Green and Sustainable Separation of Natural Products from Agro-Industrial Waste: Challenges, Potentialities, and Perspectives on Emerging Approaches Top. Curr. Chem. (IF 4.033) Pub Date : 2018-01-17 Vânia G. Zuin, Luize Z. Ramin
New generations of biorefinery combine innovative biomass waste resources from different origins, chemical extraction and/or synthesis of biomaterials, biofuels, and bioenergy via green and sustainable processes. From the very beginning, identifying and evaluating all potentially high value-added chemicals that could be removed from available renewable feedstocks requires robust, efficient, selective, reproducible, and benign analytical approaches. With this in mind, green and sustainable separation of natural products from agro-industrial waste is clearly attractive considering both socio-environmental and economic aspects. In this paper, the concepts of green and sustainable separation of natural products will be discussed, highlighting the main studies conducted on this topic over the last 10 years. The principal analytical techniques (such as solvent, microwave, ultrasound, and supercritical treatments), by-products (e.g., citrus, coffee, corn, and sugarcane waste) and target compounds (polyphenols, proteins, essential oils, etc.) will be presented, including the emerging green and sustainable separation approaches towards bioeconomy and circular economy contexts.
Oxidation of SQSTM1/p62 mediates the link between redox state and protein homeostasis Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Bernadette Carroll, Elsje G. Otten, Diego Manni, Rhoda Stefanatos, Fiona M. Menzies, Graham R. Smith, Diana Jurk, Niall Kenneth, Simon Wilkinson, Joao F. Passos, Johannes Attems, Elizabeth A. Veal, Elisa Teyssou, Danielle Seilhean, Stéphanie Millecamps, Eeva-Liisa Eskelinen, Agnieszka K. Bronowska, David C. Rubinsztein, Alberto Sanz, Viktor I. Korolchuk
Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival.
Pteropods counter mechanical damage and dissolution through extensive shell repair Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Victoria L. Peck, Rosie L. Oakes, Elizabeth M. Harper, Clara Manno, Geraint A. Tarling
The dissolution of the delicate shells of sea butterflies, or pteropods, has epitomised discussions regarding ecosystem vulnerability to ocean acidification over the last decade. However, a recent demonstration that the organic coating of the shell, the periostracum, is effective in inhibiting dissolution suggests that pteropod shells may not be as susceptible to ocean acidification as previously thought. Here we use micro-CT technology to show how, despite losing the entire thickness of the original shell in localised areas, specimens of polar species Limacina helicina maintain shell integrity by thickening the inner shell wall. One specimen collected within Fram Strait with a history of mechanical and dissolution damage generated four times the thickness of the original shell in repair material. The ability of pteropods to repair and maintain their shells, despite progressive loss, demonstrates a further resilience of these organisms to ocean acidification but at a likely metabolic cost.
Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Alec J. Hirsch, Victoria H. J. Roberts, Peta L. Grigsby, Nicole Haese, Matthias C. Schabel, Xiaojie Wang, Jamie O. Lo, Zheng Liu, Christopher D. Kroenke, Jessica L. Smith, Meredith Kelleher, Rebecca Broeckel, Craig N. Kreklywich, Christopher J. Parkins, Michael Denton, Patricia Smith, Victor DeFilippis, William Messer, Jay A. Nelson, Jon D. Hennebold, Marjorie Grafe, Lois Colgin, Anne Lewis, Rebecca Ducore, Tonya Swanson, Alfred W. Legasse, Michael K. Axthelm, Rhonda MacAllister, Ashlee V. Moses, Terry K. Morgan, Antonio E. Frias, Daniel N. Streblow
Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal growth restriction and fetal central nervous system malformations, which are outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we infect pregnant rhesus macaques and investigate the impact of persistent ZIKV infection on uteroplacental pathology, blood flow, and fetal growth and development. Despite seemingly normal fetal growth and persistent fetal-placenta-maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic effects on placental oxygen reserve accompanied by significantly decreased oxygen permeability of the placental villi. The observation of abnormal oxygen transport within the placenta appears to be a consequence of uterine vasculitis and placental villous damage in ZIKV cases. In addition, we demonstrate a robust maternal-placental-fetal inflammatory response following ZIKV infection. This animal model reveals a potential relationship between ZIKV infection and uteroplacental pathology that appears to affect oxygen delivery to the fetus during development.
Full-field thermal imaging of quasiballistic crosstalk reduction in nanoscale devices Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Amirkoushyar Ziabari, Pol Torres, Bjorn Vermeersch, Yi Xuan, Xavier Cartoixà, Alvar Torelló, Je-Hyeong Bahk, Yee Rui Koh, Maryam Parsa, Peide D. Ye, F. Xavier Alvarez, Ali Shakouri
Understanding nanoscale thermal transport is of substantial importance for designing contemporary semiconductor technologies. Heat removal from small sources is well established to be severely impeded compared to diffusive predictions due to the ballistic nature of the dominant heat carriers. Experimental observations are commonly interpreted through a reduction of effective thermal conductivity, even though most measurements only probe a single aggregate thermal metric. Here, we employ thermoreflectance thermal imaging to directly visualise the 2D temperature field produced by localised heat sources on InGaAs with characteristic widths down to 100 nm. Besides displaying effective thermal performance reductions up to 50% at the active junctions in agreement with prior studies, our steady-state thermal images reveal that, remarkably, 1–3 μm adjacent to submicron devices the crosstalk is actually reduced by up to fourfold. Submicrosecond transient imaging additionally shows responses to be faster than conventionally predicted. A possible explanation based on hydrodynamic heat transport, and some open questions, are discussed.
Phosphorylation induced cochaperone unfolding promotes kinase recruitment and client class-specific Hsp90 phosphorylation Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Ashleigh B. Bachman, Dimitra Keramisanou, Wanping Xu, Kristin Beebe, Michael A. Moses, M. V. Vasantha Kumar, Geoffrey Gray, Radwan Ebna Noor, Arjan van der Vaart, Len Neckers, Ioannis Gelis
During the Hsp90-mediated chaperoning of protein kinases, the core components of the machinery, Hsp90 and the cochaperone Cdc37, recycle between different phosphorylation states that regulate progression of the chaperone cycle. We show that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal domain and the population of folding intermediates. Unfolding facilitates Hsp90 phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a docking site to recruit non-receptor tyrosine kinases to the chaperone complex via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically regulates its interaction with Cdc37 and thus affects the chaperoning of only protein kinase clients. In summary, we find that by providing client class specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client recruitment but also shape the post-translational modification landscape of Hsp90 in a client class-specific manner.
Hypoxia-inducible factor-1α is a critical transcription factor for IL-10-producing B cells in autoimmune disease Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Xianyi Meng, Bettina Grötsch, Yubin Luo, Karl Xaver Knaup, Michael Sean Wiesener, Xiao-Xiang Chen, Jonathan Jantsch, Simon Fillatreau, Georg Schett, Aline Bozec
Hypoxia-inducible factors (HIFs) are key elements for controlling immune cell metabolism and functions. While HIFs are known to be involved in T cells and macrophages activation, their functions in B lymphocytes are poorly defined. Here, we show that hypoxia-inducible factor-1α (HIF-1α) contributes to IL-10 production by B cells. HIF-1α regulates IL-10 expression, and HIF-1α-dependent glycolysis facilitates CD1dhiCD5+ B cells expansion. Mice with B cell-specific deletion of Hif1a have reduced number of IL-10-producing B cells, which result in exacerbated collagen-induced arthritis and experimental autoimmune encephalomyelitis. Wild-type CD1dhiCD5+ B cells, but not Hif1a-deficient CD1dhiCD5+ B cells, protect recipient mice from autoimmune disease, while the protective function of Hif1a-deficient CD1dhiCD5+ B cells is restored when their defective IL-10 expression is genetically corrected. Taken together, this study demonstrates the key function of the hypoxia-associated transcription factor HIF-1α in driving IL-10 expression in CD1dhiCD5+ B cells, and in controlling their protective activity in autoimmune disease.
Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Xia Jiang, Paul F. O’Reilly, Hugues Aschard, Yi-Hsiang Hsu, J. Brent Richards, Josée Dupuis, Erik Ingelsson, David Karasik, Stefan Pilz, Diane Berry, Bryan Kestenbaum, Jusheng Zheng, Jianan Luan, Eleni Sofianopoulou, Elizabeth A. Streeten, Demetrius Albanes, Pamela L. Lutsey, Lu Yao, Weihong Tang, Michael J. Econs, Henri Wallaschofski, Henry Völzke, Ang Zhou, Chris Power, Mark I. McCarthy, Erin D. Michos, Eric Boerwinkle, Stephanie J. Weinstein, Neal D. Freedman, Wen-Yi Huang, Natasja M. Schoor, Nathalie Velde, Lisette C. P. G. M. de Groot, Anke Enneman, L. Adrienne Cupples, Sarah L. Booth, Ramachandran S. Vasan, Ching-Ti Liu, Yanhua Zhou, Samuli Ripatti, Claes Ohlsson, Liesbeth Vandenput, Mattias Lorentzon, Johan G. Eriksson, M. Kyla Shea, Denise K. Houston, Stephen B. Kritchevsky, Yongmei Liu, Kurt K. Lohman, Luigi Ferrucci, Munro Peacock, Christian Gieger, Marian Beekman, Eline Slagboom, Joris Deelen, Diana van Heemst, Marcus E. Kleber, Winfried März, Ian H. Boer, Alexis C. Wood, Jerome I. Rotter, Stephen S. Rich, Cassianne Robinson-Cohen, Martin Heijer, Marjo-Riitta Jarvelin, Alana Cavadino, Peter K. Joshi, James F. Wilson, Caroline Hayward, Lars Lind, Karl Michaëlsson, Stella Trompet, M. Carola Zillikens, Andre G. Uitterlinden, Fernando Rivadeneira, Linda Broer, Lina Zgaga, Harry Campbell, Evropi Theodoratou, Susan M. Farrington, Maria Timofeeva, Malcolm G. Dunlop, Ana M. Valdes, Emmi Tikkanen, Terho Lehtimäki, Leo-Pekka Lyytikäinen, Mika Kähönen, Olli T. Raitakari, Vera Mikkilä, M. Arfan Ikram, Naveed Sattar, J. Wouter Jukema, Nicholas J. Wareham, Claudia Langenberg, Nita G. Forouhi, Thomas E. Gundersen, Kay-Tee Khaw, Adam S. Butterworth, John Danesh, Timothy Spector, Thomas J. Wang, Elina Hyppönen, Peter Kraft, Douglas P. Kiel
Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Judith Krysiak, Andreas Unger, Lisa Beckendorf, Nazha Hamdani, Marion Frieling-Salewsky, Margaret M. Redfield, Cris G. Remedios, Farah Sheikh, Ulrich Gergs, Peter Boknik, Wolfgang A. Linke
Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. Using various binding and phosphorylation tests, cell-culture manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates with N2Bus in vitro and in sarcomeres and is antagonistic to several protein kinases, which phosphorylate N2Bus and lower titin-based passive tension. PP5 is pathologically elevated and likely contributes to hypo-phosphorylation of N2Bus in failing human hearts. Furthermore, Hsp90-activated PP5 interacts with components of a sarcomeric, N2Bus-associated, mechanosensor complex, and blocks mitogen-activated protein-kinase signaling in this complex. Our work establishes PP5 as a compartmentalized, well-controlled phosphatase in cardiomyocytes, which regulates titin properties and kinase signaling at the myofilaments.
∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Hamish Campbell, Nicholas Fleming, Imogen Roth, Sunali Mehta, Anna Wiles, Gail Williams, Claire Vennin, Nikola Arsic, Ashleigh Parkin, Marina Pajic, Fran Munro, Les McNoe, Michael Black, John McCall, Tania L. Slatter, Paul Timpson, Roger Reddel, Pierre Roux, Cristin Print, Margaret A. Baird, Antony W. Braithwaite
∆122p53 mice (a model of ∆133p53 isoform) are tumour-prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed ∆122p53 mice with IL-6 null mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence and metastasis. We also show that ∆122p53 activates RhoA-ROCK signalling leading to tumour cell invasion, which is IL-6-dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that Δ133p53 activates these pathways, resulting in invasive and migratory phenotypes in colorectal cancer cells. Gene expression analysis of colorectal tumours showed enrichment of GPCR signalling associated with ∆133TP53 mRNA. Patients with elevated ∆133TP53 mRNA levels had a shorter disease-free survival. Our results suggest that ∆133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways, and that patients whose tumours have high ∆133TP53 may benefit from therapies targeting these pathways.
Multiplex glycan bead array for high throughput and high content analyses of glycan binding proteins Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Sharad Purohit, Tiehai Li, Wanyi Guan, Xuezheng Song, Jing Song, Yanna Tian, Lei Li, Ashok Sharma, Boying Dun, David Mysona, Sharad Ghamande, Bunja Rungruang, Richard D. Cummings, Peng George Wang, Jin-Xiong She
Glycan-binding proteins (GBPs) play critical roles in diverse cellular functions such as cell adhesion, signal transduction and immune response. Studies of the interaction between GBPs and glycans have been hampered by the availability of high throughput and high-content technologies. Here we report multiplex glycan bead array (MGBA) that allows simultaneous analyses of 384 samples and up to 500 glycans in a single assay. The specificity, sensitivity and reproducibility of MGBA are evaluated using 39 plant lectins, 13 recombinant anti-glycan antibodies, and mammalian GBPs. We demonstrate the utility of this platform by the analyses of natural anti-glycan IgM and IgG antibodies in 961 human serum samples and the discovery of anti-glycan antibody biomarkers for ovarian cancer. Our data indicate that the MGBA platform is particularly suited for large population-based studies that require the analyses of large numbers of samples and glycans.
CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Xufeng Chen, Muhammad Aslam, Tim Gollisch, Kevin Allen, Jakob Engelhardt
Relay neurons in the dorsal lateral geniculate nucleus (dLGN) receive excitatory inputs from retinal ganglion cells (RGCs). Retinogeniculate synapses are characterized by a prominent short-term depression of AMPA receptor (AMPAR)-mediated currents, but the underlying mechanisms and its function for visual integration are not known. Here we identify CKAMP44 as a crucial auxiliary subunit of AMPARs in dLGN relay neurons, where it increases AMPAR-mediated current amplitudes and modulates gating of AMPARs. Importantly, CKAMP44 is responsible for the distinctive short-term depression in retinogeniculate synapses by reducing the rate of recovery from desensitization of AMPARs. Genetic deletion of CKAMP44 strongly reduces synaptic short-term depression, which leads to increased spike probability of relay neurons when activated with high-frequency inputs from retinogeniculate synapses. Finally, in vivo recordings reveal augmented ON- and OFF-responses of dLGN neurons in CKAMP44 knockout (CKAMP44−/−) mice, demonstrating the importance of CKAMP44 for modulating synaptic short-term depression and visual input integration.
Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR signalling Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Jessica E. Frith, Gina D. Kusuma, James Carthew, Fanyi Li, Nicole Cloonan, Guillermo A. Gomez, Justin J. Cooper-White
Mechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In vitro, variations in matrix mechanics invoke changes in MSC proliferation, migration and differentiation. However, when incorporating MSCs within injectable, inherently soft hydrogels, this dominance over MSC response substantially limits our ability to couple the ease of application of hydrogels with efficiently directed MSC differentiation, especially in the case of bone generation. Here, we identify differential miRNA expression in response to varying hydrogel stiffness and RhoA activity. We show that modulation of miR-100-5p and miR-143-3p can be used to bias MSC fate and provide mechanistic insight by demonstrating convergence on mTOR signalling. By modulating these mechanosensitive miRNAs, we can enhance osteogenesis in a soft 3D hydrogel. The outcomes of this study provide new understanding of the mechanisms regulating MSC mechanotransduction and differentiation, but also a novel strategy with which to drive MSC fate and significantly impact MSC-based tissue-engineering applications.
MAIT cell clonal expansion and TCR repertoire shaping in human volunteers challenged with Salmonella Paratyphi A Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Lauren J. Howson, Giorgio Napolitani, Dawn Shepherd, Hemza Ghadbane, Prathiba Kurupati, Lorena Preciado-Llanes, Margarida Rei, Hazel C. Dobinson, Malick M. Gibani, Karen Wei Weng Teng, Evan W. Newell, Natacha Veerapen, Gurdyal S. Besra, Andrew J. Pollard, Vincenzo Cerundolo
Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can detect bacteria-derived metabolites presented on MR1. Here we show, using a controlled infection of humans with live Salmonella enterica serovar Paratyphi A, that MAIT cells are activated during infection, an effect maintained even after antibiotic treatment. At the peak of infection MAIT cell T-cell receptor (TCR)β clonotypes that are over-represented prior to infection transiently contract. Select MAIT cell TCRβ clonotypes that expand after infection have stronger TCR-dependent activation than do contracted clonotypes. Our results demonstrate that host exposure to antigen may drive clonal expansion of MAIT cells with increased functional avidity, suggesting a role for specific vaccination strategies to increase the frequency and potency of MAIT cells to optimize effector function.
Atmospheric CO2 effect on stable carbon isotope composition of terrestrial fossil archives Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Vincent J. Hare, Emma Loftus, Amy Jeffrey, Christopher Bronk Ramsey
The 13C/12C ratio of C3 plant matter is thought to be controlled by the isotopic composition of atmospheric CO2 and stomatal response to environmental conditions, particularly mean annual precipitation (MAP). The effect of CO2 concentration on 13C/12C ratios is currently debated, yet crucial to reconstructing ancient environments and quantifying the carbon cycle. Here we compare high-resolution ice core measurements of atmospheric CO2 with fossil plant and faunal isotope records. We show the effect of pCO2 during the last deglaciation is stronger for gymnosperms (−1.4 ± 1.2‰) than angiosperms/fauna (−0.5 ± 1.5‰), while the contributions from changing MAP are −0.3 ± 0.6‰ and −0.4 ± 0.4‰, respectively. Previous studies have assumed that plant 13C/12C ratios are mostly determined by MAP, an assumption which is sometimes incorrect in geological time. Atmospheric effects must be taken into account when interpreting terrestrial stable carbon isotopes, with important implications for past environments and climates, and understanding plant responses to climate change.
Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Brent D. G. Page, Nicholas C. K. Valerie, Roni H. G. Wright, Olov Wallner, Rebecka Isaksson, Megan Carter, Sean G. Rudd, Olga Loseva, Ann-Sofie Jemth, Ingrid Almlöf, Jofre Font-Mateu, Sabin Llona-Minguez, Pawel Baranczewski, Fredrik Jeppsson, Evert Homan, Helena Almqvist, Hanna Axelsson, Shruti Regmi, Anna-Lena Gustavsson, Thomas Lundbäck, Martin Scobie, Kia Strömberg, Pål Stenmark, Miguel Beato, Thomas Helleday
With a diverse network of substrates, NUDIX hydrolases have emerged as a key family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells. Here, we further elucidate the physiological relevance of known NUDT5 substrates and underscore the biological requirement for NUDT5 in gene regulation and proliferation of breast cancer cells. We confirm the involvement of NUDT5 in ADP-ribose metabolism and dissociate a relationship to oxidized nucleotide sanitation. Furthermore, we identify potent NUDT5 inhibitors, which are optimized to promote maximal NUDT5 cellular target engagement by CETSA. Lead compound, TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in breast cancer cells. We herein present TH5427 as a promising, targeted inhibitor that can be used to further study NUDT5 activity and ADP-ribose metabolism.
The protective role of DOT1L in UV-induced melanomagenesis Nat. Commun. (IF 12.124) Pub Date : 2018-01-17 Bo Zhu, Shuyang Chen, Hongshen Wang, Chengqian Yin, Changpeng Han, Cong Peng, Zhaoqian Liu, Lixin Wan, Xiaoyang Zhang, Jie Zhang, Christine G. Lian, Peilin Ma, Zhi-xiang Xu, Sharon Prince, Tao Wang, Xiumei Gao, Yujiang Shi, Dali Liu, Min Liu, Wenyi Wei, Zhi Wei, Jingxuan Pan, Yongjun Wang, Zhenyu Xuan, Jay Hess, Nicholas K. Hayward, Colin R. Goding, Xiang Chen, Jun Zhou, Rutao Cui
The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis.
PredCRP: predicting and analysing the regulatory roles of CRP from its binding sites in Escherichia coli Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Ming-Ju Tsai, Jyun-Rong Wang, Chi-Dung Yang, Kuo-Ching Kao, Wen-Lin Huang, Hsi-Yuan Huang, Ching-Ping Tseng, Hsien-Da Huang, Shinn-Ying Ho
Cyclic AMP receptor protein (CRP), a global regulator in Escherichia coli, regulates more than 180 genes via two roles: activation and repression. Few methods are available for predicting the regulatory roles from the binding sites of transcription factors. This work proposes an accurate method PredCRP to derive an optimised model (named PredCRP-model) and a set of four interpretable rules (named PredCRP-ruleset) for predicting and analysing the regulatory roles of CRP from sequences of CRP-binding sites. A dataset consisting of 169 CRP-binding sites with regulatory roles strongly supported by evidence was compiled. The PredCRP-model, using 12 informative features of CRP-binding sites, and cooperating with a support vector machine achieved a training and test accuracy of 0.98 and 0.93, respectively. PredCRP-ruleset has two activation rules and two repression rules derived using the 12 features and the decision tree method C4.5. This work further screened and identified 23 previously unobserved regulatory interactions in Escherichia coli. Using quantitative PCR for validation, PredCRP-model and PredCRP-ruleset achieved a test accuracy of 0.96 (=22/23) and 0.91 (=21/23), respectively. The proposed method is suitable for designing predictors for regulatory roles of all global regulators in Escherichia coli. PredCRP can be accessed at https://github.com/NctuICLab/PredCRP .
Silver Nanoparticles in the Water Environment in Malaysia: Inspection, characterization, removal, modeling, and future perspective Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Achmad Syafiuddin, Salmiati Salmiati, Tony Hadibarata, Ahmad Beng Hong Kueh, Mohd Razman Salim, Muhammad Abbas Ahmad Zaini
The current status of silver nanoparticles (AgNPs) in the water environment in Malaysia was examined and reported. For inspection, two rivers and two sewage treatment plants (STPs) were selected. Two activated carbons derived from oil palm (ACfOPS) and coconut (ACfCS) shells were proposed as the adsorbent to remove AgNPs. It was found that the concentrations of AgNPs in the rivers and STPs are in the ranges of 0.13 to 10.16 mg L−1 and 0.13 to 20.02 mg L−1, respectively, with the highest concentration measured in July. ACfOPS and ACfCS removed up to 99.6 and 99.9% of AgNPs, respectively, from the water. The interaction mechanism between AgNPs and the activated carbon surface employed in this work was mainly the electrostatic force interaction via binding Ag+ with O− presented in the activated carbon to form AgO. Fifteen kinetic models were compared statistically to describe the removal of AgNPs. It was found that the experimental adsorption data can be best described using the mixed 1,2-order model. Therefore, this model has the potential to be a candidate for a general model to describe AgNPs adsorption using numerous materials, its validation of which has been confirmed with other material data from previous works.
Electrochemical and Friction Characteristics of Metallic Glass Composites at the Microstructural Length-scales Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Aditya Ayyagari, Vahid Hasannaeimi, Harpreet Arora, Sundeep Mukherjee
Metallic glass composites represent a unique alloy design strategy comprising of in situ crystalline dendrites in an amorphous matrix to achieve damage tolerance unseen in conventional structural materials. They are promising for a range of advanced applications including spacecraft gears, high-performance sporting goods and bio-implants, all of which demand high surface degradation resistance. Here, we evaluated the phase-specific electrochemical and friction characteristics of a Zr-based metallic glass composite, Zr56.2Ti13.8Nb5.0Cu6.9Ni5.6Be12.5, which comprised roughly of 40% by volume crystalline dendrites in an amorphous matrix. The amorphous matrix showed higher hardness and friction coefficient compared to the crystalline dendrites. But sliding reciprocating tests for the composite revealed inter-phase delamination rather than preferred wearing of one phase. Pitting during potentiodynamic polarization in NaCl solution was prevalent at the inter-phase boundary, confirming that galvanic coupling was the predominant corrosion mechanism. Scanning vibration electrode technique demonstrated that the amorphous matrix corroded much faster than the crystalline dendrites due to its unfavorable chemistry. Relative work function values measured using scanning kelvin probe showed the amorphous matrix to be more electropositive, which explain its preferred corrosion over the crystalline dendrites as well as its characteristic friction behavior. This study paves the way for careful partitioning of elements between the two phases in a metallic glass composite to tune its surface degradation behavior for a range of advanced applications.
Leptin resistance was involved in susceptibility to overweight in the striped hamster re-fed with high fat diet Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Ying Zhao, Li-Bing Chen, Si-Si Mao, Hong-Xia Min, Jing Cao
Food restriction (FR) is the most commonly used intervention to prevent the overweight. However, the lost weight is usually followed by “compensatory growth” when FR ends, resulting in overweight. The present study was aimed to examining the behavior patterns and hormones mechanisms underpinning the over-weight. Energy budget and body fat content, and several endocrine markers related to leptin signals were examined in the striped hamsters under 20% FR refed by either low-fat diet (LF group) or high-fat diet (HF group). Body mass and fat content significantly regained when FR ended, and the hamsters in HF group showed 49.1% more body fat than in LF group (P < 0.01). Digestive energy intake was higher by 20.1% in HF than LF group, while metabolic thermogenesis and behavior patterns did not differed between the two groups. Gene expression of leptin receptor and anorexigenic peptides of pro-opiomelanocortin and cocaine- and amphetamine-regulated transcript in hypothalamus were significantly up-regulated in LF group, but down-regulated in HF group. It suggests that effective leptin signals to the brain were involved in attenuation of hyperphagia in hamsters refed with LF. However, “leptin resistance” probably occurred in hamsters refed with HF, which impaired the control of hyperphagia, resulting in development of over-weight.
First estimates of Greenland shark (Somniosus microcephalus) local abundances in Arctic waters Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Brynn M. Devine, Laura J. Wheeland, Jonathan A. D. Fisher
Baited remote underwater video cameras were deployed in the Eastern Canadian Arctic, for the purpose of estimating local densities of the long-lived Greenland shark within five deep-water, data-poor regions of interest for fisheries development and marine conservation in Nunavut, Canada. A total of 31 camera deployments occurred between July-September in 2015 and 2016 during joint exploratory fishing and scientific cruises. Greenland sharks appeared at 80% of deployments. A total of 142 individuals were identified and no individuals were observed in more than one deployment. Estimates of Greenland shark abundance and biomass were calculated from averaged times of first arrival, video-derived swimming speed and length data, and local current speed estimates. Density estimates varied 1–15 fold among regions; being highest in warmer (>0 °C), deeper areas and lowest in shallow, sub-zero temperature regions. These baited camera results illustrate the ubiquity of this elusive species and suggest that Nunavut’s Lancaster Sound eco-zone may be of particular importance for Greenland shark, a potentially vulnerable Arctic species.
Increased left ventricular mass index is present in patients with type 2 diabetes without ischemic heart disease Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Jelena P. Seferovic, Milorad Tesic, Petar M. Seferovic, Katarina Lalic, Aleksandra Jotic, Tor Biering-Sørensen, Vojislav Giga, Sanja Stankovic, Natasa Milic, Ljiljana Lukic, Tanja Milicic, Marija Macesic, Jelena Stanarcic Gajovic, Nebojsa M. Lalic
Left ventricular mass index (LVMI) increase has been described in hypertension (HTN), but less is known about its association with type 2 diabetes (T2DM). As these conditions frequently co-exist, we investigated the association of T2DM, HTN and both with echocardiographic parameters, and hypothesized that patients with both had highest LVMI, followed by patients with only T2DM or HTN. Study population included 101 T2DM patients, 62 patients with HTN and no T2DM, and 76 patients with T2DM and HTN, excluded for ischemic heart disease. Demographic and clinical data, biochemical measurements, stress echocardiography, transthoracic 2D Doppler and tissue Doppler echocardiography were performed. Multivariable logistic regression was used to determine the independent association with T2DM. Linear regression models and Pearson’s correlation were used to assess the correlations between LVMI and other parameters. Patients with only T2DM had significantly greater LVMI (84.9 ± 20.3 g/m2) compared to patients with T2DM and HTN (77.9 ± 16 g/m2) and only HTN (69.8 ± 12.4 g/m2). In multivariate logistic regression analysis, T2DM was associated with LVMI (OR 1.033, 95%CI 1.003–1.065, p = 0.029). A positive correlation of LVMI was found with fasting glucose (p < 0.001) and HbA1c (p = 0.0003). Increased LVMI could be a potential, pre-symptomatic marker of myocardial structural change in T2DM.
The role of NFκB in spheroid formation of human breast cancer cells cultured on the Random Positioning Machine Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Sascha Kopp, Jayashree Sahana, Tawhidul Islam, Asbjørn Graver Petersen, Johann Bauer, Thomas J. Corydon, Herbert Schulz, Kathrin Saar, Norbert Huebner, Lasse Slumstrup, Stefan Riwaldt, Markus Wehland, Manfred Infanger, Ronald Luetzenberg, Daniela Grimm
Human MCF-7 breast cancer cells were exposed to a Random Positioning Machine (RPM). After 24 hours (h) the cells grew either adherently within a monolayer (AD) or within multicellular spheroids (MCS). AD and MCS populations were separately harvested, their cellular differences were determined performing qPCR on genes, which were differently expressed in AD and MCS cells. Gene array technology was applied to detect RPM-sensitive genes in MCF-7 cells after 24 h. Furthermore, the capability to form multicellular spheroids in vitro was compared with the intracellular distribution of NF-kappaB (NFκB) p65. NFκB was equally distributed in static control cells, but predominantly localized in the cytoplasm in AD cells and nucleus in MCS cells exposed to the RPM. Gene array analyses revealed a more than 2-fold change of only 23 genes including some whose products are affected by oxygen levels or regulate glycolysis. Significant upregulations of the mRNAs of enzymes degrading heme, of ANXA1, ANXA2, CTGF, CAV2 and ICAM1, as well as of FAS, Casp8, BAX, p53, CYC1 and PARP1 were observed in MCS cells as compared with 1g-control and AD cells. An interaction analysis of 47 investigated genes suggested that HMOX-1 and NFκB variants are activated, when multicellular spheroids are formed.
High albumin level is a predictor of favorable response to immunotherapy in autoimmune encephalitis Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Yoonhyuk Jang, Soon-Tae Lee, Tae-Joon Kim, Jin-Sun Jun, Jangsup Moon, Keun-Hwa Jung, Kyung-Il Park, Kon Chu, Sang Kun Lee
There is no known biomarker that predicts the response to immune therapy in autoimmune synaptic encephalitis. Thus, we investigated serum albumin as a prognostic biomarker of early immune therapies in patients with autoimmune encephalitis. We enrolled patients who were diagnosed with definite autoimmune encephalitis and underwent IVIg treatment at Seoul National University Hospital from 2012 to 2017. Patients were dichotomized according to serum albumin prior to IVIg administration with a cut-off level of 4.0 g/dL, which was the median value of 50% of patients. Seventeen (53.1%) of the 32 patients with definite autoimmune encephalitis who received IVIg treatment in our hospital had low serum albumin (<4.0 g/dL). The initial disease severity (mRS ≥ 4) was the sole factor that predicted low albumin in autoimmune encephalitis patients using multivariate analysis (P = 0.013). The low albumin group exhibited a worse response to immune therapy at the third and fourth weeks from IVIg administration (P < 0.01 and P = 0.012, respectively), and recovery to activities of daily life without assistance was faster in the high albumin group (log-rank test for trend, P < 0.01). Our study found that pretreatment low serum albumin was a significant indicator of autoimmune encephalitis prognosis in the short-term and long-term.
Analysis of mitochondrial function in human induced pluripotent stem cells from patients with mitochondrial diabetes due to the A3243G mutation Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Masaki Matsubara, Hajime Kanda, Hiromi Imamura, Mayumi Inoue, Michio Noguchi, Kiminori Hosoda, Akira Kakizuka, Kazuwa Nakao
We previously established human induced pluripotent stem (iPS) cells in two diabetic patients from different families with the mitochondrial A3243G mutation and isolated isogenic iPS cell clones with either undetectable or high levels of the mutation in both patients. In the present study, we analyzed the mitochondrial functions of two mutation-undetectable and two mutation-high clones in each patient through four methods to assess complex I activity, mitochondrial membrane potential, mitochondrial respiration, and mitochondrial ATP production. In the first patient, complex I activity, mitochondrial respiration, and mitochondrial ATP production were decreased in the mutation-high clones compared with the mutation-undetectable clones, and mitochondrial membrane potential was decreased in a mutation-high clone compared with a mutation-undetectable clone. In the second patient, complex I activity was decreased in one mutation-high clone compared with the other clones. The other parameters showed no differences in any clones. In addition, the complex I activity and mitochondrial respiration of the mutation-undetectable clones from both patients were located in the range of those of iPS cells from healthy subjects. The present study suggests that the mitochondrial function of the mutation-undetectable iPS cell clones obtained from two patients with the A3243G mutation is comparable to the control iPS cells.
The neural correlates of the unified percept of alcohol-related craving: a fMRI and EEG study Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Yuefeng Huang, Anusha Mohan, Dirk Ridder, Stefan Sunaert, Sven Vanneste
Alcohol addiction is accompanied by aberrant neural activity. Previously, task-based fMRI and resting-state EEG studies have revealed that craving, a critical component of addiction, is linked to abnormal activity in cortical regions including the dorsal anterior cingulate cortex (dACC), nucleus accumbens (NAcc), posterior cingulate cortex (PCC) and pregenual anterior cingulate cortex (pgACC), etc. In this study, we combine these two imaging techniques to investigate a group of alcohol-addicted patients and provide convergent evidence for the neural correlates of craving not only in alcohol but substance abuse in general. We observe abnormal BOLD signal levels in the dACC, NAcc, pgACC, PCC, amygdala, and parahippocampus (PHC) in a cue-reactivity fMRI experiment. These findings are consistent with increased beta-band activity in the dACC and pgACC in resting-state EEG. We further observe desynchronization characterized by decreased functional connectivity in cue-based fMRI and hypersynchronization characterized by increased functional connectivity between these regions in the theta frequency band. The results of our study show a consistent pattern of alcohol craving elicited by external cues and internal desires. Given the advantage of superior spatial and temporal resolution, we hypothesize a “central craving network” that integrates the different aspects of alcohol addiction into a unified percept.
Highly effective and chemically stable surface enhanced Raman scattering substrates with flower-like 3D Ag-Au hetero-nanostructures Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Ying Zhang, Chengliang Yang, Bin Xue, Zenghui Peng, Zhaoliang Cao, Quanquan Mu, Li Xuan
We demonstrated flower-like 3D Ag-Au hetero-nanostructures on an indium tin oxide glass (ITO glass) for surface enhanced Raman scattering (SERS) applications. The flower-like 3D Ag nanostructures were obtained through electrodeposition with liquid crystalline soft template which is simple, controllable and cost effective. The flower-like 3D Ag-Au hetero-nanostructures were further fabricated by galvanic replacement reaction of gold (III) chloride trihydrate (HAuCl4·3H2O) solution and flower-like Ag. The flower-like Ag-Au hetero-nanostructure exhibited stronger SERS effects and better chemical stability compared with flower-like Ag nanostructure. The localized surface plasmon resonance (LSPR) spectra, field emission scanning electron microscope (FESEM) photos and Ag-Au ratios were studied which show that the surface morphology and shape of the flower-like Ag-Au hetero-nanostructure play significant roles in enhancing SERS. The flower-like 3D Ag-Au hetero-nanostructures fabricated by electrodeposition in liquid crystalline template and galvanic replacement reaction are simple, cheap, controllable and chemical stable. It is a good candidate for applications in SERS detection and imaging.
Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin- furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Kentaro Yamane, Tetsuro Mazaki, Yasuyuki Shiozaki, Aki Yoshida, Kensuke Shinohara, Mariko Nakamura, Yasuhiro Yoshida, Di Zhou, Takashi Kitajima, Masato Tanaka, Yoshihiro Ito, Toshifumi Ozaki, Akihiro Matsukawa
The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.
Predicted impact of thermal power generation emission control measures in the Beijing-Tianjin-Hebei region on air pollution over Beijing, China Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Liqiang Wang, Pengfei Li, Shaocai Yu, Khalid Mehmood, Zhen Li, Shucheng Chang, Weiping Liu, Daniel Rosenfeld, Richard C. Flagan, John H. Seinfeld
Widespread economic growth in China has led to increasing episodes of severe air pollution, especially in major urban areas. Thermal power plants represent a particularly important class of emissions. Here we present an evaluation of the predicted effectiveness of a series of recently proposed thermal power plant emission controls in the Beijing-Tianjin-Hebei (BTH) region on air quality over Beijing using the Community Multiscale Air Quality(CMAQ) atmospheric chemical transport model to predict CO, SO2, NO2, PM2.5, and PM10 levels. A baseline simulation of the hypothetical removal of all thermal power plants in the BTH region is predicted to lead to 38%, 23%, 23%, 24%, and 24% reductions in current annual mean levels of CO, SO2, NO2, PM2.5, and PM10 in Beijing, respectively. Similar percentage reductions are predicted in the major cities in the BTH region. Simulations of the air quality impact of six proposed thermal power plant emission reduction strategies over the BTH region provide an estimate of the potential improvement in air quality in the Beijing metropolitan area, as a function of the time of year.
Structural and functional insights into S-thiolation of human serum albumins Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Fumie Nakashima, Takahiro Shibata, Kohei Kamiya, Jun Yoshitake, Ryosuke Kikuchi, Tadashi Matsushita, Isao Ishii, Juan A. Giménez-Bastida, Claus Schneider, Koji Uchida
Human serum albumin (HSA) is the most abundant serum protein, contributing to the maintenance of redox balance in the extracellular fluids. One single free cysteine residue at position 34 is believed to be a target of oxidation. However, the molecular details and functions of oxidized HSAs remain obscure. Here we analyzed serum samples from normal subjects and hyperlipidemia patients and observed an enhanced S-thiolation of HSA in the hyperlipidemia patients as compared to the control individuals. Both cysteine and homocysteine were identified as the low molecular weight thiols bound to the HSAs. Intriguingly, S-thiolations were observed not only at Cys34, but also at multiple cysteine residues in the disulfide bonds of HSA. When the serum albumins from genetically modified mice that exhibit high levels of total homocysteine in serum were analyzed, we observed an enhanced S-homocysteinylation at multiple cysteine residues. In addition, the cysteine residues in the disulfide bonds were also thiolated in recombinant HSA that had been treated with the disulfide molecules. These findings and the result that S-homocysteinylation mediated increased surface hydrophobicity and ligand binding activity of HSA offer new insights into structural and functional alternation of serum albumins via S-thiolation.
Experimental infection of cattle with Mycobacterium tuberculosis isolates shows the attenuation of the human tubercle bacillus for cattle Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Bernardo Villarreal-Ramos, Stefan Berg, Adam Whelan, Sebastien Holbert, Florence Carreras, Francisco J. Salguero, Bhagwati L. Khatri, Kerri Malone, Kevin Rue-Albrecht, Ronan Shaughnessy, Alicia Smyth, Gobena Ameni, Abraham Aseffa, Pierre Sarradin, Nathalie Winter, Martin Vordermeier, Stephen V. Gordon
The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was isolated in the early 1930s, and genetic variants are known to exist, we sought to revisit this question of attenuation of M. tuberculosis for cattle by performing a bovine experimental infection with a recent M. tuberculosis isolate. Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB surveillance project in Ethiopian cattle. We show that both M. tuberculosis strains caused reduced gross pathology and histopathology in cattle compared to M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 as the extremes in terms of infection outcome, we used RNA-Seq analysis to explore differences in the peripheral response to infection as a route to identify biomarkers of progressive disease in contrast to a more quiescent, latent infection. Our work shows the attenuation of M. tuberculosis strains for cattle, and emphasizes the potential of the bovine model as a ‘One Health’ approach to inform human TB biomarker development and post-exposure vaccine development.
Correlations between mitochondrial DNA haplogroup D5 and chronic hepatitis B virus infection in Yunnan, China Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Xiao Li, Tai-Cheng Zhou, Chang-Hui Wu, Li-Lin Tao, Rui Bi, Li-Jun Chen, De-Yao Deng, Chang Liu, Newton O. Otecko, Yang Tang, Xin Lai, Liang Zhang, Jia Wei
Mitochondrial abnormality is frequently reported in individuals with hepatitis B virus (HBV) infection, but the associated hosts’ mitochondrial genetic factors remain obscure. We hypothesized that mitochondria may affect host susceptibility to HBV infection. In this study, we aimed to detect the association between chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV infection (spontaneously recovered, SR) were analysed for mtDNA sequence variations and classified into respective haplogroups. Haplogroup frequencies were compared between HBV infected patients, HCs and SRs. Haplogroup D5 presented a higher frequency in CHBs than in HCs (P = 0.017, OR = 2.87, 95% confidence interval [CI] = (1.21–6.81)) and SRs (P = 0.049, OR = 2.90, 95% CI = 1.01–8.35). The network of haplogroup D5 revealed a distinct distribution pattern between CHBs and non-CHBs. A trend of higher viral load among CHBs with haplogroup D5 was observed. Our results indicate the risk potential of mtDNA haplogroup D5 in chronic HBV infection in Yunnan, China.
Three-dimensional migration behavior of juvenile salmonids in reservoirs and near dams Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Xinya Li, Zhiqun D. Deng, Tao Fu, Richard S. Brown, Jayson J. Martinez, Geoffrey A. McMichael, Bradly A. Trumbo, Martin L. Ahmann, Jon F. Renholds, John R. Skalski, Richard L. Townsend
To acquire 3-D tracking data on juvenile salmonids, Juvenile Salmon Acoustic Telemetry System (JSATS) cabled hydrophone arrays were deployed in the forebays of two dams on the Snake River and at a mid-reach reservoir between the dams. The depth distributions of fish were estimated by statistical analyses performed on large 3-D tracking data sets from ~33,500 individual acoustic tagged yearling and subyearling Chinook salmon and juvenile steelhead at the two dams in 2012 and subyearling Chinook salmon at the two dams and the mid-reach reservoir in 2013. This research investigated the correlation between vertical migration behavior and passage routes. The depth distributions of fish within the forebays of the dams were significantly different from fish passing the mid-reach reservoir. Fish residing deeper in the forebay tended to pass the dam using deeper powerhouse routes. This difference in depth distributions indicated that the depth distribution of fish at the mid-reach reservoir was not related to behaviors of fish passing through certain routes of the adjacent dams. For fish that were detected deeper than 17.5 m in the forebays, the probability of powerhouse passage (i.e., turbine) increased significantly. Another important finding was the variation in depth distributions during dam passage associated with the diel period, especially the crepuscular periods.
Association of S100B polymorphisms and serum S100B with risk of ischemic stroke in a Chinese population Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Yu-Lan Lu, Rong Wang, Hua-Tuo Huang, Hai-Mei Qin, Chun-Hong Liu, Yang Xiang, Chun-Fang Wang, Hong-Cheng Luo, Jun-Li Wang, Yan Lan, Ye-Sheng Wei
The levels of serum S100B were elevated in patients with ischemic stroke (IS), which may be a novel biomarker for diagnosing IS. The aim of this study was to investigate the association of S100B polymorphisms and serum S100B with IS risk. We genotyped the S100B polymorphisms rs9722, rs9984765, rs2839356, rs1051169 and rs2186358 in 396 IS patients and 398 controls using polymerase chain reaction-single base extension (SBE-PCR). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). Rs9722 was associated with an increased risk of IS (AA vs. GG: adjusted OR = 2.172, 95% CI, 1.175–4.014, P = 0.013; dominant: adjusted OR = 1.507, 95% CI, 1.071–2.123, P = 0.019; recessive: adjusted OR = 1.846, 95% CI, 1.025–3.323, P = 0.041; additive: adjusted OR=1.371, 95% CI, 1.109-1.694, P = 0.003). The A-C-C-C-A haplotype was associated with an increased risk of IS (OR = 1.325, 95% CI, 1.035–1.696, P = 0.025). In addition, individuals carrying the rs9722 GA/AA genotypes had a higher serum S100B compared with the rs9722 GG genotype in IS patients (P = 0.018). Our results suggest that the S100B gene rs9722 polymorphism may contribute to the susceptibility of IS, probably by promoting the expression of serum S100B.
The hidden cost of using low-resolution concentration data in the estimation of NH3 dry deposition fluxes Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Frederik Schrader, Martijn Schaap, Undine Zöll, Richard Kranenburg, Christian Brümmer
Long-term monitoring stations for atmospheric pollutants are often equipped with low-resolution concentration samplers. In this study, we analyse the errors associated with using monthly average ammonia concentrations as input variables for bidirectional biosphere-atmosphere exchange models, which are commonly used to estimate dry deposition fluxes. Previous studies often failed to account for a potential correlation between ammonia exchange velocities and ambient concentrations. We formally derive the exact magnitude of these errors from statistical considerations and propose a correction scheme based on parallel measurements using high-frequency analysers. In case studies using both modelled and measured ammonia concentrations and micrometeorological drivers from sites with varying pollution levels, we were able to substantially reduce bias in the predicted ammonia fluxes. Neglecting to account for these errors can, in some cases, lead to significantly biased deposition estimates compared to using high-frequency instrumentation or corrected averaging strategies. Our study presents a first step towards a unified correction scheme for data from nation-wide air pollutant monitoring networks to be used in chemical transport and air quality models.
Deep-Ultraviolet AlGaN/AlN Core-Shell Multiple Quantum Wells on AlN Nanorods via Lithography-Free Method Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Jinwan Kim, Uiho Choi, Jaedo Pyeon, Byeongchan So, Okhyun Nam
We report deep ultraviolet (UVC) emitting core-shell-type AlGaN/AlN multiple quantum wells (MQWs) on the AlN nanorods which are prepared by catalyst/lithography free process. The MQWs are grown on AlN nanorods on a sapphire substrate by polarity-selective epitaxy and etching (PSEE) using high-temperature metal organic chemical vapor deposition. The AlN nanorods prepared through PSEE have a low dislocation density because edge dislocations are bent toward neighboring N-polar AlN domains. The core–shell-type MQWs grown on AlN nanorods have three crystallographic orientations, and the final shape of the grown structure is explained by a ball-and-stick model. The photoluminescence (PL) intensity of MQWs grown on AlN nanorods is approximately 40 times higher than that of MQWs simultaneously grown on a planar structure. This result can be explained by increased internal quantum efficiency, large active volume, and increase in light extraction efficiency based on the examination in this study. Among those effects, the increase of active volume on AlN nanorods is considered to be the main reason for the enhancement of the PL intensity.
Dictionary learning-based reverberation removal enables depth-resolved photoacoustic microscopy of cortical microvasculature in the mouse brain Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Sushanth Govinahallisathyanarayana, Bo Ning, Rui Cao, Song Hu, John A. Hossack
Photoacoustic microscopy (PAM) capitalizes on the optical absorption of blood hemoglobin to enable label-free high-contrast imaging of the cerebral microvasculature in vivo. Although time-resolved ultrasonic detection equips PAM with depth-sectioning capability, most of the data at depths are often obscured by acoustic reverberant artifacts from superficial cortical layers and thus unusable. In this paper, we present a first-of-a-kind dictionary learning algorithm to remove the reverberant signal while preserving underlying microvascular anatomy. This algorithm was validated in vitro, using dyed beads embedded in an optically transparent polydimethylsiloxane phantom. Subsequently, we demonstrated in the live mouse brain that the algorithm can suppress reverberant artifacts by 21.0 ± 5.4 dB, enabling depth-resolved PAM up to 500 µm from the brain surface.
Widespread persistent changes to temperature extremes occurred earlier than predicted Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Chao Li, Yuanyuan Fang, Ken Caldeira, Xuebin Zhang, Noah S. Diffenbaugh, Anna M. Michalak
A critical question for climate mitigation and adaptation is to understand when and where the signal of changes to climate extremes have persistently emerged or will emerge from the background noise of climate variability. Here we show observational evidence that such persistent changes to temperature extremes have already occurred over large parts of the Earth. We further show that climate models forced with natural and anthropogenic historical forcings underestimate these changes. In particular, persistent changes have emerged in observations earlier and over a larger spatial extent than predicted by models. The delayed emergence in the models is linked to a combination of simulated change (‘signal’) that is weaker than observed, and simulated variability (‘noise’) that is greater than observed. Over regions where persistent changes had not occurred by the year 2000, we find that most of the observed signal-to-noise ratios lie within the 16–84% range of those simulated. Examination of simulations with and without anthropogenic forcings provides evidence that the observed changes are more likely to be anthropogenic than nature in origin. Our findings suggest that further changes to temperature extremes over parts of the Earth are likely to occur earlier than projected by the current climate models.
Newly discovered Late Triassic Baqing eclogite in central Tibet indicates an anticlockwise West–East Qiangtang collision Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Yu-Xiu Zhang, Xin Jin, Kai-Jun Zhang, Wei-Dong Sun, Jian-Ming Liu, Xiao-Yao Zhou, Li-Long Yan
The Triassic eclogite-bearing central Qiangtang metamorphic belt (CQMB) in the northern Tibetan Plateau has been debated whether it is a metamorphic core complex underthrust from the Jinsha Paleo-Tethys or an in-situ Shuanghu suture. The CQMB is thus a key issue to elucidate the crustal architecture of the northern Tibetan Plateau, the tectonics of the eastern Tethys, and the petrogenesis of Cenozoic high-K magmatism. We here report the newly discovered Baqing eclogite along the eastern extension of the CQMB near the Baqing town, central Tibet. These eclogites are characterized by the garnet + omphacite + rutile + phengite + quartz assemblages. Primary eclogite-facies metamorphic pressure–temperature estimates yield consistent minimum pressure of 25 ± 1 kbar at 730 ± 60 °C. U–Pb dating on zircons that contain inclusions (garnet + omphacite + rutile + phengite) gave eclogite-facies metamorphic ages of 223 Ma. The geochemical continental crustal signature and the presence of Paleozoic cores in the zircons indicate that the Baqing eclogite formed by continental subduction and marks an eastward-younging anticlockwise West–East Qiangtang collision along the Shuanghu suture from the Middle to Late Triassic.
Effects of silver nanocolloids on plant complex type N-glycans in Oryza sativa roots Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Risa Horiuchi, Yukari Nakajima, Shosaku Kashiwada, Nobumitsu Miyanishi
Silver nanomaterials have been mainly developed as antibacterial healthcare products worldwide, because of their antibacterial activity. However, there is little data regarding the potential risks and effects of large amounts of silver nanomaterials on plants. In contrast, N-glycans play important roles in various biological phenomena, and their structures and expressions are sensitive to ambient environmental changes. Therefore, to assesse the effects of silver nanomaterials, we focused on the correlation between N-glycans and the effects of silver nanomaterials in plants and analyzed N-glycan structures in Oryza sativa seedlings exposed to silver nanocolloids (SNCs). The phenotype analysis showed that the shoot was not affected by any SNC concentrations, whereas the high SNC exposed root was seriously damaged. Therefore, we performed comparative N-glycan analysis of roots. As a result, five of total N-glycans were significantly increased in SNC exposed roots, of which one was a free-N-glycan with one beta-N-acetylglucosamine residue at the reducing end. Our results suggest that the transition of plant complex type N-glycans, including free-N-glycans, was caused by abnormalities in O. sativa development, and free-N-glycan itself has an important role in plant development. This study originally adapted glycome transition analysis to environmental toxicology and proposed a new category called “Environmental glycobiology”.
Mercury sodium exospheric emission as a proxy for solar perturbations transit Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Stefano Orsini, Valeria Mangano, Anna Milillo, Christina Plainaki, Alessandro Mura, Jim M. Raines, Elisabetta De Angelis, Rosanna Rispoli, Francesco Lazzarotto, Alessandro Aronica
The first evidence at Mercury of direct relation between ICME transit and Na exosphere dynamics is presented, suggesting that Na emission, observed from ground, could be a proxy of planetary space weather at Mercury. The link existing between the dayside exosphere Na patterns and the solar wind-magnetosphere-surface interactions is investigated. This goal is pursued by analyzing the Na intensity hourly images, as observed by the ground-based THEMIS solar telescope during 10 selected periods between 2012 and 2013 (with seeing, σ < = 2″), when also MESSENGER data were available. Frequently, two-peak patterns of variable intensity are observed, located at high latitudes in both hemispheres. Occasionally, Na signal is instead diffused above the sub-solar region. We compare these different patterns with the in-situ time profiles of proton fluxes and magnetic field data from MESSENGER. Among these 10 cases, only in one occasion the Na signal is diffused above the subsolar region, when the MESSENGER data detect the transit of two ICMEs. The selected cases suggest that the Na emission patterns are well related to the solar wind conditions at Mercury. Hence, the exospheric Na emission patterns, observed from ground, could be considered as a ‘natural monitor’ of solar disturbances when transiting near Mercury.
Malaria infected red blood cells release small regulatory RNAs through extracellular vesicles Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Kehinde Adebayo Babatunde, Smart Mbagwu, María Andrea Hernández-Castañeda, Swamy R. Adapa, Michael Walch, Luis Filgueira, Laurent Falquet, Rays H. Y. Jiang, Ionita Ghiran, Pierre-Yves Mantel
The parasite Plasmodium falciparum causes the most severe form of malaria. Cell communication between parasites is an important mechanism to control population density and differentiation. The infected red blood cells (iRBCs) release small extracellular vesicles (EVs) that transfer cargoes between cells. The EVs synchronize the differentiation of the asexual parasites into gametocytes to initiate the transmission to the mosquito. Beside their role in parasite communication, EVs regulate vascular function. So far, the exact cargoes responsible for cellular communication remain unknown. We isolated EVs from cultured iRBCs to determine their small RNA content. We identified several types of human and plasmodial regulatory RNAs. While the miRNAs and tRNA-derived fragments were the most abundant human RNAs, we also found Y-RNAs, vault RNAs, snoRNAs and piRNAs. Interestingly, we found about 120 plasmodial RNAs, including mRNAs coding for exported proteins and proteins involved in drug resistance, as well as non-coding RNAs, such as rRNAs, small nuclear (snRNAs) and tRNAs. These data show, that iRBC-EVs carry small regulatory RNAs. A role in cellular communication is possible since the RNAs were transferred to endothelial cells. Furthermore, the presence of Plasmodium RNAs, in EVs suggests that they may be used as biomarker to track and detect disease.
Galectin-13, a different prototype galectin, does not bind β-galacto-sides and forms dimers via intermolecular disulfide bridges between Cys-136 and Cys-138 Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Jiyong Su, Yue Wang, Yunlong Si, Jin Gao, Chenyang Song, Linlin Cui, Runjie Wu, Guihua Tai, Yifa Zhou
During pregnancy, placental protein-13 (galectin-13) is highly expressed in the placenta and fetal tissue, and less so in maternal serum that is related to pre-eclampsia. To understand galectin-13 function at the molecular level, we solved its crystal structure and discovered that its dimer is stabilized by two disulfide bridges between Cys136 and Cys138 and six hydrogen bonds involving Val135, Val137, and Gln139. Native PAGE and gel filtration demonstrate that this is not a crystallization artifact because dimers also form in solution. Our biochemical studies indicate that galectin-13 ligand binding specificity is different from that of other galectins in that it does not bind β-galactosides. This is partly explained by the presence of Arg53 rather than His53 at the bottom of the carbohydrate binding site in a position that is crucial for interactions with β-galactosides. Mutating Arg53 to histidine does not re-establish normal β-galactoside binding, but rather traps cryoprotectant glycerol molecules within the ligand binding site in crystals of the R53H mutant. Moreover, unlike most other galectins, we also found that GFP-tagged galectin-13 is localized within the nucleus of HeLa and 293 T cells. Overall, galectin-13 appears to be a new type of prototype galectin with distinct properties.
The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from Drosophila to Humans Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Heng Wu, Hunkar Gizem Yesilyurt, Jimok Yoon, Jonathan R. Terman
Cellular form and function – and thus normal development and physiology – are specified via proteins that control the organization and dynamic properties of the actin cytoskeleton. Using the Drosophila model, we have recently identified an unusual actin regulatory enzyme, Mical, which is directly activated by F-actin to selectively post-translationally oxidize and destabilize filaments – regulating numerous cellular behaviors. Mical proteins are also present in mammals, but their actin regulatory properties, including comparisons among different family members, remain poorly defined. We now find that each human MICAL family member, MICAL-1, MICAL-2, and MICAL-3, directly induces F-actin dismantling and controls F-actin-mediated cellular remodeling. Specifically, each human MICAL selectively associates with F-actin, which directly induces MICALs catalytic activity. We also find that each human MICAL uses an NADPH-dependent Redox activity to post-translationally oxidize actin’s methionine (M) M44/M47 residues, directly dismantling filaments and limiting new polymerization. Genetic experiments also demonstrate that each human MICAL drives F-actin disassembly in vivo, reshaping cells and their membranous extensions. Our results go on to reveal that MsrB/SelR reductase enzymes counteract each MICAL’s effect on F-actin in vitro and in vivo. Collectively, our results therefore define the MICALs as an important phylogenetically-conserved family of catalytically-acting F-actin disassembly factors.
Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Elisa Caiola, Roberta Frapolli, Michele Tomanelli, Rossana Valerio, Alice Iezzi, Marina C. Garassino, Massimo Broggini, Mirko Marabese
Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted therapies are only used for about 15% of patients where a specific driving and druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently mutated genes in NSCLC and patients harboring these mutations do not benefit from specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was proposed as a potentially active drug in KRAS-mutated NSCLC patients, but clinical trials results were not conclusive. Here we show that the NSCLC cells’ response to sorafenib depends on the type of KRAS mutation. KRAS G12V cells respond less to sorafenib than the wild-type counterpart, in vitro and in vivo. To overcome this resistance, we used high-throughput screening with a siRNA library directed against 719 human kinases, and Wee1 was selected as a sorafenib response modulator. Inhibition of Wee1 by its specific inhibitor MK1775 in combination with sorafenib restored the KRAS mutated cells’ response to the multi-target tyrosine kinase inhibitor. This combination of the Wee1 inhibitor with sorafenib, if confirmed in models with different genetic backgrounds, might be worth investigating further as a new strategy for KRAS mutated NSCLC.
Procalcitonin as a Biomarker for Malignant Cerebral Edema in Massive Cerebral Infarction Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Yan Zhang, Gang Liu, Yuan Wang, Yingying Su, Rehana K. Leak, Guodong Cao
The objective of this study is to explore whether procalcitonin (PCT) can serve as an early biomarker of malignant cerebral edema in patients with massive cerebral infarction (MCI). Ninety-three patients with acute MCI were divided into death or survival groups based on whether they died or survived within 1 week of cerebral herniation. Differences in laboratory parameters between these two groups were analyzed by univariate analysis, followed by multivariate logistic regression analyses if the influencing factors were significantly different. Compared with the survival group, the patients in the death group had a larger cerebral infarct area, higher body temperature, neutrophil counts, PCT level, and neuron-specific enolase (NSE) level within 48 h of onset. Multivariate logistic regression analyses revealed an odds ratio (OR) of 1.830 or 1.235 for PCT and neutrophil counts respectively, suggesting that PCT and neutrophil counts are two independent risk factors for death in MCI. The area under receiver operating characteristic (ROC) curve was 0.754 for PCT, larger than that for neutrophil counts. Thus, both serum PCT levels and neutrophil counts can be used as biomarkers to predict malignant cerebral edema at the early stages after MCI, but PCT levels are superior predictors of malignant cerebral edema.
Radiological and clinical differences among three assisted technologies in pedicle screw fixation of adult degenerative scoliosis Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Yong Fan, Jin Peng Du, Ji Jun Liu, Jia Nan Zhang, Shi Chang Liu, Ding Jun Hao
The purpose of this study was to compare the clinical and radiological differences among three advanced guided technologies in adult degenerative scoliosis. A total of 1012 pedicle screws were inserted in 83 patients using a spine robot (group A), 886 screws were implanted in 75 patients using a drill guide template (group B), and 1276 screws were inserted in 109 patients using CT-based navigation (group C). Screw positions were evaluated using postoperative CT scans according to the Gertzbein and Robbins classification. Other relevant data were also collected. Perfect pedicle screw insertion (Grade A) accuracy in groups A, B, and C was 91.3%, 81.3%, and 84.1%, respectively. Clinically acceptable accuracy of screw implantation (Grades A + B) respectively was 96.0%, 90.6%, and 93.0%. Statistical analysis showed the perfect and clinically acceptable accuracy in group A was significant different compared with groups B and C. Group A exhibited the lowest intra-op radiation dose and group B showed the shortest surgical time compared with the other two groups. Robotic-assisted technology demonstrated significantly higher accuracy than the drill guide template or CT-based navigation systems for difficult screw implantations in adult degenerative scoliosis and reduced the intra-op radiation dose, although it failed to reduce surgery time.
Erratum: Sensory augmentation: integration of an auditory compass signal into human perception of space Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Frank Schumann, J. Kevin O’Regan
Erratum: Sensory augmentation: integration of an auditory compass signal into human perception of space
nNOS-positive minor-branches of the dorsal penile nerves is associated with erectile function in the bilateral cavernous injury model of rats Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Yen-Lin Chen, Ting-Ting Chao, Yi-No Wu, Meng-Chuan Chen, Ying-Hung Lin, Chun-Hou Liao, Chien-Chih Wu, Kuo-Chiang Chen, Shang-Shing P. Chou, Han-Sun Chiang
The changes in neuronal nitric oxide synthases (nNOS) in the dorsal penile nerves (DPNs) are consistent with cavernous nerve (CN) injury in rat models. However, the anatomical relationship and morphological changes between the minor branches of the DPNs and the CNs after injury have never been clearly explored. There were forty 12 week old male Sprague-Dawley rats receiving bilateral cavernous nerve injury (BCNI). Erectile function of intracavernous pressure and mean arterial pressure were measured. The histology and ultrastructure with H&E stain, Masson’s trichrome stain and immunohistochemical stains were applied on the examination of CNs and DPNs. We demonstrated communicating nerve branches between the DPNs and the CNs in rats. The greatest damage and lowest erectile function were seen in the 14th day and partially recovered in the 28th day after BCNI. The nNOS positive DPN minor branches’ number was significantly correlated with erectile function. The sub-analysis of the number of nNOS positive DPN minor branches also matched with the time course of the erectile function after BCNI. We suggest the regeneration of the DPNs minor branches would ameliorate the erectile function in BCNI rats.
Author Correction: Comparison of bacterial microbiota of the predatory mite Neoseiulus cucumeris (Acari: Phytoseiidae) and its factitious prey Tyrophagus putrescentiae (Acari: Acaridae) Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Apostolos Pekas, Eric Palevsky, Jason C. Sumner, M. Alejandra Perotti, Marta Nesvorna, Jan Hubert
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.
A novel α-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and exhibits potent analgesic activity Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Zhuguo Liu, Peter Bartels, Mahsa Sadeghi, Tianpeng Du, Qing Dai, Cui Zhu, Shuo Yu, Shuo Wang, Mingxin Dong, Ting Sun, Jiabin Guo, Shuangqing Peng, Ling Jiang, David J. Adams, Qiuyun Dai
We here describe a novel α-conopeptide, Eu1.6 from Conus eburneus, which exhibits strong anti-nociceptive activity by an unexpected mechanism of action. Unlike other α-conopeptides that largely target nicotinic acetylcholine receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the α3β4 and α7 nAChR subtypes and TTX-resistant sodium channels, and no activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG) neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type calcium channel currents in isolated mouse DRG neurons which was independent of GABAB receptor activation. In HEK293 cells expressing CaV2.2 channels alone, Eu1.6 reversibly inhibited depolarization-activated Ba2+ currents in a voltage- and state-dependent manner. Inhibition of CaV2.2 by Eu1.6 was concentration-dependent (IC50 ~1 nM). Significantly, systemic administration of Eu1.6 at doses of 2.5–5.0 μg/kg exhibited potent analgesic activities in rat partial sciatic nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had no significant side-effect on spontaneous locomotor activity, cardiac and respiratory function, and drug dependence in mice. These findings suggest α-conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and chronic pain and opens a novel option for future analgesic drug design.
Counting Caenorhabditis elegans: Protocol Optimization and Applications for Population Growth and Toxicity Studies in Liquid Medium Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Leona D. Scanlan, Steven P. Lund, Sanem Hosbas Coskun, Shannon K. Hanna, Monique E. Johnson, Christopher M. Sims, Karina Brignoni, Patricia Lapasset, Elijah J. Petersen, John T. Elliott, Bryant C. Nelson
The nematode Caenorhabditis elegans is used extensively in molecular, toxicological and genetics research. However, standardized methods for counting nematodes in liquid culture do not exist despite the wide use of nematodes and need for accurate measurements. Herein, we provide a simple and affordable counting protocol developed to maximize count accuracy and minimize variability in liquid nematode culture. Sources of variability in the counting process were identified and tested in 14 separate experiments. Three variables resulted in significant effects on nematode count: shaking of the culture, priming of pipette tips, and sampling location within a microcentrifuge tube. Between-operator variability did not have a statistically significant effect on counts, even among differently-skilled operators. The protocol was used to assess population growth rates of nematodes in two different but common liquid growth media: axenic modified Caenorhabditis elegans Habitation and Reproduction medium (mCeHR) and S-basal complete. In mCeHR, nematode populations doubled daily for 10 d. S-basal complete populations initially doubled every 12 h, but slowed within 7 d. We also detected a statistically significant difference between embryo-to-hatchling incubation period of 5 d in mCeHR compared to 4 d in S-basal complete. The developed counting method for Caenorhabditis elegans reduces variability and allows for rigorous and reliable experimentation.
Sclerotic bone lesions as a potential imaging biomarker for the diagnosis of tuberous sclerosis complex Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Susanne Brakemeier, Lars Vogt, Lisa C. Adams, Bianca Zukunft, Gerd Diederichs, Bernd Hamm, Klemens Budde, Kai-Uwe Eckardt, Marcus R. Makowski
Tuberous-sclerosis-complex (TSC) is associated with a high lifetime risk of severe complications. Clinical manifestations are largely variable and diagnosis is often missed. Sclerotic-bone-lesions (SBL) could represent a potential imaging biomarker for the diagnosis of TSC. In this study, computed tomography (CT) data sets of 49 TSC patients (31 females) were included and compared to an age/sex matched control group. Imaging features of SBLs included frequency, size and location pattern. Sensitivities, specificities and cutoff values for the diagnosis of TSC were established for the skull, thorax, and abdomen/pelvis. In TSC patients, 3439 SBLs were detected, including 665 skull SBLs, 1426 thoracal SBLs and 1348 abdominal/pelvic SBLs. In the matched control-collective, 157 SBLs could be found. The frequency of SBLs enabled a reliable differentiation between TSC patients and the control collective with the following sensitivities and specificities. Skull: ≥5 SBLs, 0.783, 1; thorax: ≥4 SBLs, 0.967, 0.967; abdomen/pelvis: ≥5 SBLs: 0.938, 0.906. SBL size was significantly larger compared to controls (p < 0.05). Based on the frequency, size and location pattern of SBLs TSC can be suspected. SBLs may serve as a potential imaging biomarker in the workup of TSC patients.
Metal-free magnetism, spin-dependent Seebeck effect, and spin-Seebeck diode effect in armchair graphene nanoribbons Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Xiao-Qin Tang, Xue-Mei Ye, Xing-Yi Tan, Da-Hua Ren
Metal-free magnetism and spin caloritronics are at the forefront of condensed-matter physics. Here, the electronic structures and thermal spin-dependent transport properties of armchair graphene nanoribbons (N-AGNRs), where N is the ribbon width (N = 5–23), are systematically studied. The results show that the indirect band gaps exhibit not only oscillatory behavior but also periodic characteristics with E 3p > E3p+1 > E3p+2 (E 3p , E3p+1 and E3p+2 are the band gaps energy) for a certain integer p, with increasing AGNR width. The magnetic ground states are ferromagnetic (FM) with a Curie temperatures (T C ) above room temperature. Furthermore, the spin-up and spin-down currents with opposite directions, generated by a temperature gradient, are almost symmetrical, indicating the appearance of the perfect spin-dependent Seebeck effect (SDSE). Moreover, thermally driven spin currents through the nanodevices induced the spin-Seebeck diode (SSD) effect. Our calculation results indicated that AGNRs can be applied in thermal spin nanodevices.
Ocular and Clinical Characteristics Associated with the Extent of Posterior Lamina Cribrosa Curve in Normal Tension Glaucoma Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Seung Hyen Lee, Tae-Woo Kim, Eun Ji Lee, Michaël J. A. Girard, Jean Martial Mari, Robert Ritch
Although normal-tension glaucoma (NTG) is pathogenetically heterogenous, there have been few attempts to subclassify NTG patients according to the mechanism and anatomy of optic nerve damage. This cross-sectional study was performed to investigate differences in the clinical and ocular characteristics between NTG patient groups stratified according to the degree of posterior lamina cribrosa (LC) curve which was assessed by calculating LC curvature index (LCCI). A total of 101 eyes of 101 treatment naïve NTG patients were included. The optic nerve head was imaged using enhanced-depth-imaging spectral-domain optical coherence tomography in three horizontal B-scan images in each eye. The patients were divided into two groups based on the magnitude of LCCI using a cutoff of known upper 95 percentile value in healthy subjects: a steeply curved LC group (Group 1, 75 eyes, 74.3%) and a relatively flat LC group (Group 2, 26 eyes, 25.7%). NTG eyes with relatively flat LC had lower intraocular pressure, and were associated with greater parapapillary structural alternation and systemic risk factors. These data suggest that assessment of LC morphology may help clinicians seek additional risk factors and make inferences about the mechanism of optic nerve damage in individual patients.
Electronic Properties of Synthetic Shrimp Pathogens-derived DNA Schottky Diodes Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Nastaran Rizan, Chan Yen Yew, Maryam Rajabpour Niknam, Jegenathan Krishnasamy, Subha Bhassu, Goh Zee Hong, Sridevi Devadas, Mohamed Shariff Mohd Din, Hairul Anuar Tajuddin, Rofina Yasmin Othman, Siew Moi Phang, Mitsumasa Iwamoto, Vengadesh Periasamy
The exciting discovery of the semiconducting-like properties of deoxyribonucleic acid (DNA) and its potential applications in molecular genetics and diagnostics in recent times has resulted in a paradigm shift in biophysics research. Recent studies in our laboratory provide a platform towards detecting charge transfer mechanism and understanding the electronic properties of DNA based on the sequence-specific electronic response, which can be applied as an alternative to identify or detect DNA. In this study, we demonstrate a novel method for identification of DNA from different shrimp viruses and bacteria using electronic properties of DNA obtained from both negative and positive bias regions in current-voltage (I–V) profiles. Characteristic electronic properties were calculated and used for quantification and further understanding in the identification process. Aquaculture in shrimp industry is a fast-growing food sector throughout the world. However, shrimp culture in many Asian countries faced a huge economic loss due to disease outbreaks. Scientists have been using specific established methods for detecting shrimp infection, but those methods do have their significant drawbacks due to many inherent factors. As such, we believe that this simple, rapid, sensitive and cost-effective tool can be used for detection and identification of DNA from different shrimp viruses and bacteria.
Prebiotic formation of cyclic dipeptides under potentially early Earth conditions Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Jianxi Ying, Rongcan Lin, Pengxiang Xu, Yile Wu, Yan Liu, Yufen Zhao
Cyclic dipeptides, also known as 2,5-diketopiperazines (DKPs), represent the simplest peptides that were first completely characterized. DKPs can catalyze the chiral selection of reactions and are considered as peptide precursors. The origin of biochemical chirality and synthesis of peptides remains abstruse problem believed to be essential precondition to origin of life. Therefore, it is reasonable to believe that the DKPs could have played a key role in the origin of life. How the formation of the DKPs through the condensation of unprotected amino acids in simulated prebiotic conditions has been unclear. Herein, it was found that cyclo-Pro-Pro could be formed directly from unprotected proline in the aqueous solution of trimetaphosphate (P3m) under mild condition with the yield up to 97%. Other amino acids were found to form proline-containing DKPs under the same conditions in spite of lower yield. During the formation process of these DKPs, P3m promotes the formation of linear dipeptides in the first step of the mechanism. The above findings are helpful and significant for understanding the formation of DKPs in the process of chemical evolution of life.
Multi-wavelength growth of nanosecond laser-induced surface damage on fused silica gratings Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Maxime Chambonneau, Laurent Lamaignère
The nanosecond laser-induced damage growth phenomenon on the exit surface of fused silica grating is investigated at 1064 nm and 355 nm separately and also simultaneously. Experiments are first carried out on damage sites on a plane fused silica sample showing two different morphologies, and a damage type is selected for ensuring the repeatability of the subsequent tests. Comparing the mono-wavelength growth results on a grating and a plane fused silica sample, the periodic surface structure is found to be an aggravating factor for damage growth. This is highly supported by calculations of the enhancement of the optical electric field intensity thanks to Finite-Difference Time-Domain simulations. Finally, the mono-wavelength results enable us to quantify a coupling occurring in the multi-wavelength configuration, which could originate from the heating of the plasma (more likely produced in the ultraviolet) preferentially by the infrared pulse. This study provides interesting results about the involvement of the surface topography in damage growth, and paves the way towards the comprehension of this phenomenon at high-energy nanosecond laser facilities where fused silica gratings are simultaneously irradiated at several wavelengths.
Determinants of population responses to environmental fluctuations Sci. Rep. (IF 4.259) Pub Date : 2018-01-17 Jose M. G. Vilar, J. Miguel Rubi
Environmental fluctuations, such as changing conditions and variable nutrient availability, are an unavoidable component of the dynamics of virtually all populations. They affect populations in ways that are often difficult to predict and sometimes lead to paradoxical outcomes. Here, we present a general analytical approach to examine how populations respond to fluctuations. We show that there exist general explicit conditions that determine to what extent fluctuations propagate to the variability of the responses and how they change the behavior of the system, including whether they promote proliferation or death and whether they facilitate coexistence or exclusion of competing species. These conditions depend on linear and nonlinear terms of the growth rate and on the characteristic times of the fluctuations. We validated our general approach through computational experiments for both stochastic and chaotic fluctuations and for multiple types of systems. From an applied point of view, our results provide an avenue for the precise control of the population behavior through fluctuations in addition to just through average properties.
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