bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma
Authors: Shiraishi Kouya , Okada Yukinori , Takahashi Atsushi , Kamatani Yoichiro , Momozawa Yukihide , Ashikawa Kyota , Kunitoh Hideo , Matsumoto Shingo , Takano Atsushi , Shimizu Kimihiro , Goto Akiteru , Tsuta Koji , Watanabe Shun-ichi , Ohe Yuichiro , Watanabe Yukio , Goto Yasushi , Nokihara Hiroshi , Furuta Koh , Yoshida Akihiko , Goto Koichi , Hishida Tomoyuki , Tsuboi Masahiro , Tsuchihara Katsuya , Miyagi Yohei , Nakayama Haruhiko , Yokose Tomoyuki , Tanaka Kazumi , Nagashima Toshiteru , Ohtaki Yoichi , Maeda Daichi , Imai Kazuhiro , Minamiya Yoshihiro , Sakamoto Hiromi , Saito Akira , Shimada Yoko , Sunami Kuniko , Saito Motonobu , Inazawa Johji , Nakamura Yusuke , Yoshida Teruhiko , Yokota Jun , Matsuda Fumihiko , Matsuo Keitaro , Daigo Yataro , Kubo Michiaki , Kohno Takashi 
Published: August 2016

AbstractLung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30–50%) than in European/Americans (10–20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10−17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10−9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.
Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding
Authors: Suyama Shigetomo , Maekawa Fumihiko , Maejima Yuko , Kubota Naoto , Kadowaki Takashi , Yada Toshihiko 
Published: August 2016

AbstractAdiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.
2-(Maleimidomethyl)-1,3-Dioxanes (MD): a Serum-Stable Self-hydrolysable Hydrophilic Alternative to Classical Maleimide Conjugation
Authors: Dovgan Igor , Kolodych Sergii , Koniev Oleksandr , Wagner Alain 
Published: August 2016

AbstractThe vast majority of antibody-drug conjugates (ADC) are prepared through amine-to-thiol conjugation. To date, N-Succinimidyl-4-(maleimidomethyl) cyclohexanecarboxylate (SMCC) has been one of the most frequently applied reagents for the preparation of ADC and other functional conjugates. However, SMCC-based conjugates suffer from limited stability in blood circulation and from a hydrophobic character of the linker, which may give rise to major pharmacokinetic implications. To address this issue, we have developed a heterobifunctional analogue of a SMCC reagent, i.e., sodium 4-(maleimidomethyl)-1,3-dioxane-5-carbonyl)oxy)-2,3,5,6- tetrafluorobenzenesulfonate (MDTF) for amine-to-thiol conjugation. By replacing the cyclohexyl ring in the SMCC structure with the 1,3-dioxane, we increased the hydrophilicity of the linker. A FRET probe based on MD linker was prepared and showed superior stability compared to the MCC linker in human plasma, as well as in a variety of aqueous buffers. A detailed investigation demonstrated an accelerated succinimide ring opening for MD linker, resulting in stabilized conjugates. Finally, the MDTF reagent was applied for the preparation of serum stable antibody-dye conjugate.
Change in atmospheric deposition during last half century and its impact on lichen community structure in Eastern Himalaya
Authors: Bajpai Rajesh , Mishra Seema , Dwivedi Sanjay , Upreti Dalip Kumar 
Published: August 2016

AbstractClimatic fluctuations largely affects species turnover and cause major shifts of terrestrial ecosystem. In the present study the five decade old herbarium specimens of lichens were compared with recent collection from Darjeeling district with respect to elements, PAHs accumulation and carbon isotope composition (δ13C) to explore the changes in climatic conditions and its impact on lichen flora. The δ13C has increased in recent specimens which is in contrast to the assumption that anthropogenic emission leads to δ13C depletion in air and increased carbon discrimination in flora. Study clearly demonstrated an increase in anthropogenic pollution and drastic decrease in precipitation while temperature showed abrupt changes during the past five decades resulting in significant change in lichen community structure. The Usneoid and Pertusorioid communities increased, while Physcioid and Cyanophycean decreased, drastically. Lobarian abolished from the study area, however, Calcicoid has been introduced in the recent past. Probably, post-industrial revolution, the abrupt changes in the environment has influenced CO2 diffusion and/C fixation of (lower) plants either as an adaptation strategy or due to toxicity of pollutants. Thus, the short term studies (≤5 decades) might reflect recent micro-environmental condition and lichen community structure can be used as model to study the global climate change.
Breaking through the strength-ductility trade-off dilemma in an Al-Si-based casting alloy
Authors: Dang B. , Zhang X. , Chen Y. Z. , Chen C. X. , Wang H. T. , Liu F. 
Published: August 2016

AbstractAl-Si-based casting alloys have a great potential in various industrial applications. Common strengthening strategies on these alloys are accompanied inevitably by sacrifice of ductility, known as strength-ductility trade-off dilemma. Here, we report a simple route by combining rapid solidification (RS) with a post-solidification heat treatment (PHT), i.e. a RS + PHT route, to break through this dilemma using a commercial Al-Si-based casting alloy (A356 alloy) as an example. It is shown that yield strength and elongation to failure of the RS + PHT processed alloy are elevated simultaneously by increasing the cooling rate upon RS, which are not influenced by subsequent T6 heat treatment. Breaking through the dilemma is attributed to the hierarchical microstructure formed by the RS + PHT route, i.e. highly dispersed nanoscale Si particles in Al dendrites and nanoscale Al particles decorated in eutectic Si. Simplicity of the RS + PHT route makes it being suitable for industrial scaling production. The strategy of engineering microstructures offers a general pathway in tailoring mechanical properties of other Al-Si-based alloys. Moreover, the remarkably enhanced ductility of A356 alloy not only permits strengthening further the material by work hardening but also enables possibly conventional solid-state forming of the material, thus extending the applications of such an alloy.
Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression
Authors: Zhang Kuo , Pan Xing , Wang Fang , Ma Jie , Su Guangyue , Dong Yingxu , Yang Jingyu , Wu Chunfu 
Published: August 2016

AbstractAntidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation.
A novel role for β2-microglobulin: a precursor of antibacterial chemokine in respiratory epithelial cells
Authors: Chiou Shean-Jaw , Wang Chan-Chi , Tseng Yan-Shen , Lee Yen-Jung , Chen Shih-Chieh , Chou Chi-Hsien , Chuang Lea-Yea , Hong Yi-Ren , Lu Chi-Yu , Chiu Chien-Chih , Chignard Michel 
Published: August 2016

AbstractWe analyzed a panel of cationic molecules secreted in the culture medium of human respiratory epithelial cells (REC) upon activation by IL-1β and different pathogen-associated molecular patterns. A 9 kDa fragment derived from β2-microglobulin (B2M) was identified and named shed 9 kDa B2M (sB2M-9). The primary structure of sB2M-9 was revealed to increase its pI value that potentially could play an important role in innate defense. sB2M-9 exhibits antibacterial activity against Gram positive Staphylococcus aureus (SA) but not against Gram negative Klebsiella pneumonia (KP). Upon its binding to SA, sB2M-9 induces clumps, a phenomenon not observed with B2M. Migration of THP-1 monocytes exposed to SA clumps was significantly greater than that to SA without clumps. sB2M-9 binds to SA, more likely as a chemokine, to facilitate THP-1 migration. As a whole, we demonstrated that REC release a novel chemokine with antibacterial activity that is shed from B2M to facilitate THP-1 migration.
Discovery of potential prognostic long non-coding RNA biomarkers for predicting the risk of tumor recurrence of breast cancer patients
Authors: Zhou Meng , Zhong Lei , Xu Wanying , Sun Yifan , Zhang Zhaoyue , Zhao Hengqiang , Yang Lei , Sun Jie 
Published: August 2016

AbstractDeregulation of long non-coding RNAs (lncRNAs) expression has been proven to be involved in the development and progression of cancer. However, expression pattern and prognostic value of lncRNAs in breast cancer recurrence remain unclear. Here, we analyzed lncRNA expression profiles of breast cancer patients who did or did not develop recurrence by repurposing existing microarray datasets from the Gene Expression Omnibus database, and identified 12 differentially expressed lncRNAs that were closely associated with tumor recurrence of breast cancer patients. We constructed a lncRNA-focus molecular signature by the risk scoring method based on the expression levels of 12 relapse-related lncRNAs from the discovery cohort, which classified patients into high-risk and low-risk groups with significantly different recurrence-free survival (HR = 2.72, 95% confidence interval 2.07–3.57; p = 4.8e-13). The 12-lncRNA signature also represented similar prognostic value in two out of three independent validation cohorts. Furthermore, the prognostic power of the 12-lncRNA signature was independent of known clinical prognostic factors in at least two cohorts. Functional analysis suggested that the predicted relapse-related lncRNAs may be involved in known breast cancer-related biological processes and pathways. Our results highlighted the potential of lncRNAs as novel candidate biomarkers to identify breast cancer patients at high risk of tumor recurrence.
Identification of the earliest collagen- and plant-based coatings from Neolithic artefacts (Nahal Hemar cave, Israel)
Authors: Solazzo Caroline , Courel Blandine , Connan Jacques , van Dongen Bart E. , Barden Holly , Penkman Kirsty , Taylor Sheila , Demarchi Beatrice , Adam Pierre , Schaeffer Philippe , Nissenbaum Arie , Bar-Yosef Ofer , Buckley Michael 
Published: August 2016

AbstractMortuary practices in human evolution record cognitive, social changes and technological innovations. The Neolithic Revolution in the Levant was a watershed in this domain that has long fascinated the archaeological community. Plaster modelled skulls are well known at Jericho and several other Neolithic sites, and in Nahal Hemar cave (Israel, ca. 8200 −7300 cal. BC) excavations yielded six unique human skulls covered with a black organic coating applied in a net pattern evoking a headdress. This small cave was used as storage for paraphernalia in the semi-arid area of the Judean desert and the dry conditions preserved other artefacts such as baskets coated with a similar dark substance. While previous analysis had revealed the presence of amino acids consistent with a collagen signature, in the present report, specific biomarkers were characterised using combined proteomic and lipid approaches. Basket samples yielded collagen and blood proteins of bovine origin (Bos genus) and a large sequence coverage of a plant protein charybdin (Charybdis genus). The skull residue samples were dominated by benzoate and cinnamate derivatives and triterpenes consistent with a styrax-type resin (Styrax officinalis), thus providing the earliest known evidence of an odoriferous plant resin used in combination with an animal product.
Nanometal Skin of Plasmonic Heterostructures for Highly Efficient Near-Field Scattering Probes
Authors: Zito Gianluigi , Rusciano Giulia , Vecchione Antonio , Pesce Giuseppe , Di Girolamo Rocco , Malafronte Anna , Sasso Antonio 
Published: August 2016

AbstractIn this work, atomic force microscopy probes are functionalized by virtue of self-assembling monolayers of block copolymer (BCP) micelles loaded either with clusters of silver nanoparticles or bimetallic heterostructures consisting of mixed species of silver and gold nanoparticles. The resulting self-organized patterns allow coating the tips with a sort of nanometal skin made of geometrically confined nanoislands. This approach favors the reproducible engineering and tuning of the plasmonic properties of the resulting structured tip by varying the nanometal loading of the micelles. The newly conceived tips are applied for experiments of tip-enhanced Raman scattering (TERS) spectroscopy and scattering-type scanning near-field optical microscopy (s-SNOM). TERS and s-SNOM probe characterizations on several standard Raman analytes and patterned nanostructures demonstrate excellent enhancement factor with the possibility of fast scanning and spatial resolution <12 nm. In fact, each metal nanoisland consists of a multiscale heterostructure that favors large scattering and near-field amplification. Then, we verify the tips to allow challenging nongap-TER spectroscopy on thick biosamples. Our approach introduces a synergistic chemical functionalization of the tips for versatile inclusion and delivery of plasmonic nanoparticles at the tip apex, which may promote the tuning of the plasmonic properties, a large enhancement and the possibility of adding new degrees of freedom for tip functionalization.
Effect of long-term combined application of organic and inorganic fertilizers on soil nematode communities within aggregates
Authors: Zhang Zhiyong , Zhang Xiaoke , Mahamood Md. , Zhang Shuiqing , Huang Shaomin , Liang Wenju 
Published: August 2016

AbstractA long-term fertilization experiment was conducted to examine the effects of different fertilization practices on nematode community composition within aggregates in a wheat-maize rotation system. The study was a randomized complete block design with three replicates. The experiment involved the following four treatments: no fertilizer, inorganic N, P and K fertilizer (NPK), NPK plus manure (NPKM) and NPK plus maize straw (NPKS). Soil samples were taken at 0–20 cm depth during the wheat harvest stage. Based on our results, NPKS contributed to soil aggregation and moisture retention, with a positive effect on soil total nitrogen accumulation, particularly within small macroaggregates (0.25–1 mm) and microaggregates (<0.25 mm). The C/N ratio was correlated to the distribution of the soil nematode community. Both manure application and straw incorporation increased the nematode functional metabolic footprints within all aggregates. Additionally, the functional metabolic footprints decreased with a decline in aggregate size. The accumulation of total nitrogen within <1 mm aggregates under NPKS might play a key role in maintaining the survival of soil nematodes. In our study, both crop straw incorporation and inorganic fertilizer application effectively improved soil physicochemical properties and were also beneficial for nematode survival within small aggregate size fractions.
Electron acceptor redox potential globally regulates transcriptomic profiling in Shewanella decolorationis S12
Authors: Lian Yingli , Yang Yonggang , Guo Jun , Wang Yan , Li Xiaojing , Fang Yun , Gan Lixia , Xu Meiying 
Published: August 2016

AbstractElectron acceptor redox potential (EARP) was presumed to be a determining factor for microbial metabolism in many natural and engineered processes. However, little is known about the potentially global effects of EARP on bacteria. In this study, we compared the physiological and transcriptomic properties of Shewanella decolorationis S12 respiring with different EARPs in microbial electrochemical systems to avoid the effects caused by the other physicochemical properties of real electron acceptor. Results showed that the metabolic activities of strain S12 were nonlinear responses to EARP. The tricarboxylic acid cycle for central carbon metabolism was down-regulated while glyoxylate shunt was up-regulated at 0.8 V compared to 0.2 and −0.2 V, which suggested that EARP is an important but not the only determinant for metabolic pathways of strain S12. Moreover, few cytochrome c genes were differentially expressed at different EARPs. The energy intensive flagella assembly and assimilatory sulfur metabolism pathways were significantly enriched at 0.8 V, which suggested strain S12 had stronger electrokinesis behavior and oxidative stress-response at high EARP. This study provides the first global information of EARP regulations on microbial metabolism, which will be helpful for understanding microorganism respiration.
Energy Bandgap and Edge States in an Epitaxially Grown Graphene/h-BN Heterostructure
Authors: Hwang Beomyong , Hwang Jeongwoon , Yoon Jong Keon , Lim Sungjun , Kim Sungmin , Lee Minjun , Kwon Jeong Hoon , Baek Hongwoo , Sung Dongchul , Kim Gunn , Hong Suklyun , Ihm Jisoon , Stroscio Joseph A. , Kuk Young 
Published: August 2016

AbstractSecuring a semiconducting bandgap is essential for applying graphene layers in switching devices. Theoretical studies have suggested a created bulk bandgap in a graphene layer by introducing an asymmetry between the A and B sub-lattice sites. A recent transport measurement demonstrated the presence of a bandgap in a graphene layer where the asymmetry was introduced by placing a graphene layer on a hexagonal boron nitride (h-BN) substrate. Similar bandgap has been observed in graphene layers on metal substrates by local probe measurements; however, this phenomenon has not been observed in graphene layers on a near-insulating substrate. Here, we present bulk bandgap-like features in a graphene layer epitaxially grown on an h-BN substrate using scanning tunneling spectroscopy. We observed edge states at zigzag edges, edge resonances at armchair edges, and bandgap-like features in the bulk.
Rescuing neuronal cell death by RAIDD- and PIDD- derived peptides and its implications for therapeutic intervention in neurodegenerative diseases
Authors: Jang Tae-Ho , Lim In-Hye , Kim Chang Min , Choi Jae Young , Kim Eun-Ae , Lee Tae-Jin , Park Hyun Ho 
Published: August 2016

AbstractCaspase-2 is known to be involved in oxidative-stress mediated neuronal cell death. In this study, we demonstrated that rotenone-induced neuronal cell death is mediated by caspase-2 activation via PIDDosome formation. Our newly designed TAT-fused peptides, which contains wild-type helix number3 (H3) from RAIDD and PIDD, blocked the PIDDosome formation in vitro. Furthermore, peptides inhibited rotenone-induced caspase-2-dependent apoptosis in neuronal cells. These results suggest that PIDD- or RAIDD-targeted peptides might be effective at protecting against rotenone-induced neurotoxicity. Our peptides are novel neuronal cell apoptosis inhibitors that might serve as a prototype for development of drugs for the treatment of neurodegenerative diseases.
Calpains are involved in asexual and sexual development, cell wall integrity and pathogenicity of the rice blast fungus
Authors: Liu Xiao-Hong , Ning Guo-Ao , Huang Lu-Yao , Zhao Ya-Hui , Dong Bo , Lu Jian-Ping , Lin Fu-Cheng 
Published: August 2016

AbstractCalpains are ubiquitous and well-conserved proteins that belong to the calcium-dependent, non-lysosomal cysteine protease family. In this study, 8 putative calpains were identified using Pfam domain analysis and BlastP searches inM. oryzae. Three single gene deletion mutants (ΔMocapn7, ΔMocapn9and ΔMocapn14) and two double gene deletion mutants (ΔMocapn4ΔMocapn7and ΔMocapn9ΔMocapn7) were obtained using the high-throughput gene knockout system. The calpain disruption mutants showed defects in colony characteristics, conidiation, sexual reproduction and cell wall integrity. The mycelia of the ΔMocapn7, ΔMocapn4ΔMocapn7and ΔMocapn9ΔMocapn7mutants showed reduced pathogenicity on rice and barley.
High power laser-driven ceramic phosphor plate for outstanding efficient white light conversion in application of automotive lighting
Authors: Song Young Hyun , Ji Eun Kyung , Jeong Byung Woo , Jung Mong Kwon , Kim Eun Young , Yoon Dae Ho 
Published: August 2016

AbstractWe report on Y3Al5O12: Ce3+ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce3+concentration. The luminous properties of the Y3Al5O12: Ce3+CPP nano phosphor are improved when compared to the Y3Al5O12: Ce3+CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce3+CPP with an optimal Ce3+content of 0.5 mol % shows 2733 lm/mm2value under high power blue radiant flux density of 19.1 W/mm2. The results indicate that Y3Al5O12: Ce3+CPP using nano phosphor can serve as a potential material for solid-state laser lighting in automotive applications.