bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mislocalisation of BEST1 in iPSC-derived retinal pigment epithelial cells from a family with autosomal dominant vitreoretinochoroidopathy (ADVIRC)
Authors: Carter David A. , Smart Matthew J. K. , Letton William V. G. , Ramsden Conor M. , Nommiste Britta , Chen Li Li , Fynes Kate , Muthiah Manickam N. , Goh Pollyanna , Lane Amelia , Powner Michael B. , Webster Andrew R. , da Cruz Lyndon , Moore Anthony T. , Coffey Peter J. , Carr Amanda-Jayne F. 
Published: September 2016

AbstractAutosomal dominant vitreoretinochoroidopathy (ADVIRC) is a rare, early-onset retinal dystrophy characterised by distinct bands of circumferential pigmentary degeneration in the peripheral retina and developmental eye defects. ADVIRC is caused by mutations in the Bestrophin1 (BEST1) gene, which encodes a transmembrane protein thought to function as an ion channel in the basolateral membrane of retinal pigment epithelial (RPE) cells. Previous studies suggest that the distinct ADVIRC phenotype results from alternative splicing of BEST1 pre-mRNA. Here, we have used induced pluripotent stem cell (iPSC) technology to investigate the effects of an ADVIRC associated BEST1 mutation (c.704T > C, p.V235A) in patient-derived iPSC-RPE. We found no evidence of alternate splicing of the BEST1 transcript in ADVIRC iPSC-RPE, however in patient-derived iPSC-RPE, BEST1 was expressed at the basolateral membrane and the apical membrane. During human eye development we show that BEST1 is expressed more abundantly in peripheral RPE compared to central RPE and is also expressed in cells of the developing retina. These results suggest that higher levels of mislocalised BEST1 expression in the periphery, from an early developmental stage, could provide a mechanism that leads to the distinct clinical phenotype observed in ADVIRC patients.
Complete mitochondrial genomes of Trisidos kiyoni and Potiarca pilula: Varied mitochondrial genome size and highly rearranged gene order in Arcidae
Authors: Sun Shao’e , Li Qi , Kong Lingfeng , Yu Hong 
Published: September 2016

AbstractWe present the complete mitochondrial genomes (mitogenomes) of Trisidos kiyoni and Potiarca pilula, both important species from the family Arcidae (Arcoida: Arcacea). Typical bivalve mtDNA features were described, such as the relatively conserved gene number (36 and 37), a high A + T content (62.73% and 61.16%), the preference for A + T-rich codons and the evidence of non-optimal codon usage. The mitogenomes of Arcidae species are exceptional for their extraordinarily large and variable sizes and substantial gene rearrangements. The mitogenome of T. kiyoni (19,614 bp) and P. pilula (28,470 bp) are the two smallest Arcidae mitogenomes. The compact mitogenomes are weakly associated with gene number and primarily reflect shrinkage of the non-coding regions. The varied size in Arcidae mitogenomes reflect a dynamic history of expansion. A significant positive correlation is observed between mitogenome size and the combined length of cox1-3, the lengths of Cytb and the combined length of rRNAs (rrnS and rrnL) (P < 0.001). Both protein coding genes (PCGs) and tRNA rearrangements is observed in P. pilula and T. kiyoni mitogenomes. This analysis imply that the complicated gene rearrangement in mitochondrial genome could be considered as one of key characters in inferring higher-level phylogenetic relationship of Arcidae.
Contrasting diets reveal metabolic plasticity in the tree-killing beetle, Anoplophora glabripennis (Cerambycidae: Lamiinae)
Authors: Mason Charles J. , Scully Erin D. , Geib Scott M. , Hoover Kelli 
Published: September 2016

AbstractWood-feeding insects encounter challenging diets containing low protein quantities, recalcitrant carbohydrate sources and plant defensive compounds. The Asian longhorned beetle (Anoplophora glabripennis) is a wood-feeding insect that attacks and kills a diversity of hardwood tree species. We compared gene expression of midguts collected from larvae feeding in a preferred tree, sugar maple, to those consuming a nutrient-rich artificial diet, to identify genes putatively involved in host plant utilization. Anoplophora glabripennis larvae exhibited differential expression of ~3600 genes in response to different diets. Genes with predicted capacity for plant and microbial carbohydrate usage, detoxification, nutrient recycling and immune-related genes relevant for facilitating interactions with microbial symbionts were upregulated in wood-feeding larvae compared to larvae feeding in artificial diet. Upregulation of genes involved in protein degradation and synthesis was also observed, suggesting that proteins incur more rapid turnover in insects consuming wood. Additionally, wood-feeding individuals exhibited elevated expression of several mitochondrial cytochrome C oxidase genes, suggesting increased aerobic respiration compared to diet-fed larvae. These results indicate that A. glabripennis modulates digestive and basal gene expression when larvae are feeding in a nutrient-poor, yet suitable host plant compared to a tractable and nutrient-rich diet that is free of plant defensive compounds.
Cyclooxygenase-2 induced β1-integrin expression in NSCLC and promoted cell invasion via the EP1/MAPK/E2F-1/FoxC2 signal pathway
Authors: Pan Jinshun , Yang Qinyi , Shao Jiaofang , Zhang Li , Ma Juan , Wang Yipin , Jiang Bing-Hua , Leng Jing , Bai Xiaoming 
Published: September 2016

AbstractCyclooxygenase-2 (COX-2) has been implicated in cell invasion in non-small-cell lung cancer (NSCLC). However, the mechanism is unclear. The present study investigated the effect of COX-2 on β1-integrin expression and cell invasion in NSCLC. COX-2 and β1-integrin were co-expressed in NSCLC tissues. COX-2 overexpression or Prostaglandin E2 (PGE2) treatment increased β1-integrin expression in NSCLC cell lines. β1-integrin silencing suppressed COX-2-mediated tumour growth and cancer cell invasion in vivo and in vitro. Prostaglandin E Receptor EP1 transfection or treatment with EP1 agonist mimicked the effect of PGE2 treatment. EP1 siRNA blocked PGE2-mediated β1-integrin expression. EP1 agonist treatment promoted Erk1/2, p38 phosphorylation and E2F-1 expression. MEK1/2 and p38 inhibitors suppressed EP1-mediated β1-integrin expression. E2F-1 silencing suppressed EP1-mediated FoxC2 and β1-integrin upregulation. ChIP and Luciferase Reporter assays identified that EP1 agonist treatment induced E2F-1 binding to FoxC2 promotor directly and improved FoxC2 transcription. FoxC2 siRNA suppressed β1-integrin expression and EP1-mediated cell invasion. Immunohistochemistry showed E2F-1, FoxC2, and EP1R were all highly expressed in the NSCLC cases. This study suggested that COX-2 upregulates β1-integrin expression and cell invasion in NSCLC by activating the MAPK/E2F-1 signalling pathway. Targeting the COX-2/EP1/PKC/MAPK/E2F-1/FoxC2/β1-integrin pathway might represent a new therapeutic strategy for the prevention and treatment of this cancer.
A new frontier in CO2 flux measurements using a highly portable DIAL laser system
Authors: Queiβer Manuel , Granieri Domenico , Burton Mike 
Published: September 2016

AbstractVolcanic CO2 emissions play a key role in the geological carbon cycle and monitoring of volcanic CO2 fluxes helps to forecast eruptions. The quantification of CO2 fluxes is challenging due to rapid dilution of magmatic CO2 in CO2-rich ambient air and the diffuse nature of many emissions, leading to large uncertainties in the global magmatic CO2 flux inventory. Here, we report measurements using a new DIAL laser remote sensing system for volcanic CO2 (CO2DIAL). Two sites in the volcanic zone of Campi Flegrei (Italy) were scanned, yielding CO2 path-amount profiles used to compute fluxes. Our results reveal a relatively high CO2 flux from Campi Flegrei, consistent with an increasing trend. Unlike previous methods, the CO2DIAL is able to measure integrated CO2 path-amounts at distances up to 2000 m using virtually any solid surface as a reflector, whilst also being highly portable. This opens a new frontier in quantification of geological and anthropogenic CO2 fluxes.
Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma
Authors: Wang Ruizhi , Luo Yu , Yang Shuohui , Lin Jiang , Gao Dongmei , Zhao Yan , Liu Jinguo , Shi Xiangyang , Wang Xiaolin 
Published: September 2016

AbstractHepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. The early and effective diagnosis has always been desired. Herein, we present the preparation and characterization of hyaluronic acid (HA)-modified, multifunctional nanoparticles (NPs) targeting CD44 receptor-expressing cancer cells for computed tomography (CT)/magnetic resonance (MR) dual-mode imaging. We first modified amine-terminated generation 5 poly(amidoamine) dendrimers (G5.NH2) with an Mn chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), fluorescein isothiocyanate (FI), and HA. Then, gold nanoparticles (AuNPs) were entrapped within the above raw product, denoted as G5.NH2-FI-DOTA-HA. The designed multifunctional NPs were formed after further Mn chelation and purification and were denoted as {(Au0)100G5.NH2-FI-DOTA(Mn)-HA}. These NPs were characterized via several different techniques. We found that the {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} NPs exhibited good water dispersibility, stability under different conditions, and cytocompatibility within a given concentration range. Because both AuNPs and Mn were present in the product, {(Au0)100G5.NH2-FI-DOTA(Mn)-HA} displayed a high X-ray attenuation intensity and favorable r1 relaxivity, which are advantageous properties for targeted CT/MR dual-mode imaging. This approach was used to image HCC cells in vitro and orthotopically transplanted HCC tumors in a unique in vivo model through the CD44 receptor-mediated endocytosis pathway. This work introduces a novel strategy for preparing multifunctional NPs via dendrimer nanotechnology.
Chronic recurrent dehydration associated with periodic water intake exacerbates hypertension and promotes renal damage in male spontaneously hypertensive rats
Authors: Hilliard Lucinda M. , Colafella Katrina M. Mirabito , Bulmer Louise L. , Puelles Victor G. , Singh Reetu R. , Ow Connie P. C. , Gaspari Tracey , Drummond Grant R. , Evans Roger G. , Vinh Antony , Denton Kate M. 
Published: September 2016

AbstractEpidemiological evidence links recurrent dehydration associated with periodic water intake with chronic kidney disease (CKD). However, minimal attention has been paid to the long-term impact of periodic water intake on the progression of CKD and underlying mechanisms involved. Therefore we investigated the chronic effects of recurrent dehydration associated with periodic water restriction on arterial pressure and kidney function and morphology in male spontaneously hypertensive rats (SHR). Arterial pressure increased and glomerular filtration rate decreased in water-restricted SHR. This was observed in association with cyclic changes in urine osmolarity, indicative of recurrent dehydration. Additionally, water-restricted SHR demonstrated greater renal fibrosis and an imbalance in favour of pro-inflammatory cytokine-producing renal T cells compared to their control counterparts. Furthermore, urinary NGAL levels were greater in water-restricted than control SHR. Taken together, our results provide significant evidence that recurrent dehydration associated with chronic periodic drinking hastens the progression of CKD and hypertension, and suggest a potential role for repetitive bouts of acute renal injury driving renal inflammatory processes in this setting. Further studies are required to elucidate the specific pathways that drive the progression of recurrent dehydration-induced kidney disease.
Identification of hepta-histidine as a candidate drug for Huntington’s disease by in silico-in vitro- in vivo-integrated screens of chemical libraries
Authors: Imamura Tomomi , Fujita Kyota , Tagawa Kazuhiko , Ikura Teikichi , Chen Xigui , Homma Hidenori , Tamura Takuya , Mao Ying , Taniguchi Juliana Bosso , Motoki Kazumi , Nakabayashi Makoto , Ito Nobutoshi , Yamada Kazunori , Tomii Kentaro , Okano Hideyuki , Kaye Julia , Finkbeiner Steven , Okazawa Hitoshi 
Published: September 2016

AbstractWe identified drug seeds for treating Huntington’s disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty-six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD.
Bound exciton and free exciton states in GaSe thin slab
Authors: Wei Chengrong , Chen Xi , Li Dian , Su Huimin , He Hongtao , Dai Jun-Feng 
Published: September 2016

AbstractThe photoluminescence (PL) and absorption experiments have been performed in GaSe slab with incident light polarized perpendicular to c-axis of sample at 10 K. An obvious energy difference of about 34 meV between exciton absorption peak and PL peak (the highest energy peak) is observed. By studying the temperature dependence of PL and absorption spectra, we attribute it to energy difference between free exciton and bound exciton states, where main exciton absorption peak comes from free exciton absorption and PL peak is attributed to recombination of bound exciton at 10 K. This strong bound exciton effect is stable up to 50 K. Moreover, the temperature dependence of integrated PL intensity and PL lifetime reveals that a non-radiative process, with activation energy extracted as 0.5 meV, dominates PL emission.
UbC-StarTrack, a clonal method to target the entire progeny of individual progenitors
Authors: Figueres-Oñate María , García-Marqués Jorge , López-Mascaraque Laura 
Published: September 2016

AbstractClonal cell analysis defines the potential of single cells and the diversity they can produce. To achieve this, we have developed a novel adaptation of the genetic tracing strategy, UbC-StarTrack, which attributes a specific and unique color-code to single neural precursors, allowing all their progeny to be tracked. We used integrable fluorescent reporters driven by a ubiquitous promoter in PiggyBac-based vectors to achieve inheritable and stable clonal cell labeling. In addition, coupling this to an inducible Cre-LoxP system avoids the expression of non-integrated reporters. To assess the utility of this system, we first analyzed images of combinatorial expression of fluorescent reporters in transfected cells and their progeny. We also validated the efficiency of the UbC-StarTrack to trace cell lineages through in vivo, in vitro and ex vivo strategies. Finally, progenitors located in the lateral ventricles were targeted at embryonic or postnatal stages to determine the diversity of neurons and glia they produce, and their clonal relationships. In this way we demonstrate that UbC-StarTrack can be used to identify all the progeny of a single cell and that it can be employed in a wide range of contexts.
Graphene as a Reversible and Spectrally Selective Fluorescence Quencher
Authors: Salihoglu Omer , Kakenov Nurbek , Balci Osman , Balci Sinan , Kocabas Coskun 
Published: September 2016

AbstractWe report reversible and spectrally selective fluorescence quenching of quantum dots (QDs) placed in close proximity to graphene. Controlling interband electronic transitions of graphene via electrostatic gating greatly modifies the fluorescence lifetime and intensity of nearby QDs via blocking of the nonradiative energy transfer between QDs and graphene. Using ionic liquid (IL) based electrolyte gating, we are able to control Fermi energy of graphene in the order of 1 eV, which yields electrically controllable fluorescence quenching of QDs in the visible spectrum. Indeed, our technique enables us to perform voltage controllable spectral selectivity among quantum dots at different emission wavelengths. We anticipate that our technique will provide tunable light-matter interaction and energy transfer that could yield hybrid QDs-graphene based optoelectronic devices with novel functionalities and additionally, may be useful as a spectroscopic ruler, for example, in bioimaging and biomolecular sensing. We propose that graphene can be used as an electrically tunable and wavelength selective fluorescence quencher.
Increased aqueous flare is associated with thickening of inner retinal layers in eyes with retinitis pigmentosa
Authors: Nagasaka Yosuke , Ito Yasuki , Ueno Shinji , Terasaki Hiroko 
Published: September 2016

AbstractRetinitis pigmentosa(RP) is a hereditary retinal disease that causes photoreceptor, outer retinal, degeneration. Although the pathogenesis is still unclear, there have been numerous reports regarding inner retinal changes in RP eyes. The aim of this study is to retrospectively evaluate the changes in the thicknesses of different retinal layers of RP eyes and its association with aqueous flare, which is used for measuring the intensity of intraocular inflammation. A total of 125 eyes of 64 patients with RP and 13 normal eyes were studied. The thicknesses of total neural retina,nerve fiber layer(NFL),ganglion cell layer(GCL),inner plexiform layer(IPL),inner nuclear layer(INL),outer layers and foveal thickness were measured in the optical coherence tomographic images. Aqueous flare was measured with a laser flare-cell meter. The associations between those parameters, visual acuity and visual field were determined in RP eyes using multivariate analysis. The results of this study showed the significant thickening of NFL, GCL and INL, the significant thinning of outer layers and the association of them with increased aqueous flare, whereas NFL and INL thickening associated with outer retinal thinning. These results can suggest the involvement of intraocular inflammation in the pathogenesis of inner retinal thickening as a secondary change following outer retinal degeneration.
Fluorescence-based assay as a new screening tool for toxic chemicals
Authors: Moczko Ewa , Mirkes Evgeny M. , Cáceres César , Gorban Alexander N. , Piletsky Sergey 
Published: September 2016

AbstractOur study involves development of fluorescent cell-based diagnostic assay as a new approach in high-throughput screening method. This highly sensitive optical assay operates similarly to e-noses and e-tongues which combine semi-specific sensors and multivariate data analysis for monitoring biochemical processes. The optical assay consists of a mixture of environmental-sensitive fluorescent dyes and human skin cells that generate fluorescence spectra patterns distinctive for particular physico-chemical and physiological conditions. Using chemometric techniques the optical signal is processed providing qualitative information about analytical characteristics of the samples. This integrated approach has been successfully applied (with sensitivity of 93% and specificity of 97%) in assessing whether particular chemical agents are irritating or not for human skin. It has several advantages compared with traditional biochemical or biological assays and can impact the new way of high-throughput screening and understanding cell activity. It also can provide reliable and reproducible method for assessing a risk of exposing people to different harmful substances, identification active compounds in toxicity screening and safety assessment of drugs, cosmetic or their specific ingredients.
Associations between metabolic syndrome and clinical benign prostatic hyperplasia in a northern urban Han Chinese population: A prospective cohort study
Authors: Zhao Si-Cong , Xia Ming , Tang Jian-Chun , Yan Yong 
Published: September 2016

AbstractBiologic rationales exist for the associations between metabolic syndrome (MetS) and benign prostatic hyperplasia (BPH). However, epidemiologic studies have yield inconsistent results. The aim of the present study was to prospectively evaluate the associations of MetS with the risk of BPH. The presence of MetS, the number of MetS components and the individual MetS components were evaluated. After adjusting for potential confounders, MetS was associated with increased risk of BPH (HR: 1.29; 95% CI, 1.08–1.50; p < 0.001). Compared with subjects without any MetS components, the HRs were 0.88 (95% CI, 0.67–1.09; p = 0.86), 1.18 (95% CI, 0.89–1.47; p = 0.29) and 1.37 (95% CI, 1.08–1.66; p = 0.014) for subjects with 1, 2, or ≥3 MetS components and there was a biologic gradient between the number of MetS components and the risk of BPH (p-trend < 0.001). Central obesity and low high-density lipoprotein cholesterol were the two main divers of the associations between these two conditions, with HRs of 1.93 (95% CI, 1.14–2.72; p = 0.001) for central obesity and 1.56 (95% CI, 1.08–2.04; p = 0.012) for low HDL-C. Our findings support the notion that MetS may be an important target for BPH prevention and intervention.
Identification of gefitinib off-targets using a structure-based systems biology approach; their validation with reverse docking and retrospective data mining
Authors: Verma Nidhi , Rai Amit Kumar , Kaushik Vibha , Brünnert Daniela , Chahar Kirti Raj , Pandey Janmejay , Goyal Pankaj 
Published: September 2016

AbstractGefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung cancer treatment. However, this drug has certain side effects and complications for which the underlying molecular mechanisms are not well understood. By systems biology based in silico analysis, we identified off-targets of gefitinib that might explain side effects of this drugs. The crystal structure of EGFR-gefitinib complex was used for binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. The top 128 hits of putative off-targets were validated by reverse docking approach. The results showed that identified off-targets have efficient binding with gefitinib. The identified human specific off-targets were confirmed and further analyzed for their links with biological process and clinical disease pathways using retrospective studies and literature mining, respectively. Noticeably, many of the identified off-targets in this study were reported in previous high-throughput screenings. Interestingly, the present study reveals that gefitinib may have positive effects in reducing brain and bone metastasis, and may be useful in defining novel gefitinib based treatment regime. We propose that a system wide approach could be useful during new drug development and to minimize side effect of the prospective drug.