bluuebunny/crossref_metadata_2025_split huggingface dataset:
FOXO3a Expression Regulated by ERK Signaling is Inversely Correlated With Y‐Box Binding Protein‐1 Expression in Prostate Cancer
Authors: Imada Kenjiro , Shiota Masaki , Kuroiwa Kentaro , Sugimoto Masaaki , Abe Tatsuro , Kohashi Kenichi , Yokomizo Akira , Eto Masatoshi , Naito Seiji , Oda Yoshinao 
Published: October 2016

BACKGROUNDFOXO3a is a member of the forkhead O transcription factors. FOXO3a induces the factors that contribute to cell cycle arrest and is considered a tumor suppressor in several malignant tumors. Y‐box binding protein‐1 (YB‐1) is a multifunctional protein whose high expression is correlated with poor prognoses in various malignant tumors. In the current study, we investigated the relationship between FOXO3a and YB‐1 to validate their functional roles in prostate cancer.METHODSWestern blotting and cytotoxicity assays were conducted in prostate cancer cells, LNCaP, and 22Rv1 cells. We also evaluated the protein expressions of FOXO3a and YB‐1 in human prostate cancer tissues, using radical prostatectomy specimens. Then, we investigated the correlations between protein expressions and clinicopathologic parameters.RESULTSWe found that both FOXO3a and YB‐1 proteins were phosphorylated by ERK signaling, resulting in FOXO3a inactivation and YB‐1 activation in LNCaP and 22Rv1 cells. Inversely, inhibition of MEK or treatment with metformin activated FOXO3a through inactivation of ERK signaling and suppressed the viability of LNCaP and 22Rv1 cells in a dose‐dependent manner. In immunohistochemical analysis, FOXO3a nuclear expression was inversely correlated with YB‐1 nuclear expression (P < 0.0001). Furthermore, high FOXO3a nuclear expression was inversely correlated with a higher Gleason grade (P < 0.0001) and higher preoperative PSA (P = 0.0437).CONCLUSIONSThese results showed that in prostate cancer, FOXO3a, and YB‐1 play inverse reciprocal roles as a tumor‐suppressor gene and oncogene, respectively, through their master regulator ERK. Prostate 77:145–153, 2017. © 2016 Wiley Periodicals, Inc.
Elevated C‐Peptides, Abdominal Obesity, and Abnormal Adipokine Profile are Associated With Higher Gleason Scores in Prostate Cancer
Authors: Di Sebastiano Katie M. , Pinthus Jehonathan H. , Duivenvoorden Wilhelmina C.M. , Patterson Laurel , Dubin Joel A. , Mourtzakis Marina 
Published: October 2016

BACKGROUNDProstate cancer development is associated with numerous lifestyle factors (i.e., physical activity, nutrition intake) and metabolic perturbations. These factors have been studied independently; here, we used an integrative approach to characterize these lifestyle and metabolic parameters in men undergoing diagnostic prostate biopsies.METHODSWe prospectively evaluated 51 consecutive men for body composition, metabolic factors including glucose‐ and lipid‐related measures, as well as lifestyle factors prior to prostate biopsy. Evaluations were performed in a blinded manner and were subsequently related to biopsy outcomes for: (i) presence or absence of cancer; and (ii) where cancer was present, Gleason score.RESULTSSerum C‐peptide concentrations were significantly greater in participants with Gleason scores ≥4 + 3 (2.8 ± 1.1 ng/ml) compared to those with Gleason 3 + 3 (1.4 ± 0.6 ng/ml) or Gleason 3 + 4 (1.3 ± 0.8 ng/ml, P = 0.002), suggesting greater insulin secretion despite lack of differences in fasting glucose concentrations. Central adiposity, measured by waist circumference, was significantly greater in participants with Gleason ≥4 + 3 (110.1 ± 7.4 cm) compared to those with Gleason 3 + 4 (102.0 ± 9.5 cm, P = 0.028). Men with Gleason ≥4 + 3 also had significantly greater leptin concentrations than those with lower Gleason scores (Gleason ≥4 + 3: 15.6 ± 3.3 ng/ml vs. Gleason 3 + 4: 8.1 ± 8.1 ng/ml, P < 0.05) and leptin:adiponectin ratio (Gleason ≥4 + 3: 9.7 ± 6.1 AU, Gleason 3 + 4: 2.9 ± 3.2, Gleason 3 + 3: 2.4 ± 2.1 AU, P = 0.013).CONCLUSIONSWe profiled a cluster of obesity‐related metabolic perturbations (C‐peptide, central adiposity, leptin, and leptin:adiponectin ratios) which may associate with more aggressive prostate cancer histology. Prostate 77:211–221, 2017. © 2016 Wiley Periodicals, Inc.
Solution structure of the Cys74 to Ala74 mutant of the recombinant catalytic domain of Zoocin A
Authors: Xing Minli , Simmonds Robin S. , Timkovich Russell 
Published: October 2016

ABSTRACTZoocin A is a Zn‐metallopeptidase secreted by Streptococcus zooepidemicus strain 4881. Its catalytic domain is responsible for cleaving the D‐alanyl‐L‐alanine peptide bond in streptococcal peptidoglycan. The solution NMR structure of the Cys74 to Ala74 mutant of the recombinant catalytic domain (rCAT C74A) has been determined. With a previous structure determination for the recombinant target recognition domain (rTRD), this completes the 3D structure of zoocin A. While the structure of rCAT C74A resembles those of the catalytic domains of lysostaphin and LytM, the substrate binding groove is wider and no tyrosine residue was observed in the active site. Proteins 2016; 85:177–181. © 2016 Wiley Periodicals, Inc.
Exciton self‐trapped on Si–Si dimers on the surface of silicon nanocrystal: Experimental evidence
Authors: Andreev B. A. , Yablonskiy A. N. , Krasilnik Z. F. , Ershov A. V. , Grachev D. A. , Gert A. V. , Gusev O. B. , Yassievich I. N. 
Published: October 2016

AbstractThe intensive photoluminescence (PL) band corresponding to the self‐trapped excitons (STEs) at surface Si–Si dimers has been observed for the multilayer periodical nanostructures (SiO/nc‐Si/) with average nanocrystal size of 2.5 and 3.5 nm. The maximum of the band is located at 1.06 m (1.17 eV) and does not depend on the nanocrystal size. The decay times of the PL band are 5.9 and 5.3 ms for the nanocrystal size of 2.5 and 3.5 nm, correspondingly. The obtained experimental results give a direct evidence of the exciton self‐trapping on the silicon nanocrystals surface predicted by G. Allan, C. Delerue, and M. Lannoo [Phys. Rev. B 76, 2961 (1996)].
Graphene screen‐printed radio‐frequency identification devices on flexible substrates
Authors: Arapov Kirill , Jaakkola Kaarle , Ermolov Vladimir , Bex Guy , Rubingh Eric , Haque Samiul , Sandberg Henrik , Abbel Robert , de With Gijsbertus , Friedrich Heiner 
Published: October 2016

Despite the great promise of printed flexible electronics from 2D crystals, and especially graphene, few scalable applications have been reported so far that can be termed roll‐to‐roll compatible. Here we combine screen printed graphene with photonic annealing to realize radio‐frequency identification devices with a reading range of up to 4 meters. Most notably our approach leads to fatigue resistant devices showing less than 1% deterioration of electrical properties after 1000 bending cycles. The bending fatigue resistance demonstrated on a variety of technologically relevant plastic and paper substrates renders the material highly suitable for various printable wearable devices, where repeatable dynamic bending stress is expected during usage. All applied printing and post‐processing methods are compatible with roll‐to‐roll manufacturing and temperature sensitive flexible substrates providing a platform for the scalable manufacturing of mechanically stable and environmentally friendly graphene printed electronics.
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Stable isotope analyses of oxygen (18O:17O:16O) and chlorine (37Cl:35Cl) in perchlorate: reference materials, calibrations, methods, and interferences
Authors: Böhlke J. K. , Mroczkowski Stanley J. , Sturchio Neil C. , Heraty Linnea J. , Richman Kent W. , Sullivan Donald B. , Griffith Kris N. , Gu Baohua , Hatzinger Paul B. 
Published: October 2016

RationalePerchlorate (ClO4−) is a common trace constituent of water, soils, and plants; it has both natural and synthetic sources and is subject to biodegradation. The stable isotope ratios of Cl and O provide three independent quantities for ClO4− source attribution and natural attenuation studies: δ37Cl, δ18O, and δ17O (or Δ17O or 17Δ) values. Documented reference materials, calibration schemes, methods, and interferences will improve the reliability of such studies.MethodsThree large batches of KClO4 with contrasting isotopic compositions were synthesized and analyzed against VSMOW‐SLAP, atmospheric O2, and international nitrate and chloride reference materials. Three analytical methods were tested for O isotopes: conversion of ClO4− to CO for continuous‐flow IRMS (CO‐CFIRMS), decomposition to O2 for dual‐inlet IRMS (O2‐DIIRMS), and decomposition to O2 with molecular‐sieve trap (O2‐DIIRMS+T). For Cl isotopes, KCl produced by thermal decomposition of KClO4 was reprecipitated as AgCl and converted into CH3Cl for DIIRMS.ResultsKClO4 isotopic reference materials (USGS37, USGS38, USGS39) represent a wide range of Cl and O isotopic compositions, including non‐mass‐dependent O isotopic variation. Isotopic fractionation and exchange can affect O isotope analyses of ClO4− depending on the decomposition method. Routine analyses can be adjusted for such effects by normalization, using reference materials prepared and analyzed as samples. Analytical errors caused by SO42−, NO3−, ReO42−, and C‐bearing contaminants include isotope mixing and fractionation effects on CO and O2, plus direct interference from CO2 in the mass spectrometer. The results highlight the importance of effective purification of ClO4− from environmental samples.ConclusionsKClO4 reference materials are available for testing methods and calibrating isotopic data for ClO4− and other substances with widely varying Cl or O isotopic compositions. Current ClO4− extraction, purification, and analysis techniques provide relative isotope‐ratio measurements with uncertainties much smaller than the range of values in environmental ClO4−, permitting isotopic evaluation of environmental ClO4− sources and natural attenuation. Copyright © 2016 John Wiley & Sons, Ltd.
Verstärkung orthotroper Stahlfahrbahnplatten mit Hochleistungsbetonen in Hinblick auf ausreichende Restlebensdauer
Authors: Unterweger Harald , Novak Friedrich 
Published: October 2016

AbstractReine Stahlbrückentragwerke mit orthotroper Fahrbahnplatte für schlanke sowie weitgespannte Tragwerke wurden im deutschsprachigen Raum sehr häufig in den 60er und 70er Jahren des vorigen Jahrhunderts errichtet. Bei der konstruktiven Auslegung stand die reine Tragsicherheit im Vordergrund, ohne rechnerische Nachweise der Ermüdungsfestigkeit des Fahrbahndecks. Der dramatische Zuwachs des Schwerverkehrs im europäischen Straßennetz in Hinblick Achslasthöhe und Schwerverkehrsfrequenz bedeutet, dass aktuell – nach etwa 50 Betriebsjahren – mitunter die rechnerische Restlebensdauer bereits erschöpft ist. Nachfolgend werden die wesentlichen Ergebnisse eines Forschungsprojekts dargestellt, mit dem herausfordernden Ziel, die bituminösen Fahrbahnbeläge durch eine Platte aus Hochleistungsbeton zu ersetzen, so dass zumindest weitere 50 Betriebsjahre möglich werden.Strengthening of orthotropic steel decks using UHPC‐concrete for additional at least 50 years in service. Steel orthotropic bridge decks for slender and long spanned girder bridges were frequently built in the 60ties and 70ties of the last century in the German‐speaking countries. In the design of such bridge decks only the ultimate load carrying capacity was considered, without fatigue aspects. Due to the dramatic increase of heavy traffic in the European road network, sometimes the calculated remaining fatigue life is exhausted, after only 50 years of service life. In the paper the relevant results of a research project are presented, with the challenging aim to increase the service life of such orthotropic bridge decks to at least 50 years after strengthening.
Unexpected Microscopically Positive Proximal Resection Margins in Esophageal Squamous Cell Carcinoma After Chemoradiotherapy: Predictors and Prognostic Significance
Authors: Chiu Chien‐Hung , Chao Yin‐Kai , Wen Yu‐Wen , Chang Hsien‐Kun , Tseng Chen‐Kan , Liu Yun‐Hen 
Published: October 2016

AbstractBackgroundEsophageal cancer has the propensity to spread in a longitudinal manner (either proximally or distally), potentially resulting in the unexpected presence of microscopic disease at grossly tumor‐free margins. The clinical significance of this phenomenon in patients treated with chemoradiotherapy (CRT) remains unclear. The purpose of this study was to investigate the prevalence, predictors, and prognostic impact of microscopically positive proximal resection margins (PPRMs) in patients with esophageal squamous cell carcinoma (ESCC) who received CRT.MethodsBetween 2000 and 2014, we identified 332 ESCC patients who underwent complete gross resection (R0/R1) following CRT. Patients were divided into two groups according to the status of the proximal resection margins on microscopic examination [negative proximal resection margins (NPRMs) vs PPRMs]. The occurrence of anastomotic leakage (AL) and anastomotic recurrence (AR) served as outcome measures.ResultsSixteen (4.8 %) patients had PPRM. The presence of PPRM was not associated with AL but was a strong predictor of AR (PPRM vs NPRM, 23.1 vs 7 %, respectively, P = 0.033). Multivariate analysis identified a resection margin length <3.5 cm [odds ratio (OR) 4.473, P = 0.022] and salvage resection (OR 3.171, P = 0.045) as independent predictors of PPRM. The estimated PPRM rates were 16.7, 6.3, and 1.3 % for patients with 2, 1, and 0 predictors, respectively.ConclusionsPPRM occurred in 4.8 % of ESCC patients following CRT and was associated with AR. An intraoperative frozen section margin analysis should be performed in patients carrying risk factors to avoid unexpected PPRM.
Preoperative Glycosylated Hemoglobin Levels Predict Anastomotic Leak After Esophagectomy with Cervical Esophagogastric Anastomosis
Authors: Okamura Akihiko , Watanabe Masayuki , Imamura Yu , Kamiya Satoshi , Yamashita Kotaro , Kurogochi Takanori , Mine Shinji 
Published: October 2016

AbstractBackgroundPatients with diabetes are considered at increased risk of delayed wound healing and infectious complications, yet the relationship between diabetes and anastomotic leak (AL) remains unclear. Given that glycosylated hemoglobin (HbA1c) is a validated indicator of the long‐term glycemic state, we evaluated the relationship between preoperative HbA1c levels and AL after esophagectomy.MethodsWe assessed 300 consecutive patients who underwent esophagectomy reconstructed with cervical esophagogastric anastomosis between 2011 and 2015. HbA1c levels were measured within 90 days before esophagectomy. We performed comparison between the patients with and without diabetes. In addition, the predictive factors for AL, as well as the relationship between HbA1c levels and AL, were investigated.ResultsAmong the 300 patients, 35 had diabetes. The overall prevalence of AL was 11.7%, and patients with diabetes had a higher prevalence of AL than those without (p = 0.045). In univariate analysis, we identified diabetes, HbA1c level, and hand‐sewn anastomosis as risk factors for AL significantly (p = 0.033, 0.009, and 0.011, respectively), but we also found previous smoking history, chronic hepatic disease, and supracarinal tumor location also showed tendencies to be risk factors (p = 0.057, 0.055, and 0.064, respectively). Multivariate logistic regression analysis indicated that chronic hepatic disease (p = 0.048), increased HbA1c level (p = 0.011), and hand‐sewn anastomosis (p = 0.021) were independent risk factors for AL.ConclusionsPreoperative HbA1c level was significantly associated with the development of AL after cervical esophagogastric anastomosis. We recommend preoperative HbA1c screening for all patients scheduled to undergo esophagectomy.
Trends in Spouses’ Shared Time in the United States, 1965–2012
Authors: Genadek Katie R. , Flood Sarah M. , Roman Joan Garcia 
Published: October 2016

AbstractDespite major demographic changes over the past 50 years and strong evidence that time spent with a spouse is important for marriages, we know very little about how time with a spouse has changed—or not—in the United States. Using time diary data from 1965–2012, we examine trends in couples’ shared time in the United States during a period of major changes in American marriages and families. We find that couples without children spent more total time together and time alone together in 2012 than they did in 1965, with total time and time alone together both peaking in 1975. For parents, time spent together increased between 1965 and 2012, most dramatically for time spent with a spouse and children. Decomposition analyses show that changes in behavior rather than changing demographics explain these trends, and we find that the increases in couples’ shared time are primarily concentrated in leisure activities.
Vitamin D receptor expression in human bone tissue and dose-dependent activation in resorbing osteoclasts
Authors: Zarei Allahdad , Morovat Alireza , Javaid Kassim , Brown Cameron P 
Published: October 2016

AbstractThe effects of vitamin D on osteoblast mineralization are well documented. Reports of the effects of vitamin D on osteoclasts, however, are conflicting, showing both inhibition and stimulation. Finding that resorbing osteoclasts in human bone express vitamin D receptor (VDR), we examined their response to different concentrations of 25-hydroxy vitamin D3 [25(OH)D3] (100 or 500 nmol·L−1) and 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] (0.1 or 0.5 nmol·L−1) metabolites in cell cultures. Specifically, CD14+ monocytes were cultured in charcoal-stripped serum in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Tartrate-resistant acid phosphatase (TRAP) histochemical staining assays and dentine resorption analysis were used to identify the size and number of osteoclast cells, number of nuclei per cell and resorption activity. The expression of VDR was detected in human bone tissue (ex vivo) by immunohistochemistry and in vitro cell cultures by western blotting. Quantitative reverse transcription-PCR (qRT-PCR) was used to determine the level of expression of vitamin D-related genes in response to vitamin D metabolites. VDR-related genes during osteoclastogenesis, shown by qRT-PCR, was stimulated in response to 500 nmol·L−1 of 25(OH)D3 and 0.1–0.5 nmol·L−1 of 1,25(OH)2D3, upregulating cytochrome P450 family 27 subfamily B member 1 (CYP27B1) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1). Osteoclast fusion transcripts transmembrane 7 subfamily member 4 (tm7sf4) and nuclear factor of activated T-cell cytoplasmic 1 (nfatc1) where downregulated in response to vitamin D metabolites. Osteoclast number and resorption activity were also increased. Both 25(OH)D3 and 1,25(OH)2D3 reduced osteoclast size and number when co-treated with RANKL and M-CSF. The evidence for VDR expression in resorbing osteoclasts in vivo and low-dose effects of 1,25(OH)2D3 on osteoclasts in vitro may therefore provide insight into the effects of clinical vitamin D treatments, further providing a counterpoint to the high-dose effects reported from in vitro experiments.
Targeting Mll1 H3K4 methyltransferase activity to guide cardiac lineage specific reprogramming of fibroblasts
Authors: Liu Liu , Lei Ienglam , Karatas Hacer , Li Yangbing , Wang Li , Gnatovskiy Leonid , Dou Yali , Wang Shaomeng , Qian Li , Wang Zhong 
Published: October 2016

AbstractGeneration of induced cardiomyocytes (iCMs) directly from fibroblasts offers a great opportunity for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate. To address this issue, we attempted to identify small molecules that could potentiate the reprogramming ability towards cardiac fate by removing inhibitory roadblocks. Using mouse embryonic fibroblasts as the starting cell source, we first screened 47 cardiac development related epigenetic and transcription factors, and identified an unexpected role of H3K4 methyltransferase Mll1 and related factor Men1 in inhibiting iCM reprogramming. We then applied small molecules (MM408 and MI503) of Mll1 pathway inhibitors and observed an improved efficiency in converting embryonic fibroblasts and cardiac fibroblasts into functional cardiomyocyte-like cells. We further observed that these inhibitors directly suppressed the expression of Mll1 target gene Ebf1 involved in adipocyte differentiation. Consequently, Mll1 inhibition significantly decreased the formation of adipocytes during iCM induction. Therefore, Mll1 inhibitors likely increased iCM efficiency by suppressing alternative lineage gene expression. Our studies show that targeting Mll1 dependent H3K4 methyltransferase activity provides specificity in the process of cardiac reprogramming. These findings shed new light on the molecular mechanisms underlying cardiac conversion of fibroblasts and provide novel targets and small molecules to improve iCM reprogramming for clinical applications.
A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome
Authors: Mathias Rasika Ann , Taub Margaret A. , Gignoux Christopher R. , Fu Wenqing , Musharoff Shaila , O'Connor Timothy D. , Vergara Candelaria , Torgerson Dara G. , Pino-Yanes Maria , Shringarpure Suyash S. , Huang Lili , Rafaels Nicholas , Boorgula Meher Preethi , Johnston Henry Richard , Ortega Victor E. , Levin Albert M. , Song Wei , Torres Raul , Padhukasahasram Badri , Eng Celeste , Mejia-Mejia Delmy-Aracely , Ferguson Trevor , Qin Zhaohui S. , Scott Alan F. , Yazdanbakhsh Maria , Wilson James G. , Marrugo Javier , Lange Leslie A. , Kumar Rajesh , Avila Pedro C. , Williams L. Keoki , Watson Harold , Ware Lorraine B. , Olopade Christopher , Olopade Olufunmilayo , Oliveira Ricardo , Ober Carole , Nicolae Dan L. , Meyers Deborah , Mayorga Alvaro , Knight-Madden Jennifer , Hartert Tina , Hansel Nadia N. , Foreman Marilyn G. , Ford Jean G. , Faruque Mezbah U. , Dunston Georgia M. , Caraballo Luis , Burchard Esteban G. , Bleecker Eugene , Araujo Maria Ilma , Herrera-Paz Edwin Francisco , Gietzen Kimberly , Grus Wendy E. , Bamshad Michael , Bustamante Carlos D. , Kenny Eimear E. , Hernandez Ryan D. , Beaty Terri H. , Ruczinski Ingo , Akey Joshua ,   CAAPA, Campbell Monica , Chavan Sameer , Foster Cassandra , Gao Li , Horowitz Edward , Ortiz Romina , Potee Joseph , Gao Jingjing , Hu Yijuan , Hansen Mark , Deshpande Aniket , Locke Devin P. , Grammer Leslie , Kim Kwang-YounA , Schleimer Robert , De La Vega Francisco M. , Szpiech Zachary A. , Oluwole Oluwafemi , Arinola Ganiyu , Correa Adolfo , Musani Solomon , Chong Jessica , Nickerson Deborah , Reiner Alexander , Maul Pissamai , Maul Trevor , Martinez Beatriz , Meza Catherine , Ayestas Gerardo , Landaverde-Torres Pamela , Erazo Said Omar Leiva , Martinez Rosella , Mayorga Luis F. , Ramos Hector , Saenz Allan , Varela Gloria , Vasquez Olga Marina , Samms-Vaughan Maureen , Wilks Rainford J. , Adegnika Akim , Ateba-Ngoa Ulysse , Barnes Kathleen C. 
Published: October 2016

AbstractThe African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow across multiple regions. Moreover, we refine estimates on the burden of deleterious variants carried across populations and how this varies with African ancestry. Our data are an important resource for empowering disease mapping studies in African-admixed individuals and will facilitate gene discovery for diseases disproportionately affecting individuals of African ancestry.