bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanocrystalline hexagonal diamond formed from glassy carbon
Authors: Shiell Thomas. B. , McCulloch Dougal G. , Bradby Jodie E. , Haberl Bianca , Boehler Reinhard , McKenzie David. R.
Published: November 2016

Carbon exhibits a large number of allotropes and its phase behaviour is still subject to significant uncertainty and intensive research. The hexagonal form of diamond, also known as lonsdaleite, was discovered in the Canyon Diablo meteorite where its formation was attributed to the extreme conditions experienced during the impact. However, it has recently been claimed that lonsdaleite does not exist as a well-defined material but is instead defective cubic diamond formed under high pressure and high temperature conditions. Here we report the synthesis of almost pure lonsdaleite in a diamond anvil cell at 100 GPa and 400 °C. The nanocrystalline material was recovered at ambient and analysed using diffraction and high resolution electron microscopy. We propose that the transformation is the result of intense radial plastic flow under compression in the diamond anvil cell, which lowers the energy barrier by “locking in” favourable stackings of graphene sheets. This strain induced transformation of the graphitic planes of the precursor to hexagonal diamond is supported by first principles calculations of transformation pathways and explains why the new phase is found in an annular region. Our findings establish that high purity lonsdaleite is readily formed under strain and hence does not require meteoritic impacts.
Versatile, sensitive liquid chromatography mass spectrometry – Implementation of 10 μm OT columns suitable for small molecules, peptides and proteins
Authors: Vehus T. , Roberg-Larsen H. , Waaler J. , Aslaksen S. , Krauss S. , Wilson S. R. , Lundanes E.
Published: November 2016

We have designed a versatile and sensitive liquid chromatographic (LC) system, featuring a monolithic trap column and a very narrow (10 μm ID) fused silica open tubular liquid chromatography (OTLC) separation column functionalized with C18-groups, for separating a wide range of molecules (from small metabolites to intact proteins). Compared to today’s capillary/nanoLC approaches, our system provides significantly enhanced sensitivity (up to several orders) with matching or improved separation efficiency, and highly repeatable chromatographic performance. The chemical properties of the trap column and the analytical column were fine-tuned to obtain practical sample loading capacities (above 2 μg), an earlier bottleneck of OTLC. Using the OTLC system (combined with Orbitrap mass spectrometry), we could perform targeted metabolomics of sub-μg amounts of exosomes with 25 attogram detection limit of a breast cancer-related hydroxylated cholesterol. With the same set-up, sensitive bottom-up proteomics (targeted and untargeted) was possible, and high-resolving intact protein analysis. In contrast to state-of-the-art packed columns, our platform performs chromatography with very little dilution and is “fit-for-all”, well suited for comprehensive analysis of limited samples, and has potential as a tool for challenges in diagnostics.
Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity
Authors: Qin Qi-Pin , Qin Jiao-Lan , Meng Ting , Yang Gui-Ai , Wei Zu-Zhuang , Liu Yan-Cheng , Liang Hong , Chen Zhen-Feng
Published: November 2016

A series of group-10 metal complexes 1–14 of oxoisoaporphine derivatives were designed and synthesized. 1–14 were more selectively cytotoxic to Hep-G2 cells comparing with normal liver cells. In vitro cytotoxicity results showed that complexes 1–6, 7, 8, 10 and 11, especially 3, were telomerase inhibitors targeting c-myc, telomeric, and bcl-2 G4s and triggered cell senescence and apoptosis; they also caused telomere/DNA damage and S phase arrest. In addition, 1–6 also caused mitochondrial dysfunction. Notably, 3 with 6-amino substituted ligand La exhibited less side effects than 6 with 8-amino substituted ligand Lb and cisplatin, but similar tumor growth inhibition efficacy in BEL-7402 xenograft model. Complex 3 has the potential to be developed as an effective anticancer agent.
CCL5/RANTES contributes to hypothalamic insulin signaling for systemic insulin responsiveness through CCR5
Authors: Chou Szu-Yi , Ajoy Reni , Changou Chun Austin , Hsieh Ya-Ting , Wang Yang-Kao , Hoffer Barry
Published: November 2016

Many neurodegenerative diseases are accompanied by metabolic disorders. CCL5/RANTES, and its receptor CCR5 are known to contribute to neuronal function as well as to metabolic disorders such as type 2 diabetes mellitus, obesity, atherosclerosis and metabolic changes after HIV infection. Herein, we found that the lack of CCR5 or CCL5 in mice impaired regulation of energy metabolism in hypothalamus. Immunostaining and co-immunoprecipitation revealed the specific expression of CCR5, associated with insulin receptors, in the hypothalamic arcuate nucleus (ARC). Both ex vivo stimulation and in vitro tissue culture studies demonstrated that the activation of insulin, and PI3K-Akt pathways were impaired in CCR5 and CCL5 deficient hypothalamus. The inhibitory phosphorylation of insulin response substrate-1 at Ser302 (IRS-1S302) but not IRS-2, by insulin was markedly increased in CCR5 and CCL5 deficient animals. Elevating CCR5/CCL5 activity induced GLUT4 membrane translocation and reduced phospho-IRS-1S302 through AMPKα-S6 Kinase. Blocking CCR5 using the antagonist, MetCCL5, abolished the de-phosphorylation of IRS-1S302 and insulin signal activation. In addition, intracerebroventricular delivery of MetCCL5 interrupted hypothalamic insulin signaling and elicited peripheral insulin responsiveness and glucose intolerance. Taken together, our data suggest that CCR5 regulates insulin signaling in hypothalamus which contributes to systemic insulin sensitivity and glucose metabolism.
Comparative photochemistry activity and antioxidant responses in male and female Populus cathayana cuttings inoculated with arbuscular mycorrhizal fungi under salt
Authors: Wu Na , Li Zhen , Wu Fei , Tang Ming
Published: November 2016

We investigated the impact of arbuscular mycorrhizal fungi (AMF) on the morphology and physiology of two genders of the typical dioecious plant Populus cathayana under salt stress. We conducted a pot experiment containing seedlings of the two genders that were subjected to salt or non-salt and filled with soil that was either inoculated with Rhizophagus intraradices or not. The results showed that males had higher mycorrhizal dependency than females. Salt stress decreased growth, the relative water content and chlorophyll fluorescence. Meanwhile, salt increased the superoxide radical (O2−), and hydrogen peroxide (H2O2) contents and antioxidant enzyme activities. Mycorrhizal male seedlings performed better than females in shoot morphological growth under both conditions and in chlorophyll fluorescence parameters, O2− and H2O2 contents, MDA concentration, proline content and antioxidant enzymes activities under salt stress. In females, under saline conditions, a lower MDA concentration and H2O2, O2− and proline contents were observed in the leaves and roots. In addition, inoculated female plants performed better in chlorophyll fluorescence parameters than non-inoculated plants. AMF inoculation had either slight or no effects on the performance of females. These findings suggested that when subjected to stress and AMF, differences in the genders existed, followed by the alleviation of the damage to P. cathayana by AMF via improving growth and photosynthesis and antioxidant systems under salt stress.
Body mass index and risk of non-melanoma skin cancer: cumulative evidence from prospective studies
Authors: Zhou Daijun , Wu Jun , Luo Gaoxing
Published: November 2016

Prospective epidemiologic studies that investigated the association between body mass index (BMI) and non-melanoma skin cancer (NMSC) yielded inconsistent findings. A dose-response meta-analysis was conducted to quantitatively summarize the evidence. PubMed and Embase databases were searched for relevant studies. Study-specific relative risk (RR) and 95% confidence interval (CI) for an increase in BMI of 5 kg/m2 was computed with the generalized least squares trend estimation, and these risk estimates were combined with the random-effects model. Nine publications were included in the final analyses, consisting of 18 independent cohorts with 22 risk estimates (971,795 participants and 50,561 NMSC cases). Results of the dose-response analyses showed a nonlinear inverse relationship between BMI and NMSC (RR = 0.88, 95% CI: 0.85–0.91, I2 = 71.2%, P-nonlinearity <0.001), which persisted when limiting to the studies with adjustment for important potential confounders including sun exposure and sensitivity factors. The risk estimates were very similar for squamous cell carcinoma and basal cell carcinoma. Sex appeared a source of heterogeneity (P-difference = 0.06), with a weaker, but still significant inverse association in men than in women. This dose-response meta-analysis suggests a nonlinear inverse association between BMI and NMSC.
Reducing GABAA-mediated inhibition improves forelimb motor function after focal cortical stroke in mice
Authors: Alia Claudia , Spalletti Cristina , Lai Stefano , Panarese Alessandro , Micera Silvestro , Caleo Matteo
Published: November 2016

A deeper understanding of post-stroke plasticity is critical to devise more effective pharmacological and rehabilitative treatments. The GABAergic system is one of the key modulators of neuronal plasticity, and plays an important role in the control of “critical periods” during brain development. Here, we report a key role for GABAergic inhibition in functional restoration following ischemia in the adult mouse forelimb motor cortex. After stroke, the majority of cortical sites in peri-infarct areas evoked simultaneous movements of forelimb, hindlimb and tail, consistent with a loss of inhibitory signalling. Accordingly, we found a delayed decrease in several GABAergic markers that accompanied cortical reorganization. To test whether reductions in GABAergic signalling were causally involved in motor improvements, we treated animals during an early post-stroke period with a benzodiazepine inverse agonist, which impairs GABAA receptor function. We found that hampering GABAA signalling led to significant restoration of function in general motor tests (i.e., gridwalk and pellet reaching tasks), with no significant impact on the kinematics of reaching movements. Improvements were persistent as they remained detectable about three weeks after treatment. These data demonstrate a key role for GABAergic inhibition in limiting motor improvements after cortical stroke.
HMGB1-mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells
Authors: Cai Yongsong , Xu Peng , Yang Le , Xu Ke , Zhu Jialin , Wu Xiaoqing , Jiang Congshan , Yuan Qiling , Wang Bo , Li Yuanbo , Qiu Yusheng
Published: November 2016

Oxymatrine (OMT) is a type of alkaloid extracted from a traditional Chinese medicinal herb, Sophora flavescens. Although the antitumor activities of OMT have been observed in various cancers, there are no reports regarding the effects of OMT on human synovial sarcoma. In the present study, we analyzed the antitumor activities of OMT in SW982 human synovial sarcoma cells and determine whether high mobility group box protein 1 (HMGB1)-mediated autophagy was associated with its therapeutic effects. We found that OMT exhibited antitumor activity in SW982 cells and facilitated increases in autophagy. Inhibition of autophagy by 3-MA or ATG7 siRNA increased the level of apoptosis, which indicated that OMT-induced autophagy protected cells from the cytotoxicity of OMT. Administration of OMT to SW982 cells increased the expression of HMGB1. When HMGB1 was inhibited via HMGB1-siRNA, OMT-induced autophagy was decreased, and apoptosis was increased. Furthermore, we found that HMGB1-siRNA significantly increased the expression of p-Akt and p-mTOR. OMT-induced autophagy may be mediated by the Akt/mTOR pathway, and HMGB1 plays a vital role in the regulation of autophagy. Therefore, we believe that combining OMT with an inhibitor of autophagy or HMGB1 may make OMT more effective in the treatment of human synovial sarcoma.
Coulomb nanoradiator-mediated, site-specific thrombolytic proton treatment with a traversing pristine Bragg peak
Authors: Jeon Jae-Kun , Han Sung-Mi , Min Soon-Ki , Seo Seung-Jun , Ihm Kyuwook , Chang Won-Seok , Kim Jong-Ki
Published: November 2016

Traversing proton beam-irradiated, mid/high-Z nanoparticles produce site-specific enhancement of X-ray photon-electron emission via the Coulomb nanoradiator (CNR) effect, resulting in a nano- to micro-scale therapeutic effect at the nanoparticle-uptake target site. Here, we demonstrate the uptake of iron oxide nanoparticles (IONs) and nanoradiator-mediated, site-specific thrombolysis without damaging the vascular endothelium in an arterial thrombosis mouse model. The enhancement of low-energy electron (LEE) emission and reactive oxygen species (ROS) production from traversing proton beam-irradiated IONs was examined. Flow recovery was only observed in CNR-treated mice, and greater than 50% removal of the thrombus was achieved. A 2.5-fold greater reduction in the thrombus-enabled flow recovery was observed in the CNR group compared with that observed in the untreated ION-only and proton-only control groups (p < 0.01). Enhancement of the X-ray photon-electron emission was evident from both the pronounced Shirley background in the electron yield and the 1.2- to 2.5-fold enhanced production of ROS by the proton-irradiated IONs, which suggests chemical degradation of the thrombus without potent emboli.
Plasmonic metalens based on coupled resonators for focusing of surface plasmons
Authors: Xu Quan , Zhang Xueqian , Xu Yuehong , Li Quan , Li Yanfeng , Ouyang Chunmei , Tian Zhen , Gu Jianqiang , Zhang Wentao , Zhang Xixiang , Han Jiaguang , Zhang Weili
Published: November 2016

As an essential functionality, flexible focusing of surface plasmons (SPs) is of particular interest in nonlinear optics and highly integrated plasmonic circuitry. Here, we developed a versatile plasmonic metalens, a metasurface comprised of coupled subwavelength resonators, whose optical responses exhibit a remarkable feature of electromagnetically induced transparency (EIT). We demonstrate numerically and experimentally how a proper spatial design of the unit elements steers SPs to arbitrary foci based on the holographic principles. More specifically, we show how to control the interaction between the constituent EIT resonators to efficiently manipulate the focusing intensity of SPs. We also demonstrated that the proposed metalens is capable of achieving frequency division multiplexing. The power and simplicity of the proposed design would offer promising opportunities for practical plasmonic devices.
Hydroxychavicol: A phytochemical targeting cutaneous fungal infections
Authors: Ali Intzar , Satti Naresh Kumar , Dutt Prabhu , Prasad Rajendra , Khan Inshad Ali
Published: November 2016

The present study was designed to investigate the potency of hydroxychavicol on selected cutaneous human pathogenic fungi by the use ofin vitroandin vivoassays and mechanistic characterization along with toxicological effects. Hydroxychavicol consistently displayed a fungicidal effect against all fungal species tested. Inoculum concentrations over the range of 104to 107 CFU/ml did not significantly alter its antifungal potential and time–kill curve results revealed concentration–dependent killing. It also inhibited the growth of biofilm generated byTrichophyton mentagrophytesandCandida parapsilosisand reduced the preformed biofilms. Hydroxychavicol was highly effective in the treatment, and mycological eradication of an experimentally induced topical infection model of dermatophytosis (tinea corporis) and cutaneous candidiasis in guinea pigs, respectively. The mode of action of hydroxychavicol appears to originate from the disruption of cell membrane integrity. Administration of hydroxychavicol in mice at 500 mg per kg of body weight by orally produced no overt toxicity. The retention capacity of hydroxychavicolin vitro, in the presence of keratin has attributed to itsin vivoeffectiveness in the guinea pig model of topical infections. Furthermore, it is suggestive of its potential use as phytochemical for topical use in cutaneous fungal infections.
Decision making processes based on social conventional rules in early adolescents with and without autism spectrum disorders
Authors: Komeda Hidetsugu , Osanai Hidekazu , Yanaoka Kaichi , Okamoto Yuko , Fujioka Toru , Arai Sumiyoshi , Inohara Keisuke , Koyasu Masuo , Kusumi Takashi , Takiguchi Shinichiro , Kawatani Masao , Kumazaki Hirokazu , Hiratani Michio , Tomoda Akemi , Kosaka Hirotaka
Published: November 2016

Autism spectrum disorder (ASD) is characterized by problems with reciprocal social interaction, repetitive behaviours/narrow interests, and impairments in the social cognition and emotional processing necessary for intention-based moral judgements. The aim of this study was to examine the information used by early adolescents with and without ASD when they judge story protagonists as good or bad. We predicted that adolescents with ASD would use protagonists’ behaviour, while typically developing (TD) adolescents would use protagonists’ characteristics when making the judgements. In Experiment 1, we measured sentence by sentence reading times and percentages for good or bad judgements. In Experiment 2, two story protagonists were presented and the participants determined which protagonist was better or worse. Experiment 1 results showed that the adolescents with ASD used protagonist behaviours and outcomes, whereas the TD adolescents used protagonist characteristics, behaviours, and outcomes. In Experiment 2, TD adolescents used characteristics information when making “bad” judgements. Taken together, in situations in which participants cannot go back and assess (Experiment 1), and in comparable situations in which all information is available (Experiment 2), adolescents with ASD do not rely on information about individual characteristics when making moral judgements.
Human mitochondrial transcriptional factor A breaks the mitochondria-mediated vicious cycle in Alzheimer’s disease
Authors: Oka Sugako , Leon Julio , Sakumi Kunihiko , Ide Tomomi , Kang Dongchon , LaFerla Frank M. , Nakabeppu Yusaku
Published: November 2016

In the mitochondria-mediated vicious cycle of Alzheimer’s disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This vicious cycle is thought to play a pivotal role in the development of AD, although the molecular mechanism remains unclear. Here, we examined the effects of human mitochondrial transcriptional factor A (hTFAM) on the pathology of a mouse model of AD (3xTg-AD), because TFAM is known to protect mitochondria from oxidative stress through maintenance of mitochondrial DNA (mtDNA). Expression of hTFAM significantly improved cognitive function, reducing accumulation of both 8-oxoguanine, an oxidized form of guanine, in mtDNA and intracellular Aβ in 3xTg-AD mice and increasing expression of transthyretin, known to inhibit Aβ aggregation. Next, we found that AD model neurons derived from human induced pluripotent stem cells carrying a mutant PSEN1(P117L) gene, exhibited mitochondrial dysfunction, accumulation of 8-oxoguanine and single-strand breaks in mtDNA, and impaired neuritogenesis with a decreased expression of transthyretin, which is known to be downregulated by oxidative stress. Extracellular treatment with recombinant hTFAM effectively suppressed these deleterious outcomes. Moreover, the treatment increased expression of transthyretin, accompanied by reduction of intracellular Aβ. These results provide new insights into potential novel therapeutic targets.
Lightweight NiFe2O4 with controllable 3D network structure and enhanced microwave absorbing properties
Authors: Wang Fen , Wang Xing , Zhu Jianfeng , Yang Haibo , Kong Xingang , Liu Xiao
Published: November 2016

3D network structure NiFe2O4 was successfully synthesized by a templated salt precipitation method using PMMA colloid crystal as templates. The morphology, phase composition and microwave absorbing properties of as-prepared samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), vector network analyzer (VNA), and so on. The results revealed that the 3D network structure was configurated with smooth spherical walls composed of NiFe2O4 nanocrystals and their pore diameters being in the range of 80–250 nm. The microwave absorption properties of the 3D network structure NiFe2O4 were crucially determined by the special structure. The synergy of intrinsic magnetic loss of magnetic NiFe2O4 and the interfacial polarization enhanced by 3D network structure and the interaction of multiple mechanisms endowed the sample with the feature of strong absorption, broad bandwidth and lightweight. There is more than one valley in the reflection loss curves and the maximum reflection loss is 27.5 dB with a bandwidth of 4 GHz. Moreover, the 3D network structure NiFe2O4 show a greater reflection loss with the same thickness comparing to the ordinary NiFe2O4 nanoparticles, which could achieve the feature of lightweight of the microwave absorbing materials.
Hidden Order and Dimensional Crossover of the Charge Density Waves in TiSe2
Authors: Chen P. , Chan Y.-H. , Fang X.-Y. , Mo S.-K. , Hussain Z. , Fedorov A.-V. , Chou M. Y. , Chiang T.-C.
Published: November 2016

Charge density wave (CDW) formation, a key physics issue for materials, arises from interactions among electrons and phonons that can also lead to superconductivity and other competing or entangled phases. The prototypical system TiSe2, with a particularly simple (2 × 2 × 2) transition and no Kohn anomalies caused by electron-phonon coupling, is a fascinating but unsolved case after decades of research. Our angle-resolved photoemission measurements of the band structure as a function of temperature, aided by first-principles calculations, reveal a hitherto undetected but crucial feature: a (2 × 2) electronic order in each layer sets in at ~232 K before the widely recognized three-dimensional structural order at ~205 K. The dimensional crossover, likely a generic feature of such layered materials, involves renormalization of different band gaps in two stages.
Mitochondrial control through nutritionally regulated global histone H3 lysine-4 demethylation
Authors: Soloveychik Maria , Xu Mengshu , Zaslaver Olga , Lee Kwanyin , Narula Ashrut , Jiang River , Rosebrock Adam P. , Caudy Amy A. , Meneghini Marc D.
Published: November 2016

Histone demethylation by Jumonji-family proteins is coupled with the decarboxylation of α-ketoglutarate (αKG) to yield succinate, prompting hypotheses that their activities are responsive to levels of these metabolites in the cell. Consistent with this paradigm we show here that the Saccharomyces cerevisiae Jumonji demethylase Jhd2 opposes the accumulation of H3K4me3 in fermenting cells only when they are nutritionally manipulated to contain an elevated αKG/succinate ratio. We also find that Jhd2 opposes H3K4me3 in respiratory cells that do not exhibit such an elevated αKG/succinate ratio. While jhd2∆ caused only limited gene expression defects in fermenting cells, transcript profiling and physiological measurements show that JHD2 restricts mitochondrial respiratory capacity in cells grown in non-fermentable carbon in an H3K4me-dependent manner. In association with these phenotypes, we find that JHD2 limits yeast proliferative capacity under physiologically challenging conditions as measured by both replicative lifespan and colony growth on non-fermentable carbon. JHD2’s impact on nutrient response may reflect an ancestral role of its gene family in mediating mitochondrial regulation.
Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo
Authors: Ciarlo Eleonora , Heinonen Tytti , Herderschee Jacobus , Fenwick Craig , Mombelli Matteo , Le Roy Didier , Roger Thierry
Published: November 2016

Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells. In proof of concept studies, propionate neither improved nor worsened morbidity and mortality parameters in models of endotoxemia and infections induced by gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae), gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) and Candida albicans. Moreover, propionate did not impair the efficacy of passive immunization and natural immunization. Therefore, propionate has no significant impact on host susceptibility to infections and the establishment of protective anti-bacterial responses. These data support the safety of propionate-based therapies, either via direct supplementation or via the diet/microbiota, to treat non-infectious inflammation-related disorders, without increasing the risk of infection.
High-Entropy Metal Diborides: A New Class of High-Entropy Materials and a New Type of Ultrahigh Temperature Ceramics
Authors: Gild Joshua , Zhang Yuanyao , Harrington Tyler , Jiang Sicong , Hu Tao , Quinn Matthew C. , Mellor William M. , Zhou Naixie , Vecchio Kenneth , Luo Jian
Published: November 2016

Seven equimolar, five-component, metal diborides were fabricated via high-energy ball milling and spark plasma sintering. Six of them, including (Hf0.2Zr0.2Ta0.2Nb0.2Ti0.2)B2, (Hf0.2Zr0.2Ta0.2Mo0.2Ti0.2)B2, (Hf0.2Zr0.2Mo0.2Nb0.2Ti0.2)B2, (Hf0.2Mo0.2Ta0.2Nb0.2Ti0.2)B2, (Mo0.2Zr0.2Ta0.2Nb0.2Ti0.2)B2, and (Hf0.2Zr0.2Ta0.2Cr0.2Ti0.2)B2, possess virtually one solid-solution boride phase of the hexagonal AlB2 structure. Revised Hume-Rothery size-difference factors are used to rationalize the formation of high-entropy solid solutions in these metal diborides. Greater than 92% of the theoretical densities have been generally achieved with largely uniform compositions from nanoscale to microscale. Aberration-corrected scanning transmission electron microscopy (AC STEM), with high-angle annular dark-field and annular bright-field (HAADF and ABF) imaging and nanoscale compositional mapping, has been conducted to confirm the formation of 2-D high-entropy metal layers, separated by rigid 2-D boron nets, without any detectable layered segregation along the c-axis. These materials represent a new type of ultra-high temperature ceramics (UHTCs) as well as a new class of high-entropy materials, which not only exemplify the first high-entropy non-oxide ceramics (borides) fabricated but also possess a unique non-cubic (hexagonal) and layered (quasi-2D) high-entropy crystal structure that markedly differs from all those reported in prior studies. Initial property assessments show that both the hardness and the oxidation resistance of these high-entropy metal diborides are generally higher/better than the average performances of five individual metal diborides made by identical fabrication processing.
Analysis of the interaction of calcitriol with the disulfide isomerase ERp57
Authors: Gaucci Elisa , Raimondo Domenico , Grillo Caterina , Cervoni Laura , Altieri Fabio , Nittari Giulio , Eufemi Margherita , Chichiarelli Silvia
Published: November 2016

Calcitriol, the active form of vitamin D3, can regulate the gene expression through the binding to the nuclear receptor VDR, but it can also display nongenomic actions, acting through a membrane-associated receptor, which has been discovered as the disulfide isomerase ERp57. The aim of our research is to identify the binding sites for calcitriol in ERp57 and to analyze their interaction. We first studied the interaction through bioinformatics and fluorimetric analyses. Subsequently, we focused on two protein mutants containing the predicted interaction domains with calcitriol: abb’-ERp57, containing the first three domains, and a’-ERp57, the fourth domain only. To consolidate the achievements we used the calorimetric approach to the whole protein and its mutants. Our results allow us to hypothesize that the interaction with the a’ domain contributes to a greater extent than the other potential binding sites to the dissociation constant, calculated as a Kd of about 10−9 M.
Calmodulin interacts with Rab3D and modulates osteoclastic bone resorption
Authors: Zhu Sipin , Chim Shek Man , Cheng Taksum , Ang Estabelle , Ng Benjamin , Lim Baysie , Chen Kai , Qiu Heng , Tickner Jennifer , Xu Huazi , Pavlos Nathan , Xu Jiake
Published: November 2016

Calmodulin is a highly versatile protein that regulates intracellular calcium homeostasis and is involved in a variety of cellular functions including cardiac excitability, synaptic plasticity and signaling transduction. During osteoclastic bone resorption, calmodulin has been reported to concentrate at the ruffled border membrane of osteoclasts where it is thought to modulate bone resorption activity in response to calcium. Here we report an interaction between calmodulin and Rab3D, a small exocytic GTPase and established regulator osteoclastic bone resorption. Using yeast two-hybrid screening together with a series of protein-protein interaction studies, we show that calmodulin interacts with Rab3D in a calcium dependent manner. Consistently, expression of a calcium insensitive form of calmodulin (i.e. CaM1234) perturbs calmodulin-Rab3D interaction as monitored by bioluminescence resonance energy transfer (BRET) assays. In osteoclasts, calmodulin and Rab3D are constitutively co-expressed during RANKL-induced osteoclast differentiation, co-occupy plasma membrane fractions by differential gradient sedimentation assay and colocalise in the ruffled border as revealed by confocal microscopy. Further, functional blockade of calmodulin-Rab3D interaction by calmidazolium chloride coincides with an attenuation of osteoclastic bone resorption. Our data imply that calmodulin- Rab3D interaction is required for efficient bone resorption by osteoclasts in vitro.
Viral and Host Characteristics of Recent and Established HIV-1 Infections in Kisumu based on a Multiassay Approach
Authors: Otecko Newton , Inzaule Seth , Odhiambo Collins , Otieno George , Opollo Valarie , Morwabe Alex , Were Kennedy , Ndiege Kenneth , Otieno Fredrick , Kim Andrea A. , Zeh Clement
Published: November 2016

Integrated approaches provide better understanding of HIV/AIDS epidemics. We optimised a multiassay algorithm (MAA) and assessed HIV incidence, correlates of recent infections, viral diversity, plus transmission clusters among participants screened for Kisumu Incidence Cohort Study (KICoS1) (2007–2009). We performed BED-CEIA, Limiting antigen (LAg) avidity, Biorad avidity, and viral load (VL) tests on HIV-positive samples. Genotypic analyses focused on HIV-1 pol gene. Correlates of testing recent by MAA were assessed using logistic regression model. Overall, 133 (12%, 95% CI: 10.2–14.1) participants were HIV-positive, of whom 11 tested recent by MAA (BED-CEIA OD-n < 0.8 + LAg avidity OD-n < 1.5 + VL > 1000 copies/mL), giving an incidence of 1.46% (95% CI: 0.58–2.35) per year. This MAA-based incidence was similar to longitudinal KICoS1 incidence. Correlates of testing recent included sexually transmitted infection (STI) treatment history (OR = 3.94, 95% CI: 1.03–15.07) and syphilis seropositivity (OR = 10.15, 95% CI: 1.51–68.22). Overall, HIV-1 subtype A (63%), D (15%), C (3%), G (1%) and recombinants (18%), two monophyletic dyads and intrinsic viral mutations (V81I, V81I/V, V108I/V and K101Q) were observed. Viral diversity mirrored known patterns in this region, while resistance mutations reflected likely non-exposure to antiretroviral drugs. Management of STIs may help address ongoing HIV transmission in this region.
Functional Involvement of a Mitogen Activated Protein Kinase Module, OsMKK3-OsMPK7-OsWRK30 in Mediating Resistance against Xanthomonas oryzae in Rice
Authors: Jalmi Siddhi Kashinath , Sinha Alok Krishna
Published: November 2016

Mitogen-activated protein kinases (MAPKs) are highly conserved signaling modules in eukaryotes, transmitting signals from upstream receptor to downstream target by phosphorelay mechanism. Here we report involvement of a poorly characterized group C MAPK of rice namely, OsMPK7 along with its upstream MAPK kinase, OsMKK3 and downstream target, OsWRKY30 during Xanthomonas oryzae infection, a causal agent of leaf blight disease in rice. X. oryzae infection resulted in induction of OsMPK7 and OsMKK3. OsMKK3 was found to physically interact and phosphorylate OsMPK7. Overexpression of OsMPK7 and OsMKK3, individually and in combinations resulted in inhibition of disease symptoms caused by X. oryzae, however silencing of OsMPK7 resulted in disease susceptibility. Furthermore, OsWRKY30 was identified as downstream target of OsMPK7 through protein-protein interaction techniques and was found to be a positive regulator of defence response against X. oryzae pathogen. The overexpression of OsMKK3-OsMPK7 upregulated genes involved in pathogenesis, cell wall structure maintenance and cell metabolism indicating possible mechanism of disease resistance. These leaves also showed restricted movement of the pathogen from the point of infection to uninfected area. Taken together, this work suggests a positive involvement of OsMKK3-OsMPK7-OsWRKY30 module in imparting disease resistance against X. oryzae infection in rice.
Changes in the Membrane-Associated Proteins of Exosomes Released from Human Macrophages after Mycobacterium tuberculosis Infection
Authors: Diaz Gustavo , Wolfe Lisa M. , Kruh-Garcia Nicole A. , Dobos Karen M.
Published: November 2016

Tuberculosis (TB) is the deadliest infectious disease worldwide. One obstacle hindering the elimination of TB is our lack of understanding of host-pathogen interactions. Exosomes, naturally loaded with microbial molecules, are circulating markers of TB. Changes in the host protein composition of exosomes from Mycobacterium tuberculosis (Mtb)-infected cells have not been described, can contribute to our understanding of the disease process, and serve as a direct source of biomarkers or as capture targets to enrich for exosomes containing microbial molecules. Here, the protein composition of exosomes from Mtb-infected and uninfected THP-1-derived macrophages was evaluated by tandem-mass-spectrometry and differences in protein abundances were assessed. Our results show that infection with Mtb leads to significant changes in the protein composition of exosomes. Specifically, 41 proteins were significantly more abundant in exosomes from Mtb-infected cells; 63% of these were predicted to be membrane associated. Thus, we used a novel biotinylation strategy to verify protein localization, and confirmed the localization of some of these proteins in the exosomal membrane. Our findings reveal another important scenario where Mtb could be influencing changes in host cells that unveil new features of the host-pathogen interaction and may also be exploited as a source of biomarkers for TB.
Genome-wide analysis of miRNAs in the ovaries of Jining Grey and Laiwu Black goats to explore the regulation of fecundity
Authors: Miao Xiangyang , Luo Qingmiao , Zhao Huijing , Qin Xiaoyu
Published: November 2016

Goat fecundity is important for agriculture and varies depending on the genetic background of the goat. Two excellent domestic breeds in China, the Jining Grey and Laiwu Black goats, have different fecundity and prolificacies. To explore the potential miRNAs that regulate the expression of the genes involved in these prolific differences and to potentially discover new miRNAs, we performed a genome-wide analysis of the miRNAs in the ovaries from these two goats using RNA-Seq technology. Thirty miRNAs were differentially expressed between the Jining Grey and Laiwu Black goats. Gene Ontology and KEGG pathway analyses revealed that the target genes of the differentially expressed miRNAs were significantly enriched in several biological processes and pathways. A protein-protein interaction analysis indicated that the miRNAs and their target genes were related to the reproduction complex regulation network. The differential miRNA expression profiles found in the ovaries between the two distinctive breeds of goats studied here provide a unique resource for addressing fecundity differences in goats.
Platycodin D potentiates proliferation inhibition and apoptosis induction upon AKT inhibition via feedback blockade in non-small cell lung cancer cells
Authors: Li Ting , Chen Xin , Chen Xiuping , Ma Dik Lung , Leung Chung Hang , Lu Jin Jian
Published: November 2016

AKT is the frequently overexpressed and constitutively active kinase within NSCLC cells and recognized as a promising target for NSCLC treatment. However, AKT inhibition relieves the feedback inhibition of upstream receptor tyrosine kinases (RTKs) that may weaken the efficiency of AKT inhibitors. Platycodin D (PD), isolated from widely-used traditional Chinese medicine Platycodonis Radix, is now found to remarkably enhance the anti-proliferative effect of AKT inhibitors. In this study, combinatorial activity of AKT inhibitor MK2206 and PD on cell proliferation, apoptosis and related signaling were disclosed. Long-term AKT inhibition induced up-regulation of RTKs, including EGFR and HER-2. Co-treatment of MK2206 with PD could abolish this feedback survival through decrease of EGFR, HER-2, and p-AKT, and profound inhibition of 4E-BP1, leading to an amplified anti-proliferative and apoptotic activity in NSCLC cells. Similarly, feedback activation in response to reduction of AKT expression by small interfering RNA (siRNA) was also blocked by PD and apoptotic effect was further enhanced. Thus, PD potentiated proliferative inhibition and apoptotic induction of both AKT inhibitor and siRNA. These findings also reveal the limitations of suppressing feedback-regulated pathways by monotherapy and establish a mechanistic rationale for a novel combination approach targeting AKT for the treatment of NSCLC.
Rapid control of pandemic H1N1 influenza by targeting NKT-cells
Authors: Artiaga Bianca L. , Yang Guan , Hutchinson Tarun E. , Loeb Julia C. , Richt Jürgen A. , Lednicky John A. , Salek-Ardakani Shahram , Driver John P.
Published: November 2016

Swine influenza A viruses (IAV) are a major cause of respiratory disease in pigs and humans. Currently approved anti-influenza therapies directly target the virus, but these approaches are losing effectiveness as new viral strains quickly develop drug resistance. To over come this challenge, there is an urgent need for more effective antiviral drugs. Here we tested the anti-influenza efficacy of the invariant natural killer T (NKT) cell superagonist, α-galactosylceramide (α-GalCer), which stimulates a wide array of anti-viral immune responses. We show that intranasal but not systemic administration of α-GalCer to piglets infected with pandemic A/California/04/2009 (CA04) H1N1 IAV ameliorated disease symptoms and resulted in the restoration of weight gain to the level of uninfected pigs. Correspondingly, viral titers in the upper-and lower-respiratory tract were reduced only in piglets that had received intranasal α-GalCer. Most significantly, lung inflammation as a consequence of virus persistence was largely prevented when NKT-cells were targeted via the respiratory route. Thus, targeting mucosal NKT-cells may provide a novel and potent platform for improving the course of disease in swine infected with seasonal and pandemic influenza viruses, and leads to the suggestion that this may also be true in humans and therefore deserves further study.
Scaling Effect of Phosphorene Nanoribbon - Uncovering the Origin of Asymmetric Current Transport
Authors: Lv Yawei , Chang Sheng , Huang Qijun , Wang Hao , He Jin
Published: November 2016

In this paper, phosphorene nanoribbons (PNRs) are theoretically studied using a multiscale simulation flow from the ab initio level to the tight binding (TB) level. The scaling effects of both armchair PNRs (aPNRs) and zigzag PNRs (zPNRs) from material properties to device properties are explored. The much larger effective mass of holes compared to that of electrons in zPNR is responsible for its asymmetric transport. However, in aPNR, not only the effective mass difference but also the non-equal density of state (DOS) distributions near valence band maximum (VBM) and conduction band minimum (CBM) lead to the asymmetric transport. This non-equal distribution phenomenon is caused by energy band degeneracies near the VBM. Based on these two different mechanisms, PNRs’ asymmetric transport characteristics at the device level are explained, and it is shown that this behaviour can be ameliorated well by reducing the ribbon width in an aPNR MOSFET. Calculation results also indicate that aPNR’s effective mass is comparable to that of a graphene nanoribbon (GNR) at the same bandgap; however, aPNR’s band gap variation is more stable and regular than that of GNR, making it a good candidate for use in low-dimensional nano devices.
NADPH oxidase gp91phox contributes to RANKL-induced osteoclast differentiation by upregulating NFATc1
Authors: Kang In Soon , Kim Chaekyun
Published: November 2016

Bone-marrow derived monocyte-macrophages (BMMs) differentiate into osteoclasts by M-CSF along subsequent RANKL stimulation possibly in collaboration with many other unknown cytokines released by pre- or mature osteoblasts. The differentiation process requires receptor activator of nuclear factor kappa-B ligand (RANKL)/RANK signaling and reactive oxygen species (ROS) such as superoxide anion (O2•−). Gp91phox, a plasma membrane subunit of NADPH oxidase (Nox), is constitutively expressed in BMMs and plays a major role in superoxide anion production. In this study, we found that mice deficient in gp91phox (gp91phox−/−) showed defects in osteoclast differentiation. Femurs of these mice produced osteoclasts at about 70% of the levels seen in femurs from wild-type mice, and accordingly exhibited excessive bone density. This abnormal bone growth in the femurs of gp91phox−/− mice resulted from impaired osteoclast differentiation. In addition, gp91phox−/− mice were defective for RANKL-induced expression of nuclear factor of activated T cells c1 (NFATc1). However, H2O2 treatment compensated for gp91phox deficiency in BMMs, almost completely rescuing osteoclast differentiation. Treating wild-type BMMs with antioxidants and superoxide inhibitors resulted in a differentiation defect resembling the phenotype of gp91phox−/− BMMs. Therefore, our results demonstrate that gp91phox-derived superoxide is important for promoting efficient osteoclast differentiation by inducing NFATc1 as a downstream signaling mediator of RANK.
A Green Route for Substrate-Independent Oil-Repellent Coatings
Authors: Xu Li-Ping , Han Da , Wu Xiuwen , Zhang Qingqing , Zhang Xueji , Wang Shutao
Published: November 2016

Oil repellent surface have lots of practical applications in many fields. Current oil repellent coating may suffer from limited liquid repellency to oils or environmental risks. In this work, we report an eco-friendly ‘green’ processes for preparing oil-repellent surface using a renewable and environmentally benign bioresource alginate. The oil-repellent coating was prepared by a two-step surface coating technique and showed stable oil repellency to many kinds of oils. The fabrication process was very simple with no need for special equipment, and this approach can be successfully employed to various substrates with different compositions, sizes and shapes, or even substrate-independent oil-repellent materials. The as-prepared coating of calcium alginate may have a good future in packaging oil-containing products and foods.
Bilayered graphene/h-BN with folded holes as new nanoelectronic materials: modeling of structures and electronic properties
Authors: Chernozatonskii Leonid A. , Demin Viсtor A. , Bellucci Stefano
Published: November 2016

The latest achievements in 2-dimensional (2D) material research have shown the perspective use of sandwich structures in nanodevices. We demonstrate the following generation of bilayer materials for electronics and optoelectronics. The atomic structures, the stability and electronic properties of Moiré graphene (G)/h-BN bilayers with folded nanoholes have been investigated theoretically by ab-initio DFT method. These perforated bilayers with folded hole edges may present electronic properties different from the properties of both graphene and monolayer nanomesh structures. The closing of the edges is realized by C-B(N) bonds that form after folding the borders of the holes. Stable ≪round≫ and ≪triangle≫ holes organization are studied and compared with similar hole forms in single layer graphene. The electronic band structures of the considered G/BN nanomeshes reveal semiconducting or metallic characteristics depending on the sizes and edge terminations of the created holes. This investigation of the new types of G/BN nanostructures with folded edges might provide a directional guide for the future of this emerging area.
TGF-β1 Induces Polypyrimidine Tract-Binding Protein to Alter Fibroblasts Proliferation and Fibronectin Deposition in Keloid
Authors: Jiao Hu , Dong Ping , Yan Li , Yang Zhigang , Lv Xiaoyan , Li Qiuchen , Zong Xianlei , Fan Jincai , Fu Xin , Liu Xia , Xiao Ran
Published: November 2016

Human dermal fibrotic disease keloid has been a clinical challenge because of its tumour-like growth and the lack of effective therapy. Dysregulated alternative splicing events have been demonstrated in tumours and fibrosis. In the current study, for the first time, it was demonstrated that the splicing regulator polypyrimidine tract-binding protein (PTB), which plays a pivotal role in tumour proliferation, invasion and metastasis, is overexpressed in keloid tissues and fibroblasts. Additionally, TGF-β1 upregulated the expressions of PTB and its upstream regulator, C-MYC, in keloid fibroblasts. Furthermore, we suppressed PTB using siRNA in keloid fibroblasts and in a keloid xenograft nude mouse model. PTB knockdown significantly slowed the proliferation of keloid fibroblasts and accelerated the regression of transplanted keloid tissues, which was accompanied by a shift in the alternative splicing of USP5 and RTN4. Moreover, when PTB was suppressed, there was a reduction in excessive deposition of FN1 and COL3A1 in transplanted keloid tissues. However, only FN1 was downregulated in keloid fibroblasts that were cultured in media supplemented with TGF-β1. Our study provides evidence for the role of PTB in keloid pathophysiology and offers a novel therapeutic target for keloids. Most importantly, the role TGF-β1 regulation of PTB may provide new insights into the mechanisms underlying inflammatory cytokine-induced fibrosis.