bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors
Authors: Lindenberger Jared J. , Kumar Veleti Sri , Wilson Brittney N. , Sucheck Steven J. , Ronning Donald R. 
Published: August 2015

AbstractGlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 Å and 4.0 Å, respectively. The maltohexaose structure reveals a dominant site for α-glucan binding. To obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with α-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 Å resolution and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-α-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 Å resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors.
The thorax morphology of Epiophlebia (Insecta: Odonata) nymphs – including remarks on ontogenesis and evolution
Authors: Büsse Sebastian , Helmker Benjamin , Hörnschemeyer Thomas 
Published: August 2015

AbstractThe species of Epiophlebia are unique among the recent Odonata in showing a mixture of morphological characters of dragonflies (Anisoptera) and damselflies (Zygoptera). The status of the four described extant species of Epiophlebia is disputable from a genetic as well as from a morphological point of view. Here we present an analysis of the thoracic musculature of different nymphal instars of Epiophlebia laidlawi and Epiophlebia superstes to elucidate their morphology and ontogenetic development. In total, 75 muscles have been identified in the thorax of Epiophlebia. This represents the highest number of thoracic muscles ever found in any odonate. It includes six muscles that are reported for the first time for Odonata and three of these are even new for Pterygota. In total, our results indicate that Epiophlebia has the most ancestral thoracic morphology among Odonata.
Ultrafast excited-state dynamics and fluorescence deactivation of near-infrared fluorescent proteins engineered from bacteriophytochromes
Authors: Zhu Jingyi , Shcherbakova Daria M. , Hontani Yusaku , Verkhusha Vladislav V. , Kennis John T. M. 
Published: August 2015

AbstractNear-infrared fluorescent proteins, iRFPs, are recently developed genetically encoded fluorescent probes for deep-tissue in vivo imaging. Their functions depend on the corresponding fluorescence efficiencies and electronic excited state properties. Here we report the electronic excited state deactivation dynamics of the most red-shifted iRFPs: iRFP702, iRFP713 and iRFP720. Complementary measurements by ultrafast broadband fluorescence and absorption spectroscopy show that single exponential decays of the excited state with 600 ~ 700 ps dominate in all three iRFPs, while photoinduced isomerization was completely inhibited. Significant kinetic isotope effects (KIE) were observed with a factor of ~1.8 in D2O and are interpreted in terms of an excited-state proton transfer (ESPT) process that deactivates the excited state in competition with fluorescence and chromophore mobility. On this basis, new approaches for rational molecular engineering may be applied to iRFPs to improve their fluorescence.
Climate changes and solar cycles recorded at the Holocene Paraná Delta and their impact on human population
Authors: Milana Juan Pablo , Kröhling Daniela 
Published: August 2015

AbstractThe Paraná delta, growing at a rate of c. 2 km2 yr−1 since 6,000 yrs, is one of the most complete records of the Late Holocene in southern South America. The evolution of this 17,400 km2 delta enclosed in Plata estuary, can be tracked by a series of 343 successive coastal-ridges showing a c.11 years period, in coincidence with sunspot cycle, also found in some North Hemisphere coastal-ridge successions. The Paraná delta shifted from fluvial, to wave-dominated and back to the present fluvial-dominated delta, in response to climate changes associated with wind activity correlating with South American glacial cycles. The wave-dominated windy period coincides with the activation of the Pampean Sand Sea, suggesting desert conditions prevailed on the Pampas between 5,300 and 1,700 yrs, in coincidence with scarce or absent pre-historic aborigine remains (“archeological silence”). Further warmer and less windy conditions allowed human repopulation. Results suggest that aside the solar forcing, both short and medium term climate changes controlled delta evolution. An important learning is that a slight cooling would turn the highly productive pampas, into that unproductive desert and, given the lack of artificial irrigation systems, changing present-day warmhouse into a cooling cycle might be economically catastrophic for the region.
Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo
Authors: Yuan Xing , Chen Hao , Li Xia , Dai Ming , Zeng Huawu , Shan Lei , Sun Qingyan , Zhang Weidong 
Published: August 2015

AbstractTargeted inhibition of protein kinase C (PKC) inhibits hepatocellular carcinoma (HCC) proliferation and metastasis. We previously reported the cytotoxicity of a series of synthetic phenyl-substituted polyoxygenated xanthone derivatives against human HCC. In the current study, the most potent natural product, isojacareubin (ISJ), was synthesized and its cellular-level antihepatoma activities were evaluated. ISJ significantly inhibited cell proliferation and was highly selective for HCC cells in comparison to nonmalignant QSG-7701 hepatocytes. Moreover, ISJ exhibited pro-apoptotic effects on HepG2 hepatoma cells, as well as impaired HepG2 cell migration and invasion. Furthermore, ISJ was a potent inhibitor of PKC, with differential actions against various PKC isotypes. ISJ selectively inhibited the expression of aPKC (PKCζ) in the cytosol and the translocation of cytosolic PKCζ to membrane site. ISJ also directly interacted with cPKC (PKCα) and nPKC (PKCδ, PKCε and PKCμ) and thereby inhibited the early response of major MAPK phosphorylation and the late response of HCC cell invasion and proliferation. In a hepatoma xenograft model, ISJ pretreatment resulted in significant antihepatoma activity in vivo. These findings identify ISJ as a promising lead compound for the development of new antihepatoma agents and may guide the search for additional selective PKC inhibitors.
Rational Design of Photonic Dust from Nanoporous Anodic Alumina Films: A Versatile Photonic Nanotool for Visual Sensing
Authors: Chen Yuting , Santos Abel , Wang Ye , Kumeria Tushar , Ho Daena , Li Junsheng , Wang Changhai , Losic Dusan 
Published: August 2015

AbstractHerein, we present a systematic study on the development, optimisation and applicability of interferometrically coloured distributed Bragg reflectors based on nanoporous anodic alumina (NAA-DBRs) in the form of films and nanoporous microparticles as visual/colorimetric analytical tools. Firstly, we synthesise a complete palette of NAA-DBRs by galvanostatic pulse anodisation approach, in which the current density is altered in a periodic fashion in order to engineer the effective medium of the resulting photonic films in depth. NAA-DBR photonic films feature vivid colours that can be tuned across the UV-visible-NIR spectrum by structural engineering. Secondly, the effective medium of the resulting photonic films is assessed systematically by visual analysis and reflectometric interference spectroscopy (RIfS) in order to establish the most optimal nanoporous platforms to develop visual/colorimetric tools. Then, we demonstrate the applicability of NAA-DBR photonic films as a chemically selective sensing platform for visual detection of mercury(II) ions. Finally, we generate a new nanomaterial, so-called photonic dust, by breaking down NAA-DBRs films into nanoporous microparticles. The resulting microparticles (μP-NAA-DBRs) display vivid colours and are sensitive towards changes in their effective medium, opening new opportunities for developing advanced photonic nanotools for a broad range of applications.
Homologues of xenobiotic metabolizing N-acetyltransferases in plant-associated fungi: Novel functions for an old enzyme family
Authors: Karagianni Eleni P. , Kontomina Evanthia , Davis Britton , Kotseli Barbara , Tsirka Theodora , Garefalaki Vasiliki , Sim Edith , Glenn Anthony E. , Boukouvala Sotiria 
Published: August 2015

AbstractPlant-pathogenic fungi and their hosts engage in chemical warfare, attacking each other with toxic products of secondary metabolism and defending themselves via an arsenal of xenobiotic metabolizing enzymes. One such enzyme is homologous to arylamine N-acetyltransferase (NAT) and has been identified in Fusarium infecting cereal plants as responsible for detoxification of host defence compound 2-benzoxazolinone. Here we investigate functional diversification of NAT enzymes in crop-compromising species of Fusarium and Aspergillus, identifying three groups of homologues: Isoenzymes of the first group are found in all species and catalyse reactions with acetyl-CoA or propionyl-CoA. The second group is restricted to the plant pathogens and is active with malonyl-CoA in Fusarium species infecting cereals. The third group generates minimal activity with acyl-CoA compounds that bind non-selectively to the proteins. We propose that fungal NAT isoenzymes may have evolved to perform diverse functions, potentially relevant to pathogen fitness, acetyl-CoA/propionyl-CoA intracellular balance and secondary metabolism.
Differences in the regeneration traits of Potamogeton crispus turions from macrophyte- and phytoplankton-dominated lakes
Authors: Xie Dong , Zhou Hengjie , Zhu Hong , Ji Haiting , Li Ning , An Shuqing 
Published: August 2015

AbstractPotamogeton crispus is widely used in submerged macrophyte restoration in China. Turions are an important means of reproduction in this species. To compare the regeneration abilities of P. crispus turions in macrophyte- and phytoplankton-dominated lakes, we collected P. crispus turions from a macrophyte-dominated lake (Liangzi Lake) and a phytoplankton-dominated lake (Taihu Lake). Both lakes are important lakes in the middle and lower reaches of the Yangtze River in China. Our field survey revealed that the turions from the phytoplankton-dominated lake had smaller sizes and higher concentrations of total nitrogen (TN) and total phosphorus (TP) than did those from the macrophyte-dominated lake. Rapid sprouting of the turions from the phytoplankton-dominated lake in 32 days was observed under experimental conditions, although the sprout sizes (heights and biomass) were smaller than those from the macrophyte-dominated lake. Compared with sprouted turions from macrophyte-dominated lake, the sprouted turions from the phytoplankton-dominated lake accumulated higher soluble sugar (SS) but lower starch and free amino acid (FAA) concentrations. A 12-day interval sprout removal treatment significantly stimulated the re-sprouting of turions from both lakes, but scale-leaf-removal treatments had no effect. This study provides evidence that the regeneration strategies of P. crispus turions differ in macrophyte- and phytoplankton-dominated lakes.
Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver
Authors: Kurtz C. Lisa , Fannin Emily E. , Toth Cynthia L. , Pearson Daniel S. , Vickers Kasey C. , Sethupathy Praveen 
Published: August 2015

AbstractMicroRNAs (miRNAs) are important regulators and potential therapeutic targets of metabolic disease. In this study we show by in vivo administration of locked nucleic acid (LNA) inhibitors that suppression of endogenous miR-29 lowers plasma cholesterol levels by ~40%, commensurate with the effect of statins and reduces fatty acid content in the liver by ~20%. Whole transcriptome sequencing of the liver reveals 883 genes dysregulated (612 down, 271 up) by inhibition of miR-29. The set of 612 down-regulated genes are most significantly over-represented in lipid synthesis pathways. Among the up-regulated genes are the anti-lipogenic deacetylase sirtuin 1 (Sirt1) and the anti-lipogenic transcription factor aryl hydrocarbon receptor (Ahr), the latter of which we demonstrate is a direct target of miR-29. In vitro radiolabeled acetate incorporation assays confirm that pharmacologic inhibition of miR-29 significantly reduces de novo cholesterol and fatty acid synthesis. Our findings indicate that miR-29 controls hepatic lipogenic programs, likely in part through regulation of Ahr and Sirt1 and therefore may represent a candidate therapeutic target for metabolic disorders such as dyslipidemia.
Deacetylation of α-tubulin and cortactin is required for HDAC6 to trigger ciliary disassembly
Authors: Ran Jie , Yang Yunfan , Li Dengwen , Liu Min , Zhou Jun 
Published: August 2015

AbstractCilia play important roles in sensing extracellular signals and directing fluid flow. Ciliary dysfunction is associated with a variety of diseases known as ciliopathies. Histone deacetylase 6 (HDAC6) has recently emerged as a major driver of ciliary disassembly, but little is known about the downstream players. Here we provide the first evidence that HDAC6-mediated deacetylation of α-tubulin and cortactin is critical for its induction of ciliary disassembly. HDAC6 is localized in the cytoplasm and enriched at the centrosome and basal body. Overexpression of HDAC6 decreases the levels of acetylated α-tubulin and cortactin without affecting the expression or localization of known ciliary regulators. We also find that overexpression of α-tubulin or cortactin or their acetylation-deficient mutants enhances the ability of HDAC6 to induce ciliary disassembly. In addition, acetylation-mimicking mutants of α-tubulin and cortactin counteract HDAC6-induced ciliary disassembly. Furthermore, HDAC6 stimulates actin polymerization and inhibition of actin polymerization abolishes the activity of HDAC6 to trigger ciliary disassembly. These findings provide mechanistic insight into the ciliary role of HDAC6 and underscore the importance of reversible acetylation in regulating ciliary homeostasis.
Quantitative and qualitative characterization of expanded CD4+ T cell clones in rheumatoid arthritis patients
Authors: Ishigaki Kazuyoshi , Shoda Hirofumi , Kochi Yuta , Yasui Tetsuro , Kadono Yuho , Tanaka Sakae , Fujio Keishi , Yamamoto Kazuhiko 
Published: August 2015

AbstractRheumatoid arthritis (RA) is an autoimmune destructive arthritis associated with CD4+ T cell-mediated immunity. Although expanded CD4+ T cell clones (ECs) has already been confirmed, the detailed characteristics of ECs have not been elucidated in RA. Using combination of a single-cell analysis and next-generation sequencing (NGS) in TCR repertoire analysis, we here revealed the detailed nature of ECs by examining peripheral blood (PB) from 5 RA patients and synovium from 1 RA patient. When we intensively investigated the single-cell transcriptome of the most expanded clones in memory CD4+ T cells (memory-mECs) in RA-PB, senescence-related transcripts were up-regulated, indicating circulating ECs were constantly stimulated. Tracking of the transcriptome shift within the same memory-mECs between PB and the synovium revealed the augmentations in senescence-related gene expression and the up-regulation of synovium-homing chemokine receptors in the synovium. Our in-depth characterization of ECs in RA successfully demonstrated the presence of the specific immunological selection pressure, which determines the phenotype of ECs. Moreover, transcriptome tracking added novel aspects to the underlying sequential immune processes. Our approach may provide new insights into the pathophysiology of RA.
Herpes virus entry mediator licenses Listeria infection induced immunopathology through control of type I interferon
Authors: Lv Mengjie , Wu Weiwei , Zhang Yuejiao , Zhu Mingzhao 
Published: August 2015

AbstractApoptosis of the splenic lymphocytes is often induced during the acute phase of Listeria infection in mice. However, the underlying mechanism remains incompletely understood. Here, we found that herpes virus entry mediator (HVEM) plays an important role for Listeria infection induced lymphocyte apoptosis. Mechanistically, HVEM is not directly involved in listeriolysin O (LLO) induced lymphocyte apoptosis or interferon beta induced T cell activation per se. Interestingly, HVEM is partially required for Listeria induced interferon (IFN)-I production in the spleen, particularly in macrophages. Consequently, the bystander activation of lymphocytes is significantly lower in HVEM deficient mice than that in wild-type (WT) mice upon Listeria infection. Thus, our results have revealed a novel role of HVEM on the regulation of IFN-I and immunopathology during Listeria infection.
Stabilization of weak ferromagnetism by strong magnetic response to epitaxial strain in multiferroic BiFeO3
Authors: Dixit Hemant , Hee Lee Jun , Krogel Jaron T. , Okamoto Satoshi , Cooper Valentino R. 
Published: August 2015

AbstractMultiferroic BiFeO3 exhibits excellent magnetoelectric coupling critical for magnetic information processing with minimal power consumption. However, the degenerate nature of the easy spin axis in the (111) plane presents roadblocks for real world applications. Here, we explore the stabilization and switchability of the weak ferromagnetic moments under applied epitaxial strain using a combination of first-principles calculations and group-theoretic analyses. We demonstrate that the antiferromagnetic moment vector can be stabilized along unique crystallographic directions ([110] and [–110]) under compressive and tensile strains. A direct coupling between the anisotropic antiferrodistortive rotations and the Dzyaloshinskii-Moria interactions drives the stabilization of the weak ferromagnetism. Furthermore, energetically competing C- and G-type magnetic orderings are observed at high compressive strains, suggesting that it may be possible to switch the weak ferromagnetism “on” and “off” under the application of strain. These findings emphasize the importance of strain and antiferrodistortive rotations as routes to enhancing induced weak ferromagnetism in multiferroic oxides.
Structural and biochemical studies reveal UbiG/Coq3 as a class of novel membrane-binding proteins
Authors: Zhu Yuwei , Wu Bo , Zhang Xu , Fan Xiaojiao , Niu Liwen , Li Xu , Wang Junfeng , Teng Maikun 
Published: August 2015

UbiG and Coq3 (orthologue in eukaryotes) are SAM-MTases (S-adenosylmethionine-dependent methyltransferases) that catalyse both O-methylation steps in CoQ biosynthesis from prokaryotes to eukaryotes. However, the detailed molecular mechanism by which they function remains elusive. In the present paper, we report that UbiG/Coq3 defines a novel class of membrane-binding proteins. Escherichia coli UbiG binds specifically to liposomes containing PG (phosphatidylglycerol) or CL (cardiolipin, or diphosphatidylglycerol), two major lipid components of the E. coli plasma membrane, whereas human and yeast Coq3 display a strong preference for liposomes enriched with CL, a signature lipid of the mitochondrial membrane. The crystal structure of UbiG from E. coli was determined at 2.1 Å (1 Å=0.1 nm) resolution. The structure exhibits a typical Class I SAM-MTase fold with several variations, including a unique insertion between strand β5 and helix α10. This insertion is highly conserved and is required for membrane binding. Mutation of the key residues renders UbiG unable to efficiently bind liposome in vitro and the mutant fails to rescue the phenotype of ΔubiG strain in vivo. Taken together, our results shed light on a novel biochemical function of the UbiG/Coq3 protein.
Functional dissection of proliferating-cell nuclear antigens (1 and 2) in human malarial parasitePlasmodium falciparum:possible involvement in DNA replication and DNA damage response
Authors: Mitra Pallabi , Banu Khadija , Deshmukh Abhijit S. , Subbarao Naidu , Dhar Suman Kumar 
Published: August 2015

Eukaryotic PCNAs (proliferating-cell nuclear antigens) play diverse roles in nucleic acid metabolism in addition to DNA replication. Plasmodium falciparum, which causes human malaria, harbours two PCNA homologues: PfPCNA1 and PfPCNA2. The functional role of two distinct PCNAs in the parasite still eludes us. In the present study, we show that, whereas both PfPCNAs share structural and biochemical properties, only PfPCNA1 functionally complements the ScPCNA mutant and forms distinct replication foci in the parasite, which PfPCNA2 fails to do. Although PfPCNA1 appears to be the primary replicative PCNA, both PfPCNA1 and PfPCNA2 participate in an active DDR (DNA-damage-response) pathway with significant accumulation in the parasite upon DNA damage induction. Interestingly, PfPCNA genes were found to be regulated not at the transcription level, but presumably at the protein stability level upon DNA damage. Such regulation of PCNA has not been shown in eukaryotes before. Moreover, overexpression of PfPCNA1 and PfPCNA2 in the parasite confers a survival edge on the parasite in a genotoxic environment. This is the first evidence of a PfPCNA-mediated DDR in the parasite and gives new insights and rationale for the presence of two PCNAs as a parasite survival strategy and its probable success.
Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma
Authors: De Alba Jorge , Otal Raquel , Calama Elena , Domenech Anna , Prats Neus , Gozzard Neil , Miralpeix Montserrat 
Published: August 2015

RNA viruses are a major cause of respiratory infections and are known to exacerbate asthma and other respiratory diseases. Our aim was to test the ability of poly(I:C) (polyinosinic:polycytidylic acid), a viral surrogate, to elicit exacerbation in a model of severe asthma driven by HDM (house dust mite) in FCA (Freund's complete adjuvant). Poly(I:C) was administered intranasally around the HDM challenge in FCA–HDM-sensitized animals. Changes in AHR (airway hyperresponsiveness), BALF (bronchoalveolar lavage fluid) inflammatory infiltrate, HDM-specific immunoglobulins and cytokine/chemokine release were evaluated at different points after the challenge. The effect of oral dexamethasone was also assessed. Exacerbation was achieved when poly(I:C) was administered 24 h before the HDM challenge and was characterized by enhanced AHR and an increase in the numbers of neutrophils, macrophages and lymphocytes in the BALF. Th1, Th2 and Th17 cytokines were also elevated at different time points after the challenge. Peribronchial and alveolar inflammation in lung tissue were also augmented. AHR and inflammatory infiltration showed reduced sensitivity to dexamethasone treatment. We have set up a model that mimics key aspects of viral exacerbation in a corticosteroid-refractory asthmatic phenotype which could be used to evaluate new therapies for this condition.