bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progesterone Receptors in Prostate Cancer: Progesterone receptor B is the isoform associated with disease progression
Authors: Grindstad Thea , Richardsen Elin , Andersen Sigve , Skjefstad Kaja , Rakaee khanehkenari Mehrdad , Donnem Tom , Ness Nora , Nordby Yngve , Bremnes Roy M. , Al-Saad Samer , Busund Lill-Tove 
Published: July 2018

AbstractThe role of steroid hormones in carcinogenesis of the prostate is to some extent unraveled thorough the effect of androgen deprivation therapy on prostate cancer (PCa) progression. Other members of the steroid hormone family, such as progesterone, are also implicated in PCa, but progesterone’s role remains undefined. This study aimed to examine the distribution of progesterone receptor isoforms (PGRA, PGRB) in PCa tissue and their association with clinical endpoints. This was conducted retrospectively by collecting radical prostatectomy specimens from 535 patients. Tissue was analyzed using tissue microarray, where representative tumor areas were carefully selected. Protein expression was evaluated through immunohistochemistry, in stromal and epithelial tissue. Associations between receptor expression and clinical data were considered using statistical survival analyses. Herein, we discovered a solely stromal PGRA- and a stromal and epithelial PGRB expression. Further, a high PGRB expression in tumor tissue was associated with an unfavorable prognosis in both univariate and multivariate analyses: Biochemical failure (HR: 2.0, 95% CI: 1.45–2.76, p < 0.001) and clinical failure (HR: 2.5, 95% CI: 1.29–4.85, p = 0.006). These findings are in agreement with our previous investigation on pan-PGR, indicating that the observed negative effect of PGR is represented by PGRB.
Metal-cation regulation of enzyme dynamics is a key factor influencing the activity of S-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa
Authors: Czyrko Justyna , Sliwiak Joanna , Imiolczyk Barbara , Gdaniec Zofia , Jaskolski Mariusz , Brzezinski Krzysztof 
Published: July 2018

AbstractS-adenosyl-l-homocysteine hydrolase from Pseudomonas aeruginosa (PaSAHase) coordinates one K+ ion and one Zn2+ ion in the substrate binding area. The cations affect the enzymatic activity and substrate binding but the molecular mechanisms of their action are unknown. Enzymatic and isothermal titration calorimetry studies demonstrated that the K+ ions stimulate the highest activity and strongest ligand binding in comparison to other alkali cations, while the Zn2+ ions inhibit the enzyme activity. PaSAHase was crystallized in the presence of adenine nucleosides and K+ or Rb+ ions. The crystal structures show that the alkali ion is coordinated in close proximity of the purine ring and a 23Na NMR study showed that the monovalent cation coordination site is formed upon ligand binding. The cation, bound in the area of a molecular hinge, orders and accurately positions the amide group of Q65 residue to allow its interaction with the ligand. Moreover, binding of potassium is required to enable unique dynamic properties of the enzyme that ensure its maximum catalytic activity. The Zn2+ ion is bound in the area of a molecular gate that regulates access to the active site. Zn2+ coordination switches the gate to a shut state and arrests the enzyme in its closed, inactive conformation.
Optical Biometry-Based Intraocular Lens Calculation and Refractive Outcomes after Phacovitrectomy for Rhegmatogenous Retinal Detachment and Epiretinal Membrane
Authors: Shiraki Nobuhiko , Wakabayashi Taku , Sakaguchi Hirokazu , Nishida Kohji 
Published: July 2018

AbstractWe investigate the refractive error after phacovitrectomy for rhegmatogenous retinal detachment (RRD; 100 eyes) and epiretinal membrane (ERM; 102 eyes). Axial lengths were measured by optical biometry in most patients. The main outcome measures were the refractive and absolute prediction errors. The overall mean refractive prediction error (ME) and mean absolute prediction error (MAE) were −0.40 ± 0.72 D and 0.62 ± 0.55 D, respectively, at 3 months postoperatively. The ME and MAE were significantly higher in the RRD group than in the ERM group (−0.63 ± 0.74 D vs −0.16 ± 0.63 D,P < 0.001 and 0.75 ± 0.62 D vs 0.49 ± 0.43 D,P = 0.002, respectively), indicating greater myopic shift in the RRD group. In the RRD group, adding +0.5 D to the preoperative predicted refractive power decreased the postoperative ME and MAE to −0.13 ± 0.74 D and 0.58 ± 0.47 D, respectively. Based on our results, we conclude that postoperative myopic shift was significantly higher in the RRD group than in the ERM group, possibly because of forward displacement of the intraocular lens by gas tamponade. The myopic shift can be minimized by adding +0.5 D to the predicted refractive power in patients undergoing phacovitrectomy for RRD.
Audiovisual Temporal Processing in Postlingually Deafened Adults with Cochlear Implants
Authors: Butera Iliza M. , Stevenson Ryan A. , Mangus Brannon D. , Woynaroski Tiffany G. , Gifford René H. , Wallace Mark T. 
Published: July 2018

AbstractFor many cochlear implant (CI) users, visual cues are vitally important for interpreting the impoverished auditory speech information that an implant conveys. Although the temporal relationship between auditory and visual stimuli is crucial for how this information is integrated, audiovisual temporal processing in CI users is poorly understood. In this study, we tested unisensory (auditory alone, visual alone) and multisensory (audiovisual) temporal processing in postlingually deafened CI users (n = 48) and normal-hearing controls (n = 54) using simultaneity judgment (SJ) and temporal order judgment (TOJ) tasks. We varied the timing onsets between the auditory and visual components of either a syllable/viseme or a simple flash/beep pairing, and participants indicated either which stimulus appeared first (TOJ) or if the pair occurred simultaneously (SJ). Results indicate that temporal binding windows—the interval within which stimuli are likely to be perceptually ‘bound’—are not significantly different between groups for either speech or non-speech stimuli. However, the point of subjective simultaneity for speech was less visually leading in CI users, who interestingly, also had improved visual-only TOJ thresholds. Further signal detection analysis suggests that this SJ shift may be due to greater visual bias within the CI group, perhaps reflecting heightened attentional allocation to visual cues.
Using whole genome scores to compare three clinical phenotyping methods in complex diseases
Authors: Song Wenyu , Huang Hailiang , Zhang Cheng-Zhong , Bates David W. , Wright Adam 
Published: July 2018

AbstractGenome-wide association studies depend on accurate ascertainment of patient phenotype. However, phenotyping is difficult, and it is often treated as an afterthought in these studies because of the expense involved. Electronic health records (EHRs) may provide higher fidelity phenotypes for genomic research than other sources such as administrative data. We used whole genome association models to evaluate different EHR and administrative data-based phenotyping methods in a cohort of 16,858 Caucasian subjects for type 1 diabetes mellitus, type 2 diabetes mellitus, coronary artery disease and breast cancer. For each disease, we trained and evaluated polygenic models using three different phenotype definitions: phenotypes derived from billing data, the clinical problem list, or a curated phenotyping algorithm. We observed that for these diseases, the curated phenotype outperformed the problem list, and the problem list outperformed administrative billing data. This suggests that using advanced EHR-derived phenotypes can further increase the power of genome-wide association studies.
An integrative omics approach to unravel toxicity mechanisms of environmental chemicals: effects of a formulated herbicide
Authors: Simões Tiago , Novais Sara C. , Natal-da-Luz Tiago , Devreese Bart , de Boer Tjalf , Roelofs Dick , Sousa José P. , van Straalen Nico M. , Lemos Marco F. L. 
Published: July 2018

AbstractThe use of integrative molecular approaches can aid in a comprehensive understanding of the effects of toxicants at different levels of biological organization, also supporting risk assessment. The present study aims to unravel the toxicity mechanisms of a widely used herbicide to the arthropod Folsomia candida exposed in a natural soil, by linking effects on reproduction, proteomics and genome-wide gene expression. The EC50 effects on reproduction over 4 weeks was 4.63 mg glyphosate/kg of soil. The formulation included a polyethoxylated tallowamine as an adjuvant, which at 50% effect on reproduction had an estimated concentration of 0.87–1.49 mg/kg of soil. No effects were observed on survival and reproduction when using the isolated active substance, pointing the toxicity of the formulated product to the co-formulant instead of the active ingredient, glyphosate. RNA sequencing and shotgun proteomics were applied to assess differential transcript and protein expressions between exposed and control organisms in time, respectively. Specific functional categories at protein and transcriptome levels were concordant with each other, despite overall limited correlations between datasets. The exposure to this formulation affected normal cellular respiration and lipid metabolism, inducing oxidative stress and leading to impairment in biological life cycle mechanisms such as molting and reproduction.
Precise Determination of the Temperature Gradients in Laser-irradiated Ultrathin Magnetic Layers for the Analysis of Thermal Spin Current
Authors: Surabhi Srivathsava , Kim Dong-Jun , Cao Van Phuoc , Dong Quoc Viet , Kim Jeong-Mok , Lee Sung Woo , Kuchi Rambabu , Lee Jae-Woong , Yoon Soon-Gil , Choi Jihoon , Park Byong-Guk , Jeong Jong-Ryul 
Published: July 2018

AbstractWe investigated the temperature distribution induced by laser irradiation of ultrathin magnetic films by applying a finite element method (FEM) to the finite difference time domain (FDTD) representation for the analysis of thermal induced spin currents. The dependency of the thermal gradient (∇T) of ultrathin magnetic films on material parameters, including the reflectivity and absorption coefficient were evaluated by examining optical effects, which indicates that reflectance (R) and the apparent absorption coefficient (α*) play important roles in the calculation of ∇T for ultrathin layers. The experimental and calculated values of R and α* for the ultrathin magnetic layers irradiated by laser-driven heat sources estimated using the combined FDTD and FEM method are in good agreement for the amorphous CoFeB and crystalline Co layers of thicknesses ranging from 3~20 nm. Our results demonstrate that the optical parameters are crucial for the estimation of the temperature gradient induced by laser illumination for the study of thermally generated spin currents and related phenomena.
Past continental shelf evolution increased Antarctic ice sheet sensitivity to climatic conditions
Authors: Colleoni Florence , De Santis Laura , Montoli Enea , Olivo Elisabetta , Sorlien Christopher C. , Bart Philip J. , Gasson Edward G. W. , Bergamasco Andrea , Sauli Chiara , Wardell Nigel , Prato Stefano 
Published: July 2018

AbstractOver the past 34 Million years, the Antarctic continental shelf has gradually deepened due to ice sheet loading, thermal subsidence, and erosion from repeated glaciations. The deepening that is recorded in the sedimentary deposits around the Antarctic margin indicates that after the mid-Miocene Climate Optimum (≈15 Ma), Antarctic Ice Sheet (AIS) dynamical response to climate conditions changed. We explore end-members for maximum AIS extent, based on ice-sheet simulations of a late-Pleistocene and a mid-Miocene glaciation. Fundamental dynamical differences emerge as a consequence of atmospheric forcing, eustatic sea level and continental shelf evolution. We show that the AIS contributed to the amplification of its own sensitivity to ocean forcing by gradually expanding and eroding the continental shelf, that probably changed its tipping points through time. The lack of past topographic and bathymetric reconstructions implies that so far, we still have an incomplete understanding of AIS fast response to past warm climate conditions, which is crucial to constrain its future evolution.
Deoxynivalenol induces structural alterations in epidermoid carcinoma cells A431 and impairs the response to biomechanical stimulation
Authors: Del Favero Giorgia , Woelflingseder Lydia , Janker Lukas , Neuditschko Benjamin , Seriani Stefano , Gallina Paolo , Sbaizero Orfeo , Gerner Christopher , Marko Doris 
Published: July 2018

AbstractMorphology together with the capability to respond to surrounding stimuli are key elements governing the spatial interaction of living cells with the environment. In this respect, biomechanical stimulation can trigger significant physiological cascades that can potentially modulate toxicity. Deoxynivalenol (DON, vomitoxin) is one of the most prevalent mycotoxins produced by Fusarium spp. and it was used to explore the delicate interaction between biomechanical stimulation and cytotoxicity in A431 cells. In fact, in addition of being a food contaminant, DON is a relevant toxin for several organ systems. The combination between biomechanical stimulation and the mycotoxin revealed how DON can impair crucial functions affecting cellular morphology, tubulin and lysosomes at concentrations even below those known to be cytotoxic in routine toxicity studies. Sub-toxic concentrations of DON (0.1–1 μM) impaired the capability of A431 cells to respond to a biomechanical stimulation that normally sustains trophic effects in these cells. Moreover, the effects of DON (0.1–10 μM) were partially modulated by the application of uniaxial stretching (0.5 Hz, 24 h, 15% deformation). Ultimately, proteomic analysis revealed the potential of DON to alter several proteins necessary for cell adhesion and cytoskeletal modulation suggesting a molecular link between biomechanics and the cytotoxic potential of the mycotoxin.
Prenatal Bisphenol A Exposure is Linked to Epigenetic Changes in Glutamate Receptor Subunit Gene Grin2b in Female Rats and Humans
Authors: Alavian-Ghavanini Ali , Lin Ping-I , Lind P. Monica , Risén Rimfors Sabina , Halin Lejonklou Margareta , Dunder Linda , Tang Mandy , Lindh Christian , Bornehag Carl-Gustaf , Rüegg Joëlle 
Published: July 2018

AbstractBisphenol A (BPA) exposure has been linked to neurodevelopmental disorders and to effects on epigenetic regulation, such as DNA methylation, at genes involved in brain function. High doses of BPA have been shown to change expression and regulation of one such gene, Grin2b, in mice. Yet, if such changes occur at relevant doses in animals and humans has not been addressed. We investigated if low-dose developmental BPA exposure affects DNA methylation and expression of Grin2b in brains of adult rats. Furthermore, we assessed associations between prenatal BPA exposure and Grin2b methylation in 7-year old children. We found that Grin2b mRNA expression was increased and DNA methylation decreased in female, but not in male rats. In humans, prenatal BPA exposure was associated with increased methylation levels in girls. Additionally, low APGAR scores, a predictor for increased risk for neurodevelopmental diseases, were associated with higher Grin2b methylation levels in girls. Thus, we could link developmental BPA exposure and low APGAR scores to changes in the epigenetic regulation of Grin2b, a gene important for neuronal function, in a sexual dimorphic fashion. Discrepancies in exact locations and directions of the DNA methylation change might reflect differences between species, analysed tissues, exposure level and/or timing.
Distribution of magnetic remanence carriers in the human brain
Authors: Gilder Stuart A. , Wack Michael , Kaub Leon , Roud Sophie C. , Petersen Nikolai , Heinsen Helmut , Hillenbrand Peter , Milz Stefan , Schmitz Christoph 
Published: July 2018

AbstractThat the human brain contains magnetite is well established; however, its spatial distribution in the brain has remained unknown. We present room temperature, remanent magnetization measurements on 822 specimens from seven dissected whole human brains in order to systematically map concentrations of magnetic remanence carriers. Median saturation remanent magnetizations from the cerebellum were approximately twice as high as those from the cerebral cortex in all seven cases (statistically significantly distinct, p = 0.016). Brain stems were over two times higher in magnetization on average than the cerebral cortex. The ventral (lowermost) horizontal layer of the cerebral cortex was consistently more magnetic than the average cerebral cortex in each of the seven studied cases. Although exceptions existed, the reproducible magnetization patterns lead us to conclude that magnetite is preferentially partitioned in the human brain, specifically in the cerebellum and brain stem.
Absorbance measurements of oxidation of homogentisic acid accelerated by the addition of alkaline solution with sodium hypochlorite pentahydrate
Authors: Tokuhara Yasunori , Shukuya Kenichi , Tanaka Masami , Sogabe Keisuke , Ejima Yasukazu , Hosokawa Sho , Ohsaki Hiroyuki , Morinishi Tatsuya , Hirakawa Eiichiro , Yatomi Yutaka , Shimosawa Tatsuo 
Published: July 2018

AbstractThe urine of patients with alkaptonuria turns dark brown due to the oxidation of homogentisic acid (HGA) to benzoquinone acetic acid (BQA), and this is accelerated by the addition of alkali. We recently reported that alkaptonuric urine and HGA after the addition of alkali showed characteristic peaks at 406 and 430 nm. In order to improve the sensitivity of our spectrometric method for the detection of HGA, we accelerated the oxidation of HGA to BQA using sodium hypochlorite pentahydrate (NaOCl·5H2O), which is a strong oxidant. In the present study, we measured the absorption spectra of alkaptonuric urine and HGA solution after the addition of sodium hydroxide (NaOH) or NaOH with NaOCl·5H2O and analyzed the oxidation reaction of HGA after alkalization using a liquid chromatography time-of-flight mass spectrometer (LC/TOF-MS) and nuclear magnetic resonance (NMR) spectrometry. We accelerated the oxidation of HGA to BQA by adding NaOH with NaOCl·5H2O, and this absorbance measurement was useful for more sensitively observing the oxidation of HGA than LC/TOF-MS and NMR spectroscopy. This quick and easy screening method may be suitable for the diagnosis of alkaptonuria.
Sirt1 activator induces proangiogenic genes in preadipocytes to rescue insulin resistance in diet-induced obese mice
Authors: Nawaz Allah , Mehmood Arshad , Kanatani Yukiko , Kado Tomonobu , Igarashi Yoshiko , Takikawa Akiko , Yamamoto Seiji , Okabe Keisuke , Nakagawa Takashi , Yagi Kunimasa , Fujisaka Shiho , Tobe Kazuyuki 
Published: July 2018

AbstractSirt1 plays an important role in regulating glucose and lipid metabolism in obese animal models. Impaired adipose tissue angiogenesis in the obese state decreases adipogenesis and thereby contributes to glucose intolerance and lipid metabolism. However, the mechanism by which Sirt1 activation affects obesity-associated impairments in angiogenesis in the adipose tissue is not fully understood. Here, we show that SRT1720 treatment induces angiogenic genes in cultured 3T3-L1 preadipocytes and ex vivo preadipocytes. siRNA-mediated knockdown of Sirt1 in 3T3-L1 preadipocytes downregulated angiogenic genes in the preadipocytes. SRT1720 treatment upregulated metabolically favorable genes and reduced inflammatory gene expressions in the adipose tissue of diet-induced obese (DIO) mice. Collectively, these findings suggest a novel role of SRT1720-induced Sirt1 activation in the induction of angiogenic genes in preadipocytes, thereby reducing inflammation and fibrosis in white adipose tissue (WAT) and promoting insulin sensitivity.
Enhancing cellulose functionalities by size reduction using media-mill
Authors: Dubey Rajni , Toh Yon-Rui , Yeh An-I 
Published: July 2018

AbstractThis study explored the feasibility of enhancing cellulose functionalities by using media milling to reduce the size of cellulose particles, and assayed various physicochemical and physiological properties of the resulting cellulose. Cellulose has been recognized as dietary fiber by USFDA due to its health benefits. However, its properties like low degradability, stiff texture, and insolubility in water limits its applicability in foods. Milling reduced the volume mean size of cellulose from 25.7 μm to 0.9 μm, which in turn increased the specific surface area (36.78-fold), and swelling capacity (9-fold). Conversely, a reduction in the bulk density (1.41 to 1.32 g/mL) and intrinsic viscosity (165.64 to 77.28 mL/g) were found. The milled cellulose also had significantly enhanced capacity for holding water and binding bile acids and sugars. Moreover, the size reduction also resulted in increased fermentability of cellulose into short chain fatty acids using three human fecal microflora samples. The increase in production of acetate (2880.60%), propionate (2738.52%), and butyrate (2865.89%) after fermentation of cellulose for 24 h were significantly enhanced by size reduction. With these improved characteristics, the milled cellulose might have beneficial physiological effects including laxation as well as reduced blood cholesterol and glucose attenuation.
Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns
Authors: Manca Sonia , Upadhyaya Bijaya , Mutai Ezra , Desaulniers Amy T. , Cederberg Rebecca A. , White Brett R. , Zempleni Janos 
Published: July 2018

AbstractExosomes participate in cell-to-cell communication, facilitated by the transfer of RNAs, proteins and lipids from donor to recipient cells. Exosomes and their RNA cargos do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as the inter-species transfer of exosomes and RNAs in bovine milk to humans. Here, we assessed the bioavailability and distribution of exosomes and their microRNA cargos from bovine, porcine and murine milk within and across species boundaries. Milk exosomes labeled with fluorophores or fluorescent fusion proteins accumulated in liver, spleen and brain following suckling, oral gavage and intravenous administration in mice and pigs. When synthetic, fluorophore-labeled microRNAs were transfected into bovine milk exosomes and administered to mice, distinct species of microRNAs demonstrated unique distribution profiles and accumulated in intestinal mucosa, spleen, liver, heart or brain. Administration of bovine milk exosomes failed to rescueDroshahomozygous knockout mice, presumably due to low bioavailability or lack of essential microRNAs.