bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Organotypic Slice Cultures and RT-QuIC (OSCAR) Assay: Implications for Translational Discovery in Protein Misfolding Diseases
Authors: Kondru Naveen , Manne Sireesha , Greenlee Justin , West Greenlee Heather , Anantharam Vellareddy , Halbur Patrick , Kanthasamy Arthi , Kanthasamy Anumantha 
Published: February 2017

AbstractProtein misfolding is a key pathological event in neurodegenerative diseases like prion diseases, synucleinopathies, and tauopathies that are collectively termed protein misfolding disorders. Prions are a prototypic model to study protein aggregation biology and therapeutic development. Attempts to develop anti-prion therapeutics have been impeded by the lack of screening models that faithfully replicate prion diseases and the lack of rapid, sensitive biological screening systems. Therefore, a sensitive model encompassing prion replication and neurotoxicity would be indispensable to the pursuit of intervention strategies. We present an ultra-sensitive screening system coupled to an ex vivo prion organotypic slice culture model to rapidly advance rationale-based high-throughput therapeutic strategies. This hybrid Organotypic Slice Culture Assay coupled with RT-QuIC (OSCAR) permits sensitive, specific and quantitative detection of prions from an infectious slice culture model on a reduced time scale. We demonstrate that the anti-prion activity of test compounds can be readily resolved based on the power and kinetics of seeding activity in the OSCAR screening platform and that the prions generated in slice cultures are biologically active. Collectively, our results imply that OSCAR is a robust model of prion diseases that offers a promising platform for understanding prion proteinopathies and advancing anti-prion therapeutics.
Targeting Thioredoxin-1 by dimethyl fumarate induces ripoptosome-mediated cell death
Authors: Schroeder Anne , Warnken Uwe , Röth Daniel , Klika Karel D. , Vobis Diana , Barnert Andrea , Bujupi Fatmire , Oberacker Tina , Schnölzer Martina , Nicolay Jan P. , Krammer Peter H. , Gülow Karsten 
Published: February 2017

AbstractConstitutively active NFκB promotes survival of many cancers, especially T-cell lymphomas and leukemias by upregulating antiapoptotic proteins such as inhibitors of apoptosis (IAPs) and FLICE-like inhibitory proteins (cFLIPs). IAPs and cFLIPs negatively regulate the ripoptosome, which mediates cell death in an apoptotic or necroptotic manner. Here, we demonstrate for the first time, that DMF antagonizes NFκB by suppressing Thioredoxin-1 (Trx1), a major regulator of NFκB transcriptional activity. DMF-mediated inhibition of NFκB causes ripoptosome formation via downregulation of IAPs and cFLIPs. In addition, DMF promotes mitochondrial Smac release and subsequent degradation of IAPs, further enhancing cell death in tumor cells displaying constitutive NFκB activity. Significantly, CTCL patients treated with DMF display substantial ripoptosome formation and caspase-3 cleavage in T-cells. DMF induces cell death predominantly in malignant or activated T-cells. Further, we show that malignant T-cells can die by both apoptosis and necroptosis, in contrast to resting T-cells, which are restricted to apoptosis upon DMF administration. In summary, our data provide new mechanistic insight in the regulation of cell death by targeting NFκB via Trx1 in cancer. Thus, interference with Trx1 activity is a novel approach for treatment of NFκB-dependent tumors.
A record of igneous evolution in Elysium, a major martian volcanic province
Authors: Susko David , Karunatillake Suniti , Kodikara Gayantha , Skok J. R. , Wray James , Heldmann Jennifer , Cousin Agnes , Judice Taylor 
Published: February 2017

AbstractA major knowledge gap exists on how eruptive compositions of a single martian volcanic province change over time. Here we seek to fill that gap by assessing the compositional evolution of Elysium, a major martian volcanic province. A unique geochemical signature overlaps with the southeastern flows of this volcano, which provides the context for this study of variability of martian magmatism. The southeastern lava fields of Elysium Planitia show distinct chemistry in the shallow subsurface (down to several decimeters) relative to the rest of the martian mid-to-low latitudes (average crust) and flows in northwest Elysium. By impact crater counting chronology we estimated the age of the southeastern province to be 0.85 ± 0.08 Ga younger than the northwestern fields. This study of the geochemical and temporal differences between the NW and SE Elysium lava fields is the first to demonstrate compositional variation within a single volcanic province on Mars. We interpret the geochemical and temporal differences between the SE and NW lava fields to be consistent with primary magmatic processes, such as mantle heterogeneity or change in depth of melt formation within the martian mantle due to crustal loading.
Thyroid nodule sizes influence the diagnostic performance of TIRADS and ultrasound patterns of 2015 ATA guidelines: a multicenter retrospective study
Authors: Xu Ting , Gu Jing-yu , Ye Xin-hua , Xu Shu-hang , Wu Yang , Shao Xin-yu , Liu De-zhen , Lu Wei-ping , Hua Fei , Shi Bi-min , Liang Jun , Xu Lan , Tang Wei , Liu Chao , Wu Xiao-hong 
Published: February 2017

AbstractTo evaluate the impact of thyroid nodule sizes on the diagnostic performance of thyroid imaging reporting and data system (TIRADS) and ultrasound patterns of 2015 American Thyroid Association (ATA) guidelines. Total 734 patients with 962 thyroid nodules were recruited in this retrospective study. All nodules were divided into three groups according to the maximal diameter (d < 10 mm, d = 10–20 mm and d > 20 mm). The ultrasound images were categorized based on TIRADS and ATA ultrasound patterns, respectively. A total of 931 (96.8%) and 906 (94.2%) patterns met the criteria for TIRADS and ATA ultrasound patterns. The AUC (0.849) and sensitivity (85.3%) of TIRADS were highest in d = 10–20 mm group. However, ATA had highest AUC (0.839) and specificity (89.8%) in d > 20 mm group. ATA ultrasound patterns had higher specificity (P = 0.04), while TI-RADS had higher sensitivity (P = 0.02). In nodules d > 20 mm, the specificity of ATA patterns was higher than TIRADS (P = 0.003). Our results indicated that nodule sizes may influence the diagnostic performance of TIRADS and ATA ultrasound patterns. The ATA patterns may yield higher specificity than TIRADS, especially in nodules larger than 20 mm.
Protective effects on liver, kidney and pancreas of enzymatic- and acidic-hydrolysis of polysaccharides by spent mushroom compost (Hypsizigus marmoreus)
Authors: Liu Min , Song Xinling , Zhang Jianjun , Zhang Chen , Gao Zheng , Li Shangshang , Jing Huijuan , Ren Zhenzhen , Wang Shouxian , Jia Le 
Published: February 2017

AbstractThe present work investigated the protective effects on liver, kidneys and pancreas of spent mushroom compost polysaccharide (SCP) and its hydrolysates (enzymatic- (ESCP) and acid-hydrolyzed SCP (ASCP)) fromHypsizigus marmoreus, in streptozotocin (STZ)-induced diabetic mice. The results showed that enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) and non-enzymatic activities (total antioxidant capacity (T-AOC)) were significantly increased, the lipid peroxide contents (lipid peroxide (LPO) and malonaldehyde (MDA)) were remarkably reduced, and the clinical parameters were observably mitigated in diabetic mice treated with these three polysaccharides. Furthermore, histological observations also indicated recovery. These conclusions demonstrated that both SCP and its hydrolysates ESCP and ASCP possessed potent antioxidant activities and can be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.
Comparative transcriptomic analysis reveals the roles of overlapping heat-/drought-responsive genes in poplars exposed to high temperature and drought
Authors: Jia Jingbo , Zhou Jing , Shi Wenguang , Cao Xu , Luo Jie , Polle Andrea , Luo Zhi-Bin 
Published: February 2017

AbstractHigh temperature (HT) and drought are both critical factors that constrain tree growth and survival under global climate change, but it is surprising that the transcriptomic reprogramming and physiological relays involved in the response to HT and/or drought remain unknown in woody plants. Thus,Populus simoniisaplings were exposed to either ambient temperature or HT combined with sufficient watering or drought. RNA-sequencing analysis showed that a large number of genes were differentially expressed in poplar roots and leaves in response to HT and/or desiccation, but only a small number of these genes were identified as overlapping heat-/drought-responsive genes that are mainly involved in RNA regulation, transport, hormone metabolism, and stress. Furthermore, the overlapping heat-/drought-responsive genes were co-expressed and formed hierarchical genetic regulatory networks under each condition compared. HT-/drought-induced transcriptomic reprogramming is linked to physiological relays in poplar roots and leaves. For instance, HT- and/or drought-induced abscisic acid accumulation and decreases in auxin and other phytohormones corresponded well with the differential expression of a few genes involved in hormone metabolism. These results suggest that overlapping heat-/drought-responsive genes will play key roles in the transcriptional and physiological reconfiguration of poplars to HT and/or drought under future climatic scenarios.
Cerebral Edema in Chronic Mountain Sickness: a New Finding
Authors: Bao Haihua , Wang Duoyao , Zhao Xipeng , Wu Youshen , Yin Guixiu , Meng Li , Wang Fangfang , Ma Lan , Hackett Peter , Ge Ri-Li 
Published: February 2017

AbstractWe observed patients with chronic mountain sickness (CMS) in our clinic who developed progressive neurological deterioration (encephalopathy) and we wished to investigate this. We studied nine such CMS patients, and compared them to 21 CMS patients without encephalopathy, and to 15 healthy control subjects without CMS. All 45 subjects lived permanently at 3200–4000 m. Measurements at 2260 m included CMS symptom score, multi-slice CT, perfusion CT, pulse oximetry (SpO2%), and hemoglobin concentration (Hb). One patient had MRI imaging but not CT; 5 had CSF pressure measurements. CMS subjects had lower SpO2, higher Hb, higher brain blood density, lower mean cerebral blood flow (CBF), and significant cerebral circulatory delay compared to controls. The nine CMS subjects with neurological deterioration showed diffuse cerebral edema on imaging and more deranged cerebral hemodynamics. CSF pressure was elevated in those with edema. We conclude that cerebral edema, a previously unrecognized complication, may develop in CMS patients and cause encephalopathy. Contributing factors appear to be exaggerated polycythemia and hypoxemia, and lower and sluggish CBF compared to CMS patients without cerebral edema; but what triggers this complication is unknown. Recognition and treatment of this serious complication will help reduce morbidity and mortality from CMS.
In silico serine β-lactamases analysis reveals a huge potential resistome in environmental and pathogenic species
Authors: Brandt Christian , Braun Sascha D. , Stein Claudia , Slickers Peter , Ehricht Ralf , Pletz Mathias W. , Makarewicz Oliwia 
Published: February 2017

AbstractThe secretion of antimicrobial compounds is an ancient mechanism with clear survival benefits for microbes competing with other microorganisms. Consequently, mechanisms that confer resistance are also ancient and may represent an underestimated reservoir in environmental bacteria. In this context, β-lactamases (BLs) are of great interest due to their long-term presence and diversification in the hospital environment, leading to the emergence of Gram-negative pathogens that are resistant to cephalosporins (extended spectrum BLs = ESBLs) and carbapenems (carbapenemases). In the current study, protein sequence databases were used to analyze BLs, and the results revealed a substantial number of unknown and functionally uncharacterized BLs in a multitude of environmental and pathogenic species. Together, these BLs represent an uncharacterized reservoir of potentially transferable resistance genes. Considering all available data, in silico approaches appear to more adequately reflect a given resistome than analyses of limited datasets. This approach leads to a more precise definition of BL clades and conserved motifs. Moreover, it may support the prediction of new resistance determinants and improve the tailored development of robust molecular diagnostics.
Risk Model for Colorectal Cancer in Spanish Population Using Environmental and Genetic Factors: Results from the MCC-Spain study
Authors: Ibáñez-Sanz Gemma , Díez-Villanueva Anna , Alonso M. Henar , Rodríguez-Moranta Francisco , Pérez-Gómez Beatriz , Bustamante Mariona , Martin Vicente , Llorca Javier , Amiano Pilar , Ardanaz Eva , Tardón Adonina , Jiménez-Moleón Jose J. , Peiró Rosana , Alguacil Juan , Navarro Carmen , Guinó Elisabet , Binefa Gemma , Fernández-Navarro Pablo , Espinosa Anna , Dávila-Batista Verónica , Molina Antonio José , Palazuelos Camilo , Castaño-Vinyals Gemma , Aragonés Nuria , Kogevinas Manolis , Pollán Marina , Moreno Victor 
Published: February 2017

AbstractColorectal cancer (CRC) screening of the average risk population is only indicated according to age. We aim to elaborate a model to stratify the risk of CRC by incorporating environmental data and single nucleotide polymorphisms (SNP). The MCC-Spain case-control study included 1336 CRC cases and 2744 controls. Subjects were interviewed on lifestyle factors, family and medical history. Twenty-one CRC susceptibility SNPs were genotyped. The environmental risk model, which included alcohol consumption, obesity, physical activity, red meat and vegetable consumption, and nonsteroidal anti-inflammatory drug use, contributed to CRC with an average per factor OR of 1.36 (95% CI 1.27 to 1.45). Family history of CRC contributed an OR of 2.25 (95% CI 1.87 to 2.72), and each additional SNP contributed an OR of 1.07 (95% CI 1.04 to 1.10). The risk of subjects with more than 25 risk alleles (5th quintile) was 82% higher (OR 1.82, 95% CI 1.11 to 2.98) than subjects with less than 19 alleles (1st quintile). This risk model, with an AUROC curve of 0.63 (95% CI 0.60 to 0.66), could be useful to stratify individuals. Environmental factors had more weight than the genetic score, which should be considered to encourage patients to achieve a healthier lifestyle.
High-Fat Diet Induces Unexpected Fatal Uterine Infections in Mice with aP2-Cre-mediated Deletion of Estrogen Receptor Alpha
Authors: Ban Zsofia , Maurischat Paul , Benz Verena , Brix Sarah , Sonnenburg Anna , Schuler Gerhard , Klopfleisch Robert , Rothe Michael , Gustafsson Jan-Åke , Foryst-Ludwig Anna , Kintscher Ulrich 
Published: February 2017

AbstractEstrogen receptor alpha (ERα) is a major regulator of metabolic processes in obesity. In this study we aimed to define the relevance of adipose tissue ERα during high-fat diet (HFD)-induced obesity using female aP2-Cre−/+/ERαfl/fl mice (atERαKO). HFD did not affect body weight or glucose metabolism in atERαKO- compared to control mice. Surprisingly, HFD feeding markedly increased mortality in atERαKO mice associated with a destructive bacterial infection of the uterus driven by commensal microbes, an alteration likely explaining the absence of a metabolic phenotype in HFD-fed atERαKO mice. In order to identify a mechanism of the exaggerated uterine infection in HFD-fed atERαKO mice, a marked reduction of uterine M2-macrophages was detected, a cell type relevant for anti-microbial defence. In parallel, atERαKO mice exhibited elevated circulating estradiol (E2) acting on E2-responsive tissue/cells such as macrophages. Accompanying cell culture experiments showed that despite E2 co-administration stearic acid (C18:0), a fatty acid elevated in plasma from HFD-fed atERαKO mice, blocks M2-polarization, a process known to be enhanced by E2. In this study we demonstrate an unexpected phenotype in HFD-fed atERαKO involving severe uterine bacterial infections likely resulting from a previously unknown negative interference between dietary FAs and ERα-signaling during anti-microbial defence.
Optical coherence tomography evaluation of pulmonary arterial vasculopathy in Systemic Sclerosis
Authors: Schwaiger Johannes P. , Loder Christopher D. , Dobarro David , Kaier Thomas , Reddecliffe Sally , Schreiber Benjamin E. , Handler Clive , Denton Christopher P. , Coghlan John G. 
Published: February 2017

AbstractOur current understanding of the pathophysiology of pulmonary vascular disease is incomplete, since information about alterations of the pulmonary vasculature in pulmonary arterial hypertension (PAH) is primarily provided by autopsy or tissue specimens. The aim of this study was to compare the distal pulmonary vasculature of <2 mm in diameter in Systemic Sclerosis (SSc) patients with (n = 17) and without (n = 5) associated PAH using Optical Coherence Tomography during Right Heart catheterization. SSc-PAH patients showed significant thickening of Intima Media Thickening Area compared to patients without PAH (27 +/− 5.8% vs. 21 +/− 1.4%, p = 0.024). A good haemodynamic response to previous targeted PAH treatment was associated with a significantly greater number of small pulmonary artery side branches <300 μm per cm vessel (3.8 +/− 1.1 vs. 1.8 +/− 1.1; p = 0.010) and not associated with Intima Media thickening Area (26 +/− 5.4% vs. 28 +/− 6.7%; p = 0.6). Unexpected evidence of pulmonary artery thrombus formation was found in 19% of SSc-PAH patients. This is the first in-vivo study demonstrating a direct link between a structural abnormality of pulmonary arteries and a response to targeted treatment in PAH. Intravascular imaging may identify subgroups that may benefit from anticoagulation.
Interplay between Penicillin-binding proteins and SEDS proteins promotes bacterial cell wall synthesis
Authors: Leclercq Sophie , Derouaux Adeline , Olatunji Samir , Fraipont Claudine , Egan Alexander J. F. , Vollmer Waldemar , Breukink Eefjan , Terrak Mohammed 
Published: February 2017

AbstractBacteria utilize specialized multi-protein machineries to synthesize the essential peptidoglycan (PG) cell wall during growth and division. The divisome controls septal PG synthesis and separation of daughter cells. In E. coli, the lipid II transporter candidate FtsW is thought to work in concert with the PG synthases penicillin-binding proteins PBP3 and PBP1b. Yet, the exact molecular mechanisms of their function in complexes are largely unknown. We show that FtsW interacts with PBP1b and lipid II and that PBP1b, FtsW and PBP3 co-purify suggesting that they form a trimeric complex. We also show that the large loop between transmembrane helices 7 and 8 of FtsW is important for the interaction with PBP3. Moreover, we found that FtsW, but not the other flippase candidate MurJ, impairs lipid II polymerization and peptide cross-linking activities of PBP1b, and that PBP3 relieves these inhibitory effects. All together the results suggest that FtsW interacts with lipid II preventing its polymerization by PBP1b unless PBP3 is also present, indicating that PBP3 facilitates lipid II release and/or its transfer to PBP1b after transport across the cytoplasmic membrane. This tight regulatory mechanism is consistent with the cell’s need to ensure appropriate use of the limited pool of lipid II.
A new method for identifying the cut ends in canalicular laceration
Authors: Peng Wenyan , Wang Yandong , Tan Bowei , Wang Haiying , Liu Xuehua , Liang Xuanwei 
Published: February 2017

AbstractTo locate the proximal and distal cut ends of the canaliculus following trauma is the most difficult part of canalicular repair, especially in patients with complex acute canalicular lacerations and late presenting canalicular lacerations. Previously, irrigation and air-injection technique are reported and widely used to locate the cut ends of lacerated canaliculus. However, we have developed a novel technique in which with a 23 Ga fiber optic light pipe is used to identify the cut ends of the canaliculus allowing silicone tube intubation of the lacrimal system. The mean time from initiation of the identification of the cut ends of the canaliculus to insertion of the silicone tube was 5 minutes. In this study, the cut ends were successfully identified by using this novel method in 33 cases of acute and late presenting canalicular laceration for canalicular reconstruction without any complications. This light-guided technique may represent an improvement in the surgical repair of canalicular lacerations.
Rainfall reduction amplifies the stimulatory effect of nitrogen addition on N2O emissions from a temperate forest soil
Authors: Geng Shicong , Chen Zhijie , Han Shijie , Wang Fang , Zhang Junhui 
Published: February 2017

AbstractSoil is a significant source of atmospheric N2O, and soil N2O emissions at a global scale are greatly affected by environment changes that include continuous deposition of atmospheric nitrogen and changing precipitation distribution. However, to date, field simulations of multiple factors that control the interaction between nitrogen deposition and precipitation on forest soil N2O emissions are scarce. In this study, we conducted a 2-year continuous assessment of N2O emissions from November 2012 to October 2014 at a nitrogen addition and rainfall reduction manipulation platform in an old broad-leaved Korean pine mixed forest at Changbai Mountain in northeastern China. We found that N2O emissions from control plots were 1.25 ± 0.22 kg N2O-N ha−1 a−1. Nitrogen addition significantly increased N2O emissions, with the emission factor of 1.59%. A 30% reduction in rainfall decreased N2O emissions by 17–45%. However, in combination, nitrogen addition and rainfall reduction increased N2O emissions by 58–140%, with the emission factor of 3.19%, and had a larger promotional effect than the addition of nitrogen alone. Our results indicated that drought slightly decreases forest soil N2O emission; however, with increasing deposition of atmospheric N in temperate forest soils, the effect of drought might become altered to increase N2O emission.
Electrical cream separator coupled with vacuum filtration for the purification of eimerian oocysts and trichostrongylid eggs
Authors: El-Ashram Saeed , Suo Xun 
Published: February 2017

AbstractSeveral methods have been proposed for separation of eimerian oocysts and trichostrongylid eggs from extraneous debris; however, these methods have been considered to be still inconvenient in terms of time and wide-ranging applications. We describe herein an alternative way using the combination of electrical cream separator and vacuum filtration for harvesting and purifying eimerian oocysts and haemonchine eggs on large-scale applications with approximately 81% and 92% recovery rates for oocysts and nematode eggs obtained from avian and ovine faeces, correspondingly. The sporulation percentages as a measure of viability in the harvested oocysts and eggs from dry faecal materials are nearly 68% and 74%, respectively, and 12 liters of faecal suspension can be processed in approximately 7.5 min. The mode of separation in terms of costs (i.e. simple laboratory equipments and comparably cheap reagents) and benefits renders the reported procedure an appropriate pursuit to harvest and purify parasite oocysts and eggs on a large scale in the shortest duration from diverse volumes of environmental samples compared to the modified traditional sucrose gradient, which can be employed on a small scale.