bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroprotective effects of pifithrin-α against traumatic brain injury in the striatum through suppression of neuroinflammation, oxidative stress, autophagy, and apoptosis
Authors: Huang Ya-Ni , Yang Ling-Yu , Greig Nigel H. , Wang Yu-Chio , Lai Chien-Cheng , Wang Jia-Yi
Published: January 2018

Cortical and hippocampal neuronal damages caused by traumatic brain injury (TBI) are associated with motor and cognitive impairments; however, only little attention paid to the striatal damage. It is known that the p53 tumor-suppressor transcription factor participated in TBI-induced secondary brain damage. We investigated how the p53 inactivator pifithrin (PFT)-α affected TBI-induced striatal neuronal damage at 24 h post-injury. Sprague-Dawley rats subjected to a controlled cortical impact were used as TBI models. We observed that p53 mRNA significantly increased, whereas p53 protein expression was distributed predominantly in neurons but not in glia cells in striatum after TBI. PFT-α improved motor deficit following TBI. PFT-α suppressed TBI-induced striatal glial activation and expression of proinflammatory cytokines. PFT-α alleviated TBI-induced oxidative damage TBI induced autophagy was evidenced by increased protein expression of Beclin-1 and shift of microtubule-associated light chain (LC)3-I to LC3-II, and decreased p62. These effects were reduced by PFT-α. Post-injury PFT-α treatment reduced the number of degenerating (FJC-positive) and apoptotic neurons. Our results suggest that PFT-α may provide neuroprotective effects via p53-dependent or -independent mechanisms depending on the cell type and timing after the TBI and can possibly be developed into a novel therapy to ameliorate TBI-induced neuronal damage.
Canagliflozin, an SGLT2 inhibitor, attenuates the development of hepatocellular carcinoma in a mouse model of human NASH
Authors: Shiba Kumiko , Tsuchiya Kyoichiro , Komiya Chikara , Miyachi Yasutaka , Mori Kentaro , Shimazu Noriko , Yamaguchi Shinobu , Ogasawara Naomi , Katoh Makoto , Itoh Michiko , Suganami Takayoshi , Ogawa Yoshihiro
Published: January 2018

Sodium glucose cotransporter 2 (SGLT2) inhibitors, an antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. It is unclear whether SGLT2 inhibition could attenuate nonalcoholic steatohepatitis (NASH) and NASH-associated hepatocellular carcinoma. We examined the preventive effects of an SGLT2 inhibitor canagliflozin (CANA) in Western diet (WD)-fed melanocortin 4 receptor-deficient (MC4R-KO) mice, a mouse model of human NASH. An eight-week CANA treatment attenuated hepatic steatosis in WD-fed MC4R-KO mice, with increased epididymal fat mass without inflammatory changes. CANA treatment for 20 weeks inhibited the development of hepatic fibrosis in WD-fed MC4R-KO mice. After one year of CANA treatment, the number of liver tumors was significantly reduced in WD-fed MC4R-KO mice. In adipose tissue, CANA suppressed the ratio of oxidative to reduced forms of glutathiones (GSSG/GSH) in WD-fed MC4R-KO mice. Treatment with GSH significantly attenuated the H2O2-induced upregulation of genes related to NADPH oxidase in 3T3-L1 adipocytes, and that of Il6, Tgfb, and Pdgfb in RAW264.7 cells. This study provides evidence that SGLT2 inhibitors represent the unique class of drugs that can attenuate or delay the onset of NASH and eventually hepatocellular carcinoma, at least partly, through “healthy adipose expansion”.
Primate modularity and evolution: first anatomical network analysis of primate head and neck musculoskeletal system
Authors: Powell Vance , Esteve-Altava Borja , Molnar Julia , Villmoare Brian , Pettit Alesha , Diogo Rui
Published: January 2018

Network theory is increasingly being used to study morphological modularity and integration. Anatomical network analysis (AnNA) is a framework for quantitatively characterizing the topological organization of anatomical structures and providing an operational way to compare structural integration and modularity. Here we apply AnNA for the first time to study the macroevolution of the musculoskeletal system of the head and neck in primates and their closest living relatives, paying special attention to the evolution of structures associated with facial and vocal communication. We show that well-defined left and right facial modules are plesiomorphic for primates, while anthropoids consistently have asymmetrical facial modules that include structures of both sides, a change likely related to the ability to display more complex, asymmetrical facial expressions. However, no clear trends in network organization were found regarding the evolution of structures related to speech. Remarkably, the increase in the number of head and neck muscles – and thus of musculoskeletal structures – in human evolution led to a decrease in network density and complexity in humans.
ITGB1-dependent upregulation of Caveolin-1 switches TGFβ signalling from tumour-suppressive to oncogenic in prostate cancer
Authors: Pellinen Teijo , Blom Sami , Sánchez Sara , Välimäki Katja , Mpindi John-Patrick , Azegrouz Hind , Strippoli Raffaele , Nieto Raquel , Vitón Mariano , Palacios Irene , Turkki Riku , Wang Yinhai , Sánchez-Alvarez Miguel , Nordling Stig , Bützow Anna , Mirtti Tuomas , Rannikko Antti , Montoya María C. , Kallioniemi Olli , del Pozo Miguel A.
Published: January 2018

Caveolin-1 (CAV1) is over-expressed in prostate cancer (PCa) and is associated with adverse prognosis, but the molecular mechanisms linking CAV1 expression to disease progression are poorly understood. Extensive gene expression correlation analysis, quantitative multiplex imaging of clinical samples, and analysis of the CAV1-dependent transcriptome, supported that CAV1 re-programmes TGFβ signalling from tumour suppressive to oncogenic (i.e. induction of SLUG, PAI-1 and suppression of CDH1, DSP, CDKN1A). Supporting such a role, CAV1 knockdown led to growth arrest and inhibition of cell invasion in prostate cancer cell lines. Rationalized RNAi screening and high-content microscopy in search for CAV1 upstream regulators revealed integrin beta1 (ITGB1) and integrin associated proteins as CAV1 regulators. Our work suggests TGFβ signalling and beta1 integrins as potential therapeutic targets in PCa over-expressing CAV1, and contributes to better understand the paradoxical dual role of TGFβ in tumour biology.
Comparison of Environmental Impact and Nutritional Quality among a European Sample Population – findings from the Food4Me study
Authors: Walker Christie , Gibney Eileen R. , Hellweg Stefanie
Published: January 2018

This study evaluates the relationship between environmental impacts and diet quality through several environmental and nutritional indicators, using data from over 1400 participants across seven European countries in the Food4Me study. Comparisons of environmental impacts and dietary quality were evaluated across country, gender groups, and dietary patterns. While there was clear variability within the different subsets, there were large differences observed in both dietary quality and environmental impacts between cultures, genders, and dietary patterns. Individuals abstaining from red meat consistently had lower impacts in combination with lower consumption of harmful nutrients (saturated fats, sodium, and sugars) while maintaining average intake of beneficial nutrients. A ‘best practice’ diet with low impacts, adequate nutrient intake, and low saturated fats, sodium, and sugars, was constructed from the sample and used as a benchmark. Recorded eating patterns were compared to this recommended diet. On average, intakes of sweets, meats, and drinks should be decreased and intakes of vegetables and cereals increased, at varying rates depending on country and gender. However, the study shows a large spread of eating patterns and recommendations for lowering environmental impacts and increasing nutritional quality vary greatly among individuals.
Metabolic Hydrolysis of Aromatic Amides in Selected Rat, Minipig, and Human In Vitro Systems
Authors: Bradshaw Peter R. , Wilson Ian D. , Gill Rachel Upcott , Butler Philip J. , Dilworth Clive , Athersuch Toby J.
Published: January 2018

The release of aromatic amines from drugs and other xenobiotics resulting from the hydrolysis of metabolically labile amide bonds presents a safety risk through several mechanisms, including geno-, hepato- and nephrotoxicity. Whilst multiple in vitro systems used for studying metabolic stability display serine hydrolase activity, responsible for the hydrolysis of amide bonds, they vary in their efficiency and selectivity. Using a range of amide-containing probe compounds (0.5–10 µM), we have investigated the hydrolytic activity of several rat, minipig and human-derived in vitro systems - including Supersomes, microsomes, S9 fractions and hepatocytes - with respect to their previously observed human in vivo metabolism. In our hands, human carboxylesterase Supersomes and rat S9 fractions systems showed relatively poor prediction of human in vivo metabolism. Rat S9 fractions, which are commonly utilised in the Ames test to assess mutagenicity, may be limited in the detection of genotoxic metabolites from aromatic amides due to their poor concordance with human in vivo amide hydrolysis. In this study, human liver microsomes and minipig subcellular fractions provided more representative models of human in vivo hydrolytic metabolism of the aromatic amide compounds tested.
The influence of spatial frequency content on facial expression processing: An ERP study using rapid serial visual presentation
Authors: Tian Jinhua , Wang Jian , Xia Tao , Zhao Wenshuang , Xu Qianru , He Weiqi
Published: January 2018

Spatial frequency (SF) contents have been shown to play an important role in emotion perception. This study employed event-related potentials (ERPs) to explore the time course of neural dynamics involved in the processing of facial expression conveying specific SF information. Participants completed a dual-target rapid serial visual presentation (RSVP) task, in which SF-filtered happy, fearful, and neutral faces were presented. The face-sensitive N170 component distinguished emotional (happy and fearful) faces from neutral faces in a low spatial frequency (LSF) condition, while only happy faces were distinguished from neutral faces in a high spatial frequency (HSF) condition. The later P3 component differentiated between the three types of emotional faces in both LSF and HSF conditions. Furthermore, LSF information elicited larger P1 amplitudes than did HSF information, while HSF information elicited larger N170 and P3 amplitudes than did LSF information. Taken together, these results suggest that emotion perception is selectively tuned to distinctive SF contents at different temporal processing stages.
Improved Tapaswini having four BB resistance genes pyramided with six genes/QTLs, resistance/tolerance to biotic and abiotic stresses in rice
Authors: Das Gitishree , Rao Gundimeda J. N. , Varier M. , Prakash A. , Prasad Dokku
Published: January 2018

Rice, a major food crop, is grown in a wide range of ecological conditions and suffers significant yield losses as it is constantly exposed to a wide range of environmental and biotic stresses. The prevalence of different biotypes/strains has necessitated assembling of numerous resistance genes/QTLs into elite genotypes to confer a broader scale of resistance. The current study reports successful pyramiding of genes/QTLs that confer tolerance/resistance to submergence (Sub1), salinity (Saltol), blast (Pi2,Pi9) and gall midge (Gm1,Gm4) to supplement the four bacterial blight resistance genes (Xa 4,xa5,xa13,Xa21) present in Improved Tapaswini, an elite cultivar. The precise transfer of genes/QTLs was accomplished through effective foreground selection and suitable gene pyramids were identified. Background selection was practiced using morphological and grain quality traits to enhance the recovery of the recurrent parental genome. In the bioassays, the pyramids exhibited higher levels of resistance/ tolerance against the target stresses. The novel feature of the study was successful pyramidization and demonstration of the function of ten genes/QTLs in a new genotype. This success can stimulate several such studies to realize the full potential of molecular plant breeding as the foundation for rice improvement.
Bismuth Telluride nanocrystal: broadband nonlinear response and its application in ultrafast photonics
Authors: Jiang Guobao , Yi Jun , Miao Lili , Tang Pinghua , Huang Huihui , Zhao Chujun , Wen Shuangchun
Published: January 2018

We come up with a hybrid liquid exfoliation method to prepare bismuth telluride nanocrystals efficiently and cost-effectively. The nonlinear transmittance of the nanocrystals has been characterized with Z-scan technique, which can manifest its broadband saturable absorption behavior experimentally. The as-fabricated nanocrystals were integrated onto fiber end facet to form a fiber compatible nonlinear absorption device with optical deposition method, which was then used to modulate the fiber laser with different cavity configurations to deliver pulsed laser successfully. The noise-like pulse and dissipative soliton have been obtained with wavelength centered at 1562 nm and 1068 nm, respectively. These results confirm the effectiveness of the hybrid liquid exfoliation method to prepare bismuth telluride into nanocrystals, and the broadband nonlinear optical response and ultrafast photonics application potential of the nanocrystals.
Dispersion of the soybean root rot by Cycloneda sanguinea (Coleoptera: Coccinellidae)
Authors: Salgado-Neto Geraldo , Vaz Marcos André Braz , Guedes Jerson Vanderlei Carús , Muniz Marlove Fátima Brião , Blume Elena , Wilcken Carlos Frederico , Castro Bárbara Monteiro de Castro e , Plata-Rueda Angelica , Zanuncio José Cola
Published: January 2018

The dispersion of pathogenic microorganisms consists of the transport of pathogens from their source to inoculate a new host. Agricultural and economic importance of the Soybean root rot justifies studying this disease, especially the role of insects as dispersers. The aim of this study was to evaluate the role of the ladybird beetle, Cycloneda sanguinea Linnaeus (Coleoptera: Coccinellidae) in the dispersion of pathogens that cause Soybean root rot. Three pathogen species, Macrophomina phaseolina (Tassi) (Sphaeropsidales: Botryosphaeriaceae), Fusarium incarnatum-equiseti species complex (FIESC), and F. commune (Skovgaard) O’Donnell & Nirenberg were isolated from the midgut of ladybird beetles and cultured. Macrophomina phaseolina was identified by morphology while for the other two species, DNA was sequenced. The DNA extracted was amplified in the Internal Transcriber Spacer (ITS) region, sequenced and compared to voucher sequences deposited in the GenBank. Sequences of nucleotide ITS1-5.8 S were identified in the regions of rDNA-ITS4 ribosomal DNA. This is the first report of Macrophomina phaseolina (Tassi) (Sphaeropsidales: Botryosphaeriaceae), Fusarium incarnatum-equiseti species complex (FIESC), and F. commune (Skovgaard) O’Donnell & Nirenberg, being dispersed by C. sanguinea in Brazilian soybean fields.
Parental age and gene expression profiles in individual human blastocysts
Authors: Kawai Kiyotaka , Harada Tatsuya , Ishikawa Tomonori , Sugiyama Rikikazu , Kawamura Toshihiro , Yoshida Atsumi , Tsutsumi Osamu , Ishino Fumitoshi , Kubota Toshiro , Kohda Takashi
Published: January 2018

The epigenetic status of the genome changes dynamically from fertilization to implantation. In addition, the physiological environment during the process of gametogenesis, including parental age, may affect the epigenome of the embryo after fertilization. It is important to clarify the influence of parental age on gene expression in the embryo in terms of transgenerational epigenetics to improve the techniques currently used in assisted reproductive medicine. Here, we performed single-embryo RNA-seq analysis on human blastocysts fertilized by intracytoplasmic sperm injection, including from relatively elderly mothers, to elucidate the effects of parental age on the embryonic gene expression profile. We identified a number of genes in which the expression levels were decreased with increasing maternal age. Among these genes, several are considered to be important for meiotic chromosomal segregation, such as PTTG1, AURKC, SMC1B and MEIKIN. Furthermore, the expression levels of certain genes critical for autophagy and embryonic growth, specifically GABARAPL1 and GABARAPL3, were negatively correlated with advanced paternal age. In addition, levels of transcripts derived from major satellite repeats also decreased as the maternal age increased. These results suggest that epigenetic modifications of the oocyte genome may change with parental age and be transmitted to the next generation.
Neuroprotection of the hypoxic-ischemic mouse brain by human CD117+CD90+CD105+ amniotic fluid stem cells
Authors: Corcelli Michelangelo , Hawkins Kate , Vlahova Filipa , Hunjan Avina , Dowding Kate , De Coppi Paolo , David Anna L. , Peebles Donald , Gressens Pierre , Hagberg Henrik , Hristova Mariya , Guillot Pascale V.
Published: January 2018

Human amniotic fluid contains two morphologically-distinct sub-populations of stem cells with regenerative potential, spindle-shaped (SS-hAFSCs) and round-shaped human amniotic fluid stem cells (RS-hAFSCs). However, it is unclear whether morphological differences correlate with functionality, and this lack of knowledge limits their translational applications. Here, we show that SS-hAFSCs and RS-hAFSCs differ in their neuro-protective ability, demonstrating that a single contralateral injection of SS-hAFSCs into hypoxic-ischemic P7 mice conferred a 47% reduction in hippocampal tissue loss and 43–45% reduction in TUNEL-positive cells in the hippocampus and striatum 48 hours after the insult, decreased microglial activation and TGFβ1 levels, and prevented demyelination. On the other hand, RS-hAFSCs failed to show such neuro-protective effects. It is possible that SS-hAFSCs exert their neuroprotection via endoglin-dependent inhibition of TGFβ1 signaling in target cells. These findings identify a sub-population of CD117+CD90+CD105+ stem cells as a promising source for the neuro-protection of the developing brain.
Nitrogen Fixation by Trichodesmium and unicellular diazotrophs in the northern South China Sea and the Kuroshio in summer
Authors: Wu Chao , Fu Fei-Xue , Sun Jun , Thangaraj Satheeswaran , Pujari Laxman
Published: January 2018

Distribution of diazotrophs and their nitrogen fixation activity were investigated in the northern South China Sea (nSCS) and the Kuroshio from July 16th to September 1st, 2009. N2 fixation activities in whole seawater and <10 μm fraction at the surface were measured by acetylene reduction assay. Higher activities were observed at the East China Sea (ECS) Kuroshio and the nSCS shelf. The nSCS basin showed a low N2 fixation activity. The <10 μm fractions (unicellular diazotrophs) contributed major portion to the whole-water activity in the survey time, indicating that nanoplanktonic cyanobacterias were the major diazotrophs in the survey area. Daily N2 fixation rates of Trichodesmium ranged from 0.11 to 9.83 pmolNtrichome−1 d−1 with an average of 4.03 pmolNtrichome−1 d−1. The Luzon Strait and the ECS Kuroshio had higher N2 fixation rates of Trichodesmium than the nSCS shelf and basin. Calculated activities of Trichodesmium at most stations were moderately low compared with that of the whole-water. The contribution of N2 fixation by the whole-water to primary production ranged from 1.7% to 18.5%. The estimated amount of new nitrogen introduced by Trichodesmium contributed up to 0.14% of the total primary production and 0.41% of the new production in the Luzon Strait.
Tungsten-based Ultrathin Absorber for Visible Regime
Authors: Rana Ahsan Sarwar , Mehmood Muhammad Qasim , Jeong Heongyeong , Kim Inki , Rho Junsuk
Published: January 2018

Utilizing solar energy requires perfect absorption of light by the photovoltaic cells, particularly solar thermophotovoltaics (STPVs), which can be eventually converted into useful electrical energy. Ultrathin nanostructures, named metasurfaces, provide an intriguing platform to develop the miniaturized solar energy absorbers that can find potential applications in integrated photonics, optical sensing, color imaging, thermal imaging and electromagnetic shielding. Therefore, the quest of novel materials and designs to develop highly efficient absorbers at minuscule scale is an open topic. In this paper, novel absorbers using tungsten-metasurface are developed which give ultrahigh absorbance over a wide frequency spectrum. The proposed designs are two-dimensional, polarization insensitive, broadband and are predicted to give better response under high temperatures ascribed to high melting point of tungsten i.e. 3422 °C. Amongst these designs, cross alignment is found optimum for tungsten, because it is impedance matched with the free space for visible spectrum. This cross arrangement is further tweaked by changing width, height and length resulting in 7 different optimized solutions giving an average absorbance greater than 98%. One, amongst these solutions, gave a maximum average absorbance of 99.3%.
Nature of spiral state and absence of electric polarisation in Sr-doped YBaCuFeO5 revealed by first-principle study
Authors: Dey Dibyendu , Nandy S. , Maitra T. , Yadav C. S. , Taraphder A.
Published: January 2018

Experimental results on YBaCuFeO5, in its incommensurate magnetic phase, appear to disagree on its ferroelectric response. Ambiguity exists on the nature of the spiral magnetic state too. Using first-principles density functional theory (DFT) calculations for the parent compound within LSDA + U + SO approximation, we reveal the nature of spiral state. The helical spiral is found to be more stable below the transition temperature as spins prefer to lie in ab plane. Dzyaloshinskii-Moriya (DM) interaction turns out to be negligibly small and the spin current mechanism is not valid in the helical spiral state, ruling out an electric polarisation from either. These results are in very good agreement with the recent, high quality, single-crystal data. We also investigate the magnetic transition in YBa1−xSrxCuFeO5 for the entire range (0 ≤ x ≤ 1) of doping. The exchange interactions are estimated as a function of doping and a quantum Monte Carlo (QMC) calculation on an effective spin Hamiltonian shows that the paramagnetic to commensurate phase transition temperature increases with doping till x = 0.5 and decreases beyond. These observations are consistent with experimental findings.
Human brain functional areas of unitary pooled activity discovered with fMRI
Authors: Huang Jie
Published: January 2018

We report the discovery of human brain functional areas of unitary pooled activity (FAUPAs) using fMRI. A FAUPA is defined as an area in which the temporal variation of the activity is the same across the entire area. This dynamically unitary activity implies a perfect temporal correlation everywhere within the FAUPA for the activity-induced BOLD response, i.e., the corresponding Pearson correlation coefficient (R) is 1 for the BOLD responses of any two locations within the FAUPA. A novel method was developed to identify the FAUPA. In this study, nine subjects had a resting-state (rs) fMRI and a task-fMRI. FAUPAs have been identified for both rs- and task-fMRI, and their determination was objective and automatic, with no a-priori knowledge. The group mean of R was 0.952 ± 0.004 for the rs-fMRI and 0.950 ± 0.002 for the task-fMRI, showing the dynamically unitary activity within each FAUPA. For the finger-tapping (FT) task, the group-mean BOLD signal time course of the FT-associated FAUPAs in the primary motor cortex was almost perfectly correlated with the FT-induced ideal response (R = 0.9330, P = 1.8 × 10−56), confirming the association of the FAUPA with the task. A task-associated FAUPA may play the role of a functional unit for a particular neural computation.
Comparative study on nutrient depletion-induced lipidome adaptations in Staphylococcus haemolyticus and Staphylococcus epidermidis
Authors: Luo Yu , Javed Muhammad Afzal , Deneer Harry
Published: January 2018

Staphylococcus species are emerging opportunistic pathogens that cause outbreaks of hospital and community-acquired infections. Some of these bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) are difficult to treat due to their resistance to multiple antibiotics. We carried out a comparative study on the lipidome adaptations in response to starvation in the two most common coagulase-negative Staphylococcus species: a S. epidermidis strain sensitive to ampicillin and erythromycin and a S. haemolyticus strain resistant to both. The predominant fatty acid composition in glycerolipids was (17:0–15:0) in both bacteria. During the exponential phase, the two bacterial lipidomes were similar. Both were dominated by diacylglycerol (DAG), phosphatidylglycerol (PG), lysyl-phosphatidylglycerol (Lysyl-PG) and Diglucosyl-diacylglycerol (DGDG). Alanyl-PG was detected in small amounts in both bacterial lipids. N-succinyl-lysyl-PG was detected only in S. haemolyticus, while lysyl-DAG only in S. epidermidis. As the two bacteria entered stationary phase, both lipidomes became essentially nitrogen-free. Both bacteria accumulated large amounts of free fatty acids. Strikingly, the lipidome of S. epidermidis became dominated by cardiolipin (CL), while that of S. haemolyticus was simplified to DGDG and PG. The S. epidermidis strain also produced acyl-phosphatidylglycerol (APG) in the stationary phase.
Eis, a novel family of arylalkylamine N-acetyltransferase (EC 2.3.1.87)
Authors: Pan Qian , Zhao Feng-Lan , Ye Bang-Ce
Published: January 2018

Enhanced intracellular survival (Eis) proteins were found to enhance the intracellular survival of mycobacteria in macrophages by acetylating aminoglycoside antibiotics to confer resistance to these antibiotics and by acetylating DUSP16/MPK-7 to suppress host innate immune defenses. Eis homologs composing of two GCN5 N-acetyltransferase regions and a sterol carrier protein fold are found widely in gram-positive bacteria. In this study, we found that Eis proteins have an unprecedented ability to acetylate many arylalkylamines, are a novel type of arylalkylamine N-acetyltransferase AANAT (EC 2.3.1.87). Sequence alignment and phyletic distribution analysis confirmed Eis belongs to a new aaNAT-like cluster. Among the cluster, we studied three typical Eis proteins: Eis_Mtb from Mycobacterium tuberculosis, Eis_Msm from Mycobacterium smegmatis, and Eis_Sen from Saccharopolyspora erythraea. Eis_Mtb prefers to acetylate histamine and octopamine, while Eis_Msm uses tyramine and octopamine as substrates. Unlike them, Eis_Sen exihibits good catalytic efficiencies for most tested arylalkylamines. Considering arylalkylamines such as histamine plays a fundamental role in immune reactions, future work linking of AANAT activity of Eis proteins to their physiological function will broaden our understanding of gram-positive pathogen-host interactions. These findings shed insights into the molecular mechanism of Eis, and reveal potential clinical implications for many gram-positive pathogens.
Radium tracing nutrient inputs through submarine groundwater discharge in the global ocean
Authors: Cho Hyung-Mi , Kim Guebuem , Kwon Eun Young , Moosdorf Nils , Garcia-Orellana Jordi , Santos Isaac R.
Published: January 2018

Riverine and atmospheric inputs are often considered as the main terrestrial sources of dissolved inorganic nitrogen (DIN), phosphorus (DIP), and silicon (DSi) in the ocean. However, the fluxes of nutrients via submarine groundwater discharge (SGD) often exceed riverine inputs in different local and regional scale settings. In this study, we provide a first approximation of global nutrient fluxes to the ocean via total SGD, including pore water fluxes, by combining a global compilation of nutrient concentrations in groundwater and the SGD-derived 228Ra fluxes. In order to avoid overestimations in calculating SGD-derived nutrient fluxes, the endmember value of nutrients in global groundwater was chosen from saline groundwater samples (salinity >10) which showed relatively lower values over all regions. The results show that the total SGD-derived fluxes of DIN, DIP, and DSi could be approximately 1.4-, 1.6-, and 0.7-fold of the river fluxes to the global ocean (Indo-Pacific and Atlantic Oceans), respectively. Although significant portions of these SGD-derived nutrient fluxes are thought to be recycled within sediment-aquifer systems over various timescales, SGD-derived nutrient fluxes should be included in the global ocean budget in order to better understand dynamic interactions at the land-ocean interface.
Phenotypic co-receptor tropism and Maraviroc sensitivity in HIV-1 subtype C from East Africa
Authors: Siddik Abu Bakar , Haas Alexandra , Rahman Md Shanawazur , Aralaguppe Shambhu Ganeshappa , Amogne Wondwossen , Bader Joelle , Klimkait Thomas , Neogi Ujjwal
Published: January 2018

Genotypic tropism testing (GTT) for co-receptor usage is a recommended tool for clinical practice before administration of the CCR5-antagonist maraviroc. For some isolates, phenotypic tropism testing (PTT) revealed discordant results with GTT. In this study, we performed a comparative study between GTT and PTT in HIV-1C from East Africa (HIV-1CEA) and compared the data with HIV-1B and 01_AE and described the maraviroc susceptibility in the CCR5-tropic strains. Patient-derived HIV-1 envgp120 region was cloned into a modified pNL4-3 plasmid expressing the luciferase gene. rPhenotyping dissected single clones from 31 HIV-1CEA infected patients and four strains with known phenotype. Additionally, 68 clones from 18 patients (HIV-1B: 5, 01_AE: 7, HIV-1CEA: 6) were used to determine the PTT in GHOST cell line. The respective V3-sequences were used for GTT. R5-tropic strains from HIV-1CEA (n = 20) and non-C (n = 12) were tested for maraviroc sensitivity in TZMbl cell line. The GTT falsely called a higher proportion of X4-tropic strains in HIV-1CET compared to PTT by both rPhenotyping and the GHOST-cell assay. When multiple clones were tested in a subset of patients’ samples, both dual-tropic and R5-tropic strains were identified for HIV-1C. Relatively higher EC50 values were observed in HIV-1C strains than the non-C strains (p = 0.002).
Corium lavas: structure and properties of molten UO2-ZrO2 under meltdown conditions
Authors: Alderman O. L. G. , Benmore C. J. , Weber J. K. R. , Skinner L. B. , Tamalonis A. J. , Sendelbach S. , Hebden A. , Williamson M. A.
Published: January 2018

In the exceedingly rare event of nuclear reactor core meltdown, uranium dioxide fuel reacts with Zircaloy cladding to produce eutectic melts which can subsequently be oxidized by coolant/moderator water. Oxidized corium liquids in the xUO2·(100 − x)ZrO2 system were produced via laser melting of UO2-ZrO2 mixtures to temperatures in excess of 3000 K. Contamination was avoided by floating the droplets on a gas stream within an aerodynamic levitator and in-situ high-energy x-ray diffraction experiments allowed structural details to be elucidated. Molecular dynamics simulations well reproduced diffraction and density data, and show less compositional variation in thermal expansion and viscosity than suggested by existing measurements. As such, corium liquids maintain their highly penetrating nature irrespective of the amount of oxidized cladding dissolved in the molten fuel. Metal-oxygen coordination numbers vary with both composition and temperature. The former is due to mismatch in native values, nUO(x = 100) ≈ 7 and nZrO(x = 0) ≈ 6, and the requirement for oxygen site stabilization. The latter provides a thermal expansion mechanism.
Prediction of HIV-1 and HIV-2 proteins by using Chou’s pseudo amino acid compositions and different classifiers
Authors: Mei Juan , Zhao Ji
Published: January 2018

Human immunodeficiency virus (HIV) is the retroviral agent that causes acquired immune deficiency syndrome (AIDS). The number of HIV caused deaths was about 4 million in 2016 alone; it was estimated that about 33 million to 46 million people worldwide living with HIV. The HIV disease is especially harmful because the progressive destruction of the immune system prevents the ability of forming specific antibodies and to maintain an efficacious killer T cell activity. Successful prediction of HIV protein has important significance for the biological and pharmacological functions. In this study, based on the concept of Chou’s pseudo amino acid (PseAA) composition and increment of diversity (ID), support vector machine (SVM), logisitic regression (LR), and multilayer perceptron (MP) were presented to predict HIV-1 proteins and HIV-2 proteins. The results of the jackknife test indicated that the highest prediction accuracy and CC values were obtained by the SVM and MP were 0.9909 and 0.9763, respectively, indicating that the classifiers presented in this study were suitable for predicting two groups of HIV proteins.
Genetic targeting of Purkinje fibres by Sema3a-CreERT2
Authors: Li Yan , Tian Xueying , Zhao Huan , He Lingjuan , Zhang Shaohua , Huang Xiuzhen , Zhang Hui , Miquerol Lucile , Zhou Bin
Published: January 2018

The maintenance of the heart rhythm and the conduction of excitatory signals require changing excitatory signals via electrical activity and coordination by communication between working and conductive cardiomyocytes. Understanding how the ventricular conduction system is established provides novel insights into the pathophysiological progress of cardiac arrhythmias. However, the major hurdle in this field is the lack of a specific genetic tool that targets the Purkinje fibres of the ventricular conduction system and no other types of cardiomyocytes or coronary vessels. Here, we generated a Sema3a-CreERT2 knock-in mouse line to test its specificity for genetically labelled Purkinje fibres. We found that Sema3a was expressed in the subendocardial layer of the trabecular myocardium in the embryonic heart and was restricted to the Purkinje fibres in the adult heart. A fate mapping study based on the Sema3a-CreERT2 line revealed that the Sema3a+ cardiomyocytes were restricted to the fate of Purkinje fibres in the perinatal but not the embryonic stage. Collectively, our study provides a new genetic tool, i.e., Sema3a-CreERT2, for studying the molecular mechanisms that regulate the function of Purkinje fibres.
Fibroblast-associated tumour microenvironment induces vascular structure-networked tumouroid
Authors: Lee Sang Woo , Kwak Hyeong Seob , Kang Myoung-Hee , Park Yun-Yong , Jeong Gi Seok
Published: January 2018

In vitro three-dimensional (3D) tumour models mimic natural cancer tissue in vivo, bridging the gap between conventional 2D in vitro testing and animal models. Stromal and cancer tissues with extracellular matrix (ECM) can provide a tumour microenvironment (TME) with cell-to-cell and cell-to-ECM interactions. These interactions induce the exchange of biophysical factors, contributing to the progression, metastasis, and drug resistance of cancer. Here, we describe a 3D in vitro lung cancer model cultured in a microfluidic channel that is able to confirm the role and function of various stromal cells in tumourigenesis, thereby representing an in vivo-like TME. We founded that biophysical factors contribute to the role of fibroblast cells in tumour formation, especially, producing a nascent vessel-like tubular structure, resulting in the formation of vascularized tumour tissue. Fibroblast cells altered the gene expression of the cancer cells to enhance metastasis, survival, and angiogenesis. The device could be used for developing and screening anti-cancer drugs through the formation of the same multicellular tumour spheroids under TME interactions. We believe this microfluidic system provides interaction of TME for cancer research by culturing stromal tissue.
Updating the genomic taxonomy and epidemiology of Campylobacter hyointestinalis
Authors: Wilkinson David A. , O’Donnell Andrew J. , Akhter Rukhshana N. , Fayaz Ahmed , Mack Hamish J. , Rogers Lynn E. , Biggs Patrick J. , French Nigel P. , Midwinter Anne C.
Published: January 2018

Campylobacter hyointestinalis is a member of an emerging group of zoonotic Campylobacter spp. that are increasingly identified in both gastric and non-gastric disease in humans. Here, we discovered C. hyointestinalis in three separate classes of New Zealand ruminant livestock; cattle, sheep and deer. To investigate the relevance of these findings we performed a systematic literature review on global C. hyointestinalis epidemiology and used comparative genomics to better understand and classify members of the species. We found that C. hyointestinalis subspecies hyointestinalis has an open pangenome, with accessory gene contents involved in many essential processes such as metabolism, virulence and defence. We observed that horizontal gene transfer is likely to have played an overwhelming role in species diversification, favouring a public-goods-like mechanism of gene ‘acquisition and resampling’ over a tree-of-life-like vertical inheritance model of evolution. As a result, simplistic gene-based inferences of taxonomy by similarity are likely to be misleading. Such genomic plasticity will also mean that local evolutionary histories likely influence key species characteristics, such as host-association and virulence. This may help explain geographical differences in reported C. hyointestinalis epidemiology and limits what characteristics may be generalised, requiring further genomic studies of C. hyointestinalis in areas where it causes disease.
Tracking hidden organic carbon in rocks using chemometrics and hyperspectral imaging
Authors: Pisapia Céline , Jamme Frédéric , Duponchel Ludovic , Ménez Bénédicte
Published: January 2018

Finding traces of life or organic components of prebiotic interest in the rock record is an appealing goal for numerous fields in Earth and space sciences. However, this is often hampered by the scarceness and highly heterogeneous distribution of organic compounds within rocks. We assess here an innovative analytical strategy combining Synchrotron radiation-based Fourier-Transform Infrared microspectroscopy (S-FTIR) and multivariate analysis techniques to track and characterize organic compounds at the pore level in complex oceanic rocks. S-FTIR hyperspectral images are analysed individually or as multiple image combinations (multiset analysis) using Principal Component Analyses (PCA) and Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS). This approach allows extracting simultaneously pure organic and mineral spectral signatures and determining their spatial distributions and relationships. MCR-ALS analysis provides resolved S-FTIR signatures of 8 pure mineral and organic components showing the close association at a micrometric scale of organic compounds and secondary clays formed during rock alteration and known to catalyse organic synthesis. These results highlights the potential of the serpentinizing oceanic lithosphere to generate and preserve organic compounds of abiotic origin, in favour of the hydrothermal theory for the origin of life.
Integrating Functional Analysis in the Next-Generation Sequencing Diagnostic Pipeline of RASopathies
Authors: Leung Gordon K. C. , Luk H. M. , Tang Vincent H. M. , Gao W. W. , Mak Christopher C. Y. , Yu Mullin H. C. , Wong W. L. , Chu Yoyo W. Y. , Yang W. L. , Wong Wilfred H. S. , Ma Alvin C. H. , Leung Anskar Y. H. , Jin D. Y. , Chan Kelvin Y. K. , Allanson Judith , Lo Ivan F. M. , Chung Brian H. Y.
Published: January 2018

RASopathies are a group of heterogeneous conditions caused by germline mutations in RAS/MAPK signalling pathway genes. With next-generation sequencing (NGS), sequencing capacity is no longer a limitation to molecular diagnosis. Instead, the rising number of variants of unknown significance (VUSs) poses challenges to clinical interpretation and genetic counselling. We investigated the potential of an integrated pipeline combining NGS and the functional assessment of variants for the diagnosis of RASopathies. We included 63 Chinese patients with RASopathies that had previously tested negative for PTPN11 and HRAS mutations. In these patients, we performed a genetic analysis of genes associated with RASopathies using a multigene NGS panel and Sanger sequencing. For the VUSs, we evaluated evidence from genetic, bioinformatic and functional data. Twenty disease-causing mutations were identified in the 63 patients, providing a primary diagnostic yield of 31.7%. Four VUSs were identified in five patients. The functional assessment supported the pathogenicity of the RAF1 and RIT1 VUSs, while the significance of two VUSs in A2ML1 remained unclear. In summary, functional analysis improved the diagnostic yield from 31.7% to 36.5%. Although technically demanding and time-consuming, a functional genetic diagnostic analysis can ease the clinical translation of these findings to aid bedside interpretation.
Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
Authors: Coleman Verena , Sa-Nguanmoo Piangkwan , Koenig Jeannette , Schulz Tim J. , Grune Tilman , Klaus Susanne , Kipp Anna P. , Ost Mario
Published: January 2018

Mitochondrial dysfunction is usually associated with various metabolic disorders and ageing. However, salutary effects in response to mild mitochondrial perturbations have been reported in multiple organisms, whereas molecular regulators of cell-autonomous stress responses remain elusive. We addressed this question by asking whether the nuclear factor erythroid-derived-like 2 (Nrf2), a transcription factor and master regulator of cellular redox status is involved in adaptive physiological responses including muscle mitohormesis. Using a transgenic mouse model with skeletal muscle-specific mitochondrial uncoupling and oxidative phosphorylation (OXPHOS) inefficiency (UCP1-transgenic, TG) we show that additional genetic ablation of Nrf2 abolishes an adaptive muscle NAD(P)H quinone dehydrogenase 1 (NQO1) and catalase induction. Deficiency of Nrf2 also leads to decreased mitochondrial respiratory performance although muscle functional integrity, fiber-type profile and mitochondrial biogenesis were not significantly altered. Importantly, Nrf2 ablation did not abolish the induction of key genes and proteins of muscle integrated stress response including the serine, one-carbon cycle, and glycine synthesis (SOG) pathway in TG mice while further increasing glutathione peroxidase (GPX) activity linked to increased GPX1 protein levels. Conclusively, our results tune down the functions controlled by Nrf2 in muscle mitohormesis and oxidative stress defense during mitochondrial OXPHOS inefficiency.
Epidemic spreading in modular time-varying networks
Authors: Nadini Matthieu , Sun Kaiyuan , Ubaldi Enrico , Starnini Michele , Rizzo Alessandro , Perra Nicola
Published: January 2018

We investigate the effects of modular and temporal connectivity patterns on epidemic spreading. To this end, we introduce and analytically characterise a model of time-varying networks with tunable modularity. Within this framework, we study the epidemic size of Susceptible-Infected-Recovered, SIR, models and the epidemic threshold of Susceptible-Infected-Susceptible, SIS, models. Interestingly, we find that while the presence of tightly connected clusters inhibits SIR processes, it speeds up SIS phenomena. In this case, we observe that modular structures induce a reduction of the threshold with respect to time-varying networks without communities. We confirm the theoretical results by means of extensive numerical simulations both on synthetic graphs as well as on a real modular and temporal network.
Poisson statistics-mediated particle/cell counting in microwell arrays
Authors: Ahrberg Christian D. , Lee Jong Min , Chung Bong Geun
Published: January 2018

Precise determination of particle or cell numbers is of importance for a wide array of applications in environmental studies, medical and biological applications, or manufacturing and monitoring applications in industrial production processes. A number of techniques ranging from manual counting to sophisticated equipment (e.g., flow cytometry) are available for this task. However, these methods are either labour intensive, prone to error, or require expensive equipment. Here, we present a fast, simple method for determining the number density of cells or microparticles using a microwell array. We analyze the light transmission of the microwells and categorize the microwells into two groups. As particles/cells contained in a microwell locally reduce the light transmission, these wells displayed a lower average transmission compared to unoccupied microwells. The number density of particles/cells can be calculated by Poisson statistics from the ratio of occupied to unoccupied microwells. Following this approach, the number densities of two different types of microparticles, as well as HeLa and E. Coli cells, ranging over four orders of magnitude were determined. Through the microwell array defined by microfabrication, a simple image recognition algorithm can be used with the formation of aggregates or irregular shaped samples providing no additional difficulty to the microwell recognition. Additionally, this method can be carried out using only simple equipment and data analysis automated by a computer program.
Advanced machine learning in action: identification of intracranial hemorrhage on computed tomography scans of the head with clinical workflow integration
Authors: Arbabshirani Mohammad R. , Fornwalt Brandon K. , Mongelluzzo Gino J. , Suever Jonathan D. , Geise Brandon D. , Patel Aalpen A. , Moore Gregory J.
Published: January 2018

Intracranial hemorrhage (ICH) requires prompt diagnosis to optimize patient outcomes. We hypothesized that machine learning algorithms could automatically analyze computed tomography (CT) of the head, prioritize radiology worklists and reduce time to diagnosis of ICH. 46,583 head CTs (~2 million images) acquired from 2007–2017 were collected from several facilities across Geisinger. A deep convolutional neural network was trained on 37,074 studies and subsequently evaluated on 9499 unseen studies. The predictive model was implemented prospectively for 3 months to re-prioritize “routine” head CT studies as “stat” on realtime radiology worklists if an ICH was detected. Time to diagnosis was compared between the re-prioritized “stat” and “routine” studies. A neuroradiologist blinded to the study reviewed false positive studies to determine whether the dictating radiologist overlooked ICH. The model achieved an area under the ROC curve of 0.846 (0.837–0.856). During implementation, 94 of 347 “routine” studies were re-prioritized to “stat”, and 60/94 had ICH identified by the radiologist. Five new cases of ICH were identified, and median time to diagnosis was significantly reduced (p < 0.0001) from 512 to 19 min. In particular, one outpatient with vague symptoms on anti-coagulation was found to have an ICH which was treated promptly with reversal of anticoagulation, resulting in a good clinical outcome. Of the 34 false positives, the blinded over-reader identified four probable ICH cases overlooked in original interpretation. In conclusion, an artificial intelligence algorithm can prioritize radiology worklists to reduce time to diagnosis of new outpatient ICH by 96% and may also identify subtle ICH overlooked by radiologists. This demonstrates the positive impact of advanced machine learning in radiology workflow optimization.
Integrating network analysis with chromatography: introducing a novel chemometry-chromatography based analytical procedure to classify the bacterial cell wall collection
Authors: Kumar Keshav , Cava Felipe
Published: January 2018

The present work integrates network analysis with chromatography and proposes a novel analytical procedure to classify the bacterial cell wall collection.
Recent advances in molecular rearrangements involving aryne intermediates
Authors: Roy Tony , Biju Akkattu T.
Published: January 2018

A concise account on the recent developments in molecular rearrangements proceeding via the aryne intermediate is presented thereby shedding light on the synthetic potential of this versatile intermediate.