bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically engineered rice endogenous 5-enolpyruvoylshikimate-3-phosphate synthase (epsps) transgene alters phenology and fitness of crop-wild hybrid offspring
Authors: Yang Xiao , Li Lei , Jiang Xiaoqi , Wang Wei , Cai Xingxing , Su Jun , Wang Feng , Lu Bao-Rong 
Published: July 2017

AbstractGenetically engineered (GE) rice endogenous epsps (5-enolpyruvoylshikimate-3-phosphate synthase) gene overexpressing EPSPS can increase glyphosate herbicide-resistance of cultivated rice. This type of epsps transgene can enhance the fecundity of rice crop-weed hybrid offspring in the absence of glyphosate, stimulating great concerns over undesired environmental impacts of transgene flow to populations of wild relatives. Here, we report the substantial alteration of phenology and fitness traits in F1-F3 crop-wild hybrid descendants derived from crosses between an epsps GE rice line and two endangered wild rice (Oryza rufipogon) populations, based on the common-garden field experiments. Under the glyphosate-free condition, transgenic hybrid lineages showed significantly earlier tillering and flowering, as well as increased fecundity and overwintering survival/regeneration abilities. In addition, a negative correlation was observed between the contents of endogenous EPSPS of wild, weedy, and cultivated rice parents and fitness differences caused by the incorporation of the epsps transgene. Namely, a lower level of endogenous EPSPS in the transgene-recipient populations displayed a more pronounced enhancement in fitness. The altered phenology and enhanced fitness of crop-wild hybrid offspring by the epsps transgene may cause unwanted environmental consequences when this type of glyphosate-resistance transgene introgressed into wild rice populations through gene flow.
Neurometabolic and electrophysiological changes during cortical spreading depolarization: multimodal approach based on a lactate-glucose dual microbiosensor arrays
Authors: Lourenço Cátia F. , Ledo Ana , Gerhardt Greg A. , Laranjinha João , Barbosa Rui M. 
Published: July 2017

AbstractSpreading depolarization (SD) is a slow propagating wave of strong depolarization of neural cells, implicated in several neuropathological conditions. The breakdown of brain homeostasis promotes significant hemodynamic and metabolic alterations, which impacts on neuronal function. In this work we aimed to develop an innovative multimodal approach, encompassing metabolic, electric and hemodynamic measurements, tailored but not limited to study SD. This was based on a novel dual-biosensor based on microelectrode arrays designed to simultaneously monitor lactate and glucose fluctuations and ongoing neuronal activity with high spatial and temporal resolution. In vitro evaluation of dual lactate-glucose microbiosensor revealed an extended linear range, high sensitivity and selectivity, fast response time and low oxygen-, temperature- and pH- dependencies. In anesthetized rats, we measured with the same array a significant drop in glucose concentration matched to a rise in lactate and concurrently with pronounced changes in the spectral profile of LFP-related currents during episodes of mechanically-evoked SD. This occurred along with the stereotypical hemodynamic response of the SD wave. Overall, this multimodal approach successfully demonstrates the capability to monitor metabolic alterations and ongoing electrical activity, thus contributing to a better understanding of the metabolic changes occurring in the brain following SD.
A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment
Authors: Nair Neha , Calle Anna Sanchez , Zahra Maram Hussein , Prieto-Vila Marta , Oo Aung Ko Ko , Hurley Laura , Vaidyanath Arun , Seno Akimasa , Masuda Junko , Iwasaki Yoshiaki , Tanaka Hiromi , Kasai Tomonari , Seno Masaharu 
Published: July 2017

AbstractCancer-associated fibroblasts (CAFs) are one of the most prominent cell types in the stromal compartment of the tumor microenvironment. CAFs support multiple aspects of cancer progression, including tumor initiation, invasion, and metastasis. The heterogeneous nature of the stromal microenvironment is attributed to the multiple sources from which the cells in this compartment originate. The present study provides the first evidence that cancer stem cells (CSCs) are one of the key sources of CAFs in the tumor niche. We generated CSC-like cells by treating mouse induced pluripotent stem cells with conditioned medium from breast cancer cell lines. The resulting cell population expressed both CSC and pluripotency markers, and the sphere-forming CSC-like cells formed subcutaneous tumors in nude mice. Intriguingly, these CSC-like cells always formed heterogeneous populations surrounded by myofibroblast-like cells. Based on this observation, we hypothesized that CSCs could be the source of the CAFs that support tumor maintenance and survival. To address this hypothesis, we induced the differentiation of spheres and purified the myofibroblast-like cells. The resulting cells exhibited a CAF-like phenotype, suggesting that they had differentiated into the subpopulations of cells that support CSC self-renewal. These findings provide novel insights into the dynamic interplay between various microenvironmental factors and CAFs in the CSC niche.
Pre-therapy liver transcriptome landscape in Indian and French patients with severe alcoholic hepatitis and steroid responsiveness
Authors: Sharma Shvetank , Maras Jaswinder S. , Das Sukanta , Hussain Shabir , Mishra Ashwani K. , Shasthry Saggere M. , Sharma Chhagan B. , Weiss Emmanuel , Elkrief Laure , Rautou Pierre-Emmanuel , Gilgenkrantz Hélène , Lotersztajn Sophie , Paradis Valérie , de la Grange Pierre , Junot Christophe , Moreau Richard , Sarin Shiv K. 
Published: July 2017

AbstractPatients with severe alcoholic hepatitis (SAH) not responding to glucocorticoid therapy have higher mortality, though they do not differ in their baseline clinical characteristics and prognostic scores from those who respond to therapy. We hypothesized that the baseline hepatic gene expression differs between responders (R) and non-responders (NR). Baseline liver transcriptome was compared between R and NR in Indian (16 each) and French (5 NR, 3 R) patients with SAH. There were differentially expressed genes (DEGs) between NR and R, in Indian (1106 over-expressed, 96 under-expressed genes) and French patients (65 over-expressed, 142 under-expressed genes). Indian NR had features of hepatocyte senescence and French NR exhibited under-expression of genes involved in cell division, indicating a central defect in the capacity of hepatocytes for self-renewal in both populations. Markers of hepatic progenitor cell proliferation were either very few (Indian patients) or absent (French patients). No DEGs were enriched in inflammatory pathways and there were no differences in nuclear receptor subfamily 3 group C member 1 (NR3C1) transcript expression and splicing between NR and R. Our results reveal that baseline hepatic transcriptome is reflective of subsequent glucocorticoid non-response and indicate impaired regenerative potential of the liver as an underlying phenomenon in NR.
Robust and accurate digital measurement for HER2 amplification in HER2 equivocal breast cancer diagnosis
Authors: Wang Yuefeng , Tsang Julia Y. S. , Cui Yongmei , Cui Ji , Lin Ying , Zhao Songli , Law Patrick T. W. , Cheung Sai Yin , Ng Enders K. O. , Tse Gary M. K. , Ke Zunfu 
Published: July 2017

AbstractCurrently, there are no recommended alternative assays for HER2 cases deemed equivocal by immunohistochemistry and fluorescent in situ hybridization. Digital PCR (ddPCR), a highly accurate method to determine DNA copy number, could be a robust alternative for clinical HER2 diagnostics. HER2 and CEP17 copy numbers were quantified using two ddPCR platforms (QX200 and RainDrop) in 102 samples of invasive breast cancers. Compared to routine assays, ddPCR gave a sensitivity and specificity of 82.8% and 97.3% respectively, with a kappa value of 0.833 (p < 0.001). Moreover, the method proved to be robust as the results from two platforms was highly correlated (R2 = 0.91; Concordance rate = 97%; κ = 0.923, P < 0.001). Its performance was further tested on 114 HER2 equivocal cases in an independent validation cohort. 75% (21/28) of cases with HER2 amplification and 95% (82/86) of HER2 non-amplified case were classified as positive and negative by ddPCR respectively (κ = 0.709, P < 0.001). Notably, in the HER2 amplified cases, a lower percentage of HER2 positive cells could be related to the discordant results. Altogether, ddPCR is a robust alternative for clinical HER2 diagnostics. However, intratumoral heterogeneity of HER2 status still pose a challenge for HER2 analysis by ddPCR.
Tauroursodeoxycholic acid enhances the development of porcine embryos derived from in vitro-matured oocytes and evaporatively dried spermatozoa
Authors: Li Xiao-Xia , Diao Yun-Fei , Wei Hai-Jun , Wang Shi-Yong , Cao Xin-Yan , Zhang Yu-Fei , Chang Tong , Li Dan-Li , Kim Min Kyu , Xu Baozeng 
Published: July 2017

AbstractEvaporative drying (ED) is an alternative technique for long-term preservation of mammalian sperm, which does not require liquid nitrogen or freeze-drying equipment, but offers advantages for storage and shipping at ambient temperature and low cost. However, the development of zygotes generated from these sperms was poor. Here, we demonstrated that the supplementation of tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, during embryo culture improved the developmental competency of embryos derived from in vitro matured pig oocytes injected intracytoplasmically with boar ED spermatozoa by reducing the production of reactive oxygen species, the DNA degradation and fragmentation, and the expression of apoptosis-related gene Bax and Bak, and by increasing the transcription of anti-apoptosis gene Bcl-XL and Bcl-2. Furthermore, TUDCA treatment promoted the blastocyst quality manifested by the total cell numbers and the ratio of inner cell mass. Taken together, our data suggest that evaporative drying would be a potentially useful method for the routine preservation of boar sperm in combination with further optimization of subsequently embryo culture conditions.
Suppression of presbyopia progression with pirenoxine eye drops: experiments on rats and non-blinded, randomized clinical trial of efficacy
Authors: Tsuneyoshi Yukari , Higuchi Akihiro , Negishi Kazuno , Tsubota Kazuo 
Published: July 2017

AbstractVarious methods can correct presbyopia, but all require devices or surgeries. Recently, supplements or warming devices to relieve presbyopic symptoms have been developed, but no eye drops have been developed. We screened certain compounds possibly related to lens degeneration and identified pirenoxine, which has been used for cataracts, as a possible new pharmacologic treatment for presbyopia. We first researched the anti-presbyopic activity of pirenoxine in rats. The lens elasticity significantly (p = 0.028) increased with exposure to tobacco smoke for 12 days, and pirenoxine eye drops significantly (p < 0.001) suppressed lens hardening, which causes presbyopia in humans. In a parallel randomized controlled clinical study of the subjects in their fifth decade of life, the objective accommodative amplitude (AA) decreased significantly (p < 0.01) by 0.16 diopter (D) in the control group, and there was no detectable change in the treatment group after a 6-month treatment period, suggesting that pirenoxine eye drops might prevent progression of presbyopia. Subjects in their sixth decade of life, in whom the AA was already nearly 0 D, did not show similar results. Pirenoxine eye drops might be a new and the first pharmacologic treatment for preventing progression of presbyopia.
DNA Self-assembly Catalyzed by Artificial Agents
Authors: Shi Chao , Wang Yifan , Zhang Menghua , Ma Cuiping 
Published: July 2017

AbstractNucleic acids have been shown to be versatile molecules and engineered to produce various nanostructures. However, the poor rate of these uncatalyzed nucleic acid reactions has restricted the development and applications. Herein, we reported a novel finding that DNA self-assembly could be nonenzymatically catalyzed by artificial agents with an increasing dissociation rate constant K2. The catalytic role of several artificial agents in DNA self-assembly was verified by real-time fluorescent detection or agarose gel electrophoresis. We found that 20% PEG 200 could significantly catalyze DNA self-assembly and increase the reaction efficiency, such as linear hybridization chain reaction (HCR) and exponential hairpin assembly (EHA). Therefore, we foresee that a fast and efficient DNA self-assembly in structural DNA nanotechnology will be desirable.
Zinc binding to RNA recognition motif of TDP-43 induces the formation of amyloid-like aggregates
Authors: Garnier Cyrille , Devred François , Byrne Deborah , Puppo Rémy , Roman Andrei Yu. , Malesinski Soazig , Golovin Andrey V. , Lebrun Régine , Ninkina Natalia N. , Tsvetkov Philipp O. 
Published: July 2017

AbstractAggregation of TDP-43 (transactive response DNA binding protein 43 kDa) is a hallmark of certain forms of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Moreover, intracellular TDP-43-positive inclusions are often found in other neurodegenerative diseases. Recently it was shown that zinc ions can provoke the aggregation of endogenous TDP-43 in cells, allowing to assume a direct interaction of TDP-43 with zinc ions. In this work, we investigated zinc binding to the 102–269 TDP-43 fragment, which comprise the two RNA recognition motifs. Using isothermal titration calorimetry, mass spectrometry, and differential scanning fluorimetry, we showed that zinc binds to this TDP-43 domain with a dissociation constant in the micromolar range and modifies its tertiary structure leading to a decrease of its thermostability. Moreover, the study by dynamic light scattering and negative stain electron microscopy demonstrated that zinc ions induce auto-association process of this TDP-43 fragment into rope-like structures. These structures are thioflavin-T-positive allowing to hypothesize the direct implication of zinc ions in pathological aggregation of TDP-43.
Neuroprotective Effects of Trigeminal Nerve Stimulation in Severe Traumatic Brain Injury
Authors: Chiluwal Amrit , Narayan Raj K. , Chaung Wayne , Mehan Neal , Wang Ping , Bouton Chad E. , Golanov Eugene V. , Li Chunyan 
Published: July 2017

AbstractFollowing traumatic brain injury (TBI), ischemia and hypoxia play a major role in further worsening of the damage, a process referred to as ‘secondary injury’. Protecting neurons from causative factors of secondary injury has been the guiding principle of modern TBI management. Stimulation of trigeminal nerve induces pressor response and improves cerebral blood flow (CBF) by activating the rostral ventrolateral medulla. Moreover, it causes cerebrovasodilation through the trigemino-cerebrovascular system and trigemino-parasympathetic reflex. These effects are capable of increasing cerebral perfusion, making trigeminal nerve stimulation (TNS) a promising strategy for TBI management. Here, we investigated the use of electrical TNS for improving CBF and brain oxygen tension (PbrO2), with the goal of decreasing secondary injury. Severe TBI was produced using controlled cortical impact (CCI) in a rat model, and TNS treatment was delivered for the first hour after CCI. In comparison to TBI group, TBI animals with TNS treatment demonstrated significantly increased systemic blood pressure, CBF and PbrO2 at the hyperacute phase of TBI. Furthermore, rats in TNS-treatment group showed significantly reduced brain edema, blood-brain barrier disruption, lesion volume, and brain cortical levels of TNF-α and IL-6. These data provide strong early evidence that TNS could be an effective neuroprotective strategy.
Biochar influences on soil CO2 and CH4 fluxes in response to wetting and drying cycles for a forest soil
Authors: Johnson Mark S. , Webster Cameron , Jassal Rachhpal S. , Hawthorne Iain , Black T. Andrew 
Published: July 2017

AbstractBiochar has been the focus of significant research efforts in agriculture, but little research has been conducted in forested ecosystems. Here, we assess CO2 and CH4 fluxes from a forest soil in response to biochar additions using a before-after-control-intervention experimental design. Soil CO2 and CH4 fluxes were measured over a series of wetting cycles by coupling soil mesocosms equipped with auto-chambers to a laser-based spectrometer for high-frequency measurements of gas fluxes and related soil processes. We found that soil CO2 fluxes were higher and CH4 fluxes were less negative (e.g. reduced CH4 uptake) for the biochar-amended soil compared to the no biochar condition. Furthermore, biochar improved soil infiltrability under wet conditions, and enhanced soil moisture levels under dry conditions. Biochar additions shifted the point of maximum soil respiration (i.e. soil CO2 efflux) to a slightly wetter soil moisture level. The point of maximum CH4 uptake was also shifted to a slightly wetter moisture level for soil with biochar. Overall differences in soil gas fluxes were found to be minor compared to the increase in soil carbon resulting from the biochar addition. Biochar may thus contribute to improved forest management through increases to soil carbon stocks and improved soil moisture levels.
Reconstructing the historical synthesis of mauveine from Perkin and Caro: procedure and details
Authors: Cova Tânia F. G. G. , Pais Alberto A. C. C. , Seixas de Melo J. Sérgio 
Published: July 2017

AbstractMauveine, an iconic dye, first synthesised in 1856 still has secrets to unveil. If nowadays one wanted to prepare the original Perkin’s mauveine, what would be the procedure? It will be described in this work and lies on the use of a 1:2:1 (mole) ratio of aniline, p-toluidine and o-toluidine. This was found from a comparison of a series of products synthesized from different proportions of these starting materials, with a set of historical samples of mauveine and further analysed with two unsupervised chemometrics methods.
A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis
Authors: Chen Yong , Gong Fang-Yuan , Li Zhen-Jun , Gong Zheng , Zhou Zhe , Ma Shu-Yan , Gao Xiao-Ming 
Published: July 2017

AbstractTofacitinib (CP-690550), an oralJanuskinase inhibitor, has shown significant efficacy in the treatment of rheumatoid arthritis through blocking the signaling pathways of pro-inflammatory cytokines. However, recent evidence suggests that long-term tofacitinib treatment is associated with increased risk of infection (e.g. tuberculosis) in patients. In the present study, we illustrate that tofacitinib administration significantly reduced the survival rate of mice given lethal or sub-lethal dose challenge with Candida albicans. This was related to the ability of tofacitinib to reverse TNFα- and IFNγ-enhanced candidacidal activity of murine polymorph nuclear cells (PMNs) and also to suppress chemokine CXCL5 expression and PMN infiltration in the infected tissues of mice. More importantly, tofacitinib significantly antagonized the ability of TNFα, IFNγ and GM-CSF to boost human PMNs in phagocytosis and direct killing ofC. albicans in vitro. It also down-regulated reactive oxygen production and neutrophil extracellular trap formation by human PMNs stimulated with yeast-derived β-glucans in the presence of TNFα, IFNγ or GM-CSF. Our data emphasizes a significantly increased risk for opportunistic fungal infection associated long-term tofacitinib treatment in humans, likely through antagonizing the PMN-boosting effect of pro-inflammatory cytokines.
Dynamics of plasma membrane surface related to the release of extracellular vesicles by mesenchymal stem cells in culture
Authors: Casado Santiago , Lobo Maria del Val Toledo , Paíno Carlos Luis 
Published: July 2017

AbstractExtracellular vesicles (exosomes and shedding vesicles) released by mesenchymal stem cells (MSCs) are regarded as a storable, cell-free alternative with comparable therapeutic potential to their parent cells. Shedding vesicles originate as bulges on the cell surface but little is known about their turnover or how their formation can be stimulated. We have used atomic force microscopy (AFM) to follow the formation dynamics of bulges in living adipose tissue-derived MSCs. AFM images showed that, in general, MSCs present hundreds of nanosized protrusions on their surface with life spans of 10–20 min. Scanning electron microscopy confirmed those images and showed that bulges are also formed on filamentous processes. Extracellular vesicles deposited on the culture surface have comparable sizes to those of bulges showing up on the cell surface. The amount of protrusions on cells treated with progesterone or PDGF-BB, two treatments that stimulate the secretion of extracellular vesicles in MSCs, was evaluated by AFM. Measurements of the cross-area at 50 nm over the cell surface provided estimates of the amount of protrusions and showed that these values increased with the stimulating treatments. Our study suggests that shedding vesicles constitute a large population of the extracellular vesicle pool.
Development of hydroxybenzoic-based platforms as a solution to deliver dietary antioxidants to mitochondria
Authors: Teixeira José , Oliveira Catarina , Amorim Ricardo , Cagide Fernando , Garrido Jorge , Ribeiro José A. , Pereira Carlos M. , Silva António F. , Andrade Paula B. , Oliveira Paulo J. , Borges Fernanda 
Published: July 2017

AbstractOxidative stress and mitochondrial dysfunction have been associated with metabolic and age-related diseases. Thus, the prevention of mitochondrial oxidative damage is nowadays a recognized pharmacological strategy to delay disease progression. Epidemiological studies suggested an association between the consumption of polyphenol-rich diet and the prevention of different pathologies, including diseases with a mitochondrial etiology. The development of mitochondrial-targeted antioxidants based on dietary antioxidants may decrease mitochondrial oxidative damage. Herein, we report the design and synthesis of two new mitochondriotropic antioxidants based on hydroxybenzoic acids (AntiOxBENs). The results obtained showed that the novel antioxidants are accumulated inside rat liver mitochondria driven by the organelle transmembrane electric potential and prevented lipid peroxidation, exhibiting low toxicity. Some of the observed effects on mitochondrial bioenergetics resulted from an increase of proton leakage through the mitochondrial inner membrane. The new derivatives present a higher lipophilicity than the parent compounds (protocatechuic and gallic acids) and similar antioxidant and iron chelating properties. AntiOxBENs are valid mitochondriotropic antioxidant prototypes, which can be optimized and used in a next future as drug candidates to prevent or slow mitochondrial oxidative stress associated to several pathologies.