bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes
Authors: van Krieken Pim P. , Dicker Andrea , Eriksson Maria , Herrera Pedro L. , Ahlgren Ulf , Berggren Per-Olof , Ilegems Erwin 
Published: September 2017

AbstractFunctional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse, a model of hyperglycemia resulting from diphtheria toxin induced beta cell ablation. A novel combination of imaging modalities was employed to study the pattern of beta cell destruction. Optical projection tomography of the pancreas and longitudinal in vivo confocal microscopy of islets transplanted into the anterior chamber of the eye allowed to investigate kinetics and tomographic location of beta cell mass decay in individual islets as well as at the entire islet population level. The correlation between beta cell mass and function was determined by complementary in vivo and ex vivo characterizations, demonstrating that beta cell function and glucose tolerance were impaired within the first two days following treatment when more than 50% of beta cell mass was remaining. Our results illustrate the importance of acquiring quantitative functional and morphological parameters to assess the functional status of the endocrine pancreas.
Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach
Authors: Gaspar H. A. , Breen G. 
Published: September 2017

AbstractUsing successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used genome-wide association study (GWAS) summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group to build a drug repositioning model for schizophrenia. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics. Each of these therapeutical classes targets different gene subnetworks. We identify 123 Bonferroni-significant druggable genes outside the MHC, and 128 FDR-significant biological pathways related to neurons, synapses, genic intolerance, membrane transport, epilepsy, and mental disorders. These results suggest that, in schizophrenia, current well-powered GWAS results can reliably detect known schizophrenia drugs and thus may hold considerable potential for the identification of new therapeutic leads. Moreover, antiepileptics and calcium channel blockers may provide repurposing opportunities. This study also reveals significant pathways in schizophrenia that were not identified previously, and provides a workflow for pathway analysis and drug repurposing using GWAS results.
Memory characteristics of silicon nanowire transistors generated by weak impact ionization
Authors: Lim Doohyeok , Kim Minsuk , Kim Yoonjoong , Kim Sangsig 
Published: September 2017

AbstractIn this study, we demonstrate the static random access memory (SRAM) characteristics generated by weak impact ionization in bendable field-effect transistors (FETs) with n+-p-n+ silicon nanowire (SiNW) channels. Our bendable SiNW FETs show not only superior switching characteristics such as an on/off current ratio of ~105 and steep subthreshold swing (~5 mV/dec) but also reliable SRAM characteristics. The SRAM characteristics originate from the positive feedback loops in the SiNW FETs generated by weak impact ionization. This paper describes in detail the operating mechanism of our device and demonstrates the potential of bendable SiNW FETs for future SRAM applications.
Label-free detection of cellular drug responses by high-throughput bright-field imaging and machine learning
Authors: Kobayashi Hirofumi , Lei Cheng , Wu Yi , Mao Ailin , Jiang Yiyue , Guo Baoshan , Ozeki Yasuyuki , Goda Keisuke 
Published: September 2017

AbstractIn the last decade, high-content screening based on multivariate single-cell imaging has been proven effective in drug discovery to evaluate drug-induced phenotypic variations. Unfortunately, this method inherently requires fluorescent labeling which has several drawbacks. Here we present a label-free method for evaluating cellular drug responses only by high-throughput bright-field imaging with the aid of machine learning algorithms. Specifically, we performed high-throughput bright-field imaging of numerous drug-treated and -untreated cells (N = ~240,000) by optofluidic time-stretch microscopy with high throughput up to 10,000 cells/s and applied machine learning to the cell images to identify their morphological variations which are too subtle for human eyes to detect. Consequently, we achieved a high accuracy of 92% in distinguishing drug-treated and -untreated cells without the need for labeling. Furthermore, we also demonstrated that dose-dependent, drug-induced morphological change from different experiments can be inferred from the classification accuracy of a single classification model. Our work lays the groundwork for label-free drug screening in pharmaceutical science and industry.
Radiation alters the cargo of exosomes released from squamous head and neck cancer cells to promote migration of recipient cells
Authors: Mutschelknaus Lisa , Azimzadeh Omid , Heider Theresa , Winkler Klaudia , Vetter Marcus , Kell Rosemarie , Tapio Soile , Merl-Pham Juliane , Huber Stephan M. , Edalat Lena , Radulović Vanja , Anastasov Nataša , Atkinson Michael J. , Moertl Simone 
Published: September 2017

AbstractRadiation is a highly efficient therapy in squamous head and neck carcinoma (HNSCC) treatment. However, local recurrence and metastasis are common complications. Recent evidence shows that cancer-cell-derived exosomes modify tumour cell movement and metastasis. In this study, we link radiation-induced changes of exosomes to their ability to promote migration of recipient HNSCC cells. We demonstrate that exosomes isolated from irradiated donor cells boost the motility of the HNSCC cells BHY and FaDu. Molecular data identified enhanced AKT-signalling, manifested through increased phospho-mTOR, phospho-rpS6 and MMP2/9 protease activity, as underlying mechanism. AKT-inhibition blocked the pro-migratory action, suggesting AKT-signalling as key player in exosome-mediated migration. Proteomic analysis of exosomes isolated from irradiated and non-irradiated BHY donor cells identified 39 up- and 36 downregulated proteins. In line with the observed pro-migratory effect of exosomes isolated from irradiated cells protein function analysis assigned the deregulated exosomal proteins to cell motility and AKT-signalling. Together, our findings demonstrate that exosomes derived from irradiated HNSCC cells confer a migratory phenotype to recipient cancer cells. This is possibly due to radiation-regulated exosomal proteins that increase AKT-signalling. We conclude that exosomes may act as driver of HNSCC progression during radiotherapy and are therefore attractive targets to improve radiation therapy strategies.
Inverse Resolution Limit of Partition Density and Detecting Overlapping Communities by Link-Surprise
Authors: Lee Juyong , Zhang Zhong-Yuan , Lee Jooyoung , Brooks Bernard R. , Ahn Yong-Yeol 
Published: September 2017

AbstractFinding overlapping communities of complex networks remains a challenge in network science. To address this challenge, one of the widely used approaches is finding the communities of links by optimizing the objective function, partition density. In this study, we show that partition density suffers from inverse resolution limit; it has a strong preference to triangles. This resolution limit makes partition density an improper objective function for global optimization. The conditions where partition density prefers triangles to larger link community structures are analytically derived and confirmed with global optimization calculations using synthetic and real-world networks. To overcome this limitation of partition density, we suggest an alternative measure, Link Surprise, to find link communities, which is suitable for global optimization. Benchmark studies demonstrate that global optimization of Link Surprise yields meaningful and more accurate link community structures than partition density optimization.
The identification of molecular target of (20S) ginsenoside Rh2 for its anti-cancer activity
Authors: Wang Yu-Shi , Lin Yingjia , Li He , Li Yang , Song Zhiguang , Jin Ying-Hua 
Published: September 2017

AbstractThe 20S ginsenoside Rh2 (G-Rh2) effectively inhibits cancer cell growth and survival in both animal models and cell lines. However, its molecular targets and mechanism of action remain largely unknown. By screening for molecules that interact with (20S)G-Rh2 in a phage display assay, we have identified Annexin A2 as a potential target that mediates its anti-cancer activity. Isothermal titration calorimetry and a cellular thermal shift assay demonstrated that (20S)G-Rh2 directly bound to either recombinant or intracellular Annexin A2. This binding inhibited the interaction between Annexin A2 and the NF-кB p50 subunit, which attenuated the nuclear translocations of NF-кB p50 subunit and reduced the transactivation activity of NF-кB. Correspond to this result, (20S)G-Rh2 treatment significantly down-regulated the expression of IAPs (inhibitors of apoptosis), the well-established NF-кB targets that promote cell survival. Moreover, (20S)G-Rh2 synergized with Annexin A2 inactivation to promote apoptosis. Taken together, this study for the first time suggests a cellular target and a molecular pathway by which (20S)G-Rh2 inhibits cancer cell growth. As over-expression of Annexin A2 was evident in human hepatoma, (20S)G-Rh2 might be a promising natural compound for targeted liver cancer therapy.
Development of persistent gastrointestinal S. aureus carriage in mice
Authors: Flaxman Amy , van Diemen Pauline M. , Yamaguchi Yuko , Allen Elizabeth , Lindemann Claudia , Rollier Christine S. , Milicic Anita , Wyllie David H. 
Published: September 2017

AbstractOne fifth to one quarter of the human population is asymptomatically, naturally and persistently colonised by Staphylococcus aureus. Observational human studies indicate that although the whole population is intermittently exposed, some individuals lose S. aureus rapidly. Others become persistent carriers, as assessed by nasal cultures, with many individuals colonised for decades. Current animal models of S. aureus colonisation are expensive and normally require antibiotics. Importantly, these animal models have not yet contributed to our poor understanding of the dichotomy in human colonisation status. Here, we identify a single strain of S. aureus found to be persistently colonising the gastrointestinal tract of BALB/c mice. Phylogenetic analyses suggest it diverged from a human ST15 lineage in the recent past. We show that murine carriage of this organism occurs in the bowel and nares, is acquired early in life, and can persist for months. Importantly, we observe the development of persistent and non-persistent gastrointestinal carriage states in genetically identical mice. We developed a needle- and antibiotic-free model in which we readily induced S. aureus colonisation of the gastrointestinal tract experimentally by environmental exposure. Using our experimental model, impact of adaptive immunity on S. aureus colonisation could be assessed. Vaccine efficacy to eliminate colonisation could also be investigated using this model.
Valence Change Bipolar Resistive Switching Accompanied With Magnetization Switching in CoFe2O4 Thin Film
Authors: Munjal Sandeep , Khare Neeraj 
Published: September 2017

AbstractResistive Switching in oxides has offered new opportunities for developing resistive random access memory (ReRAM) devices. Here we demonstrated bipolar Resistive Switching along with magnetization switching of cobalt ferrite (CFO) thin film using Al/CFO/FTO sandwich structure, which makes it a potential candidate for developing future multifunctional memory devices. The device shows good retention characteristic time (>104 seconds) and endurance performance, a good resistance ratio of high resistance state (HRS) and low resistance state (LRS) ~103. Nearly constant resistance values in LRS and HRS confirm the stability and non-volatile nature of the device. The device shows different conduction mechanisms in the HRS and LRS i.e. Schottky, Poole Frenkel and Ohmic. Magnetization of the device is also modulated by applied electric field which has been attributed to the oxygen vacancies formed/annihilated during the voltage sweep and indicates the presence of valence change mechanism (VCM) in our device. It is suggested that push/pull of oxygen ions from oxygen diffusion layer during voltage sweep is responsible for forming/rupture of oxygen vacancies conducting channels, leading to switching between LRS and HRS and for switching in magnetization in CFO thin film. Presence of VCM in our device was confirmed by X-ray Photoelectron Spectroscopy at Al/CFO interface.
Somatic Arc protein expression in hippocampal granule cells is increased in response to environmental change but independent of task-specific learning
Authors: Cleland J. P. , Willis E. F. , Bartlett P. F. , Vukovic J. 
Published: September 2017

AbstractActivated neurons express immediate-early genes, such as Arc. Expression of Arc in the hippocampal granule cell layer, an area crucial for spatial learning and memory, is increased during acquisition of spatial learning; however, it is unclear whether this effect is related to the task-specific learning process or to nonspecific aspects of the testing procedure (e.g. exposure to the testing apparatus and exploration of the environment). Herein, we show that Arc-positive cells numbers are increased to the same extent in the granule cell layer after both acquisition of a single spatial learning event in the active place avoidance task and exploration of the testing environment, as compared to naïve (i.e. caged) mice. Repeated exposure the testing apparatus and environment did not reduce Arc expression. Furthermore, Arc expression did not correlate with performance in both adult and aged animals, suggesting that exploration of the testing environment, rather than the specific acquisition of the active place avoidance task, induces Arc expression in the dentate granule cell layer. These findings thus suggest that Arc is an experience-induced immediate-early gene.
Establishing a method of short-term rainfall forecasting based on GNSS-derived PWV and its application
Authors: Yao Yibin , Shan Lulu , Zhao Qingzhi 
Published: September 2017

AbstarctGlobal Navigation Satellite System (GNSS) can effectively retrieve precipitable water vapor (PWV) with high precision and high-temporal resolution. GNSS-derived PWV can be used to reflect water vapor variation in the process of strong convection weather. By studying the relationship between time-varying PWV and rainfall, it can be found that PWV contents increase sharply before raining. Therefore, a short-term rainfall forecasting method is proposed based on GNSS-derived PWV. Then the method is validated using hourly GNSS-PWV data from Zhejiang Continuously Operating Reference Station (CORS) network of the period 1 September 2014 to 31 August 2015 and its corresponding hourly rainfall information. The results show that the forecasted correct rate can reach about 80%, while the false alarm rate is about 66%. Compared with results of the previous studies, the correct rate is improved by about 7%, and the false alarm rate is comparable. The method is also applied to other three actual rainfall events of different regions, different durations, and different types. The results show that the method has good applicability and high accuracy, which can be used for rainfall forecasting, and in the future study, it can be assimilated with traditional weather forecasting techniques to improve the forecasted accuracy.
Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo
Authors: Llavero Hurtado Maica , Fuller Heidi R. , Wong Andrew M. S. , Eaton Samantha L. , Gillingwater Thomas H. , Pennetta Giuseppa , Cooper Jonathan D. , Wishart Thomas M. 
Published: September 2017

AbstractSynapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3−/− mouse model of a juvenile form of NCL. We profiled and compared the molecular composition of anatomically-distinct, differentially-affected pre-synaptic populations from the Cln3−/− mouse brain using proteomics followed by bioinformatic analyses. Identified protein candidates were then tested using a Drosophila CLN3 model to study their ability to modify the CLN3-neurodegenerative phenotype in vivo. We identified differential perturbations in a range of molecular cascades correlating with synaptic vulnerability, including valine catabolism and rho signalling pathways. Genetic and pharmacological targeting of key ‘hub’ proteins in such pathways was sufficient to modulate phenotypic presentation in a Drosophila CLN3 model. We propose that such a workflow provides a target rich method for the identification of novel disease regulators which could be applicable to the study of other conditions where appropriate models exist.
Selection on start codons in prokaryotes and potential compensatory nucleotide substitutions
Authors: Belinky Frida , Rogozin Igor B. , Koonin Eugene V. 
Published: September 2017

AbstractReconstruction of the evolution of start codons in 36 groups of closely related bacterial and archaeal genomes reveals purifying selection affecting AUG codons. The AUG starts are replaced by GUG and especially UUG significantly less frequently than expected under the neutral expectation derived from the frequencies of the respective nucleotide triplet substitutions in non-coding regions and in 4-fold degenerate sites. Thus, AUG is the optimal start codon that is actively maintained by purifying selection. However, purifying selection on start codons is significantly weaker than the selection on the same codons in coding sequences, although the switches between the codons result in conservative amino acid substitutions. The only exception is the AUG to UUG switch that is strongly selected against among start codons. Selection on start codons is most pronounced in evolutionarily conserved, highly expressed genes. Mutation of the start codon to a sub-optimal form (GUG or UUG) tends to be compensated by mutations in the Shine-Dalgarno sequence towards a stronger translation initiation signal. Together, all these findings indicate that in prokaryotes, translation start signals are subject to weak but significant selection for maximization of initiation rate and, consequently, protein production.
Suppression of adiponectin receptor 1 promotes memory dysfunction and Alzheimer’s disease-like pathologies
Authors: Kim Min Woo , Abid Noman bin , Jo Myeong Hoon , Jo Min Gi , Yoon Gwang Ho , Kim Myeong Ok 
Published: September 2017

AbstractRecent studies on neurodegeneration have focused on dysfunction of CNS energy metabolism as well as proteinopathies. Adiponectin (ADPN), an adipocyte-derived hormone, plays a major role in the regulation of insulin sensitivity and glucose homeostasis in peripheral organs via adiponectin receptors. In spite of accumulating evidence that adiponectin has neuroprotective properties, the underlying role of adiponectin receptors has not been illuminated. Here, using gene therapy-mediated suppression with shRNA, we found that adiponectin receptor 1 (AdipoR1) suppression induces neurodegeneration as well as metabolic dysfunction. AdipoR1 knockdown mice exhibited increased body weight and abnormal plasma chemistry and also showed spatial learning and memory impairment in behavioural studies. Moreover, AdipoR1 suppression resulted in neurodegenerative phenotypes, diminished expression of the neuronal marker NeuN, and increased expression and activity of caspase 3. Furthermore, AD-like pathologies including insulin signalling dysfunction, abnormal protein aggregation and neuroinflammatory responses were highly exhibited in AdipoR1 knockdown groups, consistent with brain pathologies in ADPN knockout mice. Together, these results suggest that ADPN-AdipoR1 signalling has the potential to alleviate neurodegenerative diseases such as Alzheimer’s diseases.
CCK reduces the food intake mainly through CCK1R in Siberian sturgeon (Acipenser baerii Brandt)
Authors: Zhang Xin , Tang Ni , Qi Jinwen , Wang Shuyao , Hao Jin , Wu Yuanbing , Chen Hu , Tian Zhengzhi , Wang Bin , Chen Defang , Li Zhiqiong 
Published: September 2017

AbstractTo explore the effect of CCK on food intake in Siberian sturgeon, cck cDNA sequence of 1005 bp was obtained, and cck mRNA possessed the highest expression in brain. The expressions of cck were significantly increased after feeding 1 and 3 h, while displaying significant decrease after fasting within 15 days in brain and duodenum. Re-feeding for 3 days induced cck level returned to basic level. Acute i.p. injection experiment showed 100 and 200 ng/g BW CCK8 inhibited the food intake in 0–1 h together with the cumulative food intake within 3 h. 7 days chronic i.p. injection of 100 and 200 ng/g BW CCK8, both daily food intake and cumulative food intake were significantly decreased. In addition, chronic i.p injection of CCK8 induced the expression of feeding related factors changes including cck, ucn3, cart, apelin, pyy and npy in respective organization. Moreover, as revealed by the results, Lorglumide, the CCK1R selective antagonist, effectively reversed the inhibitory effects of CCK8 on food intake and the levels of feeding related factors. On the other hand, LY 225910, the CCK2R selective antagonist, partially reversed these effects. These results indicate CCK is a satiety factor inhibits the feeding of Siberian sturgeon primarily through CCK1R.