bluuebunny/crossref_metadata_2025 huggingface dataset:
A combined experimental and first-principle study on the oxidation mechanism of super austenitic stainless steel S32654 at 900 °C
Authors: Dong Nan , Zhang Caili , Li Huabing , Zhang Binbin , Han Peide
Published: April 2017

A combined experimental and first-principle study on the oxidation mechanism of super austenitic stainless steel S32654 at 900 °C for a short time period (1, 3, and 5 h) in air is presented. The samples exhibit excellent oxidation resistance because of the initial and gradual formation of the denser Fe- and Cr-rich layer with increasing oxidation time. Meanwhile, the Mo-rich layer gradually forms because of the Mo diffusion, which results in the formation of the oxide layer with two distinct regions: an inner Fe- and Cr-rich layer and an outer Mo-rich layer. Density functional theory is applied to investigate the diffusion behaviour of Mo atom in the Fe-Cr-Ni/Cr2O3interface and the effects of alloying elements (Fe, Ni, and Mn) on the Mo diffusion. The Mo originating from the alloy matrix tends to diffuse into the Cr2O3part, thereby resulting in the formation of the continuous Mo-rich layer, which is consistent with the experimental behaviour. Moreover, the introduction of Ni to the Cr2O3part can promote the Mo diffusion and the formation of the Mo-rich oxide layer, whereas Fe and Mn can hinder the Mo diffusion. The calculated results provide a microcosmic explanation of the experimental results.
Erratum: Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis
Authors: Sit Regina WS , Chung Vincent CH , Reeves Kenneth D. , Rabago David , Chan Keith KW , Chan Dicken CC , Wu Xinyin , Ho Robin ST , Wong Samuel YS
Published: April 2017

Scientific Reports 6: Article number: 25247; published online: 05 May 2016; updated: 07 April 2017 This Article contains errors in Tables 1, 2, 3 and 4 where references 29, 30 and 31 are incorrectly given as references 21, 22 and 30 respectively.
Correction: Corrigendum: Phosphines are ribonucleotide reductase reductants that act via C-terminal cysteines similar to thioredoxins and glutaredoxins
Authors: Domkin Vladimir , Chabes Andrei
Published: April 2017

Scientific Reports 4: Article number: 5539; published online: 02 July 2014; updated: 07 April 2017. This Article contains a typographical error in the Methods section under subheading ‘Ribonucleotide Reductase Assay’. “Supernatants were loaded onto pre-washed 2 mL Dowex AG 1X8, 200–400 in [H+]-form columns prepared by replacing the Sephadex in NAP-10 columns (Amersham Bioscience) with 2 mL of Dowex from Bio-Rad pre-packed columns”.
Correction: Corrigendum: Switch from sexual to parthenogenetic reproduction in a zebra shark
Authors: Dudgeon Christine L. , Coulton Laura , Bone Ren , Ovenden Jennifer R. , Thomas Severine
Published: April 2017

Scientific Reports 7: Article number: 40537; published online: 16 January 2017; updated: 07 April 2017. This Article contains errors in Table 1. The correct Table 1 appears below as Table 1.
North Andean origin and diversification of the largest ithomiine butterfly genus
Authors: Lisa De-Silva Donna , Mota Luísa L. , Chazot Nicolas , Mallarino Ricardo , Silva-Brandão Karina L. , Piñerez Luz Miryam Gómez , Freitas André V.L. , Lamas Gerardo , Joron Mathieu , Mallet James , Giraldo Carlos E. , Uribe Sandra , Särkinen Tiina , Knapp Sandra , Jiggins Chris D. , Willmott Keith R. , Elias Marianne
Published: April 2017

The Neotropics harbour the most diverse flora and fauna on Earth. The Andes are a major centre of diversification and source of diversity for adjacent areas in plants and vertebrates, but studies on insects remain scarce, even though they constitute the largest fraction of terrestrial biodiversity. Here, we combine molecular and morphological characters to generate a dated phylogeny of the butterfly genus Pteronymia (Nymphalidae: Danainae), which we use to infer spatial, elevational and temporal diversification patterns. We first propose six taxonomic changes that raise the generic species total to 53, making Pteronymia the most diverse genus of the tribe Ithomiini. Our biogeographic reconstruction shows that Pteronymia originated in the Northern Andes, where it diversified extensively. Some lineages colonized lowlands and adjacent montane areas, but diversification in those areas remained scarce. The recent colonization of lowland areas was reflected by an increase in the rate of evolution of species’ elevational ranges towards present. By contrast, speciation rate decelerated with time, with no extinction. The geological history of the Andes and adjacent regions have likely contributed to Pteronymia diversification by providing compartmentalized habitats and an array of biotic and abiotic conditions, and by limiting dispersal between some areas while promoting interchange across others.
Design and application of a lactulose biosensor
Authors: Wu Jieyuan , Jiang Peixia , Chen Wei , Xiong Dandan , Huang Linglan , Jia Junying , Chen Yuanyuan , Jin Jian-Ming , Tang Shuang-Yan
Published: April 2017

In this study the repressor of Escherichia coli lac operon, LacI, has been engineered for altered effector specificity. A LacI saturation mutagenesis library was subjected to Fluorescence Activated Cell Sorting (FACS) dual screening. Mutant LacI-L5 was selected and it is specifically induced by lactulose but not by other disaccharides tested (lactose, epilactose, maltose, sucrose, cellobiose and melibiose). LacI-L5 has been successfully used to construct a whole-cell lactulose biosensor which was then applied in directed evolution of cellobiose 2-epimerase (C2E) for elevated lactulose production. The mutant C2E enzyme with ~32-fold enhanced expression level was selected, demonstrating the high efficiency of the lactulose biosensor. LacI-L5 can also be used as a novel regulatory tool. This work explores the potential of engineering LacI for customized molecular biosensors which can be applied in practice.
Central nervous system and muscular bundles preserved in a 240 million year old giant bristletail (Archaeognatha: Machilidae)
Authors: Montagna Matteo , Haug Joachim T. , Strada Laura , Haug Carolin , Felber Markus , Tintori Andrea
Published: April 2017

Among the incomparably diverse group of insects no cases of central nervous system (CNS) preservation have been so far described in compression fossils. A third of the fossil insects collected from a 240–239 million year old (Ma) level at Monte San Giorgio UNESCO World Heritage (Switzerland-Italy) underwent phosphatization, resulting in the extraordinary preservation of soft tissues. Here we describeGigamachilis triassicusgen. et sp. nov. (Archaeognatha: Machiloidea: Machilidae) that, with an estimated total length of ~80 millimeters, represents the largest apterygote insect ever recorded. The holotype preserves: (i) components of the CNS represented by four abdominal ganglia, optic lobes with neuropils and compound retina; (ii) muscular bundles. Moreover,G. triassicus, possessing morphological features that prompt its assignment to the extant archaeognathan ingroup Machilidae, places the origin of modern lineages to Middle Triassic. Interestingly, at Monte San Giorgio, in the same stratigraphic unit the modern morphology ofG. triassicusco-occurs with the ancient one represented byDasyleptus triassicus(Archaeognatha: †Monura). Comparing these two types of body organization we provide a new reconstruction of the possible character evolution leading towards modern archaeognathan forms, suggesting the acquisition of novel features in a lineage of apterygote insects during the Permian or the Lower Triassic.
Reproducing the hierarchy of disorder for Morpho-inspired, broad-angle color reflection
Authors: Song Bokwang , Johansen Villads Egede , Sigmund Ole , Shin Jung H.
Published: April 2017

The scales of Morpho butterflies are covered with intricate, hierarchical ridge structures that produce a bright, blue reflection that remains stable across wide viewing angles. This effect has been researched extensively, and much understanding has been achieved using modeling that has focused on the positional disorder among the identical, multilayered ridges as the critical factor for producing angular independent color. Realizing such positional disorder of identical nanostructures is difficult, which in turn has limited experimental verification of different physical mechanisms that have been proposed. In this paper, we suggest an alternative model of inter-structural disorder that can achieve the same broad-angle color reflection, and is applicable to wafer-scale fabrication using conventional thin film technologies. Fabrication of a thin film that produces pure, stable blue across a viewing angle of more than 120 ° is demonstrated, together with a robust, conformal color coating.
Survival of human embryonic stem cells implanted in the guinea pig auditory epithelium
Authors: Lee Min Young , Hackelberg Sandra , Green Kari L. , Lunghamer Kelly G. , Kurioka Takaomi , Loomis Benjamin R. , Swiderski Donald L. , Duncan R. Keith , Raphael Yehoash
Published: April 2017

Hair cells in the mature cochlea cannot spontaneously regenerate. One potential approach for restoring hair cells is stem cell therapy. However, when cells are transplanted into scala media (SM) of the cochlea, they promptly die due to the high potassium concentration. We previously described a method for conditioning the SM to make it more hospitable to implanted cells and showed that HeLa cells could survive for up to a week using this method. Here, we evaluated the survival of human embryonic stem cells (hESC) constitutively expressing GFP (H9 Cre-LoxP) in deaf guinea pig cochleae that were pre-conditioned to reduce potassium levels. GFP-positive cells could be detected in the cochlea for at least 7 days after the injection. The cells appeared spherical or irregularly shaped, and some were aggregated. Flushing SM with sodium caprate prior to transplantation resulted in a lower proportion of stem cells expressing the pluripotency marker Oct3/4 and increased cell survival. The data demonstrate that conditioning procedures aimed at transiently reducing the concentration of potassium in the SM facilitate survival of hESCs for at least one week. During this time window, additional procedures can be applied to initiate the differentiation of the implanted hESCs into new hair cells.
Two types of peak emotional responses to music: The psychophysiology of chills and tears
Authors: Mori Kazuma , Iwanaga Makoto
Published: April 2017

People sometimes experience a strong emotional response to artworks. Previous studies have demonstrated that the peak emotional experience of chills (goose bumps or shivers) when listening to music involves psychophysiological arousal and a rewarding effect. However, many aspects of peak emotion are still not understood. The current research takes a new perspective of peak emotional response of tears (weeping, lump in the throat). A psychophysiological experiment showed that self-reported chills increased electrodermal activity and subjective arousal whereas tears produced slow respiration during heartbeat acceleration, although both chills and tears induced pleasure and deep breathing. A song that induced chills was perceived as being both happy and sad whereas a song that induced tears was perceived as sad. A tear-eliciting song was perceived as calmer than a chill-eliciting song. These results show that tears involve pleasure from sadness and that they are psychophysiologically calming; thus, psychophysiological responses permit the distinction between chills and tears. Because tears may have a cathartic effect, the functional significance of chills and tears seems to be different. We believe that the distinction of two types of peak emotions is theoretically relevant and further study of tears would contribute to more understanding of human peak emotional response.
Streptomyces pactum assisted phytoremediation in Zn/Pb smelter contaminated soil of Feng County and its impact on enzymatic activities
Authors: Ali Amjad , Guo Di , Mahar Amanullah , Ma Fang , Li Ronghua , Shen Feng , Wang Ping , Zhang Zengqiang
Published: April 2017

Anthropogenic activities, such as industrial expansion, smelting, mining and agricultural practices, have intensified the discharge of potentially toxic trace elements (PTEs) into the environment, threatening human health and other organisms. To assist phytoremediation by sorghum in soil contaminated by smelters/mines in Feng County (FC), a pot experiment was performed to examine the phytoremediation potential of Streptomyces pactum (Act12) + biochar. The results showed that root uptake of Zn and Cd was reduced by 45 and 22%, respectively, while the uptake of Pb and Cu increased by 17 and 47%, respectively. The shoot and root dry weight and chlorophyll content improved after Act12 inoculation. β-glucosidase, alkaline phosphatase and urease activities in soil improved and antioxidant activities (POD, PAL, PPO) decreased after application of Act12 + biochar due to a reduction in stress from PTEs. BCF, TF and MEA confirmed the role of Act12 in the amelioration and translocation of PTEs. PCA analysis showed a correlation between different factors that affect the translocation of PTEs. Overall, Act12 promoted the phytoremediation of PTEs. Field experiments on Act12 + biochar may provide new insights into the rehabilitation and restoration of soils contaminated by mines.
Expression, Functional Characterization, and Solid-State NMR Investigation of the G Protein-Coupled GHS Receptor in Bilayer Membranes
Authors: Schrottke Stefanie , Kaiser Anette , Vortmeier Gerrit , Els-Heindl Sylvia , Worm Dennis , Bosse Mathias , Schmidt Peter , Scheidt Holger A. , Beck-Sickinger Annette G. , Huster Daniel
Published: April 2017

The expression, functional reconstitution and first NMR characterization of the human growth hormone secretagogue (GHS) receptor reconstituted into either DMPC or POPC membranes is described. The receptor was expressed in E. coli. refolded, and reconstituted into bilayer membranes. The molecule was characterized by 15N and 13C solid-state NMR spectroscopy in the absence and in the presence of its natural agonist ghrelin or an inverse agonist. Static 15N NMR spectra of the uniformly labeled receptor are indicative of axially symmetric rotational diffusion of the G protein-coupled receptor in the membrane. In addition, about 25% of the 15N sites undergo large amplitude motions giving rise to very narrow spectral components. For an initial quantitative assessment of the receptor mobility, 1H-13C dipolar coupling values, which are scaled by molecular motions, were determined quantitatively. From these values, average order parameters, reporting the motional amplitudes of the individual receptor segments can be derived. Average backbone order parameters were determined with values between 0.56 and 0.69, corresponding to average motional amplitudes of 40–50° of these segments. Differences between the receptor dynamics in DMPC or POPC membranes were within experimental error. Furthermore, agonist or inverse agonist binding only insignificantly influenced the average molecular dynamics of the receptor.
An unbiased index to quantify participant’s phenotypic contribution to an open-access cohort
Authors: Chan Yingleong , Tung Michael , Garruss Alexander S. , Zaranek Sarah W. , Chan Ying Kai , Lunshof Jeantine E. , Zaranek Alexander W. , Ball Madeleine P. , Chou Michael F. , Lim Elaine T. , Church George M.
Published: April 2017

The Personal Genome Project (PGP) is an effort to enroll many participants to create an open-access repository of genome, health and trait data for research. However, PGP participants are not enrolled for studying any specific traits and participants choose the phenotypes to disclose. To measure the extent and willingness and to encourage and guide participants to contribute phenotypes, we developed an algorithm to score and rank the phenotypes and participants of the PGP. The scoring algorithm calculates the participation index (P-index) for every participant, where 0 indicates no reported phenotypes and 100 indicate complete phenotype reporting. We calculated the P-index for all 5,015 participants in the PGP and they ranged from 0 to 96.7. We found that participants mainly have either high scores (P-index > 90, 29.5%) or low scores (P-index < 10, 57.8%). While, there are significantly more males than female participants (1,793 versus 1,271), females tend to have on average higher P-indexes (P = 0.015). We also reported the P-indexes of participants based on demographics and states like Missouri and Massachusetts have better P-indexes than states like Utah and Minnesota. The P-index can therefore be used as an unbiased way to measure and rank participant’s phenotypic contribution towards the PGP.
Stomatin modulates the activity of the Anion Exchanger 1 (AE1, SLC4A1)
Authors: Genetet Sandrine , Desrames Alexandra , Chouali Youcef , Ripoche Pierre , Lopez Claude , Mouro-Chanteloup Isabelle
Published: April 2017

Anion Exchanger 1 (AE1) and stomatin are integral proteins of the red blood cell (RBC) membrane. Erythroid and kidney AE1 play a major role in HCO3− and Cl− exchange. Stomatins down-regulate the activity of many channels and transporters. Biochemical studies suggested an interaction of erythroid AE1 with stomatin. Moreover, we previously reported normal AE1 expression level in stomatin-deficient RBCs. Here, the ability of stomatin to modulate AE1-dependent Cl−/HCO3− exchange was evaluated using stopped-flow methods. In HEK293 cells expressing recombinant AE1 and stomatin, the permeabilities associated with AE1 activity were 30% higher in cells overexpressing stomatin, compared to cells with only endogenous stomatin expression. Ghosts from stomatin-deficient RBCs and controls were resealed in the presence of pH- or chloride-sensitive fluorescent probes and submitted to inward HCO3− and outward Cl− gradients. From alkalinization rate constants, we deduced a 47% decreased permeability to HCO3− for stomatin-deficient patients. Similarly, kinetics of Cl− efflux, followed by the probe dequenching, revealed a significant 42% decrease in patients. In situ Proximity Ligation Assays confirmed an interaction of AE1 with stomatin, in both HEK recombinant cells and RBCs. Here we show that stomatin modulates the transport activity of AE1 through a direct protein-protein interaction.
Regulatory role of G9a and LSD1 in the Transcription of Olfactory Receptors during Leukaemia Cell Differentiation
Authors: Jung Hyeonsoo , Chae Yun-Cheol , Kim Ji-Young , Jeong Oh-Seok , Kook Hoon , Seo Sang-Beom
Published: April 2017

Recent studies have reported the ectopic expression of olfactory receptors (ORs) in non-olfactory tissues, however, their physiological roles were not well elucidated. ORs are expressed in and function in different types of cancers. Here, we identified that the H3K9me2 levels of several OR promoters decreased during differentiation in the HL-60, human myeloid leukaemia cell line, by all-trans-retinoic acid (ATRA). We found that the differential OR promoters H3K9me2 levels were regulated by G9a and LSD1, resulting in the decrease of ORs transcription during HL-60 differentiation. G9a and LSD1 could regulate the expression of ORs in several non-olfactory cells via the methylation and demethylation of H3K9me2. In addition, we demonstrated that knockdown of OR significantly reduced cell proliferation. Therefore, the epigenetic regulation of ORs transcription is critical for carcinogenesis.
Integrated proteomic analysis of Brachypodium distachyon roots and leaves reveals a synergistic network in the response to drought stress and recovery
Authors: Bian Yanwei , Deng Xiong , Yan Xing , Zhou Jiaxing , Yuan Linlin , Yan Yueming
Published: April 2017

In this study, we performed the first integrated physiological and proteomic analysis of the response to drought and recovery from drought, using Brachypodium distachyon L. Roots and leaves. Drought stress resulted in leaves curling, root tips becoming darker in color and significant changes in some physiological parameters. Two-dimensional difference gel electrophoresis (2D-DIGE) identified 78 and 98 differentially accumulated protein (DAP) spots representing 68 and 73 unique proteins responding to drought stress and/or recovery in roots and leaves, respectively. Differences between the root and leaf proteome were most marked for photosynthesis, energy metabolism, and protein metabolism. In particular, some DAPs involved in energy and protein metabolism had contrasting accumulation patterns in roots and leaves. Protein-protein interaction (PPI) analysis of roots and leaves revealed complex protein interaction networks that can generate synergistic responses to drought stress and during recovery from drought. Transcript analysis using quantitative real-time polymerase chain reaction (qRT-PCR) validated the differential expression of key proteins involved in the PPI network. Our integrated physiological and proteomic analysis provides evidence for a synergistic network involved in responses to drought and active during recovery from drought, in Brachypodium roots and leaves.
Methane protects against polyethylene glycol-induced osmotic stress in maize by improving sugar and ascorbic acid metabolism
Authors: Han Bin , Duan Xingliang , Wang Yu , Zhu Kaikai , Zhang Jing , Wang Ren , Hu Huali , Qi Fang , Pan Jincheng , Yan Yuanxin , Shen Wenbiao
Published: April 2017

Although aerobic methane (CH4) release from plants leads to an intense scientific and public controversy in the recent years, the potential functions of endogenous CH4production in plants are still largely unknown. Here, we reported that polyethylene glycol (PEG)-induced osmotic stress significantly increased CH4production and soluble sugar contents in maize (Zea maysL.) root tissues. These enhancements were more pronounced in the drought stress-tolerant cultivar Zhengdan 958 (ZD958) than in the drought stress-sensitive cultivar Zhongjiangyu No.1 (ZJY1). Exogenously applied 0.65 mM CH4not only increased endogenous CH4production, but also decreased the contents of thiobarbituric acid reactive substances. PEG-induced water deficit symptoms, such as decreased biomass and relative water contents in both root and shoot tissues, were also alleviated. These beneficial responses paralleled the increases in the contents of soluble sugar and the reduced ascorbic acid (AsA), and the ratio of AsA/dehydroascorbate (DHA). Further comparison of transcript profiles of some key enzymes in sugar and AsA metabolism suggested that CH4might participate in sugar signaling, which in turn increased AsA production and recycling. Together, these results suggested that CH4might function as a gaseous molecule that enhances osmotic stress tolerance in maize by modulating sugar and AsA metabolism.
Correction: Corrigendum: Visual attention spreads broadly but selects information locally
Authors: Shioiri Satoshi , Honjyo Hajime , Kashiwase Yoshiyuki , Matsumiya Kazumichi , Kuriki Ichiro
Published: April 2017

Scientific Reports 6: Article number: 35513; published online: 19 October 2016; updated: 07 April 2017 The original version of this Article contained errors in the Supplementary Figures 2, 3, 4 and 5, where the EEG data analysed was relative to the average of the C3 and C4 electrodes. These errors do not affect the conclusions of the Article and have now been corrected in the Supplementary Information file that accompanies this Article.
Characterization of O-acetylation in sialoglycans by MALDI-MS using a combination of methylamidation and permethylation
Authors: Wu Zhaoguan , Li Henghui , Zhang Qiwei , Liu Xin , Zheng Qi , Li Jianjun
Published: April 2017

O-Acetylation of sialic acid in protein N-glycans is an important modification and can occur at either 4-, 7-, 8- or 9-position in various combinations. This modification is usually labile under alkaline reaction conditions. Consequently, a permethylation-based analytical method, which has been widely used in glycomics studies, is not suitable for profiling O-acetylation of sialic acids due to the harsh reaction conditions. Alternatively, methylamidation can be used for N-glycan analysis without affecting the base-labile modification of sialic acid. In this report, we applied both permethylation and methylamidation approaches to the analysis of O-acetylation in sialic acids. It has been demonstrated that methylamidation not only stabilizes sialic acids during MALDI processing but also allow for characterization of their O-acetylation pattern. In addition, LC-MS/MS experiments were carried out to distinguish between the O-acetylated glycans with potential isomeric structures. The repeatability of methylamidation was examined to evaluate the applicability of the approach to profiling of O-acetylation in sialic acids. In conclusion, the combination of methylamidation and permethylation methodology is a powerful MALDI-TOF MS-based tool for profiling O-acetylation in sialic acids applicable to screening of N-glycans.
PD-L1 expression in lung adenosquamous carcinomas compared with the more common variants of non-small cell lung cancer
Authors: Shi Xiaohua , Wu Shafei , Sun Jian , Liu Yuanyuan , Zeng Xuan , Liang Zhiyong
Published: April 2017

Lung adenosquamous cell carcinomas (ASCs) is a rare variant of NSCLC with a poorer prognosis and fewer treatment option than the more common variants. PD-L1 expression is reported to be the predictor of clinical response in trials of NSCLC. In our study, PD-L1 expression was evaluated via immunohistochemistry using a specific monoclonal antibody (SP263), and PD-L1 mRNA expression was evaluated via in situ hybridization. This study included 51 ASCs, 133 lung adenocarcinomas, and 83 lung squamous cell carcinomas (SCC). Similar results were obtained for PD-L1 expression measured at the mRNA and protein level (k coefficient, 0.851, P = 1.000). PD-L1 expression was significantly higher in the squamous versus glandular component of the 36 ASCs in which the components were analyzed separately. The PD-L1 expression rate was similar in the squamous cell component of ASCs and lung SCC (38.89% vs. 28.92%, P = 0.293), so does the adenocarcinoma component of ASCs and lung adenocarcinomas (11.11% vs 13.53%, P = 1.000). PD-L1 expression correlated significantly with lymphovascular invasion (P = 0.016), but not with EGFR, KRAS, and ALK mutations in lung ASCs. Anit-PD-L1 is a promising treatment option in lung ASC cases in which PD-L1 upregulated and EGFR mutations are present.
Relationship between Porcine Sperm Motility and Sperm Enzymatic Activity using Paper-based Devices
Authors: Matsuura Koji , Huang Han-Wei , Chen Ming-Cheng , Chen Yu , Cheng Chao-Min
Published: April 2017

Mammalian sperm motility has traditionally been analyzed to determine fertility using computer-assisted semen analysis (CASA) systems. To develop low-cost and robust male fertility diagnostics, we created a paper-based MTT assay and used it to estimate motile sperm concentration. When porcine sperm motility was inhibited using sperm enzyme inhibitors for sperm enzymes related to mitochondrial activity and glycolysis, we simultaneously recorded sperm motility and enzymatic reactivity using a portable motility analysis system (iSperm) and a paper-based MTT assay, respectively. When using our paper-based MTT-assay, we calculated the area mean value signal intensity (AMV) to evaluate enzymatic reactivity. Both sperm motility and AMV decreased following treatment with iodoacetamide (IODO) and 3-bromopyruvic acid (3BP), both of which are inhibitors of glycolytic enzymes including glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found a correlation between recorded motility using iSperm and AMV from our paper-based assay (P < 0.05), suggesting that a sperm-related enzymatic reaction is involved in sperm motility. Under this protocol, MTT reduction was coupled with catalysis of GAPDH and was promoted by electron transfer from NADH. Based on this inhibitor study, sperm motility can be estimated using our paper-based MTT-assay.
Unexplained Early Infantile Epileptic Encephalopathy in Han Chinese Children: Next-Generation Sequencing and Phenotype Enriching
Authors: Arafat Ahmed , Jing Peng , Ma Yuping , Pu Miao , Nan Gai , Fang He , Chen Chen , Fei Yin
Published: April 2017

Early Infantile Epileptic Encephalopathy (EIEE) presents shortly after birth with frequent, severe seizures and progressive disturbance of cerebral function. This study was to investigate a cohort of Chinese children with unexplained EIEE, infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We used targeted next-generation sequencing to identify potential pathogenic variants of 308 genes in 68 Han Chinese patients with unexplained EIEE. A filter process was performed to prioritize rare variants of potential functional significance. In all cases where parental testing was accessible, Sanger sequencing confirmed the variants and determined the parental origin. In 15% of patients (n = 10/68), we identified nine de novo pathogenic variants, and one assumed de novo pathogenic variant in the following genes: CDKL5 (n = 2), STXBP1 (n = 2), SCN1A (n = 3), KCNQ2 (n = 2), SCN8A (n = 1), four of the variants are novel variants. In 4% patients (n = 3/68), we identified three likely pathogenic variants; two assumed de novo and one X-linked in the following genes: SCN1A (n = 2) and ARX (n = 1), two of these variants are novel. Variants were assumed de novo when parental testing was not available. Our findings were first reported in Han Chinese patients with unexplained EIEE, enriching the EIEE mutation spectrum bank.
Transgenic mouse model for imaging of ATF4 translational activation-related cellular stress responses in vivo
Authors: Iwawaki Takao , Akai Ryoko , Toyoshima Takae , Takeda Naoki , Ishikawa Tomo-o , Yamamura Ken-ichi
Published: April 2017

Activating transcription factor 4 (ATF4) is a translationally activated protein that plays a role in cellular adaptation to several stresses. Because these stresses are associated with various diseases, the translational control of ATF4 needs to be evaluated from the physiological and pathological points of view. We have developed a transgenic mouse model to monitor the translational activation of ATF4 in response to cellular stress. By using this mouse model, we were able to detect nutrient starvation response, antivirus response, endoplasmic reticulum (ER) stress response, and oxidative stress in vitro and ex vivo, as well as in vivo. The reporter system introduced into our mouse model was also shown to work in a stress intensity-dependent manner and a stress duration-dependent manner. The mouse model is therefore a useful tool for imaging ATF4 translational activation at various levels, from cell cultures to whole bodies, and it has a range of useful applications in investigations on the physiological and pathological roles of ATF4-related stress and in the development of clinical drugs for treating ATF4-associated diseases.
Pathogenic traits of Salmonella Montevideo in experimental infections in vivo and in vitro
Authors: Lalsiamthara Jonathan , Lee John Hwa
Published: April 2017

Salmonella serovar Montevideo (SM) is frequently associated with human Salmonella infections and causes gastrointestinal disease, cases are common particularly among individuals who come in close contact with live poultry or poultry meat products. To characterize SM disease in chickens, the pathogenic traits and tissue predilections of the disease were investigated. Dissemination of fluorescent-tagged SM (JOL1575GFP) was monitored after oral and intramuscular mock infections of specific-pathogen-free chickens. The spleen was predominantly affected by intramuscular infection while the cecum, spleen, and minimally liver were affected by oral infection. No conspicuous illness was observed in infected birds, and histopathological examination showed minimal damage of the intestinal epithelium and splenic parenchyma though SM was readily isolated from these tissues. Levels of SM internalization by primary chicken peritoneal macrophages were similar to that of Salmonella Typhimurium. SM was more sensitive to chicken than rabbit serum complement killing. Internal egg contamination of SM mock infected layers also occurred at trace levels and lasted for a week after inoculation. This study also confirmed that SM infection in chickens is sub-clinical and asymptomatic, which suggests that latent asymptomatic carriers may excrete a large number of bacteria and transmit the pathogen by contaminating water or food sources.
Rapid and direct synthesis of complex perovskite oxides through a highly energetic planetary milling
Authors: Lee Gyoung-Ja , Park Eun-Kwang , Yang Sun-A , Park Jin-Ju , Bu Sang-Don , Lee Min-Ku
Published: April 2017

The search for a new and facile synthetic route that is simple, economical and environmentally safe is one of the most challenging issues related to the synthesis of functional complex oxides. Herein, we report the expeditious synthesis of single-phase perovskite oxides by a high-rate mechanochemical reaction, which is generally difficult through conventional milling methods. With the help of a highly energetic planetary ball mill, lead-free piezoelectric perovskite oxides of (Bi, Na)TiO3, (K, Na)NbO3and their modified complex compositions were directly synthesized with low contamination. The reaction time necessary to fully convert the micron-sized reactant powder mixture into a single-phase perovskite structure was markedly short at only 30–40 min regardless of the chemical composition. The cumulative kinetic energy required to overtake the activation period necessary for predominant formation of perovskite products was ca. 387 kJ/g for (Bi, Na)TiO3and ca. 580 kJ/g for (K, Na)NbO3. The mechanochemically derived powders, when sintered, showed piezoelectric performance capabilities comparable to those of powders obtained by conventional solid-state reaction processes. The observed mechanochemical synthetic route may lead to the realization of a rapid, one-step preparation method by which to create other promising functional oxides without time-consuming homogenization and high-temperature calcination powder procedures.
Targeting BMK1 Impairs the Drug Resistance to Combined Inhibition of BRAF and MEK1/2 in Melanoma
Authors: Song Chengli , Wang Lina , Xu Qiang , Wang Kai , Xie Dan , Yu Zhe , Jiang Kui , Liao Lujian , Yates John R. , Lee Jiing-Dwan , Yang Qingkai
Published: April 2017

Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-mutant melanoma. However, drug resistance to CIBM is inevitable and the drug resistance mechanisms still remain to be elucidated. Here, we show that BMK1 pathway contributes to the drug resistance to CIBM. Considering that ERK1/2 pathway regulates cellular processes by phosphorylating, we first performed a SILAC phosphoproteomic profiling of CIBM. Phosphorylation of 239 proteins was identified to be downregulated, while phosphorylation of 47 proteins was upregulated. Following siRNA screening of 47 upregulated proteins indicated that the knockdown of BMK1 showed the most significant ability to inhibit the proliferation of CIBM resistant cells. It was found that phosphorylation of BMK1 was enhanced in resistant cells, which suggested an association of BMK1 with drug resistance. Further study indicated that phospho-activation of BMK1 by MEK5D enhanced the resistance to CIBM. Conversely, inhibition of BMK1 by shRNAi or BMK1 inhibitor (XMD8-92) impaired not only the acquirement of resistance to CIBM, but also the proliferation of CIBM resistant cells. Further kinome-scale siRNA screening demonstrated that SRC\MEK5 cascade promotes the phospho-activation of BMK1 in response to CIBM. Our study not only provides a global phosphoproteomic view of CIBM in melanoma, but also demonstrates that inhibition of BMK1 has therapeutic potential for the treatment of melanoma.
Highly pH-responsive sensor based on amplified spontaneous emission coupled to colorimetry
Authors: Zhang Qi , Castro Smirnov Jose R. , Xia Ruidong , Pedrosa Jose M. , Rodriguez Isabel , Cabanillas-Gonzalez Juan , Huang Wei
Published: April 2017

We demonstrated a simple, directly-readable approach for high resolution pH sensing. The method was based on sharp changes in Amplified Spontaneous Emission (ASE) of a Stilbene 420 (ST) laser dye triggered by the pH-dependent absorption of Bromocresol Green (BG). The ASE threshold of BG:ST solution mixtures exhibited a strong dependence on BG absorption, which was drastically changed by the variations of the pH of BG solution. As a result, ASE on-off or off-on was observed with different pH levels achieved by ammonia doping. By changing the concentration of the BG solution and the BG:ST blend ratio, this approach allowed to detect pH changes with a sensitivity down to 0.05 in the 10–11 pH range.
Genome-wide RNA-seq of iPSC-derived motor neurons indicates selective cytoskeletal perturbation in Brown–Vialetto disease that is partially rescued by riboflavin
Authors: Rizzo Federica , Ramirez Agnese , Compagnucci Claudia , Salani Sabrina , Melzi Valentina , Bordoni Andreina , Fortunato Francesco , Niceforo Alessia , Bresolin Nereo , Comi Giacomo P. , Bertini Enrico , Nizzardo Monica , Corti Stefania
Published: April 2017

Riboflavin is essential in numerous cellular oxidation/reduction reactions but is not synthesized by mammalian cells. Riboflavin absorption occurs through the human riboflavin transporters RFVT1 and RFVT3 in the intestine and RFVT2 in the brain. Mutations in these genes are causative for the Brown–Vialetto–Van Laere (BVVL), childhood-onset syndrome characterized by a variety of cranial nerve palsies as well as by spinal cord motor neuron (MN) degeneration. Why mutations in RFVTs result in a neural cell–selective disorder is unclear. As a novel tool to gain insights into the pathomechanisms underlying the disease, we generated MNs from induced pluripotent stem cells (iPSCs) derived from BVVL patients as an in vitro disease model. BVVL-MNs explained a reduction in axon elongation, partially improved by riboflavin supplementation. RNA sequencing profiles and protein studies of the cytoskeletal structures showed a perturbation in the neurofilament composition in BVVL-MNs. Furthermore, exploring the autophagy–lysosome pathway, we observed a reduced autophagic/mitophagic flux in patient MNs. These features represent emerging pathogenetic mechanisms in BVVL-associated neurodegeneration, partially rescued by riboflavin supplementation. Our data showed that this therapeutic strategy could have some limits in rescuing all of the disease features, suggesting the need to develop complementary novel therapeutic strategies.
OncoScore: a novel, Internet-based tool to assess the oncogenic potential of genes
Authors: Piazza Rocco , Ramazzotti Daniele , Spinelli Roberta , Pirola Alessandra , De Sano Luca , Ferrari Pierangelo , Magistroni Vera , Cordani Nicoletta , Sharma Nitesh , Gambacorti-Passerini Carlo
Published: April 2017

The complicated, evolving landscape of cancer mutations poses a formidable challenge to identify cancer genes among the large lists of mutations typically generated in NGS experiments. The ability to prioritize these variants is therefore of paramount importance. To address this issue we developed OncoScore, a text-mining tool that ranks genes according to their association with cancer, based on available biomedical literature. Receiver operating characteristic curve and the area under the curve (AUC) metrics on manually curated datasets confirmed the excellent discriminating capability of OncoScore (OncoScore cut-off threshold = 21.09; AUC = 90.3%, 95% CI: 88.1–92.5%), indicating that OncoScore provides useful results in cases where an efficient prioritization of cancer-associated genes is needed.
Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis
Authors: Morita Mayu , Iwasaki Ryotaro , Sato Yuiko , Kobayashi Tami , Watanabe Ryuichi , Oike Takatsugu , Nakamura Satoshi , Keneko Yosuke , Miyamoto Kana , Ishihara Kazuyuki , Iwakura Yoichiro , Ishii Ken , Matsumoto Morio , Nakamura Masaya , Kawana Hiromasa , Nakagawa Taneaki , Miyamoto Takeshi
Published: April 2017

Various conditions, including bacterial infection, can promote osteonecrosis. For example, following invasive dental therapy with anti-bone resorptive agents, some patients develop osteonecrosis in the jaw; however, pathological mechanisms underlying these outcomes remain unknown. Here, we show that administration of anti-resorptive agents such as the bisphosphonate alendronate accelerates osteonecrosis promoted by infectious osteomyelitis. Potent suppression of bone turnover by these types of agents is considered critical for osteonecrosis development; however, using mouse models we found that acceleration of bone turnover by teriparatide injection did not prevent osteonecrosis but rather converted osteoclast progenitors to macrophages expressing inflammatory cytokines, which were required for osteonecrosis development. In fact, we demonstrate that TNFα-, IL-1α/β- or IL-6-deficient mice as well as wild-type mice administered a TNFα-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Our data provide new insight into mechanisms underlying osteonecrosis and suggest new ways to prevent it.
Snake scales, partial exposure, and the Snake Detection Theory: A human event-related potentials study
Authors: Van Strien Jan W. , Isbell Lynne A.
Published: April 2017

Studies of event-related potentials in humans have established larger early posterior negativity (EPN) in response to pictures depicting snakes than to pictures depicting other creatures. Ethological research has recently shown that macaques and wild vervet monkeys respond strongly to partially exposed snake models and scale patterns on the snake skin. Here, we examined whether snake skin patterns and partially exposed snakes elicit a larger EPN in humans. In Task 1, we employed pictures with close-ups of snake skins, lizard skins, and bird plumage. In task 2, we employed pictures of partially exposed snakes, lizards, and birds. Participants watched a random rapid serial visual presentation of these pictures. The EPN was scored as the mean activity (225–300 ms after picture onset) at occipital and parieto-occipital electrodes. Consistent with previous studies, and with the Snake Detection Theory, the EPN was significantly larger for snake skin pictures than for lizard skin and bird plumage pictures, and for lizard skin pictures than for bird plumage pictures. Likewise, the EPN was larger for partially exposed snakes than for partially exposed lizards and birds. The results suggest that the EPN snake effect is partly driven by snake skin scale patterns which are otherwise rare in nature.
Preparation and evaluation of modified cyanobacteria-derived activated carbon for H2 adsorption
Authors: Gao Jun , Xie Jing , Liu Xueyan , Hu Hui
Published: April 2017

The evidently superior adsorption of hydrogen on modified activated carbon derived from cyanobacteria
A reductant-resistant ratiometric, colorimetric and far-red fluorescent probe for rapid and ultrasensitive detection of nitroxyl
Authors: Liu Caiyun , Wang Yawei , Tang Chengcheng , Liu Fang , Ma Zhenmin , Zhao Qiang , Wang Zhongpeng , Zhu Baocun , Zhang Xiaoling
Published: April 2017

A reductant-resistant ratiometric, colorimetric and far-red fluorescent probe for rapid and ultrasensitive detection of nitroxyl was developed.
Magnetically-enabled biomarker extraction and delivery system: towards integrated ASSURED diagnostic tools
Authors: Bauer Westley S. , Kimmel Danielle W. , Adams Nicholas M. , Gibson Lauren E. , Scherr Thomas F. , Richardson Kelly A. , Conrad Joseph A. , Matakala Hellen K. , Haselton Frederick R. , Wright David W.
Published: April 2017

Diagnosis of asymptomatic malaria poses a great challenge to global disease elimination efforts.
Hybrid molecular/enzymatic catalytic cascade for complete electro-oxidation of glycerol using a promiscuous NAD-dependent formate dehydrogenase from Candida boidinii
Authors: Abdellaoui Sofiene , Seow Chavez Madelaine , Matanovic Ivana , Stephens Andrew R. , Atanassov Plamen , Minteer Shelley D.
Published: April 2017

The formate dehydrogenase fromCandida boidiniiwas combined with NH2-TEMPO to form a novel hybrid anode to oxidize glycerol to carbon dioxide at near-neutral pH.
The role of sulfur oxidation in controlling the electronic properties of sulfur-containing host molecules for phosphorescent organic light-emitting diodes
Authors: Varathan E. , Subramanian V.
Published: April 2017

Quantum chemical calculations have been used to quantify the effect of sulfur oxidation on the electronic properties of DBT based host molecules for PhOLEDs.
Integration of community structure data reveals observable effects below sediment guideline thresholds in a large estuary
Authors: Tremblay Louis A. , Clark Dana , Sinner Jim , Ellis Joanne I.
Published: April 2017

Multivariate analysis detected changes in benthic community structure below guideline levels for three metals in a large estuary.
“A Jack of Trio”-robust one-pot metal free oxidative amination, azidation and peroxidation of phenols
Authors: Sarkar Debayan , Ghosh Manoj Kumar , Rout Nilendri , Kuila Puspendu
Published: April 2017

Facile generation of quaternary carbon centres has been realised in the presence of phenyl trimethyl ammonium tribromide (PTAB) mediated oxidative dearomatisation.
CV-APC, a colorimetric and red-emitting fluorescent dual probe for the highly sensitive detection of palladium
Authors: Yan Jin-wu , Wang Xiao-lin , Zhou Lin-fu , Zhang Lei
Published: April 2017

A highly sensitive colorimetric and red-emitting fluorescent dual probe was synthesized and applied to imaging palladium species based on the Tsuji–Trost reaction.
Sulfur doped graphene as a promising metal-free electrocatalyst for oxygen reduction reaction: a DFT-D study
Authors: Lu Zhansheng , Li Shuo , Liu Chuang , He Chaozheng , Yang Xinwei , Ma Dongwei , Xu Guoliang , Yang Zongxian
Published: April 2017

As an efficient metal-free catalyst, graphene doped with heteroatoms is highly active in promoting electrochemical oxygen reduction reaction (ORR).
Synthesis and characterization of an IrO2–Fe2O3 electrocatalyst for the hydrogen evolution reaction in acidic water electrolysis
Authors: Yang Xian , Li Yande , Deng Li , Li Wenyang , Ren Zhandong , Yang Ming , Yang Xiaohong , Zhu Yuchan
Published: April 2017

An IrO2–Fe2O3 electrocatalyst was prepared for the HER in acidic water electrolysis and exhibits higher activity than IrO2.
Tethering of rhBMP-2 upon calcium phosphate cement via alendronate/heparin for localized, sustained and enhanced osteoactivity
Authors: Zhu Jiaoyang , Huang Baolin , Ding Sai , Zhang Wenjing , Ma Xiaoyu , Niu Haoyi , Yuan Yuan , Liu Changsheng
Published: April 2017

rhBMP-2 was tethered on surface of calcium phosphate cementviaalendronate–heparin. This novel delivery system can concurrently satisfy high bioactive immobilization and sustainable release of rhBMP-2, and consequently induce rapid bone regeneration.
Experimental and ab initio studies of two UV nonlinear optical materials
Authors: Lu Juanjuan , Shi Guoqiang , Wu Hongping , Wen Ming , Hou Dianwei , Yang Zhihua , Zhang Fangfang , Pan Shilie
Published: April 2017

Two new acentric polyborates, Ba3(OH)(B9O16)[B(OH)3] and Ba2.16Pb0.84(OH)(B9O16)[B(OH)3] have been synthesized hydrothermally. Their structures have been determined by single-crystal X-ray diffraction.
Improvement of the structural and electronic properties of CZTSSe solar cells from spray pyrolysis by a CuGe seed layer
Authors: Sayed M. H. , Schoneberg J. , Parisi J. , Gütay L.
Published: April 2017

A CuGe seed layer suppresses the formation of MoSe2 and the consequent decomposition reaction at the Mo/CZTSSe interface during selenization.