bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of transforming growth factor is involved in the efficacy of combined 5-fluorouracil and interferon alpha-2b therapy of advanced hepatocellular carcinoma
Authors: Okada Youhei , Wang Ting , Kasai Kazuhiro , Suzuki Kazuyuki , Takikawa Yasuhiro 
Published: March 2018

AbstractTransforming growth factor-beta (TGF-β) is critical in cancer cell invasion and metastasis. The effects of a treatment that targets TGF-β using the combination of interferon alpha (IFNα)-2b and 5-fluorouracil (5-FU) are unknown. Here, we show that the serum levels of TGF-β1 prior to the therapy correlate with increased maximum tumor diameter, which is significantly (p < 0.01) decreased after the combination therapy. 5-FU increased both the expression and secretion levels of TGF-β1 in hepatoma cells, but not in normal hepatocytes. The combination of 5-FU and IFNα-2b synergistically affected cell death. However, a TGF-β1 specific inhibitor did not affect the anti-tumor activity of 5-FU. 5-FU inhibited the phosphorylation of SMAD2 and reduced the total protein levels of SMAD2, SMAD4, and pINK4b. Conversely, 5-FU stimulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Accordingly, the protein levels of E-cadherin and claudin-1 were reduced in 5-FU-treated cells. The combination of 5-FU and IFNα-2b, and the inhibition of ERK1/2 by a specific inhibitor neutralized the effects of 5-FU on TGF-β-related signaling molecules and restored their protein levels to those observed in the control. Interestingly, the phosphorylated protein levels of SMAD2 and the total protein levels of E-cadherin and p15INK4b were increased in 5-FU-stimulated HuH-7 cells, but not in Hep G2 cells. Our data suggest that the higher efficacy of the 5-FU and IFNα-2b combination therapy was associated with the regulation of TGF-β expression, secretion, and the signals mediated by it.
Micro RNAs are involved in activation of epicardium during zebrafish heart regeneration
Authors: Ceci Marcello , Carlantoni Claudia , Missinato Maria Azzurra , Bonvissuto Davide , Di Giacomo Bruna , Contu Riccardo , Romano Nicla 
Published: March 2018

AbstractZebrafish could be an interesting translational model to understand and improve the post-infarction trial and possible regeneration in humans. The adult zebrafish is able to regenerate efficiently after resecting nearly 20% of the ventricular apex. This process requires the concert activation of the epicardium and endocardium, as well as trans-differentiation of pre-existing cardiomyocytes that together replace the lost tissue. The molecular mechanisms involved in this activation process are not completely clarified. In this work, in order to investigate if the downregulation of these miRNAs (miRs) are linked with the activation of epicardium, the expressions of miR-133a, b and miR-1 during regeneration were analysed. qPCR analyses in whole-heart, or from distinct dissected epicardial cells comparing to regenerative clot (containing cardiomyocytes, fibroblasts and endocardial cells) by a laser-micro-dissector, have indicated that already at 24 h there is a downregulation of miRs: (1) miR-133a and miR-1 in the epicardium and (2) miR-133b and miR-1 in the regenerative clot. All the miRs remain downregulated until 7 days post-surgery. With the aim to visualize the activations of heart component in combination with miRs, we developed immunohistochemistry using antibodies directed against common markers in mammals as well as zebrafish: Wilms tumour 1 (WT1), a marker of epicardium; heat-shock protein 70 (HSP70), a chaperon activated during regeneration; and the Cardiac Troponin T (cTnT), a marker of differentiated cardiomyocytes. All these markers are directly or indirectly linked to the investigated miRs. WT1 and HSP70 strongly marked the regeneration site just at 2–3 days postventricular resection. In coherence, cTnT intensively marked the regenerative portion from 7 days onwards. miRs-1 and -133 (a,b) have been strongly involved in the activation of epicardium and regenerative clot during the regeneration process in zebrafish. This study can be a useful translational model to understand the early epicardial activation in which miRs-133a and miR-1 seem to play a central role as observed in the human heart.
Constitutive ablation of caspase-6 reduces the inflammatory response and behavioural changes caused by peripheral pro-inflammatory stimuli
Authors: Ladha Safia , Qiu Xiaofan , Casal Lorenzo , Caron Nicholas S. , Ehrnhoefer Dagmar E. , Hayden Michael R. 
Published: March 2018

AbstractTraditionally, the family of caspases has been subcategorised according to their respective main roles in mediating apoptosis or inflammation. However, recent studies have revealed that caspases participate in diverse cellular functions beyond their canonical roles. Caspase-6 (C6) is one such protease known for its role as a pro-apoptotic executioner caspase and its aberrant activity in several neurodegenerative diseases. In addition to apoptosis, C6 has been shown to regulate B-cell activation and differentiation in plasma cells as well as macrophage activation. Furthermore, C6 has recently been postulated to play a role in mediating the inflammatory response through the production of TNF-α. In this study we further examine the role of C6 in mediating the inflammatory response and its contribution to the manifestation of behavioural abnormalities in mice. We find that C6 is a positive regulator of TNF-α transcription in macrophages and that ablation of C6 reduces lipopolysaccharide (LPS)-induced TNF-α levels in plasma. Furthermore, loss of C6 attenuates LPS-induced behavioural changes in mice and protects neurons from cytokine-mediated toxicity. These data further support the involvement of C6 in the inflammatory response and point to a previously unknown role for C6 in the pathophysiology of depression.
Targeting the CoREST complex with dual histone deacetylase and demethylase inhibitors
Authors: Kalin Jay H. , Wu Muzhou , Gomez Andrea V. , Song Yun , Das Jayanta , Hayward Dawn , Adejola Nkosi , Wu Mingxuan , Panova Izabela , Chung Hye Jin , Kim Edward , Roberts Holly J. , Roberts Justin M. , Prusevich Polina , Jeliazkov Jeliazko R. , Roy Burman Shourya S. , Fairall Louise , Milano Charles , Eroglu Abdulkerim , Proby Charlotte M. , Dinkova-Kostova Albena T. , Hancock Wayne W. , Gray Jeffrey J. , Bradner James E. , Valente Sergio , Mai Antonello , Anders Nicole M. , Rudek Michelle A. , Hu Yong , Ryu Byungwoo , Schwabe John W. R. , Mattevi Andrea , Alani Rhoda M. , Cole Philip A. 
Published: March 2018

AbstractHere we report corin, a synthetic hybrid agent derived from the class I HDAC inhibitor (entinostat) and an LSD1 inhibitor (tranylcypromine analog). Enzymologic analysis reveals that corin potently targets the CoREST complex and shows more sustained inhibition of CoREST complex HDAC activity compared with entinostat. Cell-based experiments demonstrate that corin exhibits a superior anti-proliferative profile against several melanoma lines and cutaneous squamous cell carcinoma lines compared to its parent monofunctional inhibitors but is less toxic to melanocytes and keratinocytes. CoREST knockdown, gene expression, and ChIP studies suggest that corin’s favorable pharmacologic effects may rely on an intact CoREST complex. Corin was also effective in slowing tumor growth in a melanoma mouse xenograft model. These studies highlight the promise of a new class of two-pronged hybrid agents that may show preferential targeting of particular epigenetic regulatory complexes and offer unique therapeutic opportunities.
Physiological and therapeutic regulation of glucose homeostasis by upper small intestinal PepT1-mediated protein sensing
Authors: Dranse Helen J. , Waise T. M. Zaved , Hamr Sophie C. , Bauer Paige V. , Abraham Mona A. , Rasmussen Brittany A. , Lam Tony K. T. 
Published: March 2018

AbstractHigh protein feeding improves glucose homeostasis in rodents and humans with diabetes, but the mechanisms that underlie this improvement remain elusive. Here we show that acute administration of casein hydrolysate directly into the upper small intestine increases glucose tolerance and inhibits glucose production in rats, independently of changes in plasma amino acids, insulin levels, and food intake. Inhibition of upper small intestinal peptide transporter 1 (PepT1), the primary oligopeptide transporter in the small intestine, reverses the preabsorptive ability of upper small intestinal casein infusion to increase glucose tolerance and suppress glucose production. The glucoregulatory role of PepT1 in the upper small intestine of healthy rats is further demonstrated by glucose homeostasis disruption following high protein feeding when PepT1 is inhibited. PepT1-mediated protein-sensing mechanisms also improve glucose homeostasis in models of early-onset insulin resistance and obesity. We demonstrate that preabsorptive upper small intestinal protein-sensing mechanisms mediated by PepT1 have beneficial effects on whole-body glucose homeostasis.
PLK1 has tumor-suppressive potential in APC-truncated colon cancer cells
Authors: Raab Monika , Sanhaji Mourad , Matthess Yves , Hörlin Albrecht , Lorenz Ioana , Dötsch Christina , Habbe Nils , Waidmann Oliver , Kurunci-Csacsko Elisabeth , Firestein Ron , Becker Sven , Strebhardt Klaus 
Published: March 2018

AbstractThe spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities. The inhibition of PLK1 in mitotic, APC-∆C-expressing cells reduces the kinetochore levels of Aurora B and hampers the recruitment of SAC component suggesting a compromised mitotic checkpoint. Furthermore, Plk1 inhibition (RNAi, pharmacological compounds) promotes the development of adenomatous polyps in two independent Apc
Min/+
mouse models. High PLK1 expression increases the survival of colon cancer patients expressing a truncated APC significantly.
Hunting regulation favors slow life histories in a large carnivore
Authors: Van de Walle Joanie , Pigeon Gabriel , Zedrosser Andreas , Swenson Jon E. , Pelletier Fanie 
Published: March 2018

AbstractAs an important extrinsic source of mortality, harvest should select for fast reproduction and accelerated life histories. However, if vulnerability to harvest depends upon female reproductive status, patterns of selectivity could diverge and favor alternative reproductive behaviors. Here, using more than 20 years of detailed data on survival and reproduction in a hunted large carnivore population, we show that protecting females with dependent young, a widespread hunting regulation, provides a survival benefit to females providing longer maternal care. This survival gain compensates for the females’ reduced reproductive output, especially at high hunting pressure, where the fitness benefit of prolonged periods of maternal care outweighs that of shorter maternal care. Our study shows that hunting regulation can indirectly promote slower life histories by modulating the fitness benefit of maternal care tactics. We provide empirical evidence that harvest regulation can induce artificial selection on female life history traits and affect demographic processes.
HIV envelope V3 region mimic embodies key features of a broadly neutralizing antibody lineage epitope
Authors: Fera Daniela , Lee Matthew S. , Wiehe Kevin , Meyerhoff R. Ryan , Piai Alessandro , Bonsignori Mattia , Aussedat Baptiste , Walkowicz William E. , Ton Therese , Zhou Jeffrey O. , Danishefsky Samuel , Haynes Barton F. , Harrison Stephen C. 
Published: March 2018

AbstractHIV-1 envelope (Env) mimetics are candidate components of prophylactic vaccines and potential therapeutics. Here we use a synthetic V3-glycopeptide (“Man9-V3”) for structural studies of an HIV Env third variable loop (V3)-glycan directed, broadly neutralizing antibody (bnAb) lineage (“DH270”), to visualize the epitope on Env and to study how affinity maturation of the lineage proceeded. Unlike many previous V3 mimetics, Man9-V3 encompasses two key features of the V3 region recognized by V3-glycan bnAbs—the conserved GDIR motif and the N332 glycan. In our structure of an antibody fragment of a lineage member, DH270.6, in complex with the V3 glycopeptide, the conformation of the antibody-bound glycopeptide conforms closely to that of the corresponding segment in an intact HIV-1 Env trimer. An additional structure identifies roles for two critical mutations in the development of breadth. The results suggest a strategy for use of a V3 glycopeptide as a vaccine immunogen.
Monitoring ultrafast vibrational dynamics of isotopic molecules with frequency modulation of high-order harmonics
Authors: He Lixin , Zhang Qingbin , Lan Pengfei , Cao Wei , Zhu Xiaosong , Zhai Chunyang , Wang Feng , Shi Wenjing , Li Muzi , Bian Xue-Bin , Lu Peixiang , Bandrauk André D. 
Published: March 2018

AbstractMolecules constituted by different isotopes are different in vibrational modes, making it possible to elucidate the mechanism of a chemical reaction via the kinetic isotope effect. However, the real-time observation of the vibrational motion of isotopic nuclei in molecules is still challenging due to its ultrashort time scale. Here we demonstrate a method to monitor the nuclear vibration of isotopic molecules with the frequency modulation of high-order harmonic generation (HHG) during the laser-molecule interaction. In the proof-of-principle experiment, we report a red shift in HHG from H2 and D2. The red shift is ascribed to dominant HHG from the stretched isotopic molecules at the trailing edge of the laser pulse. By utilizing the observed frequency shift, the laser-driven nuclear vibrations of H2 and D2 are retrieved. These findings pave an accessible route toward monitoring the ultrafast nuclear dynamics and even tracing a chemical reaction in real time.
Plasma dye coating as straightforward and widely applicable procedure for dye immobilization on polymeric materials
Authors: De Smet Lieselot , Vancoillie Gertjan , Minshall Peter , Lava Kathleen , Steyaert Iline , Schoolaert Ella , Van De Walle Elke , Dubruel Peter , De Clerck Karen , Hoogenboom Richard 
Published: March 2018

AbstractHere, we introduce a novel concept for the fabrication of colored materials with significantly reduced dye leaching through covalent immobilization of the desired dye using plasma-generated surface radicals. This plasma dye coating (PDC) procedure immobilizes a pre-adsorbed layer of a dye functionalized with a radical sensitive group on the surface through radical addition caused by a short plasma treatment. The non-specific nature of the plasma-generated surface radicals allows for a wide variety of dyes including azobenzenes and sulfonphthaleins, functionalized with radical sensitive groups to avoid significant dye degradation, to be combined with various materials including PP, PE, PA6, cellulose, and PTFE. The wide applicability, low consumption of dye, relatively short procedure time, and the possibility of continuous PDC using an atmospheric plasma reactor make this procedure economically interesting for various applications ranging from simple coloring of a material to the fabrication of chromic sensor fabrics as demonstrated by preparing a range of halochromic materials.
Observation of dose-rate dependence in a Fricke dosimeter irradiated at low dose rates with monoenergetic X-rays
Authors: O’Leary Mel , Boscolo Daria , Breslin Nicole , Brown Jeremy M. C. , Dolbnya Igor P. , Emerson Chris , Figueira Catarina , Fox Oliver J. L. , Grimes David Robert , Ivosev Vladimir , Kleppe Annette K. , McCulloch Aaron , Pape Ian , Polin Chris , Wardlow Nathan , Currell Fred J. 
Published: March 2018

AbstractAbsolute measurements of the radiolytic yield of Fe3+ in a ferrous sulphate dosimeter formulation (6 mM Fe2+), with a 20 keV x-ray monoenergetic beam, are reported. Dose-rate suppression of the radiolytic yield was observed at dose rates lower than and different in nature to those previously reported with x-rays. We present evidence that this effect is most likely to be due to recombination of free radicals radiolytically produced from water. The method used to make these measurements is also new and it provides radiolytic yields which are directly traceable to the SI standards system. The data presented provides new and exacting tests of radiation chemistry codes.
Removal of metal ions and humic acids through polyetherimide membrane with grafted bentonite clay
Authors: Hebbar Raghavendra S. , Isloor Arun M. , Prabhu Balakrishna , Inamuddin  , Asiri Abdullah M. , Ismail A. F. 
Published: March 2018

AbstractFunctional surfaces and polymers with branched structures have a major impact on physicochemical properties and performance of membrane materials. With the aim of greener approach for enhancement of permeation, fouling resistance and detrimental heavy metal ion rejection capacity of polyetherimide membrane, novel grafting of poly (4-styrenesulfonate) brushes on low cost, natural bentonite was carried out via distillation-precipitation polymerisation method and employed as a performance modifier. It has been demonstrated that, modified bentonite clay exhibited significant improvement in the hydrophilicity, porosity, and water uptake capacity with 3 wt. % of additive dosage. SEM and AFM analysis showed the increase in macrovoides and surface roughness with increased additive concentration. Moreover, the inclusion of modified bentonite displayed an increase in permeation rate and high anti-irreversible fouling properties with reversible fouling ratio of 75.6%. The humic acid rejection study revealed that, PEM-3 membrane having rejection efficiency up to 87.6% and foulants can be easily removed by simple hydraulic cleaning. Further, nanocomposite membranes can be significantly employed for the removal of hazardous heavy metal ions with a rejection rate of 80% and its tentative mechanism was discussed. Conspicuously, bentonite clay-bearing poly (4-styrenesulfonate) brushes are having a synergistic effect on physicochemical properties of nanocomposite membrane to enhance the performance in real field applications.
Functional Variants in Linc-ROR are Associated with mRNA Expression of Linc-ROR and Breast Cancer Susceptibility
Authors: Luo Chenglin , Cao Jingjing , Peng Rui , Guo Qiaoyun , Ye Hua , Wang Peng , Wang Kaijuan , Song Chunhua 
Published: March 2018

AbstractFunctional polymorphisms in Linc-ROR may change its ability of regulation by regulating Linc-ROR expression. However, these functional polymorphisms in Linc-ROR and their associations with breast cancer (BC) susceptibility were scarcely reported. In this molecular epidemiological study, four SNPs (rs6420545, rs4801078, rs1942348 and rs9636089) were selected in Linc-ROR by bioinformatics method. Unconditional logistic regression model was performed to analyze the associations between four SNPs and BC susceptibility adjusted for reproductive factors. Quantitative real-time (qRT) PCR was used to evaluate relative expression of Linc-ROR in plasma. The interactions of gene reproductive factors were assessed by Multifactor Dimensionality Reduction (MDR) method. A novel finding showed TT (OR: 1.79; 95%CI: 1.20–2.68) genotype of rs4801078 in Linc-ROR had a significant association with the higher risk of BC and the expression of Linc-ROR mRNA was closely related with the alleles of rs4801078. In addition, we found the interaction of rs4801078, number of pregnancy and menopausal status might increase BC risk (OR: 2.78; 95%CI: 2.74–3.61). Our results suggest that interactions of SNPs in Linc-ROR and reproductive factors might contribute to BC risk, and alleles of rs4801078 might affect Linc-ROR expression level.
Velocity-dependent slip weakening by the combined operation of pressure solution and foliation development
Authors: Niemeijer A. R. 
Published: March 2018

AbstractPhyllosilicate-bearing faults are characterized by an anastomosing foliation with intervening hard clasts and are believed to be long-term weak structures. Here, I present results of sliding experiments on gouges of 80 wt% quartz and 20 wt% muscovite, sheared under hydrothermal conditions at constant velocity. The results show that significant strengthening occurs over a narrow range of sliding velocities (0.03–1 μm/s). At the lowest velocity investigated, weakness is achieved after a considerable sliding distance of over 20 mm with friction reaching a value of 0.3. Microstructural observations and the application of existing models point to the operation of frictional-viscous flow (FVF), through the serial operation of frictional sliding over a weak foliation and pressure solution of intervening clasts, resulting in low frictional strength and pronounced velocity-strengthening. At higher velocities, grain size reduction becomes dominant in a localized zone, which results in disruption of the foliation and the cessation of the FVF mechanism. In natural settings, earthquakes originating elsewhere on the fault would be rapidly arrested when encountering a foliated part of the fault deforming via FVF. Furthermore, pulses of elevated slip velocity would lead to grain size reduction which would destroy the foliation and cause a long-term strengthening of the fault.
Association between Thyroid Hormone Levels and Diabetic Kidney Disease in Euthyroid Patients with Type 2 Diabetes
Authors: Zou Jian , Tian Feng , Zhang Yi , Li Zeping , Yang Chao , Chen Haixu , Zhai Jiajia , Shi Min , Xu Chao , Zhang Juan , Li Wenjuan , Xie Yonghong , Li Xiaomiao 
Published: March 2018

AbstractThe association between normal thyroid function and diabetic kidney disease (DKD) has gained increasing attention. The present study evaluated the relationship between normal thyroid hormone levels and DKD in type 2 diabetes mellitus (T2DM) patients. A total of 862 type 2 diabetes patients were enrolled in this cross-sectional study in Xi’an, Shaanxi Province, China. The subjects were evaluated for anthropometric measurements, thyroid function and DKD. Of 862 patients, 246 (28.5%) suffered from DKD, and the prevalence of DKD did not differ between men and women. The prevalence of DKD showed a significantly decreasing trend across the quartiles based on free triiodothyronine (FT3) levels (41.1%, 30.6%, 23.8%, and 18.9%, P < 0.001). In comparison with all participants categorized in the first FT3 quartile group (FT3-Q1) (<4.380), the adjusted odds ratio of DKD in the second FT3 quartile group (FT3-Q2), the third FT3 quartile group (FT3-Q3), and the fourth FT3 quartile group (FT3-Q4) were 0.655(95%CI: 0.406–1.057), 0.493(95%CI: 0.299–0.813), 0.406(0.237–0.697) (P < 0.05). Also, similar results were observed in men. Conversely, none of the FT3 groups was associated with DKD in women. The present study showed that FT3 within normal range was negatively correlated with DKD in T2DM patients.