bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractRecent 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

AbstractDi(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

AbstractIn 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

AbstractGenetic 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

AbstractNeurodegeneration 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

AbstractIn 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

AbstractDrug 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

AbstractBisphenol 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

AbstractThe 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.
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

Abstract
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.
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.
Damage evolution of coated steel pipe under cathodic-protection in soil
Authors: Li Ximing , Castaneda Homero 
Published: January 2017

Purpose
The purpose of this paper is to study the damage evolution (DE) of coated API5L-X52 steel pipe with cathodic protection (CP) in nature soil. Also, different coating conditions, intact coating and coating with artificial holiday defect are considered to study the electrochemical behavior combined with soil properties and CP potential. An approach of electrochemical impedance spectroscopy (EIS) analysis is also developed.

Design/methodology/approach
This work developed a laboratory experimental set-up of coated pipeline under CP in nature soil. The electrochemical behavior has been investigated using EIS. The CP potential provided by a DC power supplier has been adjusted and recorded to maintain the protective potential of pipe at −850 mV vs Cu/CuSO4.

Findings
Various parameters were derived from the EIS fitting data by equivalent circuit models to illustrate the three DE stages of coated carbon steel in soil. Each stage changes faster for the artificial defect coating system compared to intact coating, especially at the initial water uptake and ion transport stage. The CP potential has been proved to be correlated to the soil properties, coating conditions and DE stages of pipeline samples.

Originality/value
This work is the first one to study DE of coated pipeline system under CP in soil. It introduces an electrochemical method to study coating defects which can promote to design the deterministic model to detect coating defects of buried pipe using AC impedance technique.
Inhibition effect of E and Z conformations of 2-pyridinealdazine on mild steel corrosion in phosphoric acid
Authors: Belghiti Mohammed Elalaoui , Nahlé Ayssar , Ansari Abdeslam , Karzazi Yasser , Tighadouini S. , El Ouadi Yassir , Dafali A. , Hammouti Belkheir , Radi Smaail 
Published: January 2017

PurposeThis paper aims to study the inhibition effect of 2-pyridinealdazine on the corrosion of mild steel in an acidic medium. The inhibition effect was studied using weight loss, electrochemical impedance spectroscopy, and Tafel polarization measurements.Design/methodology/approachWeight loss measurements, potentiodynamic tests, electrochemical impedance spectroscopy, X-ray diffraction and spectral and conformational isomers analysis of A (E-PAA) and B (Z-PAA) were performed were investigated.Findings2-pyridinealdazine (PAA) acts as a good inhibitor for the corrosion of steel in 2.0 M H3PO4. The inhibition efficiency increases with an increase in inhibitor concentration but decreases with an increase in temperature.Originality/valueThis paper is intended to be added to the family of azines which are highly efficient inhibitors and can be used in the area of corrosion prevention and control.
Drivers and barriers to reshoring: a literature review on offshoring in reverse
Authors: Wiesmann Benedikt , Snoei Jochem Ronald , Hilletofth Per , Eriksson David 
Published: January 2017

Purpose
The purpose of this paper is to clarify the rather blurry concept of reshoring and its main drivers and barriers. At the same time, the paper seeks to provide a much-needed overview of the scientific theories used in previous research on reshoring.

Design/methodology/approach
The paper gathers information from previous published research. Data were collected through a systematic literature review on “reshoring” using primarily qualitative research techniques. Through a structured keyword search and subsequent elimination of papers, 22 peer-reviewed journal papers made it into the final review.

Findings
There is currently no consensus on the definition or “theory of reshoring”. Drivers and barriers could be grouped into five different sets of dynamics: global competitive dynamics, home country, host country, supply chain and firm-specific.

Research limitations/implications
Researchers need to consider the future development of the field and work toward an accepted terminology. Models about reshoring decisions need to include several decision criteria, which goes beyond financial metrics.

Practical implications
Practitioners need to carefully consider the decision to reshore as to not make rushed decisions. The final decision needs to consider factors such as quality, risk and brand reputation.

Originality/value
The paper is, to authors’ knowledge, the first overview of earlier research in a research journal. It provides a much-needed overview of an emerging field that can hold great importance for both future research and production. The constructed framework structures the dynamics (drivers and barriers) associated with reshoring.
China’s regional science and technology innovation policy
Authors: Yong’an Zhang , Zhe Geng , Jie Tian 
Published: January 2017

Purpose
Science and technology innovation policy has important strategic significance with respect to the promotion of an innovation orientation in our country, and the classification and measurement of regional science and technology innovation policy urgently require research attention.

Design/methodology/approach
In this paper, we use text mining and principal component analysis to analyze the classification and measurement of technology innovation policy based on data obtained from Zhongguancun Science Park.

Findings
The empirical results indicate that regional science and technology innovation policy can be divided into four types: authoritative, guiding, urgent and periodical. The key measurements are function type, intensity, resource supply, funding level and funding effectiveness.

Originality/value
A comparative analysis is performed to investigate the different types of regional science and technology innovation policy measurement. Additionally, the study’s limitations are discussed, and future research directions are proposed.