bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methylene Blue Assay for Estimation of Regenerative Re-EpithelializationIn Vivo
Authors: Milyavsky Maresha , Dickie Renee 
Published: February 2017

AbstractThe rapidity with which epithelial cells cover a wound surface helps determine whether scarring or scar-less healing results. As methylene blue is a vital dye that is absorbed by damaged tissue but not undamaged epidermis, it can be used to assess wound closure. We sought to develop a quantitative methylene blue exclusion assay to estimate the timeframe for re-epithelialization in regenerating appendages in zebrafish and axolotls, two classic model systems of regeneration. Following application of methylene blue to the amputation plane and extensive washing, the regenerating tail was imagedin vivountil staining was no longer visible. The percent area of the amputation plane positive for methylene blue, representing the area of the amputation plane not yet re-epithelialized, was measured for each time point. The loss of methylene blue occurred rapidly, within ~2.5 h in larval and juvenile axolotls and <1 h in adult zebrafish, consistent with high rates of re-epithelialization in these models of regeneration. The assay allows simple, rapid estimation of the time course for regenerative re-epithelialization without affecting subsequent regenerative ability. This technique will permit comparison of re-epithelialization across different strains and stages, as well as under the influence of various pharmacological inhibitors that affect regeneration.
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

AbstractHepatocellular 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

AbstractThe 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

AbstractNeuronal 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

AbstractRab 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

AbstractTooth 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

AbstractAssembly 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

AbstractBiochemical 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

AbstractSuperconductivity 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

AbstractNeuronal 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

AbstractNeutral 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

AbstractHow 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

AbstractInterface 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

AbstractThe 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

AbstractNonylphenol (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.