bluuebunny/crossref_metadata_2025 huggingface dataset:
Simvastatin-induced cell cycle arrest through inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21 accumulation in hepatocellular carcinoma cells
Authors: Wang Sin-Ting , Ho Hsiu J , Lin Jaw-Town , Shieh Jeng-Jer , Wu Chun-Ying
Published: February 2017

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis and is one of the leading causes of cancer-related death worldwide. Simvastatin, an HMG-CoA reductase inhibitor, which decreases cholesterol synthesis by inhibiting mevalonate pathways and is widely used to treat cardiovascular diseases. Simvastatin exhibits anticancer effects against several malignancies. However, the molecular mechanisms underlying the anticancer effects of simvastatin on HCC are still not well understood. In this study, we demonstrated simvastatin-induced G0/G1 arrest by inducing p21 and p27 accumulation in HepG2 and Hep3B cells. Simvastatin also promoted AMP-activated protein kinase (AMPK) activation, which induced p21 upregulation by increasing its transcription. Consistent with this finding, we found genetic silencing of AMPK reduced p21 expression; however, AMPK silencing had no effect on p27 expression in HCC cells. Simvastatin decreased Skp2 expression at the transcriptional level, which resulted in p27 accumulation by preventing proteasomal degradation, an effect mediated by signal transducer and activator of transcription 3 (STAT3) inhibition. Constitutive STAT3 activation maintained high-level Skp2 expression and lower level p27 expression and significantly prevented G0/G1 arrest in simvastatin-treated HCC cells. Mevalonate decreased simvastatin-induced AMPK activation and rescued phospho-STAT3 and Skp2 expression in HCC cells, which resulted in the prevention of G0/G1 arrest through inhibition of p21 and p27 accumulation. Moreover, simvastatin significantly decreased tumor growth in HepG2 xenograft mice. Consistently, we found that simvastatin also increased p21 and p27 expression in tumor sections by reducing Skp2 expression and inducing AMPK activation and STAT3 suppression in the same tumor tissues. Taken together, these findings are demonstrative of the existence of a novel pathway in which simvastatin induces G0/G1 arrest by upregulating p21 and p27 by activating AMPK and inhibiting the STAT3–Skp2 axis, respectively. The results identify novel targets that explain the beneficial anticancer effects of simvastatin treatment on HCC in vitro and in vivo.
Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells
Authors: Yao Zhuo , Xie Fuhua , Li Min , Liang Zirui , Xu Wenli , Yang Jianhua , Liu Chang , Li Hongwangwang , Zhou Hui , Qu Liang-Hu
Published: February 2017

The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells. Then miRNA profiling of SW480 cells revealed those intracellular signaling related to energy supply was affected by oridonin, suggesting that glucose metabolism is a potential target for CRC therapy. Moreover, our results indicated that oridonin induced metabolic imbalances by significantly inhibiting glucose uptake and reducing lactate export through significantly downregulating the protein levels of GLUT1 and MCT1 in vitro and vivo. However, the ATP level in oridonin-treated CRC cells was not decreased when oridonin blocked the glucose supply, indicating that oridonin induced autophagy process, an important ATP source in cancer cells. The observation was then supported by the results of LC3-II detection and transmission electron microscopy analysis, which confirmed the presence of autophagy. Furthermore, p-AMPK was rapidly deactivated following oridonin treatment, resulting in downregulation of GLUT1 and induction of autophagy in the cancer cells. Thus our finding helped to clarify the anticancer mechanisms of oridonin and suggested it could be applied as a glucose metabolism-targeting agent for cancer treatment.
Protein phosphatase 4 coordinates glial membrane recruitment and phagocytic clearance of degenerating axons in Drosophila
Authors: Winfree Lilly M , Speese Sean D , Logan Mary A
Published: February 2017

Neuronal damage induced by injury, stroke, or neurodegenerative disease elicits swift immune responses from glial cells, including altered gene expression, directed migration to injury sites, and glial clearance of damaged neurons through phagocytic engulfment. Collectively, these responses hinder further cellular damage, but the mechanisms that underlie these important protective glial reactions are still unclear. Here, we show that the evolutionarily conserved trimeric protein phosphatase 4 (PP4) serine/threonine phosphatase complex is a novel set of factors required for proper glial responses to nerve injury in the adult Drosophila brain. Glial-specific knockdown of PP4 results in reduced recruitment of glia to severed axons and delayed glial clearance of degenerating axonal debris. We show that PP4 functions downstream of the the glial engulfment receptor Draper to drive glial morphogenesis through the guanine nucleotide exchange factor SOS and the Rho GTPase Rac1, revealing that PP4 molecularly couples Draper to Rac1-mediated cytoskeletal remodeling to ensure glial infiltration of injury sites and timely removal of damaged neurons from the CNS.
Oncogenic role of rab escort protein 1 through EGFR and STAT3 pathway
Authors: Yun Un-Jung , Sung Jee Young , Park Seog-Yun , Ye Sang-Kyu , Shim Jaegal , Lee Jae-Seon , Hibi Masahiko , Bae Young-Ki , Kim Yong-Nyun
Published: February 2017

Rab escort protein-1 (REP1) is linked to choroideremia (CHM), an X-linked degenerative disorder caused by mutations of the gene encoding REP1 (CHM). REP1 mutant zebrafish showed excessive cell death throughout the body, including the eyes, indicating that REP1 is critical for cell survival, a hallmark of cancer. In the present study, we found that REP1 is overexpressed in human tumor tissues from cervical, lung, and colorectal cancer patients, whereas it is expressed at relatively low levels in the normal tissue counterparts. REP1 expression was also elevated in A549 lung cancer cells and HT-29 colon cancer cells compared with BEAS-2B normal lung and CCD-18Co normal colon epithelial cells, respectively. Interestingly, short interfering RNA (siRNA)-mediated REP1 knockdown-induced growth inhibition of cancer cell lines via downregulation of EGFR and inactivation of STAT3, but had a negligible effect on normal cell lines. Moreover, overexpression of REP1 in BEAS-2B cells enhanced cell growth and anchorage-independent colony formation with little increase in EGFR level and STAT3 activation. Furthermore, REP1 knockdown effectively reduced tumor growth in a mouse xenograft model via EGFR downregulation and STAT3 inactivation in vivo. These data suggest that REP1 plays an oncogenic role, driving tumorigenicity via EGFR and STAT3 signaling, and is a potential therapeutic target to control cancers.
Comprehensive genetic exploration of selective tooth agenesis of mandibular incisors by exome sequencing
Authors: Yamaguchi Tetsutaro , Hosomichi Kazuyoshi , Yano Keisuke , Kim Yong-Il , Nakaoka Hirofumi , Kimura Ryosuke , Otsuka Hirotada , Nonaka Naoko , Haga Shugo , Takahashi Masahiro , Shirota Tatsuo , Kikkawa Yoshiaki , Yamada Atsushi , Kamijo Ryutaro , Park Soo-Byung , Nakamura Masanori , Maki Koutaro , Inoue Ituro
Published: February 2017

Tooth agenesis is described as the absence of one or more teeth. It is caused by a failure in tooth development and is one of the most common human developmental anomalies. We herein report genomic analyses of selective mandibular incisor agenesis (SMIA) using exome sequencing. Two Japanese families with SMIA were subjected to exome sequencing, and family with sequence similarity 65 member A (FAM65), nuclear factor of activated T-cells 3 (NFATC3) and cadherin-related 23 gene (CDH23) were detected. In the follow-up study, 51 Japanese and 32 Korean sporadic patients with SMIA were subjected to exome analyses, and 18 reported variants in PAX9, AXIN2, EDA, EDAR, WNT10A, BMP2 and GREM2 and 27 variants of FAM65, NFATC3 and CDH23 were found in 38 patients. Our comprehensive genetic study of SMIA will pave the way for a full understanding of the genetic etiology of SMIA and provide targets for treatment.
Gel phase formation in dilute triblock copolyelectrolyte complexes
Authors: Srivastava Samanvaya , Andreev Marat , Levi Adam E. , Goldfeld David J. , Mao Jun , Heller William T. , Prabhu Vivek M. , de Pablo Juan J. , Tirrell Matthew V.
Published: February 2017

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.
Compiler-aided systematic construction of large-scale DNA strand displacement circuits using unpurified components
Authors: Thubagere Anupama J. , Thachuk Chris , Berleant Joseph , Johnson Robert F. , Ardelean Diana A. , Cherry Kevin M. , Qian Lulu
Published: February 2017

Biochemical circuits made of rationally designed DNA molecules are proofs of concept for embedding control within complex molecular environments. They hold promise for transforming the current technologies in chemistry, biology, medicine and material science by introducing programmable and responsive behaviour to diverse molecular systems. As the transformative power of a technology depends on its accessibility, two main challenges are an automated design process and simple experimental procedures. Here we demonstrate the use of circuit design software, combined with the use of unpurified strands and simplified experimental procedures, for creating a complex DNA strand displacement circuit that consists of 78 distinct species. We develop a systematic procedure for overcoming the challenges involved in using unpurified DNA strands. We also develop a model that takes synthesis errors into consideration and semi-quantitatively reproduces the experimental data. Our methods now enable even novice researchers to successfully design and construct complex DNA strand displacement circuits.
Pairing mechanism in the ferromagnetic superconductor UCoGe
Authors: Wu Beilun , Bastien Gaël , Taupin Mathieu , Paulsen Carley , Howald Ludovic , Aoki Dai , Brison Jean-Pascal
Published: February 2017

Superconductivity is a unique manifestation of quantum mechanics on a macroscopic scale, and one of the rare examples of many-body phenomena that can be explained by predictive, quantitative theories. The superconducting ground state is described as a condensate of Cooper pairs, and a major challenge has been to understand which mechanisms could lead to a bound state between two electrons, despite the large Coulomb repulsion. An even bigger challenge is to identify experimentally this pairing mechanism, notably in unconventional superconductors dominated by strong electronic correlations, like in high-Tc cuprates, iron pnictides or heavy-fermion compounds. Here we show that in the ferromagnetic superconductor UCoGe, the field dependence of the pairing strength influences dramatically its macroscopic properties like the superconducting upper critical field, in a way that can be quantitatively understood. This provides a simple demonstration of the dominant role of ferromagnetic spin fluctuations in the pairing mechanism.
Drebrin-mediated microtubule–actomyosin coupling steers cerebellar granule neuron nucleokinesis and migration pathway selection
Authors: Trivedi Niraj , Stabley Daniel R. , Cain Blake , Howell Danielle , Laumonnerie Christophe , Ramahi Joseph S. , Temirov Jamshid , Kerekes Ryan A. , Gordon-Weeks Phillip R. , Solecki David J.
Published: February 2017

Neuronal migration from a germinal zone to a final laminar position is essential for the morphogenesis of neuronal circuits. While it is hypothesized that microtubule–actomyosin crosstalk is required for a neuron’s ‘two-stroke’ nucleokinesis cycle, the molecular mechanisms controlling such crosstalk are not defined. By using the drebrin microtubule–actin crosslinking protein as an entry point into the cerebellar granule neuron system in combination with super-resolution microscopy, we investigate how these cytoskeletal systems interface during migration. Lattice light-sheet and structured illumination microscopy reveal a proximal leading process nanoscale architecture wherein f-actin and drebrin intervene between microtubules and the plasma membrane. Functional perturbations of drebrin demonstrate that proximal leading process microtubule–actomyosin coupling steers the direction of centrosome and somal migration, as well as the switch from tangential to radial migration. Finally, the Siah2 E3 ubiquitin ligase antagonizes drebrin function, suggesting a model for control of the microtubule–actomyosin interfaces during neuronal differentiation.
Electrically tunable artificial gauge potential for polaritons
Authors: Lim Hyang-Tag , Togan Emre , Kroner Martin , Miguel-Sanchez Javier , Imamoğlu Atac
Published: February 2017

Neutral particles subject to artificial gauge potentials can behave as charged particles in magnetic fields. This fascinating premise has led to demonstrations of one-way waveguides, topologically protected edge states and Landau levels for photons. In ultracold neutral atoms, effective gauge fields have allowed the emulation of matter under strong magnetic fields leading to realization of Harper-Hofstadter and Haldane models. Here we show that application of perpendicular electric and magnetic fields effects a tunable artificial gauge potential for two-dimensional microcavity exciton polaritons. For verification, we perform interferometric measurements of the associated phase accumulated during coherent polariton transport. Since the gauge potential originates from the magnetoelectric Stark effect, it can be realized for photons strongly coupled to excitations in any polarizable medium. Together with strong polariton–polariton interactions and engineered polariton lattices, artificial gauge fields could play a key role in investigation of non-equilibrium dynamics of strongly correlated photons.
Hierarchical tissue organization as a general mechanism to limit the accumulation of somatic mutations
Authors: Derényi Imre , Szöllősi Gergely J.
Published: February 2017

How can tissues generate large numbers of cells, yet keep the divisional load (the number of divisions along cell lineages) low in order to curtail the accumulation of somatic mutations and reduce the risk of cancer? To answer the question we consider a general model of hierarchically organized self-renewing tissues and show that the lifetime divisional load of such a tissue is independent of the details of the cell differentiation processes, and depends only on two structural and two dynamical parameters. Our results demonstrate that a strict analytical relationship exists between two seemingly disparate characteristics of self-renewing tissues: divisional load and tissue organization. Most remarkably, we find that a sufficient number of progressively slower dividing cell types can be almost as efficient in minimizing the divisional load, as non-renewing tissues. We argue that one of the main functions of tissue-specific stem cells and differentiation hierarchies is the prevention of cancer.
Interface confined hydrogen evolution reaction in zero valent metal nanoparticles-intercalated molybdenum disulfide
Authors: Chen Zhongxin , Leng Kai , Zhao Xiaoxu , Malkhandi Souradip , Tang Wei , Tian Bingbing , Dong Lei , Zheng Lirong , Lin Ming , Yeo Boon Siang , Loh Kian Ping
Published: February 2017

Interface confined reactions, which can modulate the bonding of reactants with catalytic centres and influence the rate of the mass transport from bulk solution, have emerged as a viable strategy for achieving highly stable and selective catalysis. Here we demonstrate that 1T′-enriched lithiated molybdenum disulfide is a highly powerful reducing agent, which can be exploited for the in-situ reduction of metal ions within the inner planes of lithiated molybdenum disulfide to form a zero valent metal-intercalated molybdenum disulfide. The confinement of platinum nanoparticles within the molybdenum disulfide layered structure leads to enhanced hydrogen evolution reaction activity and stability compared to catalysts dispersed on carbon support. In particular, the inner platinum surface is accessible to charged species like proton and metal ions, while blocking poisoning by larger sized pollutants or neutral molecules. This points a way forward for using bulk intercalated compounds for energy related applications.
Ectopic expression of Arabidopsis Target of Rapamycin (AtTOR) improves water-use efficiency and yield potential in rice
Authors: Bakshi Achala , Moin Mazahar , Kumar M. Udaya , Reddy Aramati Bindu Madhava , Ren Maozhi , Datla Raju , Siddiq E. A. , Kirti P. B.
Published: February 2017

The target of Rapamycin (TOR) present in all eukaryotes is a multifunctional protein, regulating growth, development, protein translation, ribosome biogenesis, nutrient, and energy signaling. In the present study, ectopic expression of TOR gene of Arabidopsis thaliana in a widely cultivated indica rice resulted in enhanced plant growth under water-limiting conditions conferring agronomically important water-use efficiency (WUE) trait. The AtTOR high expression lines of rice exhibited profuse tillering, increased panicle length, increased plant height, high photosynthetic efficiency, chlorophyll content and low ∆13C. Δ13C, which is inversely related to high WUE, was as low as 17‰ in two AtTOR high expression lines. These lines were also insensitive to the ABA-mediated inhibition of seed germination. The significant upregulation of 15 stress-specific genes in high expression lines indicates their contribution to abiotic stress tolerance. The constitutive expression of AtTOR is also associated with significant transcriptional upregulation of putative TOR complex-1 components, OsRaptor and OsLST8. Glucose-mediated transcriptional activation of AtTOR gene enhanced lateral root formation. Taken together, our findings indicate that TOR, in addition to its multiple cellular functions, also plays an important role in response to abiotic stress and potentially enhances WUE and yield related attributes.
Effect of environmentally-relevant concentrations of nonylphenol on sexual differentiation in zebrafish: a multi-generational study
Authors: Sun Dong , Chen Qi , He Ning , Diao Pan-pan , Jia Li-xing , Duan Shun-shan
Published: February 2017

Nonylphenol (NP) is a persistent environmental chemical that can disrupt the organism’s endocrine system, and is detected in the surface water and sea. In this study, we investigated whether NP can alter transcriptional expression of sexual differentiation-related genes. Three generations of zebrafish were exposed to 0, 2, 20 and 200 μg·L−1 of NP, and transcriptional expression of sexual differentiation genes were assessed in 10, 20 and 40 dpf in the F1 and F2 generations. Growth of zebrafish exposed to 200 μg·L−1 of NP was inhibited at 125 dpf in the F1 generation. 20 μg·L−1 of NP resulted in 80% females in the F1 generation, but had no effect on the F2 generation. In terms of the sexual differentiation genes, the transcriptional expression of cyp19a1a and esr1 genes were upregulated in 20 μg·L−1 of NP in the F1 generation. But expression of the sexual differentiation genes were not affected in the F2 generation. Overall, NP could affect sexual differentiation and gene transcriptional expression in the F1 generation. The tolerance of contaminant in the offsprings was improved at low concentration.
Consistent role of Quaternary climate change in shaping current plant functional diversity patterns across European plant orders
Authors: Ordonez Alejandro , Svenning Jens-Christian
Published: February 2017

Current and historical environmental conditions are known to determine jointly contemporary species distributions and richness patterns. However, whether historical dynamics in species distributions and richness translate to functional diversity patterns remains, for the most part, unknown. The geographic patterns of plant functional space size (richness) and packing (dispersion) for six widely distributed orders of European angiosperms were estimated using atlas distribution data and trait information. Then the relative importance of late-Quaternary glacial-interglacial climate change and contemporary environmental factors (climate, productivity, and topography) as determinants of functional diversity of evaluated orders was assesed. Functional diversity patterns of all evaluated orders exhibited prominent glacial-interglacial climate change imprints, complementing the influence of contemporary environmental conditions. The importance of Quaternary glacial-interglacial climate change factors was comparable to that of contemporary environmental factors across evaluated orders. Therefore, high long-term paleoclimate variability has imposed consistent supplementary constraints on functional diversity of multiple plant groups, a legacy that may permeate to ecosystem functioning and resilience. These findings suggest that strong near-future anthropogenic climate change may elicit long-term functional disequilibria in plant functional diversity.
Diversity in mixed species groups improves success in a novel feeder test in a wild songbird community
Authors: Freeberg Todd M. , Eppert Shannon K. , Sieving Kathryn E. , Lucas Jeffrey R.
Published: February 2017

Mixed-species groups are common and are thought to provide benefits to group members via enhanced food finding and antipredator abilities. These benefits could accrue due to larger group sizes in general but also to the diverse species composition in the groups. We tested these possibilities using a novel feeder test in a wild songbird community containing three species that varied in their dominant-subordinate status and in their nuclear-satellite roles: Carolina chickadees (Poecile carolinensis), tufted titmice (Baeolophus bicolor), and white-breasted nuthatches (Sitta carolinensis). We found that chickadees and titmice were more likely to obtain seed from the novel feeder with greater diversity of species composition in their mixed-species flocks. For successful chickadee flocks, furthermore, the latency to obtain seed from the novel feeder was shorter the more diverse their flocks were. These results in a natural setting indicate that diversity, per se, can benefit individuals in mixed-species groups in biologically meaningful contexts such as finding food in novel places.
Nardilysin regulates inflammation, metaplasia, and tumors in murine stomach
Authors: Kimura Yuto , Ikuta Kozo , Kimura Takeshi , Chiba Tsutomu , Oshima Hiroko , Oshima Masanobu , Nishi Eiichiro , Seno Hiroshi
Published: February 2017

Chronic inflammation contributes to a wide variety of human disorders. In the stomach, longstanding gastritis often results in structural alterations in the gastric mucosa, including metaplastic changes and gastric cancers. Therefore, it is important to elucidate factors that are involved in gastric inflammation. Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins. Here, we have demonstrated that Nrdc crucially regulates gastric inflammation caused byHelicobacter felisinfection or forced expression of prostaglandin E2inK19-C2mEmice. Metaplastic changes following gastric inflammation were suppressed by the deletion ofNrdc. Furthremore, the deletion ofNrdcsignificantly suppressedN-methyl-N-nitrosourea (MNU)-induced gastric tumorigenesis in the murine stomach. These data may lead to a global therapeutic approach against various gastric disorders by targeting Nrdc.
N-Acetylated Proline-Glycine-Proline Accelerates Cutaneous Wound Healing and Neovascularization by Human Endothelial Progenitor Cells
Authors: Kwon Yang Woo , Heo Soon Chul , Lee Tae Wook , Park Gyu Tae , Yoon Jung Won , Jang Il Ho , Kim Seung-Chul , Ko Hyun-Chang , Ryu Youngjae , Kang Hyeona , Ha Chang Man , Lee Sang Chul , Kim Jae Ho
Published: February 2017

Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro. Knockdown of CXCR2 expression in hEPCs abrogated the stimulatory effects of Ac-PGP on migration and tube formation. In a cutaneous wound healing model of rats and mice, topical application of Ac-PGP accelerated cutaneous wound healing with promotion of neovascularization. The positive effects of Ac-PGP on wound healing and neovascularization were blocked in CXCR2 knockout mice. In nude mice, the individual application of Ac-PGP treatment or hEPC injection accelerated wound healing by increasing neovascularization. Moreover, the combination of Ac-PGP treatment and hEPC injection further stimulated wound healing and neovascularization. Topical administration of Ac-PGP onto wound bed stimulated migration and engraftment of transplanted hEPCs into cutaneous dermal wounds. Therefore, these results suggest novel applications of Ac-PGP in promoting wound healing and augmenting the therapeutic efficacy of hEPCs.
Persistent Neuronal Activity in Anterior Cingulate Cortex Correlates with Sustained Attention in Rats Regardless of Sensory Modality
Authors: Wu Dingcheng , Deng Hanfei , Xiao Xiong , Zuo Yanfang , Sun Jingjing , Wang Zuoren
Published: February 2017

The anterior cingulate cortex (ACC) has long been thought to regulate conflict between an object of attention and distractors during goal-directed sustained attention. However, it is unclear whether ACC serves to sustained attention itself. Here, we developed a task in which the time course of sustained attention could be controlled in rats. Then, using pharmacological lesion experiments, we employed it to assess function of ACC in sustained attention. We then recorded neuronal activity in ACC using multichannel extracellular recording techniques and identified specific ACC neurons persistently activated during the period of attention. Further experiments showed that target modality had minimal influence on the neuronal activity, and distracting external sensory input during the attention period did not perturb persistent neuronal activity. Additionally, minimal trial-to-trial variability in neuronal activity observed during sustained attention supports a role for ACC neurons in that behavior. Therefore, we conclude that the ACC neuronal activity correlates with sustained attention.
Dezocine exhibits antihypersensitivity activities in neuropathy through spinal μ-opioid receptor activation and norepinephrine reuptake inhibition
Authors: Wang Yong-Xiang , Mao Xiao-Fang , Li Teng-Fei , Gong Nian , Zhang Ma-Zhong
Published: February 2017

Dezocine is the number one opioid painkiller prescribed and sold in China, occupying 44% of the nation’s opioid analgesics market today and far ahead of the gold-standard morphine. We discovered the mechanisms underlying dezocine antihypersensitivity activity and assessed their implications to antihypersensitivity tolerance. Dezocine, given subcutaneously in spinal nerve-ligated neuropathic rats, time- and dose-dependently produced mechanical antiallodynia and thermal antihyperalgesia, significantly increased ipsilateral spinal norepinephrine and serotonin levels, and induced less antiallodynic tolerance than morphine. Its mechanical antiallodynia was partially (40% or 60%) and completely (100%) attenuated by spinal μ-opioid receptor (MOR) antagonism or norepinephrine depletion/α2-adrenoceptor antagonism and combined antagonism of MORs and α2-adenoceptors, respectively. In contrast, antagonism of spinal κ-opioid receptors (KORs) and δ-opioid receptors (DORs) or depletion of spinal serotonin did not significantly alter dezocine antiallodynia. In addition, dezocine-delayed antiallodynic tolerance was accelerated by spinal norepinephrine depletion/α2-adenoceptor antagonism. Thus dezocine produces antihypersensitivity activity through spinal MOR activation and norepinephrine reuptake inhibition (NRI), but apparently not through spinal KOR and DOR activation, serotonin reuptake inhibition or other mechanisms. Our findings reclassify dezocine as the first analgesic of the recently proposed MOR-NRI, and reveal its potential as an alternative to as well as concurrent use with morphine in treating pain.
Lung, gastric and colorectal cancer mortality by occupation and industry among working-aged men in Japan
Authors: Eguchi Hisashi , Wada Koji , Prieto-Merino David , Smith Derek R.
Published: February 2017

We examined occupational and industrial differences in lung, gastric, and colorectal cancer risk among Japanese men of working age (25–64 years) using the 2010 Japanese national survey data for occupation and industry-specific death rates. Poisson regression models were used to estimate the age-adjusted incident rate ratios by lung, gastric, and colorectal cancers, with manufacturing used as the referent occupation or industry. Unemployed Japanese men and those in manufacturing had an 8–11-fold increased risk of lung, gastric and colorectal cancer. The highest mortality rates for lung and colorectal cancer by occupation were “administrative and managerial” (by occupation) and “mining” (by industry). For gastric cancer, the highest mortality rate was “agriculture” (by occupation) and “mining” (by industry). By occupation; Japanese men in service occupations, those in administrative and managerial positions, those in agriculture, forestry and fisheries, and those in professional and engineering categories had higher relative mortality risks for lung, gastric, and colorectal cancers. By industry; mining, electricity and gas, fisheries, and agriculture and forestry had the higher mortality risks for those cancers. Unemployed men had higher mortality rates than men in any occupation and industry for all three cancers. Overall, this study suggests that for Japanese men, occupations and industries may be a key social determinant of health.
Pentabromophenol suppresses TGF-β signaling by accelerating degradation of type II TGF-β receptors via caveolae-mediated endocytosis
Authors: Chen Chun-Lin , Yang Pei-Hua , Kao Yu-Chen , Chen Pei-Yu , Chung Chih-Ling , Wang Shih-Wei
Published: February 2017

Pentabromophenol (PBP), a brominated flame retardant (BFR), is widely used in various consumer products. BFRs exert adverse health effects such as neurotoxic and endocrine-disrupting effects. In this study, we found that PBP suppressed TGF-β response by accelerating the turnover rate of TGF-β receptors. PBP suppressed TGF-β-mediated cell migration, PAI-1 promoter-driven reporter gene activation, and Smad2/3 phosphorylation in various cell types. Furthermore, PBP abolished TGF-β-mediated repression of E-cadherin expression, in addition to the induction of vimentin expression and N-cadherin and fibronectin upregulation, thus blocking TGF-β-induced epithelial–mesenchymal transition in A549 and NMuMG cells. However, this inhibition was not observed with other congeners such as tribromophenol and triiodophenol. TGF-β superfamily members play key roles in regulating various biological processes including cell proliferation and migration as well as cancer development and progression. The results of this in vitro study provide a basis for studies on the detailed relationship between PBP and modulation of TGF-β signalling. Because PBP is similar to other BFRs such as polybrominated diphenyl ethers (PBDEs), additional laboratory and mechanistic studies should be performed to examine BFRs as potential risk factors for tumorigenesis and other TGF-β-related diseases.
A solution-processed quaternary oxide system obtained at low-temperature using a vertical diffusion technique
Authors: Yoon Seokhyun , Kim Si Joon , Tak Young Jun , Kim Hyun Jae
Published: February 2017

We report a method for fabricating solution-processed quaternary In-Ga-Zn-O (IGZO) thin-film transistors (TFTs) at low annealing temperatures using a vertical diffusion technique (VDT). The VDT is a deposition process for spin-coating binary and ternary oxide layers consecutively and annealing at once. With the VDT, uniform and dense quaternary oxide layers were fabricated at lower temperatures (280 °C). Compared to conventional IGZO and ternary In-Zn-O (IZO) thin films, VDT IGZO thin film had higher density of the metal-oxide bonds and lower density of the oxygen vacancies. The field-effect mobility of VDT IGZO TFT increased three times with an improved stability under positive bias stress than IZO TFT due to the reduction in oxygen vacancies. Therefore, the VDT process is a simple method that reduces the processing temperature without any additional treatment for quaternary oxide semiconductors with uniform layers.
Adaptive free-space optical communications through turbulence using self-healing Bessel beams
Authors: Li Shuhui , Wang Jian
Published: February 2017

We present a scheme to realize obstruction- and turbulence-tolerant free-space orbital angular momentum (OAM) multiplexing link by using self-healing Bessel beams accompanied by adaptive compensation techniques. Compensation of multiple 16-ary quadrature amplitude modulation (16-QAM) data carrying Bessel beams through emulated atmospheric turbulence and obstructions is demonstrated. The obtained experimental results indicate that the compensation scheme can effectively reduce the inter-channel crosstalk, improve the bit-error rate (BER) performance, and recuperate the nondiffracting property of Bessel beams. The proposed scheme might be used in future high-capacity OAM links which are affected by atmospheric turbulence and obstructions.
Dynamics of contextual modulation of perceived shape in human vision
Authors: Gheorghiu Elena , Kingdom Frederick A. A.
Published: February 2017

In biological vision, contextual modulation refers to the influence of a surround pattern on either the perception of, or the neural responses to, a target pattern. One studied form of contextual modulation deals with the effect of a surround texture on the perceived shape of a contour, in the context of the phenomenon known as the shape aftereffect. In the shape aftereffect, prolonged viewing, or adaptation to a particular contour’s shape causes a shift in the perceived shape of a subsequently viewed contour. Shape aftereffects are suppressed when the adaptor contour is surrounded by a texture of similarly-shaped contours, a surprising result given that the surround contours are all potential adaptors. Here we determine the motion and temporal properties of this form of contextual modulation. We varied the relative motion directions, speeds and temporal phases between the central adaptor contour and the surround texture and measured for each manipulation the degree to which the shape aftereffect was suppressed. Results indicate that contextual modulation of shape processing is selective to motion direction, temporal frequency and temporal phase. These selectivities are consistent with one aim of vision being to segregate contours that define objects from those that form textured surfaces.
3D Time-lapse Imaging and Quantification of Mitochondrial Dynamics
Authors: Sison Miguel , Chakrabortty Sabyasachi , Extermann Jérôme , Nahas Amir , James Marchand Paul , Lopez Antonio , Weil Tanja , Lasser Theo
Published: February 2017

We present a 3D time-lapse imaging method for monitoring mitochondrial dynamics in living HeLa cells based on photothermal optical coherence microscopy and using novel surface functionalization of gold nanoparticles. The biocompatible protein-based biopolymer coating contains multiple functional groups which impart better cellular uptake and mitochondria targeting efficiency. The high stability of the gold nanoparticles allows continuous imaging over an extended time up to 3000 seconds without significant cell damage. By combining temporal autocorrelation analysis with a classical diffusion model, we quantify mitochondrial dynamics and cast these results into 3D maps showing the heterogeneity of diffusion parameters across the whole cell volume.
Assessment of Chicken Carcass Microbiome Responses During Processing in the Presence of Commercial Antimicrobials Using a Next Generation Sequencing Approach
Authors: Ae Kim Sun , Hong Park Si , In Lee Sang , Owens Casey M. , Ricke Steven C.
Published: February 2017

The purpose of this study was to 1) identify microbial compositional changes on chicken carcasses during processing, 2) determine the antimicrobial efficacy of peracetic acid (PAA) and Amplon (blend of sulfuric acid and sodium sulfate) at a poultry processing pilot plant scale, and 3) compare microbial communities between chicken carcass rinsates and recovered bacteria from media. Birds were collected from each processing step and rinsates were applied to estimate aerobic plate count (APC) andCampylobacteras well asSalmonellaprevalence. Microbiome sequencing was utilized to identify microbial population changes over processing and antimicrobial treatments. Only the PAA treatment exhibited significant reduction of APC at the post chilling step while both Amplon and PAA yielded detectableCampylobacterreductions at all steps. Based on microbiome sequencing, Firmicutes were the predominant bacterial group at the phyla level with over 50% frequency in all steps while the relative abundance of Proteobacteria decreased as processing progressed. Overall microbiota between rinsate and APC plate microbial populations revealed generally similar patterns at the phyla level but they were different at the genus level. Both antimicrobials appeared to be effective on reducing problematic bacteria and microbiome can be utilized to identify optimal indicator microorganisms for enhancing product quality.
Modulation of yellow expression contributes to thermal plasticity of female abdominal pigmentation in Drosophila melanogaster
Authors: Gibert Jean-Michel , Mouchel-Vielh Emmanuèle , Peronnet Frédérique
Published: February 2017

Phenotypic plasticity describes the ability of a given genotype to produce distinct phenotypes in different environments. We use the temperature sensitivity of abdominal pigmentation in Drosophila melanogaster females as a model to analyse the effect of the environment on development. We reported previously that thermal plasticity of abdominal pigmentation in females involves the pigmentation gene tan (t). However, the expression of the pigmentation gene yellow (y) was also modulated by temperature in the abdominal epidermis of pharate females. We investigate here the contribution of y to female abdominal pigmentation plasticity. First, we show that y is required for the production of black Dopamine-melanin. Then, using in situ hybridization, we show that the expression of y is strongly modulated by temperature in the abdominal epidermis of pharate females but not in bristles. Interestingly, these two expression patterns are known to be controlled by distinct enhancers. However, the activity of the y-wing-body epidermal enhancer only partially mediates the effect of temperature suggesting that additional regulatory sequences are involved. In addition, we show that y and t co-expression is needed to induce strong black pigmentation indicating that y contributes to female abdominal pigmentation plasticity.
Ageing behavior of extruded Mg–8.2Gd–3.8Y–1.0Zn–0.4Zr (wt.%) alloy containing LPSO phase and γ′ precipitates
Authors: Xu C. , Nakata T. , Qiao X. G. , Zheng M. Y. , Wu K. , Kamado S.
Published: February 2017

The effect of long period stacking ordered (LPSO) phase and γ′ precipitates on the ageing behavior and mechanical properties of the extruded Mg–8.2Gd–3.8Y–1.0Zn–0.4Zr (wt.%) alloy was investigated. The results show that more β′ phases precipitate during ageing treatment in the LPSO phase containing alloy so that the LPSO phase containing alloy exhibits a higher age-hardening response than the γ′ precipitates containing alloy. The precipitation strengthening induced by β′ precipitates is the greatest contributor to the strength of the peak-aged LPSO-containing alloys. Higher strength is achieved in γ′ precipitates containing alloy due to the more effective strengthening induced by dense nanoscale γ′ precipitates than LPSO phases as well as the higher volume fraction of coarse unrecrystallized grains with strong basal texture. The extruded alloy containing γ′ precipitates after T5 peak-ageing treatment shows ultra-high tensile yield strength of 462 MPa, high ultimate tensile strength of 520 MPa, and superior elongation to failure of 10.6%.
Long-term Impact of Temporal Sequence from Childhood Obesity to Hyperinsulinemia on Adult Metabolic Syndrome and Diabetes: The Bogalusa Heart Study
Authors: Zhang Tao , Zhang Huijie , Li Ying , Li Shengxu , Fernandez Camilo , Bazzano Lydia , He Jiang , Xue Fuzhong , Chen Wei
Published: February 2017

This study aims to delineate the temporal relations between body mass index (BMI) and insulin in childhood and their impact on adult metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM).The longitudinal cohort consisted of 609 whites and 339 blacks who had BMI and fasting insulin measured twice in childhood (mean age = 10.5 years at baseline and 15.9 years at follow-up). Incident MetS and T2DM were identified in adulthood (mean age = 30.5 years). Cross-lagged panel and mediation analysis models were used. After adjusting for age, race, gender, and follow-up years, the cross-lagged path coefficient of BMI → insulin (β = 0.326, p < 0.001) was significantly greater than that of insulin → BMI (β = −0.023, p = 0.207) in childhood, with p < 0.001 for the difference in βs. The path coefficient for BMI → insulin was significantly greater in MetS than in non-MetS groups (0.510 vs 0.190, p < 0.001), and greater in hyperglycemia than in normoglycemia groups (0.503 vs 0.285, p = 0.026). The mediation effect of childhood insulin on the BMI-MetS and BMI-hyperglycemia associations was estimated at 19.2% (p < 0.001) and 18.3% (p < 0.001), respectively. These findings provide evidence that higher BMI levels precede hyperinsulinemia during childhood, and this one-directional relation plays a significant role in the development of MetS and T2DM in adult life.
MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association
Authors: Marom Shani , Friger Michael , Mishmar Dan
Published: February 2017

Human mtDNA genetic variants have traditionally been considered markers for ancient population migrations. However, during the past three decades, these variants have been associated with altered susceptibility to various phenotypes, thus supporting their importance for human health. Nevertheless, mtDNA disease association has frequently been supported only in certain populations, due either to population stratification or differential epistatic compensations among populations. To partially overcome these obstacles, we performed meta-analysis of the multiple mtDNA association studies conducted until 2016, encompassing 53,975 patients and 63,323 controls. Our findings support the association of mtDNA haplogroups and recurrent variants with specific phenotypes such as Parkinson’s disease, type 2 diabetes, longevity, and breast cancer. Strikingly, our assessment of mtDNA variants’ involvement with multiple phenotypes revealed significant impact for Caucasian haplogroups H, J, and K. Therefore, ancient mtDNA variants could be divided into those that affect specific phenotypes, versus others with a general impact on phenotype combinations. We suggest that the mtDNA could serve as a model for phenotype specificity versus allele heterogeneity.
Atomic scale structure of amorphous aluminum oxyhydroxide, oxide and oxycarbide films probed by very high field27Al nuclear magnetic resonance
Authors: Baggetto L. , Sarou-Kanian V. , Florian P. , Gleizes A. N. , Massiot D. , Vahlas C.
Published: February 2017

The atomic scale structure of aluminum in amorphous alumina films processed by direct liquid injection chemical vapor deposition from aluminum tri-isopropoxide (ATI) and dimethyl isopropoxide (DMAI) is investigated by solid-state27Al nuclear magnetic resonance at 20 T.
An insight into methanol oxidation mechanisms on RuO2(100) under an aqueous environment by DFT calculations
Authors: Sheng Tian , Ye Jin-Yu , Lin Wen-Feng , Sun Shi-Gang
Published: February 2017

In this work, we have studied methanol oxidation mechanisms on RuO2(100) by using density functional theory (DFT) calculations and ab initio molecular dynamics (MD) simulations with some explicit interfacial water molecules.
Tunable phenol remediation from wastewater using SWCNT-based, sub-nanometer porous membranes: reactive molecular dynamics simulations and DFT calculations
Authors: Moradi F. , Ganji M. Darvish , Sarrafi Y.
Published: February 2017

Reactive molecular dynamic (MD) simulations and first-principle density functional theory (DFT) calculations were used to investigate the performance of SWCNT-based, sub-nanometer porous membranes for phenol remediation from wastewater.
Characterization of fine particles using optomagnetic measurements
Authors: Fock Jeppe , Jonasson Christian , Johansson Christer , Hansen Mikkel Fougt
Published: February 2017

Measurements of optical transmission in an oscillating magnetic field are used to determine the magnetic moment and hydrodynamic size of magnetic nanoparticles.
Improving the capacity of lithium–sulfur batteries by tailoring the polysulfide adsorption efficiency of hierarchical oxygen/nitrogen-functionalized carbon host materials
Authors: Schneider Artur , Janek Jürgen , Brezesinski Torsten
Published: February 2017

O/N-functionalization of hierarchical carbon is demonstrated to be effective in enhancing the adsorption capacity for lithium polysulfide and thus the reversible capacity of Li–S cells.
Reactions of water and C1 molecules on carbide and metal-modified carbide surfaces
Authors: Wan Weiming , Tackett Brian M. , Chen Jingguang G.
Published: February 2017

This work establishes general trends for modifying the properties of TMC surfaces with metal modifiers.
Dehydrogenative coupling promoted by copper catalysts: a way to optimise and upgrade bio-alcohols
Authors: Scotti Nicola , Zaccheria Federica , Evangelisti Claudio , Psaro Rinaldo , Ravasio Nicoletta
Published: February 2017

A one-pot one-step transformation of butanol into butyl butanoate takes place with excellent yield on a Cu/ZrO2 catalyst.