bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ciliate Paramecium is a natural reservoir of Legionella pneumophila
Authors: Watanabe Kenta , Nakao Ryo , Fujishima Masahiro , Tachibana Masato , Shimizu Takashi , Watarai Masahisa 
Published: April 2016

AbstractLegionella pneumophila, the causative agent of Legionnaires’ disease, replicates within alveolar macrophages and free-living amoebae. However, the lifestyle of L. pneumophila in the environment remains largely unknown. Here we established a novel natural host model of L. pneumophila endosymbiosis using the ciliate Paramecium caudatum. We also identified Legionella endosymbiosis-modulating factor A (LefA), which contributes to the change in life stage from endosymbiosis to host lysis, enabling escape to the environment. We isolated L. pneumophila strains from the environment and they exhibited cytotoxicity toward P. caudatum and induced host lysis. Acidification of the Legionella-containing vacuole (LCV) was inhibited and enlarged LCVs including numerous bacteria were observed in P. caudatum infected with L. pneumophila. An isogenic L. pneumophila lefA mutant exhibited decreased cytotoxicity toward P. caudatum and impaired the modification of LCVs, resulting in the establishment of endosymbiosis between them. Our results suggest that L. pneumophila may have a mechanism to switch their endosymbiosis in protistan hosts in the environment.
PFKFB3 Control of Cancer Growth by Responding to Circadian Clock Outputs
Authors: Chen Lili , Zhao Jiajia , Tang Qingming , Li Honggui , Zhang Chenguang , Yu Ran , Zhao Yan , Huo Yuqing , Wu Chaodong 
Published: April 2016

AbstractCircadian clock dysregulation promotes cancer growth. Here we show that PFKFB3, the gene that encodes for inducible 6-phosphofructo-2-kinase as an essential supporting enzyme of cancer cell survival through stimulating glycolysis, mediates circadian control of carcinogenesis. In patients with tongue cancers, PFKFB3 expression in both cancers and its surrounding tissues was increased significantly compared with that in the control and was accompanied with dys-regulated expression of core circadian genes. In the in vitro systems, SCC9 tongue cancer cells displayed rhythmic expression of PFKFB3 and CLOCK that was distinct from control KC cells. Furthermore, PFKFB3 expression in SCC9 cells was stimulated by CLOCK through binding and enhancing the transcription activity of PFKFB3 promoter. Inhibition of PFKFB3 at zeitgeber time 7 (ZT7), but not at ZT19 caused significant decreases in lactate production and in cell proliferation. Consistently, PFKFB3 inhibition in mice at circadian time (CT) 7, but not CT19 significantly reduced the growth of implanted neoplasms. Taken together, these findings demonstrate PFKFB3 as a mediator of circadian control of cancer growth, thereby highlighting the importance of time-based PFKFB3 inhibition in cancer treatment.
CRISPR-Cas9D10A nickase-based genotypic and phenotypic screening to enhance genome editing
Authors: Chiang Ting-Wei Will , le Sage Carlos , Larrieu Delphine , Demir Mukerrem , Jackson Stephen P. 
Published: April 2016

AbstractThe RNA-guided Cas9 nuclease is being widely employed to engineer the genomes of various cells and organisms. Despite the efficient mutagenesis induced by Cas9, off-target effects have raised concerns over the system’s specificity. Recently a “double-nicking” strategy using catalytic mutant Cas9D10A nickase has been developed to minimise off-target effects. Here, we describe a Cas9D10A-based screening approach that combines an All-in-One Cas9D10A nickase vector with fluorescence-activated cell sorting enrichment followed by high-throughput genotypic and phenotypic clonal screening strategies to generate isogenic knockouts and knock-ins highly efficiently, with minimal off-target effects. We validated this approach by targeting genes for the DNA-damage response (DDR) proteins MDC1, 53BP1, RIF1 and P53, plus the nuclear architecture proteins Lamin A/C, in three different human cell lines. We also efficiently obtained biallelic knock-in clones, using single-stranded oligodeoxynucleotides as homologous templates, for insertion of an EcoRI recognition site at the RIF1 locus and introduction of a point mutation at the histone H2AFX locus to abolish assembly of DDR factors at sites of DNA double-strand breaks. This versatile screening approach should facilitate research aimed at defining gene functions, modelling of cancers and other diseases underpinned by genetic factors and exploring new therapeutic opportunities.
Lysine fatty acylation promotes lysosomal targeting of TNF-α
Authors: Jiang Hong , Zhang Xiaoyu , Lin Hening 
Published: April 2016

AbstractTumor necrosis factor-α (TNF-α) is a proinflammation cytokine secreted by various cells. Understanding its secretive pathway is important to understand the biological functions of TNF-α and diseases associated with TNF-α. TNF-α is one of the first proteins known be modified by lysine fatty acylation (e.g. myristoylation). We previously demonstrated that SIRT6, a member of the mammalian sirtuin family of enzymes, can remove the fatty acyl modification on TNF-α and promote its secretion. However, the mechanistic details about how lysine fatty acylation regulates TNF-α secretion have been unknown. Here we present experimental data supporting that lysine fatty acylation promotes lysosomal targeting of TNF-α. The result is an important first step toward understanding the biological functions of lysine fatty acylation.
A multiple-shape memory polymer-metal composite actuator capable of programmable control, creating complex 3D motion of bending, twisting, and oscillation
Authors: Shen Qi , Trabia Sarah , Stalbaum Tyler , Palmre Viljar , Kim Kwang , Oh Il-Kwon 
Published: April 2016

AbstractDevelopment of biomimetic actuators has been an essential motivation in the study of smart materials. However, few materials are capable of controlling complex twisting and bending deformations simultaneously or separately using a dynamic control system. Here, we report an ionic polymer-metal composite actuator having multiple-shape memory effect, and is able to perform complex motion by two external inputs, electrical and thermal. Prior to the development of this type of actuator, this capability only could be realized with existing actuator technologies by using multiple actuators or another robotic system. This paper introduces a soft multiple-shape-memory polymer-metal composite (MSMPMC) actuator having multiple degrees-of-freedom that demonstrates high maneuverability when controlled by two external inputs, electrical and thermal. These multiple inputs allow for complex motions that are routine in nature, but that would be otherwise difficult to obtain with a single actuator. To the best of the authors’ knowledge, this MSMPMC actuator is the first solitary actuator capable of multiple-input control and the resulting deformability and maneuverability.
Catechol degradation on hematite/silica–gas interface as affected by gas composition and the formation of environmentally persistent free radicals
Authors: Li Hao , Guo Huiying , Pan Bo , Liao Shaohua , Zhang Di , Yang Xikun , Min Chungang , Xing Baoshan 
Published: April 2016

AbstractEnvironmentally persistent free radicals (EPFRs) formed on a solid particle surface have received increasing attention because of their toxic effects. However, organic chemical fate regulated by EPFRs has rarely been investigated, and this information may provide the missing link in understanding their environmental behavior. Previous studies have suggested that the reduction of transition metals is involved in EPFRs formation. We thus hypothesize that an oxidative environment may inhibit EPFRs formation in particle-gas interface, which will consequently release free radicals and accelerate organic chemical degradation. Our result indicates that a 1% hematite coating on a silica surface inhibited catechol degradation in N2, especially at low catechol loadings on solid particles (SCT). However, under an O2 environment, catechol degradation decreased when SCT was <1 μg/mg but increased when SCT was >1 μg/mg. Stable organic free radicals were observed in the N2 system with g factors in the 2.0035–2.0050 range, suggesting the dominance of oxygen-centered free radicals. The introduction of O2 into the catechol degradation system substantially decreased the free radical signals and decreased the Fe(II) content. These results were observed in both dark and light irradiation systems, indicating the ubiquitous presence of EPFRs in regulating the fate of organic chemicals.
The dynamics of carbon stored in xylem sapwood to drought-induced hydraulic stress in mature trees
Authors: Yoshimura Kenichi , Saiki Shin-Taro , Yazaki Kenichi , Ogasa Mayumi Y. , Shirai Makoto , Nakano Takashi , Yoshimura Jin , Ishida Atsushi 
Published: April 2016

AbstractClimate-induced forest die-off is widespread in multiple biomes, strongly affecting the species composition, function and primary production in forest ecosystems. Hydraulic failure and carbon starvation in xylem sapwood are major hypotheses to explain drought-induced tree mortality. Because it is difficult to obtain enough field observations on drought-induced mortality in adult trees, the current understanding of the physiological mechanisms for tree die-offs is still controversial. However, the simultaneous examination of water and carbon uses throughout dehydration and rehydration processes in adult trees will contribute to clarify the roles of hydraulic failure and carbon starvation in tree wilting. Here we show the processes of the percent loss of hydraulic conductivity (PLC) and the content of nonstructural carbohydrates (NSCs) of distal branches in woody plants with contrasting water use strategy. Starch was converted to soluble sugar during PLC progression under drought, and the hydraulic conductivity recovered following water supply. The conversion of NSCs is strongly associated with PLC variations during dehydration and rehydration processes, indicating that stored carbon contributes to tree survival under drought; further carbon starvation can advance hydraulic failure. We predict that even slow-progressing drought degrades forest ecosystems via carbon starvation, causing more frequent catastrophic forest die-offs than the present projection.
Broadband absorption enhancement in plasmonic nanoshells-based ultrathin microcrystalline-Si solar cells
Authors: Raja Waseem , Bozzola Angelo , Zilio Pierfrancesco , Miele Ermanno , Panaro Simone , Wang Hai , Toma Andrea , Alabastri Alessandro , De Angelis Francesco , Zaccaria Remo Proietti 
Published: April 2016

AbstractWith the objective to conceive a plasmonic solar cell with enhanced photocurrent, we investigate the role of plasmonic nanoshells, embedded within a ultrathin microcrystalline silicon solar cell, in enhancing broadband light trapping capability of the cell and, at the same time, to reduce the parasitic loss. The thickness of the considered microcrystalline silicon (μc-Si) layer is only ~1/6 of conventional μc-Si based solar cells while the plasmonic nanoshells are formed by a combination of silica and gold, respectively core and shell. We analyze the cell optical response by varying both the geometrical and optical parameters of the overall device. In particular, the nanoshells core radius and metal thickness, the periodicity, the incident angle of the solar radiation and its wavelength are varied in the widest meaningful ranges. We further explain the reason for the absorption enhancement by calculating the electric field distribution associated to resonances of the device. We argue that both Fabry-Pérot-like and localized plasmon modes play an important role in this regard.
Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women
Authors: Wiklund Petri , Zhang Xiaobo , Pekkala Satu , Autio Reija , Kong Lingjia , Yang Yifan , Keinänen-Kiukaanniemi Sirkka , Alen Markku , Cheng Sulin 
Published: April 2016

AbstractInsulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue.
Sphingosine 1-phosphate receptor 2 (S1P2) attenuates reactive oxygen species formation and inhibits cell death: implications for otoprotective therapy
Authors: Herr Deron R. , Reolo Marie J. Y. , Peh Yee Xin , Wang Wei , Lee Chang-Wook , Rivera Rich , Paterson Ian C. , Chun Jerold 
Published: April 2016

AbstractOtotoxic drugs, such as platinum-based chemotherapeutics, often lead to permanent hearing loss through apoptosis of neuroepithelial hair cells and afferent neurons of the cochlea. There is no approved therapy for preventing or reversing this process. Our previous studies identified a G protein-coupled receptor (GPCR), S1P2, as a potential mediator of otoprotection. We therefore sought to identify a pharmacological approach to prevent cochlear degeneration via activation of S1P2. The cochleae of S1pr2−/− knockout mice were evaluated for accumulation of reactive oxygen species (ROS) with a nitro blue tetrazolium (NBT) assay. This showed that loss of S1P2 results in accumulation of ROS that precedes progressive cochlear degeneration as previously reported. These findings were supported by in vitro cell-based assays to evaluate cell viability, induction of apoptosis and accumulation of ROS following activation of S1P2 in the presence of cisplatin. We show for the first time, that activation of S1P2 with a selective receptor agonist increases cell viability and reduces cisplatin-mediated cell death by reducing ROS. Cumulatively, these results suggest that S1P2 may serve as a therapeutic target for attenuating cisplatin-mediated ototoxicity.
MiR-299-5p regulates apoptosis through autophagy in neurons and ameliorates cognitive capacity in APPswe/PS1dE9 mice
Authors: Zhang Yueqi , Liu Chengeng , Wang Jinling , Li Qiliang , Ping Hong , Gao Shichao , Wang Peichang 
Published: April 2016

AbstractAbnormalities of autophagy can result in neurodegenerative disorders such as Alzheimer’s disease (AD). Nevertheless, the regulatory mechanisms of autophagy in AD are not well understood. Here, we describe our findings that microRNA (miR)-299-5p functions as an autophagy inhibitor by suppressing Atg5 and antagonizing caspase-dependent apoptosis. We observed decreased levels of miR-299-5p both in primary neurons under conditions of starvation and in hippocampi of APPswe/PS1dE9 mice. Additionally, low levels of miR-299-5p were observed in cerebrospinal fluid of AD patients. MiR-299-5p treatment resulted in attenuation of Atg5 and autophagy in primary neurons from APPswe/PS1dE9 mice, N2a cells and SH-SY5Y cells, whereas antagomiR-299-5p enhanced autophagy. Atg5 was verified as a direct target of miR-299-5p by dual luciferase reporter assays. Furthermore, transfection of miR-299-5p into primary hippocampal neurons caused the attenuation of caspase-mediated apoptosis, which was reversed upon starvation-induced autophagy. Inhibition of autophagy by shRNA knockdown of LC3β reduced apoptotic neuron death induced by antagomiR-299-5p. Injection of agomiR-299-5p into the cerebral ventricles of AD mice inhibited both autophagy and apoptosis and also improved the cognitive performance of mice. Overall, our results suggest that miR-299-5p modulates neuron survival programs by regulating autophagy. Thus, miR-299-5p serves as a potential neuroprotective factor in AD.
SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for β-cell mass assessments
Authors: Eter Wael A. , Parween Saba , Joosten Lieke , Frielink Cathelijne , Eriksson Maria , Brom Maarten , Ahlgren Ulf , Gotthardt Martin 
Published: April 2016

AbstractSingle Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, 111In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of 111In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers.
Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma
Authors: Lennon Frances E. , Cianci Gianguido C. , Kanteti Rajani , Riehm Jacob J. , Arif Qudsia , Poroyko Valeriy A. , Lupovitch Eitan , Vigneswaran Wickii , Husain Aliya , Chen Phetcharat , Liao James K. , Sattler Martin , Kindler Hedy L. , Salgia Ravi 
Published: April 2016

AbstractMalignant mesothelioma (MM), is an intractable disease with limited therapeutic options and grim survival rates. Altered metabolic and mitochondrial functions are hallmarks of MM and most other cancers. Mitochondria exist as a dynamic network, playing a central role in cellular metabolism. MM cell lines display a spectrum of altered mitochondrial morphologies and function compared to control mesothelial cells. Fractal dimension and lacunarity measurements are a sensitive and objective method to quantify mitochondrial morphology and most importantly are a promising predictor of response to mitochondrial inhibition. Control cells have high fractal dimension and low lacunarity and are relatively insensitive to mitochondrial inhibition. MM cells exhibit a spectrum of sensitivities to mitochondrial inhibitors. Low mitochondrial fractal dimension and high lacunarity correlates with increased sensitivity to the mitochondrial inhibitor metformin. Lacunarity also correlates with sensitivity to Mdivi-1, a mitochondrial fission inhibitor. MM and control cells have similar sensitivities to cisplatin, a chemotherapeutic agent used in the treatment of MM. Neither oxidative phosphorylation nor glycolytic activity, correlated with sensitivity to either metformin or mdivi-1. Our results suggest that mitochondrial inhibition may be an effective and selective therapeutic strategy in mesothelioma, and identifies mitochondrial morphology as a possible predictor of response to targeted mitochondrial inhibition.
Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis
Authors: Zhang Jinmai , Luo Huajie , Liu Hao , Ye Wei , Luo Ray , Chen Hai-Feng 
Published: April 2016

AbstractHistone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.
Structural insights into the Escherichia coli lysine decarboxylases and molecular determinants of interaction with the AAA+ ATPase RavA
Authors: Kandiah Eaazhisai , Carriel Diego , Perard Julien , Malet Hélène , Bacia Maria , Liu Kaiyin , Chan Sze W. S. , Houry Walid A. , Ollagnier de Choudens Sandrine , Elsen Sylvie , Gutsche Irina 
Published: April 2016

AbstractThe inducible lysine decarboxylase LdcI is an important enterobacterial acid stress response enzyme whereas LdcC is its close paralogue thought to play mainly a metabolic role. A unique macromolecular cage formed by two decamers of the Escherichia coli LdcI and five hexamers of the AAA+ ATPase RavA was shown to counteract acid stress under starvation. Previously, we proposed a pseudoatomic model of the LdcI-RavA cage based on its cryo-electron microscopy map and crystal structures of an inactive LdcI decamer and a RavA monomer. We now present cryo-electron microscopy 3D reconstructions of the E. coli LdcI and LdcC, and an improved map of the LdcI bound to the LARA domain of RavA, at pH optimal for their enzymatic activity. Comparison with each other and with available structures uncovers differences between LdcI and LdcC explaining why only the acid stress response enzyme is capable of binding RavA. We identify interdomain movements associated with the pH-dependent enzyme activation and with the RavA binding. Multiple sequence alignment coupled to a phylogenetic analysis reveals that certain enterobacteria exert evolutionary pressure on the lysine decarboxylase towards the cage-like assembly with RavA, implying that this complex may have an important function under particular stress conditions.