bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Investigation of Environment-Noise Interaction in Single-Cell Organisms: The Merit of Expression Stochasticity Depends on the Quality of Environmental Fluctuations
Authors: Lück Anja , Klimmasch Lukas , Großmann Peter , Germerodt Sebastian , Kaleta Christoph
Published: January 2018

Organisms need to adapt to changing environments and they do so by using a broad spectrum of strategies. These strategies include finding the right balance between expressing genes before or when they are needed, and adjusting the degree of noise inherent in gene expression. We investigated the interplay between different nutritional environments and the inhabiting organisms’ metabolic and genetic adaptations by applying an evolutionary algorithm to an agent-based model of a concise bacterial metabolism. Our results show that constant environments and rapidly fluctuating environments produce similar adaptations in the organisms, making the predictability of the environment a major factor in determining optimal adaptation. We show that exploitation of expression noise occurs only in some types of fluctuating environment and is strongly dependent on the quality and availability of nutrients: stochasticity is generally detrimental in fluctuating environments and beneficial only at equal periods of nutrient availability and above a threshold environmental richness. Moreover, depending on the availability and nutritional value of nutrients, nutrient-dependent and stochastic expression are both strategies used to deal with environmental changes. Overall, we comprehensively characterize the interplay between the quality and periodicity of an environment and the resulting optimal deterministic and stochastic regulation strategies of nutrient-catabolizing pathways.
A Complex Network Approach for the Estimation of the Energy Demand of Electric Mobility
Authors: Mureddu Mario , Facchini Angelo , Scala Antonio , Caldarelli Guido , Damiano Alfonso
Published: January 2018

We study how renewable energy impacts regional infrastructures considering the full deployment of electric mobility at that scale. We use the Sardinia Island in Italy as a paradigmatic case study of a semi-closed system both by energy and mobility point of view. Human mobility patterns are estimated by means of census data listing the mobility dynamics of about 700,000 vehicles, the energy demand is estimated by modeling the charging behavior of electric vehicle owners. Here we show that current renewable energy production of Sardinia is able to sustain the commuter mobility even in the theoretical case of a full switch from internal combustion vehicles to electric ones. Centrality measures from network theory on the reconstructed network of commuter trips allows to identify the most important areas (hubs) involved in regional mobility. The analysis of the expected energy flows reveals long-range effects on infrastructures outside metropolitan areas and points out that the most relevant unbalances are caused by spatial segregation between production and consumption areas. Finally, results suggest the adoption of planning actions supporting the installation of renewable energy plants in areas mostly involved by the commuting mobility, avoiding spatial segregation between consumption and generation areas.
Publisher Correction: Exfoliated WS2-Nafion Composite based Electromechanical Actuators
Authors: Loeian Masoud S. , Ziolkowska Dominika A. , Khosravi Farhad , Jasinski Jacek B. , Panchapakesan Balaji
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Publisher Correction: Intra-colony disease progression induces fragmentation of coral fluorescent pigments
Authors: Caldwell Jamie M. , Ushijima Blake , Couch Courtney S. , Gates Ruth D.
Published: January 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
The Microwell-mesh: A high-throughput 3D prostate cancer spheroid and drug-testing platform
Authors: Mosaad E. O. , Chambers K. F. , Futrega K. , Clements J. A. , Doran M. R.
Published: January 2018

Treatment following early diagnosis of Prostate cancer (PCa) is increasingly successful, whilst the treatment of advanced and metastatic PCa remains challenging. A major limitation in the development of new therapies is the prediction of drug efficacy using in vitro models. Classic in vitro 2-dimensional (2D) cell monolayer cultures are hypersensitive to anti-cancer drugs. As a result, there has been a surge in the development of platforms that enable three dimensional (3D) cultures thought to better replicate natural physiology and better predict drug efficacy. A deficiency associated with most 3D culture systems is that their complexity reduces the number of replicates and combination therapies that can be feasibly evaluated. Herein, we describe the use of a microwell platform that utilises a nylon mesh to retain 3D micro-tumours in discrete microwells; termed the Microwell-mesh. The Microwell-mesh enables the manufacture of ~150 micro-tumours per well in a 48-well plate, and response to anti-tumour drugs can be readily quantified. Our results demonstrate that 3D micro-tumours, unlike 2D monolayers, are not hypersensitive to Docetaxel or Abiraterone Acetate, providing a superior platform for the evaluation of sequential drug treatment. In summary, the Microwell-mesh provides an efficient 3D micro-tumour platform for single and sequential drug screening.
Complex Formation via Hydrogen bonding between Rhodamine B and Montmorillonite in Aqueous Solution
Authors: Fang Yanfen , Zhou Ao , Yang Wei , Araya Tirusew , Huang Yingping , Zhao Ping , Johnson David , Wang Jianzhu , Ren Zhiyong Jason
Published: January 2018

This study investigates the adsorption mechanism differences among four nitrogenous dyes, sulforhodamine G (SRG), uncharged/deprotonated rhodamine B (RhB), orange II (Or II) and methyl blue (MB) by montmorillonite (MMT). MMT adsorption capacity for cationic MB was three times that of uncharged RhB and anionic SRG, while anionic Or II was not absorbed. Colloidal MMT particles have two types of surfaces, basal and edge, that interact with nitrogenous dyes very differently. The surface acidity of MMT was characterized with the pyridine adsorption method using in-situ diffuse reflectance infrared Fourier transform spectroscopy (in-situ DRIFTS). Adsorption of cationic MB was compared with the adsorption of RhB. In-situ attenuated total reflectance Fourier transform infrared (in-situ ATR-FTIR) spectroscopy indicated that a nitrogen atom on RhB complexes with a metal hydroxyl on an MMT edge through a water bridge. The highly polar edge hydroxyl is important to hydrogen bond formation. Cation ion exchange and washing experiments, as well as studies on the effect of temperature, pH and ionic strength on adsorption further clarified the adsorption mechanism. Our results provide insights into the effects of molecular structure on the adsorption of nitrogenous dyes by clay and the role of edge surfaces in the adsorption process.
Giant electrocaloric effect in a wide temperature range in PbTiO3 nanoparticle with double-vortex domain structure
Authors: Ye C. , Wang J. B. , Li B. , Zhong X. L.
Published: January 2018

Electrocaloric effect (ECE) has the potential applications in solid-state refrigeration with the features of high efficiency and environmentally friendly. Large adiabatic temperature change in a wide temperature range is needed for electrocaloric effect to meet the requirement of commercially application. In this work, giant electrocaloric effect is found in PbTiO3 nanoparticle with double-vortex domain structure in a wide temperature range by using phase field method, which the lowest and highest adiabatic temperature change (ΔT) is 7.2 K and 16.5 K, respectively. The influence of misfit strain on the ECE of PbTiO3 nanoparticle with the double-vortex domain structure is investigated, and results show that the compress misfit strain can enhance the ECE, but the tensile misfit strain reduces the ECE. This work reveals a way to obtain giant ECE of ferroelectric materials by domain engineering and strain engineering in a wide temperature range.
Magnetisation process in the rare earth tetraborides, NdB4 and HoB4
Authors: Brunt D. , Balakrishnan G. , Mayoh D. A. , Lees M. R. , Gorbunov D. , Qureshi N. , Petrenko O. A.
Published: January 2018

A field-induced magnetisation process in the frustrated antiferromagnets is often much richer compared to the materials without competing interactions. The applied field tends to stabilise unusual spin configurations which frequently results in the appearance of magnetisation plateaux. Here we report a study into the field-induced magnetisation of the two frustrated rare earth tetraborides, HoB4and NdB4. NdB4shows a fractional magnetisation plateau occurring atM/Msat ≈ $$\tfrac{{\bf{1}}}{{\bf{5}}}$$15before saturating in a field of 33 kOe. On cooling down to 0.5 K the temperature dependent susceptibility of NdB4shows an unconventional transition where the system returns to the zero field antiferromagnetic state from a higher-temperature ferrimagnetic state. We are able to reconstruct the magnetic phase diagram of NdB4from the magnetisation, susceptibility and resistivity measurements for bothH $$\parallel $$∥ candH ⊥ c. For HoB4, the most interesting behaviour is found at the lowest temperature of 0.5 K, where the field dependent magnetisation demonstrates a new fractional$$\tfrac{{\bf{1}}}{{\bf{2}}}$$12-magnetisation plateau. Further insight into the relations between the exchange interactions and single ion effects is gained through high-field magnetisation measurements in both HoB4and NdB4.
Highly selective and sensitive macrocycle-based dinuclear foldamer for fluorometric and colorimetric sensing of citrate in water
Authors: Rhaman Md Mhahabubur , Hasan Mohammad H. , Alamgir Azmain , Xu Lihua , Powell Douglas R. , Wong Bryan M. , Tandon Ritesh , Hossain Md. Alamgir
Published: January 2018

The selective detection of citrate anions is essential for various biological functions in living systems. A quantitative assessment of citrate is required for the diagnosis of various diseases in the human body; however, it is extremely challenging to develop efficient fluorescence and color-detecting molecular probes for sensing citrate in water. Herein, we report a macrocycle-based dinuclear foldamer (1) assembled with eosin Y (EY) that has been studied for anion binding by fluorescence and colorimetric techniques in water at neutral pH. Results from the fluorescence titrations reveal that the 1·EY ensemble strongly binds citrate anions, showing remarkable selectivity over a wide range of inorganic and carboxylate anions. The addition of citrate anions to the 1·EY adduct led to a large fluorescence enhancement, displaying a detectable color change under both visible and UV light in water up to 2 μmol. The biocompatibility of 1·EY as an intracellular carrier in a biological system was evaluated on primary human foreskin fibroblast (HF) cells, showing an excellent cell viability. The strong binding properties of the ensemble allow it to be used as a highly sensitive, detective probe for biologically relevant citrate anions in various applications.
Structural ensemble-based docking simulation and biophysical studies discovered new inhibitors of Hsp90 N-terminal domain
Authors: Kim Hyun-Hwi , Hyun Ja-Shil , Choi Joonhyeok , Choi Kwang-Eun , Jee Jun-Goo , Park Sung Jean
Published: January 2018

Heat shock protein 90 (Hsp90) is one of the most abundant cellular proteins and plays a substantial role in the folding of client proteins. The inhibition of Hsp90 has been regarded as an attractive therapeutic strategy for treating cancer because many oncogenic kinases are Hsp90 client proteins. In this study, we report new inhibitors that directly bind to N-terminal ATP-binding pocket of Hsp90. Optimized structure-based virtual screening predicted candidate molecules, which was followed by confirmation using biophysical and cell-based assays. Among the reported crystal structures, we chose the two structures that show the most favourable early enrichments of true-positives in the receiver operating characteristic curve. Four molecules showed significant changes in the signals of 2D [1H,15N] correlation NMR spectroscopy. Differential scanning calorimetry analysis supported the results indicating direct binding. Quantified dissociation constant values of the molecules, determined by a series of 2D NMR experiments, lie in the range of 0.1–33 μM. Growth inhibition assay with breast and lung cancer cells confirmed the cellular activities of the molecules. Cheminformatics revealed that the molecules share limited chemical similarities with known inhibitors. Molecular dynamics simulations detailed the putative binding modes of the inhibitors.
The chemical armament of reef-building corals: inter- and intra-specific variation and the identification of an unusual actinoporin in Stylophora pistilata
Authors: Ben-Ari Hanit , Paz Moran , Sher Daniel
Published: January 2018

Corals, like other cnidarians, are venomous animals that rely on stinging cells (nematocytes) and their toxins to catch prey and defend themselves against predators. However, little is known about the chemical arsenal employed by stony corals, despite their ecological importance. Here, we show large differences in the density of nematocysts and whole-body hemolytic activity between different species of reef-building corals. In the branched coral Stylophora pistillata, the tips of the branches exhibited a greater hemolytic activity than the bases. Hemolytic activity and nematocyst density were significantly lower in Stylophora that were maintained for close to a year in captivity compared to corals collected from the wild. A cysteine-containing actinoporin was identified in Stylophora following partial purification and tandem mass spectrometry. This toxin, named Δ-Pocilopotoxin-Spi1 (Δ-PCTX-Spi1) is the first hemolytic toxin to be partially isolated and characterized in true reef-building corals. Loss of hemolytic activity during chromatography suggests that this actinoporin is only one of potentially several hemolytic molecules. These results suggest that the capacity to employ offensive and defensive chemicals by corals is a dynamic trait within and between coral species, and provide a first step towards identifying the molecular components of the coral chemical armament.
Interference of chemical defence and sexual communication can shape the evolution of chemical signals
Authors: Pfeiffer Lisa , Ruther Joachim , Hofferberth John , Stökl Johannes
Published: January 2018

According to current evolutionary theory, insect pheromones can originate from extant precursor compounds being selected for information transfer. This is exemplified by females of the parasitoid wasp Leptopilina heterotoma whose defensive secretion consisting mainly of (−)-iridomyrmecin has evolved secondary functions as cue to avoid other females during host search and as female sex pheromone. To promote our understanding of pheromone evolution from defensive secretions we studied the chemical ecology of Leptopilina clavipes. We show here that L. clavipes also produces a defensive secretion that contains (−)-iridomyrmecin as major component and that females use it to detect and avoid host patches occupied by other females. However, the female sex pheromone of L. clavipes consists solely of cuticular hydrocarbons (CHCs) and males did not respond to female CHCs if presented in combination with the defensive secretion containing (−)-iridomyrmecin. This is in contrast to other species of Leptopilina, in which the iridoid compounds have no inhibiting effect or even function as sex pheromone triggering courtship behaviour. This indicates that Leptopilina species differ in the cost-benefit ratio for males searching for females, which might explain the strong divergence in the composition of the sex pheromone in the genus.
CRISPR/Cas9-mediated gene modification and gene knock out in the human-infective parasite Trichomonas vaginalis
Authors: Janssen Brian D. , Chen Yi-Pei , Molgora Brenda M. , Wang Shuqi E. , Simoes-Barbosa Augusto , Johnson Patricia J.
Published: January 2018

The sexually-transmitted parasite Trichomonas vaginalis infects ~1/4 billion people worldwide. Despite its prevalence and myriad adverse outcomes of infection, the mechanisms underlying T. vaginalis pathogenesis are poorly understood. Genetic manipulation of this single-celled eukaryote has been hindered by challenges presented by its complex, repetitive genome and inefficient methods for introducing DNA (i.e. transfection) into the parasite. Here, we have developed methods to increase transfection efficiency using nucleofection, with the goal of efficiently introducing multiple DNA elements into a single T. vaginalis cell. We then created DNA constructs required to express several components essential to drive CRISPR/Cas9-mediated DNA modification: guide RNA (gRNA), the Cas9 endonuclease, short oligonucleotides and large, linearized DNA templates. Using these technical advances, we have established CRISPR/Cas9-mediated repair of mutations in genes contained on circular DNA plasmids harbored by the parasite. We also engineered CRISPR/Cas9 directed homologous recombination to delete (i.e. knock out) two non-essential genes within the T. vaginalis genome. This first report of the use of the CRISPR/Cas9 system in T. vaginalis greatly expands the ability to manipulate the genome of this pathogen and sets the stage for testing of the role of specific genes in many biological processes.
Fourier Transform Infrared Microscopy Enables Guidance of Automated Mass Spectrometry Imaging to Predefined Tissue Morphologies
Authors: Rabe Jan-Hinrich , A. Sammour Denis , Schulz Sandra , Munteanu Bogdan , Ott Martina , Ochs Katharina , Hohenberger Peter , Marx Alexander , Platten Michael , Opitz Christiane A. , Ory Daniel S. , Hopf Carsten
Published: January 2018

Multimodal imaging combines complementary platforms for spatially resolved tissue analysis that are poised for application in life science and personalized medicine. Unlike established clinical in vivo multimodality imaging, automated workflows for in-depth multimodal molecular ex vivo tissue analysis that combine the speed and ease of spectroscopic imaging with molecular details provided by mass spectrometry imaging (MSI) are lagging behind. Here, we present an integrated approach that utilizes non-destructive Fourier transform infrared (FTIR) microscopy and matrix assisted laser desorption/ionization (MALDI) MSI for analysing single-slide tissue specimen. We show that FTIR microscopy can automatically guide high-resolution MSI data acquisition and interpretation without requiring prior histopathological tissue annotation, thus circumventing potential human-annotation-bias while achieving >90% reductions of data load and acquisition time. We apply FTIR imaging as an upstream modality to improve accuracy of tissue-morphology detection and to retrieve diagnostic molecular signatures in an automated, unbiased and spatially aware manner. We show the general applicability of multimodal FTIR-guided MALDI-MSI by demonstrating precise tumor localization in mouse brain bearing glioma xenografts and in human primary gastrointestinal stromal tumors. Finally, the presented multimodal tissue analysis method allows for morphology-sensitive lipid signature retrieval from brains of mice suffering from lipidosis caused by Niemann-Pick type C disease.
RNA-Seq analysis and comparison of corneal epithelium in keratoconus and myopia patients
Authors: You Jingjing , Corley Susan M. , Wen Li , Hodge Chris , Höllhumer Roland , Madigan Michele C. , Wilkins Marc R. , Sutton Gerard
Published: January 2018

Keratoconus is a common degenerative corneal disease that can lead to significant visual morbidity, and both genetic and environmental factors have been implicated in its pathogenesis. We compared the transcriptome of keratoconus and control epithelium using RNA-Seq. Epithelial tissues were obtained prior to surgery from keratoconus and myopia control patients, undergoing collagen cross-linking and photorefractive keratectomy, respectively. We identified major differences in keratoconus linked to cell-cell communication, cell signalling and cellular metabolism. The genes associated with the Hedgehog, Wnt and Notch1 signaling pathways were down-regulated in keratoconus. We also identified plasmolipin and Notch1 as being significantly reduced in keratoconus for both gene and protein expression (p < 0.05). Plasmolipin is a novel protein identified in human corneal epithelium, and has been demonstrated to have a key role in epithelial cell differentiation in other tissues. This study shows altered gene and protein expression of these three proteins in keratoconus, and further studies are clearly warranted to confirm the functional role of these proteins in the pathogenesis of keratoconus.
Engineered mesenchymal stem-cell-sheets patches prevents postoperative pancreatic leakage in a rat model
Authors: Kim Seong-Ryong , Yi Hye-Jin , Lee Yu Na , Park Ji Yoon , Hoffman Robert M. , Okano Teruo , Shim In Kyong , Kim Song Cheol
Published: January 2018

Post-operative pancreatic fistula (POPF) following pancreatic resection is a life-threatening surgical complication. Cell sheets were prepared and harvested using temperature-responsive culture dishes and transplanted as patches to seal POPF. Two different mesenchymal stem cell (MSC) sheets were compared in terms of the preventative ability for pancreatic leakage in a rat model. Both rat adipose-derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus maintained their cell-cell junctions and adhesion proteins with intact fibronectin on the basal side, as well as characteristics of MSCs. The rats with post-pancreatectomy rADSC- or rBMSC-sheet patches had significantly decreased abdominal fluid leakage compared with the control group, demonstrated by MR image analysis and measurement of the volume of abdominal fluid. Amylase level was significantly lower in the rats with rADSC-sheet and rBMSC-sheet patches compared with the control groups. The rADSC sheet patches had increased adhesive and immune-cytokine profiles (ICAM-1, L-selectin, TIMP-1), and the rBMSC sheets had reduced immune reactions compared to the control. This is first project looking at the feasibility of tissue engineering therapy using MSC-sheets as tissue patches preventing leakage of abdominal fluid caused by POPF.
Domain swapping and SMYD1 interactions with the PWWP domain of human hepatoma-derived growth factor
Authors: Chen Li-Ying , Huang Yen-Chieh , Huang Shih-Tsung , Hsieh Yin-Cheng , Guan Hong-Hsiang , Chen Nai-Chi , Chuankhayan Phimonphan , Yoshimura Masato , Tai Ming-Hong , Chen Chun-Jung
Published: January 2018

The human hepatoma-derived growth factor (HDGF), containing the chromatin-associated N-terminal PWWP domain capable of binding the SMYD1 promoter, participates in various cellular processes and is involved in human cancers. We report the first crystal structures of the human HDGF PWWP domain (residues 1–100) in a complex with SMYD1 of 10 bp at 2.84 Å resolution and its apo form at 3.3 Å, respectively. The structure of the apo PWWP domain comprises mainly four β-strands and two α-helices. The PWWP domain undergoes domain swapping to dramatically transform its secondary structures, altering the overall conformation from monomeric globular folding into an extended dimeric structure upon DNA binding. The flexible loop2, as a hinge loop with the partially built structure in the apo PWWP domain, notably refolds into a visible and stable α-helix in the DNA complex. The swapped PWWP domain interacts with the minor grooves of the DNA through residues Lys19, Gly22, Arg79 and Lys80 in varied ways on loops 1 and 4 of the two chains, and the structure becomes more rigid than the apo form. These novel structural findings, together with physiological and activity assays of HDGF and the PWWP domain, provide new insights into the DNA-binding mechanism of HDGF during nucleosomal functions.
Contrasting patterns of leaf trait variation among and within species during tropical dry forest succession in Costa Rica
Authors: Derroire Géraldine , Powers Jennifer S. , Hulshof Catherine M. , Cárdenas Varela Luis E. , Healey John R.
Published: January 2018

A coordinated response to environmental drivers amongst individual functional traits is central to the plant strategy concept. However, whether the trait co-ordination observed at the global scale occurs at other ecological scales (especially within species) remains an open question. Here, for sapling communities of two tropical dry forest types in Costa Rica, we show large differences amongst traits in the relative contribution of species turnover and intraspecific variation to their directional changes in response to environmental changes along a successional gradient. We studied the response of functional traits associated with the leaf economics spectrum and drought tolerance using intensive sampling to analyse inter- and intra-specific responses to environmental changes and ontogeny. Although the overall functional composition of the sapling communities changed during succession more through species turnover than through intraspecific trait variation, their relative contributions differed greatly amongst traits. For instance, community mean specific leaf area changed mostly due to intraspecific variation. Traits of the leaf economics spectrum showed decoupled responses to environmental drivers and ontogeny. These findings emphasise how divergent ecological mechanisms combine to cause great differences in changes of individual functional traits over environmental gradients and ecological scales.
Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas
Authors: Lee Ting-Fang , Tseng Yu-Chi , Nguyen Phung Anh , Li Yu-Chuan , Ho Chao-Chi , Wu Cheng-Wen
Published: January 2018

Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as an effective targeted therapy in lung adenocarcinoma, but drug resistance and tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has been reported to promote multiple cancer cell properties, such as promoting cell proliferation, epithelial-mesenchymal transition and drug resistance. This study investigated the roles of YAP in TKI-resistant lung adenocarcinoma. In TKI-sensitive cells, enhanced YAP expression leads to TKI resistant. Also, upregulated YAP expression and activation were detected in long-term TKI-induced resistant cells. With reduced YAP expression using shRNA or YAP inhibitors, TKI-resistant cells become TKI-sensitive. reduced xenograft tumor size in nude mice and Moreover, combined EGFR TKI and a YAP inhibitor, statin, prolonged survival among lung cancer patients analyzed by Taiwan National Health Insurance Research database. These observations revealed the importance of YAP in promoting TKI-resistance and combined YAP inhibition can be a potential therapy delaying the occurrence of TKI-resistance in lung adenocarcinoma.
MicroRNA-7 mediates cross-talk between metabolic signaling pathways in the liver
Authors: Singaravelu Ragunath , Quan Curtis , Powdrill Megan H. , Shaw Tyler A. , Srinivasan Prashanth , Lyn Rodney K. , Alonzi Rhea C. , Jones Daniel M. , Filip Roxana , Russell Rodney S. , Pezacki John P.
Published: January 2018

MicroRNAs (miRNAs) have emerged as critical regulators of cellular metabolism. To characterise miRNAs crucial to the maintenance of hepatic lipid homeostasis, we examined the overlap between the miRNA signature associated with inhibition of peroxisome proliferator activated receptor-α (PPAR-α) signaling, a pathway regulating fatty acid metabolism, and the miRNA profile associated with 25-hydroxycholesterol treatment, an oxysterol regulator of sterol regulatory element binding protein (SREBP) and liver X receptor (LXR) signaling. Using this strategy, we identified microRNA-7 (miR-7) as a PPAR-α regulated miRNA, which activates SREBP signaling and promotes hepatocellular lipid accumulation. This is mediated, in part, by suppression of the negative regulator of SREBP signaling: ERLIN2. miR-7 also regulates genes associated with PPAR signaling and sterol metabolism, including liver X receptor β (LXR-β), a transcriptional regulator of sterol synthesis, efflux, and excretion. Collectively, our findings highlight miR-7 as a novel mediator of cross-talk between PPAR, SREBP, and LXR signaling pathways in the liver.
Novel haemodialysis (HD) treatment employing molecular hydrogen (H2)-enriched dialysis solution improves prognosis of chronic dialysis patients: A prospective observational study
Authors: Nakayama Masaaki , Itami Noritomo , Suzuki Hodaka , Hamada Hiromi , Yamamoto Ryo , Tsunoda Kazumasa , Osaka Naoyuki , Nakano Hirofumi , Maruyama Yukio , Kabayama Shigeru , Nakazawa Ryoichi , Miyazaki Mariko , Ito Sadayoshi
Published: January 2018

Recent studies have revealed unique biological characteristics of molecular hydrogen (H2) as an anti-inflammatory agent. We developed a novel haemodialysis (E-HD) system delivering an H2 (30–80 ppb)-enriched dialysis solution by water electrolysis, and conducted a non-randomized, non-blinded, prospective observational study exploring its clinical impact. Prevalent chronic HD patients were allocated to either the E-HD (n = 161) group or the conventional HD (C-HD: n = 148) group, and received the respective HD treatments during the study. The primary endpoint was a composite of all-cause mortality and development of non-lethal cardio-cerebrovascular events (cardiac disease, apoplexy, and leg amputation due to peripheral artery disease). During the 3.28-year mean observation period, there were no differences in dialysis parameters between the two groups; however, post-dialysis hypertension was ameliorated with significant reductions in antihypertensive agents in the E-HD patients. There were 91 events (50 in the C-HD group and 41 in the E-HD group). Multivariate analysis of the Cox proportional hazards model revealed E-HD as an independent significant factor for the primary endpoint (hazard ratio 0.59; [95% confidence interval: 0.38–0.92]) after adjusting for confounding factors (age, cardiovascular disease history, serum albumin, and C-reactive protein). HD applying an H2-dissolved HD solution could improve the prognosis of chronic HD patients.
Innate IFN-γ ameliorates experimental autoimmune encephalomyelitis and promotes myeloid expansion and PDL-1 expression
Authors: White Madeleine P. J. , Webster Gill , Leonard Faith , La Flamme Anne Camille
Published: January 2018

The innate immune system plays a central role in the immune-mediated pathology of multiple sclerosis, and is a therapeutic target for progressive disease. Recently, it has been demonstrated that MIS416, a novel immunomodulatory microparticle that activates NOD-2 and TLR-9-signaling, has disease-modifying activity in multiple sclerosis models. This activity is dependent on innate IFN-γ; however, the precise immune regulatory mechanisms amplified by MIS416 have not previously been determined. Using the experimental autoimmune encephalomyelitis model, MIS416 treatment was associated with IFN-γ–dependant expansion of Treg number and increased suppressive function; however, these cells did not account for disease reduction. Additionally, MIS416 treatment stimulated increased nitric oxide production that was IFN-γ–dependant but dispensable for protection. Finally, MIS416-mediated protection was shown to correlate with IFN-γ–dependant expansion of PDL-1-expressing peripheral myeloid cells, a subset of which was found to be selectively recruited to the brain. This central nervous system trafficking was independent of neuro-inflammatory signals as it occurred in MIS416-treated healthy mice. Together, these findings provide insight into regulatory myeloid cell activities amplified by MIS416-mediated NOD-2 and TLR-9 signalling and highlight the potential importance of these cells in accessing the brain where they may act locally and contribute to the control of neuroinflammation.
Mathematical model of salt cavern leaching for gas storage in high-insoluble salt formations
Authors: Li Jinlong , Shi Xilin , Yang Chunhe , Li Yinping , Wang Tongtao , Ma Hongling
Published: January 2018

A mathematical model is established to predict the salt cavern development during leaching in high-insoluble salt formations. The salt-brine mass transfer rate is introduced, and the effects of the insoluble sediments on the development of the cavern are included. Considering the salt mass conservation in the cavern, the couple equations of the cavern shape, brine concentration and brine velocity are derived. According to the falling and accumulating rules of the insoluble particles, the governing equations of the insoluble sediments are deduced. A computer program using VC++ language is developed to obtain the numerical solution of these equations. To verify the proposed model, the leaching processes of two salt caverns of Jintan underground gas storage are simulated by the program, using the actual geological and technological parameters. The same simulation is performed by the current mainstream leaching software in China. The simulation results of the two programs are compared with the available field data. It shows that the proposed software is more accurate on the shape prediction of the cavern bottom and roof, which demonstrates the reliability and applicability of the model.
Perception during double-step saccades
Authors: Zimmermann E. , Morrone M. C. , Binda P.
Published: January 2018

How the visual system achieves perceptual stability across saccadic eye movements is a long-standing question in neuroscience. It has been proposed that an efference copy informs vision about upcoming saccades, and this might lead to shifting spatial coordinates and suppressing image motion. Here we ask whether these two aspects of visual stability are interdependent or may be dissociated under special conditions. We study a memory-guided double-step saccade task, where two saccades are executed in quick succession. Previous studies have led to the hypothesis that in this paradigm the two saccades are planned in parallel, with a single efference copy signal generated at the start of the double-step sequence, i.e. before the first saccade. In line with this hypothesis, we find that visual stability is impaired during the second saccade, which is consistent with (accurate) efference copy information being unavailable during the second saccade. However, we find that saccadic suppression is normal during the second saccade. Thus, the second saccade of a double-step sequence instantiates a dissociation between visual stability and saccadic suppression: stability is impaired even though suppression is strong.
A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis
Authors: Roach Katy M. , Sutcliffe Amanda , Matthews Laura , Elliott Gill , Newby Chris , Amrani Yassine , Bradding Peter
Published: January 2018

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with limited therapeutic options. KCa3.1 ion channels play a critical role in TGFβ1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed to develop a human lung parenchymal model of fibrogenesis and test the efficacy of the selective KCa3.1 blocker senicapoc. 2 mm3 pieces of human lung parenchyma were cultured for 7 days in DMEM ± TGFβ1 (10 ng/ml) and pro-fibrotic pathways examined by RT-PCR, immunohistochemistry and collagen secretion. Following 7 days of culture with TGFβ1, 41 IPF- and fibrosis-associated genes were significantly upregulated. Immunohistochemical staining demonstrated increased expression of ECM proteins and fibroblast-specific protein after TGFβ1-stimulation. Collagen secretion was significantly increased following TGFβ1-stimulation. These pro-fibrotic responses were attenuated by senicapoc, but not by dexamethasone. This 7 day ex vivo model of human lung fibrogenesis recapitulates pro-fibrotic events evident in IPF and is sensitive to KCa3.1 channel inhibition. By maintaining the complex cell-cell and cell-matrix interactions of human tissue, and removing cross-species heterogeneity, this model may better predict drug efficacy in clinical trials and accelerate drug development in IPF. KCa3.1 channels are a promising target for the treatment of IPF.
N-domain of angiotensin-converting enzyme hydrolyzes human and rat amyloid-β(1-16) peptides as arginine specific endopeptidase potentially enhancing risk of Alzheimer’s disease
Authors: Kugaevskaya Elena V. , Veselovsky Alexander V. , Indeykina Maria I. , Solovyeva Nina I. , Zharkova Maria S. , Popov Igor A. , Nikolaev Eugene N. , Mantsyzov Alexey B. , Makarov Alexander A. , Kozin Sergey A.
Published: January 2018

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder. Amyloid-β (Aβ) aggregation is likely to be the major cause of AD. In contrast to humans and other mammals, that share the same Aβ sequence, rats and mice are invulnerable to AD-like neurodegenerative pathologies, and Aβ of these rodents (ratAβ) has three amino acid substitutions in the metal-binding domain 1-16 (MBD). Angiotensin-converting enzyme (ACE) cleaves Aβ-derived peptide substrates, however, there are contradictions concerning the localization of the cleavage sites within Aβ and the roles of each of the two ACE catalytically active domains in the hydrolysis. In the current study by using mass spectrometry and molecular modelling we have tested a set of peptides corresponding to MBDs of Aβ and ratAβ to get insights on the interactions between ACE and these Aβ species. It has been shown that the N-domain of ACE (N-ACE) acts as an arginine specific endopeptidase on the Aβ and ratAβ MBDs with C-amidated termini, thus assuming that full-length Aβ and ratAβ can be hydrolyzed by N-ACE in the same endopeptidase mode. Taken together with the recent data on the molecular mechanism of zinc-dependent oligomerization of Aβ, our results suggest a modulating role of N-ACE in AD pathogenesis.
Site-specific randomization of the endogenous genome by a regulatable CRISPR-Cas9 piggyBac system in human cells
Authors: Ishida Kentaro , Xu Huaigeng , Sasakawa Noriko , Lung Mandy Siu Yu , Kudryashev Julia Alexandra , Gee Peter , Hotta Akitsu
Published: January 2018

Randomized mutagenesis at an endogenous chromosomal locus is a promising approach for protein engineering, functional assessment of regulatory elements, and modeling genetic variations. In mammalian cells, however, it is challenging to perform site-specific single-nucleotide substitution with single-stranded oligodeoxynucleotide (ssODN) donor templates due to insufficient homologous recombination and the infeasibility of positive selection. Here, we developed a DNA transposon based CRISPR-Cas9 regulated transcription and nuclear shuttling (CRONUS) system that enables the stable transduction of CRISPR-Cas9/sgRNA in broad cell types, but avoids undesired genome cleavage in the absence two chemical inducing molecules. Highly efficient single nucleotide alterations induced randomization of desired codons (up to 4 codons) at a defined genomic locus in various human cell lines, including human iPS cells. Thus, CRONUS provides a novel platform for modeling diseases and genetic variations.
Evaluation of in vivo digital root reconstruction based on anatomical characteristics of the periodontal ligament using cone beam computed tomography
Authors: Wang Chenxin , Liu Yi , Wang Siwei , Wang Yong , Zhao Yijiao
Published: January 2018

This study’s aim was to develop and validate an approach to automatically extract and reconstruct three-dimensional (3D) digital root models from in vivo teeth based on the anatomical characteristics of the periodontal ligament using cone beam computed tomography (CBCT) data. Prior to undergoing dental extractions for orthodontic purposes, the CBCT data of each study participant were collected and imported into Mimics software to reconstruct 3D in vivo digital root models (test models). Twenty roots of 17 teeth extracted from the study’s participants were scanned using a dental scanner to obtain 3D in vitro digital root models (reference models). The 3D morphological deviation between the reference and test models was compared; the 3D size of the bucco-lingual, mesio-distal, and root length dimensions were calculated. This approach achieved an average 3D morphological deviation of 0.21 mm, and the average size error in the bucco-lingual, mesio-distal, and root length dimensions were −0.35 mm, −0.17 mm, and 0.47 mm, respectively. This new automatic extraction approach rapidly and accurately reconstructs 3D in vivo root models with detailed morphological information, and has the potential to improve diagnostic and treatment work flow in orthodontic clinics, as well as in other areas of dentistry.
Ultraviolet-B enhances the resistance of multiple plant species to lepidopteran insect herbivory through the jasmonic acid pathway
Authors: Qi Jinfeng , Zhang Mou , Lu Chengkai , Hettenhausen Christian , Tan Qing , Cao Guoyan , Zhu Xudong , Wu Guoxing , Wu Jianqiang
Published: January 2018

Land plants protect themselves from ultraviolet-B (UV-B) by accumulating UV-absorbing metabolites, which may also function as anti-insect toxins. Previous studies have shown that UV-B enhances the resistance of different plant species to pierce-sucking pests; however, whether and how UV-B influences plant defense against chewing caterpillars are not well understood. Here we show that UV-B treatment increased Spodoptera litura herbivory-induced jasmonic acid (JA) production in Arabidopsis and thereby Arabidopsis exhibited elevated resistance to S. litura. Using mutants impaired in the biosynthesis of JA and the defensive metabolites glucosinolates (GSs), we show that the UV-B-induced resistance to S. litura is dependent on the JA-regulated GSs and an unidentified anti-insect metabolite(s). Similarly, UV-B treatment also enhanced the levels of JA-isoleucine conjugate and defense-related secondary metabolites in tobacco, rice, and maize after these plants were treated with simulated herbivory of lepidopteran insects; consistently, these plants showed elevated resistance to insect larvae. Using transgenic plants impaired in JA biosynthesis or signaling, we further demonstrate that the UV-B-enhanced defense responses also require the JA pathway in tobacco and rice. Our findings reveal a likely conserved JA-dependent mechanism by which UV-B enhances plant defense against lepidopteran insects.
Impact of climate change and human activity on soil landscapes over the past 12,300 years
Authors: Rothacker Leo , Dosseto Anthony , Francke Alexander , Chivas Allan R. , Vigier Nathalie , Kotarba-Morley Anna M. , Menozzi Davide
Published: January 2018

Soils are key to ecosystems and human societies, and their critical importance requires a better understanding of how they evolve through time. However, identifying the role of natural climate change versus human activity (e.g. agriculture) on soil evolution is difficult. Here we show that for most of the past 12,300 years soil erosion and development were impacted differently by natural climate variability, as recorded by sediments deposited in Lake Dojran (Macedonia/Greece): short-lived ( < 1,000 years) climatic shifts had no effect on soil development but impacted soil erosion. This decoupling disappeared between 3,500 and 3,100 years ago, when the sedimentary record suggests an unprecedented erosion event associated with the development of agriculture in the region. Our results show unambiguously how differently soils evolved under natural climate variability (between 12,300 and 3,500 years ago) and later in response to intensifying human impact. The transition from natural to anthropogenic landscape started just before, or at, the onset of the Greek ‘Dark Ages’ (~3,200 cal yr BP). This could represent the earliest recorded sign of a negative feedback between civilization and environmental impact, where the development of agriculture impacted soil resources, which in turn resulted in a slowdown of civilization expansion.
Alleviation of drought stress in Phyllostachys edulis by N and P application
Authors: Wu Zhi Zhuang , Ying Ye Qing , Zhang Yuan Bin , Bi Yu Fang , Wang An Ke , Du Xu Hua
Published: January 2018

The aim of this study was to explore whether nutrition supply can improve the drought tolerance of Moso bamboo under dry conditions. One-year-old seedlings were exposed to two soil water content levels [wellwatered, 70 ± 5% soil-relative-water-content (SRWC) and drought stress, 30 ± 5% SRWC] and four combinations of nitrogen (N) and phosphorus (P) supply (low-N, low-P, LNLP; low-N, high-P, LNHP; high-N, high-P, HNHP; and high-N, low-P, HNLP) for four months. Plant growth, photosynthesis, chlorophyll fluorescence, water use efficiency and cell membrane stability were determined. The results showed that drought stress significantly decreased total biomass, net-photosynthesis (Pn), stomatal-conductance (gs), leaf-chlorophyll-content (Chlleaf), PSII-quantum-yield (ΦPSII), maximum-quantum-yield-of-photosynthesis (Fv/Fm), photochemical-quenching-coefficient (qP), leaf-instantaneous-water-use efficiency (WUEi), relative-water-content (RWC), photosynthetic-N-use-efficiency (PNUE), and photosynthetic-P-use-efficiency (PPUE). N and P application was found to be effective in enhancing the concentration of leaf N, gs, and Pn while reducing the production of reactive oxygen species under both water regimes. Under LNHP, HNHP and HNLP treatments, the decreases in total biomass, Pn, Chlleaf and Fv/Fm of drought-stressed were less evident than the decreases under LNLP. The study suggests that nutrient application has the potential to mitigate the drastic effects of water stress on Moso bamboo by improving photosynthetic rate, water-use efficiency, and increasing of membrane integrity.
New insights on basivenal sclerites using 3D tools and homology of wing veins in Odonatoptera (Insecta)
Authors: Jacquelin Lauriane , Desutter-Grandcolas Laure , Chintauan-Marquier Ioana , Boistel Renaud , Zheng Daran , Prokop Jakub , Nel André
Published: January 2018

Being implied in flight, mimetism, communication, and protection, the insect wings were crucial organs for the mega diversification of this clade. Despite several attempts, the problem of wing evolution remains unresolved because the basal parts of the veins essential for vein identification are hidden in the basivenal sclerites. The homologies between wing characters thus cannot be accurately verified, while they are of primary importance to solve long-standing problems, such as the monophyly of the Palaeoptera, viz. Odonatoptera, Panephemeroptera, and Palaeozoic Palaeodictyopterida mainly known by their wings. Hitherto the tools to homologize venation were suffering several cases of exceptions, rendering them unreliable. Here we reconstruct the odonatopteran venation using fossils and a new 3D imaging tool, resulting congruent with the concept of Riek and Kukalová-Peck, with important novelties, viz. median anterior vein fused to radius and radius posterior nearly as convex as radius anterior (putative synapomorphies of Odonatoptera); subcostal anterior (ScA) fused to costal vein and most basal primary antenodal crossvein being a modified posterior branch of ScA (putative synapomorphies of Palaeoptera). These findings may reveal critical for future analyses of the relationships between fossil and extant Palaeoptera, helping to solve the evolutionary history of the insects as a whole.