bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alteration of platelet GPVI signaling in ST-elevation myocardial infarction patients demonstrated by a combination of proteomic, biochemical, and functional approaches
Authors: Vélez Paula , Ocaranza-Sánchez Raymundo , López-Otero Diego , Grigorian-Shamagian Lilian , Rosa Isaac , Guitián Esteban , García-Acuña José María , González-Juanatey José Ramón , García Ángel 
Published: December 2016

AbstractThe platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide). STEMI and SCAD samples were compared by a phosphoproteomics approach. Validations were by immunoblotting in systemic and intracoronary blood from independent cohorts of patients. Twenty-six differentially regulated proteins were identified when comparing CRP-activated systemic platelets from STEMI and SCAD patients, 4 of which were selected for validation studies: PLCɣ2, G6f, SLP-76, and Dok-2. Immunoblot analyses showed these four proteins had higher tyrosine phosphorylation levels in response to CRP in platelets from STEMI patients, being these levels more pronounced at the culprit site of coronary artery occlusion. Moreover, platelet aggregation studies showed a higher response to GPVI agonists in STEMI patients compared to SCAD controls. In conclusion, we show an altered activation state of GPVI signaling in STEMI patients, confirming this receptor as a promising anti-thrombotic target for myocardial infarction.
Fasting plasma glucose variability and all-cause mortality among type 2 diabetes patients: a dynamic cohort study in Shanghai, China
Authors: Xu Dongli , Fang Hong , Xu Wanghong , Yan Yujie , Liu Yinan , Yao Baodong 
Published: December 2016

AbstractThe study aims to examine whether the variation of fasting plasma glucose (FPG), represented by coefficient of variation (CV), independently predicts all-cause mortality among Chinese type 2 diabetes patients. This retrospective cohort study was designed based on a standardized electronic management system of diabetes patients in Shanghai, China. 8871 type 2 diabetes patients were enrolled between 1 January 2007 and 31 December 2007 and were followed-up for all-cause mortality until 31 December 2014. All patients were grouped by the quartiles of CV of FPG. 1136 patients deceased during following-up. After adjusting for other risk factors, CV of FPG was not independently associated with all-cause mortality. Stratified analysis by mean FPG levels (<7 mmol/L and ≥7 mmol/L) observed a significant modifying effect of CV of FPG (P for interact test <0.01). CV of FPG was independently associated with all-cause mortality in patients whose glucose control was poor, with the HRs (95% CI) for the second, third, fourth vs first quartiles of CV of FPG being 1.23(0.94–1.61), 1.23(0.94–1.61), and 1.63(1.25–2.13), respectively. Our results suggest that variability of FPG may be an important predictor of mortality among type 2 diabetes in China, particularly for those with their glycemic status uncontrolled.
Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients
Authors: Liu Qiwei , Li Yumei , Feng Yun , Liu Chaojie , Ma Jieliang , Li Yifei , Xiang Huifen , Ji Yazhong , Cao Yunxia , Tong Xiaowen , Xue Zhigang 
Published: December 2016

AbstractPolycystic ovary syndrome (PCOS) is a common frequent endocrine disorder among women of reproductive age. Although assisted reproductive techniques (ARTs) are used to address subfertility in PCOS women, their effectiveness is not clear. Our aim was to compare transcriptomic profiles of oocytes and cumulus cells (CCs) between women with and without PCOS, and assess the effectiveness of ARTs in treating PCOS patients. We collected oocytes and CCs from 16 patients with and without PCOS patients to categorize them into 6 groups according to oocyte nuclear maturation. Transcriptional gene expression of oocyte and CCs was determined via single-cell RNA sequencing. The ratio of fertilization and cleavage was higher in PCOS patients than in non-PCOS patients undergoing ARTs, and there was no difference in the number of high-quality embryos between the groups. Differentially expressed genes including PPP2R1A, PDGFRA, EGFR, GJA1, PTGS2, TNFAIP6, TGF-β1, CAV1, INHBB et al. were investigated as potential causes of PCOS oocytes and CCs disorder at early stages, but their expression returned to the normal level at the metaphase II (MII) stage via ARTs. In conclusion, ARTs can improve the quality of cumulus-oocyte complex (COC) and increase the ratio of fertilization and cleavage in PCOS women.
NOD2 dependent neutrophil recruitment is required for early protective immune responses against infectious Litomosoides sigmodontis L3 larvae
Authors: Ajendra Jesuthas , Specht Sabine , Ziewer Sebastian , Schiefer Andrea , Pfarr Kenneth , Parčina Marijo , Kufer Thomas A. , Hoerauf Achim , Hübner Marc P. 
Published: December 2016

AbstractNucleotide-binding oligomerization domain-containing protein 2 (NOD2) recognizes muramyl dipeptide (MDP) of bacterial cell walls, triggering NFκB-induced pro-inflammation. As most human pathogenic filariae contain Wolbachia endobacteria that synthesize the MDP-containing cell wall precursor lipid II, NOD2’s role during infection with the rodent filaria Litomosoides sigmodontis was investigated. In NFκB reporter-cells, worm-extract containing Wolbachia induced NOD2 and NOD1. NOD2-deficient mice infected with L. sigmodontis had significantly more worms than wildtype controls early in infection. Increased worm burden was not observed after subcutaneous infection, suggesting that protective NOD2-dependent immune responses occur within the skin. Flow cytometry demonstrated that neutrophil recruitment to the skin was impaired in NOD2−/− mice after intradermal injection of third stage larvae (L3), and blood neutrophil numbers were reduced after L. sigmodontis infection. PCR array supported the requirement of NOD2 for recruitment of neutrophils to the skin, as genes associated with neutrophil recruitment and activation were downregulated in NOD2−/− mice after intradermal L3 injection. Neutrophil depletion before L. sigmodontis infection increased worm recovery in wildtype mice, confirming that neutrophils are essential against invading L3 larvae. This study indicates that NOD-like receptors are implemented in first-line protective immune responses against filarial nematodes.
The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells
Authors: Wu Nai-Huei , Yang Wei , Beineke Andreas , Dijkman Ronald , Matrosovich Mikhail , Baumgärtner Wolfgang , Thiel Volker , Valentin-Weigand Peter , Meng Fandan , Herrler Georg 
Published: December 2016

AbstractVirus-host interactions in the respiratory epithelium during long term influenza virus infection are not well characterized. Therefore, we developed an air-liquid interface culture system for differentiated porcine respiratory epithelial cells to study the effect of virus-induced cellular damage. In our well-differentiated cells, α2,6-linked sialic acid is predominantly expressed on the apical surface and the basal cells mainly express α2,3-linked sialic acid. During the whole infection period, release of infectious virus was maintained at a high titre for more than seven days. The infected epithelial cells were subject to apoptosis resulting in the loss of ciliated cells together with a thinner thickness. Nevertheless, the airway epithelium maintained trans-epithelial electrical resistance and retained its barrier function. The loss of ciliated cells was compensated by the cells which contained the KRT5 basal cell marker but were not yet differentiated into ciliated cells. These specialized cells showed an increase of α2,3-linked sialic acid on the apical surface. In sum, our results help to explain the localized infection of the airway epithelium by influenza viruses. The impairment of mucociliary clearance in the epithelial cells provides an explanation why prior viral infection renders the host more susceptible to secondary co-infection by another pathogen.
Osteoarthritis and the risk of cardiovascular disease: a meta-analysis of observational studies
Authors: Wang Haoran , Bai Jing , He Bing , Hu Xinrong , Liu Dongliang 
Published: December 2016

AbstractPrevious observational studies have suggested a potential relationship between osteoarthritis (OA) and the risk of cardiovascular disease (CVD), with conflicting results. We aimed to provide a systematic and quantitative summary of the association between OA and the risk of CVD. We searched Medline and EMBASE to retrieve prospective and retrospective studies that reported risk estimates of the association between OA status and CVD risk. Pooled estimates were calculated by a random effects model. The search yielded 15 articles including a total of 358,944 participants, including 80,911 OA patients and 29,213 CVD patients. Overall, the risk of CVD was significantly increased by 24% (RR: 1.24, 95% CI: 1.12 to 1.37, P < 0.001) in patients with OA compared with the general population, with no significant publication bias. Furthermore, sensitivity analysis indicated that our results were robust and were not influenced by any one study. In conclusion, this meta-analysis provides strong evidence that OA is a significant risk factor for CVD.
Temperature and microwave near field imaging by thermo-elastic optical indicator microscopy
Authors: Lee Hanju , Arakelyan Shant , Friedman Barry , Lee Kiejin 
Published: December 2016

AbstractA high resolution imaging of the temperature and microwave near field can be a powerful tool for the non-destructive testing of materials and devices. However, it is presently a very challenging issue due to the lack of a practical measurement pathway. In this work, we propose and demonstrate experimentally a practical method resolving the issue by using a conventional CCD-based optical indicator microscope system. The present method utilizes the heat caused by an interaction between the material and an electromagnetic wave, and visualizes the heat source distribution from the measured photoelastic images. By using a slide glass coated by a metal thin film as the indicator, we obtain optically resolved temperature, electric, and magnetic microwave near field images selectively with a comparable sensitivity, response time, and bandwidth of existing methods. The present method provides a practical way to characterize the thermal and electromagnetic properties of materials and devices under various environments.
Convergent evidence for the molecular basis of musical traits
Authors: Oikkonen Jaana , Onkamo Päivi , Järvelä Irma , Kanduri Chakravarthi 
Published: December 2016

AbstractTo obtain aggregate evidence for the molecular basis of musical abilities and the effects of music, we integrated gene-level data from 105 published studies across multiple species including humans, songbirds and several other animals and used a convergent evidence method to prioritize the top candidate genes. Several of the identified top candidate genes like EGR1, FOS, ARC, BDNF and DUSP1 are known to be activity-dependent immediate early genes that respond to sensory and motor stimuli in the brain. Several other top candidate genes like MAPK10, SNCA, ARHGAP24, TET2, UBE2D3, FAM13A and NUDT9 are located on chromosome 4q21-q24, on the candidate genomic region for music abilities in humans. Functional annotation analyses showed the enrichment of genes involved in functions like cognition, learning, memory, neuronal excitation and apoptosis, long-term potentiation and CDK5 signaling pathway. Interestingly, all these biological functions are known to be essential processes underlying learning and memory that are also fundamental for musical abilities including recognition and production of sound. In summary, our study prioritized top candidate genes related to musical traits.
Detection of timescales in evolving complex systems
Authors: Darst Richard K. , Granell Clara , Arenas Alex , Gómez Sergio , Saramäki Jari , Fortunato Santo 
Published: December 2016

AbstractMost complex systems are intrinsically dynamic in nature. The evolution of a dynamic complex system is typically represented as a sequence of snapshots, where each snapshot describes the configuration of the system at a particular instant of time. This is often done by using constant intervals but a better approach would be to define dynamic intervals that match the evolution of the system’s configuration. To this end, we propose a method that aims at detecting evolutionary changes in the configuration of a complex system, and generates intervals accordingly. We show that evolutionary timescales can be identified by looking for peaks in the similarity between the sets of events on consecutive time intervals of data. Tests on simple toy models reveal that the technique is able to detect evolutionary timescales of time-varying data both when the evolution is smooth as well as when it changes sharply. This is further corroborated by analyses of several real datasets. Our method is scalable to extremely large datasets and is computationally efficient. This allows a quick, parameter-free detection of multiple timescales in the evolution of a complex system.
An Adaptation To Life In Acid Through A Novel Mevalonate Pathway
Authors: Vinokur Jeffrey M. , Cummins Matthew C. , Korman Tyler P. , Bowie James U. 
Published: December 2016

AbstractExtreme acidophiles are capable of growth at pH values near zero. Sustaining life in acidic environments requires extensive adaptations of membranes, proton pumps, and DNA repair mechanisms. Here we describe an adaptation of a core biochemical pathway, the mevalonate pathway, in extreme acidophiles. Two previously known mevalonate pathways involve ATP dependent decarboxylation of either mevalonate 5-phosphate or mevalonate 5-pyrophosphate, in which a single enzyme carries out two essential steps: (1) phosphorylation of the mevalonate moiety at the 3-OH position and (2) subsequent decarboxylation. We now demonstrate that in extreme acidophiles, decarboxylation is carried out by two separate steps: previously identified enzymes generate mevalonate 3,5-bisphosphate and a new decarboxylase we describe here, mevalonate 3,5-bisphosphate decarboxylase, produces isopentenyl phosphate. Why use two enzymes in acidophiles when one enzyme provides both functionalities in all other organisms examined to date? We find that at low pH, the dual function enzyme, mevalonate 5-phosphate decarboxylase is unable to carry out the first phosphorylation step, yet retains its ability to perform decarboxylation. We therefore propose that extreme acidophiles had to replace the dual-purpose enzyme with two specialized enzymes to efficiently produce isoprenoids in extremely acidic environments.
Characterization of the relationship between polar and lateral flagellar structural genes in the deep-sea bacterium Shewanella piezotolerans WP3
Authors: Jian Huahua , Wang Han , Zeng Xianping , Xiong Lei , Wang Fengping , Xiao Xiang 
Published: December 2016

AbstractBacteria with a dual flagellar system, which consists of a polar flagellum (PF) and several lateral flagella (LF), have been identified in diverse environments. Nevertheless, whether and how these two flagellar systems interact with each other is largely unknown. In the present study, the relationship between the structural genes for the PF and LF of the deep-sea bacterium Shewanella piezotolerans WP3 was investigated by genetic, phenotypic and phylogenetic analyses. The mutation of PF genes induced the expression of LF genes and the production of LF in liquid medium, while the defective LF genes led to a decrease in PF gene transcription. However, the level of PF flagellin remained unchanged in LF gene mutants. Further investigation showed that the flgH2 gene (encoding LF L-ring protein) can compensate for mutations of the flgH1 gene (encoding PF L-ring protein), but this compensation does not occur between the flagellar hook-filament junction proteins (FlgL1, FlgL2). Swarming motility was shown to specifically require LF genes, and PF genes cannot substitute for the LF genes in the lateral flagella synthesis. Considering the importance of flagella-dependent motility for bacterial survival in the abyssal sediment, our study thus provided a better understanding of the adaptation strategy of benthic bacteria.
ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phospholipase C γ1 and protein kinase C pathways
Authors: Wolf Cristina , Qian Yawen , Brooke Matthew A. , Kelsell David P. , Franzke Claus-Werner 
Published: December 2016

AbstractThe vitally important skin barrier is formed by extensive cross-linking activity of transglutaminases (TGs) during terminal epidermal differentiation. We have previously shown that epidermal deficiency of a disintegrin and metalloproteinase 17 (ADAM17), the principal EGFR ligand sheddase, results in postnatal skin barrier defects in mice due to impeded TG activity. However, the mechanism by which ADAM17/EGFR signalling maintains TG activity during epidermal differentiation remains elusive. Here we demonstrate that ADAM17-dependent EGFR signalling promotes TG activity in keratinocytes committed to terminal differentiation by direct induction of TG1 expression. Restored TG1 expression of EGF-stimulated differentiated Adam17−/− keratinocytes was strongly repressed by inhibitors for PLCγ1 or protein kinase C (PKC) pathways, while treatment with the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate restored TG activity in the epidermis of keratinocyte-specific Adam17−/− (AD17ΔKC) mice. Further investigations emphasized the expression of PKCη, a mediator of TGM1 transcription, to be sensitive to EGFR activation. In agreement, topical skin application of cholesterol sulfate, an activator of PKCη, significantly improved TG activity in epidermis of AD17ΔKC mice. Our results suggest ADAM17/EGFR-driven PLCγ1 and PKC pathways as important promoters of TG1 expression during terminal keratinocyte differentiation. These findings may help to identify new therapeutic targets for inflammatory skin diseases related to epidermal barrier defects.
Total supply capability considering distribution network reconfiguration under N − k transformer contingency and the decomposition method
Authors: Ding Tao , Li Cheng , Zhao Chaoyue , Wang Min 
Published: December 2016

To guarantee reliability and resilience of distribution systems, total supply capability (TSC) under N  − 1 security has become an important consideration in distribution system planning. In this study, TSC is expanded to cover N  − k contingency, and a robust N  − k TSC evaluation is proposed, while considering the effect of topology reconfiguration. In addition, the single commodity flow constraint is put forward to guarantee the topology radiality. To address this mix integer non‐convex optimisation problem, the second‐order cones are employed to relax the non‐convex constraints so that the model can be efficiently solved, then a decomposition method is applied to solve the two‐stage robust TSC model. In the case study, the proposed method is tested by a 94‐bus test system and its effectiveness is validated. Numerical results show that the proposed method outperforms the traditional methods.
Paracoccidioidomycosis in the Central Nervous System
Authors: Mesquita Filho Paulo Moacir , Hofmann Agatha , De Carli Fernanda , Araújo Moisés Augusto , Giacomelli Richard , Manfroi Gregori , Leal Elizabeth , Isbert Bruna Bley Mattar , Schwingel Daniela 
Published: December 2016

AbstractParacoccidioidomycosis is a systemic mycosis caused by the Paracoccidioides brasiliensis fungus, which is endemic in Latin America. Brazil is the country with the highest number of cases. The affection of the central nervous system (CNS), a potentially fatal condition, occurs in ∼ 12% of the cases. The following forms of presentation are identified: meningeal, which is unusual; meningoencephalitic; and pseudotumoral, the latter two being more frequent. Imaging tests are essential for the diagnosis, but the histological identification of the fungus is required for confirmation of the pathology. The clinical picture depends on the neuraxial location. We present a case of a male rural worker, with expansive lesions in the CNS compatible with paracoccidioidomycosis.
Pyometra and Pregnancy with Herlyn-Werner-Wunderlich Syndrome
Authors: Reis Maria , Vicente Ana , Cominho Joana , Gomes Andrea , Martins Luísa , Nunes Filomena 
Published: December 2016

AbstractWe describe a Herlyn-Werner-Wunderlich syndrome (HWWS) patient with previous history of infertility who got pregnant without treatment and presented a pyometra in the contralateral uterus throughout the gestational period, despite multiple antibiotic treatments. Due to the uterus' congenital anomaly and the possibility of ascending infection with subsequent abortion, this pregnancy was classified as high-risk. We believe that the partial horizontal septum in the vagina may have contributed to the closure of the gravid uterus cervix, thus ensuring that the pregnancy came to term, with an uneventful vaginal delivery.
Multidisciplinary Approach to Neoadjuvant Endocrine Therapy in Breast Cancer: A Comprehensive Review
Authors: Reinert Tomás , Ramalho Susana , Gonçalves Rodrigo , Barrios Carlos , Graudenz Marcia , Bines José 
Published: December 2016

AbstractBreast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.