bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational improvement of gp41-targeting HIV-1 fusion inhibitors: an innovatively designed Ile-Asp-Leu tail with alternative conformations
Authors: Zhu Yun , Su Shan , Qin Lili , Wang Qian , Shi Lei , Ma Zhenxuan , Tang Jianchao , Jiang Shibo , Lu Lu , Ye Sheng , Zhang Rongguang 
Published: September 2016

AbstractPeptides derived from the C-terminal heptad repeat (CHR) of HIV gp41 have been developed as effective fusion inhibitors against HIV-1, but facing the challenges of enhancing potency and stability. Here, we report a rationally designed novel HIV-1 fusion inhibitor derived from CHR-derived peptide (Trp628~Gln653, named CP), but with an innovative Ile-Asp-Leu tail (IDL) that dramatically increased the inhibitory activity by up to 100 folds. We also determined the crystal structures of artificial fusion peptides N36- and N43-L6-CP-IDL. Although the overall structures of both fusion peptides share the canonical six-helix bundle (6-HB) configuration, their IDL tails adopt two different conformations: a one-turn helix with the N36 and a hook-like structure with the longer N43. Structural comparison showed that the hook-like IDL tail possesses a larger interaction interface with NHR than the helical one. Further molecular dynamics simulations of the two 6-HBs and isolated CP-IDL peptides suggested that hook-like form of IDL tail can be stabilized by its binding to NHR trimer. Therefore, CP-IDL has potential for further development as a new HIV fusion inhibitor and this strategy could be widely used in developing artificial fusion inhibitors against HIV and other enveloped viruses.
Systemic blockade of ACVR2B ligands prevents chemotherapy-induced muscle wasting by restoring muscle protein synthesis without affecting oxidative capacity or atrogenes
Authors: Nissinen T. A. , Degerman J. , Räsänen M. , Poikonen A. R. , Koskinen S. , Mervaala E. , Pasternack A. , Ritvos O. , Kivelä R. , Hulmi J. J. 
Published: September 2016

AbstractDoxorubicin is a widely used and effective chemotherapy drug. However, cardiac and skeletal muscle toxicity of doxorubicin limits its use. Inhibiting myostatin/activin signalling can prevent muscle atrophy, but its effects in chemotherapy-induced muscle wasting are unknown. In the present study we investigated the effects of doxorubicin administration alone or combined with activin receptor ligand pathway blockade by soluble activin receptor IIB (sACVR2B-Fc). Doxorubicin administration decreased body mass, muscle size and bone mineral density/content in mice. However, these effects were prevented by sACVR2B-Fc administration. Unlike in many other wasting situations, doxorubicin induced muscle atrophy without markedly increasing typical atrogenes or protein degradation pathways. Instead, doxorubicin decreased muscle protein synthesis which was completely restored by sACVR2B-Fc. Doxorubicin administration also resulted in impaired running performance without effects on skeletal muscle mitochondrial capacity/function or capillary density. Running performance and mitochondrial function were unaltered by sACVR2B-Fc administration. Tumour experiment using Lewis lung carcinoma cells demonstrated that sACVR2B-Fc decreased the cachectic effects of chemotherapy without affecting tumour growth. These results demonstrate that blocking ACVR2B signalling may be a promising strategy to counteract chemotherapy-induced muscle wasting without damage to skeletal muscle oxidative capacity or cancer treatment.
Identification and comparative analysis of the microRNA transcriptome in roots of two contrasting tobacco genotypes in response to cadmium stress
Authors: He Xiaoyan , Zheng Weite , Cao Fangbin , Wu Feibo 
Published: September 2016

AbstractTobacco (Nicotiana tabacumL.) is more acclimated to cadmium (Cd) uptake and preferentially enriches Cd in leaves than other crops. MicroRNAs (miRNAs) play crucial roles in regulating expression of various stress response genes in plants. However, genome-wide expression of miRNAs and their target genes in response to Cd stress in tobacco are still unknown. Here, miRNA high-throughput sequencing technology was performed using two contrasting tobacco genotypes Guiyan 1 and Yunyan 2 of Cd-sensitive and tolerance. Comprehensive analysis of miRNA expression profiles in control and Cd treated plants identified 72 known (27 families) and 14 novel differentially expressed miRNAs in the two genotypes. Among them, 28 known (14 families) and 5 novel miRNAs were considered as Cd tolerance associated miRNAs, which mainly involved in cell growth, ion homeostasis, stress defense, antioxidant and hormone signaling. Finally, a hypothetical model of Cd tolerance mechanism in Yunyan 2 was presented. Our findings suggest that some miRNAs and their target genes and pathways may play critical roles in Cd tolerance.
Identification and testing of oviposition attractant chemical compounds for Musca domestica
Authors: Tang Rui , Zhang Feng , Kone N’Golopé , Chen Jing-Hua , Zhu Fen , Han Ri-Chou , Lei Chao-Liang , Kenis Marc , Huang Ling-Qiao , Wang Chen-Zhu 
Published: September 2016

AbstractOviposition attractants for the house fly Musca domestica have been investigated using electrophysiological tests, behavioural assays and field tests. Volatiles were collected via head space absorption method from fermented wheat bran, fresh wheat bran, rearing substrate residue and house fly maggots. A Y-tube olfactometer assay showed that the odor of fermented wheat bran was a significant attractant for female house flies. Bioactive compounds from fermented wheat bran for house fly females were identified by electrophysiology and mass spectrophotometry and confirmed with standard chemicals. Four electrophysiologically active compounds including ethyl palmitate, ethyl linoleate, methyl linoleate, and linoleic acid were found at a proportion of 10:24:6:0.2. Functional imaging in the female antennal lobes revealed an overlapped active pattern for all chemicals. Further multiple-choice behavioural bioassays showed that these chemicals, as well as a mixture that mimicked the naturally occurring combination, increased the attractiveness of non-preferred rearing substrates of cotton and maize powder. Finally, a field demonstration test revealed that, by adding this mimic blend into a rearing substrate used to attract and breed house flies in West Africa, egg numbers laid by females were increased. These chemicals could be utilized to improve house fly production systems or considered for lure traps.
Design, Synthesis and Evaluation of Novel Isoxazolines/Oxime Sulfonates of 2′(2′,6′)-(Di)Chloropodophyllotoxins as Insecticidal Agents
Authors: Yu Mingqiao , Liu Guangci , Zhang Yuanyuan , Feng Tao , Xu Ming , Xu Hui 
Published: September 2016

AbstractA series of 2′(2′,6′)-(di)halogeno-isoxazolopodophyllic acids-based esters, and oxime sulfonates of 2′(2′,6′)-(di)halogenopodophyllones were prepared by structural modifications of podophyllotoxin as insecticidal agents against Mythimna separata Walker. It was found that when 2′(2′,6′)-(di)halogenopodophyllones or 2′(2′,6′)-(di)chloropicropodophyllones reacted with hydroxylamine hydrochloride, the desired products were related with the configuration of their lactones. Three key single-crystal structures of Ie, IIe and IIIb were determined by X-ray diffraction. Especially compounds IIc and Vc showed the highest insecticidal activity. Moreover, some interesting results of structure-insecticidal activity relationships of tested compounds were also observed.
Exposure to Sound Vibrations Lead to Transcriptomic, Proteomic and Hormonal Changes in Arabidopsis
Authors: Ghosh Ritesh , Mishra Ratnesh Chandra , Choi Bosung , Kwon Young Sang , Bae Dong Won , Park Soo-Chul , Jeong Mi-Jeong , Bae Hanhong 
Published: September 2016

AbstractSound vibration (SV) is considered as an external mechanical force that modulates plant growth and development like other mechanical stimuli (e.g., wind, rain, touch and vibration). A number of previous and recent studies reported developmental responses in plants tailored against SV of varied frequencies. This strongly suggests the existence of sophisticated molecular mechanisms for SV perception and signal transduction. Despite this there exists a huge gap in our understanding regarding the SV-mediated molecular alterations, which is a prerequisite to gain insight into SV-mediated plant development. Herein, we investigated the global gene expression changes inArabidopsis thalianaupon treatment with five different single frequencies of SV at constant amplitude for 1 h. As a next step, we also studied the SV-mediated proteomic changes in Arabidopsis. Data suggested that like other stimuli, SV also activated signature cellular events, for example, scavenging of reactive oxygen species (ROS), alteration of primary metabolism, and hormonal signaling. Phytohormonal analysis indicated that SV-mediated responses were, in part, modulated by specific alterations in phytohormone levels; especially salicylic acid (SA). Notably, several touch regulated genes were also up-regulated by SV treatment suggesting a possible molecular crosstalk among the two mechanical stimuli, sound and touch. Overall, these results provide a molecular basis to SV triggered global transcriptomic, proteomic and hormonal changes in plant.
Electronic properties of MoS2/MoOx interfaces: Implications in Tunnel Field Effect Transistors and Hole Contacts
Authors: K. C. Santosh , Longo Roberto C. , Addou Rafik , Wallace Robert M. , Cho Kyeongjae 
Published: September 2016

AbstractIn an electronic device based on two dimensional (2D) transitional metal dichalcogenides (TMDs), finding a low resistance metal contact is critical in order to achieve the desired performance. However, due to the unusual Fermi level pinning in metal/2D TMD interface, the performance is limited. Here, we investigate the electronic properties of TMDs and transition metal oxide (TMO) interfaces (MoS2/MoO3) using density functional theory (DFT). Our results demonstrate that, due to the large work function of MoO3 and the relative band alignment with MoS2, together with small energy gap, the MoS2/MoO3 interface is a good candidate for a tunnel field effect (TFET)-type device. Moreover, if the interface is not stoichiometric because of the presence of oxygen vacancies in MoO3, the heterostructure is more suitable for p-type (hole) contacts, exhibiting an Ohmic electrical behavior as experimentally demonstrated for different TMO/TMD interfaces. Our results reveal that the defect state induced by an oxygen vacancy in the MoO3 aligns with the valance band of MoS2, showing an insignificant impact on the band gap of the TMD. This result highlights the role of oxygen vacancies in oxides on facilitating appropriate contacts at the MoS2 and MoOx (x < 3) interface, which consistently explains the available experimental observations.
MuSK Kinase Activity is Modulated By A Serine Phosphorylation Site in The Kinase Loop
Authors: Camurdanoglu B. Z. , Hrovat C. , Dürnberger G. , Madalinski M. , Mechtler K. , Herbst R. 
Published: September 2016

AbstractThe neuromuscular junction (NMJ) forms when a motor neuron contacts a muscle fibre. A reciprocal exchange of signals initiates a cascade of signalling events that result in pre- and postsynaptic differentiation. At the centre of these signalling events stands muscle specific kinase (MuSK). MuSK activation, kinase activity and subsequent downstream signalling are crucial for NMJ formation as well as maintenance. Therefore MuSK kinase activity is tightly regulated to ensure proper NMJ development. We have identified a novel serine phosphorylation site at position 751 in MuSK that is increasingly phosphorylated upon agrin stimulation. S751 is also phosphorylated in muscle tissue and its phosphorylation depends on MuSK kinase activity. A phosphomimetic mutant of S751 increases MuSK kinase activity in response to non-saturating agrin concentrations . In addition, basal MuSK and AChR phosphorylation as well as AChR cluster size are increased. We believe that the phosphorylation of S751 provides a novel mechanism to relief the autoinhibition of the MuSK activation loop. Such a lower autoinhibition could foster or stabilize MuSK kinase activation, especially during stages when no or low level of agrin are present. Phosphorylation of S751 might therefore represent a novel mechanism to modulate MuSK kinase activity during prepatterning or NMJ maintenance.
Development and characterisation of highly antibiotic resistant Bartonella bacilliformis mutants
Authors: Gomes Cláudia , Martínez-Puchol Sandra , Ruiz-Roldán Lidia , Pons Maria J. , del Valle Mendoza Juana , Ruiz Joaquim 
Published: September 2016

AbstractThe objective was to develop and characterise in vitro Bartonella bacilliformis antibiotic resistant mutants. Three B. bacilliformis strains were plated 35 or 40 times with azithromycin, chloramphenicol, ciprofloxacin or rifampicin discs. Resistance-stability was assessed performing 5 serial passages without antibiotic pressure. MICs were determined with/without Phe-Arg-β-Napthylamide and artesunate. Target alterations were screened in the 23S rRNA, rplD, rplV, gyrA, gyrB, parC, parE and rpoB genes. Chloramphenicol and ciprofloxacin resistance were the most difficult and easiest (>37.3 and 10.6 passages) to be selected, respectively. All mutants but one selected with chloramphenicol achieved high resistance levels. All rifampicin, one azithromycin and one ciprofloxacin mutants did not totally revert when cultured without antibiotic pressure. Azithromycin resistance was related to L4 substitutions Gln-66 → Lys or Gly-70 → Arg; L4 deletion Δ62–65 (Lys-Met-Tyr-Lys) or L22 insertion 83::Val-Ser-Glu-Ala-His-Val-Gly-Lys-Ser; in two chloramphenicol-resistant mutants the 23S rRNA mutation G2372A was detected. GyrA Ala-91 → Val and Asp-95 → Gly and GyrB Glu474 → Lys were detected in ciprofloxacin-resistant mutants. RpoB substitutions Gln-527 → Arg, His-540 → Tyr and Ser-545 → Phe plus Ser-588 → Tyr were detected in rifampicin-resistant mutants. In 5 mutants the effect of efflux pumps on resistance was observed. Antibiotic resistance was mainly related to target mutations and overexpression of efflux pumps, which might underlie microbiological failures during treatments.
Fast generations of tree-type three-dimensional entanglement via Lewis-Riesenfeld invariants and transitionless quantum driving
Authors: Wu Jin-Lei , Ji Xin , Zhang Shou 
Published: September 2016

AbstractRecently, a novel three-dimensional entangled state called tree-type entanglement, which is likely to have applications for improving quantum communication security, was prepared via adiabatic passage by Songet al. Here we propose two schemes for fast generating tree-type three-dimensional entanglement among three spatially separated atoms via shortcuts to adiabatic passage. With the help of quantum Zeno dynamics, two kinds of different but equivalent methods, Lewis-Riesenfeld invariants and transitionless quantum driving, are applied to construct shortcuts to adiabatic passage. The comparisons between the two methods are discussed. The strict numerical simulations show that the tree-type three-dimensional entangled states can be fast prepared with quite high fidelities and the two schemes are both robust against the variations in the parameters, atomic spontaneous emissions and the cavity-fiber photon leakages.
Characterization of CD46 and β1 integrin dynamics during sperm acrosome reaction
Authors: Frolikova Michaela , Sebkova Natasa , Ded Lukas , Dvorakova-Hortova Katerina 
Published: September 2016

AbstractThe acrosome reaction (AR) is a process of membrane fusion and lytic enzyme release, which enables sperm to penetrate the egg surroundings. It is widely recognized that specific sperm proteins form an active network prior to fertilization and their dynamic relocation is crucial for the sperm-egg fusion. The unique presence of the membrane cofactor protein CD46 in the sperm acrosomal membrane was shown, however, its behaviour and connection with other sperm proteins has not been explored further. Using super resolution microscopy, we demonstrated a dynamic CD46 reorganisation over the sperm head during the AR and its interaction with transmembrane protein integrins, which was confirmed by proximity ligation assay. Furthermore, we propose their joint involvement in actin network rearrangement. Moreover, CD46 and β1 integrins with subunit α3, but not α6, are localized into the apical acrosome and are expected to be involved in signal transduction pathways directing the acrosome stability and essential protein network rearrangements prior to gamete fusion.
True Randomness from Big Data
Authors: Papakonstantinou Periklis A. , Woodruff David P. , Yang Guang 
Published: September 2016

AbstractGenerating random bits is a difficult task, which is important for physical systems simulation, cryptography, and many applications that rely on high-quality random bits. Our contribution is to show how to generate provably random bits from uncertain events whose outcomes are routinely recorded in the form of massive data sets. These include scientific data sets, such as in astronomics, genomics, as well as data produced by individuals, such as internet search logs, sensor networks, and social network feeds. We view the generation of such data as the sampling process from a big source, which is a random variable of size at least a few gigabytes. Our view initiates the study of big sources in the randomness extraction literature. Previous approaches for big sources rely on statistical assumptions about the samples. We introduce a general method that provably extracts almost-uniform random bits from big sources and extensively validate it empirically on real data sets. The experimental findings indicate that our method is efficient enough to handle large enough sources, while previous extractor constructions are not efficient enough to be practical. Quality-wise, our method at least matches quantum randomness expanders and classical world empirical extractors as measured by standardized tests.
Analysis of heterogeneous dengue transmission in Guangdong in 2014 with multivariate time series model
Authors: Cheng Qing , Lu Xin , Wu Joseph T. , Liu Zhong , Huang Jincai 
Published: September 2016

AbstractGuangdong experienced the largest dengue epidemic in recent history. In 2014, the number of dengue cases was the highest in the previous 10 years and comprised more than 90% of all cases. In order to analyze heterogeneous transmission of dengue, a multivariate time series model decomposing dengue risk additively into endemic, autoregressive and spatiotemporal components was used to model dengue transmission. Moreover, random effects were introduced in the model to deal with heterogeneous dengue transmission and incidence levels and power law approach was embedded into the model to account for spatial interaction. There was little spatial variation in the autoregressive component. In contrast, for the endemic component, there was a pronounced heterogeneity between the Pearl River Delta area and the remaining districts. For the spatiotemporal component, there was considerable heterogeneity across districts with highest values in some western and eastern department. The results showed that the patterns driving dengue transmission were found by using clustering analysis. And endemic component contribution seems to be important in the Pearl River Delta area, where the incidence is high (95 per 100,000), while areas with relatively low incidence (4 per 100,000) are highly dependent on spatiotemporal spread and local autoregression.
Endothelial Antioxidant-1: a Key Mediator of Copper-dependent Wound Healing in vivo
Authors: Das Archita , Sudhahar Varadarajan , Chen Gin-Fu , Kim Ha Won , Youn Seock-Won , Finney Lydia , Vogt Stefan , Yang Jay , Kweon Junghun , Surenkhuu Bayasgalan , Ushio-Fukai Masuko , Fukai Tohru 
Published: September 2016

AbstractCopper (Cu), an essential nutrient, promotes wound healing, however, target of Cu action and underlying mechanisms remain elusive. Cu chaperone Antioxidant-1 (Atox1) in the cytosol supplies Cu to the secretory enzymes such as lysyl oxidase (LOX), while Atox1 in the nucleus functions as a Cu-dependent transcription factor. Using mouse cutaneous wound healing model, here we show that Cu content (by X-ray Fluorescence Microscopy) and nuclear Atox1 are increased after wounding, and that wound healing with and without Cu treatment is impaired in Atox1−/− mice. Endothelial cell (EC)-specific Atox1−/− mice and gene transfer of nuclear-target Atox1 in Atox1−/− mice reveal that Atox1 in ECs as well as transcription factor function of Atox1 are required for wound healing. Mechanistically, Atox1−/− mice show reduced Atox1 target proteins such as p47phox NADPH oxidase and cyclin D1 as well as extracellular matrix Cu enzyme LOX activity in wound tissues. This in turn results in reducing O2− production in ECs, NFkB activity, cell proliferation and collagen formation, thereby inhibiting angiogenesis, macrophage recruitment and extracellular matrix maturation. Our findings suggest that Cu-dependent transcription factor/Cu chaperone Atox1 in ECs plays an important role to sense Cu to accelerate wound angiogenesis and healing.
Migratory blackcaps can use their magnetic compass at 5 degrees inclination, but are completely random at 0 degrees inclination
Authors: Schwarze Susanne , Steenken Friederike , Thiele Nadine , Kobylkov Dmitry , Lefeldt Nele , Dreyer David , Schneider Nils-Lasse , Mouritsen Henrik 
Published: September 2016

AbstractIt is known that night-migratory songbirds use a magnetic compass measuring the magnetic inclination angle, i.e. the angle between the Earth’s surface and the magnetic field lines, but how do such birds orient at the magnetic equator? A previous study reported that birds are completely randomly oriented in a horizontal north-south magnetic field with 0° inclination angle. This seems counter-intuitive, because birds using an inclination compass should be able to separate the north-south axis from the east-west axis, so that bimodal orientation might be expected in a horizontal field. Furthermore, little is known about how shallow inclination angles migratory birds can still use for orientation. In this study, we tested the magnetic compass orientation of night-migratory Eurasian blackcaps (Sylvia atricapilla) in magnetic fields with 5° and 0° inclination. At 5° inclination, the birds oriented as well as they did in the normal 67° inclined field in Oldenburg. In contrast, they were completely randomly oriented in the horizontal field, showing no sign of bimodality. Our results indicate that the inclination limit for the magnetic compass of the blackcap is below 5° and that these birds indeed seem completely unable to use their magnetic compass for orientation in a horizontal magnetic field.
Anomalous Enhancement of Mechanical Properties in the Ammonia Adsorbed Defective Graphene
Authors: Ma Fengxian , Jiao Yalong , Gu Yuantong , Bilic Ante , Chen Ying , Chen Zhongfang , Du Aijun 
Published: September 2016

AbstractPure graphene is known as the strongest material ever discovered. However, the unavoidable defect formation in the fabrication process renders the strength of defective graphene much lower (~14%) than that of its perfect counterpart. By means of density functional theory computations, we systematically explored the effect of gas molecules (H2, N2, NH3, CO, CO2 and O2) adsorption on the mechanical strength of perfect/defective graphene. The NH3 molecule is found to play a dominant role in enhancing the strength of defective graphene by up to ~15.6%, while other gas molecules decrease the strength of graphene with varying degrees. The remarkable strength enhancement can be interpreted by the decomposition of NH3, which saturates the dangling bond and leads to charge redistribution at the defect site. The present work provides basic information for the mechanical failure of gas-adsorbed graphene and guidance for manufacturing graphene-based electromechanical devices.