bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung
Authors: Grasemann C , Herrmann R , Starschinova J , Gertsen M , Palmert M R , Grasemann H 
Published: February 2017

Abstract
Background/Objectives:
Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice.

Methods:
We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring.

Results:
Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring.

Conclusions:
These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring.
A functionally significant SNP in TP53 and breast cancer risk in African-American women
Authors: Murphy Maureen E. , Liu Song , Yao Song , Huo Dezheng , Liu Qin , Dolfi Sonia C. , Hirshfield Kim M. , Hong Chi-Chen , Hu Qiang , Olshan Andrew F. , Ogundiran Temidayo O. , Adebamowo Clement , Domchek Susan M. , Nathanson Katherine L. , Nemesure Barbara , Ambs Stefan , Blot William J. , Feng Ye , John Esther M. , Bernstein Leslie , Zheng Wei , Hu Jennifer J. , Ziegler Regina G. , Nyante Sarah , Ingles Sue A. , Press Michael F. , Deming Sandra L. , Rodriguez-Gil Jorge L. , Haiman Christopher A. , Olopade Olufunmilayo I. , Lunetta Kathryn L. , Palmer Julie R. , Ambrosone Christine B. 
Published: February 2017

AbstractA coding region polymorphism exists in the TP53 gene (Pro47Ser; rs1800371) in individuals of African descent, which reduces p53 tumor suppressor function in a mouse model. It has been unclear whether this functionally significant polymorphism alters cancer risk in humans. This analysis included 6907 women with breast cancer and 7644 controls from the AMBER, ROOT, and AABC consortia. We used multivariable logistic regression to estimate associations between the TP53 Pro47Ser allele and overall breast cancer risk. Because polymorphisms in TP53 tend to be associated with cancer risk in pre-menopausal women, we also limited our analyses to this population in the AMBER and ROOT consortia, where menopausal status was known, and conducted a fixed effects meta-analysis. In an analysis of all women in the AMBER, ROOT, and AABC consortia, we found no evidence for association of the Pro47Ser variant with breast cancer risk. However, when we restricted our analysis to only pre-menopausal women from the AMBER and ROOT consortia, there was a per allele odds ratio of 1.72 (95% confidence interval 1.08–2.76; p-value = 0.023). Although the Pro47Ser variant was not associated with overall breast cancer risk, it may increase risk among pre-menopausal women of African ancestry. Following up on more studies in human populations may better elucidate the role of this variant in breast cancer etiology. However, because of the low frequency of the polymorphism in women of African ancestry, its impact at a population level may be minimal.
MINTmap: fast and exhaustive profiling of nuclear and mitochondrial tRNA fragments from short RNA-seq data
Authors: Loher Phillipe , Telonis Aristeidis G. , Rigoutsos Isidore 
Published: February 2017

AbstractTransfer RNA fragments (tRFs) are an established class of constitutive regulatory molecules that arise from precursor and mature tRNAs. RNA deep sequencing (RNA-seq) has greatly facilitated the study of tRFs. However, the repeat nature of the tRNA templates and the idiosyncrasies of tRNA sequences necessitate the development and use of methodologies that differ markedly from those used to analyze RNA-seq data when studying microRNAs (miRNAs) or messenger RNAs (mRNAs). Here we present MINTmap (for MItochondrial and Nuclear TRF mapping), a method and a software package that was developed specifically for the quick, deterministic and exhaustive identification of tRFs in short RNA-seq datasets. In addition to identifying them, MINTmap is able to unambiguously calculate and report both raw and normalized abundances for the discovered tRFs. Furthermore, to ensure specificity, MINTmap identifies the subset of discovered tRFs that could be originating outside of tRNA space and flags them as candidate false positives. Our comparative analysis shows that MINTmap exhibits superior sensitivity and specificity to other available methods while also being exceptionally fast. The MINTmap codes are available throughhttps://github.com/TJU-CMC-Org/MINTmap/under an open source GNU GPL v3.0 license.
Mass Spectrometric Analysis of TRPM6 and TRPM7 Phosphorylation Reveals Regulatory Mechanisms of the Channel-Kinases
Authors: Cai Na , Bai Zhiyong , Nanda Vikas , Runnels Loren W. 
Published: February 2017

AbstractTRPM7 and TRPM6 were the first identified bifunctional channels to contain their own kinase domains, but how these channel-kinases are regulated is poorly understood. Previous studies identified numerous phosphorylation sites on TRPM7, but very little is known about TRPM6 phosphorylation or sites on TRPM7 transphosphorylated by TRPM6. Our mass spectrometric analysis of homomeric and heteromeric TRPM7 and TRPM6 channels identified phosphorylation sites on both proteins, as well as several prominent sites on TRPM7 that are commonly modified through autophosphorylation and transphosphorylation by TRPM6. We conducted a series of amino acid substitution analyses and identified S1777, in TRPM7’s catalytic domain, and S1565, in TRPM7’s exchange domain that mediates kinase dimerization, as potential regulatory sites. The phosphomimetic S1777D substitution disrupted catalytic activity, most likely by causing an electrostatic perturbation at the active site. The S1565D phosphomimetic substitution also inactivated the kinase but did so without interfering with kinase dimerization. Molecular modeling indicates that phosphorylation of S1565 is predicted to structurally affect TRPM7’s functionally conserved N/D loop, which is thought to influence the access of substrate to the active site pocket. We propose that phosphorylation of S1565 within the exchange domain functions as a regulatory switch to control TRPM7 catalytic activity.
High quality AlN epilayers grown on nitrided sapphire by metal organic chemical vapor deposition
Authors: Wang Jiaming , Xu Fujun , He Chenguang , Zhang Lisheng , Lu Lin , Wang Xinqiang , Qin Zhixin , Shen Bo 
Published: February 2017

AbstractInfluence of sapphire pretreatment conditions on crystalline quality of AlN epilayers has been investigated by metal organic chemical vapor deposition (MOCVD). Compared to alumination treatment, it is found that appropriate sapphire nitridation significantly straightens the surface atomic terraces and decreases the X-ray diffraction (0002) full width at half maximum (FWHM) to a minimum of 55 arcsec, indicating a great improvement of the tilting feature of the grain structures in the AlN epilayer. More importantly, there is no inversion domains (IDs) found in the AlN epilayers, which clarifies that optimal sapphire nitridation is promising in the growth of high quality AlN. It is deduced that the different interfacial atomic structures caused by various pretreatment conditions influence the orientation of the AlN nucleation layer grains, which eventually determines the tilting features of the AlN epilayers.
Induction of hair follicle dermal papilla cell properties in human induced pluripotent stem cell-derived multipotent LNGFR(+)THY-1(+) mesenchymal cells
Authors: Veraitch Ophelia , Mabuchi Yo , Matsuzaki Yumi , Sasaki Takashi , Okuno Hironobu , Tsukashima Aki , Amagai Masayuki , Okano Hideyuki , Ohyama Manabu 
Published: February 2017

AbstractThe dermal papilla (DP) is a specialised mesenchymal component of the hair follicle (HF) that plays key roles in HF morphogenesis and regeneration. Current technical difficulties in preparing trichogenic human DP cells could be overcome by the use of highly proliferative and plastic human induced pluripotent stem cells (hiPSCs). In this study, hiPSCs were differentiated into induced mesenchymal cells (iMCs) with a bone marrow stromal cell phenotype. A highly proliferative and plastic LNGFR(+)THY-1(+) subset of iMCs was subsequently programmed using retinoic acid and DP cell activating culture medium to acquire DP properties. The resultant cells (induced DP-substituting cells [iDPSCs]) exhibited up-regulated DP markers, interacted with human keratinocytes to up-regulate HF related genes, and when co-grafted with human keratinocytes in vivo gave rise to fibre structures with a hair cuticle-like coat resembling the hair shaft, as confirmed by scanning electron microscope analysis. Furthermore, iDPSCs responded to the clinically used hair growth reagent, minoxidil sulfate, to up-regulate DP genes, further supporting that they were capable of, at least in part, reproducing DP properties. Thus, LNGFR(+)THY-1(+) iMCs may provide material for HF bioengineering and drug screening for hair diseases.
Distinct signatures of dental plaque metabolic byproducts dictated by periodontal inflammatory status
Authors: Sakanaka Akito , Kuboniwa Masae , Hashino Ei , Bamba Takeshi , Fukusaki Eiichiro , Amano Atsuo 
Published: February 2017

AbstractOnset of chronic periodontitis is associated with an aberrant polymicrobial community, termed dysbiosis. Findings regarding its etiology obtained using high-throughput sequencing technique suggested that dysbiosis holds a conserved metabolic signature as an emergent property. The purpose of this study was to identify robust biomarkers for periodontal inflammation severity. Furthermore, we investigated disease-associated metabolic signatures of periodontal microbiota using a salivary metabolomics approach. Whole saliva samples were obtained from adult subjects before and after removal of supragingival plaque (debridement). Periodontal inflamed surface area (PISA) was employed as an indicator of periodontal inflammatory status. Based on multivariate analyses using pre-debridement salivary metabolomics data, we found that metabolites associated with higher PISA included cadaverine and hydrocinnamate, while uric acid and ethanolamine were associated with lower PISA. Next, we focused on dental plaque metabolic byproducts by selecting salivary metabolites significantly decreased following debridement. Metabolite set enrichment analysis revealed that polyamine metabolism, arginine and proline metabolism, butyric acid metabolism, and lysine degradation were distinctive metabolic signatures of dental plaque in the high PISA group, which may be related to the metabolic signatures of disease-associated communities. Collectively, our findings identified potential biomarkers of periodontal inflammatory status and also provide insight into metabolic signatures of dysbiotic communities.
Status of HBsAg seroprevalence in 15 million rural couples in China: a cross-sectional study
Authors: Zhang Long , Wang Yuan-Yuan , Huang Yan-Jie , Wang Qiao-Mei , Nelson Kenrad E. , Wang An-Qi , Shen Hai-Ping , Liu Xiao-Li , Zhang Yi-Ping , Yan Dong-Hai , Peng Zuo-Qi , Zhang Hong-Guang , Zhang Ya , Zhao Jun , Wang Yan , Yang Ying , He Yuan , Xu Ji-Hong , Liu Du-Jia , Guo Tong-Jun , Xin Xiao-Na , Zhou Hong , Ma Xu 
Published: February 2017

AbstractA cross-sectional analysis of prevalence of hepatitis B virus infection (HBV) among rural couples was conducted between 2010 and 2014. Serologic HBV markers, including hepatitis B surface antigen (HBsAg) and e antigen (HBeAg), were tested. Primary outcome of interest comprised HBsAg positivity in couples (both positive: F+M+, only wife positive: F+M−, only husband positive: F−M+), and secondary outcome consisted of prevalence and risk factors of HBsAg positivity among husbands or wives. Of 14,816,300 couples included, 0.7% were F+M+; 6.3% were F−M+; 4.4% were F+M−, resulting in the overall seroprevalence of 11.4%. Individually, 6.1% were HBsAg positive with a higher rate seen in husbands (7.0%) than in wives (5.2%). Wife’s HBeAg(+)/HBsAg (+) (AOR = 2.61), HBeAg(−)/HBsAg (+) (AOR = 2.23), positivity of syphilis (AOR = 1.50), living in a high-risk region (AOR = 1.46) were significantly predictors of HBsAg positivity in husbands. Prevalence and predictors of HBsAg positivity in wives had similar results. Our data show a high burden and discordant pattern of HBV infection in rural couples, and partner’s double positivity of HBeAg and HBsAg was the most significant factor of HBV infection in couples. A comprehensive strategy that emphasizes vaccination and education is needed.
SAMHD1 enhances nucleoside-analogue efficacy against HIV-1 in myeloid cells
Authors: Ordonez Paula , Kunzelmann Simone , Groom Harriet C. T. , Yap Melvyn W. , Weising Simon , Meier Chris , Bishop Kate N. , Taylor Ian A. , Stoye Jonathan P. 
Published: February 2017

AbstractSAMHD1 is an intracellular enzyme that specifically degrades deoxynucleoside triphosphates into component nucleoside and inorganic triphosphate. In myeloid-derived dendritic cells and macrophages as well as resting T-cells, SAMHD1 blocks HIV-1 infection through this dNTP triphosphohydrolase activity by reducing the cellular dNTP pool to a level that cannot support productive reverse transcription. We now show that, in addition to this direct effect on virus replication, manipulating cellular SAMHD1 activity can significantly enhance or decrease the anti-HIV-1 efficacy of nucleotide analogue reverse transcription inhibitors presumably as a result of modulating dNTP pools that compete for recruitment by viral polymerases. Further, a variety of other nucleotide-based analogues, not normally considered antiretrovirals, such as the anti-herpes drugs Aciclovir and Ganciclovir and the anti-cancer drug Clofarabine are now revealed as potent anti-HIV-1 agents, under conditions of low dNTPs. This in turn suggests novel uses for nucleotide analogues to inhibit HIV-1 in differentiated cells low in dNTPs.
FOXO1 expression in keratinocytes promotes connective tissue healing
Authors: Zhang Chenying , Lim Jason , Liu Jian , Ponugoti Bhaskar , Alsadun Sarah , Tian Chen , Vafa Rameen , Graves Dana T. 
Published: February 2017

AbstractWound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome.
RSPO3-LGR4 Regulates Osteogenic Differentiation Of Human Adipose-Derived Stem Cells Via ERK/FGF Signalling
Authors: Zhang Min , Zhang Ping , Liu Yunsong , Lv Longwei , Zhang Xiao , Liu Hao , Zhou Yongsheng 
Published: February 2017

AbstractThe four R-spondins (RSPOs) and their three related receptors, LGR4, 5 and 6, have emerged as a major ligand-receptor system with critical roles in development and stem cell survival. However, the exact roles of the RSPO-LGR system in osteogenesis remain largely unknown. In the present study, we showed that RSPO3-shRNA increased the osteogenic potential of human adipose-derived stem cells (hASCs) significantly. Mechanistically, we demonstrated that RSPO3 is a negative regulator of ERK/FGF signalling. We confirmed that inhibition of the ERK1/2 signalling pathway blocked osteogenic differentiation in hASCs, and the increased osteogenic capacity observed after RSPO3 knockdown in hASCs was reversed by inhibition of ERK signalling. Further, silencing of LGR4 inhibited the activity of ERK signalling and osteogenic differentiation of hASCs. Most importantly, we found that loss of LGR4 abrogated RSPO3-regulated osteogenesis and RSPO3-induced ERK1/2 signalling inhibition. Collectively, our data show that ERK signalling works downstream of LGR4 and RSPO3 regulates osteoblastic differentiation of hASCs possibly via the LGR4-ERK signalling.
Effects of abiotic factors on ecosystem health of Taihu Lake, China based on eco-exergy theory
Authors: Wang Ce , Bi Jun , Fath Brian D. 
Published: February 2017

AbstractA lake ecosystem is continuously exposed to environmental stressors with non-linear interrelationships between abiotic factors and aquatic organisms. Ecosystem health depicts the capacity of system to respond to external perturbations and still maintain structure and function. In this study, we explored the effects of abiotic factors on ecosystem health of Taihu Lake in 2013, China from a system-level perspective. Spatiotemporal heterogeneities of eco-exergy and specific eco-exergy served as thermodynamic indicators to represent ecosystem health in the lake. The results showed the plankton community appeared more energetic in May, and relatively healthy in Gonghu Bay with both higher eco-exergy and specific eco-exergy; a eutrophic state was likely discovered in Zhushan Bay with higher eco-exergy but lower specific eco-exergy. Gradient Boosting Machine (GBM) approach was used to explain the non-linear relationships between two indicators and abiotic factors. This analysis revealed water temperature, inorganic nutrients, and total suspended solids greatly contributed to the two indicators that increased. However, pH rise driven by inorganic carbon played an important role in undermining ecosystem health, particularly when pH was higher than 8.2. This implies that climate change with rising CO2 concentrations has the potential to aggravate eutrophication in Taihu Lake where high nutrient loads are maintained.
Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B
Authors: Peng Cheng-Yuan , Lai Hsueh-Chou , Su Wen-Pang , Lin Chia-Hsin , Chuang Po-Heng , Chen Sheng-Hung , Chen Ching-Hsiang 
Published: February 2017

AbstractEarly declines in serum hepatitis B surface (HBsAg) levels, their optimal cutoffs, and association with therapeutic endpoints in chronic hepatitis B (CHB) patients receiving entecavir treatment remain unclear. We prospectively enrolled 529 patients (195 hepatitis B e antigen [HBeAg]-positive and 334 HBeAg-negative) with a median treatment duration of 49.2 months. Median HBsAg levels declined significantly in both groups at Month 3, but only at Months 6–12 in the HBeAg-negative group. Both groups exhibited a significant HBsAg decline with each successive year of treatment. An HBsAg decline of ≥75% from baseline, assessed at Months 3 and 12 of treatment in the HBeAg-positive and -negative patients, respectively, independently predicted a virological response and HBeAg seroconversion in the HBeAg-positive patients, an HBsAg level of <100 IU/mL in the HBeAg-negative patients, and HBsAg loss in all the patients during treatment. HBsAg levels of <3,000 IU/mL at baseline combined with an HBsAg decline of ≥75% from baseline provided a predictive algorithm for HBsAg loss (positive and negative predictive values: 70% and 100%, respectively) during 5 years of treatment. The proposed cutoffs for defining an HBsAg decline may assist clinicians in early assessments of treatment responses in genotype B-infected or C-infected CHB patients receiving entecavir therapy.
Nucleobindin 1 binds to multiple types of pre-fibrillar amyloid and inhibits fibrillization
Authors: Bonito-Oliva Alessandra , Barbash Shahar , Sakmar Thomas P. , Graham W Vallen 
Published: February 2017

AbstractDuring amyloid fibril formation, amyloidogenic polypeptides misfold and self assemble into soluble pre-fibrillar aggregates, i.e., protofibrils, which elongate and mature into insoluble fibrillar aggregates. An emerging class of chaperones, chaperone-like amyloid binding proteins (CLABPs), has been shown to interfere with aggregation of particular misfolded amyloid peptides or proteins. We have discovered that the calcium-binding protein nuclebindin-1 (NUCB1) is a novel CLABP. We show that NUCB1 inhibits aggregation of islet-amyloid polypeptide associated with type 2 diabetes mellitus, a-synuclein associated with Parkinson’s disease, transthyretin V30M mutant associated with familial amyloid polyneuropathy, and Aβ42 associated with Alzheimer’s disease by stabilizing their respective protofibril intermediates. Kinetic studies employing the modeling software AmyloFit show that NUCB1 affects both primary nucleation and secondary nucleation. We hypothesize that NUCB1 binds to the common cross-β-sheet structure of protofibril aggregates to “cap” and stabilize soluble macromolecular complexes. Transmission electron microscopy and atomic force microscopy were employed to characterize the size, shape and volume distribution of multiple sources of NUCB1-capped protofibrils. Interestingly, NUCB1 prevents Aβ42 protofibril toxicity in a cellular assay. NUCB1-stabilized amyloid protofibrils could be used as immunogens to prepare conformation-specific antibodies and as novel tools to develop screens for anti-protofibril diagnostics and therapeutics.
Successive extraction of As(V), Cu(II) and P(V) ions from water using spent coffee powder as renewable bioadsorbents
Authors: Hao Linlin , Wang Peng , Valiyaveettil Suresh 
Published: February 2017

AbstractFor the first time, renewable and easy accessible pre-bleached spent coffee powder coated with polyethylenimine (PEI) and ferric ions (Coffee-PEI-Fe) was used for the successive adsorption of As(V), Cu(II) and P(V) ions from spiked water samples. Fully characterized coffee-PEI-Fe was employed for batch mode experiments. Kinetic regression analysis showed that the adsorption processes of As(V) and P(V) anions follows a pseudo-second-order model, while the adsorption of Cu(II) ions fit with a pseudo-first-order model. The maximum adsorption capacities estimated by Langmuir model for As(V), Cu(II) and P(V) ions were 83.3, 200.1, and 50.2 mg/g, respectively. The simulated results revealed that the internal diffusion is the rate-determining step for the adsorptions of As(V) and Cu(II) ions, while film diffusion is the mass transfer resistance for the adsorption of P(V) ions on the surface of coffee-PEI-Fe. The successive adsorptions of adsorbates were achieved through electrostatic attraction between adsorbent surface and adsorbates. The dynamic column adsorption behavior of the adsorbent was described by Thomas model, which showed a good agreement with the experimental values (qexp). The results presented in this paper could be used for developing efficient adsorbent from renewable materials for water purification.