bluuebunny/crossref_metadata_2025 huggingface dataset:
On the performance of pre-microRNA detection algorithms
Authors: Saçar Demirci Müşerref Duygu , Baumbach Jan , Allmer Jens
Published: August 2017

MicroRNAs are crucial for post-transcriptional gene regulation, and their dysregulation has been associated with diseases like cancer and, therefore, their analysis has become popular. The experimental discovery of miRNAs is cumbersome and, thus, many computational tools have been proposed. Here we assess 13 ab initio pre-miRNA detection approaches using all relevant, published, and novel data sets while judging algorithm performance based on ten intrinsic performance measures. We present an extensible framework, izMiR, which allows for the unbiased comparison of existing algorithms, adding new ones, and combining multiple approaches into ensemble methods. In an exhaustive attempt, we condense the results of millions of computations and show that no method is clearly superior; however, we provide a guideline for biomedical researchers to select a tool. Finally, we demonstrate that combining all of the methods into one ensemble approach, for the first time, allows reliable purely computational pre-miRNA detection in large eukaryotic genomes.
Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis
Authors: Yousri Noha A. , Bayoumy Karim , Elhaq Wessam Gad , Mohney Robert P. , Emadi Samar Al , Hammoudeh Mohammed , Halabi Hussein , Masri Basel , Badsha Humeira , Uthman Imad , Plenge Robert , Saxena Richa , Suhre Karsten , Arayssi Thurayya
Published: August 2017

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.
Stimulatory Effect of Intermittent Hypoxia on the Production of Corticosterone by Zona Fasciculata-Reticularis Cells in Rats
Authors: Hwang Guey-Shyang , Chen Chih-Chieh , Chou Jou-Chun , Chang Ling-Ling , Kan Shu-Fen , Lai Wei-Ho , Lieu Fu-Kong , Hu Sindy , Wang Paulus S. , Wang Shyi-Wu
Published: August 2017

Hypoxia or intermittent hypoxia (IH) have known to alter both synthesis and secretion of hormones. However, the effect of IH on the production of adrenal cortical steroid hormones is still unclear. The aim of present study was to explore the mechanism involved in the effect of IH on the production of corticosterone by rat ZFR cells. Male rats were exposed at 12% O2 and 88% N2 (8 hours per day) for 1, 2, or 4 days. The ZFR cells were incubated at 37 °C for 1 hour with or without ACTH, 8-Br-cAMP, calcium ion channel blockers, or steroidogenic precursors. The concentration of plasma corticosterone was increased time-dependently by administration of IH hypoxia. The basal levels of corticosterone production in cells were higher in the IH groups than in normoxic group. IH resulted in a time-dependent increase of corticosterone production in response to ACTH, 8-Br-cAMP, progesterone and deoxycorticosterone. The production of pregnenolone in response to 25-OH-C and that of progesterone in response to pregnenolone in ZFR cells were enhanced by 4-day IH. These results suggest that IH in rats increases the secretion of corticosterone via a mechanism at least in part associated with the activation of cAMP pathway and steroidogenic enzymes.
Horizontal transfer of a ß-1,6-glucanase gene from an ancestral species of fungal endophyte to a cool-season grass host
Authors: Shinozuka Hiroshi , Hettiarachchige Inoka K. , Shinozuka Maiko , Cogan Noel O. I. , Spangenberg German C. , Cocks Benjamin G. , Forster John W. , Sawbridge Timothy I.
Published: August 2017

Molecular characterisation has convincingly demonstrated some types of horizontal gene transfer in eukaryotes, but nuclear gene transfer between distantly related eukaryotic groups appears to have been rare. For angiosperms (flowering plants), nuclear gene transfer events identified to date have been confined to genes originating from prokaryotes or other plant species. In this report, evidence for ancient horizontal transfer of a fungal nuclear gene, encoding a ß-1,6-glucanase enzyme for fungal cell wall degradation, into an angiosperm lineage is presented for the first time. The gene was identified fromde novosequencing and assembly of the genome and transcriptome of perennial ryegrass, a cool-season grass species. Molecular analysis confirmed the presence of the complete gene in the genome of perennial ryegrass. No corresponding sequence was found in other plant species, apart from members of the Poeae sub-tribes Loliinae and Dactylidinae. Evidence suggests that a common ancestor of the two sub-tribes acquired the gene from a species ancestral to contemporary grass-associated fungal endophytes around 9–13 million years ago. This first report of horizontal transfer of a nuclear gene from a taxonomically distant eukaryote to modern flowering plants provides evidence for a novel adaptation mechanism in angiosperms.
Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection
Authors: Fujimoto Yousuke , Hasegawa Shunji , Matsushige Takeshi , Wakiguchi Hiroyuki , Nakamura Tamaki , Hasegawa Hideki , Nakajima Noriko , Ainai Akira , Oga Atsunori , Itoh Hiroshi , Shirabe Komei , Toda Shoichi , Atsuta Ryo , Morishima Tsuneo , Ohga Shouichi
Published: August 2017

Asthmatic patients present more rapid progression of respiratory distress after A(H1N1)pdm09 influenza infection than after seasonal infection. Here, we sought to clarify the pathophysiology of early deterioration in asthmatic patients after A(H1N1)pdm09 infection. Cytokine levels and virus titres in bronchoalveolar lavage fluid from mice with and without asthma after A(H1N1)pdm09 or seasonal H1N1 infection were examined. In asthma/A(H1N1)pdm09 mice, IL-6 and TNF-α levels peaked at 3 days post-infection and were higher than those in all other groups. IFN-γ levels in asthma/A(H1N1)pdm09 mice at 3 days post-infection were higher than in all other mice at any time point, whereas at 7 days post-infection, the levels were lowest in asthma/A(H1N1)pdm09 mice. Virus titres in asthma/A(H1N1)pdm09 mice were highest at 3 days post-infection, and decreased by 7 days post-infection, although the levels at this time point were still higher than that in any other group. Histopathological examination showed more inflammatory cell infiltration and lung tissue destruction in the asthma/A(H1N1)pdm09 group than in any other group. The distinct cytokine profiles in A(H1N1)pdm09-infected asthmatic mice indicated excessive inflammation and virus replication within a few days after infection. Thus, bronchial asthma could be a more exacerbating factor for pandemic influenza infection than for seasonal influenza infection.
Ambient particulate air pollution (PM2.5) is associated with the ratio of type 2 diabetes to obesity
Authors: Mazidi Mohsen , Speakman John R.
Published: August 2017

We used county level data for T2D prevalence across the mainland USA and matched this to county level ambient PM2.5. Multiple linear regression was used to determine the relation between prevalence of T2D with PM2.5 after adjustment for confounding factors. PM2.5 explained 6.3% of the spatial variation in obesity, and 17.9% of the spatial variation in T2D. After correcting the T2D prevalence for obesity, race, poverty, education and temperature, PM2.5 still explained 8.3% of the residual variation in males (P < 0.0001) and 11.5% in females (P < 0.0001). The effect on obesity prevalence corrected for poverty, race education and temperature was much lower and hence the ratio of T2D to obesity prevalence was significantly associated with PM2.5 in males (R2 = 11.1%, P < 0.0001) and females (R2 = 16.8%, P < 0.0001). This association was repeated across non-African countries (R2 = 14.9%, P < 0.0001). High levels of PM2.5 probably contribute to increased T2D prevalence in the USA, but have a more minor effect on the obesity. Exposure to high environmental levels of PM2.5 (relative to the USA) may explain the disproportional risk of T2D in relation to obesity in Asian populations.
Discrimination of three types of homopolymers in single-stranded DNA with solid-state nanopores through external control of the DNA motion
Authors: Akahori Rena , Yanagi Itaru , Goto Yusuke , Harada Kunio , Yokoi Takahide , Takeda Ken-ichi
Published: August 2017

To achieve DNA sequencing with solid-state nanopores, the speed of the DNA in the nanopore must be controlled to obtain sequence-specific signals. In this study, we fabricated a nanopore-sensing system equipped with a DNA motion controller. DNA strands were immobilized on a Si probe, and approach of this probe to the nanopore vicinity could be controlled using a piezo actuator and stepper motor. The area of the Si probe was larger than the area of the membrane, which meant that the immobilized DNA could enter the nanopore without the need for the probe to scan to determine the location of the nanopore in the membrane. We demonstrated that a single-stranded DNA could be inserted into and removed from a nanopore in our experimental system. The number of different ionic-current levels observed while DNA remained in the nanopore corresponded to the number of different types of homopolymers in the DNA.
Stimulation triggers endogenous activity patterns in cultured cortical networks
Authors: Pasquale Valentina , Martinoia Sergio , Chiappalone Michela
Published: August 2017

Cultures of dissociated cortical neurons represent a powerful trade-off between more realistic experimental models and abstract modeling approaches, allowing to investigate mechanisms of synchronized activity generation. These networks spontaneously alternate periods of high activity (i.e. network bursts) with periods of quiescence in a dynamic state which recalls the fluctuation of in vivo UP and DOWN states. Network bursts can also be elicited by external stimulation and their spatial propagation patterns tracked by means of multi-channel micro-electrode arrays. In this study, we used rat cortical cultures coupled to micro-electrode arrays to investigate the similarity between spontaneous and evoked activity patterns. We performed experiments by applying electrical stimulation to different network locations and demonstrated that the rank orders of electrodes during evoked and spontaneous events are remarkably similar independently from the stimulation source. We linked this result to the capability of stimulation to evoke firing in highly active and “leader” sites of the network, reliably and rapidly recruited within both spontaneous and evoked bursts. Our study provides the first evidence that spontaneous and evoked activity similarity is reliably observed also in dissociated cortical networks.
Aluminum plasmonic nanoshielding in ultraviolet inactivation of bacteria
Authors: Kunz Jeremy N. , Voronine Dmitri V. , Lu Weigang , Liege Zachary , Lee Ho Wai Howard , Zhang Zhenrong , Scully Marlan O.
Published: August 2017

Ultraviolet (UV) irradiation is an effective bacterial inactivation technique with broad applications in environmental disinfection. However, biomedical applications are limited due to the low selectivity, undesired inactivation of beneficial bacteria and damage of healthy tissue. New approaches are needed for the protection of biological cells from UV radiation for the development of controlled treatment and improved biosensors. Aluminum plasmonics offers attractive opportunities for the control of light-matter interactions in the UV range, which have not yet been explored in microbiology. Here, we investigate the effects of aluminum nanoparticles (Al NPs) prepared by sonication of aluminum foil on the UVC inactivation ofE.colibacteria and demonstrate a new radiation protection mechanism via plasmonic nanoshielding. We observe direct interaction of the bacterial cells with Al NPs and elucidate the nanoshielding mechanism via UV plasmonic resonance and nanotailing effects. Concentration and wavelength dependence studies reveal the role and range of control parameters for regulating the radiation dosage to achieve effective UVC protection. Our results provide a step towards developing improved radiation-based bacterial treatments.
Analyses of Long Non-Coding RNA and mRNA profiling using RNA sequencing in chicken testis with extreme sperm motility
Authors: Liu Yifan , Sun Yanyan , Li Yunlei , Bai Hao , Xue Fuguang , Xu Songshan , Xu Hong , Shi Lei , Yang Ning , Chen Jilan
Published: August 2017

Sperm motility is the most important indicator in evaluating roosters’ fecundity. However, the genetic mechanisms underlying chicken sperm motility is not yet clear. Long non-coding RNA (lncRNA) play epigenetic roles in reproduction. In this study, RNA sequencing was employed to profile the testis transcriptome (lncRNA and mRNA) of six Beijing-you cocks divergent in sperm motility. In total, 2,597 lncRNAs were identified in the chicken testis, including 1,267 lincRNAs, 975 anti-sense lncRNAs, and 355 intronic lncRNAs. They shared similar features with previous studies. Of these lncRNAs, 124 were differentially expressed. Among 17,690 mRNAs detected in this study, 544 were differentially expressed, including a bunch of genes with known functions on sperm motility. GO annotation analysis revealed these genes were involved in ATP binding, cilium assembly, and oxidation-reduction processes. Integrating analysis of lncRNA and mRNA profiles predicted 10 lncRNA-gene pairs, including 8 co-regulated and 2 inversely-regulated pairs. To the best of our knowledge, this is the first genome-wide investigation of the lncRNAs in the chicken testis associated with sperm motility. Our results provided a catalog of chicken testis lncRNAs and genes worthy of further studies to understand their roles in cocks’ reproductive performance regulation.
Sterol targeting drugs reveal life cycle stage-specific differences in trypanosome lipid rafts
Authors: Sharma Aabha I. , Olson Cheryl L. , Mamede João I. , Gazos-Lopes Felipe , Epting Conrad L. , Almeida Igor C. , Engman David M.
Published: August 2017

Cilia play important roles in cell signaling, facilitated by the unique lipid environment of a ciliary membrane containing high concentrations of sterol-rich lipid rafts. The African trypanosome Trypanosoma brucei is a single-celled eukaryote with a single cilium/flagellum. We tested whether flagellar sterol enrichment results from selective flagellar partitioning of specific sterol species or from general enrichment of all sterols. While all sterols are enriched in the flagellum, cholesterol is especially enriched. T. brucei cycles between its mammalian host (bloodstream cell), in which it scavenges cholesterol, and its tsetse fly host (procyclic cell), in which it both scavenges cholesterol and synthesizes ergosterol. We wondered whether the insect and mammalian life cycle stages possess chemically different lipid rafts due to different sterol utilization. Treatment of bloodstream parasites with cholesterol-specific methyl-β-cyclodextrin disrupts both membrane liquid order and localization of a raft-associated ciliary membrane calcium sensor. Treatment with ergosterol-specific amphotericin B does not. The opposite results were observed with ergosterol-rich procyclic cells. Further, these agents have opposite effects on flagellar sterol enrichment and cell metabolism in the two life cycle stages. These findings illuminate differences in the lipid rafts of an organism employing life cycle-specific sterols and have implications for treatment.
Embryonic hindbrain patterning genes delineate distinct cardio-respiratory and metabolic homeostatic populations in the adult
Authors: Sun Jenny J. , Huang Teng-Wei , Neul Jeffrey L. , Ray Russell S.
Published: August 2017

Previous studies based on mouse genetic mutations suggest that proper partitioning of the hindbrain into transient, genetically-defined segments called rhombomeres is required for normal respiratory development and function in neonates. Less clear is what role these genes and the neurons they define play in adult respiratory circuit organization. Several Cre drivers are used to access and study developmental rhombomeric domains (Eng1
Cre
, HoxA2-Cre, Egr2
Cre
, HoxB1
Cre
, and HoxA4-Cre) in the adult. However, these drivers show cumulative activity beyond the brainstem while being used in intersectional genetic experiments to map central respiratory circuitry. We crossed these drivers to conditional DREADD mouse lines to further characterize the functional contributions of Cre defined populations. In the adult, we show that acute DREADD inhibition of targeted populations results in a variety of not only respiratory phenotypes but also metabolic and temperature changes that likely play a significant role in the observed respiratory alterations. DREADD mediated excitation of targeted domains all resulted in death, with unique differences in the patterns of cardio-respiratory failure. These data add to a growing body of work aimed at understanding the role of early embryonic patterning genes in organizing adult respiratory homeostatic networks that may be perturbed in congenital pathophysiologies.
Synthesis of Nm-PHB (nanomelanin-polyhydroxy butyrate) nanocomposite film and its protective effect against biofilm-forming multi drug resistant Staphylococcus aureus
Authors: Kiran George Seghal , Jackson Stephen A. , Priyadharsini Sethu , Dobson Alan D. W. , Selvin Joseph
Published: August 2017

Melanin is a dark brown ubiquitous photosynthetic pigment which have many varied and ever expanding applications in fabrication of radio-protective materials, food packaging, cosmetics and in medicine. In this study, melanin production in a Pseudomonas sp. which was isolated from the marine sponge Tetyrina citirna was optimized employing one-factor at a time experiments and characterized for chemical nature and stability. Following sonication nucleated nanomelanin (Nm) particles were formed and evaluated for antibacterial and antioxidant properties. Nanocomposite film was fabricated using combinations (% w/v) of polyhydroxy butyrate-nanomelanin (PHB:Nm) blended with 1% glycerol. The Nm was found to be spherical in shape with a diameter of 100–140 nm and showed strong antimicrobial activity against both Gram positive and Gram negative bacteria. The Nm-PHB nanocomposite film was homogeneous, smooth, without any cracks, and flexible. XRD and DSC data indicated that the film was crystalline in nature, and was thermostable up to 281.87 °C. This study represents the first report on the synthesis of Nm and fabrication of Nm-PHB nanocomposite film which show strong protective effect against multidrug resistant Staphyloccoccus aureus. Thus this Nm-PHB nanocomposite film may find utility as packaging material for food products by protecting the food products from oxidation and bacterial contamination.
DEMETER plant DNA demethylase induces antiviral response by interferon signalling in animal cells
Authors: Mok Young Geun , Choi Ki Young , Hong Seung Hwan , Huh Jin Hoe
Published: August 2017

DNA methylation is a prominent epigenetic modification in plants and animals regulated by similar mechanisms but the process of DNA demethylation is profoundly different. Unlike vertebrates that require a series of enzymatic conversions of 5-methylcytosine (5mC) into other bases for DNA demethylation, plants utilize the DEMETER (DME) family of 5mC DNA glycosylases to catalyze a direct removal of 5mC from DNA. Here we introduced Arabidopsis DME into human HEK-293T cells to allow direct 5mC excision, and observed that direct DNA demethylation activity was successfully implemented by DME expression. In addition, DME induced diverse cellular responses such as cell proliferation inhibition, cell cycle dysregulation and S phase arrest. Microarray and methylome analyses revealed that DME upregulated a number of genes including cell cycle components, heat shock proteins, and notably, various interferon-stimulated genes. Moreover, DME-mediated DNA demethylation activated endogenous repeat elements, which are likely to form dsRNAs as viral mimics and eventually trigger interferon cascades to establish the antiviral state. This work demonstrates that plant DNA demethylase catalyzes DNA demethylation with a bypass of initial base conversion steps, and the interferon signaling plays a pivotal role to alleviate genotoxic stresses associated with DME-induced DNA demethylation in mammalian cells.
The function of the inner nuclear envelope protein SUN1 in mRNA export is regulated by phosphorylation
Authors: Li Ping , Stumpf Maria , Müller Rolf , Eichinger Ludwig , Glöckner Gernot , Noegel Angelika A.
Published: August 2017

SUN1, a component of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex, functions in mammalian mRNA export through the NXF1-dependent pathway. It associates with mRNP complexes by direct interaction with NXF1. It also binds to the NPC through association with the nuclear pore component Nup153, which is involved in mRNA export. The SUN1-NXF1 association is at least partly regulated by a protein kinase C (PKC) which phosphorylates serine 113 (S113) in the N-terminal domain leading to reduced interaction. The phosphorylation appears to be important for the SUN1 function in nuclear mRNA export since GFP-SUN1 carrying a S113A mutation was less efficient in restoring mRNA export after SUN1 knockdown as compared to the wild type protein. By contrast, GFP-SUN1-S113D resembling the phosphorylated state allowed very efficient export of poly(A)+RNA. Furthermore, probing a possible role of the LINC complex component Nesprin-2 in this process we observed impaired mRNA export in Nesprin-2 knockdown cells. This effect might be independent of SUN1 as expression of a GFP tagged SUN-domain deficient SUN1, which no longer can interact with Nesprin-2, did not affect mRNA export.
Superfluid flow above the critical velocity
Authors: Paris-Mandoki A. , Shearring J. , Mancarella F. , Fromhold T. M. , Trombettoni A. , Krüger P.
Published: August 2017

Superfluidity and superconductivity have been widely studied since the last century in many different contexts ranging from nuclear matter to atomic quantum gases. The rigidity of these systems with respect to external perturbations results in frictionless motion for superfluids and resistance-free electric current flow in superconductors. This peculiar behaviour is lost when external perturbations overcome a critical threshold, i.e. above a critical magnetic field or a critical current for superconductors. In superfluids, such as liquid helium or ultracold gases, the corresponding quantities are a critical rotation rate and a critical velocity respectively. Enhancing the critical values is of great fundamental and practical value. Here we demonstrate that superfluidity can be completely restored for specific, arbitrarily large flow velocities above the critical velocity through quantum interference-induced resonances providing a nonlinear counterpart of the Ramsauer-Townsend effect occurring in ordinary quantum mechanics. We illustrate the robustness of this phenomenon through a thorough analysis in one dimension and prove its generality by showing the persistence of the effect in non-trivial 2d systems. This has far reaching consequences for the fundamental understanding of superfluidity and superconductivity and opens up new application possibilities in quantum metrology, e.g. in rotation sensing.
Visualization of the internal structure of Didymosphenia geminata frustules using nano X-ray tomography
Authors: Zgłobicka Izabela , Li Qiong , Gluch Jürgen , Płocińska Magdalena , Noga Teresa , Dobosz Romuald , Szoszkiewicz Robert , Witkowski Andrzej , Zschech Ehrenfried , Kurzydłowski Krzysztof J.
Published: August 2017

For the first time, the three-dimensional (3D) internal structure of naturally produced Didymosphenia geminata frustules were nondestructively visualized at sub-100 nm resolution. The well-optimized hierarchical structures of these natural organisms provide insight that is needed to design novel, environmentally friendly functional materials. Diatoms, which are widely distributed in freshwater, seawater and wet soils, are well known for their intricate, siliceous cell walls called ‘frustules’. Each type of diatom has a specific morphology with various pores, ribs, minute spines, marginal ridges and elevations. In this paper, the visualization is performed using nondestructive nano X-ray computed tomography (nano-XCT). Arbitrary cross-sections through the frustules, which can be extracted from the nano-XCT 3D data set for each direction, are validated via the destructive focused ion beam (FIB) cross-sectioning of regions of interest (ROIs) and subsequent observation by scanning electron microscopy (SEM). These 3D data are essential for understanding the functionality and potential applications of diatom cells.
Circular RNAs expression profiles in human gastric cancer
Authors: Dang Yuan , Ouyang Xiaojuan , Zhang Fan , Wang Kai , Lin Youdong , Sun Baochang , Wang Yu , Wang Lie , Huang Qiaojia
Published: August 2017

Circular RNAs (circRNAs) are implicated in a variety of cancers. However, the roles of circRNAs in gastric cancer (GC) remain largely unknown. In the current study, circRNAs expression profiles were screened in GC, using 5 pairs of GC and matched non-GC tissues with circRNA chip. Preliminary results were verified with quantitative PCR (qRT-PCR). Briefly, total of 713 circRNAs were differentially expressed in GC tissues vs. non-GC tissues (fold change ≥ 2.0, p < 0.05): 191 were upregulated, whereas 522 were downregulated in GC tissues. qRT-PCR analysis of randomly selected 7 circRNAs from the 713 circRNAs in 50 paired of GC vs. non-GC control tissues confirmed the microarray data. Gene ontology (GO) and KEGG pathway analyses showed that many circRNAs are implicated in carcinogenesis. Among differentially expressed circRNAs, hsa_circ_0076304, hsa_circ_0035431, and hsa_circ_0076305 had the highest magnitude of change. These results provided a preliminary landscape of circRNAs expression profile in GC.
Increased peripheral blood inflammatory cytokine levels in amyotrophic lateral sclerosis: a meta-analysis study
Authors: Hu Yang , Cao Chang , Qin Xiao-Yan , Yu Yun , Yuan Jing , Zhao Yu , Cheng Yong
Published: August 2017

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with poorly understood etiology. Increasing evidence suggest that inflammation may play a critical role in the pathogenesis of ALS. Several studies have demonstrated altered levels of blood cytokines in ALS, but results were inconsistent. Therefore, we did a systematic review of studies comparing blood inflammatory cytokines between ALS patients and control subjects, and quantitatively combined the clinical data with a meta-analysis. The systematic review of Pubmed and Web of Science identified 25 studies encompassing 812 ALS patients and 639 control subjects. Random-effects meta-analysis demonstrated that blood tumor necrosis factor-α (TNF; Hedges’ g = 0.655; p = 0.001), TNF receptor 1 (Hedges’ g = 0.741; p < 0.001), interleukin 6 (IL-6; Hedges’ g = 0.25; p = 0.005), IL-1β (Hedges’ g = 0.296; p = 0.038), IL-8 (Hedges’ g = 0.449; p < 0.001) and vascular endothelial growth factor (Hedges’ g = 0.891; p = 0.003) levels were significantly elevated in patients with ALS compared with control subjects. These results substantially enhance our knowledge of the inflammatory response in ALS, and peripheral blood inflammatory cytokines may be used as diagnostic biomarkers for ALS in the future.
Composition formulas of Fe-based transition metals-metalloid bulk metallic glasses derived from dual-cluster model of binary eutectics
Authors: Naz Gul Jabeen , Dong Dandan , Geng Yaoxiang , Wang Yingmin , Dong Chuang
Published: August 2017

It is known that bulk metallic glasses follow simple composition formulas [cluster](glue atom)1 or 3 with 24 valence electrons within the framework of the cluster-plus-glue-atom model. Though the relevant nearest-neighbor cluster can be readily identified from a devitrification phase, the glue atoms remains poorly defined. The present work is devoted to understanding the composition rule of Fe-(B,P,C) based multi-component bulk metallic glasses, by introducing a cluster-based eutectic liquid model. This model regards a eutectic liquid to be composed of two stable liquids formulated respectively by cluster formulas for ideal metallic glasses from the two eutectic phases. The dual cluster formulas are first established for binary Fe-(B,C,P) eutectics: [Fe-Fe14]B2Fe + [B-B2Fe8]Fe ≈ Fe83.3B16.7 for eutectic Fe83B17, [P-Fe14]P + [P-Fe9]P2Fe≈Fe82.8P17.2 for Fe83P17, and [C-Fe6]Fe3 + [C-Fe9]C2Fe ≈ Fe82.6C17.4 for Fe82.7C17.3. The second formulas in these dual-cluster formulas, being respectively relevant to devitrification phases Fe2B, Fe3P, and Fe3C, well explain the compositions of existing Fe-based transition metals-metalloid bulk metallic glasses. These formulas also satisfy the 24-electron rule. The proposition of the composition formulas for good glass formers, directly from known eutectic points, constitutes a new route towards understanding and eventual designing metallic glasses of high glass forming abilities.
Time-Resolved Spectroscopic Study on the Photoredox Reaction of 2-(p-Hydroxymethyl)phenylAnthraquinone
Authors: Song Qingqing , Zhang Xiting , Ma Jiani , Guo Yan , Phillips David Lee
Published: August 2017

In this work, we report a combined time-resolved spectroscopic and density functional theory computational study on 2-(p-hydroxymethyl)phenylanthraquinone (PPAQ) in which the benzyl alcohol moiety is significantly farther away from the AQ ketone group compared to the compound 2-(1-hydroxyethyl) 9,10-anthraquinone (HEAQ) so as to investigate the photophysical and photochemical reactions of PPAQ in several solvents, especially for the photoredox reaction in a pH 2 aqueous solution. The results here indicate that PPAQ undergoes the photoredox reaction via a two-step pathway and that the low efficiency of the photoredox reaction of PPAQ compared to the related HEAQ molecule is caused by the longer distance between the benzyl alcohol moiety and the AQ ketone moieties.
Ecological and evolutionary consequences of alternative sex-change pathways in fish
Authors: Benvenuto C. , Coscia I. , Chopelet J. , Sala-Bozano M. , Mariani S.
Published: August 2017

Sequentially hermaphroditic fish change sex from male to female (protandry) or vice versa (protogyny), increasing their fitness by becoming highly fecund females or large dominant males, respectively. These life-history strategies present different social organizations and reproductive modes, from near-random mating in protandry, to aggregate- and harem-spawning in protogyny. Using a combination of theoretical and molecular approaches, we compared variance in reproductive success (Vk*) and effective population sizes (Ne) in several species of sex-changing fish. We observed that, regardless of the direction of sex change, individuals conform to the same overall strategy, producing more offspring and exhibiting greater Vk* in the second sex. However, protogynous species show greater Vk*, especially pronounced in haremic species, resulting in an overall reduction of Ne compared to protandrous species. Collectively and independently, our results demonstrate that the direction of sex change is a pivotal variable in predicting demographic changes and resilience in sex-changing fish, many of which sustain highly valued and vulnerable fisheries worldwide.
Reversible inactivation of a peptidoglycan transpeptidase by a β-lactam antibiotic mediated by β-lactam-ring recyclization in the enzyme active site
Authors: Edoo Zainab , Arthur Michel , Hugonnet Jean-Emmanuel
Published: August 2017

β-lactam antibiotics act as suicide substrates of transpeptidases responsible for the last cross-linking step of peptidoglycan synthesis in the bacterial cell wall. Nucleophilic attack of the β-lactam carbonyl by the catalytic residue (Ser or Cys) of transpeptidases results in the opening of the β-lactam ring and in the formation of a stable acyl-enzyme. The acylation reaction is considered as irreversible due to the strain of the β-lactam ring. In contradiction with this widely accepted but poorly demonstrated premise, we show here that the acylation of the L,D-transpeptidase Ldtfm from Enterococcus faecium by the β-lactam nitrocefin is reversible, leading to limited antibacterial activity. Experimentally, two independent methods based on spectrophotometry and mass spectrometry provided evidence that recyclization of the β-lactam ring within the active site of Ldtfm regenerates native nitrocefin. Ring strain is therefore not sufficient to account for irreversible acylation of peptidoglycan transpeptidases observed for most β-lactam antibiotics.
Identification of novel molecular signatures of IgA nephropathy through an integrative -omics analysis
Authors: Krochmal Magdalena , Cisek Katryna , Filip Szymon , Markoska Katerina , Orange Clare , Zoidakis Jerome , Gakiopoulou Chara , Spasovski Goce , Mischak Harald , Delles Christian , Vlahou Antonia , Jankowski Joachim
Published: August 2017

IgA nephropathy (IgAN) is the most prevalent among primary glomerular diseases worldwide. Although our understanding of IgAN has advanced significantly, its underlying biology and potential drug targets are still unexplored. We investigated a combinatorial approach for the analysis of IgAN-relevant -omics data, aiming at identification of novel molecular signatures of the disease. Nine published urinary proteomics datasets were collected and the reported differentially expressed proteins in IgAN vs. healthy controls were integrated into known biological pathways. Proteins participating in these pathways were subjected to multi-step assessment, including investigation of IgAN transcriptomics datasets (Nephroseq database), their reported protein-protein interactions (STRING database), kidney tissue expression (Human Protein Atlas) and literature mining. Through this process, from an initial dataset of 232 proteins significantly associated with IgAN, 20 pathways were predicted, yielding 657 proteins for further analysis. Step-wise evaluation highlighted 20 proteins of possibly high relevance to IgAN and/or kidney disease. Experimental validation of 3 predicted relevant proteins, adenylyl cyclase-associated protein 1 (CAP1), SHC-transforming protein 1 (SHC1) and prolylcarboxypeptidase (PRCP) was performed by immunostaining of human kidney sections. Collectively, this study presents an integrative procedure for -omics data exploitation, giving rise to biologically relevant results.
A pulsed-air model of blue whale B call vocalizations
Authors: Dziak R. P. , Haxel J. H. , Lau T.-K. , Heimlich S. , Caplan-Auerbach J. , Mellinger D. K. , Matsumoto H. , Mate B.
Published: August 2017

Blue whale sound production has been thought to occur by Helmholtz resonance via air flowing from the lungs into the upper respiratory spaces. This implies that the frequency of blue whale vocalizations might be directly proportional to the size of their sound-producing organs. Here we present a sound production mechanism where the fundamental and overtone frequencies of blue whale B calls can be well modeled using a series of short-duration (<1 s) wavelets. We propose that the likely source of these wavelets are pneumatic pulses caused by opening and closing of respiratory valves during air recirculation between the lungs and laryngeal sac. This vocal production model is similar to those proposed for humpback whales, where valve open/closure and vocal fold oscillation is passively driven by airflow between the lungs and upper respiratory spaces, and implies call frequencies could be actively changed by the animal to center fundamental tones at different frequency bands during the call series.
Mapping the spatial variability of HIV infection in Sub-Saharan Africa: Effective information for localized HIV prevention and control
Authors: Cuadros Diego F. , Li Jingjing , Branscum Adam J. , Akullian Adam , Jia Peng , Mziray Elizabeth N. , Tanser Frank
Published: August 2017

Under the premise that in a resource-constrained environment such as Sub-Saharan Africa it is not possible to do everything, to everyone, everywhere, detailed geographical knowledge about the HIV epidemic becomes essential to tailor programmatic responses to specific local needs. However, the design and evaluation of national HIV programs often rely on aggregated national level data. Against this background, here we proposed a model to produce high-resolution maps of intranational estimates of HIV prevalence in Kenya, Malawi, Mozambique and Tanzania based on spatial variables. The HIV prevalence maps generated highlight the stark spatial disparities in the epidemic within a country, and localize areas where both the burden and drivers of the HIV epidemic are concentrated. Under an era focused on optimal allocation of evidence-based interventions for populations at greatest risk in areas of greatest HIV burden, as proposed by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United States President’s Emergency Plan for AIDS Relief (PEPFAR), such maps provide essential information that strategically targets geographic areas and populations where resources can achieve the greatest impact.
Increasing the doping efficiency by surface energy control for ultra-transparent graphene conductors
Authors: Chang Kai-Wen , Hsieh Ya-Ping , Ting Chu-Chi , Su Yen-Hsun , Hofmann Mario
Published: August 2017

Graphene’s attractiveness in many applications is limited by its high resistance. Extrinsic doping has shown promise to overcome this challenge but graphene’s performance remains below industry requirements. This issue is caused by a limited charge transfer efficiency (CTE) between dopant and graphene. Using AuCl3 as a model system, we measure CTE as low as 5% of the expected values due to the geometrical capacitance of small adsorbate clusters. We here demonstrate a strategy for enhancing the CTE by a two-step optimization of graphene’s surface energy prior to AuCl3 doping. First, exposure to UV ozone modified the hydrophilicity of graphene and was found to decrease the cluster’s geometric capacitance, which had a direct effect on the CTE. Occurrence of lattice defects at high UV exposure, however, deteriorated graphene’s transport characteristics and limited the effectiveness of this pretreatment step. Thus, prior to UV exposure, a functionalized polymer layer was introduced that could further enhance graphene’s surface energy while protecting it from damage. Combination of these treatment steps were found to increase the AuCl3 charge transfer efficiency to 70% and lower the sheet resistance to 106 Ω/γ at 97% transmittance which represents the highest reported performance for doped single layer graphene and is on par with commercially available transparent conductors.
The open architecture of HD-PTP phosphatase provides new insights into the mechanism of regulation of ESCRT function
Authors: Gahloth Deepankar , Heaven Graham , Jowitt Thomas A. , Mould A. Paul , Bella Jordi , Baldock Clair , Woodman Philip , Tabernero Lydia
Published: August 2017

HD-PTP is a tumour suppressor phosphatase that controls endocytosis, down-regulation of mitogenic receptors and cell migration. Central to its role is the specific recruitment of critical endosomal sorting complexes required for transport (ESCRTs). However, the molecular mechanisms that enable HD-PTP to regulate ESCRT function are unknown. We have characterised the molecular architecture of the entire ESCRT binding region of HD-PTP using small angle X-ray scattering and hydrodynamic analyses. We show that HD-PTP adopts an open and extended conformation, optimal for concomitant interactions with multiple ESCRTs, which contrasts with the compact conformation of the related ESCRT regulator Alix. We demonstrate that the HD-PTP open conformation is functionally competent for binding cellular protein partners. Our analyses rationalise the functional cooperation of HD-PTP with ESCRT-0, ESCRT-I and ESCRT-III and support a model for regulation of ESCRT function by displacement of ESCRT subunits, which is crucial in determining the fate of ubiquitinated cargo.
Spacial Energy Distribution Manipulation with Multi-focus Huygens Metamirror
Authors: Wang Zhuochao , Ding Xumin , Zhang Kuang , Wu Qun
Published: August 2017

Huygens metasurface is a planar array of crossed electric and magnetic dipoles, which provide specific surface current to tailor the electromagnetic field distribution. By changing the geometrical parameters of the proposed unit cell, the manipulation range of reflection phase can achieve 2π, while the amplitude of the reflection coefficient can keep above 0.993. Based on the designed Huygens meta-atoms, a novel multi-focus Huygens metamirror is proposed at microwave range in this paper. Utilizing the meta-atoms with the desired reflection phase distribution as calculated, the incident plane wave can be converged to designated points in any desired fashion including focal number, location and intensity distribution, which exhibits outstanding manipulation capability. Our research on Huygens metamirror provides a fascinating design of multi-focus imaging in microwave region, which makes it potential applications in antenna and imaging systems.
Controlling congestion on complex networks: fairness, efficiency and network structure
Authors: Buzna Ľuboš , Carvalho Rui
Published: August 2017

We consider two elementary (max-flow and uniform-flow) and two realistic (max-min fairness and proportional fairness) congestion control schemes, and analyse how the algorithms and network structure affect throughput, the fairness of flow allocation, and the location of bottleneck edges. The more realistic proportional fairness and max-min fairness algorithms have similar throughput, but path flow allocations are more unequal in scale-free than in random regular networks. Scale-free networks have lower throughput than their random regular counterparts in the uniform-flow algorithm, which is favoured in the complex networks literature. We show, however, that this relation is reversed on all other congestion control algorithms for a region of the parameter space given by the degree exponent γ and average degree 〈k〉. Moreover, the uniform-flow algorithm severely underestimates the network throughput of congested networks, and a rich phenomenology of path flow allocations is only present in the more realistic α-fair family of algorithms. Finally, we show that the number of paths passing through an edge characterises the location of a wide range of bottleneck edges in these algorithms. Such identification of bottlenecks could provide a bridge between the two fields of complex networks and congestion control.
Rate of entropy model for irreversible processes in living systems
Authors: Zivieri R. , Pacini N. , Finocchio G. , Carpentieri M.
Published: August 2017

In living systems, it is crucial to study the exchange of entropy that plays a fundamental role in the understanding of irreversible chemical reactions. However, there are not yet works able to describe in a systematic way the rate of entropy production associated to irreversible processes. Hence, here we develop a theoretical model to compute the rate of entropy in the minimum living system. In particular, we apply the model to the most interesting and relevant case of metabolic network, the glucose catabolism in normal and cancer cells. We show, (i) the rate of internal entropy is mainly due to irreversible chemical reactions, and (ii) the rate of external entropy is mostly correlated to the heat flow towards the intercellular environment. The future applications of our model could be of fundamental importance for a more complete understanding of self-renewal and physiopatologic processes and could potentially be a support for cancer detection.
Comparative Genomic and Regulatory Analyses of Natamycin Production of Streptomyces lydicus A02
Authors: Wu Huiling , Liu Weicheng , Shi Lingling , Si Kaiwei , Liu Ting , Dong Dan , Zhang Taotao , Zhao Juan , Liu Dewen , Tian Zhaofeng , Yue Yuesen , Zhang Hong , Xuelian Bai , Liang Yong
Published: August 2017

Streptomyces lydicus A02 is used by industry because it has a higher natamycin-producing capacity than the reference strain S. natalensis ATCC 27448. We sequenced the complete genome of A02 using next-generation sequencing platforms, and to achieve better sequence coverage and genome assembly, we utilized single-molecule real-time (SMRT) sequencing. The assembled genome comprises a 9,307,519-bp linear chromosome with a GC content of 70.67%, and contained 8,888 predicted genes. Comparative genomics and natamycin biosynthetic gene cluster (BGC) analysis showed that BGC are highly conserved among evolutionarily diverse strains, and they also shared closer genome evolution compared with other Streptomyces species. Forty gene clusters were predicted to involve in the secondary metabolism of A02, and it was richly displayed in two-component signal transduction systems (TCS) in the genome, indicating a complex regulatory systems and high diversity of metabolites. Disruption of the phoP gene of the phoR-phoP TCS and nsdA gene confirmed phosphate sensitivity and global negative regulation of natamycin production. The genome sequence and analyses presented in this study provide an important molecular basis for research on natamycin production in Streptomyces, which could facilitate rational genome modification to improve the industrial use of A02.
Nm23-H1-stabilized hnRNPA2/B1 promotes internal ribosomal entry site (IRES)-mediated translation of Sp1 in the lung cancer progression
Authors: Hung Chia-Yang , Wang Yi-Chang , Chuang Jian-Ying , Young Ming-Jer , Liaw Hungjiun , Chang Wen-Chang , Hung Jan-Jong
Published: August 2017

Our recent studies have indicated that specificity protein-1 (Sp1) accumulates substantially in the early stage of lung cancer but is partially decreased in the late stages, which is an important factor in the progression of the cancer. In this study, we found that Nm23-H1 and hnRNPA2/B1 could be recruited to the 5′UTR of Sp1 mRNA. In investigating the clinical relevance of Nm23-H1/Sp1 levels, we found a positive correlation between lung cancer patients with poor prognosis and low levels of Sp1 and Nm23-H1, suggesting an association between Nm23-H1/Sp1 levels and survival rate. Knockdown of Nm23-H1 inhibits lung cancer growth but increases lung cancer cell malignancy, which could be rescued by overexpression of Sp1, indicating that Nm23-H1-induced Sp1 expression is critical for lung cancer progression. We also found that Nm23-H1 increases the protein stability of hnRNPA2/B1and is thereby co-recruited to the 5′UTR of Sp1 mRNA to regulate cap-independent translational activity. Since the Sp1 level is tightly regulated during lung cancer progression, understanding the molecular mechanisms underlying the regulation by Nm23-H1/hnRNPA2B1 of Sp1 expression in the various stages of lung cancer will be beneficial for lung cancer therapy in the future.