bluuebunny/crossref_metadata_2025 huggingface dataset:
Ack promotes tissue growth via phosphorylation and suppression of the Hippo pathway component Expanded
Authors: Hu Lianxin , Xu Jiajun , Yin Meng-Xin , Zhang Liguo , Lu Yi , Wu Wenqing , Xue Zhaoyu , Ho Margaret S , Gao Guanjun , Zhao Yun , Zhang Lei
Published: February 2016

Non-receptor tyrosine kinase activated cdc42 kinase was reported to participate in several types of cancers in mammals. It is also believed to have an anti-apoptotic function inDrosophila. Here, we report the identification ofDrosophilaactivated cdc42 kinase as a growth promoter and a novel Hippo signaling pathway regulator. We find that activated cdc42 kinase promotes tissue growth through modulating Yorkie activity. Furthermore, we demonstrate that activated cdc42 kinase interacts with Expanded and induces tyrosine phosphorylation of Expanded on multiple sites. We propose a model that activated cdc42 kinase negatively regulates Expanded by changing its phosphorylation status to promote tissue growth. Moreover, we show thatackgenetically interacts withmerlinandexpanded. Thus, we identifyDrosophilaactivated cdc42 kinase as a Hippo pathway regulator.
Correlation detection strategies in microbial data sets vary widely in sensitivity and precision
Authors: Weiss Sophie , Van Treuren Will , Lozupone Catherine , Faust Karoline , Friedman Jonathan , Deng Ye , Xia Li Charlie , Xu Zhenjiang Zech , Ursell Luke , Alm Eric J , Birmingham Amanda , Cram Jacob A , Fuhrman Jed A , Raes Jeroen , Sun Fengzhu , Zhou Jizhong , Knight Rob
Published: February 2016

Disruption of healthy microbial communities has been linked to numerous diseases, yet microbial interactions are little understood. This is due in part to the large number of bacteria, and the much larger number of interactions (easily in the millions), making experimental investigation very difficult at best and necessitating the nascent field of computational exploration through microbial correlation networks. We benchmark the performance of eight correlation techniques on simulated and real data in response to challenges specific to microbiome studies: fractional sampling of ribosomal RNA sequences, uneven sampling depths, rare microbes and a high proportion of zero counts. Also tested is the ability to distinguish signals from noise, and detect a range of ecological and time-series relationships. Finally, we provide specific recommendations for correlation technique usage. Although some methods perform better than others, there is still considerable need for improvement in current techniques.
An interactive web-based application for Comprehensive Analysis of RNAi-screen Data
Authors: Dutta Bhaskar , Azhir Alaleh , Merino Louis-Henri , Guo Yongjian , Revanur Swetha , Madhamshettiwar Piyush B. , Germain Ronald N. , Smith Jennifer A. , Simpson Kaylene J. , Martin Scott E. , Buehler Eugen , Fraser Iain D. C.
Published: February 2016

RNAi screens are widely used in functional genomics. Although the screen data can be susceptible to a number of experimental biases, many of these can be corrected by computational analysis. For this purpose, here we have developed a web-based platform for integrated analysis and visualization of RNAi screen data named CARD (for Comprehensive Analysis of RNAi Data; available at https://card.niaid.nih.gov). CARD allows the user to seamlessly carry out sequential steps in a rigorous data analysis workflow, including normalization, off-target analysis, integration of gene expression data, optimal thresholds for hit selection and network/pathway analysis. To evaluate the utility of CARD, we describe analysis of three genome-scale siRNA screens and demonstrate: (i) a significant increase both in selection of subsequently validated hits and in rejection of false positives, (ii) an increased overlap of hits from independent screens of the same biology and (iii) insight to microRNA (miRNA) activity based on siRNA seed enrichment.
Fear of large carnivores causes a trophic cascade
Authors: Suraci Justin P. , Clinchy Michael , Dill Lawrence M. , Roberts Devin , Zanette Liana Y.
Published: February 2016

The fear large carnivores inspire, independent of their direct killing of prey, may itself cause cascading effects down food webs potentially critical for conserving ecosystem function, particularly by affecting large herbivores and mesocarnivores. However, the evidence of this has been repeatedly challenged because it remains experimentally untested. Here we show that experimentally manipulating fear itself in free-living mesocarnivore (raccoon) populations using month-long playbacks of large carnivore vocalizations caused just such cascading effects, reducing mesocarnivore foraging to the benefit of the mesocarnivore’s prey, which in turn affected a competitor and prey of the mesocarnivore’s prey. We further report that by experimentally restoring the fear of large carnivores in our study system, where most large carnivores have been extirpated, we succeeded in reversing this mesocarnivore’s impacts. We suggest that our results reinforce the need to conserve large carnivores given the significant “ecosystem service” the fear of them provides.
Localized soft elasticity in liquid crystal elastomers
Authors: Ware Taylor H. , Biggins John S. , Shick Andreas F. , Warner Mark , White Timothy J.
Published: February 2016

Synthetic approaches to prepare designer materials that localize deformation, by combining rigidity and compliance in a single material, have been widely sought. Bottom-up approaches, such as the self-organization of liquid crystals, offer potential advantages over top–down patterning methods such as photolithographic control of crosslink density, relating to the ease of preparation and fidelity of resolution. Here, we report on the directed self-assembly of materials with spatial and hierarchical variation in mechanical anisotropy. The highly nonlinear mechanical properties of the liquid crystalline elastomers examined here enables strain to be locally reduced >15-fold without introducing compositional variation or other heterogeneities. Each domain (⩾0.01 mm2) exhibits anisotropic nonlinear response to load based on the alignment of the molecular orientation with the loading axis. Accordingly, we design monoliths that localize deformation in uniaxial and biaxial tension, shear, bending and crack propagation, and subsequently demonstrate substrates for globally deformable yet locally stiff electronics.
Investigation on the effects of the atmospheric pressure plasma on wound healing in diabetic rats
Authors: Fathollah Sara , Mirpour Shahriar , Mansouri Parvin , Dehpour Ahmad Reza , Ghoranneviss Mahmood , Rahimi Nastaran , Safaie Naraghi Zahra , Chalangari Reza , Chalangari Katalin Martits
Published: February 2016

It is estimated that 15 percent of individuals with diabetes mellitus suffer from diabetic ulcers worldwide. The aim of this study is to present a non-thermal atmospheric plasma treatment as a novel therapy for diabetic wounds. The plasma consists of ionized helium gas that is produced by a high-voltage (8 kV) and high-frequency (6 kHz) power supply. Diabetes was induced in rats via an intravascular injection of streptozotocin. The plasma was then introduced to artificial xerograph wounds in the rats for 10 minutes. Immunohistochemistry assays was performed to determine the level of transforming growth factor (TGF-β1) cytokine. The results showed a low healing rate in the diabetic wounds compared with the wound-healing rate in non-diabetic animals (P < 0.05). Moreover, the results noted that plasma enhanced the wound-healing rate in the non-diabetic rats (P < 0.05) and significant wound contraction occurred after the plasma treatment compared with untreated diabetic wounds (P < 0.05). Histological analyses revealed the formation of an epidermis layer, neovascularization and cell proliferation. The plasma treatment also resulted in the release of TGF-β1 cytokine from cells in the tissue medium. The findings of this study demonstrate the effect of plasma treatment for wound healing in diabetic rats.
A bizarre theropod from the Early Cretaceous of Japan highlighting mosaic evolution among coelurosaurians
Authors: Azuma Yoichi , Xu Xing , Shibata Masateru , Kawabe Soichiro , Miyata Kazunori , Imai Takuya
Published: February 2016

Our understanding of coelurosaurian evolution, particularly of bird origins, has been greatly improved, mainly due to numerous recently discovered fossils worldwide. Nearly all these discoveries are referable to the previously known coelurosaurian subgroups. Here, we report a new theropod,Fukuivenator paradoxus, gen. et sp. nov., based on a nearly complete specimen from the Lower Cretaceous Kitadani Formation of the Tetori Group, Fukui, Japan. WhileFukuivenatorpossesses a large number of morphological features unknown in any other theropod, it has a combination of primitive and derived features seen in different theropod subgroups, notably dromaeosaurid dinosaurs. Computed-tomography data indicate thatFukuivenatorpossesses inner ears whose morphology is intermediate between those of birds and non-avian dinosaurs. Our phylogenetic analysis recoversFukuivenatoras a basally branching maniraptoran theropod, yet is unable to refer it to any known coelurosaurian subgroups. The discovery ofFukuivenatorconsiderably increases the morphological disparity of coelurosaurian dinosaurs and highlights the high levels of homoplasy in coelurosaurian evolution.
Reversed ageing of Fe3O4 nanoparticles by hydrogen plasma
Authors: Schmitz-Antoniak Carolin , Schmitz Detlef , Warland Anne , Svechkina Nataliya , Salamon Soma , Piamonteze Cinthia , Wende Heiko
Published: February 2016

Magnetite (Fe3O4) nanoparticles suffer from severe ageing effects when exposed to air even when they are dispersed in a solvent limiting their applications. In this work, we show that this ageing can be fully reversed by a hydrogen plasma treatment. By x-ray absorption spectroscopy and its associated magnetic circular dichroism, the electronic structure and magnetic properties were studied before and after the plasma treatment and compared to results of freshly prepared magnetite nanoparticles. While aged magnetite nanoparticles exhibit a more γ-Fe2O3 like behaviour, the hydrogen plasma yields pure Fe3O4 nanoparticles. Monitoring the temperature dependence of the intra-atomic spin dipole contribution to the dichroic spectra gives evidence that the structural, electronic and magnetic properties of plasma treated magnetite nanoparticles can outperform the ones of the freshly prepared batch.
Quantitative Histomorphometry of the Healthy Peritoneum
Authors: Schaefer Betti , Bartosova Maria , Macher-Goeppinger Stephan , Ujszaszi Akos , Wallwiener Markus , Nyarangi-Dix Joanne , Sallay Peter , Burkhardt Dorothea , Querfeld Uwe , Pfeifle Viktoria , Lahrmann Bernd , Schwenger Vedat , Wühl Elke , Holland-Cunz Stefan , Schaefer Franz , Schmitt Claus P.
Published: February 2016

The peritoneum plays an essential role in preventing abdominal frictions and adhesions and can be utilized as a dialysis membrane. Its physiological ultrastructure, however, has not yet been studied systematically. 106 standardized peritoneal and 69 omental specimens were obtained from 107 patients (0.1–60 years) undergoing surgery for disease not affecting the peritoneum for automated quantitative histomorphometry and immunohistochemistry. The mesothelial cell layer morphology and protein expression pattern is similar across all age groups. Infants below one year have a thinner submesothelium; inflammation, profibrotic activity and mesothelial cell translocation is largely absent in all age groups. Peritoneal blood capillaries, lymphatics and nerve fibers locate in three distinct submesothelial layers. Blood vessel density and endothelial surface area follow a U-shaped curve with highest values in infants below one year and lowest values in children aged 7–12 years. Lymphatic vessel density is much lower and again highest in infants. Omental blood capillary density correlates with parietal peritoneal findings, whereas only few lymphatic vessels are present. The healthy peritoneum exhibits major thus far unknown particularities, pertaining to functionally relevant structures and subject to substantial changes with age. The reference ranges established here provide a framework for future histomorphometric analyses and peritoneal transport modeling approaches.
High-energy X-ray focusing and applications to pair distribution function investigation of Pt and Au nanoparticles at high pressures
Authors: Hong Xinguo , Ehm Lars , Zhong Zhong , Ghose Sanjit , Duffy Thomas S. , Weidner Donald J.
Published: February 2016

We report development of micro-focusing optics for high-energy x-rays by combining a sagittally bent Laue crystal monchromator with Kirkpatrick-Baez (K–B) X-ray focusing mirrors. The optical system is able to provide a clean, high-flux X-ray beam suitable for pair distribution function (PDF) measurements at high pressure using a diamond anvil cell (DAC). A focused beam of moderate size (10–15 μm) has been achieved at energies of 66 and 81 keV. PDF data for nanocrystalline platinum (n-Pt) were collected at 12.5 GPa with a single 5 s X-ray exposure, showing that the in-situ compression, decompression and relaxation behavior of samples in the DAC can be investigated with this technique. PDFs of n-Pt and nano Au (n-Au) under quasi-hydrostatic loading to as high as 71 GPa indicate the existence of substantial reduction of grain or domain size for Pt and Au nanoparticles at pressures below 10 GPa. The coupling of sagittally bent Laue crystals with K–B mirrors provides a useful means to focus high-energy synchrotron X-rays from a bending magnet or wiggler source.
Evaluating the Small-World-Ness of a Sampled Network: Functional Connectivity of Entorhinal-Hippocampal Circuitry
Authors: She Qi , Chen Guanrong , Chan Rosa H. M.
Published: February 2016

The amount of publicly accessible experimental data has gradually increased in recent years, which makes it possible to reconsider many longstanding questions in neuroscience. In this paper, an efficient framework is presented for reconstructing functional connectivity using experimental spike-train data. A modified generalized linear model (GLM) with L1-norm penalty was used to investigate 10 datasets. These datasets contain spike-train data collected from the entorhinal-hippocampal region in the brains of rats performing different tasks. The analysis shows that entorhinal-hippocampal network of well-trained rats demonstrated significant small-world features. It is found that the connectivity structure generated by distance-dependent models is responsible for the observed small-world features of the reconstructed networks. The models are utilized to simulate a subset of units recorded from a large biological neural network using multiple electrodes. Two metrics for quantifying the small-world-ness both suggest that the reconstructed network from the sampled nodes estimates a more prominent small-world-ness feature than that of the original unknown network when the number of recorded neurons is small. Finally, this study shows that it is feasible to adjust the estimated small-world-ness results based on the number of neurons recorded to provide a more accurate reference of the network property.
Intraoperative Dexmedetomidine Promotes Postoperative Analgesia and Recovery in Patients after Abdominal Hysterectomy: a Double-Blind, Randomized Clinical Trial
Authors: Ge Dong-Jian , Qi Bin , Tang Gang , Li Jin-Yu
Published: February 2016

Surgery-induced acute postoperative pain and stress response can lead to prolonged convalescence. The present study was designed to investigate the effects of intraoperative dexmedetomidine on postoperative analgesia and recovery following abdominal hysterectomy surgeries. Sixty-four patients scheduled for abdominal hysterectomy under general anesthesia were divided into two groups that were maintained using propofol/remifentanil/dexmedetomidine (PRD) or propofol/remifentanil/saline (PRS). During surgery, patients in the PRD group had a lower bispectral index (BIS) value, which indicated a deeper anesthetic state, and a higher sedation score immediately after extubation than patients in the PRS group. During the first 24 hours post-surgery, PRD patients consumed less morphine with patient-controlled analgesia (PCA) and had lower scores on a visual analogue scale (VAS) than their controls from the PRS group. The global 40-item quality of recovery questionnaire and 9-question fatigue severity score both showed higher recovery scores from day 3 after surgery in the PRD group. with the data are considered together, intraoperative administration of dexmedetomidine appeared to promote the analgesic properties of morphine-based PCA and to expedite recovery following surgery in patients undergoing abdominal hysterectomy.
Bioconversion of methane to lactate by an obligate methanotrophic bacterium
Authors: Henard Calvin A. , Smith Holly , Dowe Nancy , Kalyuzhnaya Marina G. , Pienkos Philip T. , Guarnieri Michael T.
Published: February 2016

Methane is the second most abundant greenhouse gas (GHG), with nearly 60% of emissions derived from anthropogenic sources. Microbial conversion of methane to fuels and value-added chemicals offers a means to reduce GHG emissions, while also valorizing this otherwise squandered high-volume, high-energy gas. However, to date, advances in methane biocatalysis have been constrained by the low-productivity and limited genetic tractability of natural methane-consuming microbes. Here, leveraging recent identification of a novel, tractable methanotrophic bacterium, Methylomicrobium buryatense, we demonstrate microbial biocatalysis of methane to lactate, an industrial platform chemical. Heterologous overexpression of a Lactobacillus helveticus L-lactate dehydrogenase in M. buryatense resulted in an initial titer of 0.06 g lactate/L from methane. Cultivation in a 5 L continuously stirred tank bioreactor enabled production of 0.8 g lactate/L, representing a 13-fold improvement compared to the initial titer. The yields (0.05 g lactate/g methane) and productivity (0.008 g lactate/L/h) indicate the need and opportunity for future strain improvement. Additionally, real-time analysis of methane utilization implicated gas-to-liquid transfer and/or microbial methane consumption as process limitations. This work opens the door to develop an array of methanotrophic bacterial strain-engineering strategies currently employed for biocatalytic sugar upgrading to “green” chemicals and fuels.
PE11, a PE/PPE family protein of Mycobacterium tuberculosis is involved in cell wall remodeling and virulence
Authors: Singh Parul , Rao Rameshwaram Nagender , Reddy Jala Ram Chandra , Prasad RBN , Kotturu Sandeep Kumar , Ghosh Sudip , Mukhopadhyay Sangita
Published: February 2016

The role of the unique proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins in the pathophysiology and virulence ofMycobacterium tuberculosisis not clearly understood. One of the PE family proteins, PE11 (LipX or Rv1169c), specific to pathogenic mycobacteria is found to be over-expressed during infection of macrophages and in active TB patients. In this study, we report thatM. smegmatisexpressing PE11 (Msmeg-PE11) exhibited altered colony morphology and cell wall lipid composition leading to a marked increase in resistance against various environmental stressors and antibiotics. The cell envelope ofMsmeg-PE11also had greater amount of glycolipids and polar lipids.Msmeg-PE11was found to have better survival rate in infected macrophages. Mice infected withMsmeg-PE11had higher bacterial load, showed exacerbated organ pathology and mortality. The liver and lung ofMsmeg-PE11-infected mice also had higher levels of IL-10, IL-4 and TNF-α cytokines, indicating a potential role of this protein in mycobacterial virulence.
The role of WWOX polymorphisms on COPD susceptibility and pulmonary function traits in Chinese: a case-control study and family-based analysis
Authors: Xie Chenli , Chen Xiaoliang , Qiu Fuman , Zhang Lisha , Wu Di , Chen Jiansong , Yang Lei , Lu Jiachun
Published: February 2016

Single nucleotide polymorphisms (SNPs) in the WW domain containing oxidoreductase (WWOX) gene were recently identified to be quantitative trait loci for lung function and thus likely to be susceptible biomarkers for COPD. However, the associations between WWOX SNPs and COPD risk are still unclear. Here, by conducting a two-center case-control study including 1511 COPD cases and 1677 controls and a family-based analysis comprising 95 nuclear pedigrees, we tested the associations between five SNPs that are rs10220974C >T, rs3764340C >G, rs12918952G >A, rs383362G >T, rs12828G >A of WWOX and COPD risk as well as the hereditary inclination of these loci among COPD families. We found that the SNP rs383362G >T was significantly associated with an increased risk of COPD in a T allele-number dependent-manner (OR = 1.30, 95%CI = 1.11 - 1.52). The T allele was more prone to over transmit to sick children and sibs than the G allele (Z = 2.900, P = 0.004). Moreover, the forced expiratory volume in one second/forced vital capacity (FEV1/FVC), FEV1/predicted-FEV1 and annual FEV1 also significantly decreased in the rs383362T carriers compared to the rs383362GG carriers. For other SNPs, no significant association was observed for COPD and pulmonary function. Taken together, our data demonstrated that the SNP rs383362G >T of WWOX plays a role in COPD inheritance.
Differences on photosynthetic limitations between leaf margins and leaf centers under potassium deficiency for Brassica napus L.
Authors: Lu Zhifeng , Ren Tao , Pan Yonghui , Li Xiaokun , Cong Rihuan , Lu Jianwei
Published: February 2016

Analyzing the proportions of stomatal (SL), mesophyll conductance (MCL) and biochemical limitations (BL) imposed by potassium (K) deficit and evaluating their relationships to leaf K status will be helpful to understand the mechanism underlying the inhibition of K deficiency on photosynthesis (A). A quantitative limitation analysis of K deficiency on photosynthesis was performed on leaf margins and centers under K deficiency and sufficient K supply treatments of Brassica napus L. Potassium deficiency decreased A, stomatal (gs) and mesophyll conductance (gm) of margins, SL, MCL and BL accounted for 23.9%, 33.0% and 43.1% of the total limitations. While for leaf centers, relatively low limitations occurred. Nonlinear curve fitting analysis indicated that each limiting factor generated at same leaf K status (1.07%). Although MCL was the main component of limitations when A began to fall, BL replaced it at a leaf K concentration below 0.78%. Up-regulated MCL was related to lower surface area of chloroplasts exposed to intercellular airspaces (Sc/S) and larger cytosol diffusion resistance but not the cell wall thickness. Our results highlighted that photosynthetic limitations appear simultaneously under K deficiency and vary with increasing K deficiency intensity.
Genetic editing of HLA expression in hematopoietic stem cells to broaden their human application
Authors: Torikai Hiroki , Mi Tiejuan , Gragert Loren , Maiers Martin , Najjar Amer , Ang Sonny , Maiti Sourindra , Dai Jianliang , Switzer Kirsten C. , Huls Helen , Dulay Gladys P. , Reik Andreas , Rebar Edward J. , Holmes Michael C. , Gregory Philip D. , Champlin Richard E. , Shpall Elizabeth J. , Cooper Laurence J. N.
Published: February 2016

Mismatch of human leukocyte antigens (HLA) adversely impacts the outcome of patients after allogeneic hematopoietic stem-cell transplantation (alloHSCT). This translates into the clinical requirement to timely identify suitable HLA-matched donors which in turn curtails the chances of recipients, especially those from a racial minority, to successfully undergo alloHSCT. We thus sought to broaden the existing pool of registered unrelated donors based on analysis that eliminating the expression of the HLA-A increases the chance for finding a donor matched at HLA-B, -C and -DRB1 regardless of a patient’s race. Elimination of HLA-A expression in HSC was achieved using artificial zinc finger nucleases designed to target HLA-A alleles. Significantly, these engineered HSCs maintain their ability to engraft and reconstitute hematopoiesis in immunocompromised mice. This introduced loss of HLA-A expression decreases the need to recruit large number of donors to match with potential recipients and has particular importance for patients whose HLA repertoire is under-represented in the current donor pool. Furthermore, the genetic engineering of stem cells provides a translational approach to HLA-match a limited number of third-party donors with a wide number of recipients.
Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition
Authors: Park Dohyun , Jeong Heeyoon , Lee Mi Nam , Koh Ara , Kwon Ohman , Yang Yong Ryoul , Noh Jungeun , Suh Pann-Ghill , Park Hwangseo , Ryu Sung Ho
Published: February 2016

Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction.
Plasmodium falciparum PfSET7: enzymatic characterization and cellular localization of a novel protein methyltransferase in sporozoite, liver and erythrocytic stage parasites
Authors: Chen Patty B. , Ding Shuai , Zanghì Gigliola , Soulard Valérie , DiMaggio Peter A. , Fuchter Matthew J. , Mecheri Salah , Mazier Dominique , Scherf Artur , Malmquist Nicholas A.
Published: February 2016

Epigenetic control via reversible histone methylation regulates transcriptional activation throughout the malaria parasite genome, controls the repression of multi-copy virulence gene families and determines sexual stage commitment. Plasmodium falciparum encodes ten predicted SET domain-containing protein methyltransferases, six of which have been shown to be refractory to knock-out in blood stage parasites. We have expressed and purified the first recombinant malaria methyltransferase in sufficient quantities to perform a full enzymatic characterization and reveal the ill-defined PfSET7 is an AdoMet-dependent histone H3 lysine methyltransferase with highest activity towards lysines 4 and 9. Steady-state kinetics of the PfSET7 enzyme are similar to previously characterized histone methyltransferase enzymes from other organisms, however, PfSET7 displays specific protein substrate preference towards nucleosomes with pre-existing histone H3 lysine 14 acetylation. Interestingly, PfSET7 localizes to distinct cytoplasmic foci adjacent to the nucleus in erythrocytic and liver stage parasites and throughout the cytoplasm in salivary gland sporozoites. Characterized recombinant PfSET7 now allows for target based inhibitor discovery. Specific PfSET7 inhibitors can aid in further investigating the biological role of this specific methyltransferase in transmission, hepatic and blood stage parasites and may ultimately lead to the development of suitable antimalarial drug candidates against this novel class of essential parasite enzymes.
Pressure dependence of electronic structure and superconductivity of the MnX (X = N, P, As, Sb)
Authors: Chong XiaoYu , Jiang YeHua , Zhou Rong , Feng Jing
Published: February 2016

A recently experimental discovered (Cheng et al., Phys. Rev. Lett. 114, 117001 (2015)) of superconductivity on the border of long-range magnetic order in the itinerant-electron helimagnet MnP via the application of high pressure makes MnP the first Mn-based superconductor. In this paper, we carry out first-principles calculations on MnX (X = N, P, As, Sb) and find superconducting critical temperature TC of MnP sharply increases near the critical pressure PC ≈ 8 GPa, which is in good agreement with the experiments. Electron-phonon coupling constant λ and electronic density of states at the Fermi level N (EF) are found to increase with pressure for MnP, which lead to the increase of TC of MnP. Moreover, we also find that the TC of MnAs and MnSb are higher than MnP, implying that the MnAs and MnSb may be the more potential Mn-based superconducting materials.
Low-temperature growth of layered molybdenum disulphide with controlled clusters
Authors: Mun Jihun , Kim Yeongseok , Kang Il-Suk , Lim Sung Kyu , Lee Sang Jun , Kim Jeong Won , Park Hyun Min , Kim Taesung , Kang Sang-Woo
Published: February 2016

Layered molybdenum disulphide was grown at a low-temperature of 350 °C using chemical vapour deposition by elaborately controlling the cluster size. The molybdenum disulphide grown under various sulphur-reaction-gas to molybdenum-precursor partial-pressure ratios were examined. Using spectroscopy and microscopy, the effect of the cluster size on the layered growth was investigated in terms of the morphology, grain size, and impurity incorporation. Triangular single-crystal domains were grown at an optimized sulphur-reaction-gas to molybdenum-precursor partial-pressure ratio. Furthermore, it is proved that the nucleation sites on the silicon-dioxide substrate were related with the grain size. A polycrystalline monolayer with the 100-nm grain size was grown on a nucleation site confined substrate by high-vacuum annealing. In addition, a field-effect transistor was fabricated with a MoS2 monolayer and exhibited a mobility and on/off ratio of 0.15 cm2 V−1 s−1 and 105, respectively.
Sirt1 AS lncRNA interacts with its mRNA to inhibit muscle formation by attenuating function of miR-34a
Authors: Wang Guo-qiang , Wang Yu , Xiong Yan , Chen Xiao-Chang , Ma Mei-ling , Cai Rui , Gao Yun , Sun Yun-mei , Yang Gong-She , Pang Wei-Jun
Published: February 2016

Recent studies demonstrate the functions of long non-coding RNAs (lncRNAs) in mediating gene expression at the transcriptional or translational level. Our previous study identified a Sirt1 antisense (AS) lncRNA transcribed from the Sirt1 AS strand. However, its role and regulatory mechanism is still unknown in myogenesis. Here, functional analyses showed that Sirt1 AS lncRNA overexpression promoted myoblast proliferation, but inhibited differentiation. Mechanistically, Sirt1 AS lncRNA was found to activate its sense gene, Sirt1. The luciferase assay provided evidences that Sirt1 AS lncRNA interacted with Sirt1 3′ UTR and rescued Sirt1 transcriptional suppression by competing with miR-34a. In addition, RNA stability assay showed that Sirt1 AS lncRNA prolonged Sirt1 mRNA half-life from 2 to 10 h. Ribonuclease protection assay further indicated that it fully bound to Sirt1 mRNA in the myoblast cytoplasm. Moreover, Sirt1 AS overexpression led to less mouse weight than the control because of less lean mass and greater levels of Sirt1, whereas the fat mass and levels of miR-34a were not altered. Based on the findings, a novel regulatory mechanism was found that Sirt1 AS lncRNA preferably interacted with Sirt1 mRNA forming RNA duplex to promote Sirt1 translation by competing with miR-34a, inhibiting muscle formation.
Hepatic fat content is a determinant of metabolic phenotypes and increased carotid intima-media thickness in obese adults
Authors: Zhang Huijie , Ma Zhimin , Pan Lingling , Xu Yanfang , Shao Jin , Huang Zhufeng , Chen Zheng , Sun Qian , Liu Changqin , Lin Mingzhu , Yang Shuyu , Li Xuejun
Published: February 2016

Individuals with metabolically healthy obesity (MHO) are at relatively low risk for the development of metabolic abnormalities and subclinical atherosclerosis. This study aims to examine whether hepatic fat accumulation determines metabolic phenotype of obesity and associated with subclinical atherosclerosis. A total of 485 obese adults (aged 40–65 years) who received magnetic resonance spectroscopy were divided into metabolically abnormally obesity (MAO) and MHO groups according to metabolic status. MHO individuals had lower levels of intrahepatic triglyceride (IHTG) content and carotid intima-media thickness (CIMT) than MAO individuals. In multivariable linear regression analyses, IHTG content was independently associated with metabolic syndrome components and CIMT. Based on receiver operating characteristic curve analysis, the IHTG content displayed a higher area under the curve (AUC) for detecting the MAO phenotype (AUC = 0.70, 95%CI = 0.65–0.75) and increased CIMT (AUC = 0.60, 95%CI = 0.54–0.66) than BMI, waist circumference and body fat percent. MHO individuals were 1.9 times (p < 0.001) more likely to have metabolic syndrome per 1 SD change in IHTG content in multivariable-adjusted models. Likewise, the risk for high CIMT increased 29% per 1 SD change in IHTG content [OR (95% CI):1.29(1.01–1.64)]. These findings suggest that hepatic fat is a potential predictor of metabolically unhealthy obesity phenotype and subclinical atherosclerosis.
The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B
Authors: Lu Shaoyong , Jang Hyunbum , Nussinov Ruth , Zhang Jian
Published: February 2016

Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP–GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer.
Disentangling the determinants of species richness of vascular plants and mammals from national to regional scales
Authors: Xu Haigen , Cao Mingchang , Wu Yi , Cai Lei , Cao Yun , Wu Jun , Lei Juncheng , Le Zhifang , Ding Hui , Cui Peng
Published: February 2016

Understanding the spatial patterns in species richness gets new implication for biodiversity conservation in the context of climate change and intensified human intervention. Here, we created a database of the geographical distribution of 30,519 vascular plant species and 565 mammal species from 2,376 counties across China and disentangled the determinants that explain species richness patterns both at national and regional scales using spatial linear models. We found that the determinants of species richness patterns varied among regions: elevational range was the most powerful predictor for the species richness of plants and mammals across China. However, species richness patterns in the Qinghai-Tibetan Plateau Region (QTR) are quite unique, where net primary productivity was the most important predictor. We also detected that elevational range was positively related to plant species richness when it is less than 1,900 m, whereas the relationship was not significant when elevational range is larger than 1,900 m. It indicated that elevational range often emerges as the predominant controlling factor within the regions where energy is sufficient. The effects of land use on mammal species richness should attract special attention. Our study suggests that region-specific conservation policies should be developed based on the regional features of species richness.
Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement
Authors: Looi Chung Yen , Duta Mihaela , Brem Anna-Katharine , Huber Stefan , Nuerk Hans-Christoph , Cohen Kadosh Roi
Published: February 2016

Cognitive training offers the potential for individualised learning, prevention of cognitive decline and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.
Colour Polymorphism Protects Prey Individuals and Populations Against Predation
Authors: Karpestam Einat , Merilaita Sami , Forsman Anders
Published: February 2016

Colour pattern polymorphism in animals can influence and be influenced by interactions between predators and prey. However, few studies have examined whether polymorphism is adaptive and there is no evidence that the co-occurrence of two or more natural prey colour variants can increase survival of populations. Here we show that visual predators that exploit polymorphic prey suffer from reduced performance and further provide rare evidence in support of the hypothesis that prey colour polymorphism may afford protection against predators for both individuals and populations. This protective effect provides a probable explanation for the longstanding, evolutionary puzzle of the existence of colour polymorphisms. We also propose that this protective effect can provide an adaptive explanation for search image formation in predators rather than search image formation explaining polymorphism.
Genetic variants in ultraconserved regions associate with prostate cancer recurrence and survival
Authors: Bao Bo-Ying , Lin Victor C. , Yu Chia-Cheng , Yin Hsin-Ling , Chang Ta-Yuan , Lu Te-Ling , Lee Hong-Zin , Pao Jiunn-Bey , Huang Chao-Yuan , Huang Shu-Pin
Published: February 2016

Ultraconserved regions (UCRs) are DNA segments of longer than 200 bp in length that are completely conserved between human, rat, and mouse genomes. Recent studies have shown that UCRs are frequently located at fragile sites involved in cancers, and their levels of transcription can be altered during human tumorigenesis. We systematically evaluated 14 common single-nucleotide polymorphisms (SNPs) within UCRs in three cohorts of prostate cancer patients, to test the hypothesis that these UCR SNPs might influence clinical outcomes. Examination using multivariate analysis adjusted for known clinicopathologic factors found association between rs8004379 and recurrence in localized disease [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.41–0.91, P = 0.015], which was confirmed in the replication set (HR 0.70, 95% CI 0.51–0.96, P = 0.027). Remarkably, a consistent association of rs8004379 with a decreased risk for prostate cancer-specific mortality was also observed in the advanced prostate cancer patient group (HR 0.48, 95% CI 0.32–0.70, P < 0.001). Additional in silico analysis suggests that rs8004379 tends to affect NPAS3 expression, which in turn was found to be correlated with patient prognosis. In conclusion, our findings suggest that SNPs within UCRs may be valuable prognostic biomarkers for assessing prostate cancer treatment response and survival.
Anthropogenic disturbances are key to maintaining the biodiversity of grasslands
Authors: Yuan Z. Y. , Jiao F. , Li Y. H. , Kallenbach Robert L.
Published: February 2016

Although anthropogenic disturbances are often perceived as detrimental to plant biodiversity, the relationship between biodiversity and disturbance remains unclear. Opinions diverge on how natural diversity is generated and maintained. We conducted a large-scale investigation of a temperate grassland system in Inner Mongolia and assessed the richness-disturbance relationship using grazing intensity, the primary anthropogenic disturbance in the region. Vascular plant-species richness peaked at an intermediate level of anthropogenic disturbance. Our results support the Intermediate Disturbance Hypothesis, which provides a valid and useful measure of biodiversity at a metacommunity scale, indicating that anthropogenic disturbances are necessary to conserve the biodiversity of grassland systems.
Antipsychotic pharmacogenomics in first episode psychosis: a role for glutamate genes
Authors: Stevenson J M , Reilly J L , Harris M S H , Patel S R , Weiden P J , Prasad K M , Badner J A , Nimgaonkar V L , Keshavan M S , Sweeney J A , Bishop J R
Published: February 2016

Genetic factors may underlie beneficial and adverse responses to antipsychotic treatment. These relationships may be easier to identify among patients early in the course of disease who have limited exposure to antipsychotic drugs. We examined 86 first episode patients (schizophrenia, psychotic bipolar disorder and major depressive disorder with psychotic features) who had minimal to no prior antipsychotic exposure in a 6-week pharmacogenomic study of antipsychotic treatment response. Response was measured by change in Brief Psychiatric Rating Scale total score. Risperidone monotherapy was the primary antipsychotic treatment. Pharmacogenomic association studies were completed to (1) examine candidate single-nucleotide polymorphisms (SNPs) in genes known to be involved with glutamate signaling, and (2) conduct an exploratory genome-wide association study of symptom response to identify potential novel associations for future investigation. Two SNPs in GRM7 (rs2069062 and rs2014195) were significantly associated with antipsychotic response in candidate gene analysis, as were two SNPs in the human glutamate receptor delta 2 (GRID2) gene (rs9307122 and rs1875705) in genome-wide association analysis. Further examination of these findings with those from a separate risperidone-treated study sample demonstrated that top SNPs in both studies were overrepresented in glutamate genes and that there were similarities in neurodevelopmental gene categories associated with drug response from both study samples. These associations indicate a role for gene variants related to glutamate signaling and antipsychotic response with more broad association patterns indicating the potential importance of genes involved in neuronal development.
Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers
Authors: Booij L , Welfeld K , Leyton M , Dagher A , Boileau I , Sibon I , Baker G B , Diksic M , Soucy J-P , Pruessner J C , Cawley-Fiset E , Casey K F , Benkelfat C
Published: February 2016

Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean±s.d.=22.1±3.4 years) [11C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg−1, by mouth; n=8) or placebo (3 × lactose, by mouth; n=9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P⩽0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P<0.04), and voxel-based analyses showed larger stress-induced decreases in [11C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [11C]raclopride binding, primarily in the sensorimotor striatum (P<0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked.
Smart Materials as Forward Osmosis Draw Solutes
Authors: Chen Shucheng , Lu Xianmao
Published: February 2016

With the growing global demand for fresh water for consumption, it is of great importance to find novel technologies to produce fresh water efficiently. In recent years, forward osmosis (FO) has emerged as a promising membrane technology for seawater desalination and wastewater treatment. A crucial requirement for an efficient FO process is to find a draw solute that is able to generate a high water flux and can be regenerated via facile recovery methods. Smart materials exhibit advantages as FO draw agents to lower the energy cost of regeneration as they can respond to stimuli to undergo physical or chemical changes that facilitate separation from solvents. Therefore, increasing research efforts have been devoted to the design of smart draw solutes. This chapter aims to review the recent development of various smart draw solutes. It begins with a general introduction to the FO process. Next, hydrophilic magnetic nanoparticles and stimuli-responsive magnetic nanoparticles are discussed, followed by the study of smart polyelectrolytes, solvents and hydrogels. The concluding remarks present future perspectives on using smart draw solutes for FO processes.