bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycoplasma bovis NADH oxidase functions as both a NADH oxidizing and O2 reducing enzyme and an adhesin
Authors: Zhao Gang , Zhang Hui , Chen Xi , Zhu Xifang , Guo Yusi , He Chenfei , Anwar Khan Farhan , Chen Yingyu , Hu Changmin , Chen Huanchun , Guo Aizhen 
Published: February 2017

AbstractMycoplasma bovis causes considerable economic losses in the cattle industry worldwide. In mycoplasmal infections, adhesion to the host cell is of the utmost importance. In this study, the amino acid sequence of NOX was predicted to have enzymatic domains. The nox gene was then cloned and expressed in Escherichia coli. The enzymatic activity of recombinant NOX (rNOX) was confirmed based on its capacity to oxidize NADH to NAD+ and reduce O2 to H2O2. The adherence of rNOX to embryonic bovine lung (EBL) cells was confirmed with confocal laser scanning microscopy, enzyme-linked immunosorbent assay, and flow cytometry. Both preblocking EBL cells with purified rNOX and preneutralizing M. bovis with polyclonal antiserum to rNOX significantly reduced the adherence of M. bovis to EBL cells. Mycoplasma bovisNOX–expressed a truncated NOX protein at a level 10-fold less than that of the wild type. The capacities of M. bovisNOX– for cell adhesion and H2O2 production were also significantly reduced. The rNOX was further used to pan phage displaying lung cDNA library and fibronectin was determined to be potential ligand. In conclusion, M. bovis NOX functions as both an active NADH oxidase and adhesin, and is therefore a potential virulence factor.
A c-Myc-regulated stem cell-like signature in high-risk neuroblastoma: A systematic discovery (Target neuroblastoma ESC-like signature)
Authors: Yang Xinan , Tang Fangming , Shin Jisu , Cunningham John M. 
Published: February 2017

Abstractc-Myc dysregulation is hypothesized to account for the ‘stemness’ – self-renewal and pluripotency – shared between embryonic stem cells (ESCs) and adult aggressive tumours. High-risk neuroblastoma (HR-NB) is the most frequent, aggressive, extracranial solid tumour in childhood. Using HR-NB as a platform, we performed a network analysis of transcriptome data and presented a c-Myc subnetwork enriched for genes previously reported as ESC-like cancer signatures. A subsequent drug-gene interaction analysis identified a pharmacogenomic agent that preferentially interacted with this HR-NB-specific, ESC-like signature. This agent, Roniciclib (BAY 1000394), inhibited neuroblastoma cell growth and induced apoptosis in vitro. It also repressed the expression of the oncogene c-Myc and the neural ESC marker CDK2 in vitro, which was accompanied by altered expression of the c-Myc-targeted cell cycle regulators CCND1, CDKN1A and CDKN2D in a time-dependent manner. Further investigation into this HR-NB-specific ESC-like signature in 295 and 243 independent patients revealed and validated the general prognostic index of CDK2 and CDKN3 compared with CDKN2D and CDKN1B. These findings highlight the very potent therapeutic benefits of Roniciclib in HR-NB through the targeting of c-Myc-regulated, ESC-like tumorigenesis. This work provides a hypothesis-driven systems computational model that facilitates the translation of genomic and transcriptomic signatures to molecular mechanisms underlying high-risk tumours.
Differential expression of the protein kinase A subunits in normal adrenal glands and adrenocortical adenomas
Authors: Weigand Isabel , Ronchi Cristina L. , Rizk-Rabin Marthe , Dalmazi Guido Di , Wild Vanessa , Bathon Kerstin , Rubin Beatrice , Calebiro Davide , Beuschlein Felix , Bertherat Jérôme , Fassnacht Martin , Sbiera Silviu 
Published: February 2017

AbstractSomatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30–40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.
Usp7-dependent histone H3 deubiquitylation regulates maintenance of DNA methylation
Authors: Yamaguchi Luna , Nishiyama Atsuya , Misaki Toshinori , Johmura Yoshikazu , Ueda Jun , Arita Kyohei , Nagao Koji , Obuse Chikashi , Nakanishi Makoto 
Published: February 2017

AbstractUhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA methylation sites during DNA replication. Usp7 deubiquitylates ubiquitylated histone H3 in vitro. Inhibition of Usp7 activity or its depletion in egg extracts results in enhanced and extended binding of Dnmt1 to chromatin, suppressing DNA methylation. Depletion of Usp7 in HeLa cells causes enhanced histone H3 ubiquitylation and enlargement of Dnmt1 nuclear foci during DNA replication. Our results thus suggest that Usp7 is a key factor that regulates maintenance of DNA methylation.
Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data
Authors: Fontana Andrea , Ortega Moreno Lorena , Lamacchia Olga , De Bonis Concetta , Salvemini Lucia , De Cosmo Salvatore , Cignarelli Mauro , Copetti Massimiliano , Trischitta Vincenzo , Menzaghi Claudia 
Published: February 2017

AbstractResistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and all-cause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n = 350), Gargano Mortality Study (n = 698) and Foggia Mortality Study (n = 431), from Italy. GRS was strongly associated with serum resistin in a non-linear fashion (overall p = 3.5 * 10−7) with effect size modest for GRS = 1 and 2 and much higher for GRS >3, with respect to GRS = 0. A significant non-linear association was observed also between GRS and all-cause mortality (overall p = 3.3 * 10−2), with a low effect size for GRS = 1 and 2, and nearly doubled for GRS ≥ 3, with respect to GRS = 0. Based on the above-reported associations, each genetic equivalent SD increase in log-resistin levels showed a causal hazard ratio of all-cause mortality equal to 2.17 (95%CI: 1.22–3.87), thus providing evidence for a causal role of resistin in shaping the risk of mortality in diabetic patients.
Rescue of the MERTK phagocytic defect in a human iPSC disease model using translational read-through inducing drugs
Authors: Ramsden Conor M. , Nommiste Britta , R. Lane Amelia , Carr Amanda-Jayne F. , Powner Michael B. , J. K. Smart Matthew , Chen Li Li , Muthiah Manickam N. , Webster Andrew R. , Moore Anthony T. , Cheetham Michael E. , da Cruz Lyndon , Coffey Peter J. 
Published: February 2017

AbstractInherited retinal dystrophies are an important cause of blindness, for which currently there are no effective treatments. In order to study this heterogeneous group of diseases, adequate disease models are required in order to better understand pathology and to test potential therapies. Induced pluripotent stem cells offer a new way to recapitulate patient specific diseases in vitro, providing an almost limitless amount of material to study. We used fibroblast-derived induced pluripotent stem cells to generate retinal pigment epithelium (RPE) from an individual suffering from retinitis pigmentosa associated with biallelic variants in MERTK. MERTK has an essential role in phagocytosis, one of the major functions of the RPE. The MERTK deficiency in this individual results from a nonsense variant and so the MERTK-RPE cells were subsequently treated with two translational readthrough inducing drugs (G418 & PTC124) to investigate potential restoration of expression of the affected gene and production of a full-length protein. The data show that PTC124 was able to reinstate phagocytosis of labeled photoreceptor outer segments at a reduced, but significant level. These findings represent a confirmation of the usefulness of iPSC derived disease specific models in investigating the pathogenesis and screening potential treatments for these rare blinding disorders.
Three-dimensional mouse brain cytoarchitecture revealed by laboratory-based x-ray phase-contrast tomography
Authors: Töpperwien Mareike , Krenkel Martin , Vincenz Daniel , Stöber Franziska , Oelschlegel Anja M. , Goldschmidt Jürgen , Salditt Tim 
Published: February 2017

AbstractStudies of brain cytoarchitecture in mammals are routinely performed by serial sectioning of the specimen and staining of the sections. The procedure is labor-intensive and the 3D architecture can only be determined after aligning individual 2D sections, leading to a reconstructed volume with non-isotropic resolution. Propagation-based x-ray phase-contrast tomography offers a unique potential for high-resolution 3D imaging of intact biological specimen due to the high penetration depth and potential resolution. We here show that even compact laboratory CT at an optimized liquid-metal jet microfocus source combined with suitable phase-retrieval algorithms and a novel tissue preparation can provide cellular and subcellular resolution in millimeter sized samples of mouse brain. We removed water and lipids from entire mouse brains and measured the remaining dry tissue matrix in air, lowering absorption but increasing phase contrast. We present single-cell resolution images of mouse brain cytoarchitecture and show that axons can be revealed in myelinated fiber bundles. In contrast to optical 3D techniques our approach does neither require staining of cells nor tissue clearing, procedures that are increasingly difficult to apply with increasing sample and brain sizes. The approach thus opens a novel route for high-resolution high-throughput studies of brain architecture in mammals.
A comparison of host gene expression signatures associated with infection in vitro by the Makona and Ecran (Mayinga) variants of Ebola virus
Authors: Bosworth Andrew , Dowall Stuart D. , Garcia-Dorival Isabel , Rickett Natasha Y. , Bruce Christine B. , Matthews David A. , Fang Yongxiang , Aljabr Waleed , Kenny John , Nelson Charlotte , Laws Thomas R. , Williamson E. Diane , Stewart James P. , Carroll Miles W. , Hewson Roger , Hiscox Julian A. 
Published: February 2017

AbstractThe Ebola virus (EBOV) variant Makona (which emerged in 2013) was the causative agent of the largest outbreak of Ebola Virus Disease recorded. Differences in virus-host interactions between viral variants have potential consequences for transmission, disease severity and mortality. A detailed profile of the cellular changes induced by the Makona variant compared with other Ebola virus variants was lacking. In this study, A549 cells, a human cell line with a robust innate response, were infected with the Makona variant or with the Ecran variant originating from the 1976 outbreak in Central Africa. The abundance of viral and cellular mRNA transcripts was profiled using RNASeq and differential gene expression analysis performed. Differences in effects of each virus on the expression of interferon-stimulated genes were also investigated in A549 NPro cells where the type 1 interferon response had been attenuated. Cellular transcriptomic changes were compared with those induced by human respiratory syncytial virus (HRSV), a virus with a similar genome organisation and replication strategy to EBOV. Pathway and gene ontology analysis revealed differential expression of functionally important genes; including genes involved in the inflammatory response, cell proliferation, leukocyte extravasation and cholesterol biosynthesis. Whilst there was overlap with HRSV, there was unique commonality to the EBOV variants.
Calcium pre-conditioning substitution enhances viability and glucose sensitivity of pancreatic beta-cells encapsulated using polyelectrolyte multilayer coating method
Authors: Nikravesh Niusha , Cox Sophie C. , Birdi Gurpreet , Williams Richard L. , Grover Liam M. 
Published: February 2017

AbstractType I diabetics are dependent on daily insulin injections. A therapy capable of immunoisolating pancreatic beta-cells and providing normoglycaemia is an alternative since it would avoid the late complications associated with insulin use. Here, 3D-concave agarose micro-wells were used to culture robust pancreatic MIN-6 cell spheroids within 24 hours that were shown to exhibit cell-cell contact and uniform size (201 ± 2 μm). A polyelectrolyte multilayer (PEM) approach using alginate and poly-l-lysine was employed to coat cell spheroids. In comparison to conventional PEM, use of a novel Ca2+ pre-coating step enhanced beta-cells viability (89 ± 6%) and metabolic activity since it reduced the toxic effect of the cationic polymer. Pre-coating was achieved by treating MIN-6 spheroids with calcium chloride, which enabled the adhesion of anionic polymer to the cells surface. Pre-coated cells coated with four bilayers of polymers were successfully immunoisolated from FITC-mouse antibody and pro-inflammatory cytokines. Novel PEM coated cells were shown to secret significantly (P < 0.05) different amounts of insulin in response to changes in glucose concentration (2 vs. 20 mM). This work presents a 3D culture model and novel PEM coating procedure that enhances viability, maintains functionality and immunoisolates beta-cells, which is a promising step towards an alternative therapy to insulin.
Venomics of Tropidolaemus wagleri, the sexually dimorphic temple pit viper: Unveiling a deeply conserved atypical toxin arsenal
Authors: Tan Choo Hock , Tan Kae Yi , Yap Michelle Khai Khun , Tan Nget Hong 
Published: February 2017

AbstractTropidolaemus wagleri (temple pit viper) is a medically important snake in Southeast Asia. It displays distinct sexual dimorphism and prey specificity, however its venomics and inter-sex venom variation have not been thoroughly investigated. Applying reverse-phase HPLC, we demonstrated that the venom profiles were not significantly affected by sex and geographical locality (Peninsular Malaya, insular Penang, insular Sumatra) of the snakes. Essentially, venoms of both sexes share comparable intravenous median lethal dose (LD50) (0.56–0.63 μg/g) and cause neurotoxic envenomation in mice. LCMS/MS identified six waglerin forms as the predominant lethal principles, comprising 38.2% of total venom proteins. Fourteen other toxin-protein families identified include phospholipase A2, serine proteinase, snaclec and metalloproteinase. In mice, HPLC fractions containing these proteins showed insignificant contribution to the overall venom lethality. Besides, the unique elution pattern of approximately 34.5% of non-lethal, low molecular mass proteins (3–5 kDa) on HPLC could be potential biomarker for this primitive crotalid species. Together, the study unveiled the venom proteome of T. wagleri that is atypical among many pit vipers as it comprises abundant neurotoxic peptides (waglerins) but little hemotoxic proteinases. The findings also revealed that the venom is relatively well conserved intraspecifically despite the drastic morphological differences between sexes.
A longitudinal study of cerebral blood flow under hypoxia at high altitude using 3D pseudo-continuous arterial spin labeling
Authors: Liu Wenjia , Liu Jie , Lou Xin , Zheng Dandan , Wu Bing , Wang Danny J. J. , Ma Lin 
Published: February 2017

AbstractChanges in cerebral blood flow (CBF) may occur with acute exposure to high altitude; however, the CBF of the brain parenchyma has not been studied to date. In this study, identical magnetic resonance scans using arterial spin labeling (ASL) were performed to study the haemodynamic changes at both sea level and high altitude. We found that with acute exposure to high altitude, the CBF in acute mountain sickness (AMS) subjects was higher (P < 0.05), while the CBF of non-AMS subjects was lower (P > 0.05) compared with those at sea level. Moreover, magnetic resonance angiography in both AMS and non-AMS subjects showed a significant increase in the cross-sectional areas of the internal carotid, basilar, and middle cerebral arteries on the first day at high altitude. These findings support that AMS may be related to increased CBF rather than vasodilation; these results contradict most previous studies that reported no relationship between CBF changes and the occurrence of AMS. This discrepancy may be attributed to the use of ASL for CBF measurement at both sea level and high altitude in this study, which has substantial advantages over transcranial Doppler for the assessment of CBF.
Thermoelectric SnS and SnS-SnSe solid solutions prepared by mechanical alloying and spark plasma sintering: Anisotropic thermoelectric properties
Authors: Asfandiyar  , Wei Tian-Ran , Li Zhiliang , Sun Fu-Hua , Pan Yu , Wu Chao-Feng , Farooq Muhammad Umer , Tang Huaichao , Li Fu , Li Bo , Li Jing-Feng 
Published: February 2017

AbstractP–type SnS compound and SnS1−xSex solid solutions were prepared by mechanical alloying followed by spark plasma sintering (SPS) and their thermoelectric properties were then studied in different compositions (x = 0.0, 0.2, 0.5, 0.8) along the directions parallel (//) and perpendicular (⊥) to the SPS–pressurizing direction in the temperature range 323–823 Κ. SnS compound and SnS1−xSex solid solutions exhibited anisotropic thermoelectric performance and showed higher power factor and thermal conductivity along the direction ⊥ than the // one. The thermal conductivity decreased with increasing contents of Se and fell to 0.36 W m−1 K−1 at 823 K for the composition SnS0.5Se0.5. With increasing selenium content (x) the formation of solid solutions substantially improved the electrical conductivity due to the increased carrier concentration. Hence, the optimized power factor and reduced thermal conductivity resulted in a maximum ZT value of 0.64 at 823 K for SnS0.2Se0.8 along the parallel direction.
Exogenous melatonin reduces somatic cell count of milk in Holstein cows
Authors: Yang Minghui , Shi Jianmin , Tian Jianhua , Tao Jingli , Chai Menglong , Wang Jing , Xu Zhiyuan , Song Yukun , Zhu Kuanfeng , Ji Pengyun , Liu Guoshi 
Published: February 2017

AbstractHigh somatic cell counts in milk caused by mastitis significantly influence the quality of milk and result in substantial annual economic loss. This study evaluated the beneficial effects of melatonin (MT) on milk somatic cell count (SCC) in cows. To examine the effects of melatonin on SCC, one hundred twenty cows were divided into four groups based on milk SCC. In each group, half of the cows were treated with melatonin (S.C.). Melatonin treatment significantly reduced milk SCC. To explore the potential mechanism, 20 cows with relatively high SCC were selected to evaluate the biochemical and immunological profiles of their blood after melatonin treatment. Treatment with MT significantly reduced SCC in milk, lowered serum cortisol concentrations and increased the levels of albumin, alanine transaminase and lactate dehydrogenase. Following treatment with MT, the concentration of IgG and IgM rose transiently then decreased significantly, similar to changes observed for white blood cells and lymphocytes. In conclusion, MT treatment improved the quality of milk by reducing SCC. This may be due to melatonin improving immune activity in cows.
The influences of four types of soil on the growth, physiological and biochemical characteristics of Lycoris aurea (L’ Her.) Herb
Authors: Quan Miaohua , Liang Juan 
Published: February 2017

AbstractBased on the characteristics of Lycoris aurea (L. aurea) natural distribution and local soil types, we selected four representative types of soil, including humus soil, sandy soil, garden soil and yellow-brown soil, for conducting the cultivation experiments to investigate key soil factors influencing its growth and development and to select the soil types suitable for cultivating it. We found that there existed significant differences in the contents of mineral elements and the activities of soil enzymes (urease, phosphatase, sucrase and catalase) etc. Among which, the contents of organic matters, alkali-hydrolysable nitrogen, Ca and Mg as well as the activities of soil enzymes in humus soil were the highest ones. In yellow-brown soil, except for Fe, the values of all the other items were the lowest ones. Net photosynthetic rate (Pn), biomass and lycorine content in humus soil were all the highest ones, which were increased by 31.02, 69.39 and 55.79%, respectively, as compared to those of yellow-brown soil. Stepwise multiple regression analysis and path analysis indicated that alkali-hydrolysable nitrogen, and Ca etc. were key soil factors influencing Pn, biomass and lycorine content of L. aurea. Thus, humus soil can be used as medium suitable for artificial cultivation of L. aurea.
Association of Renal Elasticity and Renal Function Progression in Patients with Chronic Kidney Disease Evaluated by Real-Time Ultrasound Elastography
Authors: Lin Hugo You-Hsien , Lee Yu-Li , Lin Kun-Der , Chiu Yi-Wen , Shin Shyi-Jang , Hwang Shang-Jyh , Chen Hung-Chun , Hung Chi-Chih 
Published: February 2017

AbstractGlomerulosclerosis and tubulointerstitial fibrosis are associated with lower renal parenchymal elasticity. This study was designed to evaluate the predictive ability of renal elasticity in patients with chronic kidney disease (CKD). 148 non-CKD patients and 227 patients with CKD were recruited. 145 (38.7%) were female, 166 (73.1%) had diabetes, the mean estimated glomerular filtration rate (eGFR) was 33.9 ± 15.8 ml/min/1.73 m2 and the median urinary protein-to-creatinine ratio (UPCR) 502 (122–1491) mg/g. Patients with later stages of CKD had lower renal elasticity values, indicating stiffer kidneys (p < 0.001), and smaller kidney (p < 0.001). Renal elasticity correlated with log-transformed UPCR (β = −7.544, P < 0.001). Renal length correlated with age (β = −0.231, P < 0.001), sex (β = −3.730, P < 0.001), serum albumin level (β = −3.024, P = 0.001), body mass index (β = 0.390, P = 0.009) and eGFR (β = 0.146, P < 0.001). In fully-adjusted logistic regression model, the odds ratio (OR) per 10 unit change in renal elasticity for rapid renal deterioration was 0.928 (95% CI, 0.864–0.997; P = 0.042). The OR per 1 mm change in renal length for rapid renal deterioration was 1.022 (95% CI, 0.994–1.050; P = 0.125). Renal elasticity is associated with proteinuria and rapid renal deterioration in patients with CKD.