bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient generation of B2m-null pigs via injection of zygote with TALENs
Authors: Wang Yong , Du Yinan , Zhou Xiaoyang , Wang Lulu , Li Jian , Wang Fengchao , Huang Zhengen , Huang Xingxu , Wei Hong
Published: December 2016

Donor major histocompatibility complex class I (MHC I) molecules are the main targets of the host immune response after organ allotransplantation. Whether and how MHC I-deficiency of pig donor tissues affects rejection after xenotransplantation has not been assessed. Beta2-microglobulin (B2M) is indispensable for the assembly of MHC I receptors and therefore provides an effective target to disrupt cell surface MHC I expression. Here, we report the one-step generation of mutant pigs with targeted disruptions in B2m by injection of porcine zygotes with B2m exon 2-specific TALENs. After germline transmission of mutant B2m alleles, we obtained F1 pigs with biallelic B2m frameshift mutations. F1 pigs lacked detectable B2M expression in tissues derived from the three germ layers, and their lymphocytes were devoid of MHC I surface receptors. Skin grafts from B2M deficient pigs exhibited remarkably prolonged survival on xenogeneic wounds compared to tissues of non-mutant littermates. Mutant founder pigs with bi-allelic disruption in B2m and B2M deficient F1 offspring did not display visible abnormalities, suggesting that pigs are tolerant to B2M deficiency. In summary, we show the efficient generation of pigs with germline mutations in B2m, and demonstrate a beneficial effect of donor MHC I-deficiency on xenotransplantation.
The role of the unusual threonine string in the conversion of prion protein
Authors: Abskharon Romany , Wang Fei , Vander Stel Kayla J. , Sinniah Kumar , Ma Jiyan
Published: December 2016

The conversion of normal prion protein (PrP) into pathogenic PrP conformers is central to prion disease, but the mechanism remains unclear. The α-helix 2 of PrP contains a string of four threonines, which is unusual due to the high propensity of threonine to form β-sheets. This structural feature was proposed as the basis for initiating PrP conversion, but experimental results have been conflicting. We studied the role of the threonine string on PrP conversion by analyzing mouse Prnpa and Prnpb polymorphism that contains a polymorphic residue at the beginning of the threonine string, and PrP mutants in which threonine 191 was replaced by valine, alanine, or proline. The PMCA (protein misfolding cyclic amplification) assay was able to recapitulate the in vivo transmission barrier between PrPa and PrPb. Relative to PMCA, the amyloid fibril growth assay is less restrictive, but it did reflect certain properties of in vivo prion transmission. Our results suggest a plausible theory explaining the apparently contradictory results in the role of the threonine string in PrP conversion and provide novel insights into the complicated relationship among PrP stability, seeded conformational change, and prion structure, which is critical for understanding the molecular basis of prion infectivity.
Shared and unique patterns of phenotypic diversification along a stream gradient in two congeneric species
Authors: Jourdan Jonas , Krause Sarah T. , Lazar V. Max , Zimmer Claudia , Sommer-Trembo Carolin , Arias-Rodriguez Lenin , Klaus Sebastian , Riesch Rüdiger , Plath Martin
Published: December 2016

Stream ecosystems show gradual variation of various selection factors, which can result in a zonation of species distributions and gradient evolution of morphological and life-history traits within species. Identifying the selective agents underlying such phenotypic evolution is challenging as different species could show shared and/or unique (species-specific) responses to components of the river gradient. We studied a stream gradient inhabited by two mosquitofishes (genus Gambusia) in the Río Grijalva basin in southern Mexico and found a patchy distribution pattern of both congeners along a stretch of 100 km, whereby one species was usually dominant at a given site. We uncovered both shared and unique patterns of diversification: some components of the stream gradient, including differences in piscine predation pressure, drove shared patterns of phenotypic divergence, especially in females. Other components of the gradient, particularly abiotic factors (max. annual temperature and temperature range) resulted in unique patterns of divergence, especially in males. Our study highlights the complexity of selective regimes in stream ecosystems. It exemplifies that even closely related, congeneric species can respond in unique ways to the same components of the river gradient and shows how both sexes can exhibit quite different patterns of divergence in multivariate phenotypic character suites.
Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen
Authors: Cox Jonathan A. G. , Mugumbate Grace , Del Peral Laura Vela-Glez , Jankute Monika , Abrahams Katherine A. , Jervis Peter , Jackenkroll Stefan , Perez Arancha , Alemparte Carlos , Esquivias Jorge , Lelièvre Joël , Ramon Fernando , Barros David , Ballell Lluis , Besra Gurdyal S.
Published: December 2016

High-throughput phenotypic screens have re-emerged as screening tools in antibiotic discovery. The advent of such technologies has rapidly accelerated the identification of ‘hit’ compounds. A pre-requisite to medicinal chemistry optimisation programmes required to improve the drug-like properties of a ‘hit’ molecule is identification of its mode of action. Herein, we have combined phenotypic screening with a biased target-specific screen. The inosine monophosphate dehydrogenase (IMPDH) protein GuaB2 has been identified as a drugable target in Mycobacterium tuberculosis, however previously identified compounds lack the desired characteristics necessary for further development into lead-like molecules. This study has identified 7 new chemical series from a high-throughput resistance-based phenotypic screen using Mycobacterium bovis BCG over-expressing GuaB2. Hit compounds were identified in a single shot high-throughput screen, validated by dose response and subjected to further biochemical analysis. The compounds were also assessed using molecular docking experiments, providing a platform for their further optimisation using medicinal chemistry. This work demonstrates the versatility and potential of GuaB2 as an anti-tubercular drug target.
Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space
Authors: Indo Hiroko P. , Majima Hideyuki J. , Terada Masahiro , Suenaga Shigeaki , Tomita Kazuo , Yamada Shin , Higashibata Akira , Ishioka Noriaki , Kanekura Takuro , Nonaka Ikuya , Hawkins Clare L. , Davies Michael J. , Clair Daret K. St , Mukai Chiaki
Published: December 2016

The effects of long-term exposure to extreme space conditions on astronauts were investigated by analyzing hair samples from ten astronauts who had spent six months on the International Space Station (ISS). Two samples were collected before, during and after their stays in the ISS; hereafter, referred to as Preflight, Inflight and Postflight, respectively. The ratios of mitochondrial (mt) to nuclear (n) DNA and mtRNA to nRNA were analyzed via quantitative PCR. The combined data of Preflight, Inflight and Postflight show a significant reduction in the mtDNA/nDNA in Inflight, and significant reductions in the mtRNA/nRNA ratios in both the Inflight and Postflight samples. The mtRNA/mtDNA ratios were relatively constant, except in the Postflight samples. Using the same samples, the expression of redox and signal transduction related genes, MnSOD, CuZnSOD, Nrf2, Keap1, GPx4 and Catalase was also examined. The results of the combined data from Preflight, Inflight and Postflight show a significant decrease in the expression of all of the redox-related genes in the samples collected Postflight, with the exception of Catalase, which show no change. This decreased expression may contribute to increased oxidative stress Inflight resulting in the mitochondrial damage that is apparent Postflight.
The Management and Prognostic Prediction of Adenocarcinoma of Appendix
Authors: Xie Xin , Zhou Zhangjian , Song Yongchun , Li Wenhan , Diao Dongmei , Dang Chengxue , Zhang Hao
Published: December 2016

Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation.
Multicenter evaluation of crystal violet decolorization assay (CVDA) for rapid detection of isoniazid and rifampicin resistance in Mycobacterium tuberculosis
Authors: Coban Ahmet Yilmaz , Akbal Ahmet Ugur , Bicmen Can , Albay Ali , Sig Ali Korhan , Uzun Meltem , Selale Deniz Sertel , Ozkutuk Nuri , Surucuoglu Suheyla , Albayrak Nurhan , Ucarman Nilay , Ozkutuk Aydan , Esen Nuran , Ceyhan Ismail , Ozyurt Mustafa , Bektore Bayhan , Aslan Gonul , Delialioğlu Nuran , Alp Alpaslan
Published: December 2016

The aim of this multicenter study was to evaluate the performance of the crystal violet decolorization assay (CVDA) for detection of multidrug resistant tuberculosis (MDR-TB). This study was performed in 11 centers in two phases. A total of 156 isolates were tested for INH and RIF resistance. In the phase I, 106 clinical isolates were tested in the Center 1–7. In the phase 2, 156 clinical isolates were tested in the center 1–6, center 8–11. Eighty six of 156 tested isolates were the same in phase I. Agreements were 96.2–96.8% for INH and 98.1–98.7% for RIF in the phase I-II, respectively. Mean time to obtain the results in the phase I was 14.3 ± 5.4 days. In the phase II, mean time to obtain the results was 11.6 ± 3.5 days. Test results were obtained within 14days for 62.3% (66/106) of isolates in the phase I and 81.4% (127/156) of isolates in the phase II. In conclusion, CVDA is rapid, reliable, inexpensive, and easy to perform for rapid detection of MDR-TB isolates. In addition, it could be adapted for drug susceptibility testing with all drugs both in developed and developing countries.
New cell motility model observed in parasitic cnidarian Sphaerospora molnari (Myxozoa:Myxosporea) blood stages in fish
Authors: Hartigan A. , Estensoro I. , Vancová M. , Bílý T. , Patra S. , Eszterbauer E. , Holzer A. S.
Published: December 2016

Cellular motility is essential for microscopic parasites, it is used to reach the host, migrate through tissues, or evade host immune reactions. Many cells employ an evolutionary conserved motor protein– actin, to crawl or glide along a substrate. We describe the peculiar movement of Sphaerospora molnari, a myxozoan parasite with proliferating blood stages in its host, common carp. Myxozoa are highly adapted parasitic cnidarians alternately infecting vertebrates and invertebrates. S. molnari blood stages (SMBS) have developed a unique “dancing” behaviour, using the external membrane as a motility effector to rotate and move the cell. SMBS movement is exceptionally fast compared to other myxozoans, non-directional and constant. The movement is based on two cytoplasmic actins that are highly divergent from those of other metazoans. We produced a specific polyclonal actin antibody for the staining and immunolabelling of S. molnari’s microfilaments since we found that neither commercial antibodies nor phalloidin recognised the protein or microfilaments. We show the in situ localization of this actin in the parasite and discuss the importance of this motility for evasion from the cellular host immune response in vitro. This new type of motility holds key insights into the evolution of cellular motility and associated proteins.
Brusatol inhibits HIF-1 signaling pathway and suppresses glucose uptake under hypoxic conditions in HCT116 cells
Authors: Lu Yapeng , Wang Bo , Shi Qian , Wang Xueting , Wang Dang , Zhu Li
Published: December 2016

Hypoxia-inducible factor-1 (HIF-1) is an important transcription factor that induces adaptive responses upon low oxygen conditions in human cancers and triggers off a poor prognostic outcome of conventional treatments. In this study, we discovered for the first time that brusatol (BRU), a quassinoid extracted from Brucea Esters, has the capability to inhibit HIF-1 signaling pathway. We found that BRU concentration-dependently down-regulated HIF-1α protein levels under hypoxia or CoCl2-induced mimic hypoxia in HCT116 cells without causing significant cytotoxicity. Besides, the transactivation activity of HIF-1 was suppressed by BRU under hypoxic conditions, as well as the expression of HIF-1 target genes, including VEGF, GLUT1, HK2 and LDHA. In addition, BRU can also decrease glucose consumption under hypoxia through inhibition of HIF-1 signaling pathway. Further studies revealed that the inhibitory effect of BRU on HIF-1 signaling pathway might be attributed to promoting degradation of HIF-1α. Interestingly, intracellular reactive oxygen species (ROS) levels and mitochondrial ROS level were both decreased by BRU treatment, indicating the involvment of mitochondrial ROS regulation in the action of BRU. Taken together, these results provided clear evidence for BRU-mediated HIF-1α regulation and suggested its therapeutic potential in colon tumors.
Declining Prevalence of Disease Vectors Under Climate Change
Authors: Escobar Luis E. , Romero-Alvarez Daniel , Leon Renato , Lepe-Lopez Manuel A. , Craft Meggan E. , Borbor-Cordova Mercy J. , Svenning Jens-Christian
Published: December 2016

More than half of the world population is at risk of vector-borne diseases including dengue fever, chikungunya, zika, yellow fever, leishmaniasis, chagas disease, and malaria, with highest incidences in tropical regions. In Ecuador, vector-borne diseases are present from coastal and Amazonian regions to the Andes Mountains; however, a detailed characterization of the distribution of their vectors has never been carried out. We estimate the distribution of 14 vectors of the above vector-borne diseases under present-day and future climates. Our results consistently suggest that climate warming is likely threatening some vector species with extinction, locally or completely. These results suggest that climate change could reduce the burden of specific vector species. Other vector species are likely to shift and constrain their geographic range to the highlands in Ecuador potentially affecting novel areas and populations. These forecasts show the need for development of early prevention strategies for vector species currently absent in areas projected as suitable under future climate conditions. Informed interventions could reduce the risk of human exposure to vector species with distributional shifts, in response to current and future climate changes. Based on the mixed effects of future climate on human exposure to disease vectors, we argue that research on vector-borne diseases should be cross-scale and include climatic, demographic, and landscape factors, as well as forces facilitating disease transmission at fine scales.
Enhanced Conversion Efficiency of III–V Triple-junction Solar Cells with Graphene Quantum Dots
Authors: Lin Tzu-Neng , Santiago Svette Reina Merden S. , Zheng Jie-An , Chao Yu-Chiang , Yuan Chi-Tsu , Shen Ji-Lin , Wu Chih-Hung , Lin Cheng- An J. , Liu Wei-Ren , Cheng Ming-Chiang , Chou Wu-Ching
Published: December 2016

Graphene has been used to synthesize graphene quantum dots (GQDs) via pulsed laser ablation. By depositing the synthesized GQDs on the surface of InGaP/InGaAs/Ge triple-junction solar cells, the short-circuit current, fill factor, and conversion efficiency were enhanced remarkably. As the GQD concentration is increased, the conversion efficiency in the solar cell increases accordingly. A conversion efficiency of 33.2% for InGaP/InGaAs/Ge triple-junction solar cells has been achieved at the GQD concentration of 1.2 mg/ml, corresponding to a 35% enhancement compared to the cell without GQDs. On the basis of time-resolved photoluminescence, external quantum efficiency, and work-function measurements, we suggest that the efficiency enhancement in the InGaP/InGaAs/Ge triple-junction solar cells is primarily caused by the carrier injection from GQDs to the InGaP top subcell.
The involvement of dityrosine crosslinking in α-synuclein assembly and deposition in Lewy Bodies in Parkinson’s disease
Authors: Al-Hilaly Youssra K. , Biasetti Luca , Blakeman Ben J. F. , Pollack Saskia J. , Zibaee Shahin , Abdul-Sada Alaa , Thorpe Julian R. , Xue Wei-Feng , Serpell Louise C.
Published: December 2016

Parkinson’s disease (PD) is characterized by intracellular, insoluble Lewy bodies composed of highly stable α-synuclein (α-syn) amyloid fibrils. α-synuclein is an intrinsically disordered protein that has the capacity to assemble to form β-sheet rich fibrils. Oxidiative stress and metal rich environments have been implicated in triggering assembly. Here, we have explored the composition of Lewy bodies in post-mortem tissue using electron microscopy and immunogold labeling and revealed dityrosine crosslinks in Lewy bodies in brain tissue from PD patients. In vitro, we show that dityrosine cross-links in α-syn are formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress by fluorescence and confirmed using mass-spectrometry. A covalently cross-linked dimer isolated by SDS-PAGE and mass analysis showed that dityrosine dimer was formed via the coupling of Y39-Y39 to give a homo dimer peptide that may play a key role in formation of oligomeric and seeds for fibril formation. Atomic force microscopy analysis reveals that the covalent dityrosine contributes to the stabilization of α-syn assemblies. Thus, the presence of oxidative stress induced dityrosine could play an important role in assembly and toxicity of α-syn in PD.
CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα
Authors: Nakagawa Yoshimi , Satoh Aoi , Tezuka Hitomi , Han Song-iee , Takei Kenta , Iwasaki Hitoshi , Yatoh Shigeru , Yahagi Naoya , Suzuki Hiroaki , Iwasaki Yasumasa , Sone Hirohito , Matsuzaka Takashi , Yamada Nobuhiro , Shimano Hitoshi
Published: December 2016

CREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3−/− mice exhibited reduction of expression of genes for fatty oxidation and ketogenesis comparable to Ppara−/− mice. Most of the genes were further suppressed in double knockout mice indicating independent contribution of hepatic CREB3L3. During fasting, dependency of ketogenesis on CREB3L3 is lesser extents than Ppara−/− mice suggesting importance of adipose PPARα for supply of FFA and hyperlipidemia in Creb3l3−/− mice. In conclusion CREB3L3 plays a crucial role in hepatic adaptation to energy starvation via two pathways: direct related gene regulation and an auto-loop activation of PPARα. Furthermore, as KD-fed Creb3l3−/− mice exhibited severe fatty liver, activating inflammation, CREB3L3 could be a therapeutic target for NAFLD.
Sensitive and accurate quantification of human malaria parasites using droplet digital PCR (ddPCR)
Authors: Koepfli Cristian , Nguitragool Wang , Hofmann Natalie E. , Robinson Leanne J. , Ome-Kaius Maria , Sattabongkot Jetsumon , Felger Ingrid , Mueller Ivo
Published: December 2016

Accurate quantification of parasite density in the human host is essential for understanding the biology and pathology of malaria. Semi-quantitative molecular methods are widely applied, but the need for an external standard curve makes it difficult to compare parasite density estimates across studies. Droplet digital PCR (ddPCR) allows direct quantification without the need for a standard curve. ddPCR was used to diagnose and quantify P. falciparum and P. vivax in clinical patients as well as in asymptomatic samples. ddPCR yielded highly reproducible measurements across the range of parasite densities observed in humans, and showed higher sensitivity than qPCR to diagnose P. falciparum, and equal sensitivity for P. vivax. Correspondence in quantification was very high (>0.95) between qPCR and ddPCR. Quantification between technical replicates by ddPCR differed 1.5–1.7-fold, compared to 2.4–6.2-fold by qPCR. ddPCR facilitates parasite quantification for studies where absolute densities are required, and will increase comparability of results reported from different laboratories.
Establishment of the cytoplasmic incompatibility-inducing Wolbachia strain wMel in an important agricultural pest insect
Authors: Zhou Xiao-Fei , Li Zheng-Xi
Published: December 2016

ThewMelWolbachiastrain was known for cytoplasmic incompatibility (CI)-induction and blocking the transmission of dengue. However, it is unknown whether it can establish and induce CI in a non-dipteran host insect. Here we artificially transferredwMel fromDrosophila melanogasterinto the whiteflyBemisia tabaci. Fluorescencein situhybridisation demonstrated thatwMel had successfully transfected the new host. Reciprocal crossing was conducted withwMel-transfected and wild-type isofemale lines, indicating thatwMel could induce a strong CI without imposing significant cost on host fecundity. We then determined the maternal transmission efficiency ofwMel in the offspring generations, showing a fluctuating trend over a period of 12 generations. We thus detected the titre ofwMel during different developmental stages and in different generations by using real-time quantitative PCR, revealing a similar fluctuating mode, but it was not significantly correlated with the dynamics of transmission efficiency. These results suggest thatwMel can be established inB.tabaci, a distantly related pest insect of agricultural importance; moreover, it can induce a strong CI phenotype in the recipient host insect, suggesting a potential for its use in biological control ofB. tabaci.
Interplay of multiple synaptic plasticity features in filamentary memristive devices for neuromorphic computing
Authors: La Barbera Selina , Vincent Adrien F. , Vuillaume Dominique , Querlioz Damien , Alibart Fabien
Published: December 2016

Bio-inspired computing represents today a major challenge at different levels ranging from material science for the design of innovative devices and circuits to computer science for the understanding of the key features required for processing of natural data. In this paper, we propose a detail analysis of resistive switching dynamics in electrochemical metallization cells for synaptic plasticity implementation. We show how filament stability associated to joule effect during switching can be used to emulate key synaptic features such as short term to long term plasticity transition and spike timing dependent plasticity. Furthermore, an interplay between these different synaptic features is demonstrated for object motion detection in a spike-based neuromorphic circuit. System level simulation presents robust learning and promising synaptic operation paving the way to complex bio-inspired computing systems composed of innovative memory devices.
An adenylyl cyclase with a phosphodiesterase domain in basal plants with a motile sperm system
Authors: Kasahara Masahiro , Suetsugu Noriyuki , Urano Yuki , Yamamoto Chiaki , Ohmori Mikiya , Takada Yuki , Okuda Shujiro , Nishiyama Tomoaki , Sakayama Hidetoshi , Kohchi Takayuki , Takahashi Fumio
Published: December 2016

Adenylyl cyclase (AC), which produces the signalling molecule cAMP, has numerous important cellular functions in diverse organisms from prokaryotes to eukaryotes. Here we report the identification and characterization of an AC gene from the liverwort Marchantia polymorpha. The encoded protein has both a C-terminal AC catalytic domain similar to those of class III ACs and an N-terminal cyclic nucleotide phosphodiesterase (PDE) domain that degrades cyclic nucleotides, thus we designated the gene MpCAPE (COMBINEDAC withPDE). Biochemical analyses of recombinant proteins showed that MpCAPE has both AC and PDE activities. In MpCAPE-promoter-GUS lines, GUS activity was specifically detected in the male sexual organ, the antheridium, suggesting MpCAPE and thus cAMP signalling may be involved in the male reproductive process. CAPE orthologues are distributed only in basal land plants and charophytes that use motile sperm as the male gamete. CAPE is a subclass of class III AC and may be important in male organ and cell development in basal plants.
Mitochondrial Phylogenomics yields Strongly Supported Hypotheses for Ascaridomorph Nematodes
Authors: Liu Guo-Hua , Nadler Steven A. , Liu Shan-Shan , Podolska Magdalena , D’Amelio Stefano , Shao Renfu , Gasser Robin B. , Zhu Xing-Quan
Published: December 2016

Ascaridomorph nematodes threaten the health of humans and other animals worldwide. Despite their medical, veterinary and economic importance, the identification of species lineages and establishing their phylogenetic relationships have proved difficult in some cases. Many working hypotheses regarding the phylogeny of ascaridomorphs have been based on single-locus data, most typically nuclear ribosomal RNA. Such single-locus hypotheses lack independent corroboration, and for nuclear rRNA typically lack resolution for deep relationships. As an alternative approach, we analyzed the mitochondrial (mt) genomes of anisakids (~14 kb) from different fish hosts in multiple countries, in combination with those of other ascaridomorphs available in the GenBank database. The circular mt genomes range from 13,948-14,019 bp in size and encode 12 protein-coding genes, 2 ribosomal RNAs and 22 transfer RNA genes. Our analysis showed that thePseudoterranova decipienscomplex consists of at least six cryptic species. In contrast, the hypothesis thatContracaecum ogmorhinirepresents a complex of cryptic species is not supported by mt genome data. Our analysis recovered several fundamental and uncontroversial ascaridomorph clades, including the monophyly of superfamilies and families, except for Ascaridiidae, which was consistent with the results based on nuclear rRNA analysis. In conclusion, mt genome analysis provided new insights into the phylogeny and taxonomy of ascaridomorph nematodes.
Broadband and wide-angle RCS reduction using a 2-bit coding ultrathin metasurface at terahertz frequencies
Authors: Liang Lanju , Wei Minggui , Yan Xin , Wei Dequan , Liang Dachuan , Han Jiaguang , Ding Xin , Zhang GaoYa , Yao Jianquan
Published: December 2016

A novel broadband and wide-angle 2-bit coding metasurface for radar cross section (RCS) reduction is proposed and characterized at terahertz (THz) frequencies. The ultrathin metasurface is composed of four digital elements based on a metallic double cross line structure. The reflection phase difference of neighboring elements is approximately 90° over a broadband THz frequency. The mechanism of RCS reduction is achieved by optimizing the coding element sequences, which redirects the electromagnetic energies to all directions in broad frequencies. An RCS reduction of less than −10 dB bandwidth from 0.7 THz to 1.3 THz is achieved in the experimental and numerical simulations. The simulation results also show that broadband RCS reduction can be achieved at an incident angle below 60° for TE and TM polarizations under flat and curve coding metasurfaces. These results open a new approach to flexibly control THz waves and may offer widespread applications for novel THz devices.
A cloud-based workflow to quantify transcript-expression levels in public cancer compendia
Authors: Tatlow PJ , Piccolo Stephen R.
Published: December 2016

Public compendia of sequencing data are now measured in petabytes. Accordingly, it is infeasible for researchers to transfer these data to local computers. Recently, the National Cancer Institute began exploring opportunities to work with molecular data in cloud-computing environments. With this approach, it becomes possible for scientists to take their tools to the data and thereby avoid large data transfers. It also becomes feasible to scale computing resources to the needs of a given analysis. We quantified transcript-expression levels for 12,307 RNA-Sequencing samples from the Cancer Cell Line Encyclopedia and The Cancer Genome Atlas. We used two cloud-based configurations and examined the performance and cost profiles of each configuration. Using preemptible virtual machines, we processed the samples for as little as $0.09 (USD) per sample. As the samples were processed, we collected performance metrics, which helped us track the duration of each processing step and quantified computational resources used at different stages of sample processing. Although the computational demands of reference alignment and expression quantification have decreased considerably, there remains a critical need for researchers to optimize preprocessing steps. We have stored the software, scripts, and processed data in a publicly accessible repository (https://osf.io/gqrz9).
Recombinant Marek’s disease virus type 1 provides full protection against very virulent Marek’s and infectious bursal disease viruses in chickens
Authors: Li Kai , Liu Yongzhen , Liu Changjun , Gao Li , Zhang Yanping , Cui Hongyu , Gao Yulong , Qi Xiaole , Zhong Li , Wang Xiaomei
Published: December 2016

Marek’s disease virus (MDV) is a preferred vector in the construction of recombinant vaccines. However, bivalent vaccine based on MDV that confers full protection against both very virulent Marek’s and infectious bursal disease virus (IBDV) infections in chickens has not been produced. Here we developed a system utilizing overlapping fosmid DNAs transfection that rescues an MDV type 1 (MDV1) vaccine strain. Using this system, we inserted the IBDV VP2 gene at MDV1 genome sites UL41, US10 and US2. The VP2 protein was stably expressed in the recombinant MDV-infected cells and self-assembled into IBDV subviral particles. Insertion of the VP2 gene did not affect the replication phenotype of MDV in cell cultures, nor did it increase the virulence of the MDV vaccine strain in chickens. After challenge with very virulent IBDV, r814US2VP2 conferred full protection, whereas r814UL41VP2 and r814US10VP2 provided partial or no protection. All the three recombinant vaccines provided full protection against very virulent MDV challenge in chickens. These results demonstrated that r814US2VP2 could be used as a promising bivalent vaccine against both Marek’s and infectious bursal diseases in chickens.
A structural insight into the negative effects of opioids in analgesia by modulating the TLR4 signaling: An in silico approach
Authors: Shah Masaud , Anwar Muhammad Ayaz , Yesudhas Dhanusha , Krishnan Jayalakshmi , Choi Sangdun
Published: December 2016

Opioids are considered the gold standard therapy for pain. However, TLR-dependent negative effects in analgesia have highlighted the complexities in the pharmacodynamics of opioids. While successive studies have reported that morphine and Morphine-3-glucuronide (M3G) activate the TLR4 pathway, the structural details of this mechanism are lacking. Here, we have utilized various computational tools to reveal the structural dynamics of the opioid-bound TLR4/MD2 complex, and have proposed a potential TLR4 activation mechanism. Our results support previous findings, and include the novel insight that the stable binding of morphine and naloxone, but not M3G, in the MD2 cavity, is TLR4 dependent. Morphine interacts with MD2 near its Phe126 loop to induce the active conformation (MD2C); however, this binding is likely reversible, and the complex gains stability upon interaction with TLR4. M3G also induces the MD2Cstate, with both the Phe126 loop and the H1 loop being involved in MD2-M3G complex stability. Remarkably, naloxone, which requires TLR4 interaction for complex stability, switches the conformation of the gating loop to the inactive state (MD2°). Cumulatively, our findings suggest that ligand binding and receptor clustering occur successively in opioid-induced TLR4 signaling, and that MD2 plasticity and pocket hydrophobicity are crucial for the recognition and accommodation of ligands.
Huangqin-tang ameliorates dextran sodium sulphate-induced colitis by regulating intestinal epithelial cell homeostasis, inflammation and immune response
Authors: Zou Ying , Lin Jiantao , Li Wenyang , Wu Zhuguo , He Zhiwei , Huang Guoliang , Wang Jian , Ye Caiguo , Cheng Xiaoyan , Ding Congcong , Zheng Xuebao , Chi Honggang
Published: December 2016

Huangqin-tang (HQT) is a traditional Chinese medicine (TCM) formula widely used for the treatment of inflammatory bowel disease in China. However, the molecular mechanisms by which HQT protects the colon are unclear. We studied the protective effects of HQT and the underlying mechanisms in an experimental mouse model and in vitro. In vivo, dextran sodium sulphate (DSS)-induced acute and chronic colitis were significantly ameliorated by HQT as gauged by phenotypic, histopathologic and inflammatory manifestations of the disease. Mechanistically, DSS-induced nuclear factor-κB (NF-κB) signalling was inhibited by HQT. Moreover, HQT-treated mice demonstrated significant changes in cell apoptosis, expression of apoptosis-associated genes such as caspase-3, bax, bcl-2, and intestinal permeability. HQT also increased occluding and zonula occludens-1 (ZO-1), inhibited cell proliferation (Ki67), and increased regulatory T cells numbers, protein expression of Foxp3 and IL-10 in the colonic tissue. In vitro, HQT down-regulated production of pro-inflammatory cytokines and supressed the NF-κB signalling pathway in lipopolysaccharides-induced RAW 264.7 macrophages. Our study suggests that HQT plays a critical role in regulating intestinal epithelial cell homeostasis, inflammation and immune response in colitis and offers novel therapeutic options in the management of inflammatory bowel disease.
Sustained maternal hyperoxygenation improves aortic arch dimensions in fetuses with coarctation
Authors: Zeng Shi , Zhou Jiawei , Peng Qinghai , Deng Wen , Zhang Ming , Zhao Yili , Wang Tao , Zhou Qichang
Published: December 2016

The aim was to investigate the impact of maternal hyperoxygenation (HO) on cardiac dimensions in fetuses with isolated Coarctation (CoA). Fetal echocardiography was performed serially in 48 fetuses with CoA and gestation age matched normal fetues. The Z-scores for the mitral valve (MV), tricuspid valve (TV), aortic valve (AV), ascending aorta (AAo), isthmus, pulmonary valve (PV), main pulmonary artery (MPA), and descending aorta (DAo) were measured and compared among normal fetuses, CoA fetuses with oxygen and CoA fetuses with air. In the group with oxygen, 6 L/min oxygen was administered to the mother using a face mask. Regression analyses were performed to identify potential factors for HO outcome. The left heart dimension Z-scores increased gradually during HO therapy periods, especially at 4 weeks after oxygen therapy (P < 0.05). As for the case group with air, the left heart dimension remained unchanged. The duration of HO was associated with aortic arch Z-scores (adjusted R2 = 0.199, 0.60 for AAO and isthmus, respectively). Sustained maternal middle-flow oxygenation can be safely used to improve left heart dimensions in fetuses with isolated CoA. The duration of HO were associated with treatment outcome. These findings may provide useful information for developing novel treatment strategies.
TracMouse: A computer aided movement analysis script for the mouse inverted horizontal grid test
Authors: Niewiadomski W. , Palasz E. , Skupinska M. , Zylinski M. , Steczkowska M. , Gasiorowska A. , Niewiadomska G. , Riedel G.
Published: December 2016

In rodents, detection and quantification of motor impairments is difficult. The traction test (inverted grid with mice clinging to the underside) currently has no objective rating system. We here developed and validated the semi-automatic MATLAB script TracMouse for unbiased detection of video-recorded movement patterns. High precision videos were analyzed by: (i) principal identification of anatomical paw details frame-by-frame by an experimentally blinded rater; (ii) automatic retrieval of proxies by TracMouse for individual paws. The basic states of Hold and Step were discriminated as duration and frequency, and these principle parameters were converted into static and dynamic endpoints and their discriminating power assessed in a dopaminergic lesion model. Relative to hind paws, forepaws performed ~4 times more steps, they were ~20% longer, and Hold duration was ~5 times shorter in normal C57Bl/6 mice. Thus, forepaw steps were classified as exploratory, hind paw movement as locomotive. Multiple novel features pertaining to paw sequence, step lengths and exploratory touches were accessible through TracMouse and revealed subtle Parkinsonian phenotypes. Novel proxies using TracMouse revealed previously unidentified features of movement and may aid the understanding of (i) brain circuits related to motor planning and execution, and (ii) phenotype detection in experimental models of movement disorders.
Ginsenoside Rg1 attenuates ultraviolet B-induced glucocortisides resistance in keratinocytes via Nrf2/HDAC2 signalling
Authors: Li Jun , Liu Dong , Wu Jinfeng , Zhang Daniel , Cheng Binbin , Zhang Yani , Yin Zifei , Wang Yuan , Du Juan , Ling Changquan
Published: December 2016

Oxidative stress, which occurs after ultraviolet (UV) radiation, usually results in Glucocorticoid (GC) resistance and the subsequent development of skin inflammation. One approach to protecting the skin against UV radiation is the use of antioxidants. The ginsenoside Rg1 is a novel natural antioxidant isolated from the medicinal plant Panax ginseng C.A. Mey. We demonstrated that UVB exposure exacerbated inflammation and reduced both the level of the glucocorticoid receptor (GR) and the efficacy of dexamethasone (Dex) in human keratinocytes (HaCaT cells). Pretreatment with Rg1 increased the expression of GR and restored Dex responsiveness to inflammation in UVB-irradiated HaCaT cells. Mechanistically, Rg1 rescued UVB-induced HDAC2 degradation. HDAC2 knockdown partially abolished the Rg1-induced up-regulation of GR and the enhancement of GC sensitivity. In addition, Rg1 reduced the production of reactive oxygen species (ROS), which preceded the up-regulation of HDAC2, and consequent sensitization of cells to Dex. Moreover, Rg1 treatment promoted the translocation and activation of Nrf2. Nrf2 knockdown partially abolished the Rg1-induced decrease of ROS production and increase of HDAC2. Rg1 also potentiated the anti-inflammatory effects of Dex in UVB-irradiated mouse skin. In conclusion, we demonstrated that Rg1 attenuated UVB-induced GC insensitivity. Notably, these effects were partially mediated by the Nrf2/HDAC2 pathway.
Effect of hydrothermal pretreatment on the structural changes of alkaline ethanol lignin from wheat straw
Authors: Chen Xue , Li Hanyin , Sun Shaoni , Cao Xuefei , Sun Runcang
Published: December 2016

Due to the enormous abundance of lignin and its unique aromatic nature, lignin has great potential for the production of industrially useful fuels, chemicals, and materials. However, the rigid and compact structure of the plant cell walls significantly blocks the separation of lignin. In this study, wheat straw was hydrothermally pretreated at different temperatures (120–200 °C) followed by post-treatment with 70% ethanol containing 1% NaOH to improve the isolation of lignin. Results demonstrated that the content of associated carbohydrates of the lignin fractions was gradually reduced with the increment of the hydrothermal severity. The structure of the lignins changed regularly with the increase of the pretreatment temperature from 120 to 200 °C. In particular, the contents ofβ-O-4′,β-β′,β-5′ linkages and aliphatic OH in the lignins showed a tendency of decrease, while the content of phenolic OH and thermal stability of the lignin fractions increased steadily as the increment of the pretreatment temperature.
Protein knotting through concatenation significantly reduces folding stability
Authors: Hsu Shang-Te Danny
Published: December 2016

Concatenation by covalent linkage of two protomers of an intertwined all-helical HP0242 homodimer from Helicobacter pylori results in the first example of an engineered knotted protein. While concatenation does not affect the native structure according to X-ray crystallography, the folding kinetics is substantially slower compared to the parent homodimer. Using NMR hydrogen-deuterium exchange analysis, we showed here that concatenation destabilises significantly the knotted structure in solution, with some regions close to the covalent linkage being destabilised by as much as 5 kcal mol−1. Structural mapping of chemical shift perturbations induced by concatenation revealed a pattern that is similar to the effect induced by concentrated chaotrophic agent. Our results suggested that the design strategy of protein knotting by concatenation may be thermodynamically unfavourable due to covalent constrains imposed on the flexible fraying ends of the template structure, leading to rugged free energy landscape with increased propensity to form off-pathway folding intermediates.
Graphene damage effects on radiation-resistance and configuration of copper–graphene nanocomposite under irradiation: A molecular dynamics study
Authors: Huang Hai , Tang Xiaobin , Chen Feida , Liu Jian , Li Huan , Chen Da
Published: December 2016

Metal–graphene nanocomposite is a kind of potential radiation tolerant material. Graphene damage of the composite is inevitable within radiation environments. In this paper, two kinds of copper–graphene nanocomposite (CGNC) systems containing perfect graphene and prefabricated damage graphene, respectively, were adopted to expound the influences of graphene damage on the properties (radiation-resistance and configuration) of CGNC under irradiation by atomistic simulations. In the CGNC containing perfect graphene, the increasing graphene damage induced by the increase of the number of cascades, did not obviously impair the role of copper–graphene interface in keeping the properties of CGNC. In the CGNC containing prefabricated damage graphene, the properties of CGNC would significantly deteriorate once the radius of prefabricated damage exceeds 10 Å, and even stacking fault tetrahedral would occur in the CGNC. The results highlighted that prefabricated graphene damage have greater effects on the change of the properties of CGNC. Therefore, it is very necessary to maintain the structural integrity of graphene for improving the radiation-resistance and configuration of CGNC.
N-terminal lipid conjugation of amyloid β(1–40) leads to the formation of highly ordered N-terminally extended fibrils
Authors: Adler Juliane , Scheidt Holger A. , Lemmnitzer Katharina , Krueger Martin , Huster Daniel
Published: December 2016

Fibril formation of amyloid β(1–40) (Aβ(1–40)) peptides N-terminally lipid modified with saturated octanoyl or palmitoyl lipid chains was investigated.
Inverted organic solar cells enhanced by grating-coupled surface plasmons and waveguide modes
Authors: Hara Kazuma , Lertvachirapaiboon Chutiparn , Ishikawa Ryousuke , Ohdaira Yasuo , Shinbo Kazunari , Kato Keizo , Kaneko Futao , Baba Akira
Published: December 2016

A schematic of the fabricated UL-AuNP-enhanced OSCs.
To each his own: isonitriles for all flavors. Functionalized isocyanides as valuable tools in organic synthesis
Authors: Giustiniano Mariateresa , Basso Andrea , Mercalli Valentina , Massarotti Alberto , Novellino Ettore , Tron Gian Cesare , Zhu Jieping
Published: December 2016

This review provides a comprehensive overview on the preparation and synthetic applications of functionalized isocyanides.
The binuclear dual emitter [Br(CO)3Re(P⋯N)(N⋯P)Re(CO)3Br] (P⋯N): 3-chloro-6-(4-diphenylphosphinyl)butoxypyridazine, a new bridging P,N-bidentate ligand resulting from the ring opening of tetrahydrofuran
Authors: Saldías Marianela , Manzur Jorge , Palacios Rodrigo E. , Gómez María L. , Fuente Julio De La , Günther Germán , Pizarro Nancy , Vega Andrés
Published: December 2016

The bimetallic ReI compound BrRe(P⋯N)(N⋯P)ReBr have dual emitting nature, with emission from and states.
Scaling behavior of moisture-induced grain degradation in polycrystalline hybrid perovskite thin films
Authors: Wang Qi , Chen Bo , Liu Ye , Deng Yehao , Bai Yang , Dong Qingfeng , Huang Jinsong
Published: December 2016

The degradation rate of CH3NH3PbI3 perovskite films, made by a known deposition method, is found to be roughly proportional to the grain size.
Characterizing the uptake, accumulation and toxicity of silver sulfide nanoparticles in plants
Authors: Wang Peng , Lombi Enzo , Sun Shengkai , Scheckel Kirk G. , Malysheva Anzhela , McKenna Brigid A. , Menzies Neal W. , Zhao Fang-Jie , Kopittke Peter M.
Published: December 2016

Plants take up Ag2S-NPs without a marked selectivity in regard to particle size and without substantial transformation during upward translocation.
Reversible transition between isotropic and anisotropic thermal transport in elastic polyurethane foams
Authors: Chau M. , Kopera B. A. F. , Machado V. R. , Tehrani S. M. , Winnik M. A. , Kumacheva E. , Retsch M.
Published: December 2016

The general concept of adjustable isotropic and anisotropic thermal conductivity in biphasic materials is demonstrated by freeze-casting polyurethane foams.
Carbazole modified salicylaldimines and their difluoroboron complexes: effect of the tert-butyl and trifluoromethyl terminal groups on organogelation and piezofluorochromism
Authors: Sun Jiabao , Sun Jingbo , Mi Wenhua , Xue Pengchong , Zhao Jinyu , Zhai Lu , Lu Ran
Published: December 2016

Luminescent nanofibers were generated from nontraditional π-gelators based on salicylaldimines and their difluoroboron complex bearing tert-butyl carbazole and trifluoromethylbenzene.
Oxidative coupling of 1-(2-methyl-4-phenylquinolin-3-yl)ethanone with ethanol and unexpected deacetylative synthesis of 3-hydroxy quinoline
Authors: Chauhan Parul , Ravi Makthala , Kant Ruchir , Yadav Prem. P.
Published: December 2016

An efficient, one pot method for the synthesis of α,β-epoxy ketone and hydroxylation has been developed from 1-(2-methyl-4-phenylquinolin-3-yl)ethanone with alcohol under mild conditions.
Synthesis of quinazolinones via radical cyclization of α-azidyl benzamides
Authors: Yang Tonghao , Wang Weixia , Wei Dian , Zhang Tianqi , Han Bing , Yu Wei
Published: December 2016

Under visible light irradiation with N-bromosuccinimide, α-azidyl benzamides can be transformed into quinazolinones in high efficiency via cascade radical processes.
Retraction: Synergetic effects of ultrasound combined with Fenton pretreatment that accelerates wasted activated sludge anaerobic fermentation to produce volatile fatty acids
Authors: Bao Hongxu , Zhang Hao , Yang Hua , Jiang Lei , Liu Yichen , Shen Manli , Su Hongzhi , Liu Wenzong , Wang Aijie
Published: December 2016

Retraction of ‘Synergetic effects of ultrasound combined with Fenton pretreatment that accelerates wasted activated sludge anaerobic fermentation to produce volatile fatty acids’ by Hongxu Bao et al., RSC Advances, 2016, DOI: 10.1039/c6ra19028f