bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhythmic low-field magnetic stimulation may improve depression by increasing brain-derived neurotrophic factor
Authors: Xiao Le , Correll Christoph U. , Feng Lei , Xiang Yu-Tao , Feng Yuan , Hu Chang-Qing , Li Rena , Wang Gang 
Published: February 2018

BackgroundLow-field magnetic stimulation (LFMS) has mood-elevating effect, and the increase of brain-derived neurotrophic factor (BDNF) is associated with antidepressant treatment. We evaluated the effects and association with BDNF of rhythmic LFMS in the treatment of major depressive disorder (MDD).MethodsA total of 22 MDD patients were randomized to rhythmic alpha stimulation (RAS) or rhythmic delta stimulation (RDS), with 5 sessions per week, lasting for 6 weeks. Outcomes assessments included the 17-item Hamilton Depression Rating Scale (HAMD–17), the Hamilton Anxiety Rating Scale (HAMA), and the Clinical Global Impressions–Severity scale (CGI–S) at baseline and at weeks 1, 2, 3, 4, and 6. Serum BDNF level was measured at baseline and at weeks 2, 4, and 6.ResultsHAMD–17, HAMA, and CGI–S scores were significantly reduced with both RAS and RDS. RAS patients had numerically greater reductions in HAMD–17 scores than RDS patients (8.9 ± 7.4 vs. 6.2 ± 6.2, effect size [ES]=0.40), while RDS patients had greater improvement in HAMA scores (8.2 ± 8.0 vs. 5.3 ± 5.8, ES=0.42). RAS was associated with clinically relevant advantages in response (54.5% vs. 18.2%, number-needed-to-treat [NNT]=3) and remission (36.4% vs. 9.1%, NNT=4). BDNF increased significantly during the 6-week study period (p&lt;0.05), with greater increases in RAS at weeks 4 and 6 (ES=0.66—0.76) and statistical superiority at week 2 (p=0.034, ES=1.23). Baseline BDNF in the 8 responders (24.8±9.0 ng/ml) was lower than in the 14 nonresponders (31.1±7.3 ng/ml, p=0.083, ES=–0.79), and BDNF increased more in responders (8.9±7.8 ng/ml) than in nonresponders (1.8±3.5 ng/ml, p=0.044). The change in BDNF at week 2 was the most strongly predicted response (p=0.016).ConclusionsRhythmic LFMS was effective for MDD. BDNF may moderate/mediate the efficacy of LFMS.
The consequences of very late exposure to BSL as an L1
Authors: WOLL BENCIE 
Published: February 2018

Mayberry and Kluender (2017) make an important contribution to our understanding of the CPL, reporting the striking differences in regions of brain activation in Martin, a deaf man with very late exposure to an L1, compared to other deaf individuals, when processing single signs of ASL. They conclude: “The unique effects of AoA . . . suggest that the hierarchical structure of language and the architecture of the brain language processing system arise from their interaction over the course of early childhood when brain maturation and language acquisition are temporally synchronized.”
TRAF6 regulates EGF-induced cell transformation and cSCC malignant phenotype through CD147/EGFR
Authors: Zhang Xu , Wu Lisha , Xiao Ta , Tang Ling , Jia Xuekun , Guo Yeye , Zhang JiangLin , Li Jie , He Yijing , Su Juan , Zhao Shuang , Tao Juan , Zhou Jianda , Chen Xiang , Peng Cong 
Published: February 2018

AbstractTRAF6, a well-known adapter molecule, plays pivotal role in TLR/IL-1R associated signaling pathway. Although TRAF6 has been shown to have oncogenic activity in various malignant tumors, the details remain unclear. In this study, we demonstrated that TRAF6 facilitates Ras (G12V) and EGF-induced cellular transformation through EGFR. Silencing of TRAF6 expression significantly downregulated AP-1 activity, as well as MMP-2,9 expression after EGF stimulation. Furthermore, we found that TRAF6 plays an essential role in cutaneous squamous cell carcinoma (cSCC) malignant phenotypes, affecting cell growth and migration. CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is over-expressed in tumors and induces tumorigenesis. Our results showed that CD147 formed complex with EGFR and TRAF6. Knockdown of TRAF6 disrupted the CD147-EGFR complex, thereby inducing EGFR endocytosis. Therefore, TRAF6 might be a novel molecular target for cSCC prevention or therapy.
Dysfunctional immunoregulation in human liver allograft rejection associated with compromised galectin-1/CD7 pathway function
Authors: Wei Sidong , Cao Ding , Liu Zuojin , Li Jinheng , Wu Hao , Gong Jianping , Liu Yiming , Wu Yakun 
Published: February 2018

AbstractRegulatory T cells in rejected allograft patients display an inability to control responder T cells. Galectin-1 (Gal1) inhibits responder T cells through binding CD7. We investigated whether the dysfunctional immunoregulation in liver allograft rejection patients results from reduced regulatory T-cell Gal1 expression and/or responder T-cell CD7 expression. Circulating regulatory T cells and responder T cells were profiled from 31 acute rejection transplant patients, 85 transplant patients in remission, and 40 healthy controls. CD7+ and CD7− responder T cells were co-cultured with regulatory T cells to assess regulatory T-cell suppressor function. Gal1-small interfering RNA was used to silence regulatory T-cell Gal1. The CD7+ cell percentage was inversely correlated with AST, ALT, and GGT levels. The proportions of CD7+ responder T cells and Gal1+ regulatory T cells were higher in healthy controls than in transplant patients in remission and lowest in acute rejection transplant patients. Notably, CD7+ responder T-cell susceptibility to Gal1+ regulatory T-cell control was ranked in the same manner. Silencing Gal1 expression in regulatory T cells reduced their ability to suppress CD7+ (but not CD7−) responder T cells. Additionally, the proportions of CD43+ and CD45+ responder T cells were higher in healthy controls than in acute rejection transplant patients. CD43 co-expression (but not CD45 co-expression) on CD7+ responder T cells promoted their apoptosis in a Gal1-dependent manner. In sum, dysfunctional immunoregulation in liver allograft rejection patients can be partly attributed to reduced regulatory T-cell Gal1 expression and reduced responder T-cell CD7 expression. Responder T-cell CD43 downregulation in acute rejection patients may further contribute to reduced responder T-cell responsiveness to regulatory T-cell control.
GRK5 functions as an oncogenic factor in non-small-cell lung cancer
Authors: Jiang Li-Ping , Fan Song-Qing , Xiong Qiu-Xia , Zhou Yong-Chun , Yang Zuo-Zhang , Li Gao-Feng , Huang Yun-Chao , Wu Meng-Ge , Shen Qiu-Shuo , Liu Kun , Yang Cui-Ping , Chen Yong-Bin 
Published: February 2018

AbstractLung cancer is the leading cause of cancer-related deaths worldwide, and non-small-cell lung cancer (NSCLC) accounts for about 80% of all cases, which is the major subgroup of lung cancer. G protein-coupled receptor kinase 5 (GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological conditions including cancer. Here, we found that GRK5 expression was significantly increased in 539 NSCLC cancerous tissues than that in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also showed intensive higher positive staining percentage in female and adenocarcinoma (ADC) NSCLC patients than that in male and squamous cell carcinoma (SCC) patients, respectively. In addition, GRK5 high expression NSCLC patients had a worse overall survival rate than the low expression patients. We provided evidence showing that both the mRNA and protein expression levels of GRK5 were increased in NSCLC cancerous cell lines (GLC-82, SPC-A-1, H520, H838, H358, A549, and H1299) comparing with that in normal human bronchial epithelium cell line (BEAS-2B), and identified many GRK5 mutations in NSCLC cancerous tissues. In addition, we found that depletion of GRK5 inhibited NSCLC cancerous cell proliferation, migration in vitro, and xenograft tumor formation in vivo. Furthermore, GRK5 knockdown promoted cell cycle arrest at G2/M phase and induced cellular apoptosis. In summary, our data reveal an oncogenic role of GRK5 in NSCLC progression, indicating that GRK5 could be used as a new therapeutic target in future.
Induction of ER and mitochondrial stress by the alkylphosphocholine erufosine in oral squamous cell carcinoma cells
Authors: Ansari Shariq S. , Sharma Ashwini K. , Soni Himanshu , Ali Doaa M. , Tews Björn , König Rainer , Eibl Hansjörg , Berger Martin R. 
Published: February 2018

AbstractEndoplasmic reticulum (ER) plays an essential role in cell function and survival. Accumulation of unfolded or misfolded proteins in the lumen of the ER activates the unfolded protein response (UPR), resulting in ER stress and subsequent apoptosis. The alkylphosphocholine erufosine is a known Akt-mTOR inhibitor in oral squamous cell carcinoma (OSCC). In the present study, we evaluate erufosine’s role to induce ER and mitochondrial stress leading to autophagy, apoptosis, and ROS induction. The cellular toxicity of erufosine was determined in two OSCC cell lines and gene expression and enrichment analyses were performed. A positive enrichment of ER stress upon erufosine exposure was observed, which was verified at protein levels for the ER stress sensors and their downstream mediators. Knockdown and pharmacological inhibition of the ER stress sensors PERK and XBP1 revealed their involvement into erufosine’s cellular effects, including proliferation, apoptosis, and autophagy induction. Autophagy was confirmed by increased acidic vacuoles and LC3-B levels. Upon erufosine exposure, calcium influx into the cytoplasm of the two OSCC cell lines was seen. Apoptosis was confirmed by nuclear staining, Annexin-V, and immunoblotting of caspases. The induction of mitochondrial stress upon erufosine exposure was predicted by gene set enrichment analysis (GSEA) and shown by erufosine’s effect on mitochondrial membrane potential, ATP, and ROS production in OSCC cells. These data show that ER and mitochondrial targeting by erufosine represents a new facet of its mechanism of action as well as a promising new framework in the treatment of head and neck cancers.
Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation
Authors: Simões Ana P. , Silva Carla G. , Marques Joana M. , Pochmann Daniela , Porciúncula Lisiane O. , Ferreira Sofia , Oses Jean P. , Beleza Rui O. , Real Joana I. , Köfalvi Attila , Bahr Ben A. , Lerma Juan , Cunha Rodrigo A. , Rodrigues Ricardo J. 
Published: February 2018

AbstractDespite the characteristic etiologies and phenotypes, different brain disorders rely on common pathogenic events. Glutamate-induced neurotoxicity is a pathogenic event shared by different brain disorders. Another event occurring in different brain pathological conditions is the increase of the extracellular ATP levels, which is now recognized as a danger and harmful signal in the brain, as heralded by the ability of P2 receptors (P2Rs) to affect a wide range of brain disorders. Yet, how ATP and P2R contribute to neurodegeneration remains poorly defined. For that purpose, we now examined the contribution of extracellular ATP and P2Rs to glutamate-induced neurodegeneration. We found both in vitro and in vivo that ATP/ADP through the activation of P2Y1R contributes to glutamate-induced neuronal death in the rat hippocampus. We found in cultured rat hippocampal neurons that the exposure to glutamate (100 µM) for 30 min triggers a sustained increase of extracellular ATP levels, which contributes to NMDA receptor (NMDAR)-mediated hippocampal neuronal death through the activation of P2Y1R. We also determined that P2Y1R is involved in excitotoxicity in vivo as the blockade of P2Y1R significantly attenuated rat hippocampal neuronal death upon the systemic administration of kainic acid or upon the intrahippocampal injection of quinolinic acid. This contribution of P2Y1R fades with increasing intensity of excitotoxic conditions, which indicates that P2Y1R is not contributing directly to neurodegeneration, rather behaving as a catalyst decreasing the threshold from which glutamate becomes neurotoxic. Moreover, we unraveled that such excitotoxicity process began with an early synaptotoxicity that was also prevented/attenuated by the antagonism of P2Y1R, both in vitro and in vivo. This should rely on the observed glutamate-induced calpain-mediated axonal cytoskeleton damage, most likely favored by a P2Y1R-driven increase of NMDAR-mediated Ca2+ entry selectively in axons. This may constitute a degenerative mechanism shared by different brain diseases, particularly relevant at initial pathogenic stages.
ALCAM+ stromal cells: role in giant cell tumor of bone progression
Authors: Zhou Zhenhua , Li Yan , Wang Xudong , Hu Jingjing , Kuang Muyu , Wang Zhiwei , Li Song , Xu Weidong , Xiao Jianru 
Published: February 2018

AbstractGiant cell tumor of bone(GCTB) is a special benign tumor with variable aggressiveness and recurrence rate. Increasing evidences suggest that a subset of cells called cancer stem cells (CSCs) are present as cancer-initiating cells in a range of malignant tumors. However, the role of CSCs in benign tumor such as GCTB remains unknown, and the connection between the presence of CSCs and biological characteristics of GCTB is unclear. To investigate this issue, we screened a panel of markers of normal stem cells and CSCs and found ALCAM+ stromal cells possessed characteristics of stem-like cells. Subsequently a series of experiments such cell proliferation, migration and invasion assays were performed to investigate the biological characteristics of ALCAM+ stromal cells in vivo and in vitro. The clinical significance of ALCAM expression were further evaluated using Kaplan-Meier analyses. The ALCAM+ GCTB cells showed the stem cell properties of self renewal and had the capacity to differentiate in vitro. The ALCAM+ GCTB cells showed increased resistance for chemotherapy- or radiation-induced cell death. ALCAM knockdown reduced stem/progenitor characteristics in GCTB Cells. Furthermore, ALCAM expression was associated with outcome in GCTB patients. Our work demonstrates for the first time ALCAM+ tumorigenic sub-population within stromal GCTB cells and may represent a potential therapeutic target in aggressive and recurrent GCTBs.
Contribution of TMEM16F to pyroptotic cell death
Authors: Ousingsawat Jiraporn , Wanitchakool Podchanart , Schreiber Rainer , Kunzelmann Karl 
Published: February 2018

AbstractPyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X7 is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca2+ activated phospholipid scramblase and ion channel TMEM16F has been shown earlier to control cellular effects downstream of purinergic P2X7 receptors that ultimately lead to cell death. As pyroptotic cell death is accompanied by an increases in intracellular Ca2+, we asked whether TMEM16F is activated during pyroptosis. The N-terminal cleavage product of gasdermin D (GD-N) is an executioner of pyroptosis by forming large plasma membrane pores. Expression of GD-N enhanced basal Ca2+ levels and induced cell death. We observed that GD-N induced cell death in HEK293 and HAP1 cells, which was depending on expression of endogenous TMEM16F. GD-N activated large whole cell currents that were suppressed by knockdown or inhibition of TMEM16F. The results suggest that whole cell currents induced by the pore forming domain of gasdermin-D, are at least in part due to activation of TMEM16F. Knockdown of other TMEM16 paralogues expressed in HAP1 cells suggest TMEM16F as a crucial element during pyroptosis and excluded a role of other TMEM16 proteins. Thus TMEM16F supports pyroptosis and other forms of inflammatory cell death such as ferroptosis. Its potent inhibition by tannic acid may be part of the anti-inflammatory effects of flavonoids.
The genomic tool-kit of the truffle Tuber melanosporum programmed cell death
Authors: Zarivi Osvaldo , Cesare Patrizia , Poma Anna Maria , Colafarina Sabrina , Bonfigli Antonella , Kohler Annegret , Aimola Pierpaolo , Ragnelli Anna Maria , Pacioni Giovanni , Miranda Michele 
Published: February 2018

AbstractA survey of the truffle Tuber melanosporum genome has shown the presence of 67 programmed cell death (PCD)-related genes. The 67 genes are all expressed during fruit body (FB) development of T. melanosporum development; their expression has been detected by DNA microarrays and qPCR. A set of 14 PCD-related genes have been chosen, those with the highest identities to the homologs of other species, for a deeper investigation. That PCD occurs during T. melanosporum development has been demonstrated by the TUNEL reaction and transmission electron microscopy. The findings of this work, in addition to the discovery of PCD-related genes in the T. melanosporum genome and their expression during the differentiation and development of the FB, would suggest that one of the PCD subroutines, maybe autophagy, is involved in the FB ripening, i.e., sporogenesis.
Lkb1 deficiency confers glutamine dependency in polycystic kidney disease
Authors: Flowers Ebony M. , Sudderth Jessica , Zacharias Lauren , Mernaugh Glenda , Zent Roy , DeBerardinis Ralph J. , Carroll Thomas J. 
Published: February 2018

AbstractPolycystic kidney disease (PKD) is a common genetic disorder characterized by the growth of fluid-filled cysts in the kidneys. Several studies reported that the serine-threonine kinase Lkb1 is dysregulated in PKD. Here we show that genetic ablation of Lkb1 in the embryonic ureteric bud has no effects on tubule formation, maintenance, or growth. However, co-ablation of Lkb1 and Tsc1, an mTOR repressor, results in an early developing, aggressive form of PKD. We find that both loss of Lkb1 and loss of Pkd1 render cells dependent on glutamine for growth. Metabolomics analysis suggests that Lkb1 mutant kidneys require glutamine for non-essential amino acid and glutathione metabolism. Inhibition of glutamine metabolism in both Lkb1/Tsc1 and Pkd1 mutant mice significantly reduces cyst progression. Thus, we identify a role for Lkb1 in glutamine metabolism within the kidney epithelia and suggest that drugs targeting glutamine metabolism may help reduce cyst number and/or size in PKD.
Sodium enhances indium-gallium interdiffusion in copper indium gallium diselenide photovoltaic absorbers
Authors: Colombara Diego , Werner Florian , Schwarz Torsten , Cañero Infante Ingrid , Fleming Yves , Valle Nathalie , Spindler Conrad , Vacchieri Erica , Rey Germain , Guennou Mael , Bouttemy Muriel , Manjón Alba Garzón , Peral Alonso Inmaculada , Melchiorre Michele , El Adib Brahime , Gault Baptiste , Raabe Dierk , Dale Phillip J. , Siebentritt Susanne 
Published: February 2018

AbstractCopper indium gallium diselenide-based technology provides the most efficient solar energy conversion among all thin-film photovoltaic devices. This is possible due to engineered gallium depth gradients and alkali extrinsic doping. Sodium is well known to impede interdiffusion of indium and gallium in polycrystalline Cu(In,Ga)Se2 films, thus influencing the gallium depth distribution. Here, however, sodium is shown to have the opposite effect in monocrystalline gallium-free CuInSe2 grown on GaAs substrates. Gallium in-diffusion from the substrates is enhanced when sodium is incorporated into the film, leading to Cu(In,Ga)Se2 and Cu(In,Ga)3Se5 phase formation. These results show that sodium does not decrease per se indium and gallium interdiffusion. Instead, it is suggested that sodium promotes indium and gallium intragrain diffusion, while it hinders intergrain diffusion by segregating at grain boundaries. The deeper understanding of dopant-mediated atomic diffusion mechanisms should lead to more effective chemical and electrical passivation strategies, and more efficient solar cells.
Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement
Authors: Shi Y. Z. , Xiong S. , Zhang Y. , Chin L. K. , Chen Y. –Y. , Zhang J. B. , Zhang T. H. , Ser W. , Larrson A. , Lim S. H. , Wu J. H. , Chen T. N. , Yang Z. C. , Hao Y. L. , Liedberg B. , Yap P. H. , Wang K. , Tsai D. P. , Qiu C.-W. , Liu A. Q. 
Published: February 2018

AbstractParticle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer’s theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.
A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets
Authors: Hobor Fruzsina , Dallmann Andre , Ball Neil J. , Cicchini Carla , Battistelli Cecilia , Ogrodowicz Roksana W. , Christodoulou Evangelos , Martin Stephen R. , Castello Alfredo , Tripodi Marco , Taylor Ian A. , Ramos Andres 
Published: February 2018

AbstractExosomal miRNA transfer is a mechanism for cell–cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip’s amino-terminal domain, which was previously thought to mediate protein–protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip’s RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5′ to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences.
Marangoni-driven flower-like patterning of an evaporating drop spreading on a liquid substrate
Authors: Wodlei F. , Sebilleau J. , Magnaudet J. , Pimienta V. 
Published: February 2018

AbstractDrop motility at liquid surfaces is attracting growing interest because of its potential applications in microfluidics and artificial cell design. Here we report the unique highly ordered pattern that sets in when a millimeter-size drop of dichloromethane spreads on an aqueous substrate under the influence of surface tension, both phases containing a surfactant. Evaporation induces a Marangoni flow that forces the development of a marked rim at the periphery of the spreading film. At some point this rim breaks up, giving rise to a ring of droplets, which modifies the aqueous phase properties in such a way that the film recoils. The process repeats itself, yielding regular large-amplitude pulsations. Wrinkles form at the film surface due to an evaporative instability. During the dewetting stage, they emit equally spaced radial strings of droplets which, combined with those previously expelled from the rim, make the top view of the system resemble a flower.