bluuebunny/crossref_metadata_2025 huggingface dataset:
Shared peptide binding of HLA Class I and II alleles associate with cutaneous nevirapine hypersensitivity and identify novel risk alleles
Authors: Pavlos Rebecca , McKinnon Elizabeth J. , Ostrov David A. , Peters Bjoern , Buus Soren , Koelle David , Chopra Abha , Schutte Ryan , Rive Craig , Redwood Alec , Restrepo Susana , Bracey Austin , Kaever Thomas , Myers Paisley , Speers Ellen , Malaker Stacy A. , Shabanowitz Jeffrey , Jing Yuan , Gaudieri Silvana , Hunt Donald F. , Carrington Mary , Haas David W. , Mallal Simon , Phillips Elizabeth J.
Published: August 2017

Genes of the human leukocyte antigen (HLA) system encode cell-surface proteins involved in regulation of immune responses, and the way drugs interact with the HLA peptide binding groove is important in the immunopathogenesis of T-cell mediated drug hypersensitivity syndromes. Nevirapine (NVP), is an HIV-1 antiretroviral with treatment-limiting hypersensitivity reactions (HSRs) associated with multiple class I and II HLA alleles. Here we utilize a novel analytical approach to explore these multi-allelic associations by systematically examining HLA molecules for similarities in peptide binding specificities and binding pocket structure. We demonstrate that primary predisposition to cutaneous NVP HSR, seen across ancestral groups, can be attributed to a cluster of HLA-C alleles sharing a common binding groove F pocket withHLA-C*04:01. An independent association with a group of class II alleles which share the HLA-DRB1-P4 pocket is also observed. In contrast, NVP HSR protection is afforded by a cluster of HLA-B alleles defined by a characteristic peptide binding groove B pocket. The results suggest drug-specific interactions within the antigen binding cleft can be shared across HLA molecules with similar binding pockets. We thereby provide an explanation for multiple HLA associations with cutaneous NVP HSR and advance insight into its pathogenic mechanisms.
Use of Biocompatible Sorafenib-gold Nanoconjugates for Reversal of Drug Resistance in Human Hepatoblatoma Cells
Authors: Vishwakarma Sandeep Kumar , Sharmila Priyanka , Bardia Avinash , Chandrakala Lakkireddy , Raju N. , Sravani G. , Sastry B. V. S. , Habeeb Md Aejaz , Khan Aleem Ahmed , Dhayal Marshal
Published: August 2017

The present study identifies the potential of highly biocompatible SF-GNP nano-conjugate to enhance the chemotherapeutic response to combat drug resistance in cancer cells. We developed a stable colloidal suspension of sorafenib-gold nanoconjugate (SF-GNP) of <10 nm size in aqueous medium for reverting the cancer drug resistance in SF-resistant HepG2 cells in a 3D ex-vivo model system. In-vivo biocompatibility assay of SF-GNPs showed absence of systemic toxicological effects including hematological, biochemical and histological parameters. More importantly, the histopathological analysis of vital organs such as liver, brain, lung, kidney and heart showed very least or no sign of inflammation, cell infiltration, necrosis, tissue disorganization or fibrotic reactions after intra-peritoneal administration of SF-GNP nanoconjugates in animals. However, SF-GNP nanoconjugates significantly reduced (>80%) the percentage cell survival and the size and number of SF resistant solid tumor colonies of HepG2 cells in 3D model system. The exposure of SF-GNP nanoconjugate to SF resistant HepG2 cell colonies also provided evidence for anti-proliferative effect and reversal of drug resistance by elucidating the molecular regulatory mechanisms of extracellular matrix factor (CD147), tumor growth factor (TGF-β), hepatoma upregulated protein (hURP) and drug transporter (ABCG-2).
A single-molecule assessment of the protective effect of DMSO against DNA double-strand breaks induced by photo-and γ-ray-irradiation, and freezing
Authors: Noda Masami , Ma Yue , Yoshikawa Yuko , Imanaka Tadayuki , Mori Toshiaki , Furuta Masakazu , Tsuruyama Tatsuaki , Yoshikawa Kenichi
Published: August 2017

Dimethyl sulfoxide (DMSO) is widely used as a cryoprotectant for organs, tissues, and cell suspension in storage. In addition, DMSO is known to be a useful free radical scavenger and a radio-protectant. To date, many in vitro assays using cultured cells have been performed for analysing the protective effect of DMSO against genomic DNA damage; however, currently it has been rather difficult to detect DNA double strand breaks (DSBs) in a quantitative manner. In the present study, we aimed to observe the extent of DNA damage by use of single molecular observation with a fluorescence microscope to evaluate DSBs induced by photo- and γ-ray-irradiation, or freeze/thawing in variable concentrations of DMSO. As a result, we found that 2% DMSO conferred the maximum protective effect against all of the injury sources tested, and these effects were maintained at higher concentrations. Further, DMSO showed a significantly higher protective effect against freezing-induced damage than against photo- and γ-ray-irradiation-induced damage. Our study provides significant data for the optimization of DNA cryopreservation with DMSO, as well as for the usage of DNA as the protective agent against the injuries caused by active oxygen and radiations.
Fusion protein analysis reveals the precise regulation between Hsp70 and Hsp100 during protein disaggregation
Authors: Hayashi Sayaka , Nakazaki Yosuke , Kagii Kei , Imamura Hiromi , Watanabe Yo-hei
Published: August 2017

ClpB, a bacterial Hsp100, is a ring-shaped AAA+ chaperone that can reactivate aggregated proteins in cooperation with DnaK, a bacterial Hsp70, and its co-factors. ClpB subunits comprise two AAA+ modules with an interstitial rod-shaped M-domain. The M-domain regulates ClpB ATPase activity and interacts directly with the DnaK nucleotide-binding domain (NBD). Here, to clarify how these functions contribute to the disaggregation process, we constructed ClpB, DnaK, and aggregated YFP fusion proteins in various combinations. Notably, i) DnaK activates ClpB only when the DnaK substrate-binding domain (SBD) is in the closed conformation, affording high DnaK-peptide affinity; ii) although NBD alone can activate ClpB, SBD is required for disaggregation; and iii) tethering aggregated proteins to the activated ClpB obviates SBD requirements. These results indicate that DnaK activates ClpB only when the SBD tightly holds aggregated proteins adjacent to ClpB for effective disaggregation.
A Preliminary Investigation of the Association of Sleep With Inflammation and Oxidative Stress Biomarkers and Functional Outcomes After Stroke Rehabilitation
Authors: Yeh Ting-ting , Hsieh Yu-wei , Wu Ching-yi , Wang Jong-shyan , Lin Keh-chung , Chen Chia-ling
Published: August 2017

This study examined the association of sleep with inflammation and oxidative stress biomarkers, and with functional outcomes, after stroke rehabilitation. The rehabilitation effects on biomarkers and functional outcomes were also evaluated. Twenty subacute stroke survivors received 4 weeks of upper limb rehabilitation. Baseline inflammatory (i.e., soluble intercellular adhesion molecule-1, sICAM-1) and oxidative stress biomarkers (i.e., glutathione peroxidase, GPx and malondialdehyde, MDA) were assessed, as were sleep outcomes. Positive correlations were observed between baseline level of sICAM-1 and number of awakenings at post-treatment (ρ = 0.51,p < 0.05) as well as between baseline level of MDA and post-performance time of the Wolf Motor Function Test (WMFT-time) (ρ = 0.46,p < 0.05). In addition, MDA levels were significantly decreased, and functional outcomes of the modified Rankin Scale (mRS), functional ability scale of the WMFT, and Stroke Impact Scale (SIS-total, and SIS-physical function) were improved after the rehabilitation. This pilot study emphasizes the relationship among biomarkers, sleep, and functional outcomes after stroke rehabilitation. Oxidative stress markers may be useful predictors of functional outcomes in subacute stroke survivors.
The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis
Authors: Hanna Samer J. , McCoy-Simandle Kessler , Miskolci Veronika , Guo Peng , Cammer Michael , Hodgson Louis , Cox Dianne
Published: August 2017

Macrophage interactions with other cells, either locally or at distances, are imperative in both normal and pathological conditions. While soluble means of communication can transmit signals between different cells, it does not account for all long distance macrophage interactions. Recently described tunneling nanotubes (TNTs) are membranous channels that connect cells together and allow for transfer of signals, vesicles, and organelles. However, very little is known about the mechanism by which these structures are formed. Here we investigated the signaling pathways involved in TNT formation by macrophages using multiple imaging techniques including super-resolution microscopy (3D-SIM) and live-cell imaging including the use of FRET-based Rho GTPase biosensors. We found that formation of TNTs required the activity and differential localization of Cdc42 and Rac1. The downstream Rho GTPase effectors mediating actin polymerization through Arp2/3 nucleation, Wiskott-Aldrich syndrome protein (WASP) and WASP family verprolin-homologous 2 (WAVE2) proteins are also important, and both pathways act together during TNT biogenesis. Finally, TNT function as measured by transfer of cellular material between cells was reduced following depletion of a single factor demonstrating the importance of these factors in TNTs. Given that the characterization of TNT formation is still unclear in the field; this study provides new insights and would enhance the understanding of TNT formation towards investigating new markers.
Mortierella alpina CS10E4, an oleaginous fungal endophyte of Crocus sativus L. enhances apocarotenoid biosynthesis and stress tolerance in the host plant
Authors: Wani Zahoor Ahmed , Kumar Amit , Sultan Phalisteen , Bindu Kushal , Riyaz-Ul-Hassan Syed , Ashraf Nasheeman
Published: August 2017

Crocus sativus is the only plant species which produces apocarotenoids like crocin, picrocrocin and safranal in significant amounts. These compounds impart organoleptic properties to saffron (dried stigmas of Crocus flower) making it world’s costliest spice. Crocus apocarotenoids have tremendous medicinal properties as well. Effect of endophytes on Crocus apocarotenoid production and the molecular mechanism involved has not been reported so far. Here we studied the effect of an oleaginous fungal endophyte, Mortierella alpina CS10E4 on Crocus growth, apocarotenoid metabolism and tolerance to corm rot disease. The results demonstrated that there was a significant improvement in many morphological and physiological traits in endophyte treated Crocus plants including total biomass and size of corms, stigma biomass, number of apical sprouting buds, and number of adventitious roots. The endophyte also shifted metabolic flux towards enhanced production of apocarotenoids by modulating the expression of key pathway genes. Further, M. alpina CS10E4 enhanced tolerance to corm rot disease by releasing arachidonic acid which acts as conserved defense signal and induces jasmonic acid production in endophyte treated Crocus corms. This is first report on effect of a fungal endophyte on Crocus apocarotenoid metabolism and stress tolerance.
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

The 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

Air 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

A 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

Transforming 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

Comparison 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

The 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

Metastatic 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

There 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

We 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

Leucine-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

This 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

To 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

Central 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

Diabetic 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

The 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.
Fungal community assemblage of different soil compartments in mangrove ecosystem
Authors: Sanka Loganathachetti Dinesh , Poosakkannu Anbu , Muthuraman Sundararaman
Published: August 2017

The fungal communities of different soil compartments in mangrove ecosystem are poorly studied. We sequenced the internal transcribed spacer (ITS) regions to characterize the fungal communities in Avicennia marina root-associated soils (rhizosphere and pneumatophore) and bulk soil compartments. The rhizosphere but not pneumatophore soil compartment had significantly lower fungal species richness than bulk soil. However, bulk soil fungal diversity (Shannon diversity index) was significantly higher than both pneumatophore and rhizosphere soil compartments. The different soil compartments significantly affected the fungal community composition. Pairwise sample analyses showed that bulk soil microbial community composition significantly different from rhizosphere and pneumatophore soil compartments. There was, however no significant difference observed between rhizosphere and pneumatophore soil fungal community composition and they shared relatively more OTUs between them. Further, there was a significant correlation observed between fungal community compositional changes and carbon or nitrogen availability of different soil compartments. These results suggest that few characteristics such as fungal richness and taxa abundance of rhizosphere and pneumatophore soil compartments were significantly different in mangrove ecosystem.
Genome-wide Target Enrichment-aided Chip Design: a 66 K SNP Chip for Cashmere Goat
Authors: Qiao Xian , Su Rui , Wang Yang , Wang Ruijun , Yang Ting , Li Xiaokai , Chen Wei , He Shiyang , Jiang Yu , Xu Qiwu , Wan Wenting , Zhang Yaolei , Zhang Wenguang , Chen Jiang , Liu Bin , Liu Xin , Fan Yixing , Chen Duoyuan , Jiang Huaizhi , Fang Dongming , Liu Zhihong , Wang Xiaowen , Zhang Yanjun , Mao Danqing , Wang Zhiying , Di Ran , Zhao Qianjun , Zhong Tao , Yang Huanming , Wang Jian , Wang Wen , Dong Yang , Chen Xiaoli , Xu Xun , Li Jinquan
Published: August 2017

Compared with the commercially available single nucleotide polymorphism (SNP) chip based on the Bead Chip technology, the solution hybrid selection (SHS)-based target enrichment SNP chip is not only design-flexible, but also cost-effective for genotype sequencing. In this study, we propose to design an animal SNP chip using the SHS-based target enrichment strategy for the first time. As an update to the international collaboration on goat research, a 66 K SNP chip for cashmere goat was created from the whole-genome sequencing data of 73 individuals. Verification of this 66 K SNP chip with the whole-genome sequencing data of 436 cashmere goats showed that the SNP call rates was between 95.3% and 99.8%. The average sequencing depth for target SNPs were 40X. The capture regions were shown to be 200 bp that flank target SNPs. This chip was further tested in a genome-wide association analysis of cashmere fineness (fiber diameter). Several top hit loci were found marginally associated with signaling pathways involved in hair growth. These results demonstrate that the 66 K SNP chip is a useful tool in the genomic analyses of cashmere goats. The successful chip design shows that the SHS-based target enrichment strategy could be applied to SNP chip design in other species.
ATP-sensitive inwardly rectifying potassium channel regulation of viral infections in honey bees
Authors: O’Neal Scott T. , Swale Daniel R. , Anderson Troy D.
Published: August 2017

Honey bees are economically important pollinators of a wide variety of crops that have attracted the attention of both researchers and the public alike due to unusual declines in the numbers of managed colonies in some parts of the world. Viral infections are thought to be a significant factor contributing to these declines, but viruses have proven a challenging pathogen to study in a bee model and interactions between viruses and the bee antiviral immune response remain poorly understood. In the work described here, we have demonstrated the use of flock house virus (FHV) as a model system for virus infection in bees and revealed an important role for the regulation of the bee antiviral immune response by ATP-sensitive inwardly rectifying potassium (KATP) channels. We have shown that treatment with the KATP channel agonist pinacidil increases survival of bees while decreasing viral replication following infection with FHV, whereas treatment with the KATP channel antagonist tolbutamide decreases survival and increases viral replication. Our results suggest that KATP channels provide a significant link between cellular metabolism and the antiviral immune response in bees.
Reversible surface functionalisation of emulsion-templated porous polymers using dithiophenol maleimide functional macromolecules
Authors: Eissa A. M. , Wilson P. , Chen C. , Collins J. , Walker M. , Haddleton D. M. , Cameron N. R.
Published: August 2017

Reversible, easy-to-monitor approach to the surface functionalisation of thiol–acrylate polyHIPEs that can be utilised in a wide range of applications.
A new photoactivatable near-infrared-emitting QCy7 fluorophore for single-molecule super-resolution microscopy
Authors: Klötzner Dean-Paulos , Klehs Kathrin , Heilemann Mike , Heckel Alexander
Published: August 2017

In this work we present a new photoactivatable QCy7-based fluorophore and demonstrate its application in single-molecule super-resolution microscopy.
Rare Co/Fe-MOFs exhibiting high catalytic activity in electrochemical aptasensors for ultrasensitive detection of ochratoxin A
Authors: Wang Zhen , Yu Hua , Han Jing , Xie Gang , Chen Sanping
Published: August 2017

The high-performance of NH2-Co-MOF towards thionine catalysis was first demonstrated and applied to construct an electrochemical aptasensor.
Topotactic transition of α-Co(OH)2to β-Co(OH)2anchored on CoO nanoparticles during electrochemical water oxidation: synergistic electrocatalytic effects
Authors: Kundu Sumana , Malik Bibhudatta , Prabhakaran Amrutha , Pattanayak Deepak K. , Pillai Vijayamohanan K.
Published: August 2017

Synergistic effect of a β-Co(OH)2–CoO hybrid in enhancing the electrocatalytic activity for water oxidation.
Engineering defects and photocatalytic activity of TiO2 nanoparticles by thermal treatments in NH3 and subsequent surface chemical etchings
Authors: Yu Xiaomei , Wang Yunfei , Kim Yu Kwon
Published: August 2017

TiO2 nanoparticles with N dopants were prepared by thermal treatments in NH3 and their surface defects were controlled by post chemical etching in HF to find out the influence of the N dopants on photoactivity.
Neutron vibrational spectroscopic studies of novel tire-derived carbon materials
Authors: Li Yunchao , Cheng Yongqiang , Daemen Luke L. , Veith Gabriel M. , Levine Alan M. , Lee Richard J. , Mahurin Shannon M. , Dai Sheng , Naskar Amit K. , Paranthaman Mariappan Parans
Published: August 2017

The surface properties of tire-derived carbon materials were studied by neutron vibrational spectroscopy, Raman and XPS etc. to relate to their performance as energy storage materials.
On the bulk transport process and its impact on the electrode behavior of mixed conducting electrodes for SOFCs
Authors: Li Wenyuan , Guan Bo , Yang Tao , Zhang Nan , Zhang Xinxin , Liu Xingbo
Published: August 2017

The contribution of the electrical field and concentration gradient on the bulk transport of oxygen ions in the MIEC electrodes of SOFC is deconvoluted. A case study of LSCF is carried out.
Theoretical study on the reaction mechanism of hydrogenation of furfural to furfuryl alcohol on Lewis acidic BEA zeolites: effects of defect structure and tetravalent metals substitution
Authors: Injongkol Yuwanda , Maihom Thana , Treesukul Piti , Sirijaraensre Jakkapan , Boekfa Bundet , Limtrakul Jumras
Published: August 2017

We examined the catalytic roles of the defect structure and tetravalent-metal substitution on Lewis acidic BEA Zeolites for the furfural hydrogenation reaction using the DFT approach.
Co-assembly behaviour of Janus nanoparticles and amphiphilic block copolymers in dilute solution
Authors: Li Qing , Wang Liquan , Lin Jiaping
Published: August 2017

This work not only provides insights into assembly behaviors of Janus nanoparticle solutions, but also offers strategies for permeable membranes.
Interfacial properties of borophene contacts with two-dimensional semiconductors
Authors: Yang Jie , Quhe Ruge , Feng Shenyan , Zhang Qiaoxuan , Lei Ming , Lu Jing
Published: August 2017

Interfacial properties of β12phase borophene contacts with other common two-dimensional materials (transition-metal dichalcogenides, group IV-enes and group V-enes) have been systematically studied using a density functional theory (DFT) method.
Theoretical understanding on the selectivity of acrolein hydrogenation over silver surfaces: the non-Horiuti–Polanyi mechanism is the key
Authors: Wang Kaili , Yang Bo
Published: August 2017

The significance of the non-Horiuti–Polanyi mechanism in understanding heterogeneous catalytic hydrogenation reactions is highlighted.
Hoveyda–Grubbs catalyst analogues bearing the derivatives of N-phenylpyrrol in the carbene ligand – structure, stability, activity and unique ruthenium–phenyl interactions
Authors: Grudzień K. , Trzaskowski B. , Smoleń M. , Gajda R. , Woźniak K. , Grela K.
Published: August 2017

N-Phenylpyrrole-2,6-diisopropylphenyl ruthenium complex and its perbrominated derivative are active in ring-closing metathesis at 80 °C, but inactive at room temperature.
Unprecedented tetranuclear complexes with “weighing balance shaped” topology: single crystal structures, unusual EPR spectra, magnetic properties and antioxidant activity
Authors: Singh Yogendra , Patel Ram N. , Singh Yogendra Pratap , Patel Abhay K. , Patel Neetu , Singh Rita , Butcher Raymond J. , Jasinski Jerry P. , Colacio Enrique , Palacios Maria A.
Published: August 2017

Two new copper(ii) complexes have been synthesized and characterized by single crystal X-ray diffraction.
Carbon nitride assisted chemoselective C–H bond photo-oxidation of alkylphenolethoxylates in water medium
Authors: Ilkaeva M. , Krivtsov I. , Bartashevich E. , Khainakov S. A. , García J. R. , Díaz E. , Ordóñez S.
Published: August 2017

H2O2-modified carbon nitride chemoselectively photo-oxidises the methyl group of alkylphenoxylate molecule 2-(4-methylphenoxy)ehanol in water medium.
Super impact absorbing bio-alloys from inedible plants
Authors: Kawada Jumpei , Kitou Masayuki , Mouri Makoto , Kato Yuichi , Katagiri Yoshihide , Matsushita Mitsumasa , Ario Toshiyuki , Kitou Osamu , Usuki Arimitsu
Published: August 2017

Injection molded bio-alloys from inedible plants showed a “salami-like structure in a co-continuous phase” and had superior impact strength with good stiffness, making bio-alloys feasible for applications.
An immunoinformatics approach to promiscuous peptide design for the Plasmodium falciparum erythrocyte membrane protein-1
Authors: Khan Nazam , Kumar Rajender , Chauhan Shakti , Farooq Umar
Published: August 2017

Plasmodium falciparumerythrocyte membrane protein-1 (Pfemp-1), a variant adhesion molecule, can act as a key component of immunity against malaria.
Three dimensional molybdenum oxide/polyaniline hybrid nanosheet networks with outstanding optical and electrochemical properties
Authors: Zhang Kun , Wang Yuemin , Ma Xiaoxuan , Zhang Hangchuan , Hou Shuai , Zhao Jiupeng , Li Xingang , Qiang Liangsheng , Li Yao
Published: August 2017

The hybrid nanosheet networks own complementary dual-electrochromism, fast switching speed and better cycling stability.
Construction of flexible metal–organic framework (MOF) papers through MOF growth on filter paper and their selective dye capture
Authors: Park Jeehyun , Oh Moonhyun
Published: August 2017

ZIF nanoparticle-incorporated filter papers display an outstanding ability to capture and separate organic dyes in a convenient manner.
Electronic effects on a one-pot aromatization cascade involving alkynyl-Prins cyclization, Friedel–Crafts alkylation and dehydration to tricyclic benzo[f]isochromenes
Authors: Hinkle Robert J. , Chen Yuzhou , Nofi Colleen P. , Lewis Shane E.
Published: August 2017

A short, efficient cyclization/aromatization cascade affords tricyclic 1,4-dihydro-2H-benzo[f]isochromenes. Electronic factors suggest concerted alkynyl-Prins and Friedel–Crafts reactions in the sequence.
An organocatalytic cis-selective approach to bicyclic δ-lactones
Authors: Kowalczyk Dorota , Albrecht Łukasz
Published: August 2017

An organocatalytic cis-selective synthetic strategy for the preparation of biologically relevant bicyclic δ-lactones is described.
Highly efficient, one-pot synthesis of novel bis-spirooxindoles with skeletal diversity via sequential multi-component reaction in PEG-400 as a biodegradable solvent
Authors: Safari Ensieh , Maryamabadi Ammar , Hasaninejad Alireza
Published: August 2017

A green, efficient, multi-component protocol has been developed for synthesis of novel bis-spirooxindoles in short reaction time, easy workup and excellent yields.
A ratiometric fluorescent probe for imaging and quantifying anti-apoptotic effects of GSH under temperature stress
Authors: Han Xiaoyue , Song Xinyu , Yu Fabiao , Chen Lingxin
Published: August 2017

A ratiometric fluorescent probe for imaging and quantifying concentration fluctuations and anti-apoptotic effects of GSH under hypothermia and hyperthermia in HepG2 and HepG2/DDP xenografts.
Tunable emergent structures and traveling waves in mixtures of passive and contact-triggered-active particles
Authors: Agrawal Mayank , Bruss Isaac R. , Glotzer Sharon C.
Published: August 2017

Systems with contact-triggered activity exhibit tunable structure and dynamics, that can be deployed to fabricate novel and reconfigurable colloidal materials.