bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Metabolic Acidosis Activates Renal Tubular Sodium Chloride Cotransporter through Angiotension II-dependent WNK4-SPAK Phosphorylation Pathway
Authors: Fang Yu-Wei , Yang Sung-Sen , Cheng Chih-Jen , Tseng Min-Hua , Hsu Hui-Min , Lin Shih-Hua 
Published: January 2016

AbstractThe mechanism by which chronic metabolic acidosis (CMA) regulates sodium (Na+)-chloride (Cl−) cotransporter (NCC) in the renal distal convoluted tubules remains unexplored. We examined the role of STE20/SPS1-related proline/alanine-rich kinase (SPAK) and with-no-lysine kinase 4 (WNK4) on expression of NCC in mouse models of CMA. CMA was induced by NH4Cl in wild type mice (WTA mice), SPAK and WNK4 knockout mice. The quantities of Ncc mRNA, expression of total NCC, phosphorylated (p)-NCC, SPAK and WNK4 in the kidneys as well as NCC inhibition with hydrochlorothiazide and Na+ balance were evaluated. Relative to WT mice, WTA mice had similar levels of Ncc mRNA, but increased expression of total and p-NCC, SPAK and WNK4 and an exaggerated response to hydrochlorothiazide which could not be observed in SPAK or WNK4 knockout mice with CMA. In WTA mice, increased plasma renin activity, aldosterone and angiotensin II concentrations accompanied by a significantly negative Na+ balance. High Na+ diet abolished the enhanced NCC expression in WTA mice. Furthermore, an angiotensin II type 1 receptor blocker rather than a mineralocorticoid receptor antagonist exerted a marked inhibition on Na+ reabsorption and NCC phosphorylation in WTA mice. CMA increases WNK4-SPAK-dependent NCC phosphorylation and appears to be secondary to previous natriuresis with volume-dependent angiotensin II activation.
Immune cell impact of three differently coated lipid nanocapsules: pluronic, chitosan and polyethylene glycol
Authors: Farace Cristiano , Sánchez-Moreno Paola , Orecchioni Marco , Manetti Roberto , Sgarrella Francesco , Asara Yolande , Peula-García José M. , Marchal Juan A. , Madeddu Roberto , Delogu Lucia G. 
Published: January 2016

AbstractLipid nanocapsules (NCs) represent promising tools in clinical practice for diagnosis and therapy applications. However, the NC appropriate functionalization is essential to guarantee high biocompatibility and molecule loading ability. In any medical application, the immune system-impact of differently functionalized NCs still remains to be fully understood. A comprehensive study on the action exerted on human peripheral blood mononuclear cells (PBMCs) and major immune subpopulations by three different NC coatings: pluronic, chitosan and polyethylene glycol-polylactic acid (PEG) is reported. After a deep particle characterization, the uptake was assessed by flow-cytometry and confocal microscopy, focusing then on apoptosis, necrosis and proliferation impact in T cells and monocytes. Cell functionality by cell diameter variations, different activation marker analysis and cytokine assays were performed. We demonstrated that the NCs impact on the immune cell response is strongly correlated to their coating. Pluronic-NCs were able to induce immunomodulation of innate immunity inducing monocyte activations. Immunomodulation was observed in monocytes and T lymphocytes treated with Chitosan-NCs. Conversely, PEG-NCs were completely inert. These findings are of particular value towards a pre-selection of specific NC coatings depending on biomedical purposes for pre-clinical investigations; i.e. the immune-specific action of particular NC coating can be excellent for immunotherapy applications.
Distinct effects of β1 integrin on cell proliferation and cellular signaling in MDA-MB-231 breast cancer cells
Authors: Hou Sicong , Isaji Tomoya , Hang Qinglei , Im Sanghun , Fukuda Tomohiko , Gu Jianguo 
Published: January 2016

AbstractAn aberrant expression of integrin β1 has been implicated in breast cancer progression. Here, we compared the cell behaviors of wild-type (WT), β1 gene deleted (KO) and β1 gene restored (Res) MDA-MB-231 cells. Surprisingly, the expression of β1 exhibited opposite effects on cell proliferation. These effects were dependent on cell densities and they showed an up-regulation of cell proliferation when cells were cultured under sparse conditions and a down-regulation of cell growth under dense conditions. By comparison with WT cells, the phosphorylation levels of ERK in KO cells were consistently suppressed under sparse culture conditions, but consistently up-regulated under dense culture conditions. The phosphorylation levels of EGFR were increased in the KO cells. By contrast, the phosphorylation levels of AKT were decreased in the KO cells. The abilities for both colony and tumor formation were significantly suppressed in the KO cells, suggesting that β1 plays an important role in cell survival signaling for tumorigenesis. These aberrant phenotypes in the KO cells were rescued in the Res cells. Taken together, these results clearly showed the distinct roles of β1 in cancer cells: the inhibition of cell growth and the promotion of cell survival, which may shed light on cancer therapies.
Electronic resonances in broadband stimulated Raman spectroscopy
Authors: Batignani G. , Pontecorvo E. , Giovannetti G. , Ferrante C. , Fumero G. , Scopigno T. 
Published: January 2016

AbstractSpontaneous Raman spectroscopy is a formidable tool to probe molecular vibrations. Under electronic resonance conditions, the cross section can be selectively enhanced enabling structural sensitivity to specific chromophores and reaction centers. The addition of an ultrashort, broadband femtosecond pulse to the excitation field allows for coherent stimulation of diverse molecular vibrations. Within such a scheme, vibrational spectra are engraved onto a highly directional field and can be heterodyne detected overwhelming fluorescence and other incoherent signals. At variance with spontaneous resonance Raman, however, interpreting the spectral information is not straightforward, due to the manifold of field interactions concurring to the third order nonlinear response. Taking as an example vibrational spectra of heme proteins excited in the Soret band, we introduce a general approach to extract the stimulated Raman excitation profiles from complex spectral lineshapes. Specifically, by a quantum treatment of the matter through density matrix description of the third order nonlinear polarization, we identify the contributions which generate the Raman bands, by taking into account for the cross section of each process.
A Flow-Through Cell Electroporation Device for Rapidly and Efficiently Transfecting Massive Amounts of Cells in vitro and ex vivo
Authors: Zhao Deyao , Huang Dong , Li Yang , Wu Mengxi , Zhong Wenfeng , Cheng Qiang , Wang Xiaoxia , Wu Yidi , Zhou Xiao , Wei Zewen , Li Zhihong , Liang Zicai 
Published: January 2016

AbstractContinuous cell electroporation is an appealing non-viral approach for genetically transfecting a large number of cells. Yet the traditional macro-scale devices suffer from the unsatisfactory transfection efficiency and/or cell viability due to their high voltage, while the emerging microfluidic electroporation devices is still limited by their low cell processing speed. Here we present a flow-through cell electroporation device integrating large-sized flow tube and small-spaced distributed needle electrode array. Relatively large flow tube enables high flow rate, simple flow characterization and low shear force, while well-organized needle array electrodes produce an even-distributed electric field with low voltage. Thus the difficulties for seeking the fine balance between high flow rate and low electroporation voltage were steered clear. Efficient in vitro electrotransfection of plasmid DNA was demonstrated in several hard-to-transfect cell lines. Furthermore, we also explored ex vivo electroporated mouse erythrocyte as the carrier of RNA. The strong ability of RNA loading and short exposure time of freshly isolated cells jointly ensured a high yield of valid carrier erythrocytes, which further successfully delivered RNA into targeted tissue. Both in vitro and ex vivo electrotransfection could be accomplished at high cell processing speed (20 million cells per minute) which remarkably outperforms previous devices.
Structural Variant Detection by Large-scale Sequencing Reveals New Evolutionary Evidence on Breed Divergence between Chinese and European Pigs
Authors: Zhao Pengju , Li Junhui , Kang Huimin , Wang Haifei , Fan Ziyao , Yin Zongjun , Wang Jiafu , Zhang Qin , Wang Zhiquan , Liu Jian-Feng 
Published: January 2016

AbstractIn this study, we performed a genome-wide SV detection among the genomes of thirteen pigs from diverse Chinese and European originated breeds by next genetation sequencing and constrcuted a single-nucleotide resolution map involving 56,930 putative SVs. We firstly identified a SV hotspot spanning 35 Mb region on the X chromosome specifically in the genomes of Chinese originated individuals. Further scrutinizing this region by large-scale sequencing data of extra 111 individuals, we obtained the confirmatory evidence on our initial finding. Moreover, thirty five SV-related genes within the hotspot region, being of importance for reproduction ability, rendered significant different evolution rates between Chinese and European originated breeds. The SV hotspot identified herein offers a novel evidence for assessing phylogenetic relationships, as well as likely explains the genetic difference of corresponding phenotypes and features, among Chinese and European pig breeds. Furthermore, we employed various SVs to infer genetic structure of individuls surveyed. We found SVs can clearly detect the difference of genetic background among individuals. This clues us that genome-wide SVs can capture majority of geneic variation and be applied into cladistic analyses. Characterizing whole genome SVs demonstrated that SVs are significantly enriched/depleted with various genomic features.
Transgenic FingRs for Live Mapping of Synaptic Dynamics in Genetically-Defined Neurons
Authors: Son Jong-Hyun , Keefe Matthew D. , Stevenson Tamara J. , Barrios Joshua P. , Anjewierden Scott , Newton James B. , Douglass Adam D. , Bonkowsky Joshua L. 
Published: January 2016

AbstractTools for genetically-determined visualization of synaptic circuits and interactions are necessary to build connectomics of the vertebrate brain and to screen synaptic properties in neurological disease models. Here we develop a transgenic FingR (fibronectin intrabodies generated by mRNA display) technology for monitoring synapses in live zebrafish. We demonstrate FingR labeling of defined excitatory and inhibitory synapses and show FingR applicability for dissecting synapse dynamics in normal and disease states. Using our system we show that chronic hypoxia, associated with neurological defects in preterm birth, affects dopaminergic neuron synapse number depending on the developmental timing of hypoxia.
Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment
Authors: Aini Hailati , Itaka Keiji , Fujisawa Ayano , Uchida Hirokuni , Uchida Satoshi , Fukushima Shigeto , Kataoka Kazunori , Saito Taku , Chung Ung-il , Ohba Shinsuke 
Published: January 2016

AbstractOsteoarthritis (OA) is a chronic degenerative joint disease and a major health problem in the elderly population. No disease-modifying osteoarthritis drug (DMOAD) has been made available for clinical use. Here we present a disease-modifying strategy for OA, focusing on messenger RNA (mRNA) delivery of a therapeutic transcription factor using polyethylene glycol (PEG)-polyamino acid block copolymer-based polyplex nanomicelles. When polyplex nanomicelles carrying the cartilage-anabolic, runt-related transcription factor (RUNX) 1 mRNA were injected into mouse OA knee joints, OA progression was significantly suppressed compared with the non-treatment control. Expressions of cartilage-anabolic markers and proliferation were augmented in articular chondrocytes of the RUNX1-injected knees. Thus, this study provides a proof of concept of the treatment of degenerative diseases such as OA by the in situ mRNA delivery of therapeutic transcription factors; the presented approach will directly connect basic findings on disease-protective or tissue-regenerating factors to disease treatment.
Bixin protects mice against ventilation-induced lung injury in an NRF2-dependent manner
Authors: Tao Shasha , Rojo de la Vega Montserrat , Quijada Hector , Wondrak Georg T. , Wang Ting , Garcia Joe G. N. , Zhang Donna D. 
Published: January 2016

AbstractMechanical ventilation (MV) is a therapeutic intervention widely used in the clinic to assist patients that have difficulty breathing due to lung edema, trauma, or general anesthesia. However, MV causes ventilator-induced lung injury (VILI), a condition characterized by increased permeability of the alveolar-capillary barrier that results in edema, hemorrhage and neutrophil infiltration, leading to exacerbated lung inflammation and oxidative stress. This study explored the feasibility of using bixin, a canonical NRF2 inducer identified during the current study, to ameliorate lung damage in a murine VILI model. In vitro, bixin was found to activate the NRF2 signaling pathway through blockage of ubiquitylation and degradation of NRF2 in a KEAP1-C151 dependent manner; intraperitoneal (IP) injection of bixin led to pulmonary upregulation of the NRF2 response in vivo. Remarkably, IP administration of bixin restored normal lung morphology and attenuated inflammatory response and oxidative DNA damage following MV. This observed beneficial effect of bixin derived from induction of the NRF2 cytoprotective response since it was only observed in Nrf2+/+ but not in Nrf2−/− mice. This is the first study providing proof-of-concept that NRF2 activators can be developed into pharmacological agents for clinical use to prevent patients from lung injury during MV treatment.
Visualization of terahertz surface waves propagation on metal foils
Authors: Wang Xinke , Wang Sen , Sun Wenfeng , Feng Shengfei , Han Peng , Yan Haitao , Ye Jiasheng , Zhang Yan 
Published: January 2016

AbstractExploitation of surface plasmonic devices (SPDs) in the terahertz (THz) band is always beneficial for broadening the application potential of THz technologies. To clarify features of SPDs, a practical characterization means is essential for accurately observing the complex field distribution of a THz surface wave (TSW). Here, a THz digital holographic imaging system is employed to coherently exhibit temporal variations and spectral properties of TSWs activated by a rectangular or semicircular slit structure on metal foils. Advantages of the imaging system are comprehensively elucidated, including the exclusive measurement of TSWs and fall-off of the time consumption. Numerical simulations of experimental procedures further verify the imaging measurement accuracy. It can be anticipated that this imaging system will provide a versatile tool for analyzing the performance and principle of SPDs.
Bcl6 Sets a Threshold for Antiviral Signaling by Restraining IRF7 Transcriptional Program
Authors: Xu Feng , Kang Yanhua , Zhuang Ningtong , Lu Zhe , Zhang Hang , Xu Dakang , Ding Yina , Yin Hongping , Shi Liyun 
Published: January 2016

AbstractThe coordination of restraining and priming of antiviral signaling constitute a fundamental aspect of immunological functions. However, we currently know little about the molecular events that can translate the pathogenic cues into the appropriate code for antiviral defense. Our present study reports a specific role of B cell lymphoma (Bcl)6 as a checkpoint in the initiation of the host response to cytosolic RNA viruses. Remarkably, Bcl6 specifically binds to the interferon-regulatory factor (IRF)7 loci and restrains its transcription, thereby functioning as a negative regulator for interferon (IFN)-β production and antiviral responses. The signal-controlled turnover of the Bcl6, most likely mediated by microRNA-127, coordinates the antiviral response and inflammatory sequelae. Accordingly, de-repression of Bcl6 resulted in a phenotypic conversion of macrophages into highly potent IFN-producing cells and rendered mice more resistant to pathogenic RNA virus infection. The failure to remove the Bcl6 regulator, however, impedes the antiviral signaling and exaggerates viral pneumonia in mice. We thus reveal a novel key molecular checkpoint to orchestrate antiviral innate immunity.
Inactivation of Ricin Toxin by Nanosecond Pulsed Electric Fields Including Evidences from Cell and Animal Toxicity
Authors: Wei Kai , Li Wei , Gao Shan , Ji Bin , Zang Yating , Su Bo , Wang Kaile , Yao Maosheng , Zhang Jue , Wang Jinglin 
Published: January 2016

AbstractRicin is one of the most toxic and easily produced plant protein toxin extracted from the castor oil plant and it has been classified as a chemical warfare agent. Here, nanosecond pulsed electric fields (nsPEFs) at 30 kV/cm (pulse durations: 10 ns, 100 ns and 300 ns) were applied to inactivating ricin up to 4.2 μg/mL. To investigate the efficacy, cells and mice were tested against the ricin treated by the nsPEFs via direct intraperitoneal injection and inhalation exposure. Results showed that nsPEFs treatments can effectively reduce the toxicity of the ricin. Without the nsPEFs treatment, 100% of mice were killed upon the 4 μg ricin injection on the first day, however 40% of the mice survived the ricin treated by the nsPEFs. Compared to injection, inhalation exposure even with higher ricin dose required longer time to observe mice fatality. Pathological observations revealed damages to heart, lung, kidney and stomach after the ricin exposure, more pronounced for lung and kidney including severe bleeding. Sodium dodecyl sulfate polyacrylamide gel electrophoresis(SDS-PAGE) and circular dichroism (CD) analyses revealed that although the primary structure of ricin was not altered, its secondary structures (beta-sheet and beta-turn) underwent transition upon the nsPEFs treatment.
Treponema pallidum (syphilis) antigen TpF1 induces angiogenesis through the activation of the IL-8 pathway
Authors: Pozzobon Tommaso , Facchinello Nicola , Bossi Fleur , Capitani Nagaja , Benagiano Marisa , Di Benedetto Giulietta , Zennaro Cristina , West Nicole , Codolo Gaia , Bernardini Marialina , Baldari Cosima Tatiana , D’Elios Mario Milco , Pellegrini Luca , Argenton Francesco , de Bernard Marina 
Published: January 2016

AbstractOver 10 million people every year become infected by Treponema pallidum and develop syphilis, a disease with broad symptomatology that, due to the difficulty to eradicate the pathogen from the highly vascularized secondary sites of infection, is still treated with injections of penicillin. Unlike most other bacterial pathogens, T. pallidum infection produces indeed a strong angiogenic response whose mechanism of activation, however, remains unknown. Here, we report that one of the major antigen of T. pallidum, the TpF1 protein, has growth factor-like activity on primary cultures of human endothelial cells and activates specific T cells able to promote tissue factor production. The growth factor-like activity is mediated by the secretion of IL-8 but not of VEGF, two known angiogenic factors. The pathogen’s factor signals IL-8 secretion through the activation of the CREB/NF-κB signalling pathway. These findings are recapitulated in an animal model, zebrafish, where we observed that TpF1 injection stimulates angiogenesis and IL-8, but not VEGF, secretion. This study suggests that the angiogenic response observed during secondary syphilis is triggered by TpF1 and that pharmacological therapies directed to inhibit IL-8 response in patients should be explored to treat this disease.
Comparison of bacterial communities of conventional and A-stage activated sludge systems
Authors: Gonzalez-Martinez Alejandro , Rodriguez-Sanchez Alejandro , Lotti Tommaso , Garcia-Ruiz Maria-Jesus , Osorio Francisco , Gonzalez-Lopez Jesus , van Loosdrecht Mark C. M. 
Published: January 2016

AbstractThe bacterial community structure of 10 different wastewater treatment systems and their influents has been investigated through pyrosequencing, yielding a total of 283486 reads. These bioreactors had different technological configurations: conventional activated sludge (CAS) systems and very highly loaded A-stage systems. A-stage processes are proposed as the first step in an energy producing municipal wastewater treatment process. Pyrosequencing analysis indicated that bacterial community structure of all influents was similar. Also the bacterial community of all CAS bioreactors was similar. Bacterial community structure of A-stage bioreactors showed a more case-specific pattern. A core of genera was consistently found for all influents, all CAS bioreactors and all A-stage bioreactors, respectively, showing that different geographical locations in The Netherlands and Spain did not affect the functional bacterial communities in these technologies. The ecological roles of these bacteria were discussed. Influents and A-stage bioreactors shared several core genera, while none of these were shared with CAS bioreactors communities. This difference is thought to reside in the different operational conditions of the two technologies. This study shows that bacterial community structure of CAS and A-stage bioreactors are mostly driven by solids retention time (SRT) and hydraulic retention time (HRT), as suggested by multivariate redundancy analysis.
AGE-RAGE signal generates a specific NF-κB RelA “barcode” that directs collagen I expression
Authors: Peng Yunqian , Kim Ji-Min , Park Hal-Sol , Yang Annie , Islam Celia , Lakatta Edward G. , Lin Li 
Published: January 2016

AbstractAdvanced glycation end products (AGEs) are sugar-modified biomolecules that accumulate in the body with advancing age and are implicated in the development of multiple age-associated structural and functional abnormities and diseases. It has been well documented that AGEs signal via their receptor RAGE to activate several cellular programs including NF-κB, leading to inflammation. A large number of stimuli can activate NF-κB; yet different stimuli, or the same stimulus for NF-κB in different cellular settings, produce a very different transcriptional landscape and physiological outcome. The NF-κB barcode hypothesis posits that cellular network dynamics generate signal-specific post-translational modifications, or a “barcode” to NF-κB and that a signature “barcode” mediates a specific gene expression pattern. In the current study, we established that AGE-RAGE signaling results in NF-κB activation that directs collagen Ia1 and Ia2 expression. We further demonstrated that AGE-RAGE signal induces phosphorylation of RelA at three specific residues, T254, S311 and S536. These modifications are required for transcription of collagen I genes and are a consequence of cellular network dynamics. The increase of collagen content is a hallmark of arterial aging and our work provides a potential mechanistic link between RAGE signaling, NF-κB activation and aging-associated arterial alterations in structure and function.