bluuebunny/crossref_metadata_2025 huggingface dataset:
The powdery mildew-resistant Arabidopsis mlo2 mlo6 mlo12 triple mutant displays altered infection phenotypes with diverse types of phytopathogens
Authors: Acevedo-Garcia Johanna , Gruner Katrin , Reinstädler Anja , Kemen Ariane , Kemen Eric , Cao Lingxue , Takken Frank L. W. , Reitz Marco U. , Schäfer Patrick , O’Connell Richard J. , Kusch Stefan , Kuhn Hannah , Panstruga Ralph
Published: August 2017

Arabidopsis thaliana mlo2 mlo6 mlo12 triple mutant plants exhibit complete immunity against infection by otherwise virulent obligate biotrophic powdery mildew fungi such as Golovinomyces orontii. While this phenotype is well documented, the interaction profile of the triple mutant with other microbes is underexplored and incomplete. Here, we thoroughly assessed and quantified the infection phenotypes of two independent powdery mildew-resistant triple mutant lines with a range of microbes. These microorganisms belong to three kingdoms of life, engage in diverse trophic lifestyles, and deploy different infection strategies. We found that interactions with microbes that do not directly enter leaf epidermal cells were seemingly unaltered or showed even enhanced microbial growth or symptom formation in the mlo2 mlo6 mlo12 triple mutants, as shown for Pseudomonas syringae and Fusarium oxysporum. By contrast, the mlo2 mlo6 mlo12 triple mutants exhibited reduced host cell entry rates by Colletotrichum higginsianum, a fungal pathogen showing direct penetration of leaf epidermal cells comparable to G. orontii. Together with previous findings, the results of this study strengthen the notion that mutations in genes MLO2, MLO6 and MLO12 not only restrict powdery mildew colonization, but also affect interactions with a number of other phytopathogens.
Genomic DNA variation confirmed Seriola lalandi comprises three different populations in the Pacific, but with recent divergence
Authors: Premachandra H. K. A. , la Cruz Fabiola Lafarga-De , Takeuchi Yutaka , Miller Adam , Fielder Stewart , O’Connor Wayne , Frère Celine H. , Nguyen Nguyen Hong , Bar Ido , Knibb Wayne
Published: August 2017

Captive breeding programs and aquaculture production have commenced worldwide for the globally distributed yellowtail kingfish (Seriola lalandi), and captive bred fingerlings are being shipped from the Southern Hemisphere to be farmed in the Northern Hemisphere. It was recently proposed that PacificS.lalandicomprise at least three distinct species that diverged more than 2 million years ago. Here, we tested the hypothesis of different “species” in the Pacific using novel genomic data (namely single nucleotide polymorphisms and diversity array technology markers), as well as mtDNA and DNA microsatellite variation. These new data support the hypothesis of population subdivision between the Northeast Pacific, Northwest Pacific and South Pacific, and genetic divergence indicates restriction to the gene flow between hemispheres. However, our estimates of maximum mtDNA and nuclear DNA divergences of 2.43% and 0.67%, respectively, were within the ranges more commonly observed for populations within species than species within genera. Accordingly our data support the more traditional view thatS.lalandiin the Pacific comprises three distinct populations rather than the subdivisions into several species.
A novel approach to low-temperature synthesis of cubic HfO2 nanostructures and their cytotoxicity
Authors: Kumar Neeraj , George Blassan Plackal Adimuriyil , Abrahamse Heidi , Parashar Vyom , Ray Suprakas Sinha , Ngila Jane Catherine
Published: August 2017

The development of a strategy to stabilise the cubic phase of HfO2 at lower temperatures is necessary for the emergence of unique properties that are not realised in the thermodynamically stable monoclinic phase. A very high temperature (>2600 °C) is required to produce the cubic phase of HfO2, whereas the monoclinic phase is stable at low temperature. Here, a novel rapid synthesis strategy was designed to develop highly crystalline, pure cubic-phase HfO2 nanoparticles (size <10 nm) using microwave irradiation. Furthermore, the as-prepared nanoparticles were converted to different morphologies (spherical nanoparticles and nanoplates) without compromising the cubic phase by employing a post-hydrothermal treatment in the presence of surface modifiers. The cytotoxicities and proliferative profiles of the synthesised cubic HfO2 nanostructures were investigated over the MCF-7 breast cancer cell line, along with caspase-3/7 activities. The low-temperature phase stabilisation was significantly attributed to surface imperfections (defects and deformations) induced in the crystal lattice by the desirable presence of Na2S·xH2O and NaOH. Our work provides unprecedented insight into the stabilisation of nanoscale cubic-phase HfO2 in ambient environments; the method could be extended to other challenging phases of nanomaterials.
Maximum Power Point Tracking for Cascaded PV-Converter Modules Using Two-Stage Particle Swarm Optimization
Authors: Mao Mingxuan , Duan Qichang , Zhang Li , Chen Hao , Hu Bei , Duan Pan
Published: August 2017

The paper presents a novel two-stage particle swarm optimization (PSO) for the maximum power point tracking (MPPT) control of a PV system consisting of cascaded PV-converter modules, under partial shading conditions (PSCs). In this scheme, the grouping method of the shuffled frog leaping algorithm (SFLA) is incorporated with the basic PSO algorithm, ensuring fast and accurate searching of the global extremum. An adaptive speed factor is also introduced to improve its convergence speed. A PWM algorithm enabling permuted switching of the PV sources is applied. The method enables this PV system to achieve the maximum power generation for any number of PV and converter modules. Simulation studies of the proposed MPPT scheme are performed on a system having two chained PV buck-converter modules and a dc-ac H-bridge connected at its terminals for supplying an AC load. The results show that this type of PV system allows each module to achieve the maximum power generation according its illumination level without affecting the others, and the proposed new control method gives significantly higher power output compared with the conventional P&O and PSO methods.
Mapping the ‘Two-component system’ network in rice
Authors: Sharan Ashutosh , Soni Praveen , Nongpiur Ramsong Chantre , Singla-Pareek Sneh L. , Pareek Ashwani
Published: August 2017

Two-component system (TCS) in plants is a histidine to aspartate phosphorelay based signaling system. Rice genome has multifarious TCS signaling machinery comprising of 11 histidine kinases (OsHKs), 5 histidine phosphotransferases (OsHPTs) and 36 response regulators (OsRRs). However, how these TCS members interact with each other and comprehend diverse signaling cascades remains unmapped. Using a highly stringent yeast two-hybrid (Y2H) platform and extensive in planta bimolecular fluorescence complementation (BiFC) assays, distinct arrays of interaction between various TCS proteins have been identified in the present study. Based on these results, an interactome map of TCS proteins has been assembled. This map clearly shows a cross talk in signaling, mediated by different sensory OsHKs. It also highlights OsHPTs as the interaction hubs, which interact with OsRRs, mostly in a redundant fashion. Remarkably, interactions between type-A and type-B OsRRs have also been revealed for the first time. These observations suggest that feedback regulation by type-A OsRRs may also be mediated by interference in signaling at the level of type-B OsRRs, in addition to OsHPTs, as known previously. The interactome map presented here provides a starting point for in-depth molecular investigations for signal(s) transmitted by various TCS modules into diverse biological processes.
Quantum illumination reveals phase-shift inducing cloaking
Authors: Las Heras U. , Di Candia R. , Fedorov K. G. , Deppe F. , Sanz M. , Solano E.
Published: August 2017

In quantum illumination entangled light is employed to enhance the detection accuracy of an object when compared with the best classical protocol. On the other hand, cloaking is a stealth technology based on covering a target with a material deflecting the light around the object to avoid its detection. Here, we propose a quantum illumination protocol especially adapted to quantum microwave technology. This protocol seizes the phase-shift induced by some cloaking techniques, such as scattering reduction, allowing for a 3 dB improvement in the detection of a cloaked target. The method can also be employed for the detection of a phase-shift in bright environments in different frequency regimes. Finally, we study the minimal efficiency required by the photocounter for which the quantum illumination protocol still shows a gain with respect to the classical protocol.
Evaluation of the concentration of point defects in GaN
Authors: Reshchikov M. A. , Usikov A. , Helava H. , Makarov Yu. , Prozheeva V. , Makkonen I. , Tuomisto F. , Leach J. H. , Udwary K.
Published: August 2017

Photoluminescence (PL) was used to estimate the concentration of point defects in GaN. The results are compared with data from positron annihilation spectroscopy (PAS), secondary ion mass spectrometry (SIMS), and deep level transient spectroscopy (DLTS). Defect-related PL intensity in undoped GaN grown by hydride vapor phase epitaxy increases linearly with the concentration of related defects only up to 1016 cm−3. At higher concentrations, the PL intensity associated with individual defects tends to saturate, and accordingly, does not directly correlate with the concentration of defects. For this reason, SIMS analysis, with relatively high detection limits, may not be helpful for classifying unidentified point defects in GaN. Additionally, we highlight challenges in correlating defects identified by PL with those by PAS and DLTS methods.
Gene Expression Profiling of Cutaneous Injured and Non-Injured Nociceptors in SNI Animal Model of Neuropathic Pain
Authors: Berta Temugin , Perrin Florence E. , Pertin Marie , Tonello Raquel , Liu Yen-Chin , Chamessian Alexander , Kato Ann C. , Ji Ru-Rong , Decosterd Isabelle
Published: August 2017

Nociceptors are a particular subtype of dorsal root ganglion (DRG) neurons that detect noxious stimuli and elicit pain. Although recent efforts have been made to reveal the molecular profile of nociceptors in normal conditions, little is known about how this profile changes in pathological conditions. In this study we exploited laser capture microdissection to specifically collect individual injured and non-injured nociceptive DRG neurons and to define their gene profiling in rat spared nerve injury (SNI) model of neuropathic pain. We found minimal transcriptional changes in non-injured neurons at 7 days after SNI. In contrast, several novel transcripts were altered in injured nociceptors, and the global signature of these LCM-captured neurons differed markedly from that the gene expression patterns found previously using whole DRG tissue following SNI. Pathway analysis of the transcriptomic profile of the injured nociceptors revealed oxidative stress as a key biological process. We validated the increase of caspase-6 (CASP6) in small-sized DRG neurons and its functional role in SNI- and paclitaxel-induced neuropathic pain. Our results demonstrate that the identification of gene regulation in a specific population of DRG neurons (e.g., nociceptors) is an effective strategy to reveal new mechanisms and therapeutic targets for neuropathic pain from different origins.
Acute respiratory infections in hospitalized children in Vientiane, Lao PDR – the importance of Respiratory Syncytial Virus
Authors: Nguyen Van Hoan , Dubot-Pérès Audrey , Russell Fiona M. , Dance David A. B. , Vilivong Keoudomphone , Phommachan Souphatsone , Syladeth Chanthaphone , Lai Jana , Lim Ruth , Morpeth Melinda , Mayxay Mayfong , Newton Paul N. , Richet Hervé , De Lamballerie Xavier
Published: August 2017

The Human respiratory syncytial virus (RSV) is one of the most important viral pathogens, causing epidemics of acute respiratory infection (ARI), especially bronchiolitis and pneumonia, in children worldwide. To investigate the RSV burden in Laos, we conducted a one-year study in children <5 years old admitted to Mahosot Hospital, Vientiane Capital, to describe clinical and epidemiological characteristics and predictive factors for severity of RSV-associated ARI. Pooled nasal and throat swabs were tested using multiplex real-time PCR for 33 respiratory pathogens (FTD® kit). A total of 383 patients were included, 277 (72.3%) of whom presented with pneumonia. 377 (98.4%) patients were positive for at least one microorganism, of which RSV was the most common virus (41.0%), with a peak observed between June and September, corresponding to the rainy season. Most RSV inpatients had pneumonia (84.1%), of whom 35% had severe pneumonia. Children <3-months old were a high-risk group for severe pneumonia, independently of RSV infection. Our study suggests that RSV infection is frequent in Laos and commonly associated with pneumonia in hospitalized young children. Further investigations are required to provide a better overall view of the Lao nationwide epidemiology and public health burden of RSV infection over time.
Analytical performance of reagent for assaying tau protein in human plasma and feasibility study screening neurodegenerative diseases
Authors: Yang Shieh-Yueh , Chiu Ming-Jang , Chen Ta-Fu , Lin Chin-Hsien , Jeng Jiann-Shing , Tang Sung-Chun , Lee Yen-Fu , Yang Che-Chuan , Liu Bing-Hsien , Chen Hsin-Hsien , Wu Chau-Chung
Published: August 2017

Immunomagnetic reduction (IMR), which involves the use of antibody-functionalized magnetic nanoparticles to specifically label target biomarkers, was utilized to develop an assay for total tau protein in human plasma. The analytic properties of the IMR assay on tau protein were investigated. The limit of detection was found to be 0.026 pg/ml. Other properties such as Hook effect, assay linearity, dilution recovery range, reagent stability, interference test, and spiked recovery were also characterized. The ultra-sensitive IMR assay was applied to detect the plasma tau protein levels of subjects with prevalent neurodegenerative diseases, such as Alzheimer’s disease (AD), mild cognitive impairment (MCI) due to AD, Parkinson’s disease (PD), frontotemporal dementia (FTD) and vascular dementia (VD). The concentrations of plasma tau protein in patients with VD, PD, MCI due to AD, FTD, and AD patients were higher than that of healthy controls. Using an ROC curve analysis, the cutoff value for discriminating dementia patients from healthy controls was 17.43 pg/ml, resulting in 0.856 and 0.727 for clinical sensitivity and specificity, respectively. The area under the ROC curve was 0.908. These results imply that the IMR plasma tau assay would be useful to screen for prevalent neurodegenerative diseases.
Metagenomic analysis reveals a green sulfur bacterium as a potential coral symbiont
Authors: Cai Lin , Zhou Guowei , Tian Ren-Mao , Tong Haoya , Zhang Weipeng , Sun Jin , Ding Wei , Wong Yue Him , Xie James Y. , Qiu Jian-Wen , Liu Sheng , Huang Hui , Qian Pei-Yuan
Published: August 2017

Coral reefs are ecologically significant habitats. Coral-algal symbiosis confers ecological success on coral reefs and coral-microbial symbiosis is also vital to coral reefs. However, current understanding of coral-microbial symbiosis on a genomic scale is largely unknown. Here we report a potential microbial symbiont in corals revealed by metagenomics-based genomic study. Microbial cells in coral were enriched for metagenomic analysis and a high-quality draft genome of “Candidatus Prosthecochloris korallensis” was recovered by metagenome assembly and genome binning. Phylogenetic analysis shows “Ca. P. korallensis” belongs to the Prosthecochloris clade and is clustered with two Prosthecochloris clones derived from Caribbean corals. Genomic analysis reveals “Ca. P. korallensis” has potentially important ecological functions including anoxygenic photosynthesis, carbon fixation via the reductive tricarboxylic acid (rTCA) cycle, nitrogen fixation, and sulfur oxidization. Core metabolic pathway analysis suggests “Ca. P. korallensis” is a green sulfur bacterium capable of photoautotrophy or mixotrophy. Potential host-microbial interaction reveals a symbiotic relationship: “Ca. P. korallensis” might provide organic and nitrogenous nutrients to its host and detoxify sulfide for the host; the host might provide “Ca. P. korallensis” with an anaerobic environment for survival, carbon dioxide and acetate for growth, and hydrogen sulfide as an electron donor for photosynthesis.
Activation of autophagy attenuates EtOH-LPS-induced hepatic steatosis and injury through MD2 associated TLR4 signaling
Authors: Kong Xiaoxia , Yang Ying , Ren Li , Shao Tuo , Li Fengyuan , Zhao Cuiqing , Liu Liming , Zhang Hongyu , McClain Craig J. , Feng Wenke
Published: August 2017

Autophagy serves as a protective mechanism to degrade damaged organelles and proteins. Acute alcohol exposure is known to activate the hepatic autophagy response, whereas chronic alcohol exposure slows autophagosome formation along with an elevation of gut-derived endotoxin. In the current study, we examined whether lipopolysaccharide (LPS) administration decreased autophagic response in the liver of mice treated by short-term alcohol and whether activation of autophagy by rapamycin attenuates EtOH-LPS-induced liver steatosis and injury. We demonstrated that ten-day alcohol feeding primed the liver to LPS-induced lipid accumulation and liver injury with significantly increased hepatic steatosis and serum AST level as well as hepatic cellular NF-κB activation. LPS increased alcohol-mediated reactive oxygen species (ROS) formation while reducing autophagy activation. These deleterious effects were attenuated by rapamycin administration in mice. The protective effects of rapamycin are associated with decreased cellular MD2/TLR4 expression and interaction in Raw264.7 cells. Taken together, our results demonstrated that enhanced gut-derived LPS decreases the hepatic autophagosome numbers in response to alcohol exposure, and activation of autophagy by rapamycin protects from EtOH-LPS-induced liver injury, probably through reduced macrophage expression and interaction of TLR4/MD2 signaling complex.
CLE peptide-encoding gene families in Medicago truncatula and Lotus japonicus, compared with those of soybean, common bean and Arabidopsis
Authors: Hastwell April H. , de Bang Thomas C. , Gresshoff Peter M. , Ferguson Brett J.
Published: August 2017

CLE peptide hormones are critical regulators of many cell proliferation and differentiation mechanisms in plants. These 12-13 amino acid glycosylated peptides play vital roles in a diverse range of plant tissues, including the shoot, root and vasculature. CLE peptides are also involved in controlling legume nodulation. Here, the entire family of CLE peptide-encoding genes was identified in Medicago truncatula (52) and Lotus japonicus (53), including pseudogenes and non-functional sequences that were identified. An array of bioinformatic techniques were used to compare and contrast these complete CLE peptide-encoding gene families with those of fellow legumes, Glycine max and Phaseolus vulgaris, in addition to the model plant Arabidopsis thaliana. This approach provided insight into the evolution of CLE peptide families and enabled us to establish putative M. truncatula and L. japonicus orthologues. This includes orthologues of nodulation-suppressing CLE peptides and AtCLE40 that controls the stem cell population of the root apical meristem. A transcriptional meta-analysis was also conducted to help elucidate the function of the CLE peptide family members. Collectively, our analyses considerably increased the number of annotated CLE peptides in the model legume species, M. truncatula and L. japonicus, and substantially enhanced the knowledgebase of this critical class of peptide hormones.
The impact of immigration on microbial community composition in full-scale anaerobic digesters
Authors: Kirkegaard Rasmus H. , McIlroy Simon J. , Kristensen Jannie M. , Nierychlo Marta , Karst Søren M. , Dueholm Morten S. , Albertsen Mads , Nielsen Per H.
Published: August 2017

Anaerobic digestion is widely applied to treat organic waste at wastewater treatment plants. Characterisation of the underlying microbiology represents a source of information to develop strategies for improved operation. Hence, we investigated microbial communities of thirty-two full-scale anaerobic digesters over a six-year period using 16S rRNA gene amplicon sequencing. Sampling of the sludge fed into these systems revealed that several of the most abundant populations were likely inactive and immigrating with the influent. This observation indicates that a failure to consider immigration will interfere with correlation analysis and give an inaccurate picture of the growing microbial community. Furthermore, several abundant OTUs could not be classified to genus level with commonly applied taxonomies, making inference of their function unreliable and comparison to other studies problematic. As such, the existing MiDAS taxonomy was updated to include these abundant phylotypes. The communities of individual digesters surveyed were remarkably similar – with only 300 OTUs representing 80% of the total reads across all plants, and 15% of these identified as non-growing and possibly inactive immigrating microbes. By identifying abundant and growing taxa in anaerobic digestion, this study paves the way for targeted characterisation of the process-important organisms towards an in-depth understanding of the microbiology.
A systematic model identification method for chemical transformation pathways – the case of heroin biomarkers in wastewater
Authors: Ramin Pedram , Valverde-Pérez Borja , Polesel Fabio , Locatelli Luca , Plósz Benedek Gy.
Published: August 2017

This study presents a novel statistical approach for identifying sequenced chemical transformation pathways in combination with reaction kinetics models. The proposed method relies on sound uncertainty propagation by considering parameter ranges and associated probability distribution obtained at any given transformation pathway levels as priors for parameter estimation at any subsequent transformation levels. The method was applied to calibrate a model predicting the transformation in untreated wastewater of six biomarkers, excreted following human metabolism of heroin and codeine. The method developed was compared to parameter estimation methods commonly encountered in literature (i.e., estimation of all parameters at the same time and parameter estimation with fix values for upstream parameters) by assessing the model prediction accuracy, parameter identifiability and uncertainty analysis. Results obtained suggest that the method developed has the potential to outperform conventional approaches in terms of prediction accuracy, transformation pathway identification and parameter identifiability. This method can be used in conjunction with optimal experimental designs to effectively identify model structures and parameters. This method can also offer a platform to promote a closer interaction between analytical chemists and modellers to identify models for biochemical transformation pathways, being a prominent example for the emerging field of wastewater-based epidemiology.
Light-patterning of synthetic tissues with single droplet resolution
Authors: Booth Michael J. , Restrepo Schild Vanessa , Box Stuart J. , Bayley Hagan
Published: August 2017

Synthetic tissues can be generated by forming networks of aqueous droplets in lipid-containing oil. Each droplet contains a cell-free expression system and is connected to its neighbor through a lipid bilayer. In the present work, we have demonstrated precise external control of such networks by activating protein expression within single droplets, by using light-activated DNA to encode either a fluorescent or a pore-forming protein. By controlling the extent of activation, synthetic tissues were generated with graded levels of protein expression in patterns of single droplets. Further, we have demonstrated reversible activation within individual compartments in synthetic tissues by turning a fluorescent protein on-and-off. This is the first example of the high-resolution patterning of droplet networks, following their formation. Single-droplet control will be essential to power subsets of compartments within synthetic tissues or to stimulate subsets of cells when synthetic tissues are interfaced with living tissues.
Analysis and evaluation of the entropy indices of a static network structure
Authors: Cai Meng , Cui Ying , Stanley H. Eugene
Published: August 2017

Although degree distribution entropy (DDE), SD structure entropy (SDSE), Wu structure entropy (WSE) and FB structure entropy (FBSE) are four static network structure entropy indices widely used to quantify the heterogeneity of a complex network, previous studies have paid little attention to their differing abilities to describe network structure. We calculate these four structure entropies for four benchmark networks and compare the results by measuring the ability of each index to characterize network heterogeneity. We find that SDSE and FBSE more accurately characterize network heterogeneity than WSE and DDE. We also find that existing benchmark networks fail to distinguish SDSE and FBSE because they cannot discriminate local and global network heterogeneity. We solve this problem by proposing an evolving caveman network that reveals the differences between structure entropy indices by comparing the sensitivities during the network evolutionary process. Mathematical analysis and computational simulation both indicate that FBSE describes the global topology variation in the evolutionary process of a caveman network, and that the other three structure entropy indices reflect only local network heterogeneity. Our study offers an expansive view of the structural complexity of networks and expands our understanding of complex network behavior.
Achievability of 3D planned bimaxillary osteotomies: maxilla-first versus mandible-first surgery
Authors: Liebregts Jeroen , Baan Frank , de Koning Martien , Ongkosuwito Edwin , Bergé Stefaan , Maal Thomas , Xi Tong
Published: August 2017

The present study was aimed to investigate the effects of sequencing a two-component surgical procedure for correcting malpositioned jaws (bimaxillary osteotomies); specifically, surgical repositioning of the upper jaw—maxilla, and the lower jaw—mandible. Within a population of 116 patients requiring bimaxillary osteotomies, the investigators analyzed whether there were statistically significant differences in postoperative outcome as measured by concordance with a preoperative digital 3D virtual treatment plan. In one group of subjects (n = 58), the maxillary surgical procedure preceded the mandibular surgery. In the second group (n = 58), the mandibular procedure preceded the maxillary surgical procedure. A semi-automated analysis tool (OrthoGnathicAnalyser) was applied to assess the concordance of the postoperative maxillary and mandibular position with the cone beam CT-based 3D virtual treatment planning in an effort to minimize observer variability. The results demonstrated that in most instances, the maxilla-first surgical approach yielded closer concordance with the 3D virtual treatment plan than a mandibular-first procedure. In selected circumstances, such as a planned counterclockwise rotation of both jaws, the mandible-first sequence resulted in more predictable displacements of the jaws.
BIRC3 is a biomarker of mesenchymal habitat of glioblastoma, and a mediator of survival adaptation in hypoxia-driven glioblastoma habitats
Authors: Wang Dapeng , Berglund Anders E. , Kenchappa Rajappa S. , MacAulay Robert J. , Mulé James J. , Etame Arnold B.
Published: August 2017

Tumor hypoxia is an established facilitator of survival adaptation and mesenchymal transformation in glioblastoma (GBM). The underlying mechanisms that direct hypoxia-mediated survival in GBM habitats are unclear. We previously identified BIRC3 as a mediator of therapeutic resistance in GBM to standard temozolomide (TMZ) chemotherapy and radiotherapy (RT). Here we report that BIRC3 is a biomarker of the hypoxia-mediated adaptive mesenchymal phenotype of GBM. Specifically, in the TCGA dataset elevated BIRC3 gene expression was identified as a superior and selective biomarker of mesenchymal GBM versus neural, proneural and classical subtypes. Further, BIRC3 protein was highly expressed in the tumor cell niches compared to the perivascular niche across multiple regions in GBM patient tissue microarrays. Tumor hypoxia was found to mechanistically induce BIRC3 expression through HIF1-alpha signaling in GBM cells. Moreover, in human GBM xenografts robust BIRC3 expression was noted within hypoxic regions of the tumor. Importantly, selective inhibition of BIRC3 reversed therapeutic resistance of GBM cells to RT in hypoxic microenvironments through enhanced activation of caspases. Collectively, we have uncovered a novel role for BIRC3 as a targetable biomarker and mediator of hypoxia-driven habitats in GBM.
Trans-omics approaches used to characterise fish nutritional biorhythms in leopard coral grouper (Plectropomus leopardus)
Authors: Mekuchi Miyuki , Sakata Kenji , Yamaguchi Tomofumi , Koiso Masahiko , Kikuchi Jun
Published: August 2017

Aquaculture is now a major supplier of fish, and has the potential to be a major source of protein in the future. Leopard coral groupers are traded in Asian markets as superior fish, and production via aquaculture has commenced. As feeding efficiency is of great concern in aquaculture, we sought to examine the metabolism of leopard coral groupers using trans-omics approaches. Metabolic mechanisms were comprehensively analysed using transcriptomic and metabolomic techniques. This study focused on the dynamics of muscular metabolites and gene expression. The omics data were discussed in light of circadian rhythms and fasting/feeding. The obtained data suggest that branched-chain amino acids played a role in energy generation in the fish muscle tissues during fasting. Moreover, glycolysis, TCA cycles, and purine metabolic substances exhibited circadian patterns, and gene expression also varied. This study is the first step to understanding the metabolic mechanisms of the leopard coral grouper.
Structural basis for therapeutic inhibition of influenza A polymerase PB2 subunit
Authors: Ma Xiaolei , Xie Lili , Wartchow Charles , Warne Robert , Xu Yongjin , Rivkin Alexey , Tully David , Shia Steven , Uehara Kyoko , Baldwin Dianna M. , Muiru Gladys , Zhong Weidong , Zaror Isabel , Bussiere Dirksen E. , Leonard Vincent H. J.
Published: August 2017

Influenza virus uses a unique mechanism to initiate viral transcription named cap-snatching. The PB2 subunit of the viral heterotrimeric RNA polymerase binds the cap structure of cellular pre-mRNA to promote its cleavage by the PA subunit. The resulting 11–13 capped oligomer is used by the PB1 polymerase subunit to initiate transcription of viral proteins. VX-787 is an inhibitor of the influenza A virus pre-mRNA cap-binding protein PB2. This clinical stage compound was shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery. However, the binding of this molecule in the context of an extended form of the PB2 subunit has remained elusive. Here we generated a collection of PB2 truncations to identify a PB2 protein representative of its structure in the viral heterotrimeric protein. We present the crystal structure of VX-787 bound to a PB2 construct that recapitulates VX-787's biological antiviral activity in vitro. This co-structure reveals more extensive interactions than previously identified and provides insight into the observed resistance profile, affinity, binding kinetics, and conformational rearrangements induced by VX-787.
The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis
Authors: Liu Zhengtao , Que Shuping , Zhou Lin , Zheng Shusen , Romeo Stefano , Mardinoglu Adil , Valenti Luca
Published: August 2017

The impact of Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant, which causes hepatocellular fat retention by altering lipoprotein secretion, on liver damage and metabolic traits in chronic hepatitis C patients is still debated. We performed a systematic review and meta-analysis to clarify this relationship. Four studies with a total of 4325 patients were included. The risk of histologically-determined advanced steatosis, fibrosis, and cirrhosis (but not of severe inflammation) were increased in carriers of the TM6SF2 variant (P < 0.05). Unlike the inconsistent association with steatosis severity, due to the confounding effect of infection by the genotype-3 hepatitis C virus, the TM6SF2 variant was robustly associated with advanced fibrosis (OR = 1.07; 95% confidence interval [CI] = 1.01–1.14) and in particular with cirrhosis (OR = 2.05; 95% CI = 1.39–3.02). Regarding metabolic features, individuals positive for the TM6SF2 variant exhibited 5.8–12.0% lower levels of circulating triglycerides and non-HDL cholesterol (P < 0.05). Carriers of the variant were leaner, but there was high heterogeneity across studies (I2 = 97.2%). No significant association was observed between the TM6SF2 variant and insulin resistance or hepatitis C viral load (both P > 0.05). In conclusion, the TM6SF2 E167K variant promotes the development of steatosis, fibrosis and cirrhosis in patients with chronic hepatitis C. Conversely, this variant reduces circulating atherogenic lipid fractions.
Identification and ranking of environmental threats with ecosystem vulnerability distributions
Authors: Zijp Michiel C. , Huijbregts Mark A. J. , Schipper Aafke M. , Mulder Christian , Posthuma Leo
Published: August 2017

Responses of ecosystems to human-induced stress vary in space and time, because both stressors and ecosystem vulnerabilities vary in space and time. Presently, ecosystem impact assessments mainly take into account variation in stressors, without considering variation in ecosystem vulnerability. We developed a method to address ecosystem vulnerability variation by quantifying ecosystem vulnerability distributions (EVDs) based on monitoring data of local species compositions and environmental conditions. The method incorporates spatial variation of both abiotic and biotic variables to quantify variation in responses among species and ecosystems. We show that EVDs can be derived based on a selection of locations, existing monitoring data and a selected impact boundary, and can be used in stressor identification and ranking for a region. A case study on Ohio’s freshwater ecosystems, with freshwater fish as target species group, showed that physical habitat impairment and nutrient loads ranked highest as current stressors, with species losses higher than 5% for at least 6% of the locations. EVDs complement existing approaches of stressor assessment and management, which typically account only for variability in stressors, by accounting for variation in the vulnerability of the responding ecosystems.
The conserved tyrosine residue 940 plays a key structural role in membrane interaction of Bordetella adenylate cyclase toxin
Authors: Masin Jiri , Roderova Jana , Osickova Adriana , Novak Petr , Bumba Ladislav , Fiser Radovan , Sebo Peter , Osicka Radim
Published: August 2017

The adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) translocates its adenylate cyclase (AC) enzyme domain into target cells in a step that depends on membrane cholesterol content. We thus examined what role in toxin activities is played by the five putative cholesterol recognition amino acid consensus (CRAC) motifs predicted in CyaA hemolysin moiety. CRAC-disrupting phenylalanine substitutions had no impact on toxin activities and these were not inhibited by free cholesterol, showing that the putative CRAC motifs are not involved in cholesterol binding. However, helix-breaking proline substitutions in these segments uncovered a structural role of the Y632, Y658, Y725 and Y738 residues in AC domain delivery and pore formation by CyaA. Substitutions of Y940 of the fifth motif, conserved in the acylated domains of related RTX toxins, did not impact on fatty-acylation of CyaA by CyaC and the CyaA-Y940F mutant was intact for toxin activities on erythrocytes and myeloid cells. However, the Y940A or Y940P substitutions disrupted the capacity of CyaA to insert into artificial lipid bilayers or target cell membranes. The aromatic ring of tyrosine 940 side chain thus appears to play a key structural role in molecular interactions that initiate CyaA penetration into target membranes.
Compact flexible multi-pass rotary delay line using spinning micro-machined mirrors
Authors: Fleddermann Roland , Lee Woei Ming , Huang Keshu , Campbell Geoff T. , Lam Ping Koy , Chow Jong H.
Published: August 2017

We propose a new method to extend the path length tunability of rotary delay-lines. This method was shown to achieve a duty cycle of >80% and repetition rates of over 40 kHz. The new method relies on a new multi-segmented micro-machined mirror and serial injection of a single reflection onto separate segments of this mirror. The tunability is provided by the relative positioning of each reflective point on the mirror segments. There are two distinct modes of operation: synchronous and asynchronous. By simply manipulating the spatial position of the returning paths over the respective mirror segments, we can switch between increasing the repetition rate (asynchronous mode) or the total delay path (synchronous mode). We experimentally demonstrated up to 8 m/s scans with repetition rates of up to 42.7 kHz. Furthermore, we present numerical simulations of 18 reflection points to illustrate possibility of achieving a scan speed of up to 80 m/s. Through intermediate combinations of synchronous and asynchronous operation modes with 4 or more passes, we also show that the system can simultaneously increase both repetition rate and scan depth.
Fungal Hybrid B heme peroxidases – unique fusions of a heme peroxidase domain with a carbohydrate-binding domain
Authors: Zámocký Marcel , Janeček Štefan , Obinger Christian
Published: August 2017

Heme peroxidases, essential peroxide converting oxidoreductases are divided into four independently evolved superfamilies. Within the largest one – the peroxidase-catalase superfamily - two hybrid lineages were described recently. Whereas Hybrid A heme peroxidases represent intermediate enzymes between ascorbate peroxidases and cytochrome c peroxidases, Hybrid B heme peroxidases are unique fusion proteins comprised of a conserved N-terminal heme peroxidase domain and a C-terminal domain of various sugar binding motifs. So far these peculiar peroxidases are only found in the kingdom of Fungi. Here we present a phylogenetic reconstruction of the whole superfamily with focus on Hybrid B peroxidases. We analyse the domain assembly and putative structure and function of the newly discovered oligosaccharide binding domains. Two distinct carbohydrate binding modules (CBM21 and CBM34) are shown to occur in phytopathogenic ascomycetous orthologs of Hybrid B heme peroxidases only. Based on multiple sequence alignment and homology modeling the structure-function relationships are discussed with respect to physiological function. A concerted action of peroxide cleavage with specific cell-wall carbohydrate binding can support phytopathogens survival within the plant host.
Antisense oligonucleotide and thyroid hormone conjugates for obesity treatment
Authors: Cao Yang , Matsubara Tomoko , Zhao Can , Gao Wei , Peng Linxiu , Shan Jinjun , Liu Zhengxia , Yuan Fang , Tang Lingyi , Li Peixin , Guan Zhibin , Fang Zhuyuan , Lu Xiang , Huang Hu , Yang Qin
Published: August 2017

Using the principle of antibody-drug conjugates that deliver highly potent cytotoxic agents to cancer cells for cancer therapy, we here report the synthesis of antisense-oligonucleotides (ASO) and thyroid hormone T3 conjugates for obesity treatment. ASOs primarily target fat and liver with poor penetrance to other organs. Pharmacological T3 treatment increases energy expenditure and causes weight loss, but is contraindicated for obesity treatment due to systemic effects on multiple organs. We hypothesize that ASO-T3 conjugates may knock down target genes and enrich T3 action in fat and liver. Two established ASOs are tested. Nicotinamide N-methyltransferase (NNMT)-ASO prevents diet-induced obesity in mice. Apolipoprotein B (ApoB)-ASO is an FDA approved drug for treating familial hypercholesterolemia. NNMT-ASO and ApoB-ASO are chemically conjugated with T3 using a non-cleavable sulfo-SMCC linker. Both NNMT-ASO-T3 (NAT3) and ApoB-ASO-T3 (AAT3) enhance thyroid hormone receptor activity. Treating obese mice with NAT3 or AAT3 decreases adiposity and increases lean mass. ASO-T3 enhances white fat browning, decreases genes for fatty acid synthesis in liver, and shows limited effects on T3 target genes in heart and muscle. Furthermore, AAT3 augments LDL cholesterol-lowering effects of ApoB-ASO. Therefore, ASO and hormone/drug conjugation may provide a novel strategy for obesity and hyperlipidemia treatment.
Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways
Authors: Alsanie W. F. , Penna V. , Schachner M. , Thompson L. H. , Parish C. L.
Published: August 2017

Abnormal development of ventral midbrain (VM) dopaminergic (DA) pathways, essential for motor and cognitive function, may underpin a number of neurological disorders and thereby highlight the importance of understanding the birth and connectivity of the associated neurons. While a number of regulators of VM DA neurogenesis are known, processes involved in later developmental events, including terminal differentiation and axon morphogenesis, are less well understood. Recent transcriptional analysis studies of the developing VM identified genes expressed during these stages, including the cell adhesion molecule with homology to L1 (Chl1). Here, we map the temporal and spatial expression of CHL1 and assess functional roles of substrate-bound and soluble-forms of the protein during VM DA development. Results showed early CHL1 in the VM, corresponding with roles in DA progenitor migration and differentiation. Subsequently, we demonstrated roles for CHL1 in both axonal extension and repulsion, selectively of DA neurons, suggestive of a role in guidance towards forebrain targets and away from hindbrain nuclei. In part, CHL1 mediates these roles through homophilic CHL1-CHL1 interactions. Collectively, these findings enhance our knowledge of VM DA pathways development, and may provide new insights into understanding DA developmental conditions such as autism spectrum disorders.
Complete sequences of two novel bla
NDM-1-harbouring plasmids from two Acinetobacter towneri isolates in China associated with the acquisition of Tn125
Authors: Zou Dayang , Huang Yong , Liu Wei , Yang Zhan , Dong Derong , Huang Simo , He Xiaoming , Ao Da , Liu Ningwei , Wang Shengshu , Wang Yong , Tong Yigang , Yuan Jing , Huang Liuyu
Published: August 2017

Two novel New Delhi metallo-β-lactamase-1 (NDM-1)-positive plasmids containing a complete composite transposon, Tn125, from two respective Acinetobacter towneri isolates were characterized. Plasmid pNDM-GJ01 (30,293 bp) isolated from A. towneri G165 did not show homology to any known plasmid structure, except for the transposon Tn125 containing blaNDM-1. A novel repB gene and two XRE-type transcriptional regulators were found in pNDM-GJ01. Plasmid pNDM-GJ02 (62,011 bp) isolated from A. towneri G295 showed the highest homology to pBJAB0715 (41% coverage, 99% nucleotide identity). In addition to the blaNDM-1-harbouring transposon Tn125, pNDM-GJ02 also had an IS26-composite transposon, which contains ISCR1 and two class 1 integrons carrying different cassette arrays. Both clinical isolates were highly resistant to β-lactams and susceptible to tigecycline and colistin. Ten other resistance genes were detected in G295, and one other resistance gene was detected in G165. No transconjugant was obtained from any of the donors by broth and filter mating. The emergence of these two novel plasmids carrying NDM-1 in Acinetobacter spp., pNDM-GJ01 and pNDM-GJ02, suggests Tn125 mobile integration.
Assessing the relationship between surface urban heat islands and landscape patterns across climatic zones in China
Authors: Yang Qiquan , Huang Xin , Li Jiayi
Published: August 2017

The urban heat island (UHI) effect exerts a great influence on the Earth’s environment and human health and has been the subject of considerable attention. Landscape patterns are among the most important factors relevant to surface UHIs (SUHIs); however, the relationship between SUHIs and landscape patterns is poorly understood over large areas. In this study, the surface UHI intensity (SUHII) is defined as the temperature difference between urban and suburban areas, and the landscape patterns are quantified by the urban-suburban differences in several typical landscape metrics (ΔLMs). Temperature and land-cover classification datasets based on satellite observations were applied to analyze the relationship between SUHII and ΔLMs in 332 cities/city agglomerations distributed in different climatic zones of China. The results indicate that SUHII and its correlations with ΔLMs are profoundly influenced by seasonal, diurnal, and climatic factors. The impacts of different land-cover types on SUHIs are different, and the landscape patterns of the built-up and vegetation (including forest, grassland, and cultivated land) classes have the most significant effects on SUHIs. The results of this study will help us to gain a deeper understanding of the relationship between the SUHI effect and landscape patterns.
Combined effects of increased temperature and endocrine disrupting pollutants on sex determination, survival, and development across generations
Authors: DeCourten Bethany M. , Brander Susanne M.
Published: August 2017

Understanding the combined effects of anthropogenic impacts such as climate change and pollution on aquatic ecosystems is critical. However, little is known about how predicted temperature increases may affect the activity of endocrine disrupting compounds (EDCs), particularly in species with plasticity in sex determination. We investigated the effects of a concomitant increase in temperature and exposure to estrogenic EDCs on reproduction and development in an estuarine model organism (Menidia beryllina) across multiple generations. Parents (P) were exposed to environmental levels of the estrogenic insecticide bifenthrin or ethinylestradiol (EE2) at 22 °C and 28 °C for 14 days prior to the initiation of spawning trials. Embryos in the F1 generation were exposed to EDCs until 21 days post hatch (dph), reared to adulthood in clean water at elevated temperatures, and spawned. F1 sex ratios were significantly influenced by elevated temperature and EDCs, potentially altering adaptive development. We also observed fewer viable offspring and increased developmental deformities in the F1 and F2 generations, with a greater impact on F2 juveniles. These findings enhance our understanding of responses to EDCs in the context of climate change and may demonstrate heritable effects. Our study represents the first multigenerational assessment of elevated temperatures in combination with environmentally relevant concentrations of commonly detected endocrine disruptors in a model vertebrate species.