bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2
Authors: Chen Chia-Lin , Huang Jeffrey Y. , Wang Chun-Hsiang , Tahara Stanley M , Zhou Lin , Kondo Yasuteru , Schechter Joel , Su Lishan , Lai Michael M C. , Wakita Takaji , Cosset François-Loïc , Jung Jae U , Machida Keigo
Published: January 2017

B-cell infection by hepatitis C virus (HCV) has been a controversial topic. To examine whether HCV has a genetically determined lymphotropism through a co-receptor specific for the infection by lymphotropic HCV, we established an infectious clone and chimeric virus of hepatotropic and lymphotropic HCV strains derived from an HCV-positive B-cell lymphoma. The viral envelope and 5′-UTR sequences of the lymphotropic HCV strain were responsible for the lymphotropism. Silencing of the virus sensor, RIGI, or overexpression of microRNA-122 promoted persistent viral replication in B cells. By cDNA library screening, we identified an immune cell-specific, co-stimulatory receptor B7.2 (CD86) as a co-receptor of lymphotropic HCV. Infection of B cells by HCV inhibited the recall reaction to antigen stimulation. Together, a co-receptor B7.2 enabled lymphotropic HCV to infect memory B cells, leading to inhibition of memory B-cell function and persistent HCV infection in HCV-infected hosts.
Suppressed decomposition of organometal halide perovskites by impermeable electron-extraction layers in inverted solar cells
Authors: Brinkmann K.O. , Zhao J. , Pourdavoud N. , Becker T. , Hu T. , Olthof S. , Meerholz K. , Hoffmann L. , Gahlmann T. , Heiderhoff R. , Oszajca M. F. , Luechinger N. A. , Rogalla D. , Chen Y. , Cheng B. , Riedl T
Published: January 2017

The area of thin-film photovoltaics has been overwhelmed by organometal halide perovskites. Unfortunately, serious stability concerns arise with perovskite solar cells. For example, methyl-ammonium lead iodide is known to decompose in the presence of water and, more severely, even under inert conditions at elevated temperatures. Here, we demonstrate inverted perovskite solar cells, in which the decomposition of the perovskite is significantly mitigated even at elevated temperatures. Specifically, we introduce a bilayered electron-extraction interlayer consisting of aluminium-doped zinc oxide and tin oxide. We evidence tin oxide grown by atomic layer deposition does form an outstandingly dense gas permeation barrier that effectively hinders the ingress of moisture towards the perovskite and—more importantly—it prevents the egress of decomposition products of the perovskite. Thereby, the overall decomposition of the perovskite is significantly suppressed, leading to an outstanding device stability.
Structure of actomyosin rigour complex at 5.2 Å resolution and insights into the ATPase cycle mechanism
Authors: Fujii Takashi , Namba Keiichi
Published: January 2017

Muscle contraction is driven by cyclic association and dissociation of myosin head of the thick filament with thin actin filament coupled with ATP binding and hydrolysis by myosin. However, because of the absence of actomyosin rigour structure at high resolution, it still remains unclear how the strong binding of myosin to actin filament triggers the release of hydrolysis products and how ATP binding causes their dissociation. Here we report the structure of mammalian skeletal muscle actomyosin rigour complex at 5.2 Å resolution by electron cryomicroscopy. Comparison with the structures of myosin in various states shows a distinctly large conformational change, providing insights into the ATPase-coupled reaction cycle of actomyosin. Based on our observations, we hypothesize that asymmetric binding along the actin filament could function as a Brownian ratchet by favouring directionally biased thermal motions of myosin and actin.
Identification of microsporidia host-exposed proteins reveals a repertoire of rapidly evolving proteins
Authors: Reinke Aaron W. , Balla Keir M. , Bennett Eric J. , Troemel Emily R.
Published: January 2017

Pathogens use a variety of secreted and surface proteins to interact with and manipulate their hosts, but a systematic approach for identifying such proteins has been lacking. To identify these ‘host-exposed’ proteins, we used spatially restricted enzymatic tagging followed by mass spectrometry analysis of Caenorhabditis elegans infected with two species of Nematocida microsporidia. We identified 82 microsporidia proteins inside of intestinal cells, including several pathogen proteins in the nucleus. These microsporidia proteins are enriched in targeting signals, are rapidly evolving and belong to large Nematocida-specific gene families. We also find that large, species-specific families are common throughout microsporidia species. Our data suggest that the use of a large number of rapidly evolving species-specific proteins represents a common strategy for microsporidia to interact with their hosts. The unbiased method described here for identifying potential pathogen effectors represents a powerful approach to study a broad range of pathogens.
A general-purpose machine learning framework for predicting properties of inorganic materials
Authors: Ward Logan , Agrawal Ankit , Choudhary Alok , Wolverton Christopher
Published: January 2017

A very active area of materials research is to devise methods that use machine learning to automatically extract predictive models from existing materials data. While prior examples have demonstrated successful models for some applications, many more applications exist where machine learning can make a strong impact. To enable faster development of machine-learning-based models for such applications, we have created a framework capable of being applied to a broad range of materials data. Our method works by using a chemically diverse list of attributes, which we demonstrate are suitable for describing a wide variety of properties, and a novel method for partitioning the data set into groups of similar materials to boost the predictive accuracy. In this manuscript, we demonstrate how this new method can be used to predict diverse properties of crystalline and amorphous materials, such as band gap energy and glass-forming ability.
Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide
Authors: Mesnage Robin , Renney George , Séralini Gilles-Eric , Ward Malcolm , Antoniou Michael N.
Published: January 2017

The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q < 0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p < 0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure.
Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse
Authors: Horváth Ádám , Menghis Awt , Botz Bálint , Borbély Éva , Kemény Ágnes , Tékus Valéria , Csepregi Janka Zsófia , Mócsai Attila , Juhász Tamás , Zákány Róza , Bogdán Dóra , Mátyus Péter , Keeble Julie , Pintér Erika , Helyes Zsuzsanna
Published: January 2017

Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.p./day) were investigated in the K/BxN serum-transfer and complete Freund’s adjuvant (CFA)-evoked active immunization models compared to the reference SSAO inhibitor LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema by plethysmometry, clinical severity by scoring, joint function by grid test, myeloperoxidase activity by luminescence, vascular leakage by fluorescencein vivoimaging, histopathological changes by semiquantitative evaluation, and cytokines by Luminex assay. SzV-1287 significantly inhibited hyperalgesia and oedema in both models. Plasma leakage and keratinocyte chemoattractant production in the tibiotarsal joint, but not myeloperoxidase activity was significantly reduced by SzV-1287 in K/BxN-arthritis. SzV-1287 did not influence vascular and cellular mechanisms in CFA-arthritis, but significantly decreased histopathological alterations. There was no difference in the anti-hyperalgesic and anti-inflammatory actions of SzV-1287 and LJP-1207, but only SzV-1287 decreased CFA-induced tissue damage. Unlike SzV-1287, LJP-1207 induced cartilage destruction, which was confirmedin vitro. SzV-1287 exerts potent analgesic and anti-inflammatory actions in chronic arthritis models of distinct mechanisms, without inducing cartilage damage.
Polypurine reverse-Hoogsteen (PPRH) oligonucleotides can form triplexes with their target sequences even under conditions where they fold into G-quadruplexes
Authors: Solé Anna , Delagoutte Emmanuelle , Ciudad Carlos J. , Noé Véronique , Alberti Patrizia
Published: January 2017

Polypurine reverse-Hoogsteen (PPRH) oligonucleotides are non-modified DNA molecules composed of two mirror-symmetrical polypurine stretches linked by a five-thymidine loop. They can fold into reverse-Hoogsteen hairpins and bind to their polypyrimidine target sequence by Watson-Crick bonds forming a three-stranded structure. They have been successfully used to knockdown gene expression and to repair single-point mutations in cells. In this work, we provide an in vitro characterization (UV and fluorescence spectroscopy, gel electrophoresis and nuclease assays) of the structure and stability of two repair-PPRH oligonucleotides and of the complexes they form with their single-stranded targets. We show that one PPRH oligonucleotide forms a hairpin, while the other folds, in potassium, into a guanine-quadruplex (G4). However, the hairpin-prone oligonucleotide does not form a triplex with its single-stranded target, while the G4-prone oligonucleotide converts from a G4 into a reverse-Hoogsteen hairpin forming a triplex with its target sequence. Our work proves, in particular, that folding of a PPRH oligonucleotide into a G4 does not necessarily impair sequence-specific DNA recognition by triplex formation. It also illustrates an original example of DNA structural conversion of a G4 into a reverse-Hoogsteen hairpin driven by triplex formation; this kind of conversion might occur at particular loci of genomic DNA.
Laser printed nano-gratings: orientation and period peculiarities
Authors: Stankevič Valdemar , Račiukaitis Gediminas , Bragheri Francesca , Wang Xuewen , Gamaly Eugene G. , Osellame Roberto , Juodkazis Saulius
Published: January 2017

Understanding of material behaviour at nanoscale under intense laser excitation is becoming critical for future application of nanotechnologies. Nanograting formation by linearly polarised ultra-short laser pulses has been studied systematically in fused silica for various pulse energies at 3D laser printing/writing conditions, typically used for the industrial fabrication of optical elements. The period of the nanogratings revealed a dependence on the orientation of the scanning direction. A tilt of the nanograting wave vector at a fixed laser polarisation was also observed. The mechanism responsible for this peculiar dependency of several features of the nanogratings on the writing direction is qualitatively explained by considering the heat transport flux in the presence of a linearly polarised electric field, rather than by temporal and spatial chirp of the laser beam. The confirmed vectorial nature of the light-matter interaction opens new control of material processing with nanoscale precision.
Regulation of FADS2 transcription by SREBP-1 and PPAR-α influences LC-PUFA biosynthesis in fish
Authors: Dong Xiaojing , Tan Peng , Cai Zuonan , Xu Hanlin , Li Jingqi , Ren Wei , Xu Houguo , Zuo Rantao , Zhou Jianfeng , Mai Kangsen , Ai Qinghui
Published: January 2017

The present study was conducted to explore the mechanisms leading to differences among fishes in the ability to biosynthesize long-chain polyunsaturated fatty acids (LC-PUFAs). Replacement of fish oil with vegetable oil caused varied degrees of increase in 18-carbon fatty acid content and decrease in n-3 LC-PUFA content in the muscle and liver of rainbow trout (Oncorhynchus mykiss), Japanese seabass (Lateolabrax japonicus) and large yellow croaker (Larimichthys crocea), suggesting that these fishes have differing abilities to biosynthesize LC-PUFAs. Fish oil replacement also led to significantly up-regulated expression of FADS2 and SREBP-1 but different responses of the two PPAR-α homologues in the livers of these three fishes. An in vitro experiment indicated that the basic transcription activity of the FADS2 promoter was significantly higher in rainbow trout than in Japanese seabass or large yellow croaker, which was consistent with their LC-PUFA biosynthetic abilities. In addition, SREBP-1 and PPAR-α up-regulated FADS2 promoter activity. These regulatory effects varied considerably between SREBP-1 and PPAR-α, as well as among the three fishes. Taken together, the differences in regulatory activities of the two transcription factors targeting FADS2 may be responsible for the different LC-PUFA biosynthetic abilities in these three fishes that have adapted to different ambient salinity.
Weissella cibaria WIKIM28 ameliorates atopic dermatitis-like skin lesions by inducing tolerogenic dendritic cells and regulatory T cells in BALB/c mice
Authors: Lim Seul Ki , Kwon Min-Sung , Lee Jieun , Oh Young Joon , Jang Ja-Young , Lee Jong-Hee , Park Hae Woong , Nam Young-Do , Seo Myung-Ji , Roh Seong Woon , Choi Hak-Jong
Published: January 2017

The occurrence of atopic dermatitis (AD), a chronic inflammatory skin disease, has been increasing steadily in children and adults in recent decades. In this study, we evaluated the ability of the lactic acid bacterium Weissella cibaria WIKIM28 isolated from gatkimchi, a Korean fermented vegetable preparation made from mustard leaves, to suppress the development of AD induced by 2,4-dinitrochlorobenzene in a murine model. Oral administration of W. cibaria WIKIM28 reduced AD-like skin lesions, epidermal thickening, and serum immunoglobulin E levels. Furthermore, the production of type 2 helper T (Th2) cytokines such as interleukin (IL)-4, IL-5, and IL-13 decreased in peripheral lymph node cells. Moreover, the intake of W. cibaria WIKIM28 increased the proportion of CD4+CD25+Foxp3+ regulatory T (Treg) cells in mesenteric lymph nodes (MLNs) and IL-10 levels in polyclonally stimulated MLN cells. In conclusion, the oral administration of W. cibaria WIKIM28 isolated from gatkimchi ameliorated AD-like symptoms by suppressing allergic Th2 responses and inducing Treg responses. These results suggest that W. cibaria WIKIM28 may be applicable as a probiotic for the prevention and amelioration of AD.
Computational and biochemical characterization of two partially overlapping interfaces and multiple weak-affinity K-Ras dimers
Authors: Prakash Priyanka , Sayyed-Ahmad Abdallah , Cho Kwang-Jin , Dolino Drew M. , Chen Wei , Li Hongyang , Grant Barry J. , Hancock John F. , Gorfe Alemayehu A.
Published: January 2017

Recent studies found that membrane-bound K-Ras dimers are important for biological function. However, the structure and thermodynamic stability of these complexes remained unknown because they are hard to probe by conventional approaches. Combining data from a wide range of computational and experimental approaches, here we describe the structure, dynamics, energetics and mechanism of assembly of multiple K-Ras dimers. Utilizing a range of techniques for the detection of reactive surfaces, protein-protein docking and molecular simulations, we found that two largely polar and partially overlapping surfaces underlie the formation of multiple K-Ras dimers. For validation we used mutagenesis, electron microscopy and biochemical assays under non-denaturing conditions. We show that partial disruption of a predicted interface through charge reversal mutation of apposed residues reduces oligomerization while introduction of cysteines at these positions enhanced dimerization likely through the formation of an intermolecular disulfide bond. Free energy calculations indicated that K-Ras dimerization involves direct but weak protein-protein interactions in solution, consistent with the notion that dimerization is facilitated by membrane binding. Taken together, our atomically detailed analyses provide unique mechanistic insights into K-Ras dimer formation and membrane organization as well as the conformational fluctuations and equilibrium thermodynamics underlying these processes.
Di2-ethylhexyl phthalate disrupts thyroid hormone homeostasis through activating the Ras/Akt/TRHr pathway and inducing hepatic enzymes
Authors: Ye Hanfeng , Ha Mei , Yang Min , Yue Ping , Xie Zhengyuan , Liu Changjiang
Published: January 2017

Di(2-ethylhexyl) phthalate (DEHP), as a widespread environmental pollutant and an endocrine disruptor, can disturb the homeostasis of thyroid hormones (THs). In order to elucidate roles of the MAPK and PI3K/Akt pathways and hepatic enzymes in thyroid-disrupting effects of DEHP, Sprague-Dawley rats were dosed with DEHP by gavage for 30 consecutive days; Nthy-ori 3-1 cells were treated with DEHP with NAC, k-Ras siRNA or inhibitors (U0126 and wortmannin). Results showed that DEHP led to histopathologic changes in rat thyroid and liver, such as the decrease in thyroid follicular cavity diameter, hepatocyte edema. Triiodothyronine (T3), thyroxine (T4) and thyrotropin releasing hormone (TRH) were reduced. DEHP caused ROS production, oxidative stress and k-Ras upregulation, thereby activating the ERK and Akt pathways in vivo and in vitro. Moreover, TRH receptor (TRHr) level was elevated after the activation of the Akt pathway and was downregulated after the inhibition of the Akt pathway. However, TRHr was not modulated by the ERK pathway. Additionally, hepatic enzymes, including Ugt1a1, CYP2b1, Sult1e1, and Sult2b1, were significantly induced after DEHP exposure. Taken together, DEHP can perturb TH homeostasis and reduce TH levels. The activated Ras/Akt/TRHr pathway and induced hepatic enzymes play vital roles in thyroid-disrupting effects of DEHP.
Analytical studies on ascosin, candicidin and levorin multicomponent antifungal antibiotic complexes. The stereostructure of ascosin A2
Authors: Szczeblewski Paweł , Laskowski Tomasz , Kubacki Bartosz , Dziergowska Marta , Liczmańska Magda , Grynda Jakub , Kubica Paweł , Kot-Wasik Agata , Borowski Edward
Published: January 2017

In the class of polyene macrolides, there is a subgroup of aromatic heptaenes, which exhibit the highest antifungal activity within this type of antibiotics. Yet, due to their complex nature, aromatic heptaenes were not extensively studied and their potential as drugs is currently underexploited. Moreover, there are many inconsistencies in the literature regarding the composition and the structures of the individual components of the aromatic heptaene complexes. Inspired by one of such cases, herein we conducted the analytical studies on ascosin, candicidin and levorin using HPLC-DAD-(ESI)Q-TOF techniques. The resulting chromatograms and the molecular masses of the individual components of these three complexes strongly indicated that the major components of ascosin, candicidin and levorin are structurally identical. In order to validate these results, the main component of previously structurally uncharacterized ascosin was derivatized, isolated and subjected to 2D NMR studies. The resulting structure of the ascosin’s main component, herein named ascosin A2, was shown to be identical with the earlier reported structures of the main components of candicidin and levorin complexes: candicidin D and levorin A2. In the end, all the structural knowledge regarding these three antibiotic complexes was gathered, systematized and completed, and the new nomenclature was proposed.
Impaired novelty acquisition and synaptic plasticity in congenital hyperammonemia caused by hepatic glutamine synthetase deficiency
Authors: Chepkova Aisa N. , Sergeeva Olga A. , Görg Boris , Haas Helmut L. , Klöcker Nikolaj , Häussinger Dieter
Published: January 2017

Genetic defects in ammonia metabolism can produce irreversible damage of the developing CNS causing an impairment of cognitive and motor functions. We investigated alterations in behavior, synaptic plasticity and gene expression in the hippocampus and dorsal striatum of transgenic mice with systemic hyperammonemia resulting from conditional knockout of hepatic glutamine synthetase (LGS-ko). These mice showed reduced exploratory activity and delayed habituation to a novel environment. Field potential recordings from LGS-ko brain slices revealed significantly reduced magnitude of electrically-induced long-term potentiation (LTP) in both CA3-CA1 hippocampal and corticostriatal synaptic transmission. Corticostriatal but not hippocampal slices from LGS-ko brains demonstrated also significant alterations in long-lasting effects evoked by pharmacological activation of glutamate receptors. Real-time RT-PCR revealed distinct patterns of dysregulated gene expression in the hippocampus and striatum of LGS-ko mice: LGS-ko hippocampus showed significantly modified expression of mRNAs for mGluR1, GluN2B subunit of NMDAR, and A1 adenosine receptors while altered expression of mRNAs for D1 dopamine receptors, the M1 cholinoreceptor and the acetylcholine-synthetizing enzyme choline-acetyltransferase was observed in LGS-ko striatum. Thus, inborn systemic hyperammonemia resulted in significant deficits in novelty acquisition and disturbed synaptic plasticity in corticostriatal and hippocampal pathways involved in learning and goal-directed behavior.
Increase in α-tubulin modifications in the neuronal processes of hippocampal neurons in both kainic acid-induced epileptic seizure and Alzheimer’s disease
Authors: Vu Hang Thi , Akatsu Hiroyasu , Hashizume Yoshio , Setou Mitsutoshi , Ikegami Koji
Published: January 2017

Neurodegeneration includes acute changes and slow-developing alterations, both of which partly involve common cellular machinery. During neurodegeneration, neuronal processes are impaired along with dysregulated post-translational modifications (PTMs) of cytoskeletal proteins. In neuronal processes, tubulin undergoes unique PTMs including a branched form of modification called glutamylation and loss of the C-terminal tyrosine residue and the penultimate glutamic acid residue forming Δ2-tubulin. Here, we investigated the state of two PTMs, glutamylation and Δ2 form, in both acute and slow-developing neurodegenerations, using a newly generated monoclonal antibody, DTE41, which had 2-fold higher affinity to glutamylated Δ2-tubulin, than to unmodified Δ2-tubulin. DTE41 recognised glutamylated Δ2-tubulin preferentially in immunostaining than in enzyme-linked immunosorbent assay and immunoblotting. In normal mouse brain, DTE41 stained molecular layer of the cerebellum as well as synapse-rich regions in pyramidal neurons of the cerebral cortex. In kainic acid-induced epileptic seizure, DTE41-labelled signals were increased in the hippocampal CA3 region, especially in the stratum lucidum. In the hippocampi of post-mortem patients with Alzheimer’s disease, intensities of DTE41 staining were increased in mossy fibres in the CA3 region as well as in apical dendrites of the pyramidal neurons. Our findings indicate that glutamylation on Δ2-tubulin is increased in both acute and slow-developing neurodegeneration.
Theoretical insight into OH- and Cl-initiated oxidation of CF3OCH(CF3)2 and CF3OCF2CF2H & fate of CF3OC(X•)(CF3)2 and CF3OCF2CF2X• radicals (X=O, O2)
Authors: Bai Feng-Yang , Ma Yuan , Lv Shuang , Pan Xiu-Mei , Jia Xiu-Juan
Published: January 2017

In this study, the mechanistic and kinetic analysis for reactions of CF3OCH(CF3)2 and CF3OCF2CF2H with OH radicals and Cl atoms have been performed at the CCSD(T)//B3LYP/6-311++G(d,p) level. Kinetic isotope effects for reactions CF3OCH(CF3)2/CF3OCD(CF3)2 and CF3OCF2CF2H/CF3OCF2CF2D with OH and Cl were estimated so as to provide the theoretical estimation for future laboratory investigation. All rate constants, computed by canonical variational transition state theory (CVT) with the small-curvature tunneling correction (SCT), are in reasonable agreement with the limited experimental data. Standard enthalpies of formation for the species were also calculated. Atmospheric lifetime and global warming potentials (GWPs) of the reaction species were estimated, the large lifetimes and GWPs show that the environmental impact of them cannot be ignored. The organic nitrates can be produced by the further oxidation of CF3OC(•)(CF3)2 and CF3OCF2CF2• in the presence of O2 and NO. The subsequent decomposition pathways of CF3OC(O•)(CF3)2 and CF3OCF2CF2O• radicals were studied in detail. The derived Arrhenius expressions for the rate coefficients over 230–350 K are: kT(1) = 5.00 × 10−24T3.57 exp(−849.73/T), kT(2) = 1.79 × 10−24T4.84 exp(−4262.65/T), kT(3) = 1.94 × 10−24T4.18 exp(−884.26/T), and kT(4) = 9.44 × 10−28T5.25 exp(−913.45/T) cm3 molecule−1 s−1.
Drug Response Prediction as a Link Prediction Problem
Authors: Stanfield Zachary , Coşkun Mustafa , Koyutürk Mehmet
Published: January 2017

Drug response prediction is a well-studied problem in which the molecular profile of a given sample is used to predict the effect of a given drug on that sample. Effective solutions to this problem hold the key for precision medicine. In cancer research, genomic data from cell lines are often utilized as features to develop machine learning models predictive of drug response. Molecular networks provide a functional context for the integration of genomic features, thereby resulting in robust and reproducible predictive models. However, inclusion of network data increases dimensionality and poses additional challenges for common machine learning tasks. To overcome these challenges, we here formulate drug response prediction as a link prediction problem. For this purpose, we represent drug response data for a large cohort of cell lines as a heterogeneous network. Using this network, we compute “network profiles” for cell lines and drugs. We then use the associations between these profiles to predict links between drugs and cell lines. Through leave-one-out cross validation and cross-classification on independent datasets, we show that this approach leads to accurate and reproducible classification of sensitive and resistant cell line-drug pairs, with 85% accuracy. We also examine the biological relevance of the network profiles.
Long-term exposure to a ‘safe’ dose of bisphenol A reduced protein acetylation in adult rat testes
Authors: Chen Zhuo , Zuo Xuezhi , He Dongliang , Ding Shibin , Xu Fangyi , Yang Huiqin , Jin Xin , Fan Ying , Ying Li , Tian Chong , Ying Chenjiang
Published: January 2017

Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a ‘safe’ dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor β (ERβ) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a ‘safe’ dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERβ for binding to Cav-1.
Redundant functions of I-BAR family members, IRSp53 and IRTKS, are essential for embryonic development
Authors: Chou Ai Mei , Sem Kai Ping , Lam Wei Jun , Ahmed Sohail , Lim Chin Yan
Published: January 2017

The insulin receptor substrate of 53 kDa, IRSp53, is an adaptor protein that works with activated GTPases, Cdc42 and Rac, to modulate actin dynamics and generate membrane protrusions in response to cell signaling. Adult mice that lack IRSp53 fail to regulate synaptic plasticity and exhibit hippocampus-associated learning deficiencies. Here, we show that 60% of IRSp53 null embryos die at mid to late gestation, indicating a vital IRSp53 function in embryonic development. We find that IRSp53 KO embryos displayed pleiotropic phenotypes such as developmental delay, oligodactyly and subcutaneous edema, and died of severely impaired cardiac and placental development. We further show that double knockout of IRSp53 and its closest family member, IRTKS, resulted in exacerbated placental abnormalities, particularly in spongiotrophoblast differentiation and development, giving rise to complete embryonic lethality. Hence, our findings demonstrate a hitherto under-appreciated IRSp53 function in embryonic development, and further establish an essential genetic interaction between IRSp53 and IRTKS in placental formation.
Determination of phenolic compounds in extracts of Amazonian medicinal plants by liquid chromatography-electrospray tandem mass spectrometry
Authors: Faccin Henrique , Loose Roberta Fabricio , Viana Carine , Lameira Osmar A. , de Carvalho Leandro Machado
Published: January 2017

A method for the separation, identification and quantification of 24 phenolic compounds using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) was developed and validated.
Facile fabrication of a magnetically smart PTX-loaded Cys–Fe3O4/CuS@BSA nano-drug for imaging-guided chemo-photothermal therapy
Authors: Ren Lanfang , Liu Xijian , Wang Qian , Zhang Lijuan , Deng Guoying , Zhou Feng , Lu Jie
Published: January 2017

A PTX-loaded Cys-Fe3O4/CuS@BSA nano-drug was synthesized for MR and NIR imaging-guided chemo-photothermal combination therapy of cancer via a facile fabrication method.
Two 2-D multifunctional cobalt(ii) compounds: field-induced single-ion magnetism and catalytic oxidation of benzylic C–H bonds
Authors: Ma Ranran , Chen Zhiwei , Cao Fan , Wang Suna , Huang Xianqiang , Li Yunwu , Lu Jing , Li Dacheng , Dou Jianmin
Published: January 2017

Two 2-D multifunctional cobalt(ii) compounds were reported with both field-induced single-ion magnetism and catalytic oxidation of benzylic C–H bonds.
Two {Dy2} single-molecule magnets formed via an in situ reaction by capturing CO2from atmosphere under ambient conditions
Authors: Zhang Kun , Guo Fu-Sheng , Wang Yao-Yu
Published: January 2017

Under ambient conditions, CO2was captured from the atmosphere, and then reduced and sequestrated into two {Dy2} single-molecule magnets.
All-wood, low tortuosity, aqueous, biodegradable supercapacitors with ultra-high capacitance
Authors: Chen Chaoji , Zhang Ying , Li Yiju , Dai Jiaqi , Song Jianwei , Yao Yonggang , Gong Yunhui , Kierzewski Iain , Xie Jia , Hu Liangbing
Published: January 2017

Natural wood-based materials are directly utilized to construct ultra-thick all-wood-structured supercapacitors with ultra-high capacitance and energy density.
Benzotriazole (BT) and BT plant metabolites in crops irrigated with recycled water
Authors: LeFevre Gregory H. , Lipsky Alicia , Hyland Katherine C. , Blaine Andrea C. , Higgins Christopher P. , Luthy Richard G.
Published: January 2017

Novel benzotriazole plant metabolites were quantified for the first time in crops irrigated with recycled water, demonstrating an exposure route.
Anti-glycation and anti-oxidative effects of a phenolic-enriched maple syrup extract and its protective effects on normal human colon cells
Authors: Liu Weixi , Wei Zhengxi , Ma Hang , Cai Ang , Liu Yongqiang , Sun Jiadong , DaSilva Nicholas A. , Johnson Shelby L. , Kirschenbaum Louis J. , Cho Bongsup P. , Dain Joel A. , Rowley David C. , Shaikh Zahir A. , Seeram Navindra P.
Published: January 2017

Phenolic-enriched maple syrup extract (MSX) inhibits the formation of AGEs and protects normal/non-tumorigenic human colon cells from oxidative stress.
A computational model predicts genetic nodes that allow switching between species-specific responses in a conserved signaling network
Authors: Dawes Adriana T. , Wu David , Mahalak Karley K. , Zitnik Edward M. , Kravtsova Natalia , Su Haiwei , Chamberlin Helen M.
Published: January 2017

Alterations to only specific parameters in a model including EGF, Wnt and Notch lead to cell behavior differences.
Vesicles of double hydrophilic pullulan and poly(acrylamide) block copolymers: a combination of synthetic- and bio-derived blocks
Authors: Willersinn Jochen , Bogomolova Anna , Cabré Marc Brunet , Schmidt Bernhard V. K. J.
Published: January 2017

The formation of vesicular structures with average diameters from 200 to 300 nm consisting of double hydrophilic diblock copolymers pullulan-b-poly(N,N-dimethylacrylamide) and pullulan-b-poly(N-ethylacrylamide) in aqueous solution is described.
Simultaneous determination of aminoglycoside antibiotics in feeds using high performance liquid chromatography with evaporative light scattering detection
Authors: Liu Qingying , Li Jiufeng , Song Xuqin , Zhang Meiyu , Li Erfen , Gao Fuming , He Limin
Published: January 2017

A HPLC-ELSD method was developed for the simultaneous detection of ten aminoglycoside antibiotics.
TOPO mediated rapid hydrothermal synthesis and study of electrochemical performance of nano-structured copper oxide thin films
Authors: Teli A. M. , Navathe G. J. , Patil D. S. , Jadhav P. R. , Patil S. B. , Dongale T. D. , Karanjkar M. M. , Shin Jae Cheol , Patil P. S.
Published: January 2017

This paper reports the synthesis of trioctylphosphine oxide (TOPO) assisted copper oxide (CuO) electrodes by a rapid hydrothermal technique.
A two-dimensional hexagonal boron nitride/polymer nanocomposite for flexible resistive switching devices
Authors: Siddiqui Ghayas Uddin , Rehman Muhammad Muqeet , Yang Young-Jin , Choi Kyung Hyun
Published: January 2017

Organic–inorganic hybrid nanocomposites are an attractive choice for various electronic device applications.
Weak Intermolecular Forces, but High Melting Points
Authors: Gao Jiabin , Djaidi Djamal , Marjo Christopher E. , Bhadbhade Mohan M. , Ung Alison T. , Bishop Roger
Published: January 2017

The poorly soluble racemic compound 6,6a,13,13a-tetrahydropentaleno[1,2-b:4,5-b′]diquinoline (4) has an exceptionally high melting point range of 352–354°C despite its low molar mass (308.38) and a structure containing only 40 atoms (38 of which are C and H). Analysis of the X-ray crystal structure and Hirshfeld surface of 4, along with comparison with its isostructural homologue 2, reveals how this occurs in the absence of Pauling-type hydrogen bonding. Excellent complementarity between homochiral molecules of 4 allows formation of enantiomerically pure layers using C–H⋯π, aromatic π⋯π, and C–H⋯N interactions. The alternating layers of opposite handedness are then crosslinked by means of aza-1,3-peri hydrogen interactions. This bifurcated C–H⋯N⋯H–C motif acts as a molecular clip creating a highly rigid network structure. The role of weaker intermolecular forces in influencing the solubility and bioavailability of potential drug molecules is discussed in the context of the popular Lipinski ‘rule of 5’ guidelines.
Shot peening of austempered ductile iron gears
Authors: Zammit Ann , Bonnici Matthew , Mhaede Mansour , Wan Rui , Wagner Lothar
Published: January 2017

This study investigates the suitability of shot peening as a surface treatment for austempered ductile iron (ADI) gears to lengthen their service life. Several studies have shown that shot peening prolongs the bending fatigue life of components. However, from the few works conducted on the tribological behaviour of ADI, it is not clear whether an improvement exists by shot peening. Hence, this work was conducted to study the contact fatigue resistance of shot peened ADI gears. Tests on as-ADI and shot peened ADI gears, as well as carburised steel gears were carried out. The results showed that the carburised steel gears exhibited superior performance and withstood the longest number of cycles before failure. The shot peened gears survived the lowest number of cycles. The poor performance after shot peening was attributed to an increase in the surface roughness induced by the peening process. In fact, the negative impact resulting from the roughened surface is greater than the benefits prompted by the induced compressive residual stresses, higher surface hardness and stress-induced austenite to martensite transformation.
Comparative analysis of the complete mitochondrial genomes of three geographical topmouth culter (Culter alburnus) groups and implications for their phylogenetics
Authors: Shi Jianwu , Wang Dexia , Wang Junhua , sheng Junqing , Peng Kou , Hu Beijuan , Zeng Liugen , Xiao Minghe , Hong Yijiang
Published: January 2017

Topmouth culter (C. alburnus) is an important commercial fish in China. We compared the nucleotide variations in the mtDNA genomes among three geographical groups of Culter alburnus: Liangzi Lake, Hubei Province (referred to as LZH); Taihu Lake, Jiangsu Province (TH); and Poyang Lake, Jiangxi Province (PYH). The similarity of whole mtDNA genomes ranged from 0.992 to 0.999. The similarity among 13 protein-coding genes, 2 rRNA genes, and the D-loop sequences was found to range from 0.982 to 0.996. This is useful data for future designing work for making specific molecular marker for distinguishing individuals of C. alburnus from the three geographical groups. An extended termination-associated sequence (ETAS) and several conserved blocks (CSB-F, CSB-E, CSB-D, CSB1, CSB2, and CSB3) were identified in the mtDNA control regions. A phylogenetic analysis shows a monophyletic relationship of the LZF-female and the LZF-male. However, the analysis also showed paraphyletic relationships for the other two geological groups. This result will be useful for the future breeding work of C. alburnus.
Orbital friction stir lap welding in tubular parts of aluminium alloy AA5083
Authors: Jamshidi Aval H. , Falahati Naghibi M.
Published: January 2017

In this study, orbital friction stir lap welding of 360 mm diameter AA5083-H321 tube to 350 mm diameter AA5083-O flange was investigated. The influence of rotational and travel speed of tool with triangular frustum pin on the metallurgical structure and mechanical properties of orbital friction stir lap welded samples were studied. The results indicated that defect free orbital lap joints are successfully obtained using tool rotational speed of 650 and 800 rev min−1 with a constant travel speed of 40 mm min−1. The strengthening mechanism in the stir zone is solid solution strengthening and dislocation looping. The maximum joint strength was achieved at a welding speed of 650 rev min−1 and 40 mm min−1. Failure of tensile shear test samples occurred far from the friction stir welding zone.
Management of Asiatic Citrus Canker Under Field Conditions in Saudi Arabia Using Bacteriophages and Acibenzolar-S-Methyl
Authors: Ibrahim Yasser E. , Saleh Amgad A. , Al-Saleh Mohammed A.
Published: January 2017

Applications of formulated bacteriophages with skim milk and sucrose or nonformulated bacteriophages combined with acibenzolar-S-methyl (ASM) were compared with copper bactericides applications for suppressing Asiatic citrus canker (ACC) caused by Xanthomonas citri subsp. citri (Xcc) on leaves under greenhouse and field conditions in Saudi Arabia. Bacteriophages were applied one day prior to inoculation of Mexican lime (Citrus aurantifolia) plants with Xcc, then twice a week until the end of the trials. Copper hydroxide was applied once prior to inoculation and then every seven days afterward, whereas ASM was applied one week prior to inoculation and then every 21 days afterward. Under greenhouse conditions, the incidence of ACC on leaves was reduced significantly from 75.2 to 12.8% or 18.3% for plants treated with copper hydroxide or bacteriophages in combination with ASM, respectively. Applications of formulated phages in combination with ASM as soil drench under field conditions significantly decreased disease incidence by 14.8% (Trial 1) and 16.8% (Trial 2) compared with untreated control plants. Overall, the Xcc-inoculated plants treated with bacteriophages + ASM combination showed significant ACC reduction under greenhouse and field conditions. The bacteriophages + ASM combination tested in these trials can be an effective tool in the integrated management programs of Asiatic citrus canker disease.
Timing of Apple Fruit Infection by Neofabraea perennans and Neofabraea kienholzii in Relation to Bull’s-eye Rot Development in Stored Apple Fruit
Authors: Aguilar C. G. , Mazzola M. , Xiao C. L.
Published: January 2017

Bull’s-eye rot is a postharvest disease of pome fruit in the U.S. Pacific Northwest. The disease is caused by the fungi Neofabraea kienholzii, N. malicorticis, N. perennans, and N. vagabunda. Fruit infection by these pathogens is initiated in the orchard during the fruit-growing season but remains latent at harvest. For fruit held in postharvest cold storage, bull’s-eye rot symptom development is slow to progress, requiring at least 3 months before symptoms are first visible. In order to determine the timing of preharvest fruit infection in relation to bull’s-eye rot development in cold storage, ‘Red Delicious’ and ‘Fuji’ apple fruit were inoculated with a conidial suspension of N. perennans or N. kienholzii at different inoculation timings throughout the fruit growing seasons of 2012 to 2014. Fruit were harvested and stored at 0°C for up to 10 months, during which time disease incidence was recorded periodically. Results from this study demonstrate that apple fruit infection by either pathogen may occur at any point during the growing season. However, infections occurring over the 8-week period immediately prior to harvest yield a higher incidence of bull’s-eye rot in stored fruit compared with infections initiated earlier in the growing season.
Use of an Analog Scale in the Treatment of Patients With Bipolar Disorder to Optimize Assessment and Clinical Outcome
Authors: PRESKORN SHELDON H.
Published: January 2017

This column explains how a clinician can use an analog scale for patients with bipolar disorder: (1) to elucidate the course of the illness in a specific patient and (2) to assess response to treatment. This scale complements other standardized rating scales, such as the Young Mania Rating Scale, because its anchors are tailored to each specific patient in terms of the worst depressive or hypomanic/manic episode (ie, a −10 or +10, respectively) the person has ever experienced. The scale also allows clinicians to track how the individual patient’s episodes have responded to treatment in the past, including whether the patient ever has achieved a full remission (ie, score of 0) following the initial onset of the disorder. The scale can then be used to assess how the patient in an acute or chronic active episode responds to new treatment, whether somatic and/or psychotherapeutic, and how that compares with historical responses to previous treatments. Going forward, the scale can be used to assess the course of the patient’s illness (eg, episodic with full recovery or chronic with more severe episodes and increasing residual symptoms). Through use of this analog scale, the patient also develops a better understanding of his or her illness, including how episodes develop and resolve and whether there are factors (eg, interpersonal relationships, inflammatory processes, substance use) that either aggravate and/or are aggravated by the disorder. This simple scale thus fulfills many purposes including history gathering, monitoring the usefulness of different treatment interventions, and patient education.
Psychotherapy, Parity, and Ethical Utilization Management
Authors: PLAKUN ERIC M.
Published: January 2017

Managed care has long functioned with the assumption of a split in clinical and ethical responsibility for treatment. The insurance company clinician has been seen as owing a primary obligation to the insurance company and its utilization management standards, while the treating clinician is seen as holding primary clinical and ethical responsibility for the patient and the treatment. This article explores the potential impact of mental health parity mandates and recent clarifications of the American Psychiatric Association’s ethical code on this split for psychiatrists and other clinicians who develop utilization management standards or serve as utilization reviewers.
Electrochemical evaluation of AZ 31 magnesium alloy in two simulated biological solutions
Authors: Yazdani Meghdad , Afshar Abdollah , Mohammadi Namdar , Paranj Behrooz
Published: January 2017

Purpose

This paper aims to investigate the corrosion behavior of AZ31 alloy as a prospective biomedical implant in two different simulated biological solutions and various immersion times.

Design/methodology/approach

Results of electrochemical experiments indicated that corrosion resistance of specimens immersed for 24 h was superior, suggesting that the surface layer is capable of protecting alloy.

Findings

Scanning electron micrographs revealed that this layer abounds with cracks, exhibiting optimum quality in 24 h immersion time, after which it begins to develop corrosion pits. Energy dispersive spectroscopy analysis suggested that the layer is mainly composed of magnesium hydroxide with precipitates of P and Ca containing species present on its surface, which is an indication of biocompatibility.

Originality/value

Finally, corrosion performance of Mg alloy was found to be slightly better in Lac-simulated biological solution (SBF) solution, which is more representative of actual physiological environment as compared to conventional SBF solutions.