bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic relevance of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors
Authors: Song Yu-Li , Yu Run , Qiao Xin-Wei , Bai Chun-Mei , Lu Chong-Mei , Xiao Yu , Zhong Ding-Rong , Chen Jie , Zhao Yu-Pei , Zhang Tai-Ping , Song Tian-Tian , Gao He-Li , Wan Ying-Hua , Shen Lin , Chen Jie , Lv Bin , Hao Jian-Jiang , Zhang Ye , Tang Laura , Chen Yuan-Jia 
Published: May 2017

AbstractPrognostic biomarkers for the pancreatic neuroendocrine tumors are needed. Proteomic study on insulinoma has been rarely reported. We identified the differential expression of proteins between insulinoma and their paired tissues by proteomic analysis, and evaluated the prognostic significance of specific proteins in pancreatic neuroendocrine tumors including insulinoma. The differential expression of select proteins was validated in more than 300 tumors using immunohistochemical staining and western blot. Methylation of UCH-L1 promoter in tumors was examined by methylation specific PCR and validated by sequencing. The concurrent expression of UCH-L1 and α-internexin was correlated with the prognosis in 2 independent collectives of patients with tumors. Sixty-two and 219 proteins were significantly down-regulated and up-regulated in insulinomas, respectively. Demethylation of UCH-L1 promoter was associated with UCH-L1 expression in tumors (p = 0.002). The concurrent expression of UCH-L1 and α-internexin in pancreatic neuroendocrine tumors was significantly associated with better overall survival and disease-free survival in the combination of both cohorts (log rank p = 3.90 × 10−4 and p = 3.75 × 10−5, respectively) and in each of cohorts. The prognostic value of both proteins was also validated in patients with stage II and III tumors (p = 0.017 and p = 0.006, respectively). The proteins UCH-L1 and α-internexin could be independent prognostic biomarkers of pancreatic neuroendocrine tumors.
Interleukin 22 attenuated angiotensin II induced acute lung injury through inhibiting the apoptosis of pulmonary microvascular endothelial cells
Authors: Wu Zhiyong , Hu Zhipeng , Cai Xin , Ren Wei , Dai Feifeng , Liu Huagang , Chang Jinxing , Li Bowen 
Published: May 2017

AbstractApoptosis of pulmonary microvascular endothelial cells (PMVECs) was considered to be closely related to the pathogenesis of acute lung injury (ALI). We aim to investigate whether IL-22 plays protective roles in lung injury through inhibiting the apoptosis of PMVECs. ALI model was induced through subcutaneous infusion of angiotensin II (Ang II). Lung injury and infiltration of inflammatory cells were evaluated by determining the PaO2/FiO2, calculation of dry to weight ratio in lung, and immunohistochemisty analysis. Apoptosis of PMVECs was determined using TUNEL assay and flow cytometry, respectively. Immunofluorescence and Western blot analysis were used to determine the expression and localization of STAT3, as well as the nucleus transmission of STAT3 from cytoplasm after IL22 treatment. Pathological findings showed ALI was induced 1 week after AngII infusion. IL22 inhibited the AngII-induced ALI, attenuated the edema in lung and the infiltration of inflammatory cells. Also, it contributed to the apoptosis of PMVECs induced by AngII. Meanwhile, significant increase was noticed in the expression of STAT3, phosphorylation of Y705-STAT3, and migration from cytoplasm to the nucleus after IL-22 treatment (P < 0.05). The activation of STAT3 by IL22 showed significant attenuation after AG490 treatment. Our data indicated that IL22 showed protective effects on lung injury through inhibiting the AngII-induced PMVECs apoptosis and PMVEC barrier injury by activating the JAK2/STAT3 signaling pathway.
Myelination of the brain in Major Depressive Disorder: An in vivo quantitative magnetic resonance imaging study
Authors: Sacchet Matthew D. , Gotlib Ian H. 
Published: May 2017

AbstractEvidence from post-mortem, genetic, neuroimaging, and non-human animal research suggests that Major Depressive Disorder (MDD) is associated with abnormalities in brain myelin content. Brain regions implicated in this research, and in MDD more generally, include the nucleus accumbens (NAcc), lateral prefrontal cortex (LPFC), insula, subgenual anterior cingulate cortex (sgACC), and medial prefrontal cortex (mPFC). We examined whether MDD is characterized by reduced myelin at the whole-brain level and in NAcc, LPFC, insula, sgACC, and mPFC. Quantitative magnetic resonance imaging (qMRI) permits the assessment of myelin content, in vivo, in the human brain through the measure of R1. In this study we used qMRI to measure R1 in 40 MDD and 40 healthy control (CTL) participants. We found that the MDD participants had lower levels of myelin than did the CTL participants at the whole-brain level and in the NAcc, and that myelin in the LPFC was reduced in MDD participants who had experienced a greater number of depressive episodes. Although further research is needed to elucidate the role of myelin in affecting emotional, cognitive, behavioral, and clinical aspects of MDD, the current study provides important new evidence that a fundamental property of brain composition, myelin, is altered in this disorder.
In-situ STEM imaging of growth and phase change of individual CuAlX precipitates in Al alloy
Authors: Liu Chunhui , Malladi Sairam K. , Xu Qiang , Chen Jianghua , Tichelaar Frans D. , Zhuge Xiaodong , Zandbergen Henny W. 
Published: May 2017

AbstractAge-hardening in Al alloys has been used for over a century to improve its mechanical properties. However, the lack of direct observation limits our understanding of the dynamic nature of the evolution of nanoprecipitates during age-hardening. Using in-situ (scanning) transmission electron microscopy (S/TEM) while heating an Al-Cu alloy, we were able to follow the growth of individual nanoprecipitates at atomic scale. The heat treatments carried out at 140, 160, 180 and 200 °C reveal a temperature dependence on the kinetics of precipitation and three kinds of interactions of nano-precipitates. These are precipitate-matrix, precipitate-dislocation, and precipitate-precipitate interactions. The diffusion of Cu and Al during these interactions, results in diffusion-controlled individual precipitate growth, an accelerated growth when interactions with dislocations occur and a size dependent precipitate-precipitate interaction: growth and shrinkage. Precipitates can grow and shrink at opposite ends at the same time resulting in an effective displacement. Furthermore, the evolution of the crystal structure within an individual nanoprecipiate, specifically the mechanism of formation of the strengthening phase, θ′, during heat-treatment is elucidated by following the same precipitate through its intermediate stages for the first time using in-situ S/TEM studies.
Revealing genome-scale transcriptional regulatory landscape of OmpR highlights its expanded regulatory roles under osmotic stress in Escherichia coli K-12 MG1655
Authors: Seo Sang Woo , Gao Ye , Kim Donghyuk , Szubin Richard , Yang Jina , Cho Byung-Kwan , Palsson Bernhard O. 
Published: May 2017

AbstractA transcription factor (TF), OmpR, plays a critical role in transcriptional regulation of the osmotic stress response in bacteria. Here, we reveal a genome-scale OmpR regulon in Escherichia coli K-12 MG1655. Integrative data analysis reveals that a total of 37 genes in 24 transcription units (TUs) belong to OmpR regulon. Among them, 26 genes show more than two-fold changes in expression level in an OmpR knock-out strain. Specifically, we find that: 1) OmpR regulates mostly membrane-located gene products involved in diverse fundamental biological processes, such as narU (encoding nitrate/nitrite transporter), ompX (encoding outer membrane protein X), and nuoN (encoding NADH:ubiquinone oxidoreductase); 2) by investigating co-regulation of entire sets of genes regulated by other stress-response TFs, stresses are surprisingly independently regulated among each other; and, 3) a detailed investigation of the physiological roles of the newly discovered OmpR regulon genes reveals that activation of narU represents a novel strategy to significantly improve osmotic stress tolerance of E. coli. Thus, the genome-scale approach to elucidating regulons comprehensively identifies regulated genes and leads to fundamental discoveries related to stress responses.
Room-temperature soft mode and ferroelectric like polarization in SrTiO3 ultrathin films: Infrared and ab initio study
Authors: Peng Wei-wei , Tétot Robert , Niu Gang , Amzallag Emilie , Vilquin Bertrand , Brubach Jean-Blaise , Roy Pascale 
Published: May 2017

AbstractDue to the remarkable possibilities of epitaxially growing strontium titanate (SrTiO3 or STO) on silicon, this oxide is widely used as a buffer layer for integrating other perovskite oxides which allows for the development of various functional electronic devices on silicon. Moreover, STO is known to be an incipient ferroelectric in bulk but may become ferroelectric when in the form of strained ultrathin films. Given the importance of the potential applications for electronics if this property is demonstrated, we performed a spectroscopic study of STO on Si(001) templates coupling experimental and ab initio investigations. We selected six samples of ultrathin films: three strained samples (of thickness 4, 9 and 48 nm) and three relaxed samples (of equivalent thickness). Their infrared spectra show that both the mechanical stress and the thickness play major roles: higher energy modes evolve as soft modes in thinner strained films. In order to support these observations, the dynamical ab initio calculations allowed deriving the conditions for STO films to become ferroelectric at room temperature as shown by the development of a soft mode and the divergence of the in-plane dielectric constant.
A data mining approach using cortical thickness for diagnosis and characterization of essential tremor
Authors: Serrano J. Ignacio , Romero Juan P. , Castillo Ma Dolores del , Rocon Eduardo , Louis Elan D. , Benito-León Julián 
Published: May 2017

AbstractEssential tremor (ET) is one of the most prevalent movement disorders. Being that it is a common disorder, its diagnosis is considered routine. However, misdiagnoses may occur regularly. Over the past decade, several studies have identified brain morphometric changes in ET, but these changes remain poorly understood. Here, we tested the informativeness of measuring cortical thickness for the purposes of ET diagnosis, applying feature selection and machine learning methods to a study sample of 18 patients with ET and 18 age- and sex-matched healthy control subjects. We found that cortical thickness features alone distinguished the two, ET from controls, with 81% diagnostic accuracy. More specifically, roughness (i.e., the standard deviation of cortical thickness) of the right inferior parietal and right fusiform areas was shown to play a key role in ET characterization. Moreover, these features allowed us to identify subgroups of ET patients as well as healthy subjects at risk for ET. Since treatment of tremors is disease specific, accurate and early diagnosis plays an important role in tremor management. Supporting the clinical diagnosis with novel computer approaches based on the objective evaluation of neuroimage data, like the one presented here, may represent a significant step in this direction.
Chitosan-Dextran sulfate coated doxorubicin loaded PLGA-PVA-nanoparticles caused apoptosis in doxorubicin resistance breast cancer cells through induction of DNA damage
Authors: Siddharth Sumit , Nayak Anmada , Nayak Deepika , Bindhani Birendra Kumar , Kundu Chanakya Nath 
Published: May 2017

AbstractTo overcome the toxicity, pharmacokinetics and drug resistance associated with doxorubicin (DOX), a strategy was developed by encapsulating DOX- loaded-PLGA-PVA- nanoparticles within chitosan-dextran sulfate nanoparticles (CS-DS) [CS-DS-coated-DOX-loaded -PLGA-PVA-NP] and study the sensitivity against DOX- resistance- breast cancer cells (MCF-7-DOX-R). These CS-DS and PLGA-PVA double coated DOX are spherical, stable, polydispersed and have zeta potential +2.89 mV. MCF-7- DOX-R cells were derived by exposing increasing doses of DOX in MCF-7 cells. These cells were resistance to 500 nM of DOX while parental cells were susceptible at 150 nM. The double coated NP caused more cytotoxicity in cancer and MCF-7-DOX-R cells without affecting the normal cells in comparison to DOX-loaded-PLGA-PVA-NP. These NP enhances the uptake of DOX in MCF-7-DOX-R cells and caused apoptosis by increasing apoptotic nuclei, Bax/Bcl-xL ratio, cleaved product PARP-1, tumor suppressor gene p21, p53, topoisomerase inhibition activity, DNA damage and decreasing the migratory potential of cells. An increased S phase arrest was noted in DOX and DOX- loaded- PLGA-PVA-NP treated cells but reduction of S phase and simultaneous increase of Sub-G1 was observed in double coated-NP. Thus, data revealed that CS-DS- DOX- loaded PLGA-PVA- NP caused DOX-resistance cell death by inducing inhibition of topoisomerase activity followed by DNA damage.
Selection of a horizontal reference plane in 3D evaluation: Identifying facial asymmetry and occlusal cant in orthognathic surgery planning
Authors: Lonic Daniel , Sundoro Ali , Lin Hsiu-Hsia , Lin Pei-Ju , Lo Lun-Jou 
Published: May 2017

AbstractFacial asymmetry and dental occlusal cant have been detected in two-dimensional cephalometry using different horizontal reference lines, but equivalent 3-dimensional (3D) reference planes have not been thoroughly investigated. In this study, 3D cone-beam computed tomography scans of 83 consecutive patients were evaluated using a standardized 3D frame and three horizontal reference planes, Supraorbitale (Sor), Frontozygomatic (Z), and Frankfurt horizontal (FH) for cant detection. Canting was defined as a vertical difference between left and right sides of 2 mm or more, and in at least two investigated planes. Concordance for negative canting was found in 38 patients, and for positive canting in 22 patients. Discordance in cant detection was found in 23 patients (28%). 29 patients were found to have canting in at least 2 planes. The FH plane was discordant to the other two planes in 4 patients, the Sor plane in 7 patients and the Z plane in 12 patients. Youden’s index showed the highest performance for FH (0.878), followed by Sor (0.823) and Z plane (0.762). This study revealed that the FH plane was the best method for cant detection in 3D imaging. The FH plane and Sor plane can be combined if orbital asymmetry is suspected.
Super-Enhancers and Broad H3K4me3 Domains Form Complex Gene Regulatory Circuits Involving Chromatin Interactions
Authors: Cao Fan , Fang Yiwen , Tan Hong Kee , Goh Yufen , Choy Jocelyn Yeen Hui , Koh Bryan Thean Howe , Hao Tan Jiong , Bertin Nicolas , Ramadass Aroul , Hunter Ewan , Green Jayne , Salter Matthew , Akoulitchev Alexandre , Wang Wilson , Chng Wee Joo , Tenen Daniel G. , Fullwood Melissa J. 
Published: May 2017

AbstractStretched histone regions, such as super-enhancers and broad H3K4me3 domains, are associated with maintenance of cell identity and cancer. We connected super-enhancers and broad H3K4me3 domains in the K562 chronic myelogenous leukemia cell line as well as the MCF-7 breast cancer cell line with chromatin interactions. Super-enhancers and broad H3K4me3 domains showed higher association with chromatin interactions than their typical counterparts. Interestingly, we identified a subset of super-enhancers that overlap with broad H3K4me3 domains and show high association with cancer-associated genes including tumor suppressor genes. Besides cell lines, we could observe chromatin interactions by a Chromosome Conformation Capture (3C)-based method, in primary human samples. Several chromatin interactions involving super-enhancers and broad H3K4me3 domains are constitutive and can be found in both cancer and normal samples. Taken together, these results reveal a new layer of complexity in gene regulation by super-enhancers and broad H3K4me3 domains.
Drought and child mortality: a meta-analysis of small-scale surveys from Ethiopia
Authors: Delbiso Tefera Darge , Altare Chiara , Rodriguez-Llanes Jose Manuel , Doocy Shannon , Guha-Sapir Debarati 
Published: May 2017

AbstractDespite the intuitive connection between drought and mortality, we still lack a sound quantitative synthesis of evidence drawn from the available data. In this study, we estimate the pooled under-five death rates (U5DR) and assess the effect of drought on child death in Ethiopia. Small-scale mortality surveys were searched from the Complex Emergency Database and then aggregated spatially and temporally with drought exposure data from the Global Drought Monitor and food insecurity data from the Famine Early Warning Systems Network. A Bayesian Poisson meta-analysis was performed on 88 surveys conducted in Ethiopia between 2009 and 2014, consisting of 55,219 under-five children. The pooled U5DR was estimated at 0.323/10,000/day (95% credible interval, CrI: 0.254–0.397), which is below both the emergency and the baseline death rate thresholds of sub-Saharan Africa. We failed to find a plausible association between drought and U5DR. However, minimal food insecure areas showed elevated U5DR compared to stressed food insecure areas. Furthermore, the U5DR increases as the prevalence of acute malnutrition increases. Targeted interventions to improve the underlying causes of child malnutrition are crucial. Further, revising and updating the existing mortality thresholds, both the baseline and the emergency, is recommended.
Evaluation of Arteriolar Smooth Muscle Cell Function in an Ex Vivo Microvascular Network Model
Authors: Motherwell Jessica M. , Azimi Mohammad S. , Spicer Kristine , Alves Natascha G. , Hodges Nicholas A. , Breslin Jerome W. , Katakam Prasad V. G. , Murfee Walter L. 
Published: May 2017

AbstractAn emerging challenge in tissue engineering biomimetic models is recapitulating the physiological complexity associated with real tissues. Recently, our laboratory introduced the rat mesentery culture model as an ex vivo experimental platform for investigating the multi-cellular dynamics involved in angiogenesis within an intact microvascular network using time-lapse imaging. A critical question remains whether the vessels maintain their functionality. The objective of this study was to determine whether vascular smooth muscle cells in cultured microvascular networks maintain the ability to constrict. Adult rat mesenteric tissues were harvested and cultured for three days in either MEM or MEM plus 10% serum. On Day 0 and Day 3 live microvascular networks were visualized with FITC conjugated BSI-lectin labeling and arteriole diameters were compared before and five minutes after topical exposure to vasoconstrictors (50 mM KCl and 20 nM Endothelin-1). Arterioles displayed a vasoconstriction response to KCl and endothelin for each experimental group. However, the Day 3 serum cultured networks were angiogenic, characterized by increased vessel density, and displayed a decreased vasoconstriction response compared to Day 0 networks. The results support the physiological relevance of the rat mesentery culture model as a biomimetic tool for investigating microvascular growth and function ex vivo.
Response of coral calcification and calcifying fluid composition to thermally induced bleaching stress
Authors: D’Olivo J. P. , McCulloch M. T. 
Published: May 2017

AbstractSevere, global-scale thermal stress events like those of 1998 and 2016, are becoming more frequent and intense, potentially compromising the future of coral reefs. Here we report the effects of the 1998 bleaching event on coral calcification as well as the composition of the calcifying fluid (cf) from which corals precipitate their calcium carbonate skeletons. This was investigated by using the Sr/Ca, Li/Mg (temperature), and boron isotopes (δ11B) and B/Ca (carbonate chemistry) proxies in a Porites sp. coral. Following the summer of 1998 the coral exhibited a prolonged period (~18 months) of reduced calcification (~60%) and a breakdown in the seasonality of the geochemical proxies. However, the maintenance of elevated dissolved inorganic carbon (DICcf; >×2 seawater) and pHcf (>8.3 compared to seawater ~8.0) even during severe stress of 1998 indicate that a minimum threshold of high aragonite saturation state (Ωcf) of ~14 (~×4 seawater), is an essential pre-requisite for coral calcification. However, despite maintaining elevated levels of Ωcf even under severe stress, coral growth is still impaired. We attribute this to reductions in either the effective active volume of calcification and/or DICcf as bleaching compromises the photosynthetically fixed carbon pool available to the coral.
Identification of a novel chalcone derivative that inhibits Notch signaling in T-cell acute lymphoblastic leukemia
Authors: Mori Mattia , Tottone Luca , Quaglio Deborah , Zhdanovskaya Nadezda , Ingallina Cinzia , Fusto Marisa , Ghirga Francesca , Peruzzi Giovanna , Crestoni Maria Elisa , Simeoni Fabrizio , Giulimondi Francesca , Talora Claudio , Botta Bruno , Screpanti Isabella , Palermo Rocco 
Published: May 2017

AbstractNotch signaling is considered a rational target in the therapy of several cancers, particularly those harbouring Notch gain of function mutations, including T-cell acute lymphoblastic leukemia (T-ALL). Although currently available Notch-blocking agents are showing anti-tumor activity in preclinical studies, they are not effective in all the patients and often cause severe side-effects, limiting their widespread therapeutic use. Here, by functional and biological analysis of the most representative molecules of an in house library of natural products, we have designed and synthetized the chalcone-derivative 8 possessing Notch inhibitory activity at low micro molar concentration in T-ALL cell lines. Structure-activity relationships were afforded for the chalcone scaffold. Short term treatments with compound 8 resulted in a dose-dependent decrease of Notch signaling activity, halted cell cycle progression and induced apoptosis, thus affecting leukemia cell growth. Taken together, our data indicate that 8 is a novel Notch inhibitor, candidate for further investigation and development as an additional therapeutic option against Notch-dependent cancers.
FK866 attenuates acute hepatic failure through c-jun-N-terminal kinase (JNK)-dependent autophagy
Authors: Guo Enshuang , Li Renlong , Yang Jiankun , Zhang Jun , Li Anyi , Yang Yan , Liu Shenpei , Liu Anding , Jiang Xiaojing 
Published: May 2017

AbstractFK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy. In vivo, Mice were pretreated with FK866 at 24, 12, and 0.5 h before treatment with GaIN/LPS and ConA. 3-methyladenine (3MA) or rapamycin were used to determine the role of autophagy in FK866-conferred hepatoprotection. In primary hepatocytes, autophagy was inhibited by 3MA or autophagy-related protein 7 (Atg7) small interfering RNA (siRNA). JNK was suppressed by SP600125 or Jnk siRNA. FK866 alleviated hepatotoxicity and increased autophagy while decreased JNK activation. Suppression of autophagy abolished the FK866-conferred protection. Inhibition of JNK increased autophagy and exhibited strongly protective effect. Collectively, FK866 could ameliorate GaIN/LPS and ConA-induced ALF through induction of autophagy while suppression of JNK. These findings suggest that FK866 acts as a simple and applicable preconditioning intervention to protect against ALF; autophagy and JNK may also provide therapeutic targets for ALF treatment.