bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ruthenium(II) Complexes with 2-Phenylimidazo[4,5-f][1,10]phenanthroline Derivatives that Strongly Combat Cisplatin-Resistant Tumor Cells
Authors: Zeng Leli , Chen Yu , Liu Jiangping , Huang Huaiyi , Guan Ruilin , Ji Liangnian , Chao Hui 
Published: January 2016

AbstractCisplatin was the first metal-based therapeutic agent approved for the treatment of human cancers, but its clinical activity is greatly limited by tumor drug resistance. This work utilized the parent complex [Ru(phen)2(PIP)]2+ (1) to develop three Ru(II) complexes (2–4) with different positional modifications. These compounds exhibited similar or superior cytotoxicities compared to cisplatin in HeLa, A549 and multidrug-resistant (A549R) tumor cell lines. Complex 4, the most potent member of the series, was highly active against A549R cancer cells (IC50 = 0.8 μM). This complex exhibited 178-fold better activity than cisplatin (IC50 = 142.5 μM) in A549R cells. 3D multicellular A549R tumor spheroids were also used to confirm the high proliferative and cytotoxic activity of complex 4. Complex 4 had the greatest cellular uptake and had a tendency to accumulate in the mitochondria of A549R cells. Further mechanistic studies showed that complex 4 induced A549R cell apoptosis via inhibition of thioredoxin reductase (TrxR), elevated intracellular ROS levels, mitochondrial dysfunction and cell cycle arrest, making it an outstanding candidate for overcoming cisplatin resistance.
Stabilizing Off-pathway Oligomers by Polyphenol Nanoassemblies for IAPP Aggregation Inhibition
Authors: Nedumpully-Govindan Praveen , Kakinen Aleksandr , Pilkington Emily H. , Davis Thomas P. , Chun Ke Pu , Ding Feng 
Published: January 2016

AbstractExperimental studies have shown that many naturally occurring polyphenols have inhibitory effect on the aggregation of several proteins. Here, we use discrete molecular dynamics (DMD) simulations and high-throughput dynamic light scattering (DLS) experiments to study the anti-aggregation effects of two polyphenols, curcumin and resveratrol, on the aggregation of islet amyloid polypeptide (IAPP or amylin). Our DMD simulations suggest that the aggregation inhibition is caused by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols. Our analysis indicates that IAPP-polyphenol hydrogen bonds and π-π stacking combined with hydrophobic interactions are responsible for the stabilization of oligomers. The presence of small oligomers is confirmed with DLS measurements in which nanometer-sized oligomers are found to be stable for up to 7.5 hours, the time frame within which IAPP aggregates in the absence of polyphenols. Our study offers a general anti-aggregation mechanism for polyphenols and further provides a computational framework for the future design of anti-amyloid aggregation therapeutics.
Teratocarcinomas Arising from Allogeneic Induced Pluripotent Stem Cell-Derived Cardiac Tissue Constructs Provoked Host Immune Rejection in Mice
Authors: Kawamura Ai , Miyagawa Shigeru , Fukushima Satsuki , Kawamura Takuji , Kashiyama Noriyuki , Ito Emiko , Watabe Tadashi , Masuda Shigeo , Toda Koichi , Hatazawa Jun , Morii Eiichi , Sawa Yoshiki 
Published: January 2016

AbstractTransplantation of induced pluripotent stem cell-derived cardiac tissue constructs is a promising regenerative treatment for cardiac failure: however, its tumourigenic potential is concerning. We hypothesised that the tumourigenic potential may be eliminated by the host immune response after allogeneic cell transplantation. Scaffold-free iPSC-derived cardaic tissue sheets of C57BL/6 mouse origin were transplanted into the cardiac surface of syngeneic C57BL/6 mice and allogeneic BALB/c mice with or without tacrolimus injection. Syngeneic mice and tacrolimus-injected immunosuppressed allogeneic mice formed teratocarcinomas with identical phenotypes, characteristic and time courses, as assessed by imaging tools including 18F-fluorodeoxyglucose-positron emission tomography. In contrast, temporarily immunosuppressed allogeneic mice, following cessation of tacrolimus injection displayed diminished progression of the teratocarcinoma, accompanied by an accumulation of CD4/CD8-positive T cells and finally achieved complete elimination of the teratocarcinoma. Our results indicated that malignant teratocarcinomas arising from induced pluripotent stem cell-derived cardiac tissue constructs provoked T cell-related host immune rejection to arrest tumour growth in murine allogeneic transplantation models.
Single-Cell Electrical Phenotyping Enabling the Classification of Mouse Tumor Samples
Authors: Zhao Yang , Jiang Mei , Chen Deyong , Zhao Xiaoting , Xue Chengcheng , Hao Rui , Yue Wentao , Wang Junbo , Chen Jian 
Published: January 2016

AbstractSingle-cell electrical phenotyping (e.g., specific membrane capacitance (Cm) and cytoplasm conductivity (σp)) has long been regarded as potential label-free biophysical markers in tumor status evaluation. However, previous studies only reported the differentiation of tumor cell lines without classifying real tumor samples using cellular electrical properties. In this study, two types of mouse tumor models were constructed by injecting two types of tumor cell lines (A549 and H1299), respectively. Then tumor portions were retrieved for immunohistochemistry studies and single-cell electrical phenotyping based on home-developed microfluidic platforms. Immunohistochemistry results of tumor samples confirmed the adenocarcinoma and large-cell carcinoma characteristics for A549 and H1299 based tumor samples, respectively. Meanwhile, cellular Cm and σp were characterized as 2.25 ± 0.50 μF/cm2 and 0.96 ± 0.20 S/m for A549 based tumor samples (ncell = 1336, Mouse I, II, III) and 1.76 ± 0.54 μF/cm2 and 1.35 ± 0.28 S/m for H1299 based tumor samples (ncell = 1442, Mouse IV, V, VI). Significant differences in Cm and σp were observed between these two types of tumor samples, validating the feasibility of using Cm and σp for mouse tumor classification.
The mammalian homologue of yeast Afg1 ATPase (lactation elevated 1) mediates degradation of nuclear-encoded complex IV subunits
Authors: Cesnekova Jana , Rodinova Marie , Hansikova Hana , Houstek Josef , Zeman Jiri , Stiburek Lukas 
Published: January 2016

Mitochondrial protein homeostasis is crucial for cellular function and integrity and is therefore maintained by several classes of proteins possessing chaperone and/or proteolytic activities. In the present study, we focused on characterization of LACE1 (lactation elevated 1) function in mitochondrial protein homeostasis. LACE1 is the human homologue of yeast mitochondrial Afg1 (ATPase family gene 1) ATPase, a member of the SEC18-NSF, PAS1, CDC48-VCP, TBP family. Yeast Afg1 was shown to mediate degradation of mitochondrially encoded complex IV subunits, and, on the basis of its similarity to CDC48 (p97/VCP), it was suggested to facilitate extraction of polytopic membrane proteins. We show that LACE1, which is a mitochondrial integral membrane protein, exists as part of three complexes of approximately 140, 400 and 500 kDa and is essential for maintenance of fused mitochondrial reticulum and lamellar cristae morphology. We demonstrate that LACE1 mediates degradation of nuclear-encoded complex IV subunits COX4 (cytochrome c oxidase 4), COX5A and COX6A, and is required for normal activity of complexes III and IV of the respiratory chain. Using affinity purification of LACE1–FLAG expressed in a LACE1-knockdown background, we show that the protein interacts physically with COX4 and COX5A subunits of complex IV and with mitochondrial inner-membrane protease YME1L. Finally, we demonstrate by ectopic expression of both K142A Walker A and E214Q Walker B mutants, that an intact ATPase domain is essential for LACE1-mediated degradation of nuclear-encoded complex IV subunits. Thus the present study establishes LACE1 as a novel factor with a crucial role in mitochondrial protein homeostasis.
Injury, reflex impairment, and survival of beam-trawled flatfish
Authors: Uhlmann Sebastian S. , Theunynck Ruben , Ampe Bart , Desender Marieke , Soetaert Maarten , Depestele Jochen 
Published: January 2016

AbstractUnder the “high survival” exemption of the European landing obligation or discard ban, monitoring vitality and survival of European flatfish becomes relevant to a discard-intensive beam trawl fishery. The reflex action mortality predictor (RAMP) method may be useful in this context. It involves scoring for the presence or absence of natural animal reflexes to generate an impairment score which is then correlated with post-release or discard mortality. In our first experiment, we determined suitable candidate reflexes for acclimated, laboratory-held European plaice (Pleuronectes platessa) and common sole (Solea solea). In a second experiment, we quantified reflex impairment of commercially trawled-and-handled plaice and sole in response to commercial fishing stressors. In a third experiment, we tested whether a combined reflex impairment and injury (vitality) score of plaice was correlated with delayed post-release mortality to establish RAMP. Five-hundred fourteen trawled-and-discarded plaice and 176 sole were assessed for experimentally confirmed reflexes such as righting, evasion, stabilise, and tail grab, among others. Of these fish, 316 plaice were monitored for at least 14 d in captivity, alongside 60 control plaice. All control fish survived, together with an average of 50% (±29 SD) plaice after being trawled from conventional, 60 min trawls and sorted on-board a coastal beam trawler. Stressors such as trawl duration, wave height, air, and seawater temperature were not as relevant as a vitality score and total length in predicting post-release survival probability. In the second experiment where survival was not assessed, reflex impairment of plaice became more frequent with prolonged air exposure. For sole, a researcher handling-and-reflex scoring bias rather than a fishing stressor may have confounded results. Scoring a larger number of individuals for injuries and reflexes from a representative selection of trawls and trips may allow for a fleet-scale discard survival estimate to facilitate implementation of the discard ban.
Near-infrared spectroscopy of M dwarfs. III. Carbon and oxygen abundances in late M dwarfs, including the dusty rapid rotator 2MASSI J1835379+325954
Authors: Tsuji Takashi , Nakajima Tadashi 
Published: January 2016

Abstract
Carbon and oxygen abundances of eight late M dwarfs are determined based on the near-infrared spectra of medium resolution (R = λ/Δ λ ≈ 20000). In late M dwarfs, dust forms in their photospheres for Teff below about 2600 K, and this case applies to the M8.5 dwarf 2MASSI J1835379+325954 (hereafter 2MASS 1835+32) whose Teff is 2275 K. The other seven objects with Teff above 2600 K are analyzed with dust-free models. For the case of 2MASS 1835+32 analyzed with the dusty model, the surface temperature is higher by about 600 K due to the blanketing effect of the dust grains, mainly composed of iron grains, and the carbon and oxygen abundances are higher by 0.25 and 0.15 dex, respectively, compared to the analysis by the dust-free model. Once dust forms in the photosphere, the dust works as a kind of thermostat and the temperatures of the surface layers remain nearly the same as the condensation temperatures of the dust grains. For this reason, the temperatures of the surface layers of dusty dwarfs are relatively insensitive to the fundamental parameters, including Teff. In addition, it appears that 2MASS 1835+32 is a rapid rotator, for which its equivalent widths (EWs) are thought to remain unchanged by the rotational broadening. This is, however, true only when the true continuum is well defined. Otherwise, the pseudo-continuum level depends on the rotational velocity and hence the EWs as well. For this reason, the derived abundances depend on the rotational velocity assumed: for the values of Vrotsin i = 37.6 and 44.0 km s−1 available in the literature, the derived carbon and oxygen abundances differ by 0.23 and 0.14 dex, respectively, and we find that the higher value provides a better account of the observed spectrum. The resulting carbon and oxygen abundances in the eight late M dwarfs show no systematic difference from our results for the early and middle M dwarfs, and confirm the higher AO/AC ratio at the lower metallicity. In late M dwarfs, CO and H2O remain as excellent abundance indicators of carbon and oxygen, respectively, except for additional uncertainty due to complexity associated with dust formation in the latest M dwarfs.
PEDLA: predicting enhancers with a deep learning-based algorithmic framework
Authors: Liu Feng , Li Hao , Ren Chao , Bo Xiaochen , Shu Wenjie 
Published: January 2016

AbstractTranscriptional enhancers are non-coding segments of DNA that play a central role in the spatiotemporal regulation of gene expression programs. However, systematically and precisely predicting enhancers remain a major challenge. Although existing methods have achieved some success in enhancer prediction, they still suffer from many issues. We developed a deep learning-based algorithmic framework named PEDLA (https://github.com/wenjiegroup/PEDLA), which can directly learn an enhancer predictor from massively heterogeneous data and generalize in ways that are mostly consistent across various cell types/tissues. We first trained PEDLA with 1,114-dimensional heterogeneous features in H1 cells, and we demonstrated that our PEDLA framework integrates diverse heterogeneous features and gives state-of-the-art performance relative to five existing methods for enhancer prediction. We further extended PEDLA to iteratively learn from 22 training cell types/tissues. Our results showed that PEDLA manifested superior performance consistency in both training and independent test sets. On average, PEDLA achieved 95.0% accuracy and a 96.8% geometric mean (GM) across 22 training cell types/tissues, as well as 95.7% accuracy and a 96.8% GM across 20 independent test cell types/tissues. Together, our work illustrates the power of harnessing state-of-the-art deep learning techniques to consistently identify regulatory elements at a genome-wide scale from massively heterogeneous data across diverse cell types/tissues.
Genome-wide identification and characterisation of HOT regions in the human genome
Authors: Li Hao , Liu Feng , Ren Chao , Bo Xiaochen , Shu Wenjie 
Published: January 2016

AbstractHOT (high-occupancy target) regions, which are bound by a surprisingly large number of transcription factors, are considered to be among the most intriguing findings of recent years. An improved understanding of the roles that HOT regions play in biology would be afforded by knowing the constellation of factors that constitute these domains and by identifying HOT regions across the spectrum of human cell types. We characterised and validated HOT regions in embryonic stem cells (ESCs) and produced a catalogue of HOT regions in a broad range of human cell types. We found that HOT regions are associated with genes that control and define the developmental processes of the respective cell and tissue types. We also showed evidence of the developmental persistence of HOT regions at primitive enhancers and demonstrate unique signatures of HOT regions that distinguish them from typical enhancers and super-enhancers. Finally, we performed an epigenetic analysis to reveal the dynamic epigenetic regulation of HOT regions upon H1 differentiation. Taken together, our results provide a resource for the functional exploration of HOT regions and extend our understanding of the key roles of HOT regions in development and differentiation.
Long single-molecule reads can resolve the complexity of the Influenza virus composed of rare, closely related mutant variants
Authors: Artyomenko Alexander , Wu Nicholas C , Mangul Serghei , Eskin Eleazar , Sun Ren , Zelikovsky Alex 
Published: January 2016

AbstractAs a result of a high rate of mutations and recombination events, an RNA-virus exists as a heterogeneous “swarm” of mutant variants. The long read length offered by single-molecule sequencing technologies allows each mutant variant to be sequenced in a single pass. However, high error rate limits the ability to reconstruct heterogeneous viral population composed of rare, related mutant variants. In this paper, we present 2SNV, a method able to tolerate the high error-rate of the single-molecule protocol and reconstruct mutant variants. 2SNV uses linkage between single nucleotide variations to efficiently distinguish them from read errors. To benchmark the sensitivity of 2SNV, we performed a single-molecule sequencing experiment on a sample containing a titrated level of known viral mutant variants. Our method is able to accurately reconstruct clone with frequency of 0.2% and distinguish clones that differed in only two nucleotides distantly located on the genome. 2SNV outperforms existing methods for full-length viral mutant reconstruction. The open source implementation of 2SNV is freely available for download athttp://alan.cs.gsu.edu/NGS/?q=content/2snv
The Genealogical Sorting Index and species delimitations
Authors: Winter David J. , Trewick Steven A. , Waters Jon M. , Spencer Hamish G. 
Published: January 2016

AbstractThe Genealogical Sorting Index (gsi) has been widely used in species-delimitation studies, where it is usually interpreted as a measure of the degree to which each of several predefined groups of specimens display a pattern of divergent evolution in a phylogenetic tree. Here we show that thegsivalue obtained for a given group is highly dependent on the structure of the tree outside of the group of interest. By calculating thegsifrom simulated datasets we demonstrate this dependence undermines some of desirable properties of the statistic. We also review the use of thegsidelimitation studies, and show that thegsihas typically been used under scenarios in which it is expected to produce large and statistically significant results for samples that are not divergent from all other populations and thus should not be considered species. Our proposed solution to this problem performs better than thegsiin under these conditions. Nevertheless, we show that our modified approach can produce positive results for populations that are connected by substantial levels of gene flow, and are thus unlikely to represent distinct species. We stress that the properties ofgsimade clear in this manuscript must be taken into account if the statistic is used in species-delimitation studies. More generally, we argue that the results of genetic species-delimitation methods need to be interpreted in the light the biological and ecological setting of a study, and not treated as the final test applied to hypotheses generated by other data.
Robust Lineage Reconstruction from High-Dimensional Single-Cell Data
Authors: Giecold Gregory , Marco Eugenio , Trippa Lorenzo , Yuan Guo-Cheng 
Published: January 2016

AbstractSingle-cell gene expression data provide invaluable resources for systematic characterization of cellular hierarchy in multi-cellular organisms. However, cell lineage reconstruction is still often associated with significant uncertainty due to technological constraints. Such uncertainties have not been taken into account in current methods. We present ECLAIR, a novel computational method for the statistical inference of cell lineage relationships from single-cell gene expression data. ECLAIR uses an ensemble approach to improve the robustness of lineage predictions, and provides a quantitative estimate of the uncertainty of lineage branchings. We show that the application of ECLAIR to published datasets successfully reconstructs known lineage relationships and significantly improves the robustness of predictions. In conclusion, ECLAIR is a powerful bioinformatics tool for single-cell data analysis. It can be used for robust lineage reconstruction with quantitative estimate of prediction accuracy.
A gene regulatory network for apical organ neurogenesis and its spatial control in sea star embryos
Authors: Cheatle Jarvela Alys M. , Yankura Kristen A. , Hinman Veronica F. 
Published: January 2016

AbstractHow neural stem cells generate the correct number and type of differentiated neurons in appropriate places is an important question in developmental biology. Although nervous systems are diverse across phyla, many taxa have a larva that forms an anterior concentration of neurons, or apical organ. The number of neurons in these organs is highly variable. We show that neurogenesis in the sea star larvae begins withsoxc-expressing multipotent progenitors. These give rise to restricted progenitors that expresslhx2/9.Soxc- andlhx2/9-expressing cells are capable of undergoing both asymmetric divisions, which allow for progression towards a particular neural fate, and symmetric proliferative divisions. Nested concentric domains of gene expression along the anterior-posterior (AP) axis, which have been observed in a great diversity of metazoans, control neurogenesis in the sea star by promoting particular division modes and progression towards becoming a neuron. This work, therefore, explains how spatial patterning in the ectoderm controls progression of neurogenesis. Modification to the sizes of these AP territories provides a simple mechanism to explain the diversity of neuron number found among apical organs.Summary StatementThe progression of apical organ neurogenesis in the sea star is controlled by regulatory anterior-posterior patterning domains.
Discharge against medical advice from a Tehran emergency department
Authors: Hadadi Azar , Khashayar Patricia , Karbakhsh Mojgan , Vasheghani Farahani Ali 
Published: January 2016

Purpose
– The purpose of this paper is to identify the main reasons for discharge against medical advice (DAMA) in the emergency department (ED) of a teaching hospital in Tehran, Iran.

Design/methodology/approach
– This cross-sectional study was conducted on all the patients who left the ED of a referral teaching hospital against medical advice (AMA) in 2008. A questionnaire was filled out for each patient to determine the reasons behind patient leaving AMA.

Findings
– In total, 12.8 percent of the patients left the hospital AMA. Dissatisfaction with being observed in the ED, having a feeling of recovery and hospital personnel encouraging patients to leave the hospital were the main reasons for leaving the hospital AMA.

Practical implications
– Like many other centers, the results showed that poor communication skill and work overload were the main contributing factors to DAMA. The center managed to improve patient satisfaction and thus lowered DAMA rates following this study. Considering the similarities reported in the reports and that of other studies, it could be concluded that policy makers in other centers can also benefit from the results to adopt effective approaches to reduce DAMA rate.

Originality/value
– To the knowledge no study has evaluated the rate and the reasons behind DAMA in the Iranian EDs.