bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ectopic activation of WNT signaling in human embryonal carcinoma cells and its effects in short- and long-term in vitro culture
Authors: Atlasi Yaser , van Dorsten Rebecca T. , Sacchetti Andrea , Joosten Rosalie , Oosterhuis J. Wolter , Looijenga Leendert H. J. , Fodde Riccardo 
Published: August 2019

AbstractHuman embryonal carcinoma (EC) cells comprise the pluripotent stem cells of malignant non-seminomatous germ cell tumors (GCTs) and represent the malignant counterpart of embryonic stem cells (ESCs). WNT/β-catenin signaling has been implicated in regulating adult and embryonic stem cells although its role in EC cells is less investigated. Here, we studied WNT signaling in a panel of representative pluripotent and nullipotent human EC cell lines. We found that EC cell lines show distinct levels of intrinsic WNT signaling and respond differently to ectopic WNT activation. Short-term activation of WNT signaling induced a differentiation-response in the pluripotent EC cells (NT2 and NCCIT) whereas the nullipotent EC cells (TERA1 and 2102Ep) were refractory and maintained high levels of OCT4 and SSEA4 expression. Long-term activation of WNT signaling in NCCIT and, to a lesser extent, TERA1 cells led to (re)gain of OCT4 expression and a switch from SSEA4 to SSEA1 surface antigens ultimately resulting in OCT4+/SSEA4−/SSEA1+ profile. Cisplatin treatment indicated that the OCT4+/SSEA4−/SSEA1+ NCCIT cells became more resistant to chemotherapy treatment. Our findings are of particular interest for the GCT and ES cell biology and shed light on the role of WNT signaling in human EC cells.
Impacts of Long-term Fertilization on the Molecular Structure of Humic Acid and Organic Carbon Content in Soil Aggregates in Black Soil
Authors: Zhang Jiuming , Chi Fengqin , Wei Dan , Zhou Baoku , Cai Shanshan , Li Yan , Kuang Enjun , Sun Lei , Li Lu-Jun 
Published: August 2019

AbstractSoil aggregates are the basic units of soil structure, and their composition and carbon (C) stability directly affect soil fertility. As cementing agents, humic substances play an important role in the formation and stability of soil aggregates. Long-term fertilization not only changes the structure of humic acid (HA), but also affects the content and stability of organic C in soil aggregates. In this study, based on a long-term fertilization experiment, the relationship between the molecular structure of HA and the stability of organic C in the aggregates was examined. Compared with the non-fertilization control (CK), both the application of organic manure alone (M) and organic manure combined with inorganic fertilizer application (MNPK) increased organic C content in the bulk soil and in HA. In addition, the application of organic manure (M, MNPK) favored the formation of macroaggregates (>0.25 mm) and showed a higher organic C contents of soil aggregates with different sizes than the CK. Moreover, the content of aliphatic C, the ratios of aliphatic C/aromatic C and alkyl C/O-alkyl C was increased with the application of organic fertilizer. A significant negative correlation was observed between aromatic C and organic C content of the aggregates with sizes of >2 mm, 2–0.25 mm, and 0.25–0.053 mm (P < 0.05). The findings indicated that organic fertilization treatments (M and MNPK) increased the aliphatic C content of HA, which favored the increase in the organic C content and stability of the aggregates.
Emergent dynamics of extremes in a population driven by common information sources and new social media algorithms
Authors: Johnson N. F. , Manrique P. , Zheng M. , Cao Z. , Botero J. , Huang S. , Aden N. , Song C. , Leady J. , Velasquez N. , Restrepo E. M. 
Published: August 2019

AbstractWe quantify how and when extreme subpopulations emerge in a model society despite everyone having the same information and available resources – and show that counterintuitively these extremes will likely be enhanced over time by new social media algorithms designed to reduce division. We verify our analysis mathematically, and show it reproduces (a) the time-dependent behavior observed in controlled experiments on humans, (b) the findings of a recent study of online behavior by Facebook concerning the impact of ‘soft’ and ‘hard’ news, (c) the observed temporal emergence of extremes in U.S. House of Representatives voting, and (d) the real-time emergence of a division in national opinion during the ongoing peace process in Colombia. We uncover a novel societal tipping point which is a ‘ghost’ of a nearby saddle-node bifurcation from dynamical systems theory, and which provides a novel policy opportunity for preventing extremes from emerging.
Effect of Prior Local Treatment and Prostate-Specific Antigen Kinetics during Androgen-Deprivation Therapy on the Survival of Castration-Resistant Prostate Cancer
Authors: Hah Yoon Soo , Lee Jong Soo , Rha Koon Ho , Hong Sung Joon , Chung Byung Ha , Koo Kyo Chul 
Published: August 2019

AbstractProstate-specific antigen (PSA) kinetics predicts survival in castration-resistant prostate cancer (CRPC); however, the influence of prior treatment on this relationship is unclear. Patients with CRPC were stratified according to time to PSA nadir and time to CRPC progression to investigate their prognostic significance on prostate cancer-specific survival (PCSS) and whether PSA kinetics may serve as prognosticators regardless of prior local treatment. This multicenter retrospective study included 295 patients diagnosed with CRPC between September 2009 and November 2017. PSA kinetics during androgen-deprivation therapy (ADT) including %PSA decline, PSA nadir level, time to PSA nadir, and time to CRPC progression was investigated. Subgroup analysis was performed according to the prior history of local curative treatment. Patients who did not receive prior local treatment with ≥6 months to PSA nadir and <12 months to CRPC, showed lower PCSS rates than those with <6 months to PSA nadir (23.3% vs. 45.3%; p = 0.031) and ≥12 months to CRPC (20.0% vs. 47.8%; p = 0.001). In patients who had received local treatment, PSA kinetic parameters did not influence PCSS. Our results indicate that time to PSA nadir and time to CRPC progression are prognosticators of PCSS in patients with CRPC who did not previously receive curative local treatment.
Long-term cardiovascular disorders in the STOX1 mouse model of preeclampsia
Authors: Miralles Francisco , Collinot Hélène , Boumerdassi Yasmine , Ducat Aurélien , Duché Angéline , Renault Gilles , Marchiol Carmen , Lagoutte Isabelle , Bertholle Céline , Andrieu Muriel , Jacques Sébastien , Méhats Céline , Vaiman Daniel 
Published: August 2019

AbstractAdverse long-term cardiovascular (CV) consequences of PE are well established in women. However, the mechanism responsible for that risk remains unknown. Here, we mated wild-type female mice of the FVB/N strain to STOX1A-overexpressing mice to mimic severe PE and investigated the long-term consequences on the maternal cardiovascular system. Ultrasonography parameters were analyzed in mice before pregnancy and at 3 and 6 months post-pregnancy. At 6 months post-pregnancy, cardiac stress test induced by dobutamine injection revealed an abnormal ultrasonography Doppler profile in mice with previous PE. Eight months post-pregnancy, the heart, endothelial cells (ECs) and plasma of females were analyzed and compared to controls. The heart of mice with PE showed left-ventricular hypertrophy associated with altered histology (fibrosis). Transcriptomic analysis revealed the deregulation of 1149 genes in purified ECs and of 165 genes in the hearts, many being involved in heart hypertrophy. In ECs, the upregulated genes were associated with inflammation and cellular stress. Systems biology analysis identified interleukin 6 (IL-6) as a hub gene connecting these pathways. Plasma profiling of 33 cytokines showed that, 8 of them (Cxcl13, Cxcl16, Cxcl11, IL-16, IL-10, IL-2, IL-4 and Ccl1) allowed to discriminate mice with previous PE from controls. Thus, PE triggers female long-term CV consequences on the STOX1 mouse model.
Osteostimulatory effect of biocomposite scaffold containing phytomolecule diosmin by Integrin/FAK/ERK signaling pathway in mouse mesenchymal stem cells
Authors: Chandran S. Viji , Vairamani M. , Selvamurugan N. 
Published: August 2019

AbstractNon-availability of an ideal alternative for autografts in treating critical-size bone defects is a major challenge in orthopedics. Phytocompounds have been proven to enhance osteogenesis via various osteogenic signaling pathways, but its decreased bioavailability and increased renal clearance limit its application. In this study, we designed a biocomposite scaffold comprising gelatin (Gel) and nanohydroxyapatite (nHAp) incorporated with diosmin (DM) and we investigated its bone forming potentialin vitroandin vivo. Physiochemical characterization of the scaffold showed that DM had no effect on altering the material characteristics of the scaffold. The addition of DM enhanced the osteoblast differentiation potential of the scaffold in mouse mesenchymal stem cells at both cellular and molecular levels, possibly via the integrin-mediated activation of FAK and ERK signaling components. Using the rat tibial bone defective model, we identified the effect of DM in Gel/nHAp scaffold on enhancing bone formationin vivo. Based on our results, we suggest that Gel/nHAp/DM can be a potential therapeutic agent in scaffold-mediated bone regeneration.
The regulation of the sulfur amino acid biosynthetic pathway in Cryptococcus neoformans: the relationship of Cys3, Calcineurin, and Gpp2 phosphatases
Authors: de Melo Amanda Teixeira , Martho Kevin Felipe , Roberto Thiago Nunes , Nishiduka Erika S. , Machado Joel , Brustolini Otávio J. B. , Tashima Alexandre K. , Vasconcelos Ana Tereza , Vallim Marcelo A. , Pascon Renata C. 
Published: August 2019

AbstractCryptococcosis is a fungal disease caused by C. neoformans. To adapt and survive in diverse ecological niches, including the animal host, this opportunistic pathogen relies on its ability to uptake nutrients, such as carbon, nitrogen, iron, phosphate, sulfur, and amino acids. Genetic circuits play a role in the response to environmental changes, modulating gene expression and adjusting the microbial metabolism to the nutrients available for the best energy usage and survival. We studied the sulfur amino acid biosynthesis and its implications on C. neoformans biology and virulence. CNAG_04798 encodes a BZip protein and was annotated as CYS3, which has been considered an essential gene. However, we demonstrated that CYS3 is not essential, in fact, its knockout led to sulfur amino acids auxotroph. Western blots and fluorescence microscopy indicated that GFP-Cys3, which is expressed from a constitutive promoter, localizes to the nucleus in rich medium (YEPD); the addition of methionine and cysteine as sole nitrogen source (SD–N + Met/Cys) led to reduced nuclear localization and protein degradation. By proteomics, we identified and confirmed physical interaction among Gpp2, Cna1, Cnb1 and GFP-Cys3. Deletion of the calcineurin and GPP2 genes in a GFP-Cys3 background demonstrated that calcineurin is required to maintain Cys3 high protein levels in YEPD and that deletion of GPP2 causes GFP-Cys3 to persist in the presence of sulfur amino acids. Global transcriptional profile of mutant and wild type by RNAseq revealed that Cys3 controls all branches of the sulfur amino acid biosynthesis, and sulfur starvation leads to induction of several amino acid biosynthetic routes. In addition, we found that Cys3 is required for virulence in Galleria mellonella animal model.
Oil palm concessions in southern Myanmar consist mostly of unconverted forest
Authors: Nomura Keiko , Mitchard Edward T. A. , Patenaude Genevieve , Bastide Joan , Oswald Patrick , Nwe Thazin 
Published: August 2019

AbstractThe increased demand for palm oil has led to an expansion of oil palm concessions in the tropics, and the clearing of abundant forest as a result. However, concessions are typically incompletely planted to varying degrees, leaving much land unused. The remaining forests within such concessions are at high risk of deforestation, as there are normally no legal hurdles to their clearance, therefore making them excellent targets for conservation. We investigated the location of oil palm plantations and the other major crop – rubber plantations in southern Myanmar, and compared them to concession boundaries. Our results show that rubber plantations cover much larger areas than oil palm in the region, indicating that rubber is the region’s preferred crop. Furthermore, only 15% of the total concession area is currently planted with oil palm (49,000 ha), while 25,000 ha is planted outside concession boundaries. While this may in part be due to uncertain and/or changing boundaries, this leaves most of the concession area available for other land uses, including forest conservation and communities’ livelihood needs. Reconsidering the remaining concession areas can also significantly reduce future emission risks from the region.
An automated pipeline for the screening of diverse monoterpene synthase libraries
Authors: Leferink Nicole G. H. , Dunstan Mark S. , Hollywood Katherine A. , Swainston Neil , Currin Andrew , Jervis Adrian J. , Takano Eriko , Scrutton Nigel S. 
Published: August 2019

AbstractMonoterpenoids are a structurally diverse group of natural products with applications as pharmaceuticals, flavourings, fragrances, pesticides, and biofuels. Recent advances in synthetic biology offer new routes to this chemical diversity through the introduction of heterologous isoprenoid production pathways into engineered microorganisms. Due to the nature of the branched reaction mechanism, monoterpene synthases often produce multiple products when expressed in monoterpenoid production platforms. Rational engineering of terpene synthases is challenging due to a lack of correlation between protein sequence and cyclisation reaction catalysed. Directed evolution offers an attractive alternative protein engineering strategy as limited prior sequence-function knowledge is required. However, directed evolution of terpene synthases is hampered by the lack of a convenient high-throughput screening assay for the detection of multiple volatile terpene products. Here we applied an automated pipeline for the screening of diverse monoterpene synthase libraries, employing robotic liquid handling platforms coupled to GC-MS, and automated data extraction. We used the pipeline to screen pinene synthase variant libraries, with mutations in three areas of plasticity, capable of producing multiple monoterpene products. We successfully identified variants with altered product profiles and demonstrated good agreement between the results of the automated screen and traditional shake-flask cultures. In addition, useful insights into the cyclisation reaction catalysed by pinene synthase were obtained, including the identification of positions with the highest level of plasticity, and the significance of region 2 in carbocation cyclisation. The results obtained will aid the prediction and design of novel terpene synthase activities towards clean monoterpenoid products.
Facial Pre-Touch Space Differentiates the Level of Openness Among Individuals
Authors: Keshmiri Soheil , Shiomi Masahiro , Shatani Kodai , Minato Takashi , Ishiguro Hiroshi 
Published: August 2019

AbstractSocial and cognitive psychology provide a rich map of our personality landscape. What appears to be unexplored is the correspondence between these findings and our behavioural responses during day-to-day life interaction. In this article, we utilize cluster analysis to show that the individuals’ facial pre-touch space can be divided into three well-defined subspaces and that within the first two immediate clusters around the face area such distance information significantly correlate with their openness in the five-factor model (FFM). In these two clusters, we also identify that the individuals’ facial pre-touch space can predict their level of openness that are further categorized into six distinct levels with a highly above chance accuracy. Our results suggest that such personality factors as openness are not only reflected in individuals’ behavioural responses but also these responses allow for a fine-grained categorization of individuals’ personality.
Predicting Breast Cancer in Breast Imaging Reporting and Data System (BI-RADS) Ultrasound Category 4 or 5 Lesions: A Nomogram Combining Radiomics and BI-RADS
Authors: Luo Wei-quan , Huang Qing-xiu , Huang Xiao-wen , Hu Hang-tong , Zeng Fu-qiang , Wang Wei 
Published: August 2019

AbstractRadiomics reflects the texture and morphological features of tumours by quantitatively analysing the grey values of medical images. We aim to develop a nomogram incorporating radiomics and the Breast Imaging Reporting and Data System (BI-RADS) for predicting breast cancer in BI-RADS ultrasound (US) category 4 or 5 lesions. From January 2017 to August 2018, a total of 315 pathologically proven breast lesions were included. Patients from the study population were divided into a training group (n = 211) and a validation group (n = 104) according to a cut-off date of March 1st, 2018. Each lesion was assigned a category (4A, 4B, 4C or 5) according to the second edition of the American College of Radiology (ACR) BI-RADS US. A radiomics score was generated from the US image. A nomogram was developed based on the results of multivariate regression analysis from the training group. Discrimination, calibration and clinical usefulness of the nomogram for predicting breast cancer were assessed in the validation group. The radiomics score included 9 selected radiomics features. The radiomics score and BI-RADS category were independently associated with breast malignancy. The nomogram incorporating the radiomics score and BI-RADS category showed better discrimination (area under the receiver operating characteristic curve [AUC]: 0.928; 95% confidence interval [CI]: 0.876, 0.980) between malignant and benign lesions than either the radiomics score (P = 0.029) or BI-RADS category (P = 0.011). The nomogram demonstrated good calibration and clinical usefulness. In conclusion, the nomogram combining the radiomics score and BI-RADS category is potentially useful for predicting breast malignancy in BI-RADS US category 4 or 5 lesions.
Assessing the role of surface glycans of extracellular vesicles on cellular uptake
Authors: Williams Charles , Pazos Raquel , Royo Félix , González Esperanza , Roura-Ferrer Meritxell , Martinez Aitor , Gamiz Jorge , Reichardt Niels-Christian , Falcón-Pérez Juan M 
Published: August 2019

AbstractExtracellular vesicles (EVs) are important mediators of cell-cell communication in a broad variety of physiological contexts. However, there is ambiguity around the fundamental mechanisms by which these effects are transduced, particularly in relation to their uptake by recipient cells. Multiple modes of cellular entry have been suggested and we have further explored the role of glycans as potential determinants of uptake, using EVs from the murine hepatic cell lines AML12 and MLP29 as independent yet comparable models. Lectin microarray technology was employed to define the surface glycosylation patterns of EVs. Glycosidases PNGase F and neuraminidase which cleave N-glycans and terminal sialic acids, respectively, were used to analyze the relevance of these modifications to EV surface glycans on the uptake of fluorescently labelled EVs by a panel of cells representing a variety of tissues. Flow cytometry revealed an increase in affinity for EVs modified by both glycosidase treatments. High-content screening exhibited a broader range of responses with different cell types preferring different vesicle glycosylation states. We also found differences in vesicle charge after treatment with glycosidases. We conclude that glycans are key players in the tuning of EV uptake, through charge-based effects, direct glycan recognition or both, supporting glycoengineering as a toolkit for therapy development.
Osteoporose – gibt es Indikationen für eine Vitamin-D-Therapie?
Authors: Schlereth Florian , Badenhoop Klaus 
Published: August 2019

AbstractAdequate intake of vitamin D and calcium are fundamental for the treatment of osteoporosis. A normal vitamin D status is required for optimal intestinal calcium absorption. However, general calcium and vitamin D supplementation is not sufficient for prevention of osteoporotic fractures in persons older than 50 years. Nevertheless, vitamin D deficiency should be avoided and corrected. In particular, parts of the population with increased risk for vitamin D deficiency (immobilized or older individuals, swarthy, migrants) should be tested. Secondary causes of vitamin D deficiency should be identified and treated.
Beurteilung und akutes Management der dekompensierten Klappenvitien auf der Intensivstation – eine aktuelle Übersicht
Authors: Reith Sebastian , Napp Andreas 
Published: August 2019

ZusammenfassungDie akute valvuläre Dysfunktion ist eine zunehmend häufigere und kritische Ursache einer intensivmedizinischen Behandlung einer dekompensierten Herzinsuffizienz mit dem Auftreten eines kardiogenen Schocks als der schwerwiegendsten Form. Während es definierte Leitlinien sowohl für die Diagnostik und Therapie der Herzinsuffizienz als auch für stabile Patienten mit Herzklappenfehlern gibt, ist die Datenlage bei akut valvulär dekompensierten Patienten begrenzt. Bei drohender oder bestehender Organdysfunktion trotz Ausschöpfung aller medikamentösen Therapieoptionen stehen neben den chirurgischen Klappenoperationen verschiedene Katheter-interventionelle Therapieoptionen wie das TAVI- und das MitraClip-Verfahren zur Verfügung. Darüber hinaus haben zuletzt die Ballonvalvuloplastie bei der Aortenklappenstenose sowie perkutane Kreislaufunterstützungssysteme einen wachsenden Stellenwert bei der Behandlung und hämodynamischen Stabilisierung von dekompensierten Klappenpatienten auf der Intensivstation erlangt.
Personalisierte Osteoporose-Therapie
Authors: Schulz Karoline , Kalscheuer Hannes , Lehnert Hendrik 
Published: August 2019

AbstractIn Germany, over six million people suffer from osteoporosis. Nearly half of the women over 70 years and nearly 20 % of men at the same age are affected. The clinical and socioeconomical relevance of the disease lies in osteoporotic fractures leading to extensive bone-associated morbidity, increased mortality and health care costs. Fracture risk algorithms and guidelines for the diagnosis and treatment of osteoporosis help to assess the individual fracture risk. By calculating the individual fracture risk, the indication for specific osteoporosis treatment can objectively be determined. A consequent specific osteoporosis therapy is required for patients with a high fracture risk and is essential to prevent osteoporotic fractures and their consequences. As first-line therapy a drug with a proven fracture-reducing effect should be taken. However, for successful osteoporosis therapy, many individual factors have to be considered. A personalized treatment approach should be established according to the severity of the disease, the patient’s sex and comorbidities as well as the possible additive and side effects of the drug.