bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a new pathway that activates lumisterol in vivo to biologically active hydroxylumisterols
Authors: Slominski Andrzej T. , Kim Tae-Kang , Hobrath Judith V. , Janjetovic Zorica , Oak Allen S. W. , Postlethwaite Arnold , Lin Zongtao , Li Wei , Takeda Yukimasa , Jetten Anton M. , Tuckey Robert C. 
Published: September 2017

AbstractUsing LC/qTOF-MS we detected lumisterol, 20-hydroxylumisterol, 22-hydroxylumisterol, 24-hydroxylumisterol, 20,22-dihydroxylumisterol, pregnalumisterol, 17-hydroxypregnalumisterol and 17,20-dihydroxypregnalumisterol in human serum and epidermis, and the porcine adrenal gland. The hydroxylumisterols inhibited proliferation of human skin cells in a cell type-dependent fashion with predominant effects on epidermal keratinocytes. They also inhibited melanoma proliferation in both monolayer and soft agar. 20-Hydroxylumisterol stimulated the expression of several genes, including those associated with keratinocyte differentiation and antioxidative responses, while inhibiting the expression of others includingRORAandRORC. Molecular modeling and studies on VDRE-transcriptional activity excludes action through the genomic site of the VDR. However, their favorable interactions with the A-pocket in conjunction with VDR translocation studies suggest they may act on this non-genomic VDR site. Inhibition of RORα and RORγ transactivation activities in a Tet-on CHO cell reporter system, RORα co-activator assays and inhibition of (RORE)-LUC reporter activity in skin cells, in conjunction with molecular modeling, identified RORα and RORγ as excellent receptor candidates for the hydroxylumisterols. Thus, we have discovered a new biologically relevant, lumisterogenic pathway, the metabolites of which display biological activity. This opens a new area of endocrine research on the effects of the hydroxylumisterols on different pathways in different cells and the mechanisms involved.
Oscillations of ultra-weak photon emission from cancer and non-cancer cells stressed by culture medium change and TNF-α
Authors: Madl Pierre , Verwanger Thomas , Geppert Mark , Scholkmann Felix 
Published: September 2017

AbstractCells spontaneously emit photons in the UV to visible/near-infrared range (ultra-weak photon emission, UPE). Perturbations of the cells’ state cause changes in UPE (evoked UPE). The aim of the present study was to analyze the evoked UPE dynamics of cells caused by two types of cell perturbations (stressors): (i) a cell culture medium change, and (ii) application of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α). Four types of human cell lines were used (squamous cell carcinoma cells, A431; adenocarcinomic alveolar basal epithelial cells, A549; p53-deficient keratinocytes, HaCaT, and cervical cancer cells, HeLa). In addition to the medium change, TNF-α was applied at different concentrations (5, 10, 20, and 40 ng/mL) and UPE measurements were performed after incubation times of 0, 30, 60, 90 min, 2, 5, 12, 24, 48 h. It was observed that (i) the change of cell culture medium (without added TNF-α) induces a cell type-specific transient increase in UPE with the largest UPE increase observed in A549 cells, (ii) the addition of TNF-α induces a cell type-specific and dose-dependent change in UPE, and (iii) stressed cell cultures in general exhibit oscillatory UPE changes.
Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity
Authors: Kapoor Abhijeet , Martinez-Rosell Gerard , Provasi Davide , de Fabritiis Gianni , Filizola Marta 
Published: September 2017

AbstractWhile the therapeutic effect of opioids analgesics is mainly attributed to µ-opioid receptor (MOR) activation leading to G protein signaling, their side effects have mostly been linked to β-arrestin signaling. To shed light on the dynamic and kinetic elements underlying MOR functional selectivity, we carried out close to half millisecond high-throughput molecular dynamics simulations of MOR bound to a classical opioid drug (morphine) or a potent G protein-biased agonist (TRV-130). Statistical analyses of Markov state models built using this large simulation dataset combined with information theory enabled, for the first time: a) Identification of four distinct metastable regions along the activation pathway, b) Kinetic evidence of a different dynamic behavior of the receptor bound to a classical or G protein-biased opioid agonist, c) Identification of kinetically distinct conformational states to be used for the rational design of functionally selective ligands that may eventually be developed into improved drugs; d) Characterization of multiple activation/deactivation pathways of MOR, and e) Suggestion from calculated transition timescales that MOR conformational changes are not the rate-limiting step in receptor activation.
Laminarinase from Flavobacterium sp. reveals the structural basis of thermostability and substrate specificity
Authors: Qin Hui-Min , Miyakawa Takuya , Inoue Akira , Nakamura Akira , Nishiyama Ryuji , Ojima Takao , Tanokura Masaru 
Published: September 2017

AbstractLaminarinase from Flavobacterium sp. strain UMI-01, a new member of the glycosyl hydrolase 16 family of a marine bacterium associated with seaweeds, mainly degrades β-1,3-glucosyl linkages of β-glucan (such as laminarin) through the hydrolysis of glycosidic bonds. We determined the crystal structure of ULam111 at 1.60-Å resolution to understand the structural basis for its thermostability and substrate specificity. A calcium-binding motif located on the opposite side of the β-sheet from catalytic cleft increased its degrading activity and thermostability. The disulfide bridge Cys31-Cys34, located on the β2-β3 loop near the substrate-binding site, is responsible for the thermostability of ULam111. The substrates of β-1,3-linked laminarin and β-1,3-1,4-linked glucan bound to the catalytic cleft in a completely different mode at subsite -3. Asn33 and Trp113, together with Phe212, formed hydrogen bonds with preferred substrates to degrade β-1,3-linked laminarin based on the structural comparisons. Our structural information provides new insights concerning thermostability and substrate recognition that will enable the design of industrial biocatalysts.
Unexpected viscoelastic deformation of tight sandstone: Insights and predictions from the fractional Maxwell model
Authors: Ding Xiang , Zhang Guangqing , Zhao Bo , Wang Yan 
Published: September 2017

AbstractTight gas is one important unconventional hydrocarbon resource that is stored in tight sandstone, whose mechanical property greatly influences the tight gas production process and is commonly believed to be simply elastic when designing the stimulation plan. However, the experimental evidence provided in this work surprisingly shows that tight sandstone can deform in a viscoelastic way. Such an unexpected observation poses a challenge in accurately modelling the deformation process. We solve this problem by adopting the fractional Maxwell model to successfully derive the constitutive equation of tight sandstone, based on which not only all the experimental data can be interpreted quantitatively, but also reasonable and consistent predictions as to tight sandstone’s long-term deformation behaviour can be made. We then investigate the typicality of our results in China’s Changqing oilfield, which is one major centre of tight gas production and where the rock samples for experiments are obtained. It is estimated that a non-negligible portion of 18% tight sandstone samples in this area will probably display viscoelasticity. Finally, our work implies that the mechanical properties of other materials may also need further scrutiny to possibly uncover any unexpected behaviour, overlooking which may result in misleading predictions.
Mechanistic insight into internal conversion process within Q-bands of chlorophyll a
Authors: Meneghin Elena , Leonardo Cristina , Volpato Andrea , Bolzonello Luca , Collini Elisabetta 
Published: September 2017

AbstractThe non-radiative relaxation of the excitation energy from higher energy states to the lowest energy state in chlorophylls is a crucial preliminary step for the process of photosynthesis. Despite the continuous theoretical and experimental efforts to clarify the ultrafast dynamics of this process, it still represents the object of an intense investigation because the ultrafast timescale and the congestion of the involved states makes its characterization particularly challenging. Here we exploit 2D electronic spectroscopy and recently developed data analysis tools to provide more detailed insights into the mechanism of internal conversion within the Q-bands of chlorophyll a. The measurements confirmed the timescale of the overall internal conversion rate (170 fs) and captured the presence of a previously unidentified ultrafast (40 fs) intermediate step, involving vibronic levels of the lowest excited state.
Characterization of influenza A viruses with polymorphism in PB2 residues 701 and 702
Authors: Chin Alex W. H. , Leong Nathaniel K. C. , Nicholls John M. , Poon Leo L. M. 
Published: September 2017

AbstractThe 701 and 702 positions of influenza PB2 polymerase subunit are previously shown to have roles on host range. Limited polymorphisms at these two residues are identified in natural isolates, thereby limiting the study of their role in the polymerase. In this study, we generated 31 viable viruses by random mutagenesis at this region, indicating that these positions can tolerate a wide range of amino acids. These mutants demonstrated varying polymerase activities and viral replication rates in mammalian and avian cells. Notably, some mutants displayed enhanced polymerase activity, yet their replication kinetics were comparable to the wild-type virus. Surface electrostatic charge predication on the PB2 structural model revealed that the viral polymerase activity in mammalian cells generally increases as this region becomes more positively charged. One of the mutants (701A/702E) showed much reduced pathogenicity in mice while others had a pathogenicity similar to the wild-type level. Distinct tissue tropisms of the PB2-701/702 mutants were observed in infected chicken embryos. Overall, this study demonstrates that the PB2-701/702 region has a high degree of sequence plasticity and sequence changes in this region can alter virus phenotypes in vitro and in vivo.
Predicted effects of observed changes in the mRNA and microRNA transcriptome of lung neutrophils during S. pneumoniae pneumonia in mice
Authors: Gomez John C. , Dang Hong , Kanke Matthew , Hagan Robert S. , Mock Jason R. , Kelada Samir N. P. , Sethupathy Praveen , Doerschuk Claire M. 
Published: September 2017

AbstractThe complex role of neutrophils in modulating the inflammatory response is increasingly appreciated. Our studies profiled the expression of mRNAs and microRNAs (miRs) in lung neutrophils in mice during S. pneumoniae pneumonia and performed in depth in silico analyses. Lung neutrophils were isolated 24 hours after intratracheal instillation of PBS or S. pneumoniae, and differentially expressed (DE) mRNAs and miRs were identified. Lung neutrophils from mice with S. pneumoniae pneumonia contained 4127 DE mRNAs, 36% of which were upregulated at least 2-fold. During pneumonia, lung neutrophils increase expression of pattern recognition receptors, receptors for inflammatory mediators, transcription factors including NF-κB and AP-1, Nrf2 targets, cytokines, chemokines and other inflammatory mediators. Interestingly, neutrophils responded to Type I interferons, whereas they both produced and responded to Type II interferon. Expression of regulators of the inflammatory and immune response was verified at the mRNA and protein level. Of approximately 1100 miRs queried, 31 increased and 67 decreased more than 2-fold in neutrophils from S. pneumoniae pneumonia. Network analyses of potential DE miR-target DE mRNA interactions revealed candidate key regulatory miRs. Thus, S. pneumoniae modulates mRNA and miR expression by lung neutrophils, increasing their ability to respond and facilitating host defense.
Adolescent THC Exposure Causes Enduring Prefrontal Cortical Disruption of GABAergic Inhibition and Dysregulation of Sub-Cortical Dopamine Function
Authors: Renard Justine , Szkudlarek Hanna J. , Kramar Cecilia P. , Jobson Christina E. L. , Moura Kyra , Rushlow Walter J. , Laviolette Steven R. 
Published: September 2017

AbstractChronic adolescent marijuana use has been linked to the later development of psychiatric diseases such as schizophrenia. GABAergic hypofunction in the prefrontal cortex (PFC) is a cardinal pathological feature of schizophrenia and may be a mechanism by which the PFC loses its ability to regulate sub-cortical dopamine (DA) resulting in schizophrenia-like neuropsychopathology. In the present study, we exposed adolescent rats to Δ-9-tetra-hydrocannabinol (THC), the psychoactive component in marijuana. At adulthood, we characterized the functionality of PFC GABAergic neurotransmission and its regulation of sub-cortical DA function using molecular, behavioral andin-vivoelectrophysiological analyses. Our findings revealed a persistent attenuation of PFC GABAergic function combined with a hyperactive neuronal state in PFC neurons and associated disruptions in cortical gamma oscillatory activity. These PFC abnormalities were accompanied by hyperactive DAergic neuronal activity in the ventral tegmental area (VTA) and behavioral and cognitive abnormalities similar to those observed in psychiatric disorders. Remarkably, these neuronal and behavioral effects were reversed by pharmacological activation of GABAAreceptors in the PFC. Together, these results identify a mechanistic link between dysregulated frontal cortical GABAergic inhibition and sub-cortical DAergic dysregulation, characteristic of well-established neuropsychiatric endophenotypes.
Clinical characteristics and risk factors for developing bone metastases in patients with breast cancer
Authors: Chen Wen-Zhao , Shen Jun-Feng , Zhou Yang , Chen Xuan-Yin , Liu Jia-Ming , Liu Zhi-Li 
Published: September 2017

AbstractThe risk factors for predicting bone metastases in patients with breast cancer are still controversial. Here, a total of 2133 patients with breast cancer, including 327 with bone metastases (15.33%) and 1806 without bone metastases (84.67%) were retrospective reviewed from January 2005 to December 2015. The spine was found to be the most common site for bone metastases, followed by ribs (57.5%), pelvis (54.1%) and sternum (44.3%). The results indicated that axillary lymph node metastases and the concentrations of CA125, CA153, ALP and hemoglobin were the independent risk factors for bone metastases in patients with breast cancer. The receiver operating characteristics (ROC) curves showed that combined axillary lymph node metastases, high CA153 and ALP, with low hemoglobin were the most accurate biomarkers for predicting bone metastases in breast cancer [area under the curve = 0.900], and the sensitivity and specificity for the prediction were 78.5% and 87.8%, respectively. Therefore, breast cancer patients with more axillary lymph node metastases, high serum concentrations of CA125, CA153, ALP and low level of hemoglobin were closely related to bone metastases. Combined axillary lymph node metastases, CA153, ALP with hemoglobin have the highest predictive accuracy for bone metastases in breast cancer.
Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration
Authors: Wang Junling , Han Xuemei , Leu Nicolae Adrian , Sterling Stephanie , Kurosaka Satoshi , Fina Marie , Lee Virginia M. , Dong Dawei W. , Yates John R. , Kashina Anna 
Published: September 2017

AbstractAlpha synuclein (α-syn) is a central player in neurodegeneration, but the mechanisms triggering its pathology are not fully understood. Here we found that α-syn is a highly efficient substrate for arginyltransferase ATE1 and is arginylated in vivo by a novel mid-chain mechanism that targets the acidic side chains of E46 and E83. Lack of arginylation leads to increased α-syn aggregation and causes the formation of larger pathological aggregates in neurons, accompanied by impairments in its ability to be cleared via normal degradation pathways. In the mouse brain, lack of arginylation leads to an increase in α-syn’s insoluble fraction, accompanied by behavioral changes characteristic for neurodegenerative pathology. Our data show that lack of arginylation in the brain leads to neurodegeneration, and suggests that α-syn arginylation can be a previously unknown factor that facilitates normal α-syn folding and function in vivo.
Pixelated Checkerboard Metasurface for Ultra-Wideband Radar Cross Section Reduction
Authors: Haji-Ahmadi Mohammad-Javad , Nayyeri Vahid , Soleimani Mohammad , Ramahi Omar M. 
Published: September 2017

AbstractIn this paper we designed and fabricated a metasurface working as a radar cross section (RCS) reducer over an ultra wide band of frequency from 3.8 to 10.7 GHz. The designed metasurface is a chessboard-like surface made of alternating tiles, with each tile composed of identical unit cells. We develop a novel, simple, highly robust and fully automated approach for designing the unit cells. First, a topology optimization algorithm is used to engineer the shape of the two unit cells. The area of each unit cell is pixelated. A particle swarm optimization algorithm is applied wherein each pixel corresponds to a bit having a binary value of 1 or 0 indicating metallization or no metallization. With the objective of reducing the RCS over a specified frequency range, the optimization algorithm is then linked to a full wave three-dimensional electromagnetic simulator. To validate the design procedure, a surface was designed, fabricated and experimentally tested showing significantly enhanced performance than previous works. Additionally, angular analysis is also presented showing good stability and wide-angle behavior of the designed RCS reducer. The automated design procedure has a wide range of applications and can be easily extended to design surfaces for antennas, energy harvesters, noise mitigation in electronic circuit boards amongst others.
Highly Effective Broad Spectrum Chimeric Larvicide That Targets Vector Mosquitoes Using a Lipophilic Protein
Authors: Bideshi Dennis K. , Park Hyun-Woo , Hice Robert H. , Wirth Margaret C. , Federici Brian A. 
Published: September 2017

AbstractTwo mosquitocidal bacteria, Bacillus thuringiensis subsp. israelensis (Bti) and Lysinibacillus sphaericus (Ls) are the active ingredients of commercial larvicides used widely to control vector mosquitoes. Bti’s efficacy is due to synergistic interactions among four proteins, Cry4Aa, Cry4Ba, Cry11Aa, and Cyt1Aa, whereas Ls’s activity is caused by Bin, a heterodimer consisting of BinA, the toxin, and BinB, a midgut-binding protein. Cyt1Aa is lipophilic and synergizes Bti Cry proteins by increasing midgut binding. We fused Bti’s Cyt1Aa to Ls’s BinA yielding a broad-spectrum chimeric protein highly mosquitocidal to important vector species including Anopheles gambiae, Culex quinquefasciatus, and Aedes aegypti, the latter an important Zika and Dengue virus vector insensitive to Ls Bin. Aside from its vector control potential, our bioassay data, in contrast to numerous other reports, provide strong evidence that BinA does not require conformational interactions with BinB or microvillar membrane lipids to bind to its intracellular target and kill mosquitoes.
Characterization and Identification of a woody lesion mimic mutant lmd, showing defence response and resistance to Alternaria alternate in birch
Authors: Li Ranhong , Chen Su , Liu Guifeng , Han Rui , Jiang Jing 
Published: September 2017

AbstractLesion mimic mutants (LMM) usually show spontaneous cell death and enhanced defence responses similar to hypersensitive response (HR) in plants. Many LMM have been reported in rice, wheat, maize, barley, Arabidopsis, etc., but little was reported in xylophyta. BpGH3.5 is an early auxin-response factor which regulates root elongation in birch. Here, we found a T-DNA insertion mutant in a BpGH3.5 transgenic line named lmd showing typical LMM characters and early leaf senescence in Betula platyphylla × B. pendula. lmd showed H2O2 accumulation, increased SA level and enhanced resistance to Alternaria alternate, compared with oe21 (another BpGH3.5 transgenic line) and NT (non-transgenic line). Cellular structure observation showed that programmed cell death occurred in lmd leaves. Stereomicroscope observation and Evans’ blue staining indicated that lmd is a member of initiation class of LMM. Transcriptome analysis indicated that defence response-related pathways were enriched. Southern-blot indicated that there were two insertion sites in lmd genome. Genome re-sequencing and thermal asymmetric interlaced PCR (TAIL-PCR) confirmed the two insertion sites, one of which is a T-DNA insertion in the promoter of BpEIL1 that may account for the lesion mimic phenotype. This study will benefit future research on programmed cell death, HR and disease resistance in woody plants.
Analysis and comparison of the wolf microbiome under different environmental factors using three different data of Next Generation Sequencing
Authors: Wu Xiaoyang , Zhang Huanxin , Chen Jun , Shang Shuai , Yan Jiakuo , Chen Yao , Tang Xuexi , Zhang Honghai 
Published: September 2017

AbstractNext Generation Sequencing has been widely used to characterize the prevalence of fecal bacteria in many different species. In this study, we attempted to employ a low-cost and high-throughput sequencing model to discern information pertaining to the wolf microbiota. It is hoped that this model will allow researchers to elucidate potential protective factors in relation to endangered wolf species. We propose three high-throughput sequencing models to reveal information pertaining to the micro-ecology of the wolf. Our analyses advised that, among the three models, more than 100,000 sequences are more appropriate to retrieve the communities’ richness and diversity of micro-ecology. In addition, the top five wolf microbiome OTUs (99%) were members of the following five phyla: Bacteroidetes, Fusobacteria, Firmicutes, Proteobacteria, and Actinobacteria. While Alloprevotella, Clostridium_sensu_stricto_1, Anaerobiospirillum, Faecalibactreium and Streptococcus were shared by all samples, their relative abundances were differentially represented between domestic dogs and other wolves. Our findings suggest that altitude, human interference, age, and climate all contribute towards the micro-ecology of the wolf. Specifically, we observed that genera Succinivibrio and Turicibacter are significantly related to altitude and human interference (including hunting practices).