLINGER. We demonstrate that models drawing from a genome-wide set of SNPs are able to predict expression for more genes than the ones built on cis neighborhood only. Results indicate that these new models significantly improve accuracy for a large number of genes. Thanks to a penalized linear model, we also show that the number of features used in our models remains comparable to the cis-only models. Finally, SLINGER application on seven Wellcome Trust Case-Control Consortium genome-wide association studies demonstrate that compared to a cis-only approach, our models lead to associations with greater fidelity to actual gene expression values.
Public reporting as a prescriptions quality improvement measure in primary care settings in China: variations in effects associated with diagnoses
Authors: Tang Yuqing , Liu Chaojie , Zhang Xinping
Published: December 2016

The overprovision and irrational use of antibiotics and injections are a major public health concern. Public reporting has been adopted as a strategy to encourage good prescribing practices. This study evaluated the effects of public reporting on antibiotic and injection prescriptions in urban and rural primary care settings in Hubei province, China. A randomized control trial was conducted, with 10 primary care institutions being subject to public reporting and another 10 serving as controls. Prescription indicators were publicly reported monthly over a one-year period. Prescriptions for bronchitis, gastritis and hypertension before and after the intervention were collected. Difference-in-difference tests were performed to estimate the effect size of the intervention on five prescription indicators: percentage of prescriptions containing antibiotics; percentage of prescriptions containing two or more antibiotics; percentage of prescriptions containing injections; percentage of prescriptions containing antibiotic injections; and average prescription cost. Public reporting had varied effects on prescriptions for different diagnoses. It reduced antibiotic prescribing for gastritis. Prescriptions containing injections, especially antibiotic injections, also declined, but only for gastritis. A reduction of prescription costs was noted for bronchitis and gastritis. Public reporting has the potential to encourage good prescribing practices. Its effects vary with different disease conditions.
Prognostic value of pulmonary congestion assessed by lung ultrasound imaging during heart failure hospitalisation: A two-centre cohort study
Authors: Coiro Stefano , Porot Guillaume , Rossignol Patrick , Ambrosio Giuseppe , Carluccio Erberto , Tritto Isabella , Huttin Olivier , Lemoine Simon , Sadoul Nicolas , Donal Erwan , Zannad Faiez , Girerd Nicolas
Published: December 2016

Pulmonary congestion assessed at discharge by lung ultrasonography predicts poor prognosis in heart failure (HF) patients. We investigated the association of B-lines with indices of hemodynamic congestion [BNP, E/e’, pulmonary systolic arterial pressure (PAPs)] in HF patients, and their prognostic value overall and according to concomitant atrial fibrillation (AF), reduced (≤40%) ejection fraction (EF), and timing of quantification during hospitalisation for heart failure (HHF). In 110 HHF patients, B-lines were highly discriminative of BNP >400 pg/ml (AUC ≥ 0.80 for all), and moderately discriminative of PAPs >50 mmHg (AUC = 0.68, 0.56 to 0.80); conversely, B-lines poorly discriminated average E/e’ ≥ 15, except at discharge. B-line count significantly predicted mid-term recurrent HHF or death (overall and in subgroups), regardless of AF status, EF, and timing of quantification during HHF (all p for interaction >0.10). regardless, B-lines ≥30 at discharge were most predictive of outcome (HR = 7.11, 2.06–24.48; p = 0.002) while B-lines ≥45 early during HHF were most predictive of outcome (HR = 9.20, 1.82–46.61; p = 0.007). Lung ultrasound was able to identify patients with high BNP levels, but not with increased E/e’, also showing a prognostic role regardless of AF status, EF or timing of quantification; best B-line cut-off appears to vary according to the timing of quantification during hospitalization.
A Balanced Mixture of Antagonistic Pressures Promotes the Evolution of Parallel Movement
Authors: Demšar Jure , Štrumbelj Erik , Lebar Bajec Iztok
Published: December 2016

A common hypothesis about the origins of collective behaviour suggests that animals might live and move in groups to increase their chances of surviving predator attacks. This hypothesis is supported by several studies that use computational models to simulate natural evolution. These studies, however, either tune an ad-hoc model to ‘reproduce’ collective behaviour, or concentrate on a single type of predation pressure, or infer the emergence of collective behaviour from an increase in prey density. In nature, prey are often targeted by multiple predator species simultaneously and this might have played a pivotal role in the evolution of collective behaviour. We expand on previous research by using an evolutionary rule-based system to simulate the evolution of prey behaviour when prey are subject to multiple simultaneous predation pressures. We analyse the evolved behaviour via prey density, polarization, and angular momentum. Our results suggest that a mixture of antagonistic external pressures that simultaneously steer prey towards grouping and dispersing might be required for prey individuals to evolve dynamic parallel movement.
Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia
Authors: Qi Jian , Chen Chen , Meng Qing-Xi , Wu Yan , Wu Haitao , Zhao Ting-Bao
Published: December 2016

Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund’s Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression. And, microglia were also significantly activated with the presence of increased Iba-1 expression. Intrathecal administration of c-fos antisense oligodeoxynucleotides (ASO) or minocycline (a specific microglia inhibitor) attenuated mechanical allodynia. Moreover, intrathecal administration of c-fos ASO significantly suppressed the activation of neurons and microglia. Interestingly, inhibition of microglia activation by minocycline significantly suppressed the activation of both neurons and microglia in spinal dorsal horn. P38 inhibitor SB203580 suppressed IL-6 production, and inhibition of IL-6 receptor (IL-6R) activation by tocilizumab suppressed Fos expression. Together, our data suggest that the presence of a “crosstalk” between activated microglia and neurons in the spinal dorsal horn, which might contribute to the stress-induced hyperactivated state, leading to an increased pain sensitivity.
Preliminary effectiveness of breast cancer screening among 1.22 million Chinese females and different cancer patterns between urban and rural women
Authors: Huang Yubei , Dai Hongji , Song Fengju , Li Haixin , Yan Ye , Yang Zhenhua , Ye Zhaoxiang , Zhang Sheng , Liu Hong , Cao Yali , Xiong Li , Luo Yahong , Pan Tie , Ma Xiangjun , Wang Jie , Song Xiuling , Leng Ling , Zhang Yeping , Sun Jie , Wang Jialin , Ma Hengmin , Kong Lingzhi , Lei Zhenglong , Wang Yaogang , Peishan Wang , Han Jiali , Hao Xishan , Chen Kexin
Published: December 2016

To determine the preliminary effectiveness of breast cancer screening among Chinese females, 1226714 women aged 35–69 years first received clinical breast examinations. Urban women with suspected cancer received mammography followed by breast ultrasound (BUS), while rural suspected women underwent BUS followed by mammography. After one-year follow-up, 223 and 431 breast cancers were detected among urban and rural women (respectively), with overall detection rates of 0.56/1000 and 0.52/1000. Higher detection rates were significantly associated with older age at screening for both urban and rural women; additionally, urban women were at significantly higher risk if they had no job, no insurance, or were obese; additional risk factors specific to rural women included Han nationality, higher income, being unmarried, and having a family history of cancer (all P values < 0.05). Among screening-detected breast cancers in urban vs. rural women, 46.2% and 38.8% (respectively) were early stage, 62.5% and 66.3% were ≤2 centimeters, 38.0% and 47.3% included lymph-node involvement, and 14.0% and 6.0% were identified as carcinoma in situ. All abovementioned cancer characteristics were significantly better than clinic-detected cancers (all P values < 0.001). In conclusion, several important differences were found between urban and rural women in screening effectiveness and patterns of cancer distribution.