bluuebunny/crossref_metadata_2025_split huggingface dataset:
The microRNA-200/Zeb1 axis regulates ECM-dependent β1-integrin/FAK signaling, cancer cell invasion and metastasis through CRKL
Authors: Ungewiss Christin , Rizvi Zain H. , Roybal Jonathon D. , Peng David H. , Gold Kathryn A. , Shin Dong-Hoon , Creighton Chad J. , Gibbons Don L. 
Published: January 2016

AbstractTumor cell metastasis is a complex process that has been mechanistically linked to the epithelial-mesenchymal transition (EMT). The double-negative feedback loop between the microRNA-200 family and the Zeb1 transcriptional repressor is a master EMT regulator, but there is incomplete understanding of how miR-200 suppresses invasion. Our recent efforts have focused on the tumor cell-matrix interactions essential to tumor cell activation. Herein we utilized both our Kras/p53 mutant mouse model and human lung cancer cell lines to demonstrate that upon miR-200 loss integrin β1-collagen I interactions drive 3D in vitro migration/invasion and in vivo metastases. Zeb1-dependent EMT enhances tumor cell responsiveness to the ECM composition and activates FAK/Src pathway signaling by de-repression of the direct miR-200 target, CRKL. We demonstrate that CRKL serves as an adaptor molecule to facilitate focal adhesion formation, mediates outside-in signaling through Itgβ1 to drive cell invasion and inside-out signaling that maintains tumor cell-matrix contacts required for cell invasion. Importantly, CRKL levels in pan-cancer TCGA analyses were predictive of survival and CRKL knockdown suppressed experimental metastases in vivo without affecting primary tumor growth. Our findings highlight the critical ECM-tumor cell interactions regulated by miR-200/Zeb1-dependent EMT that activate intracellular signaling pathways responsible for tumor cell invasion and metastasis.
Shift from complementarity to facilitation on P uptake by intercropped wheat neighboring with faba bean when available soil P is depleted
Authors: Li Chunjie , Dong Yan , Li Haigang , Shen Jianbo , Zhang Fusuo 
Published: January 2016

AbstractRhizosphere processes stimulate overyielding and facilitative phosphorus (P) uptake in cereal/legume intercropping systems. However, little is known about when and how rhizosphere alteration of legumes plays a role in improving P uptake by cereals. Wheat was grown isolated, monocropped or intercropped with faba bean in pots with low-P soil. The biomass, P content, carboxylates and phosphatases activity were measured in 15 destructive samplings. Intraspecific competition of the biomass and P uptake of monocropped wheat was not significant before 40 and 36 days after sowing (DAS), whereas there was interspecific competition of biomass of intercropped wheat before 66 DAS. However, afterwards, the increments of the biomass and P uptake of the intercropped wheat were 1.3–1.9 and 1.9–2.3 times of increment of monocropped wheat. Meanwhile, the concentrations of malate and citrate and the acid phosphatase activity in the rhizospheres of intercropped wheat were significantly increased, which suggested that wheat/faba bean intercropping is efficient in P utilization due to complementary P uptake in the early growth stage and the positive interactions of the rhizosphere processes when the soil P was depleted.
Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts
Authors: Cao Long-Hui , Li Hui-Ting , Lin Wen-Qian , Tan Hong-Ying , Xie Lan , Zhong Zhong-Jian , Zhou Jian-Hua 
Published: January 2016

AbstractMorphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 μg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 μg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an in vivo nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models in vitro and in vivo by inhibiting cisplatin-induced apoptosis and decreasing neovascularization.
Neural mechanisms supporting evaluation of others’ errors in real-life like conditions
Authors: Jääskeläinen Iiro P. , Halme Hanna-Leena , Agam Yigal , Glerean Enrico , Lahnakoski Juha M , Sams Mikko , Tapani Karoliina , Ahveninen Jyrki , Manoach Dara S. 
Published: January 2016

AbstractThe ability to evaluate others’ errors makes it possible to learn from their mistakes without the need for first-hand trial-and-error experiences. Here, we compared functional magnetic resonance imaging activation to self-committed errors during a computer game to a variety of errors committed by others during movie clips (e.g., figure skaters falling down and persons behaving inappropriately). While viewing errors by others there was activation in lateral and medial temporal lobe structures, posterior cingulate cortex, precuneus and medial prefrontal cortex possibly reflecting simulation and storing for future use alternative action sequences that could have led to successful behaviors. During both self- and other-committed errors activation was seen in the striatum, temporoparietal junction and inferior frontal gyrus. These areas may be components of a generic error processing mechanism. The ecological validity of the stimuli seemed to matter, since we largely failed to see activations when subjects observed errors by another player in the computer game, as opposed to observing errors in the rich real-life like human behaviors depicted in the movie clips.
Restriction of protein synthesis abolishes senescence features at cellular and organismal levels
Authors: Takauji Yuki , Wada Takumi , Takeda Asuka , Kudo Ikuru , Miki Kensuke , Fujii Michihiko , Ayusawa Dai 
Published: January 2016

AbstractCellular senescence or its equivalence is induced by treatment of cells with an appropriate inducer of senescence in various cell types. Mild restriction of cytoplasmic protein synthesis prevented induction of all aspects of cellular senescence in normal and tumor-derived human cells. It allowed the cells to continuously grow with no sign of senescent features in the presence of various inducers. It also delayed replicative senescence in normal human fibroblasts. Moreover, it allowed for growth of the cells that had entered a senescent state. When adult worms of the nematode C. elegans were grown under protein-restricted conditions, their average and maximal lifespans were significantly extended. These results suggest that accumulation of cytoplasmic proteins due to imbalance in macromolecule synthesis is a fundamental cause of cellular senescence.
Altered brain energetics induces mitochondrial fission arrest in Alzheimer’s Disease
Authors: Zhang Liang , Trushin Sergey , Christensen Trace A. , Bachmeier Benjamin V. , Gateno Benjamin , Schroeder Andreas , Yao Jia , Itoh Kie , Sesaki Hiromi , Poon Wayne W. , Gylys Karen H. , Patterson Emily R. , Parisi Joseph E. , Diaz Brinton Roberta , Salisbury Jeffrey L. , Trushina Eugenia 
Published: January 2016

AbstractAltered brain metabolism is associated with progression of Alzheimer’s Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, “mitochondria-on-a-string” (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.
Dynamics of Fluoride Bioavailability in the Biofilms of Different Oral Surfaces after Amine Fluoride and Sodium Fluoride Application
Authors: Naumova Ella A. , Dickten Christoph , Jung Rico , Krauss Florian , Rübesamen Henrik , Schmütsch Katharina , Sandulescu Tudor , Zimmer Stefan , Arnold Wolfgang H. 
Published: January 2016

AbstractIt was the aim of this study to investigate differences in fluoride bioavailability in different oral areas after the application of amine fluoride (AmF) and sodium fluoride (NaF). The null hypothesis suggested no differences in the fluoride bioavailability. The tongue coating was removed and biofilm samples from the palate, oral floor and cheeks were collected. All subjects brushed their teeth with toothpaste containing AmF or NaF. Specimens were collected before, as well as immediately after and at 30 and 120 minutes after tooth brushing. The fluoride concentration was determined. The area under the curve was calculated for each location and compared statistically. In the tongue coating, fluoride concentration increased faster after NaF application than after AmF application. After 30 minutes, the fluoride concentration decreased and remained stable until 120 minutes after AmF application and returned to baseline after NaF application. The difference between the baseline and the endpoint measurements was statistically significant. The fluoride concentration in the tongue coating remained at a higher level compared with the baseline for up to 120 minutes post-brushing. This may indicate that the tongue coating is a major reservoir for fluoride bioavailability. The results also indicate an unequal fluoride distribution in the oral cavity.
Quasi-particles ultrafastly releasing kink bosons to form Fermi arcs in a cuprate superconductor
Authors: Ishida Y. , Saitoh T. , Mochiku T. , Nakane T. , Hirata K. , Shin S. 
Published: January 2016

AbstractIn a conventional framework, superconductivity is lost at a critical temperature (Tc) because, at higher temperatures, gluing bosons can no longer bind two electrons into a Cooper pair. In high-Tc cuprates, it is still unknown how superconductivity vanishes at Tc. We provide evidence that the so-called ≲70-meV kink bosons that dress the quasi-particle excitations are playing a key role in the loss of superconductivity in a cuprate. We irradiated a 170-fs laser pulse on Bi2Sr2CaCu2O8+δ and monitored the responses of the superconducting gap and dressed quasi-particles by time- and angle-resolved photoemission spectroscopy. We observe an ultrafast loss of superconducting gap near the d-wave node, or light-induced Fermi arcs, which is accompanied by spectral broadenings and weight redistributions occurring within the kink binding energy. We discuss that the underlying mechanism of the spectral broadening that induce the Fermi arc is the undressing of quasi-particles from the kink bosons. The loss mechanism is beyond the conventional framework and can accept the unconventional phenomena such as the signatures of Cooper pairs remaining at temperatures above Tc.
Missense mutation in DISC1 C-terminal coiled-coil has GSK3β signaling and sex-dependent behavioral effects in mice
Authors: Dachtler James , Elliott Christina , Rodgers R. John , Baillie George S. , Clapcote Steven J. 
Published: January 2016

AbstractDisrupted-in-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and affective disorders. The full-length DISC1 protein consists of an N-terminal ‘head’ domain and a C-terminal tail domain that contains several predicted coiled-coils, structural motifs involved in protein-protein interactions. To probe the in vivo effects of missense mutation of DISC1’s C-terminal tail, we tested mice carrying mutation D453G within a predicted α-helical coiled-coil region. We report that, relative to wild-type littermates, female DISC1D453G mice exhibited novelty-induced hyperlocomotion, an anxiogenic profile in the elevated plus-maze and open field tests and reduced social exploration of unfamiliar mice. Male DISC1D453G mice displayed a deficit in passive avoidance, while neither males nor females exhibited any impairment in startle reactivity or prepulse inhibition. Whole brain homogenates showed normal levels of DISC1 protein, but decreased binding of DISC1 to GSK3β, decreased phospho-inhibition of GSK3β at serine 9 and decreased levels of β-catenin in DISC1D453G mice of either sex. Interrupted GSK3β signaling may thus be part of the mechanism underlying the behavioral phenotype associated with D453G, in common with the previously described N-terminal domain mutations Q31L and L100P in mice and the schizophrenia risk-conferring variant R264Q in humans.
Aim-less translation: loss of Saccharomyces cerevisiae mitochondrial translation initiation factor mIF3/Aim23 leads to unbalanced protein synthesis
Authors: Kuzmenko Anton , Derbikova Ksenia , Salvatori Roger , Tankov Stoyan , Atkinson Gemma C. , Tenson Tanel , Ott Martin , Kamenski Piotr , Hauryliuk Vasili 
Published: January 2016

AbstractThe mitochondrial genome almost exclusively encodes a handful of transmembrane constituents of the oxidative phosphorylation (OXPHOS) system. Coordinated expression of these genes ensures the correct stoichiometry of the system’s components. Translation initiation in mitochondria is assisted by two general initiation factors mIF2 and mIF3, orthologues of which in bacteria are indispensible for protein synthesis and viability. mIF3 was thought to be absent inSaccharomyces cerevisiaeuntil we recently identified mitochondrial protein Aim23 as the missing orthologue. Here we show that, surprisingly, loss of mIF3/Aim23 inS. cerevisiaedoes not indiscriminately abrogate mitochondrial translation but rather causes an imbalance in protein production: the rate of synthesis of the Atp9 subunit of F1F0ATP synthase (complex V) is increased, while expression of Cox1, Cox2 and Cox3 subunits of cytochromecoxidase (complex IV) is repressed. Our results provide one more example of deviation of mitochondrial translation from its bacterial origins.
Evaluation of Post Cessation Weight Gain in a 1-Year Randomized Smoking Cessation Trial of Electronic Cigarettes
Authors: Russo Cristina , Cibella Fabio , Caponnetto Pasquale , Campagna Davide , Maglia Marilena , Frazzetto Evelise , Mondati Enrico , Caruso Massimo , Polosa Riccardo 
Published: January 2016

AbstractStop smoking it is often associated to weight gain that is one of the most important causes for relapse. This is the first study to describe long-term changes in body weight in smokers invited to quit or reduce smoking by switching to ECs. Conventional cigarettes consumption and body weight were measured prospectively in a randomized controlled trial of smokers invited to switch to ECs. Post cessation weight changes from baseline at week-12, -24 and -52 were compared among 1) high, medium and zero nicotine strength products and 2) pooled continuous smoking failure, smoking reduction and abstinence phenotypes. Saliva cotinine levels and appetite levels were also measured. No significant changes in body weight were observed among high, medium and zero nicotine strength products. Differences among continuous smoking phenotypes were significant only at week-12 (p = 0.010) and week-24 (p = 0.012) with quitters gaining 2.4{plus minus}4.3 Kg and 2.9{plus minus}4.4 Kg respectively. However, weight gain at week-52 (1.5{plus minus}5.0 Kg) was no longer significant compared to Failures and Reducers. No confounding factors could explain the significant changes in body weight. Smokers who quit smoking by switching to ECs may limit their post-cessation weight gain, with substantial reversal in weight gain being manifest at late time points.
Blood-based gene expression signatures of medication-free outpatients with major depressive disorder: integrative genome-wide and candidate gene analyses
Authors: Hori Hiroaki , Sasayama Daimei , Teraishi Toshiya , Yamamoto Noriko , Nakamura Seiji , Ota Miho , Hattori Kotaro , Kim Yoshiharu , Higuchi Teruhiko , Kunugi Hiroshi 
Published: January 2016

AbstractSeveral microarray-based studies have investigated gene expression profiles in major depressive disorder (MDD), yet with highly variable findings. We examined blood-based genome-wide expression signatures of MDD, focusing on molecular pathways and networks underlying differentially expressed genes (DEGs) and behaviours of hypothesis-driven, evidence-based candidate genes for depression. Agilent human whole-genome arrays were used to measure gene expression in 14 medication-free outpatients with MDD who were at least moderately ill and 14 healthy controls matched pairwise for age and sex. After filtering, we compared expression of entire probes between patients and controls and identified DEGs. The DEGs were evaluated by pathway and network analyses. For the candidate gene analysis, we utilized 169 previously prioritized genes and examined their case-control separation efficiency and correlational co-expression network in patients relative to controls. The 317 screened DEGs mapped to a significantly over-represented pathway, the “synaptic transmission” pathway. The protein-protein interaction network was also significantly enriched, in which a number of key molecules for depression were included. The co-expression network of candidate genes was markedly disrupted in patients. This study provided evidence for an altered molecular network along with several key molecules in MDD and confirmed that the candidate genes are worthwhile targets for depression research.
Shifts in methanogen community structure and function across a coastal marsh transect: effects of exotic Spartina alterniflora invasion
Authors: Yuan Junji , Ding Weixin , Liu Deyan , Kang Hojeong , Xiang Jian , Lin Yongxin 
Published: January 2016

AbstractInvasion of Spartina alterniflora in coastal areas of China increased methane (CH4) emissions. To elucidate the underlying mechanisms, we measured CH4 production potential, methanogen community structure and biogeochemical factors along a coastal wetland transect comprised of five habitat regions: open water, bare tidal flat, invasive S. alterniflora marsh and native Suaeda salsa and Phragmites australis marshes. CH4 production potential in S. alterniflora marsh was 10 times higher than that in other regions and it was significantly correlated with soil organic carbon, dissolved organic carbon and trimethylamine concentrations, but was not correlated with acetate or formate concentrations. Although the diversity of methanogens was lowest in S. alterniflora marsh, invasion increased methanogen abundance by 3.48-fold, compared with native S. salsa and P. australis marshes due to increase of facultative Methanosarcinaceae rather than acetotrophic and hydrogenotrophic methanogens. Ordination analyses suggested that trimethylamine was the primary factor regulating shift in methanogen community structure. Addition of trimethylamine increased CH4 production rates by 1255-fold but only by 5.61- and 11.4-fold for acetate and H2/CO2, respectively. S. alterniflora invasion elevated concentration of non-competitive trimethylamine and shifted methanogen community from acetotrophic to facultative methanogens, which together facilitated increased CH4 production potential.
Dual modulation of Ras-Mnk and PI3K-AKT-mTOR pathways: A Novel c-FLIP inhibitory mechanism of 3-AWA mediated translational attenuation through dephosphorylation of eIF4E
Authors: ur Rasool Reyaz , Rah Bilal , Amin Hina , Nayak Debasis , Chakraborty Souneek , Rawoof Abdul , Mintoo Mubashir Javed , Yousuf Khalid , Mukherjee Debaraj , Kumar Lekha Dinesh , Mondhe Dilip Manikaro , Goswami Anindya 
Published: January 2016

AbstractThe eukaryotic translation initiation factor 4E (eIF4E) is considered as a key survival protein involved in cell cycle progression, transformation and apoptosis resistance. Herein, we demonstrate that medicinal plant derivative 3-AWA (from Withaferin A) suppressed the proliferation and metastasis of CaP cells through abrogation of eIF4E activation and expression via c-FLIP dependent mechanism. This translational attenuation prevents the de novo synthesis of major players of metastatic cascades viz. c-FLIP, c-Myc and cyclin D1. Moreover, the suppression of c-FLIP due to inhibition of translation initiation complex by 3-AWA enhanced FAS trafficking, BID and caspase 8 cleavage. Further ectopically restored c-Myc and GFP-HRas mediated activation of eIF4E was reduced by 3-AWA in transformed NIH3T3 cells. Detailed underlying mechanisms revealed that 3-AWA inhibited Ras-Mnk and PI3-AKT-mTOR, two major pathways through which eIF4E converges upon eIF4F hub. In addition to in vitro studies, we confirmed that 3-AWA efficiently suppressed tumor growth and metastasis in different mouse models. Given that 3-AWA inhibits c-FLIP through abrogation of translation initiation by co-targeting mTOR and Mnk-eIF4E, it (3-AWA) can be exploited as a lead pharmacophore for promising anti-cancer therapeutic development.
Direct ultrasensitive electrochemical biosensing of pathogenic DNA using homogeneous target-initiated transcription amplification
Authors: Yan Yurong , Ding Shijia , Zhao Dan , Yuan Rui , Zhang Yuhong , Cheng Wei 
Published: January 2016

AbstractSensitive and specific methodologies for detection of pathogenic gene at the point-of-care are still urgent demands in rapid diagnosis of infectious diseases. This work develops a simple and pragmatic electrochemical biosensing strategy for ultrasensitive and specific detection of pathogenic nucleic acids directly by integrating homogeneous target-initiated transcription amplification (HTITA) with interfacial sensing process in single analysis system. The homogeneous recognition and specific binding of target DNA with the designed hairpin probe triggered circular primer extension reaction to form DNA double-strands which contained T7 RNA polymerase promoter and served as templates for in vitro transcription amplification. The HTITA protocol resulted in numerous single-stranded RNA products which could synchronously hybridized with the detection probes and immobilized capture probes for enzyme-amplified electrochemical detection on the biosensor surface. The proposed electrochemical biosensing strategy showed very high sensitivity and selectivity for target DNA with a dynamic response range from 1 fM to 100 pM. Using salmonella as a model, the established strategy was successfully applied to directly detect invA gene from genomic DNA extract. This proposed strategy presented a simple, pragmatic platform toward ultrasensitive nucleic acids detection and would become a versatile and powerful tool for point-of-care pathogen identification.