bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the molecular basis of agonist/antagonist mechanism of human mu opioid receptor through gaussian accelerated molecular dynamics method
Authors: Wang Yeng-Tseng , Chan Yang-Hsiang 
Published: August 2017

AbstractThe most powerful analgesic and addictive properties of opiate alkaloids are mediated by the μ opioid receptor (MOR). The MOR has been extensively investigated as a drug target in the twentieth century, with numerous compounds of varying efficacy being identified. We employed molecular dynamics and Gaussian accelerated molecular dynamics techniques to identify the binding mechanisms of MORs to BU72 (agonist) and β-funaltrexamine (antagonist). Our approach theoretically suggests that the 34 residues (Lys209–Phe221 and Ile301–Cys321) of the MORs were the key regions enabling the two compounds to bind to the active site of the MORs. When the MORs were in the holo form, the key region was in the open conformation. When the MORs were in the apo form, the key region was in the closed conformation. The key region might be responsible for the selectivity of new MOR agonists and antagonists.
Constructing ordinal partition transition networks from multivariate time series
Authors: Zhang Jiayang , Zhou Jie , Tang Ming , Guo Heng , Small Michael , Zou Yong 
Published: August 2017

AbstractA growing number of algorithms have been proposed to map a scalar time series into ordinal partition transition networks. However, most observable phenomena in the empirical sciences are of a multivariate nature. We construct ordinal partition transition networks for multivariate time series. This approach yields weighted directed networks representing the pattern transition properties of time series in velocity space, which hence provides dynamic insights of the underling system. Furthermore, we propose a measure of entropy to characterize ordinal partition transition dynamics, which is sensitive to capturing the possible local geometric changes of phase space trajectories. We demonstrate the applicability of pattern transition networks to capture phase coherence to non-coherence transitions, and to characterize paths to phase synchronizations. Therefore, we conclude that the ordinal partition transition network approach provides complementary insight to the traditional symbolic analysis of nonlinear multivariate time series.
Measurement of caveolin-1 densities in the cell membrane for quantification of caveolar deformation after exposure to hypotonic membrane tension
Authors: Tachikawa Masashi , Morone Nobuhiro , Senju Yosuke , Sugiura Tadao , Hanawa-Suetsugu Kyoko , Mochizuki Atsushi , Suetsugu Shiro 
Published: August 2017

AbstractCaveolae are abundant flask-shaped invaginations of plasma membranes that buffer membrane tension through their deformation. Few quantitative studies on the deformation of caveolae have been reported. Each caveola contains approximately 150 caveolin-1 proteins. In this study, we estimated the extent of caveolar deformation by measuring the density of caveolin-1 projected onto a two-dimensional (2D) plane. The caveolin-1 in a flattened caveola is assumed to have approximately one-quarter of the density of the caveolin-1 in a flask-shaped caveola. The proportion of one-quarter-density caveolin-1 increased after increasing the tension of the plasma membrane through hypo-osmotic treatment. The one-quarter-density caveolin-1 was soluble in detergent and formed a continuous population with the caveolin-1 in the caveolae of cells under isotonic culture. The distinct, dispersed lower-density caveolin-1 was soluble in detergent and increased after the application of tension, suggesting that the hypo-osmotic tension induced the dispersion of caveolin-1 from the caveolae, possibly through flattened caveolar intermediates.
Comparison of Pathogenicity-Related Genes in the Current Pseudorabies Virus Outbreak in China
Authors: Tang Yan-Dong , Liu Ji-Ting , Wang Tong-Yun , Sun Ming-Xia , Tian Zhi-Jun , Cai Xue-Hui 
Published: August 2017

AbstractThere is currently a pandemic of pseudorabies virus (PRV) variant strains in China. Despite extensive research on PRV variant strains in the past two years, few studies have investigated PRV pathogenicity-related genes. To determine which gene(s) is/are linked to PRV virulence, ten putative virulence genes were knocked out using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 technology. The pathogenicity of these mutants was evaluated in a mouse model. Our results demonstrated that of the ten tested genes, the thymidine kinase (TK) and glycoprotein M (gM) knockout mutants displayed significantly reduced virulence. However, mutants of other putative virulence genes, such as glycoprotein E (gE), glycoprotein I (gI), Us2, Us9, Us3, glycoprotein G (gG), glycoprotein N (gN) and early protein 0 (EP0), did not exhibit significantly reduced virulence compared to that of the wild-type PRV. To our knowledge, this study is the first to compare virulence genes from the current pandemic PRV variant strain. This study will provide a valuable reference for scientists to design effective live attenuated vaccines in the future.
NEDD4-family E3 ligase dysfunction due to PKHD1/Pkhd1 defects suggests a mechanistic model for ARPKD pathobiology
Authors: Kaimori Jun-ya , Lin Cheng-Chao , Outeda Patricia , Garcia-Gonzalez Miguel A. , Menezes Luis F. , Hartung Erum A. , Li Ao , Wu Guanqing , Fujita Hideaki , Sato Yasunori , Nakanuma Yasuni , Yamamoto Satoko , Ichimaru Naotsugu , Takahara Shiro , Isaka Yoshitaka , Watnick Terry , Onuchic Luiz F. , Guay-Woodford Lisa M. , Germino Gregory G. 
Published: August 2017

AbstractAutosomal recessive polycystic kidney disease (ARPKD) is an important childhood nephropathy, occurring 1 in 20,000 live births. The major clinical phenotypes are expressed in the kidney with dilatation of the collecting ducts, systemic hypertension, and progressive renal insufficiency, and in the liver with biliary dysgenesis, portal tract fibrosis, and portal hypertension. The systemic hypertension has been attributed to enhanced distal sodium reabsorption in the kidney, the structural defects have been ascribed to altered cellular morphology, and fibrosis to increased TGF-β signaling in the kidney and biliary tract, respectively. The pathogenic mechanisms underlying these abnormalities have not been determined. In the current report, we find that disrupting PKHD1 results in altered sub-cellular localization and function of the C2-WWW-HECT domain E3 family of ligases regulating these processes. We also demonstrate altered activity of RhoA and increased TGF-β signaling and ENaC activity. Linking these phenomena, we found that vesicles containing the PKHD1/Pkhd1 gene product, FPC, also contain the NEDD4 ubiquitin ligase interacting protein, NDFIP2, which interacts with multiple members of the C2-WWW-HECT domain E3 family of ligases. Our results provide a mechanistic explanation for both the cellular effects and in vivo phenotypic abnormalities in mice and humans that result from Pkhd1/PKHD1 mutation.
A novel signature for stratifying the molecular heterogeneity of the tissue-infiltrating T-cell receptor repertoire reflects gastric cancer prognosis
Authors: Kuang Manchao , Cheng Jieyao , Zhang Chengli , Feng Lin , Xu Xue , Zhang Yajing , Zu Ming , Cui Jianfang , Yu Hang , Zhang Kaitai , Yang Aiming , Cheng Shujun 
Published: August 2017

AbstractMany basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis. Moreover, to illustrate the relationship between the local molecular phenotype and TCR repertoire of the microenvironment, whole-genome gene expression microarray analysis of the corresponding gastric precancerous lesions and early gastric cancer tissues was conducted. Our results showed that the degree of variation in the TCR repertoire gradually increased during tumourigenesis. Integrative analysis of microarray data and the TCR repertoire variation index using the network-based Clique Percolation Method identified an 11-gene module related to the inflammatory response that can predict the overall survival of gastric cancer (GC) patients. In conclusion, our results revealed the multistage heterogeneity of tissue-infiltrating TCR repertoire during carcinogenesis. We report a novel way for identifying prognostic biomarkers for GC patients and improves our understanding of immune responses during gastric carcinogenesis.
Triglycerides and Open Angle Glaucoma – A Meta-analysis with meta-regression
Authors: Pertl Laura , Mossböck Georg , Wedrich Andreas , Weger Martin , Königsbrügge Oliver , Silbernagel Günther , Posch Florian 
Published: August 2017

AbstractAlthough intraocular pressure is the main the risk factor for the development of glaucoma, other risk factors such as vascular dysfunction might play an additional pathogenic role. Hypertriglyceridemia, which may lead to vascular dysfunction, has been implicated in the development of glaucoma. The objective of this meta-analysis was to investigate the association of triglyceride levels with the risk of glaucoma in case-control studies. Seventeen case-control studies were included investigating the difference in triglyceride levels in patients with glaucoma (N = 1 391) compared to subjects without glaucoma (N = 25 575). In random effects meta-analysis, the pooled mean triglyceride level across all studies and patients with and without glaucoma was 132.9 mg/dL (95%CI: 124.0–141.7). Patients with glaucoma had significantly higher mean triglyceride levels than patients without glaucoma (absolute difference = 14.2 mg/dL, 95%CI: 5.8–22.5, p < 0.0001). A considerable amount of heterogeneity of included studies was observed (I2 = 66.2%, heterogeneity χ2 = 47.4 on 16 degrees of freedom, p < 0.0001). In conclusion, this meta-analysis of case-control studies found that patients with glaucoma had higher mean triglyceride levels than patients without glaucoma. This finding is consistent with the concept that hypertriglyceridemia represents an additional risk factor for glaucoma. Whether this association is causal and/or might be modified by glaucoma medications remains to be investigated.
Magnesium Chloride promotes Osteogenesis through Notch signaling activation and expansion of Mesenchymal Stem Cells
Authors: Díaz-Tocados Juan M. , Herencia Carmen , Martínez-Moreno Julio M. , Montes de Oca Addy , Rodríguez-Ortiz Maria E. , Vergara Noemi , Blanco Alfonso , Steppan Sonja , Almadén Yolanda , Rodríguez Mariano , Muñoz-Castañeda Juan R. 
Published: August 2017

AbstractMesenchymal stem cells (MSC) are osteoblasts progenitors and a variety of studies suggest that they may play an important role for the health in the field of bone regeneration. Magnesium supplementation is gaining importance as adjuvant treatment to improve osteogenesis, although the mechanisms involving this process are not well understood. The objective of this study was to investigate the effects of magnesium on MSC differentiation. Here we show that in rat bone marrow MSC, magnesium chloride increases MSC proliferation in a dose-dependent manner promoting osteogenic differentiation and mineralization. These effects are reduced by 2-APB administration, an inhibitor of magnesium channel TRPM7. Of note, magnesium supplementation did not increase the canonical Wnt/β-catenin pathway, although it promoted the activation of Notch1 signaling, which was also decreased by addition of 2-APB. Electron microscopy showed higher proliferation, organization and maturation of osteoblasts in bone decellularized scaffolds after magnesium addition. In summary, our results demonstrate that magnesium chloride enhances MSC proliferation by Notch1 signaling activation and induces osteogenic differentiation, shedding light on the understanding of the role of magnesium during bone regeneration.
Sexual conflict and the evolution of genitalia: male damselflies remove more sperm when mating with a heterospecific female
Authors: Cordero-Rivera Adolfo 
Published: August 2017

AbstractIn Calopteryx damselflies, males remove rivals’ sperm stored by the female, thereby reducing sperm competition. This behaviour may create a sexual conflict, because females could lose the sperm stored in the spermatheca, used for long-term storage. Comparative evidence suggested antagonistic coevolution between sexes, which might prompt the evolution of narrow spermathecal ducts, or longer spermathecae, hindering sperm removal. Calopteryx haemorrhoidalis and C. splendens coexist and sometimes hybridize. Therefore, here I predicted that if females coevolve with conspecific males, heterospecific males should have an advantage when interspecific matings occur because females will show less resistance to them than to conspecific males. By hand-pairing females to males of both species, I found that in intraspecific and interspecific matings, sperm was almost completely removed from the bursa (97–100%), but only partially from the spermathecae, with more spermathecal removal in interspecific (63–71%) than intraspecific matings (14–33%). This suggests that heterospecific males are more efficient in sperm removal as predicted by a sexually-antagonistic coevolutionary scenario. Furthermore, in most cases, only the left spermatheca was emptied, suggesting that the evolution of more than one spermatheca might also be a female counter-adaptation to regain control over fertilization.
DNA methylation of the RUNX2 P1 promoter mediates MMP13 transcription in chondrocytes
Authors: Takahashi Atsushi , de Andrés María C. , Hashimoto Ko , Itoi Eiji , Otero Miguel , Goldring Mary B. , Oreffo Richard O. C. 
Published: August 2017

AbstractThe Runt-related transcription factor 2 (RUNX2) is critical for bone formation as well as chondrocyte maturation. Matrix metalloproteinase (MMP)-13 is a major contributor to cartilage degradation in osteoarthritis (OA). We and others have shown that the abnormal MMP13 gene expression in OA chondrocytes is controlled by changes in the DNA methylation status of specific CpG sites of the proximal promoter, as well as by the actions of different transactivators, including RUNX2. The present study aimed to determine the influence of the methylation status of specific CpG sites in the RUNX2 promoter on RUNX2-driven MMP13 gene expression in OA chondrocytes. We observed a significant correlation between MMP13 mRNA levels and RUNX2 gene expression in human OA chondrocytes. RUNX2 overexpression enhanced MMP13 promoter activity, independent of the MMP13 promoter methylation status. A significant negative correlation was observed between RUNX2 mRNA levels in OA chondrocytes and the percentage methylation of the CpG sites in the RUNX2 P1 promoter. Accordingly, the activity of the wild type RUNX2 promoter was decreased upon methylation treatment in vitro. We conclude that RUNX2 gene transcription is regulated by the methylation status of specific CpG sites in the promoter and may determine RUNX2 availability in OA cartilage for transactivation of genes such as MMP13.
Baculovirus infection induces disruption of the nuclear lamina
Authors: Zhang Xiaomei , Xu Kaiyan , Wei Denghui , Wu Wenbi , Yang Kai , Yuan Meijin 
Published: August 2017

AbstractBaculovirus nucleocapsids egress from the nucleus primarily via budding at the nuclear membrane. The nuclear lamina underlying the nuclear membrane represents a substantial barrier to nuclear egress. Whether the nuclear lamina undergoes disruption during baculovirus infection remains unknown. In this report, we generated a clonal cell line, Sf9-L, that stably expresses GFP-tagged Drosophila lamin B. GFP autofluorescence colocalized with immunofluorescent anti-lamin B at the nuclear rim of Sf9-L cells, indicating GFP-lamin B was incorporated into the nuclear lamina. Meanwhile, virus was able to replicate normally in Sf9-L cells. Next, we investigated alterations to the nuclear lamina during baculovirus infection in Sf9-L cells. A portion of GFP-lamin B localized diffusely at the nuclear rim, and some GFP-lamin B was redistributed within the nucleus during the late phase of infection, suggesting the nuclear lamina was partially disrupted. Immunoelectron microscopy revealed associations between GFP-lamin B and the edges of the electron-dense stromal mattes of the virogenic stroma, intranuclear microvesicles, and ODV envelopes and nucleocapsids within the nucleus, indicating the release of some GFP-lamin B from the nuclear lamina. Additionally, GFP-lamin B phosphorylation increased upon infection. Based on these data, baculovirus infection induced lamin B phosphorylation and disruption of the nuclear lamina.
Comparison of neonatal outcomes following progesterone use during ovarian stimulation with frozen-thawed embryo transfer
Authors: Zhu Xiuxian , Ye Hongjuan , Fu Yonglun 
Published: August 2017

AbstractProgesterone soft capsules (brand name: Utrogestan) were demonstrated to be an effective oral alternative to prevent premature LH surges both in normal-ovulatory and polycystic ovarian syndrome (PCOS) patients. However, its safety in terms of neonatal outcomes is unclear. To evaluate whether Utrogestan use increase the risk of adverse neonatal outcomes compared with short protocol in patients undergoing IVF/ICSI treatments in combination with frozen-thawed embryo transfer (FET), we performed a retrospective analysis including 1008 FET cycles, with embryos originated from either Utrogestan + hMG protocol (n = 499), or short protocol (n = 509), which led to 546 live-born infants. The neonatal characteristics regarding preterm birth (PTB), low birth weight (LBW), gestational age and mode of delivery were comparable in the two groups. The incidence of live-birth defect was 0.68% (2/293) in the Utrogestan + hMG protocol compared with 0.79% (2/253) in the short protocol. No early neonatal death or intrauterine death were recorded in either group. To date, the data do not indicate an elevated rate of abnormality at birth after progesterone use during ovarian stimulation but further study with larger populations is needed to confirm these results.
Prognostic value of programmed cell death protein 1 expression on CD8+ T lymphocytes in pancreatic cancer
Authors: Shen Tao , Zhou Liangjing , Shen Hua , Shi Chengfei , Jia Shengnan , Ding Guo Ping , Cao Liping 
Published: August 2017

AbstractPancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC). Expression of PD-1 protein on CD8+ TILs correlated with overall survival and clinicopathological characteristics such as clinical stage, N classification, and M classification. Similar findings were observed for the expression of PD-1 protein on peripheral CD8+ T cells, whereas its expression on peripheral CD4+ T cells showed no significance. Comparison of the levels of PD-1 protein expressed by peripheral CD8+ T cells before and 4 weeks after surgery indicated that preoperative and postoperative status of peripheral PD-1 expression was unchanged. Our findings showed that PD-1 protein expressed by peripheral or tumour-infiltrated CD8+ T cells was a promising biomarker for diagnosis and prognosis in PDAC and might help guide future immunotherapies.
Hyperspectral Imaging for Predicting the Internal Quality of Kiwifruits Based on Variable Selection Algorithms and Chemometric Models
Authors: Zhu Hongyan , Chu Bingquan , Fan Yangyang , Tao Xiaoya , Yin Wenxin , He Yong 
Published: August 2017

AbstractWe investigated the feasibility and potentiality of determining firmness, soluble solids content (SSC), and pH in kiwifruits using hyperspectral imaging, combined with variable selection methods and calibration models. The images were acquired by a push-broom hyperspectral reflectance imaging system covering two spectral ranges. Weighted regression coefficients (BW), successive projections algorithm (SPA) and genetic algorithm–partial least square (GAPLS) were compared and evaluated for the selection of effective wavelengths. Moreover, multiple linear regression (MLR), partial least squares regression and least squares support vector machine (LS-SVM) were developed to predict quality attributes quantitatively using effective wavelengths. The established models, particularly SPA-MLR, SPA-LS-SVM and GAPLS-LS-SVM, performed well. The SPA-MLR models for firmness (R
pre
= 0.9812, RPD = 5.17) and SSC (R
pre
= 0.9523, RPD = 3.26) at 380–1023 nm showed excellent performance, whereas GAPLS-LS-SVM was the optimal model at 874–1734 nm for predicting pH (R
pre
= 0.9070, RPD = 2.60). Image processing algorithms were developed to transfer the predictive model in every pixel to generate prediction maps that visualize the spatial distribution of firmness and SSC. Hence, the results clearly demonstrated that hyperspectral imaging has the potential as a fast and non-invasive method to predict the quality attributes of kiwifruits.
To What Extent Are the Terminal Stages of Sepsis, Septic Shock, Systemic Inflammatory Response Syndrome, and Multiple Organ Dysfunction Syndrome Actually Driven by a Prion/Amyloid Form of Fibrin?
Authors: Kell Douglas , Pretorius Etheresia 
Published: August 2017

AbstractA well-established development of increasing disease severity leads from sepsis through systemic inflammatory response syndrome, septic shock, multiple organ dysfunction syndrome, and cellular and organismal death. Less commonly discussed are the equally well-established coagulopathies that accompany this. We argue that a lipopolysaccharide-initiated (often disseminated intravascular) coagulation is accompanied by a proteolysis of fibrinogen such that formed fibrin is both inflammatory and resistant to fibrinolysis. In particular, we argue that the form of fibrin generated is amyloid in nature because much of its normal α-helical content is transformed to β-sheets, as occurs with other proteins in established amyloidogenic and prion diseases. We hypothesize that these processes of amyloidogenic clotting and the attendant coagulopathies play a role in the passage along the aforementioned pathways to organismal death, and that their inhibition would be of significant therapeutic value, a claim for which there is considerable emerging evidence.