bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMPs as new insulin sensitizers: enhanced glucose uptake in mature 3T3-L1 adipocytes via PPARγ and GLUT4 upregulation
Authors: Schreiber Isabelle , Dörpholz Gina , Ott Claus-Eric , Kragesteen Bjørt , Schanze Nancy , Lee Cory Thomas , Köhrle Josef , Mundlos Stefan , Ruschke Karen , Knaus Petra 
Published: December 2017

AbstractInsulin-resistance is the main cause of type 2 diabetes. Here we describe the identification and characterization of BMP2 and BMP6 as new insulin-sensitizing growth factors in mature adipocytes. We show that BMP2 and BMP6 lead to enhanced insulin-mediated glucose uptake in both insulin-sensitive and -insensitive adipocytes. We exclude a direct effect of BMP2 or BMP6 on translocation of GLUT4 to the plasma membrane and demonstrate that these BMPs increase GLUT4 protein levels equipotent to Rosiglitazone. BMPs induce expression of PPARγ as the crucial mediator for the insulin-sensitizing effect. A comprehensive RNA-Seq analysis in mature adipocytes revealed regulation of both BMP/Smad and PPARγ target genes. The effects of BMP2 and BMP6 are not completely redundant and include regulation of genes involved in glucose and fatty acid metabolism and adipokine expression. Collectively, these findings suggest the BMP2 and BMP6 pathway(s) as promising new drug targets to treat insulin resistance.
Stromal Versican Regulates Tumor Growth by Promoting Angiogenesis
Authors: Asano Keiichi , Nelson Courtney M. , Nandadasa Sumeda , Aramaki-Hattori Noriko , Lindner Daniel J. , Alban Tyler , Inagaki Junko , Ohtsuki Takashi , Oohashi Toshitaka , Apte Suneel S. , Hirohata Satoshi 
Published: December 2017

AbstractThe proteoglycan versican is implicated in growth and metastases of several cancers. Here we investigated a potential contribution of stromal versican to tumor growth and angiogenesis. We initially determined versican expression by several cancer cell lines. Among these, MDA-MB231 and B16F10 had none to minimal expression in contrast to Lewis lung carcinoma (LLC). Notably, tumors arising from these cell lines had higher versican levels than the cell lines themselves suggesting a contribution from the host-derived tumor stroma. In LLC-derived tumors, both the tumor and stroma expressed versican at high levels. Thus, tumor stroma can make a significant contribution to tumor versican content. Versican localized preferentially to the vicinity of tumor vasculature and macrophages in the tumor. However, an ADAMTS protease-generated versican fragment uniquely localized to vascular endothelium. To specifically determine the impact of host/stroma-derived versican we therefore compared growth of tumors from B16F10 cells, which produced littleversican, inVcanhdf/+mice and wild-type littermates. Tumors inVcanhdf/+mice had reduced growth with a lower capillary density and accumulation of capillaries at the tumor periphery. These findings illustrate the variability of tumor cell line expression of versican, and demonstrate that versican is consistently contributed by the stromal tissue, where it contributes to tumor angiogenesis.
Deciphering transcriptional regulation in human embryonic stem cells specified towards a trophoblast fate
Authors: Jain Ashish , Ezashi Toshihiko , Roberts R. Michael , Tuteja Geetu 
Published: December 2017

AbstractDifferentiated human embryonic stem cells (hESC) continue to provide a model for studying early trophoblast cells (TB), but many questions have been raised regarding their true identity. Therefore, we carried out a global and unbiased analysis on previously published transcriptomic profiles for hESC differentiated to TB by means of bone morphogenetic protein-4 and inhibitors of activin A and fibroblast growth factor-2 signaling (BAP treatment). Our results confirm that BAP treated hESC (ESCd) lack a mesoderm signature and are a subtype of placental cells unlike those present at term. ESCd display a high level of expression of genes implicated in migration and invasion compared to commonly used, immortalized TB cell lines and primary cells from term placenta. Co-expression network analysis also identified gene modules involved in cell migration and adhesion, processes that are likely critical during the beginning stages of placentation. Finally, protein-protein interaction analysis predicted several additional genes that may play important roles in early stages of placental development. Together, our analyses provide novel insights into the transcriptional programs that are active in ESCd.
Virtual screening for inhibitors of the human TSLP:TSLPR interaction
Authors: Van Rompaey Dries , Verstraete Kenneth , Peelman Frank , Savvides Savvas N. , Augustyns Koen , Van Der Veken Pieter , De Winter Hans 
Published: December 2017

AbstractThe pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Rα), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted anin silicocharacterization of the TSLP:TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently testedin vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP:alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP:TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-of-principle for use of fragments in the inhibition of TSLP:TSLPR complexation.
Optimization of cotton variety registration criteria aided with a genotype-by-trait biplot analysis
Authors: Xu Naiyin , Fok Michel , Li Jian , Yang Xiaoni , Yan Weikai 
Published: December 2017

AbstractChina is one of the largest cotton producing countries in the world thanks to high yields, on which a variety registration system has mainly focused, so that a lack of quality is nowadays acknowledged as a weak point of the cotton industry in that country. The objective of this study was to check the hypothesis that bias in cultivar selection in favor of yield has been maintained through the application of an imperfect selection index (SI), but that a better outcome is possible. Our demonstration is based on an analysis of the data from ten years of cotton variety trials using genotype-by-trait biplots, implemented both for the cultivar selection index (SI) currently applied in China and for an adjusted selection index (ASI) that more effectively took into account the antagonism between yield and quality traits. The main findings were: 1) significant negative associations between yield and fiber quality hindered their simultaneous improvement; 2) registered genotypes were mainly determined by the SI which was primarily yield-oriented; 3) no progress in fiber quality was recorded unlike yield; 4) balanced progress in yield and quality is possible through an adjusted selection index (ASI) guided by genotype-by-trait biplot analysis.
A tyrosinase, mTyr-CNK, that is functionally available as a monophenol monooxygenase
Authors: Do Hyunsu , Kang Eungsu , Yang Byeongseon , Cha Hyung Joon , Choi Yoo Seong 
Published: December 2017

AbstractTyrosinase efficiently catalyzes the ortho-hydroxylation of monophenols and the oxidation of diphenols without any additional cofactors. Although it is of significant interest for the biosynthesis of catechol derivatives, the rapid catechol oxidase activity and inactivation of tyrosinase have hampered its practical utilization as a monophenol monooxygenase. Here, we prepared a functional tyrosinase that exhibited a distinguished monophenolase/diphenolase activity ratio (Vmax mono/ Vmax di = 3.83) and enhanced catalytic efficiency against L-tyrosine (k
cat
= 3.33 ± 0.18 s−1, K
m
= 2.12 ± 0.14 mM at 20 °C and pH 6.0). This enzyme was still highly active in ice water (>80%), and its activity was well conserved below 30 °C. In vitro DOPA modification, with a remarkably high yield as a monophenol monooxygenase, was achieved by the enzyme taking advantage of these biocatalytic properties. These results demonstrate the strong potential for this enzyme’s use as a monophenol monooxygenase in biomedical and industrial applications.
Suitability of various chromatographic and spectroscopic techniques for analysis and kinetic degradation study of trelagliptin
Authors: Zaghary Wafaa A. , Mowaka Shereen , Hassan Mostafa A. , Ayoub Bassam M. 
Published: December 2017

AbstractMultifaceted comparative analytical methods for trelagliptin (TRL) were investigated, applied to ZAFATEK tablets and HPLC-UV was selected for a degradation kinetic study. UPLC-MS/MS (Method I), UPLC-UV (Method II), HPLC-UV (Method III), UHPLC-UV (Method IV) and direct UV (Method V) methods were developed. Methods (I-V) showed satisfactory results using TRL concentration ranges of 50–800 ng/mL, 2.5–80 μg/mL, 5–100 μg/mL, 5–100 μg/mL and 5–50 μg/mL, respectively. Multiple Reaction Monitoring (MRM) of the transition pairs of m/z 358.176 to 134.127 for TRL and m/z 340.18 to 116.08 for alogliptin (IS) were employed utilizing positive mode Electrospray Ionization (ESI). The degradation kinetic study (Method VI) was carried out using 1 N HCl based on three different temperatures (70 °C, 80 °C and 90 °C). Through the optimized method-3, a good chromatographic separation of TRL from its major degradation product was achieved. Arrhenius plot was used in the kinetic study and the apparent 1st order degradation rate constant (K), t1/2, t90, and the activation energies were calculated for each temperature and at 25 °C. The optimized UPLC-MS/MS method is suitable for further TRL assay either in biological fluids or in the presence of impurities.
CO2 Mineralization and Utilization using Steel Slag for Establishing a Waste-to-Resource Supply Chain
Authors: Pan Shu-Yuan , Chung Tai-Chun , Ho Chang-Ching , Hou Chin-Jen , Chen Yi-Hung , Chiang Pen-Chi 
Published: December 2017

AbstractBoth steelmaking via an electric arc furnace and manufacturing of portland cement are energy-intensive and resource-exploiting processes, with great amounts of carbon dioxide (CO2) emission and alkaline solid waste generation. In fact, most CO2 capture and storage technologies are currently too expensive to be widely applied in industries. Moreover, proper stabilization prior to utilization of electric arc furnace slag are still challenging due to its high alkalinity, heavy metal leaching potentials and volume instability. Here we deploy an integrated approach to mineralizing flue gas CO2 using electric arc furnace slag while utilizing the reacted product as supplementary cementitious materials to establish a waste-to-resource supply chain toward a circular economy. We found that the flue gas CO2 was rapidly mineralized into calcite precipitates using electric arc furnace slag. The carbonated slag can be successfully utilized as green construction materials in blended cement mortar. By this modulus, the global CO2 reduction potential using iron and steel slags was estimated to be ~138 million tons per year.
Structural insight into a CE15 esterase from the marine bacterial metagenome
Authors: De Santi Concetta , Gani Osman ABSM , Helland Ronny , Williamson Adele 
Published: December 2017

AbstractThe family 15 carbohydrate esterase (CE15) MZ0003, which derives from a marine Arctic metagenome, has a broader substrate scope than other members of this family. Here we report the crystal structure of MZ0003, which reveals that residues comprising the catalytic triad differ from previously-characterized fungal homologs, and resolves three large loop regions that are unique to this bacterial sub-clade. The catalytic triad of the bacterial CE15, which includes Asp 332 as its third member, closely resembles that of family 1 carbohydrate esterases (CE1), despite the overall lower structural similarity with members of this family. Two of the three loop regions form a subdomain that deepens the active site pocket and includes several basic residues that contribute to the high positive charge surrounding the active site. Docking simulations predict specific interactions with the sugar moiety of glucuronic-acid substrates, and with aromatically-substituted derivatives that serve as model compounds for the lignin-carbohydrate complex of plant cell walls. Molecular dynamics simulations indicate considerable flexibility of the sub-domain in the substrate-bound form, suggesting plasticity to accommodate different substrates is possible. The findings from this first reported structure of a bacterial member of the CE15 family provide insight into the basis of its broader substrate specificity.
Studies of two-dimensional h-BN and MoS2 for potential diffusion barrier application in copper interconnect technology
Authors: Lo Chun-Li , Catalano Massimo , Smithe Kirby K. H. , Wang Luhua , Zhang Shengjiao , Pop Eric , Kim Moon J. , Chen Zhihong 
Published: December 2017

AbstractCopper interconnects in modern integrated circuits require a barrier layer to prevent Cu diffusion into surrounding dielectrics. However, conventional barrier materials like TaN are highly resistive compared to Cu and will occupy a large fraction of the cross-section of ultra-scaled Cu interconnects due to their thickness scaling limits at 2–3 nm, which will significantly increase the Cu line resistance. It is well understood that ultrathin, effective diffusion barriers are required to continue the interconnect scaling. In this study, a new class of two-dimensional (2D) materials, hexagonal boron nitride (h-BN) and molybdenum disulfide (MoS2), is explored as alternative Cu diffusion barriers. Based on time-dependent dielectric breakdown measurements and scanning transmission electron microscopy imaging coupled with energy dispersive X-ray spectroscopy and electron energy loss spectroscopy characterizations, these 2D materials are shown to be promising barrier solutions for Cu interconnect technology. The predicted lifetime of devices with directly deposited 2D barriers can achieve three orders of magnitude improvement compared to control devices without barriers.
Biomechanical Implications of an Oblique Knee Joint Line
Authors: Hooper Jessica , Walker Peter , Hsu Tzu-Ting , Kurtz Anton , Reynolds Ryan , Hennessy Daniel , Chu Alice 
Published: November 2017

AbstractSurgical correction of multiapical deformities of the lower limb requires careful preoperative planning. Surgeons must account for the potential creation of secondary deformity, such as knee joint line obliquity, and the risks associated with accepting these changes in limb alignment. In this study, we evaluate the effect of knee joint obliquity on tibial plateau contact pressures and knee instability. Three cadaveric knees were dissected and put through biomechanical testing to simulate loading of an oblique knee joint. We observed < 1 mm femoral displacement (proxy measure of instability) between 15 degrees of varus tilt and 10 degrees of valgus tilt, and greater increases in tibial plateau contact pressures with valgus tilt than with varus tilt. Our results suggest that, if the creation of a secondary coronal plane deformity at the knee joint cannot be avoided, up to 15 degrees of varus or 10 degrees of valgus alignment can be tolerated by an otherwise structurally normal knee.
Die Sägepalme
Authors: Niedenthal Tobias 
Published: December 2017

ZusammenfassungVon den nordamerikanischen Ureinwohnern wurde die Sägepalme (Serenoa repens (W. Bartram) Small) vielfältig genutzt, eine medizinische Verwendung lässt sich aber nicht sicher nachweisen. Als Arzneipflanze hatte die Sägepalme eine erste Blüte im späten 19. und frühen 20. Jahrhundert, als verschiedene Zubereitungen in der Pflanzenheilkunde und der Homöopathie beliebt waren. Neue wissenschaftliche Impulse kamen gegen Ende des 20. Jahrhunderts aus Europa, wo Sägepalmenfrüchte heute zur symptomatischen Behandlung der benignen Prostatahyperplasie (BPH) anerkannt sind. Daneben werden auch topische Anwendungen erforscht.
Subtyping of Patients with Primary Aldosteronism: An Update
Authors: Lenders Jacques , Eisenhofer Graeme , Reincke Martin 
Published: December 2017

AbstractPrimary aldosteronism (PA) comprises two main subtypes: unilateral aldosteronism, mainly caused by aldosterone-producing adenoma; and bilateral adrenal hyperplasia. Establishing the correct subtype in patients with PA is indispensible for choice of treatment. In addition to established methods, alternative tests are evolving for subtyping. Computed tomography (CT) and adrenal venous sampling (AVS) are currently recommended in the guidelines for the diagnostic work-up of patients with PA. CT cannot be used as a stand-alone test for subtyping because of its limited accuracy but may be used in combination with other tests such as AVS or functional imaging. Nevertheless CT remains mandatory to exclude adrenocortical carcinoma. AVS provides the most accurate test to detect excessive secretion of aldosterone from an adrenal mass but has several practical limitations and disadvantages. Therefore, alternative non-invasive and patient-friendly methods are required to determine the need for adrenalectomy. Functional imaging with specific molecular positron emission tomographic ligands is a potential alternative method that may replace AVS for subclassifying patients with PA. The results of preliminary studies of 11C-metomidate are promising but ligands incorporating radionuclides with longer half-lives that selectively bind to CYP11B2 are needed. Steroid profiling provides another method for subtyping and selecting patients for adrenalectomy, but this technology is in its infancy and prospective outcome-based studies are required to determine if this technique may provide an alternative to AVS.
Metastasierung kutaner Plattenepithelkarzinome im HNO-Bereich
Authors: Dellweg Alexander , Mantei Thomas 
Published: December 2017

Zusammenfassung
Hintergrund Kutane Plattenepithelkarzinome können lymphogen sowohl nach intraparotideal, als auch nach zervikal metastasieren.
Prognostisch scheinen sich gemäß mehreren Studien die beiden Metastasierungswege zu unterscheiden. Wir möchten mit klinikeigenen Daten das
Metastasierungsverhalten hinsichtlich der Prognose untersuchen.
Material und Methoden In die retrospektive Studie aufgenommen wurden 29 Kaukasier mit einem Plattenepithelkarzinom der Haut im
Kopf-Halsbereich, welche sich zwischen 2004 und 2016 an unserer Hals-Nasen-Ohren-Klinik vorgestellt haben. Bei allen Patienten wurde eine
Tumorresektion mit Neck dissection durchgeführt. Sowohl das präoperative Staging, wie auch die Nachsorge erfolgten mittels Ultraschall oder
Computertomographie (konventionell oder PET Scan). Die Patienten wurden nach Metastasierungsverhalten eingeteilt und die entsprechenden
Überlebensraten wurden ermittelt.
Ergebnisse 11 Patienten hatten zervikale Metastasen, 4 Patienten parotideale Metastasen, 5 Patienten hatten beides. Bei 9 Patienten
wurde eine prophylaktische Neck dissection bei cN0 durchgeführt. Ein lokoregionäres Tumorrezidiv trat in insgesamt 24 % der Fälle auf, davon
waren alle mit einer zervikalen Metastasierung assoziiert. Die 5-Jahres Überlebensrate betrug in diesen Fällen 71 %. Im Gegensatz dazu
betrug diese bei alleiniger parotidealer Metastasierung 100 %. Im Rahmen der prophylaktischen Neck dissection wurden in einem Fall okkulte
Metastasen diagnostiziert.
Schlussfolgerungen Eine zervikale Metastasierung geht im Gegensatz zu einer alleinigen parotidealen Metastasierung mit einer
schlechteren Prognose einher. Die Überlebensrate nach chirurgischer Therapie, sowie gegebenenfalls zusätzlichen adjuvanten Radiotherapie ist
insgesamt gut (79 %). Die Rolle einer prophylaktischen Neck dissection bei cN0 und entsprechenden Risikofaktoren ist nicht abschließend
geklärt.
New Pharmacological Opportunities for Betulinic Acid
Authors: Ríos José , Máñez Salvador 
Published: December 2017

AbstractBetulinic acid is a naturally occurring pentacyclic lupane-type triterpenoid usually isolated from birch trees, but present in many other botanical sources. It is found in different plant organs, both as a free aglycon and as glycosyl derivatives. A wide range of pharmacological activities has been described for this triterpenoid, including antiviral and antitumor effects. In addition, several other interesting properties have been identified in the fields of immunity and metabolism, namely antidiabetic, antihyperlipidemic, and anti-inflammatory activities. Taken together, these latter three properties make betulinic acid a highly interesting prospect for treating metabolic syndrome. The present review focuses on the therapeutic potential of this agent, along with several of its semisynthetic derivatives, which could open new frontiers in the use of natural product-based medicines.
Selected reaction monitoring approach for validating peptide biomarkers
Authors: Wang Qing , Zhang Ming , Tomita Tyler , Vogelstein Joshua T. , Zhou Shibin , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert 
Published: December 2017

Significance
With the advent of advanced proteomic technologies, a unique generation of plasma biomarkers is likely to arise in the foreseeable future. One of the fundamental practical problems in developing such biomarkers for clinical use is the lack of a high-throughput, robust, and reproducible system for validating candidate biomarkers. Here, we report the development of a system that is suitable for validating a large number of candidate biomarkers in a quantitative and massively parallel manner. In addition to describing this system [called sequential analysis of fractionated eluates by selected reaction monitoring (SAFE-SRM)], we have used it to discover a peptide biomarker for ovarian cancer that may prove to have clinical value.
Intercultural translation and indigenous articulation in higher education
Authors: Borge Janetti Gabriela 
Published: December 2017

AbstractIntercultural translation is a salient feature of communicative interactions in multilingual institutional spaces. This article draws on a concept of intercultural translation that functions as a linguistically radical strategy through which other ways of knowing and being are introduced, with particular emphasis on institutions, multilingualism, and less-translated languages. It describes the modes in which indigenous actors used intercultural translation to modify Mexico’s institutional tutoring program in higher education. It focuses on the selective appropriation of words and meanings, the standardization of concepts, and the configuring of an intercultural frame of reference, whereby members of an intercultural Mexican university introduced the Yucatec Maya wordiknalas a hybrid educational system. In sum, the article posits intercultural translation as a critical communicative practice ubiquitous to the dynamics of language in socio-cultural spaces.