bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair Pathways
Authors: Sha Yan , Vartanian Vladimir , Owen Nichole , Mengden Koon Stephanie J. , Calkins Marcus J. , Thompson Courtney S. , Mirafzali Zahra , Mir Sara , Goldsmith Lisa E. , He Huaping , Luo Chun , Brown Scott M. , Doetsch Paul W. , Kaempf Andy , Lim Jeong Y. , McCullough Amanda K. , Lloyd R. Stephen
Published: January 2018

The molecular basis for ultraviolet (UV) light-induced nonmelanoma and melanoma skin cancers centers on cumulative genomic instability caused by inefficient DNA repair of dipyrimidine photoproducts. Inefficient DNA repair and subsequent translesion replication past these DNA lesions generate distinct molecular signatures of tandem CC to TT and C to T transitions at dipyrimidine sites. Since previous efforts to develop experimental strategies to enhance the repair capacity of basal keratinocytes have been limited, we have engineered the N-terminally truncated form (Δ228) UV endonuclease (UVDE) from Schizosaccharomyces pombe to include a TAT cell-penetrating peptide sequence with or without a nuclear localization signal (NLS): UVDE-TAT and UVDE-NLS-TAT. Further, a NLS was engineered onto a pyrimidine dimer glycosylase from Paramecium bursaria chlorella virus-1 (cv-pdg-NLS). Purified enzymes were encapsulated into liposomes and topically delivered to the dorsal surface of SKH1 hairless mice in a UVB-induced carcinogenesis study. Total tumor burden was significantly reduced in mice receiving either UVDE-TAT or UVDE-NLS-TAT versus control empty liposomes and time to death was significantly reduced with the UVDE-NLS-TAT. These data suggest that efficient delivery of exogenous enzymes for the initiation of repair of UVB-induced DNA damage may protect from UVB induction of squamous and basal cell carcinomas.
Cardiovascular Function of Modern Pigs Does not Comply with Allometric Scaling Laws
Authors: van Essen Gerard J. , te Lintel Hekkert Maaike , Sorop Oana , Heinonen Ilkka , van der Velden Jolanda , Merkus Daphne , Duncker Dirk J.
Published: January 2018

Growing concerns have been expressed regarding cardiovascular performance in modern farm pigs, which has been proposed as a critical factor contributing to the reduced adaptability of modern pigs to stress. Here we tested the hypothesis that cardiac dimensions and pump function in modern heavy farm pigs are disproportionally low for their body weight, and investigated potential underlying mechanisms. The results from the present study indeed demonstrate disproportionally low values for stroke volume and cardiac output in pigs with bodyweights over 150 kg. Importantly, these low values were not the result of impaired left ventricular (LV) systolic contractile function, but were due to a disproportionally small LV end-diastolic volume. The latter was associated with changes in determinants of LV passive stiffness, including (i) an increase in LV myocardial collagen, (ii) a shift from the compliant N2BA titin isoform towards the stiff N2B, and (iii) a marked elevation of aortic blood pressure. Taken together, these results demonstrate reduced pumping capacity of the hearts of heavy modern pigs, due to structural abnormalities in the LV myocardium.
New live screening of plant-nematode interactions in the rhizosphere
Authors: O’Callaghan Felicity E. , Braga Roberto A. , Neilson Roy , MacFarlane Stuart A. , Dupuy Lionel X.
Published: January 2018

Free living nematodes (FLN) are microscopic worms found in all soils. While many FLN species are beneficial to crops, some species cause significant damage by feeding on roots and vectoring viruses. With the planned legislative removal of traditionally used chemical treatments, identification of new ways to manage FLN populations has become a high priority. For this, more powerful screening systems are required to rapidly assess threats to crops and identify treatments efficiently. Here, we have developed new live assays for testing nematode responses to treatment by combining transparent soil microcosms, a new light sheet imaging technique termed Biospeckle Selective Plane Illumination Microscopy (BSPIM) for fast nematode detection, and Confocal Laser Scanning Microscopy for high resolution imaging. We show that BSPIM increased signal to noise ratios by up to 60 fold and allowed the automatic detection of FLN in transparent soil samples of 1.5 mL. Growing plant root systems were rapidly scanned for nematode abundance and activity, and FLN feeding behaviour and responses to chemical compounds observed in soil-like conditions. This approach could be used for direct monitoring of FLN activity either to develop new compounds that target economically damaging herbivorous nematodes or ensuring that beneficial species are not negatively impacted.
Transspinal Direct Current Stimulation Produces Persistent Plasticity in Human Motor Pathways
Authors: Murray Lynda M. , Tahayori Behdad , Knikou Maria
Published: January 2018

The spinal cord is an integration center for descending, ascending, and segmental neural signals. Noninvasive transspinal stimulation may thus constitute an effective method for concomitant modulation of local and distal neural circuits. In this study, we established changes in cortical excitability and input/output function of corticospinal and spinal neural circuits before, at 0–15 and at 30–45 minutes after cathodal, anodal, and sham transspinal direct current stimulation (tsDCS) to the thoracic region in healthy individuals. We found that intracortical inhibition was different among stimulation polarities, however remained unchanged over time. Intracortical facilitation increased after cathodal and anodal tsDCS delivered with subjects seated, and decreased after cathodal tsDCS delivered with subjects lying supine. Both cathodal and anodal tsDCS increased corticospinal excitability, yet facilitation was larger and persisted for 30 minutes post stimulation only when cathodal tsDCS was delivered with subjects lying supine. Spinal input/output reflex function was decreased by cathodal and not anodal tsDCS. These changes may be attributed to altered spontaneous neural activity and membrane potentials of corticomotoneuronal cells by tsDCS involving similar mechanisms to those mediating motor learning. Our findings indicate that thoracic tsDCS has the ability to concomitantly alter cortical, corticospinal, and spinal motor output in humans.
Magnetic Chern Insulators in a monolayer of Transition Metal Trichalcogenides
Authors: Mishra Archana , Lee SungBin
Published: January 2018

A monolayer of transition metal trichalcogenides has received a lot of attention as potential two dimensional magnetic materials. The system has a honeycomb structure of transition metal ions, where both spin-orbit coupling and electron correlation effect play an important role. Here, motivated by these transition metal series with effective doping or mixed valence case, we propose the possible realization of magnetic Chern insulators at quarter filled honeycomb lattice. We show that the interplay of intrinsic spin-orbit coupling and electron correlation opens a wide region of ferromagnetic Chern insulating phases in between metals and normal insulators. Within the mean field approximation, we present the phase diagram of a quarter filled Kane-Mele Hubbard model and also discuss the effects of Rashba spin-orbit coupling and nearest neighbor interactions on it.
RFA Guardian: Comprehensive Simulation of Radiofrequency Ablation Treatment of Liver Tumors
Authors: Voglreiter Philip , Mariappan Panchatcharam , Pollari Mika , Flanagan Ronan , Blanco Sequeiros Roberto , Portugaller Rupert Horst , Fütterer Jurgen , Schmalstieg Dieter , Kolesnik Marina , Moche Michael
Published: January 2018

The RFA Guardian is a comprehensive application for high-performance patient-specific simulation of radiofrequency ablation of liver tumors. We address a wide range of usage scenarios. These include pre-interventional planning, sampling of the parameter space for uncertainty estimation, treatment evaluation and, in the worst case, failure analysis. The RFA Guardian is the first of its kind that exhibits sufficient performance for simulating treatment outcomes during the intervention. We achieve this by combining a large number of high-performance image processing, biomechanical simulation and visualization techniques into a generalized technical workflow. Further, we wrap the feature set into a single, integrated application, which exploits all available resources of standard consumer hardware, including massively parallel computing on graphics processing units. This allows us to predict or reproduce treatment outcomes on a single personal computer with high computational performance and high accuracy. The resulting low demand for infrastructure enables easy and cost-efficient integration into the clinical routine. We present a number of evaluation cases from the clinical practice where users performed the whole technical workflow from patient-specific modeling to final validation and highlight the opportunities arising from our fast, accurate prediction techniques.
Direct observation of the effects of cellulose synthesis inhibitors using live cell imaging of Cellulose Synthase (CESA) in Physcomitrella patens
Authors: Tran Mai L. , McCarthy Thomas W. , Sun Hao , Wu Shu-Zon , Norris Joanna H. , Bezanilla Magdalena , Vidali Luis , Anderson Charles T. , Roberts Alison W.
Published: January 2018

Results from live cell imaging of fluorescently tagged Cellulose Synthase (CESA) proteins in Cellulose Synthesis Complexes (CSCs) have enhanced our understanding of cellulose biosynthesis, including the mechanisms of action of cellulose synthesis inhibitors. However, this method has been applied only in Arabidopsis thaliana and Brachypodium distachyon thus far. Results from freeze fracture electron microscopy of protonemal filaments of the moss Funaria hygrometrica indicate that a cellulose synthesis inhibitor, 2,6-dichlorobenzonitrile (DCB), fragments CSCs and clears them from the plasma membrane. This differs from Arabidopsis, in which DCB causes CSC accumulation in the plasma membrane and a different cellulose synthesis inhibitor, isoxaben, clears CSCs from the plasma membrane. In this study, live cell imaging of the moss Physcomitrella patens indicated that DCB and isoxaben have little effect on protonemal growth rates, and that only DCB causes tip rupture. Live cell imaging of mEGFP-PpCESA5 and mEGFP-PpCESA8 showed that DCB and isoxaben substantially reduced CSC movement, but had no measureable effect on CSC density in the plasma membrane. These results suggest that DCB and isoxaben have similar effects on CSC movement in P. patens and Arabidopsis, but have different effects on CSC intracellular trafficking, cell growth and cell integrity in these divergent plant lineages.
Deeply-sourced formate fuels sulfate reducers but not methanogens at Lost City hydrothermal field
Authors: Lang Susan Q. , Früh-Green Gretchen L. , Bernasconi Stefano M. , Brazelton William J. , Schrenk Matthew O. , McGonigle Julia M.
Published: January 2018

Hydrogen produced during water-rock serpentinization reactions can drive the synthesis of organic compounds both biotically and abiotically. We investigated abiotic carbon production and microbial metabolic pathways at the high energy but low diversity serpentinite-hosted Lost City hydrothermal field. Compound-specific 14C data demonstrates that formate is mantle-derived and abiotic in some locations and has an additional, seawater-derived component in others. Lipids produced by the dominant member of the archaeal community, the Lost City Methanosarcinales, largely lack 14C, but metagenomic evidence suggests they cannot use formate for methanogenesis. Instead, sulfate-reducing bacteria may be the primary consumers of formate in Lost City chimneys. Paradoxically, the archaeal phylotype that numerically dominates the chimney microbial communities appears ill suited to live in pure hydrothermal fluids without the co-occurrence of organisms that can liberate CO2. Considering the lack of dissolved inorganic carbon in such systems, the ability to utilize formate may be a key trait for survival in pristine serpentinite-hosted environments.
The PII signaling protein from red algae represents an evolutionary link between cyanobacterial and Chloroplastida PII proteins
Authors: Lapina Tatyana , Selim Khaled A. , Forchhammer Karl , Ermilova Elena
Published: January 2018

PII superfamily consists of widespread signal transduction proteins found in all domains of life. Whereas they are well-studied in Archaea, Bacteria and Chloroplastida, no PII homolog has been analyzed in Rhodophyta (red algae), where PII is encoded by a chloroplast localized glnB gene. Here, we characterized relevant sensory properties of PII from the red alga Porphyra purpurea (PpPII) in comparison to PII proteins from different phyla of oxygenic phototrophs (cyanobacteria, Chlamydomonas and Physcomitrella) to assess evolutionary conservation versus adaptive properties. Like its cyanobacterial counterparts, PpPII binds ATP/ADP and 2-oxoglutarate in synergy with ATP. However, green algae and land plant PII proteins lost the ability to bind ADP. In contrast to PII proteins from green algae and land plants, PpPII enhances the activity of N-acetyl-L-glutamate kinase (NAGK) and relieves it from feedback inhibition by arginine in a glutamine-independent manner. Like PII from Chloroplastida, PpPII is not able to interact with the cyanobacterial transcriptional co-activator PipX. These data emphasize the conserved role of NAGK as a major PII-interactor throughout the evolution of oxygenic phototrophs, and confirms the specific role of PipX for cyanobacteria. Our results highlight the PII signaling system in red algae as an evolutionary intermediate between Cyanobacteria and Chlorophyta.
Consensus Clustering of temporal profiles for the identification of metabolic markers of pre-diabetes in childhood (EarlyBird 73)
Authors: Lauria Mario , Persico Maria , Dordevic Nikola , Cominetti Ornella , Matone Alice , Hosking Joanne , Jeffery Alison , Pinkney Jonathan , Da Silva Laeticia , Priami Corrado , Montoliu Ivan , Martin François-Pierre
Published: January 2018

In longitudinal clinical studies, methodologies available for the analysis of multivariate data with multivariate methods are relatively limited. Here, we present Consensus Clustering (CClust) a new computational method based on clustering of time profiles and posterior identification of correlation between clusters and predictors. Subjects are first clustered in groups according to a response variable temporal profile, using a robust consensus-based strategy. To discover which of the remaining variables are associated with the resulting groups, a non-parametric hypothesis test is performed between groups at every time point, and then the results are aggregated according to the Fisher method. Our approach is tested through its application to the EarlyBird cohort database, which contains temporal variations of clinical, metabolic, and anthropometric profiles in a population of 150 children followed-up annually from age 5 to age 16. Our results show that our consensus-based method is able to overcome the problem of the approach-dependent results produced by current clustering algorithms, producing groups defined according to Insulin Resistance (IR) and biological age (Tanner Score). Moreover, it provides meaningful biological results confirmed by hypothesis testing with most of the main clinical variables. These results position CClust as a valid alternative for the analysis of multivariate longitudinal data.
Iron-related toxicity of single-walled carbon nanotubes and crocidolite fibres in human mesothelial cells investigated by Synchrotron XRF microscopy
Authors: Cammisuli Francesca , Giordani Silvia , Gianoncelli Alessandra , Rizzardi Clara , Radillo Lucia , Zweyer Marina , Da Ros Tatiana , Salomé Murielle , Melato Mauro , Pascolo Lorella
Published: January 2018

Carbon nanotubes (CNTs) are promising products in industry and medicine, but there are several human health concerns since their fibrous structure resembles asbestos. The presence of transition metals, mainly iron, in the fibres seems also implicated in the pathogenetic mechanisms. To unravel the role of iron at mesothelial level, we compared the chemical changes induced in MeT-5A cells by the exposure to asbestos (crocidolite) or CNTs at different content of iron impurities (raw-SWCNTs, purified- and highly purified-SWCNTs). We applied synchrotron-based X-Ray Fluorescence (XRF) microscopy and soft X-ray imaging (absorption and phase contrast images) to monitor chemical and morphological changes of the exposed cells. In parallel, we performed a ferritin assay. X-ray microscopy imaging and XRF well localize the crocidolite fibres interacting with cells, as well as the damage-related morphological changes. Differently, CNTs presence could be only partially evinced by low energy XRF through carbon distribution and sometimes iron co-localisation. Compared to controls, the cells treated with raw-SWCNTs and crocidolite fibres showed a severe alteration of iron distribution and content, with concomitant stimulation of ferritin production. Interestingly, highly purified nanotubes did not altered iron metabolism. The data provide new insights for possible CNTs effects at mesothelial/pleural level in humans.
Peripheral iron levels in children with attention-deficit hyperactivity disorder: a systematic review and meta-analysis
Authors: Tseng Ping-Tao , Cheng Yu-Shian , Yen Cheng-Fang , Chen Yen-Wen , Stubbs Brendon , Whiteley Paul , Carvalho Andre F. , Li Dian-Jeng , Chen Tien-Yu , Yang Wei-Cheng , Tang Chia-Hung , Chu Che-Sheng , Yang Wei-Chieh , Liang Hsin-Yi , Wu Ching-Kuan , Lin Pao-Yen
Published: January 2018

There is growing recognition that the risk of attention-deficit hyperactivity disorder (ADHD) in children may be influenced by micronutrient deficiencies, including iron. We conducted this meta-analysis to examine the association between ADHD and iron levels/iron deficiency (ID). We searched for the databases of the PubMed, ScienceDirect, Cochrane CENTRAL, and ClinicalTrials.gov up to August 9th, 2017. Primary outcomes were differences in peripheral iron levels in children with ADHD versus healthy controls (HCs) and the severity of ADHD symptoms in children with/without ID (Hedges’ g) and the pooled adjusted odds ratio (OR) of the association between ADHD and ID. Overall, seventeen articles met the inclusion criteria. Peripheral serum ferritin levels were significantly lower in ADHD children (children with ADHD = 1560, HCs = 4691, Hedges’ g = −0.246, p = 0.013), but no significant difference in serum iron or transferrin levels. In addition, the severity of ADHD was significantly higher in the children with ID than those without ID (with ID = 79, without ID = 76, Hedges’ g = 0.888, p = 0.002), and there was a significant association between ADHD and ID (OR = 1.636, p = 0.031). Our results suggest that ADHD is associated with lower serum ferritin levels and ID. Future longitudinal studies are required to confirm these associations and to elucidate potential mechanisms.
Regional evaluation of childhood acute lymphoblastic leukemia genetic susceptibility loci among Japanese
Authors: Urayama Kevin Y. , Takagi Masatoshi , Kawaguchi Takahisa , Matsuo Keitaro , Tanaka Yoichi , Ayukawa Yoko , Arakawa Yuki , Hasegawa Daisuke , Yuza Yuki , Kaneko Takashi , Noguchi Yasushi , Taneyama Yuichi , Ota Setsuo , Inukai Takeshi , Yanagimachi Masakatsu , Keino Dai , Koike Kazutoshi , Toyama Daisuke , Nakazawa Yozo , Kurosawa Hidemitsu , Nakamura Kozue , Moriwaki Koichi , Goto Hiroaki , Sekinaka Yujin , Morita Daisuke , Kato Motohiro , Takita Junko , Tanaka Toshihiro , Inazawa Johji , Koh Katsuyoshi , Ishida Yasushi , Ohara Akira , Mizutani Shuki , Matsuda Fumihiko , Manabe Atsushi
Published: January 2018

Genome-wide association studies (GWAS) performed mostly in populations of European and Hispanic ancestry have confirmed an inherited genetic basis for childhood acute lymphoblastic leukemia (ALL), but these associations are less clear in other races/ethnicities. DNA samples from ALL patients (aged 0–19 years) previously enrolled onto a Tokyo Children’s Cancer Study Group trial were collected during 2013–2015, and underwent single nucleotide polymorphism (SNP) microarray genotyping resulting in 527 B-cell ALL for analysis. Cases and control data for 3,882 samples from the Nagahama Study Group and Aichi Cancer Center Study were combined, and association analyses across 10 previous GWAS-identified regions were performed after targeted SNP imputation. Linkage disequilibrium (LD) patterns in Japanese and other populations were evaluated using the varLD score based on 1000 Genomes data. Risk associations for ARID5B (rs10821936, OR = 1.84, P = 6 × 10−17) and PIP4K2A (rs7088318, OR = 0.76, P = 2 × 10−4) directly transferred to Japanese, and the IKZF1 association was detected by an alternate SNP (rs1451367, OR = 1.52, P = 2 × 10−6). Marked regional LD differences between Japanese and Europeans was observed for most of the remaining loci for which associations did not transfer, including CEBPE, CDKN2A, CDKN2B, and ELK3. This study represents a first step towards characterizing the role of genetic susceptibility in childhood ALL risk in Japanese.
Study on regeneration of waste powder activated carbon through pyrolysis and its adsorption capacity of phosphorus
Authors: Li Yi , Jin Hailan , Liu Wenbo , Su Hang , Lu Yao , Li Jianfen
Published: January 2018

The regeneration of WPAC through pyrolysis and its adsorption capacity of phosphorus were studied. The optimum conditions for WPAC regeneration were 650 °C and 2 h which resulted in a recovery of BET surface and total pore volume with a value of 1161.4 m2/g and 1.2176 m3/g. WPAC had a maximum PO43−-P adsorption capacity of 9.65 mg/g which was 48.93% of PAC, while RWPAC had a maximum PO43−-P adsorption capacity of 15.31 mg/g which was 77.64% of PAC. The kinetic analysis revealed that Langmuir model could well describe the adsorption process of PAC, WPAC and RWPAC on PO43−-P and the PO43−-P adsorption followed the pseudo-second-order model.
Circulating microRNA signature for the diagnosis of childhood dilated cardiomyopathy
Authors: Jiao Meng , You Hong-Zhao , Yang Xin-Ying , Yuan Hui , Li Yu-Lin , Liu Wen-Xian , Jin Mei , Du Jie
Published: January 2018

Circulating miRNAs are proposed as a biomarker of heart disease. This study evaluated whether circulating miRNAs could be used as a biomarker for childhood dilated cardiomyopathy (CDCM). A total of 28 participants were enrolled in a discovery set, including patients with CDCM (n = 16) and healthy children (n = 12). The cardiac function of patients with CDCM was characterized by echocardiography and serum miRNA profiles of all participants were assessed by miRNA sequencing. After miRNA profiling, we quantitatively confirmed 148 regulated miRNAs in patients with CDCM compared with healthy subjects, and none were downregulated. Validation of candidate miRNAs was assessed by quantitative real-time polymerase chain reaction in other patients with CDCM (n = 30) and healthy controls (n = 16). A unique signature comprising mir-142-5p, mir-143-3p, mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy subjects. Importantly, we observed an increase in mir-126-3p or let-7g in parallel with a robust decrease in the ejection fraction in patients with CDCM, which could differentiate heart failure patients from non-heart failure patients with CDCM. Moreover, mir-126-3p and let-7g were significantly negatively associated with the left ventricular ejection fraction. This study shows that a signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM and assessing heart failure.
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer
Authors: Sclafani Francesco , Chau Ian , Cunningham David , Hahne Jens C. , Vlachogiannis George , Eltahir Zakaria , Lampis Andrea , Braconi Chiara , Kalaitzaki Eleftheria , De Castro David Gonzalez , Wotherspoon Andrew , Capdevila Jaume , Glimelius Bengt , Tarazona Noelia , Begum Ruwaida , Lote Hazel , Hulkki Wilson Sanna , Mentrasti Giulia , Brown Gina , Tait Diana , Oates Jacqueline , Valeri Nicola
Published: January 2018

There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA analysis revealed KRAS mutations that were not previously found in tissue. Twenty-two of these (84.6%) were detected following repeat tissue testing by ddPCR. Overall, the ctDNA detection rate in the KRAS mutant population was 66%. Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient selection for cetuximab. While this study confirms the feasibility of ctDNA analysis in LARC and the high sensitivity of ddPCR, larger series are needed to better address the role of ctDNA as a prognostic or predictive tool in this setting.
Differential tolerance to nickel between Dreissena polymorpha and Dreissena rostriformis bugensis populations
Authors: Potet Marine , Giambérini Laure , Pain-Devin Sandrine , Louis Fanny , Bertrand Carole , Devin Simon
Published: January 2018

Differential tolerance to stress is partly responsible for the heterogeneity of biomarker responses between populations of a sentinel species. Although currently used for freshwater biomonitoring, studies concerning inter-populational variability in tolerance to contaminants for the zebra mussel (Dreissena polymorpha) are scarce. Moreover, this well-known invader is currently replaced by another, the quagga mussel (Dreissena rostriformis bugensis). To evaluate the differential tolerance between dreissenids, several populations of both species were exposed to a high concentration of nickel. A LT50 (time when 50% of individuals were dead) was established for each population. Biomarker responses and internal nickel concentration were also measured, to link tolerance with physiological status. Results evidenced that D. polymorpha populations are more heterogeneous and more tolerant than D. r. bugensis ones. For D. polymorpha populations only, LT50 values were positively correlated with the nickel contamination in situ, with higher anti-oxidative defences and a higher Integrated Biomarker Response value in the field. Such findings may be explained by local adaptation and invasion dynamic within each species. The significance of this differential tolerance when using biomarker responses for biomonitoring purposes is thus discussed.
Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells
Authors: Song Anping , Zhu Ling , Gorantla Gowthami , Berdysz Olimpia , Amici Stephanie A. , Guerau-de-Arellano Mireia , Madalena Kathryn M. , Lerch Jessica K. , Liu Xiaoyu , Quan Ning
Published: January 2018

Interleukin 1 is a pleiotropic cytokine that mediates diverse functions through its receptor, type I interleukin 1 receptor (IL-1R1). Most previous studies have focused on the expression and function of IL-1R1 in immune cells. Here we performed a comprehensive mapping of IL-1R1 distribution in multiple peripheral tissues using our IL-1R1 reporter (IL-1R1GR/GR) mice. This method yielded the highest sensitivity ofin situdetection of IL-1R1 mRNA and protein. Besides validating previously reported IL-1R1 expression in the endocrine tissues including pituitary and pancreas, our results refuted previously reported exclusive IL-1R1 expression in neurons of the spinal cord dorsal horn and dorsal root ganglia (DRG). Instead, IL-1R1 expression was detected in endothelial cells within DRG, spinal cord, pancreas, colon, muscles and many immune organs. In addition, gp38+fibroblastic reticular cells (FRCs), rather than tissue macrophages or other immune cells, were found to express high levels of IL-1R1 in colon and many immune organs. A functional test of spleen FRCs showed that they responded rapidly to systemic IL-1β stimulationin vivo. Taken together, this study provides a rigorous re-examination of IL-1R1 expression in peripheral tissues and reveals tissue FRCs as a previously unappreciated novel high IL-1R1-expressing cell type in peripheral IL-1 signaling.
Ultrathin silicon oxynitride layer on GaN for dangling-bond-free GaN/insulator interface
Authors: Nishio Kengo , Yayama Tomoe , Miyazaki Takehide , Taoka Noriyuki , Shimizu Mitsuaki
Published: January 2018

Despite the scientific and technological importance of removing interface dangling bonds, even an ideal model of a dangling-bond-free interface between GaN and an insulator has not been known. The formation of an atomically thin ordered buffer layer between crystalline GaN and amorphous SiO2 would be a key to synthesize a dangling-bond-free GaN/SiO2 interface. Here, we predict that a silicon oxynitride (Si4O5N3) layer can epitaxially grow on a GaN(0001) surface without creating dangling bonds at the interface. Our ab initio calculations show that the GaN/Si4O5N3 structure is more stable than silicon-oxide-terminated GaN(0001) surfaces. The electronic properties of the GaN/Si4O5N3 structure can be tuned by modifying the chemical components near the interface. We also propose a possible approach to experimentally synthesize the GaN/Si4O5N3 structure.
Capturing expert uncertainty in spatial cumulative impact assessments
Authors: Jones Alice R. , Doubleday Zoë A. , Prowse Thomas A. A. , Wiltshire Kathryn H. , Deveney Marty R. , Ward Tim , Scrivens Sally L. , Cassey Phillip , O’Connell Laura G. , Gillanders Bronwyn M.
Published: January 2018

Understanding the spatial distribution of human impacts on marine environments is necessary for maintaining healthy ecosystems and supporting ‘blue economies’. Realistic assessments of impact must consider the cumulative impacts of multiple, coincident threats and the differing vulnerabilities of ecosystems to these threats. Expert knowledge is often used to assess impact in marine ecosystems because empirical data are lacking; however, this introduces uncertainty into the results. As part of a spatial cumulative impact assessment for Spencer Gulf, South Australia, we asked experts to estimate score ranges (best-case, most-likely and worst-case), which accounted for their uncertainty about the effect of 32 threats on eight ecosystems. Expert scores were combined with data on the spatial pattern and intensity of threats to generate cumulative impact maps based on each of the three scoring scenarios, as well as simulations and maps of uncertainty. We compared our method, which explicitly accounts for the experts’ knowledge-based uncertainty, with other approaches and found that it provides smaller uncertainty bounds, leading to more constrained assessment results. Collecting these additional data on experts’ knowledge-based uncertainty provides transparency and simplifies interpretation of the outputs from spatial cumulative impact assessments, facilitating their application for sustainable resource management and conservation.
Repeated photon and C-ion irradiations in vivo have different impact on alteration of tumor characteristics
Authors: Sato Katsutoshi , Nitta Nobuhiro , Aoki Ichio , Imai Takashi , Shimokawa Takashi
Published: January 2018

Precise characterization of tumor recurrence and regrowth after radiotherapy are important for prognostic understanding of the therapeutic effect. Here, we established a novel in vivo mouse model for evaluating the characteristics of regrown tumor after repeated photon and carbon ion (C-ion) irradiations. The results showed that tumor growth rate, lung metastasis, shortening of the survival of the tumor-bearing mice, and tumor microvessel formation were promoted 2- to 3-fold, and expression of angiogenic and metastatic genes increased 1.5- to 15-fold in regrown tumors after repeated photon irradiations, whereas repeated C-ion irradiations did not alter these characteristics. Interestingly, both repeated photon and C-ion irradiations did not generate radioresistance, which is generally acquired for in vitro treatment. Our results demonstrated that the repetition of photon, and not C-ion, irradiations in vivo alter the characteristics of the regrown tumor, making it more aggressive without acquisition of radioresistance.
Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies
Authors: Juenemann Katrin , Jansen Anne H. P. , van Riel Luigi , Merkx Remco , Mulder Monique P. C. , An Heeseon , Statsyuk Alexander , Kirstein Janine , Ovaa Huib , Reits Eric A.
Published: January 2018

Many neurodegenerative diseases, such as Huntington’s disease, are hallmarked by the formation of intracellular inclusion bodies (IBs) that are decorated with ubiquitin, proteasomes and chaperones. The apparent enrichment of ubiquitin and components involved in protein quality control at IBs suggests local ubiquitin-dependent enzymatic activity. In this study, we examine recruitment of ubiquitin to IBs of polyglutamine-expanded huntingtin fragments (mHtt) by using synthesized TAMRA-labeled ubiquitin moieties. We show that intracellular TAMRA-ubiquitin is dynamic at mHtt IBs and is incorporated into poly-ubiquitin chains of intracellular substrates, such as mHtt, in a conjugation-dependent manner. Furthermore, we report that mHtt IBs recruit catalytically active enzymes involved in (de)-ubiquitination processes based on novel activity-based probes. However, we also find that the overexpression of the GFP-ubiquitin reporter, unlike the endogenous ubiquitin and TAMRA-ubiquitin, becomes irreversibly sequestered as a ring-like structure around the mHtt IBs, suggesting a methodical disadvantage of GFP-tagged ubiquitin. Our data provide supportive evidence for dynamic recruitment of ubiquitin and ubiquitin (de)-conjugating activity at mHtt initiated IBs.
The microRNA regulatory landscape of MSC-derived exosomes: a systems view
Authors: Ferguson Scott W. , Wang Jinli , Lee Christine J. , Liu Maixian , Neelamegham Sriram , Canty John M. , Nguyen Juliane
Published: January 2018

Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a variety of diseases including ischemic heart injury, liver fibrosis, and cerebrovascular disease. Despite an increasing number of studies reporting the therapeutic effects of MSC exosomes, the underlying molecular mechanisms and their miRNA complement are poorly characterized. Here we microRNA (miRNA)-profiled MSC exosomes and conducted a network analysis to identify the dominant biological processes and pathways modulated by exosomal miRNAs. At a system level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis processes in line with observed cardiovascular regenerative effects. Targeted pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-β and PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and increased angiogenesis in HUVECs. The intrinsic beneficial effects were further improved by virus-free enrichment of MSC exosomes with network-informed regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte proliferation. The data presented here help define the miRNA landscape of MSC exosomes, establish their biological functions through network analyses at a system level, and provide a platform for modulating the overall phenotypic effects of exosomes.
Efficient inhibition of African swine fever virus replication by CRISPR/Cas9 targeting of the viral p30 gene (CP204L)
Authors: Hübner Alexandra , Petersen Bjoern , Keil Günther M. , Niemann Heiner , Mettenleiter Thomas C. , Fuchs Walter
Published: January 2018

African swine fever is a devastating viral disease of domestic and wild pigs against which no vaccine or therapy is available. Therefore, we applied the CRISPR (clustered regularly interspaced short palindromic repeats) – Cas9 nuclease system to target the double-stranded DNA genome of African swine fever virus (ASFV). To this end, a permissive wild boar lung (WSL) cell line was modified by stable transfection with a plasmid encoding Cas9 and a guide RNA targeting codons 71 to 78 of the phosphoprotein p30 gene (CP204L) of ASFV. Due to targeted Cas9 cleavage of the virus genome, plaque formation of ASFV was completely abrogated and virus yields were reduced by four orders of magnitude. The specificity of these effects could be demonstrated by using a natural ASFV isolate and escape mutants possessing nucleotide exchanges within the target sequence, which were not inhibited in the Cas9-expressing cell line. Growth of the cell line was not affected by transgene expression which, as well as virus inhibition, proved to be stable over at least 50 passages. Thus, CRISPR-Cas9 mediated targeting of the ASFV p30 gene is a valid strategy to convey resistance against ASF infection, which may also be applied in its natural animal host.
Annual shifts of flow regime alteration: new insights from the Chaishitan Reservoir in China
Authors: Zhang Yongyong , Zhai Xiaoyan , Zhao Tongtiegang
Published: January 2018

Reservoir regulation is variable for flow regime alterations and mainly depends on operational objectives and hydro-meteorological conditions. In this study, the flow regime metrics (i.e., magnitude, variability and frequency, duration, timing and rate of change) are adopted to describe variations in both long-term inflow and outflow series of the Chaishitan Reservoir in China. Deviations between the inflow and outflow metrics are calculated to assess the flow regime alterations at annual scale. Further, dimensions of both time and flow regimes are reduced by multivariate statistical analysis, and the regulation patterns and their annual shifts are identified. Results show that: four regulation patterns are identified from 2004 to 2015. The regulation is gradually enhanced over time with typical features of different hydrological years. In dry years, the pattern is slightly regulated flow regimes with slightly discharging stored water and flattening outflow, moderate stability and intermittency. In normal years, the pattern is slightly regulated flow regimes with extremely increasing flow magnitude in the pre-nonflood season, high stability and slight intermittency. In wet years, the pattern is moderately regulated flow regimes with moderately decreasing flow magnitude in the flood season but extremely increasing flow magnitude in the nonflood season, slight stability and high intermittency.
3D virtual histology of murine kidneys –high resolution visualization of pathological alterations by micro computed tomography
Authors: Missbach-Guentner Jeannine , Pinkert-Leetsch Diana , Dullin Christian , Ufartes Roser , Hornung Daniel , Tampe Bjoern , Zeisberg Michael , Alves Frauke
Published: January 2018

The increasing number of patients with end stage chronic kidney disease not only calls for novel therapeutics but also for pioneering research using convincing preclinical disease models and innovative analytical techniques. The aim of this study was to introduce a virtual histology approach using micro computed tomography (µCT) for the entire murine kidney in order to close the gap between single slice planar histology and a 3D high resolution dataset. An ex vivo staining protocol based on phosphotungstic acid diffusion was adapted to enhance renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the detection of the renal cortex, medulla and pelvis in greater detail, (ii) the analysis of morphological alterations, (iii) the quantification of the volume as well as the radio-opacity of these portions and (iv) the quantification of renal fibrotic remodeling based on altered radio-opacity using the unilateral ureteral obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will in future help to refine the outcome of preclinical research on kidney associated murine disease models.
The Transmission and Evolution of HIV-1 Quasispecies within One Couple: a Follow-up Study based on Next-Generation Sequencing
Authors: Yu Fengjiao , Wen Yujie , Wang Jibao , Gong Yurong , Feng Kaidi , Ye Runhua , Jiang Yan , Zhao Qi , Pan Pinliang , Wu Hao , Duan Song , Su Bin , Qiu Maofeng
Published: January 2018

Next-generation sequencing (NGS) has been successfully used to trace HIV-1 infection. In this study, we investigated the transmission and evolution of HIV-1 quasispecies in a couple infected through heterosexual behavior. A heterosexual couple in which both partners were infected with HIV-1 was followed up for 54 months. Blood samples including whole-blood and plasma samples, were collected at various time points. After HIV-1 subtyping, NGS (Miseq platform) was used to sequence the env region of the HIV-1 quasispecies. Genetic distances were calculated, and phylogenetic trees were generated. We found both partners were infected with HIV-1 subtype circulating recombinant form (CRF), CRF65_cpx. The quasispecies distribution was relatively tightly clustered in the phylogenetic tree during early infection. Over time, the distribution of HIV-1 quasispecies gradually became more dispersed at 12th months, with a progressive increase in gene diversity. By 37th months, the sequences obtained for both partners formed different clusters in the phylogenetic tree. These results suggest that the HIV-1 contact tracing results generated by the Miseq platform may be more reliable than other conventional sequencing methods, which can provide important information about the transmission and evolution of HIV-1. Our findings may help to better target preventative interventions for promoting public health.
Effects of processing on structural, mechanical and biological properties of collagen-based substrates for regenerative medicine
Authors: Terzi A. , Storelli E. , Bettini S. , Sibillano T. , Altamura D. , Salvatore L. , Madaghiele M. , Romano A. , Siliqi D. , Ladisa M. , De Caro L. , Quattrini A. , Valli L. , Sannino A. , Giannini C.
Published: January 2018

The aim of this work was to investigate the structural features of type I collagen isoforms and collagen-based films at atomic and molecular scales, in order to evaluate whether and to what extent different protocols of slurry synthesis may change the protein structure and the final properties of the developed scaffolds. Wide Angle X-ray Scattering data on raw materials demonstrated the preferential orientation of collagen molecules in equine tendon-derived collagens, while randomly oriented molecules were found in bovine skin collagens, together with a lower crystalline degree, analyzed by the assessment of FWHM (Full Width at Half Maximum), and a certain degree of salt contamination. WAXS and FT-IR (Fourier Transform Infrared) analyses on bovine collagen-based films, showed that mechanical homogenization of slurry in acidic solution was the treatment ensuring a high content of super-organization of collagen into triple helices and a high crystalline domain into the material. In vitro tests on rat Schwannoma cells showed that Schwann cell differentiation into myelinating cells was dependent on the specific collagen film being used, and was found to be stimulated in case of homogenization-treated samples. Finally DHT/EDC crosslinking treatment was shown to affect mechanical stiffness of films depending on collagen source and processing conditions.
Strength of shear bands in fluid-saturated rocks: a nonlinear effect of competition between dilation and fluid flow
Authors: Shilko Evgeny V. , Dimaki Andrey V. , Psakhie Sergey G.
Published: January 2018

This study shows the significant and nonlinear effect of the competition between dilation and fluid flow on the shear strength of constrained shear bands in fluid-saturated rocks. This effect is conditioned by the contribution of the pore pressure to the yield stress and strength. The pore pressure is controlled by the dilation of the pore space in the solid skeleton of the shear band during plastic deformation and by squeezing of pores in surrounding blocks by the dilating shear band due to the high stiffness of the host massif. A generalized equation has been derived to describe the dependence of the shear band strength on the ratio of strain rate to fluid flow rate.
Sedimentological constraints on the initial uplift of the West Bogda Mountains in Mid-Permian
Authors: Wang Jian , Cao Ying-chang , Wang Xin-tong , Liu Ke-yu , Wang Zhu-kun , Xu Qi-song
Published: January 2018

The Late Paleozoic is considered to be an important stage in the evolution of the Central Asian Orogenic Belt (CAOB). The Bogda Mountains, a northeastern branch of the Tianshan Mountains, record the complete Paleozoic history of the Tianshan orogenic belt. The tectonic and sedimentary evolution of the west Bogda area and the timing of initial uplift of the West Bogda Mountains were investigated based on detailed sedimentological study of outcrops, including lithology, sedimentary structures, rock and isotopic compositions and paleocurrent directions. At the end of the Early Permian, the West Bogda Trough was closed and an island arc was formed. The sedimentary and subsidence center of the Middle Permian inherited that of the Early Permian. The west Bogda area became an inherited catchment area, and developed a widespread shallow, deep and then shallow lacustrine succession during the Mid-Permian. At the end of the Mid-Permian, strong intracontinental collision caused the initial uplift of the West Bogda Mountains. Sedimentological evidence further confirmed that the West Bogda Mountains was a rift basin in the Carboniferous-Early Permian, and subsequently entered the Late Paleozoic large-scale intracontinental orogeny in the region.
Efficacy of bisphosphonates in the treatment of femoral head osteonecrosis: A PRISMA-compliant meta-analysis of animal studies and clinical trials
Authors: Li Donghai , Yang Zhouyuan , Wei Zhun , Kang Pengde
Published: January 2018

This study aimed to determine whether bisphosphonates exert an effect on preventing femoral head collapse after osteonecrosis of the femoral head (ONFH) in an animal model and in clinical trials. A systematic literature search was performed for studies published up to January 2017. Twenty-three articles (16 animal studies, seven clinical trials) were included in the meta-analysis. We found that the bisphosphonate group obtained significant improvement in epiphyseal quotients (MD = 15.32; 95% CI, 9.25–21.39) and provided better performance on bone volume (SMD = 1.57; 95% CI, 0.94–2.20), trabecular number (SMD = 1.30; 95% CI, 0.80–1.79), trabecular thickness (SMD = 0.77; 95% CI, 0.10–1.43) and trabecular separation (SMD = −1.44; 95% CI, −1.70 to −0.58) in the animal model. However, the bisphosphonate group did not achieve better results in pain score, Harris score, the occurrence rate of femoral head collapse, or total hip arthroplasty in the clinical trials. In conclusion, despite bisphosphonates significantly improving bone remodeling outcomes in animal models, no significant efficacy was observed in the treatment of ONFH in the clinical studies. Further studies are required to solve the discordant outcomes between the animal and clinical studies.