bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast wide-volume functional imaging of engineered in vitro brain tissues
Authors: Palazzolo G. , Moroni M. , Soloperto A. , Aletti G. , Naldi G. , Vassalli M. , Nieus T. , Difato F. 
Published: August 2017

AbstractThe need for in vitro models that mimic the human brain to replace animal testing and allow high-throughput screening has driven scientists to develop new tools that reproduce tissue-like features on a chip. Three-dimensional (3D) in vitro cultures are emerging as an unmatched platform that preserves the complexity of cell-to-cell connections within a tissue, improves cell survival, and boosts neuronal differentiation. In this context, new and flexible imaging approaches are required to monitor the functional states of 3D networks. Herein, we propose an experimental model based on 3D neuronal networks in an alginate hydrogel, a tunable wide-volume imaging approach, and an efficient denoising algorithm to resolve, down to single cell resolution, the 3D activity of hundreds of neurons expressing the calcium sensor GCaMP6s. Furthermore, we implemented a 3D co-culture system mimicking the contiguous interfaces of distinct brain tissues such as the cortical-hippocampal interface. The analysis of the network activity of single and layered neuronal co-cultures revealed cell-type-specific activities and an organization of neuronal subpopulations that changed in the two culture configurations. Overall, our experimental platform represents a simple, powerful and cost-effective platform for developing and monitoring living 3D layered brain tissue on chip structures with high resolution and high throughput.
Association of ambient Particulate matter 2.5 with intensive care unit admission due to pneumonia: a distributed lag non-linear model
Authors: Zhang Zhongheng , Hong Yucai , Liu Ning 
Published: August 2017

AbstractAir pollution in China has become a major environmental problem. There is a lack of evidence on the impact of haze (especially PM2.5) on intensive care unit admission due to pneumonia (ICUp). We hypothesized that PM2.5 was independently associated with ICUp and there was a non-linear time lag effect. All ICU admissions occurred from January 1, 2014 to December 31, 2016 in Sir Run-Run Shaw hospital were included in the study. The primary reasons for admission were categorized into pneumonia and non-pneumonia. Distributed lag non-linear model (DLNM) was built to account for the effect of air quality parameters in both value and temporal lag dimensions. There was a total of 7487 ICU admissions during the study period, including 391 admissions due to pneumonia. The DLNM showed that the relative risk (RR) of ICUp increased with PM2.5 concentrations. At a PM2.5 concentration of 200 mcg/m3, the RR increased from 1.06 (95% CI: 0.57–1.95) at day 0 to 1.40 (95% CI: 1.05–1.86) at day 3, and returned normal at day 6 (RR: 1.13; 95% CI: 0.83–1.55). The study showed that PM2.5 was independently associated with the risk of ICUp, and the maximum effect occurred at 3 to 4 days after exposure.
Enhanced anaerobically digested swine wastewater treatment by the composite of polyaluminum chloride (PAC) and Bacillus megatherium G106 derived EPS
Authors: Guo Junyuan , Huang Yang , Chen Cheng , Xiao Yu , Chen Jing , Jian Biyu 
Published: August 2017

AbstractA strain was isolated from biological sludge to produce EPS by using anaerobically digested swine wastewater (ADSW). Potential of the EPS in ADSW treatment were discussed. Results showed that the optimal fermentation medium for EPS production was determined as 4 g K2HPO4, 2 g KH2PO4, and 2 g sucrose dissolved in 1 L ADSW. After fermentation for 60 h, 2.98 g EPS with main backbone of polysaccharides can be extracted from 1 L of fermentation broth. The EPS showed good performances in ADSW treatment, after conditioned by this EPS, removal efficiencies of COD, ammonia, and TP reached 70.2%, 76.5% and 82.8%, respectively, which were higher than that obtained when chemicals were selected as conditioning agents. Removal efficiencies were further improved when the EPS and polyaluminum chloride (PAC) were used simultaneously, and finally reached 91.6%, 90.8%, and 92.5%, respectively, under the optimized conditioning process by the composite of EPS of 16 mg/L, PAC of 12 g/L, pH of 7.5, and agitation speed of 200 r/min.
Silencing of TGF-β1 in tumor cells impacts MMP-9 in tumor microenvironment
Authors: Moore-Smith Lakisha D. , Isayeva Tatyana , Lee Joo Hyoung , Frost Andra , Ponnazhagan Selvarangan 
Published: August 2017

AbstractTransforming growth factor (TGF)-β1 contributes to autocrine and paracrine functions in the tumor microenvironment (TME). The present study examined the effects of TGF-β1 crosstalk in TME and its role in mediating tumor formation and progression by targeted abrogation of TGF-β1 expression in metastatic cells in situ. Using species-specific primers, we found a significant increase in MMP-9 gene expression in the tumor-reactive stroma during late-stage metastasis in the lung. This effect was also confirmed in cancer-associated fibroblasts (CAFs) when co-cultured with the tumor cells. Knockdown of TGF-β1 expression in the tumor cells negatively affected matrix metalloproteinase (MMP)-9 gene expression. Fibroblasts, cultured in the presence of tumor cells with intact TGF-β1, showed a significant increase in proliferation rate, as well as expression of VEGF, bFGF, and SDF-1, which was not seen when TGF-β1 expression was abrogated in tumor cells. Absence of TGF-β1 in tumor cells also failed to result in myofibroblast differentiation. Co-implantation of CAFs and tumor cells with either intact TGF-β1 expression or devoid of TGF-β1 in vivo showed a significant increase in tumor growth kinetics in both cell types, suggesting a possible activation TGF-β receptor signaling in tumor cells in response to TGF-β from the TME.
Thermodynamic and Kinetic Analyses of Iron Response Element (IRE)-mRNA Binding to Iron Regulatory Protein, IRP1
Authors: Khan Mateen A. , Walden William E. , Theil Elizabeth C. , Goss Dixie J. 
Published: August 2017

AbstractComparison of kinetic and thermodynamic properties of IRP1 (iron regulatory protein1) binding to FRT (ferritin) and ACO2 (aconitase2) IRE-RNAs, with or without Mn2+, revealed differences specific to each IRE-RNA. Conserved among animal mRNAs, IRE-RNA structures are noncoding and bind Fe2+ to regulate biosynthesis rates of the encoded, iron homeostatic proteins. IRP1 protein binds IRE-RNA, inhibiting mRNA activity; Fe2+ decreases IRE-mRNA/IRP1 binding, increasing encoded protein synthesis. Here, we observed heat, 5 °C to 30 °C, increased IRP1 binding to IRE-RNA 4-fold (FRT IRE-RNA) or 3-fold (ACO2 IRE-RNA), which was enthalpy driven and entropy favorable. Mn2+ (50 µM, 25 °C) increased IRE-RNA/IRP1 binding (Kd) 12-fold (FRT IRE-RNA) or 6-fold (ACO2 IRE-RNA); enthalpic contributions decreased ~61% (FRT) or ~32% (ACO2), and entropic contributions increased ~39% (FRT) or ~68% (ACO2). IRE-RNA/IRP1 binding changed activation energies: FRT IRE-RNA 47.0 ± 2.5 kJ/mol, ACO2 IRE-RNA 35.0 ± 2.0 kJ/mol. Mn2+ (50 µM) decreased the activation energy of RNA-IRP1 binding for both IRE-RNAs. The observations suggest decreased RNA hydrogen bonding and changed RNA conformation upon IRP1 binding and illustrate how small, conserved, sequence differences among IRE-mRNAs selectively influence thermodynamic and kinetic selectivity of the protein/RNA interactions.
ESCRT-III Membrane Trafficking Misregulation Contributes To Fragile X Syndrome Synaptic Defects
Authors: Vita Dominic J. , Broadie Kendal 
Published: August 2017

AbstractThe leading cause of heritable intellectual disability (ID) and autism spectrum disorders (ASD), Fragile X syndrome (FXS), is caused by loss of the mRNA-binding translational suppressor Fragile X Mental Retardation Protein (FMRP). In the Drosophila FXS disease model, we found FMRP binds shrub mRNA (human Chmp4) to repress Shrub expression, causing overexpression during the disease state early-use critical period. The FXS hallmark is synaptic overelaboration causing circuit hyperconnectivity. Testing innervation of a central brain learning/memory center, we found FMRP loss and Shrub overexpression similarly increase connectivity. The ESCRT-III core protein Shrub has a central role in endosome-to-multivesicular body membrane trafficking, with synaptic requirements resembling FMRP. Consistently, we found FMRP loss and Shrub overexpression similarly elevate endosomes and result in the arrested accumulation of enlarged intraluminal vesicles within synaptic boutons. Importantly, genetic correction of Shrub levels in the FXS model prevents synaptic membrane trafficking defects and strongly restores innervation. These results reveal a new molecular mechanism underpinning the FXS disease state.
Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers
Authors: Liu Yang , Maccarini Paolo , Palmer Gregory M. , Etienne Wiguins , Zhao Yulin , Lee Chen-Ting , Ma Xiumei , Inman Brant A. , Vo-Dinh Tuan 
Published: August 2017

AbstractMetastatic spread is the mechanism in more than 90 percent of cancer deaths and current therapeutic options, such as systemic chemotherapy, are often ineffective. Here we provide a proof of principle for a novel two-pronged modality referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) having the potential to safely eradicate both primary tumors and distant metastatic foci. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)–mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells. Delayed rechallenge with MB49 cancer cells injection in mice that appeared cured by SYMPHONY did not lead to new tumor formation after 60 days observation, indicating that SYMPHONY treatment induced effective long-lasting immunity against MB49 cancer cells.
Delta inulin-based adjuvants promote the generation of polyfunctional CD4+ T cell responses and protection against Mycobacterium tuberculosis infection
Authors: Counoupas Claudio , Pinto Rachel , Nagalingam Gayathri , Britton Warwick J. , Petrovsky Nikolai , Triccas James A. 
Published: August 2017

AbstractThere is an urgent need for the rational design of safe and effective vaccines to protect against chronic bacterial pathogens such as Mycobacterium tuberculosis. Advax™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. In this report we determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. The fusion protein CysVac2, comprising the M. tuberculosis antigens Ag85B (Rv1886c) and CysD (Rv1285) formulated with Advax provided significant protection in the lungs of M. tuberculosis-infected mice. Protection was associated with the generation of CysVac2-specific multifunctional CD4+ T cells (IFN-γ+TNF+IL-2+). Addition to Advax of the TLR9 agonist, CpG oligonucleotide (AdvaxCpG), improved both the immunogenicity and protective efficacy of CysVac2. Immunisation with CysVac2/AdvaxCpG resulted in heightened release of the chemoattractants, CXCL1, CCL3, and TNF, and rapid influx of monocytes and neutrophils to the site of vaccination, with pronounced early priming of CysVac2-specific CD4+ T cells. As delta inulin adjuvants have shown an excellent safety and tolerability profile in humans, CysVac2/AdvaxCpG is a strong candidate for further preclinical evaluation for progression to human trials.
EGFR is a pivotal regulator of thrombin-mediated inflammation in primary human nucleus pulposus culture
Authors: Huang Bor-Ren , Chen Tzu-Sheng , Bau Da-Tian , Chuang I-Chen , Tsai Cheng-Fang , Chang Pei-Chun , Lu Dah-Yuu 
Published: August 2017

AbstractWe found that the coagulation and cytokine pathways were important mechanisms involve in the degeneration of intervertebral discs (IVD) using a microarray approach to analyze gene expression in different grades of specimens. Furthermore, using a cytokine/chemokine array, a significant increase in CXCL8 expression was observed in human nucleus pulposus (NP) cells after thrombin treatment. The enhancement of CXCL8 expression by thrombin was activated by the PAR1 receptor. Importantly, analysis of degenerated human NP tissue samples showed that EGFR expression positively correlated with the grade of tissue degeneration. In NP cells, thrombin caused an increase in phosphorylation of the EGFR at the Tyr1068, and treatment with the pharmacological EGFR inhibitor, AG1473 effectively blocked thrombin-enhanced CXCL8 production. Surprisingly, inhibition of STAT3 for 24 h decreased expression of EGFR. Treatment with thrombin also increased Akt and GSK3α/β activation; this activation was also blocked by EGFR inhibitor. Although c-Src, ERK, and FAK were activated by thrombin, only c-Src and ERK were involved in the STAT3/CXCL8 induction. Our findings indicate that stimulation of an inflammatory response in NP cells by thrombin is part of a specific pathophysiology that modulates the EGFR activation through activation of Src/ERK/STAT3 signaling.
Cryo-EM analysis of homodimeric full-length LRRK2 and LRRK1 protein complexes
Authors: Sejwal Kushal , Chami Mohamed , Rémigy Hervé , Vancraenenbroeck Renée , Sibran William , Sütterlin Rosmarie , Baumgartner Paul , McLeod Robert , Chartier-Harlin Marie-Christine , Baekelandt Veerle , Stahlberg Henning , Taymans Jean-Marc 
Published: August 2017

AbstractLeucine-rich repeat kinase 2 (LRRK2) is a large multidomain protein implicated in the pathogenesis of both familial and sporadic Parkinson’s disease (PD), and currently one of the most promising therapeutic targets for drug design in Parkinson’s disease. In contrast, LRRK1, the closest homologue to LRRK2, does not play any role in PD. Here, we use cryo-electron microscopy (cryo-EM) and single particle analysis to gain structural insight into the full-length dimeric structures of LRRK2 and LRRK1. Differential scanning fluorimetry-based screening of purification buffers showed that elution of the purified LRRK2 protein in a high pH buffer is beneficial in obtaining high quality cryo-EM images. Next, analysis of the 3D maps generated from the cryo-EM data show 16 and 25 Å resolution structures of full length LRRK2 and LRRK1, respectively, revealing the overall shape of the dimers with two-fold symmetric orientations of the protomers that is closely similar between the two proteins. These results suggest that dimerization mechanisms of both LRRKs are closely related and hence that specificities in functions of each LRRK are likely derived from LRRK2 and LRRK1’s other biochemical functions. To our knowledge, this study is the first to provide 3D structural insights in LRRK2 and LRRK1 dimers in parallel.
Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair
Authors: Packard René R. Sevag , Baek Kyung In , Beebe Tyler , Jen Nelson , Ding Yichen , Shi Feng , Fei Peng , Kang Bong Jin , Chen Po-Heng , Gau Jonathan , Chen Michael , Tang Jonathan Y. , Shih Yu-Huan , Ding Yonghe , Li Debiao , Xu Xiaolei , Hsiai Tzung K. 
Published: August 2017

AbstractThis study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P < 0.05, n = 7–19). Doxorubicin-injected fish developed ventricular diastolic dysfunction and worsening global cardiac function evidenced by elevated E/A ratios and myocardial performance indexes quantified by pulsed-wave Doppler ultrasound at day 30, followed by normalization at day 60 (P < 0.05, n = 9–20). Treatment with the γ-secretase inhibitor, DAPT, to inhibit cleavage and release of Notch Intracellular Domain (NICD) blocked cardiac architectural regeneration and restoration of ventricular function at day 60 (P < 0.05, n = 6–14). Our approach provides a high-throughput model with translational implications for drug discovery and genetic modifiers of chemotherapy-induced cardiomyopathy.
Intravoxel incoherent motion diffusion-weighted imaging for discriminating the pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer
Authors: Lu Wen , Jing Hou , Ju-Mei Zhou , Shao-Lin Nie , Fang Cao , Xiao-Ping Yu , Qiang Lu , Biao Zeng , Su-Yu Zhu , Ying Hu 
Published: August 2017

AbstractTo investigate the usefulness of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in discriminating the pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC), 42 patients underwent preoperative IVIM-DWI before (pre-nCRT) and after nCRT (post-nCRT). The values of pre-nCRT and post-nCRT IVIM-DWI parameters (ADC, D, D* andf), together with the percentage changes (∆% parametric value) induced by nCRT, were compared between the pCR (tumour regression grade [TRG] 4) and non-pCR (TRG 0, 1, 2 or 3) groups and between the GR (TRG 3 or 4) and PR (TRG 0, 1 or 2) groups based on the Dworak TRG system. After nCRT, the ADC and D values for LARC increased significantly (allP < 0.05). The TRG score revealed a positive correlation with pref(r = 0.357,P = 0.020), postD (r = 0.551,P < 0.001) and Δ%D (r = 0.605,P < 0.001). The pCR group (n = 10) had higher preD*, pref, postD, ∆%ADC and ∆%D values than the non-pCR group (n = 32) (allP < 0.05). The GR group (n = 15) exhibited higher postD, ∆%ADC and ∆%D values than the PR group (n = 27) (allP < 0.05). Based on ROC analysis, ∆%D had a higher area under the curve value than ∆%ADC (P = 0.009) in discriminating the pCR from non-pCR groups. In conclusion, IVIM-DWI may be helpful in identifying the pCR to nCRT for LARC and is more accurate than traditional DWI.
Intradialytic Central Venous Oxygen Saturation is Associated with Clinical Outcomes in Hemodialysis Patients
Authors: Chan Lili , Zhang Hanjie , Meyring-Wösten Anna , Campos Israel , Fuertinger Doris , Thijssen Stephan , Kotanko Peter 
Published: August 2017

AbstractCentral venous oxygen saturation (ScvO2) in the superior vena cava is predominantly determined by cardiac output, arterial oxygen content, and oxygen consumption by the upper body. While abnormal ScvO2 levels are associated with morbidity and mortality in non-uremic populations, ScvO2 has received little attention in hemodialysis patients. From 1/2012 to 8/2015, 232 chronic hemodialysis patients with central venous catheters as vascular access had their ScvO2 monitored during a 6-month baseline period and followed for up to 36 months. Patients were stratified into upper and lower two tertiles by a ScvO2 of 61.1%. Survival analysis employed Kaplan-Meier curves and adjusted Cox proportional hazards models. Patients in the lower tertiles of ScvO2 were older, had longer hemodialysis vintage, lower systolic blood pressure, lower ultrafiltration rates, higher leukocyte counts and neutrophil-to-lymphocyte ratios. Kaplan-Meier analysis indicated a shorter survival time in the lower tertiles of ScvO2 (P = 0.005, log-rank test). In adjusted Cox analysis, a 1 percent point decrease in mean ScvO2 was associated with a 4% increase in mortality (HR 1.04 [95% CI 1.01–1.08], P = 0.044), indicating that low﻿ ScvO2 is associated with poor outcomes. Research on the relative contributions of cardiac output and other factors is warranted to further elucidate the pathophysiology underlying this novel finding.
Periostin-binding DNA aptamer treatment attenuates renal fibrosis under diabetic conditions
Authors: Um Jae Eun , Park Jung Tak , Nam Bo Young , Lee Jung Pyo , Jung Jong Ha , Kim Youndong , Kim Seonghun , Park Jimin , Wu Meiyan , Han Seung Hyeok , Yoo Tae-Hyun , Kang Shin-Wook 
Published: August 2017

AbstractDiabetic nephropathy, the major cause of chronic kidney disease, is associated with progressive renal fibrosis. Recently, accumulation of periostin, an extracellular matrix protein, was shown to augment renal fibrosis. Aptamers have higher binding affinities without developing the common side effects of antibodies. Thus, we evaluated the effect of periostin inhibition by an aptamer-based inhibitor on renal fibrosis under diabetic conditions. In vitro, transforming growth factor-β1 (TGF-β1) treatment significantly upregulated periostin, fibronectin, and type I collagen mRNA and protein expressions in inner medullary collecting duct (IMCD) cells. These increases were attenuated significantly in periostin-binding DNA aptamer (PA)-treated IMCD cells exposed to TGF-β1. In vivo, PA treatment attenuated the increased blood urea nitrogen levels in the diabetic mice significantly. Fibronectin and type I collagen mRNA and protein expressions increased significantly in the kidneys of diabetic mice: PA administration abrogated these increases significantly. Immunohistochemistry and Sirius Red staining also revealed that fibronectin expression was significantly higher and tubulointersititial fibrosis was significantly worse in diabetic mice kidneys compared with control mice. These changes were ameliorated by PA treatment. These findings suggested that inhibition of periostin using a DNA aptamer could be a potential therapeutic strategy against renal fibrosis in diabetic nephropathy.
Nitenpyram seed treatment effectively controls against the mirid bug Apolygus lucorum in cotton seedlings
Authors: Zhang Zhengqun , Wang Yao , Zhao Yunhe , Li Beixing , Lin Jin , Zhang Xuefeng , Liu Feng , Mu Wei 
Published: August 2017

AbstractThe mirid bug Apolygus lucorum (Meyer-Dür) has become a major pest in cotton fields and has led to significant yield losses due to the widespread use of transgenic Bt cotton in China. Eight neonicotinoid seed treatments were investigated to determine their effects on the management of A. lucorum in cotton fields. All neonicotinoid seed treatments reduced the cotton damage caused by A. lucorum, and nitenpyram at the rate of 4 g/kg seed showed the most favorable efficacy in suppressing A. lucorum populations throughout the cotton seedling stage. The neonicotinoid seed treatments had no effect on the emergence rate of cotton seeds. Although the neonicotinoid seed treatments were not significantly different from the spray treatments in the cotton yield, the seed treatments reduced the need for three pesticide applications and showed a tremendous advantage in labor costs throughout the cotton seedling stage. Overall, the neonicotinoid seed treatments, particularly the nitenpyram seed treatment, can provide effective protection and should play an important role in the management of early season A. lucorum in Bt cotton fields.