Separate Fe-S Scaffold And Carrier Functions For SufB2C2 And SufA During In Vitro Maturation Of [2Fe-2S] Fdx

PubMed Central

Chahal, Harsimranjit K.; Outten, F. Wayne

2012-01-01

Iron-sulfur (Fe-S) clusters are inorganic cofactors required for a variety of biological processes. In vivo biogenesis of Fe-S clusters proceeds via complex pathways involving multiple protein complexes. In the Suf Fe-S cluster biogenesis system, SufB may be a scaffold for nascent Fe-S cluster assembly whereas SufA is proposed to act as either a scaffold or an Fe-S cluster carrier from the scaffold to target apo-proteins. However, SufB can form multiple stable complexes with other Suf proteins, such as SufB2C2 and SufBC2D and the specific functions of these complexes in Fe-S cluster assembly are not clear. Here we compare the ability of the SufB2C2 and SufBC2D complexes as well as SufA to promote in vitro maturation of the [2Fe-2S] ferredoxin (Fdx). We found that SufB2C2 was most proficient as a scaffold for de novo assembly of holo-Fdx using sulfide and iron as freely available building blocks while SufA was best at direct transfer of a pre-formed Fe-S cluster to Fdx. Furthermore, cluster transfer from [4Fe-4S] SufB2C2 or SufBC2D to Fdx will proceed through a SufA intermediate to Fdx is SufA is present. Finally, addition of ATP repressed cluster transfer from [4Fe-4S] SufB2C2 to Fdx and from SufBC2D to [2Fe-2S] SufA or Fdx. These studies indicate that SufB2C2 can serve as a terminal scaffold to load the SufA Fe-S cluster carrier for in vitro maturation of [2Fe-2S] enzymes like Fdx. This work is the first to systematically compare the cluster transfer rates of a scaffold (SufB) to the transfer rates of a carrier (SufA) under the same conditions to the same target enzyme and is also the first to reconstitute the full transfer pathway (from scaffold to carrier to target enzyme) in a single reaction. PMID:23018275

Identification of a New Isoindole-2-yl Scaffold as a Qo and Qi Dual Inhibitor of Cytochrome bc 1 Complex: Virtual Screening, Synthesis, and Biochemical Assay.

PubMed

Azizian, Homa; Bagherzadeh, Kowsar; Shahbazi, Sophia; Sharifi, Niusha; Amanlou, Massoud

2017-09-18

Respiratory chain ubiquinol-cytochrome (cyt) c oxidoreductase (cyt bc 1 or complex III) has been demonstrated as a promising target for numerous antibiotics and fungicide applications. In this study, a virtual screening of NCI diversity database was carried out in order to find novel Qo/Qi cyt bc 1 complex inhibitors. Structure-based virtual screening and molecular docking methodology were employed to further screen compounds with inhibition activity against cyt bc 1 complex after extensive reliability validation protocol with cross-docking method and identification of the best score functions. Subsequently, the application of rational filtering procedure over the target database resulted in the elucidation of a novel class of cyt bc 1 complex potent inhibitors with comparable binding energies and biological activities to those of the standard inhibitor, antimycin.

Mutational Analysis of the QRRQ Motif in the Yeast Hig1 Type 2 Protein Rcf1 Reveals a Regulatory Role for the Cytochrome c Oxidase Complex*

PubMed Central

Garlich, Joshua; Strecker, Valentina; Wittig, Ilka; Stuart, Rosemary A.

2017-01-01

The yeast Rcf1 protein is a member of the conserved family of proteins termed the hypoxia-induced gene (domain) 1 (Hig1 or HIGD1) family. Rcf1 interacts with components of the mitochondrial oxidative phosphorylation system, in particular the cytochrome bc1 (complex III)-cytochrome c oxidase (complex IV) supercomplex (termed III-IV) and the ADP/ATP carrier proteins. Rcf1 plays a role in the assembly and modulation of the activity of complex IV; however, the molecular basis for how Rcf1 influences the activity of complex IV is currently unknown. Hig1 type 2 isoforms, which include the Rcf1 protein, are characterized in part by the presence of a conserved motif, (Q/I)X3(R/H)XRX3Q, termed here the QRRQ motif. We show that mutation of conserved residues within the Rcf1 QRRQ motif alters the interactions between Rcf1 and partner proteins and results in the destabilization of complex IV and alteration of its enzymatic properties. Our findings indicate that Rcf1 does not serve as a stoichiometric component, i.e. as a subunit of complex IV, to support its activity. Rather, we propose that Rcf1 serves to dynamically interact with complex IV during its assembly process and, in doing so, regulates a late maturation step of complex IV. We speculate that the Rcf1/Hig1 proteins play a role in the incorporation and/or remodeling of lipids, in particular cardiolipin, into complex IV and. possibly, other mitochondrial proteins such as ADP/ATP carrier proteins. PMID:28167530

Self-assembling HA/PEI/dsRNA-p21 ternary complexes for CD44 mediated small active RNA delivery to colorectal cancer.

PubMed

Feng, Chen-Lin; Han, Yan-Xing; Guo, Hui-Hui; Ma, Xiao-Lei; Wang, Zhi-Qiang; Wang, Lu-Lu; Zheng, Wen-Sheng; Jiang, Jian-Dong

2017-11-01

Our previous work proved that sequence specific double strand RNA (dsRNA-p21) effectively activated p21 gene expression of colorectal cancer (CRC) cells and consequently suppressed CRC growth. However, efficient delivery system is a significant challenge to achieve sufficient therapy. In this study, a self-assembled HA/PEI/dsRNA-p21 ternary complex (TC-dsRNA-p21) was developed for the tumor-target delivery of dsRNA-p21 into CRC cells. Hyaluronic acid (HA) was introduced to shield the PEI/dsRNA-p21 binary complexes (BC-dsRNA-p21) for reducing the cytotoxicity of PEI and for increasing the tumor-targeted intracellular uptake by cancer cells through HA-CD44 mediated endocytosis. Comparing to the BC-dsRNA-p21, the TC-dsRNA-p21 showed increase in size, decrease in zeta potential, low cytotoxicity as well as high stability in physiological conditions due to the anionic shielding. Confocal microscopy analysis and flow cytometry confirmed that TC-dsRNA-p21 had high transfection efficiency in the CD44-abundant Lovo cells, as compared with binary complex. In vitro physiological experiment showed that, comparing to the control group, the TC-dsRNA-p21 effectively activated the expression of p21 mRNA and P21 protein, causing blockage of cell cycle at G 0 /G 1 phase and suppression of cancer cell proliferation as well as colony formation. Furthermore, in vivo distribution experiment demonstrated that the TC-dsRNA-p21 could effectively accumulate at rectal wall for up to 10 h, following in situ application. These findings indicated that TC-dsRNA-p21 might hold great potential for delivering dsRNA-p21 to treat CRC.

Assembly of barcode-like nucleic acid nanostructures.

PubMed

Wang, Pengfei; Tian, Cheng; Li, Xiang; Mao, Chengde

2014-10-15

Barcode-like (BC) nanopatterns from programmed self-assembly of nucleic acids (DNA and RNA) are reported. BC nanostructures are generated by the introduction of open spaces at selected sites to an otherwise closely packed, plain, rectangle nucleic acid nanostructure. This strategy is applied to nanostructures assembled from both origami approach and single stranded tile approach. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Binding of the respiratory chain inhibitor ametoctradin to the mitochondrial bc1 complex.

PubMed

Fehr, Marcus; Wolf, Antje; Stammler, Gerd

2016-03-01

Ametoctradin is an agricultural fungicide that inhibits the mitochondrial bc1 complex of oomycetes. The bc1 complex has two quinone binding sites that can be addressed by inhibitors. Depending on their binding sites and binding modes, the inhibitors show different degrees of cross-resistance that need to be considered when designing spray programmes for agricultural fungicides. The binding site of ametoctradin was unknown. Cross-resistance analyses, the reduction of isolated Pythium sp. bc1 complex in the presence of different inhibitors and molecular modelling studies were used to analyse the binding site and binding mode of ametoctradin. All three approaches provide data supporting the argument that ametoctradin binds to the Pythium bc1 complex similarly to stigmatellin. The binding mode of ametoctradin differs from other agricultural fungicides such as cyazofamid and the strobilurins. This explains the lack of cross-resistance with strobilurins and related inhibitors, where resistance is mainly caused by G143A amino acid exchange. Accordingly, mixtures or alternating applications of these fungicides and ametoctradin can help to minimise the risk of the emergence of new resistant isolates. © 2015 Society of Chemical Industry.

Initial assembly steps of a translocase for folded proteins

PubMed Central

Blümmel, Anne-Sophie; Haag, Laura A.; Eimer, Ekaterina; Müller, Matthias; Fröbel, Julia

2015-01-01

The so-called Tat (twin-arginine translocation) system transports completely folded proteins across cellular membranes of archaea, prokaryotes and plant chloroplasts. Tat-directed proteins are distinguished by a conserved twin-arginine (RR-) motif in their signal sequences. Many Tat systems are based on the membrane proteins TatA, TatB and TatC, of which TatB and TatC are known to cooperate in binding RR-signal peptides and to form higher-order oligomeric structures. We have now elucidated the fine architecture of TatBC oligomers assembled to form closed intramembrane substrate-binding cavities. The identification of distinct homonymous and heteronymous contacts between TatB and TatC suggest that TatB monomers coalesce into dome-like TatB structures that are surrounded by outer rings of TatC monomers. We also show that these TatBC complexes are approached by TatA protomers through their N-termini, which thereby establish contacts with TatB and membrane-inserted RR-precursors. PMID:26068441

Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer

DTIC Science & Technology

2011-05-01

Briefly, the electron transfer activities of complex I/III (NADH dehydrogenase/cytochrome bc1 complex: catalyzes the electron transfer from NADH to...ferricytochrome c) and complex II/III (succinate dehydrogenase/cytochrome bc1 complex: catalyzes the electron transfer from succinate to ferricytochrome...The electron transfer activity of complex IV (cytochrome c oxidase: catalyzes the final step of the respiratory chain by transferring electrons from

Activation of EVI1 transcription by the LEF1/β-catenin complex with p53-alteration in myeloid blast crisis of chronic myeloid leukemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manachai, Nawin; Saito, Yusuke; Nakahata, Shingo

The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blast crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined. Here, we demonstrate the transcriptional activity of EVI1more » is dependent on activation of lymphoid enhancer-binding factor 1 (LEF1)/β-catenin complex by BCR-ABL with loss of p53 function during CML-BC. The activation of β-catenin is partly dependent on BCR-ABL expression through enhanced GSK3β phosphorylation, and EVI1 expression is directly enhanced by the LEF1/β-catenin complex bound to the EVI1 promoter region. Moreover, the loss of p53 expression is inversely correlated with high expression of EVI1 in CML leukemia cells with an aggressive phase of CML, and a portion of the activation mechanism of EVI1 expression is dependent on β-catenin activation through GSK3β phosphorylation by loss of p53. Therefore, we found that the EVI1 activation in CML-BC is dependent on LEF1/β-catenin activation by BCR-ABL expression with loss of p53 function, representing a novel selective therapeutic approach targeting myeloid blast crisis progression. - Highlights: • Transcriptional regulation of EVI1 in CML-BC is proposed. • EVI1 transcription is directly regulated by LEF1/β-catenin complex in CML-BC. • Loss of p53 function as a key regulator for β-catenin-EVI1 in CML myeloid-BC. • The LEF1/β-catenin binding site on the EVI1 promoter is a new target for CML-BC.« less

Co-expression, purification and characterization of the lipase and foldase of Burkholderia contaminans LTEB11.

PubMed

Alnoch, Robson Carlos; Stefanello, Adriano Alves; Paula Martini, Viviane; Richter, Jeferson Luiz; Mateo, Cesar; Souza, Emanuel Maltempi de; Mitchell, David Alexander; Muller-Santos, Marcelo; Krieger, Nadia

2018-05-30

Genes encoding lipase LipBC (lipA) and foldase LifBC (lipB) were identified in the genome of Burkholderia contaminans LTEB11. Analysis of the predicted amino acid sequence of lipA showed its high identity with lipases from Pseudomonas luteola (91%), Burkholderia cepacia (96%) and Burkholderia lata (97%), and classified LipBC lipase in the lipase subfamily I.2. The genes lipA and lipB were amplified and cloned into expression vectors pET28a(+) and pT7-7, respectively. His-tagged LipBC and native LifBC were co-expressed in Escherichia coli and purified. LipBC and LifBC have molecular weights of 35.9 kDa and 37 kDa, respectively, and remain complexed after purification. The Lip-LifBC complex was active and stable over a wide range of pH values (6.5-10) and temperatures (25-45 °C), with the highest specific activity (1426 U mg -1 ) being against tributyrin. The Lip-LifBC complex immobilized on Sepabeads was able to catalyze the synthesis of ethyl-oleate in n‑hexane with an activity of 4 U g -1 , maintaining high conversion (>80%) over 5 reaction cycles of 6 h at 45 °C. The results obtained in this work provide a basis for the development of applications of recombinant LipBC in biocatalysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Hybrid fusions show that inter-monomer electron transfer robustly supports cytochrome bc{sub 1} function in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ekiert, Robert; Czapla, Monika; Sarewicz, Marcin

2014-08-22

Highlights: • We used hybrid fusion bc{sub 1} complex to test inter-monomer electron transfer in vivo. • Cross-inactivated complexes were able to sustain photoheterotrophic growth. • Inter-monomer electron transfer supports catalytic cycle in vivo. • bc{sub 1} dimer is functional even when cytochrome b subunits come from different species. - Abstract: Electronic connection between Q{sub o} and Q{sub i} quinone catalytic sites of dimeric cytochrome bc{sub 1} is a central feature of the energy-conserving Q cycle. While both the intra- and inter-monomer electron transfers were shown to connect the sites in the enzyme, mechanistic and physiological significance of the lattermore » remains unclear. Here, using a series of mutated hybrid cytochrome bc{sub 1}-like complexes, we show that inter-monomer electron transfer robustly sustains the function of the enzyme in vivo, even when the two subunits in a dimer come from different species. This indicates that minimal requirement for bioenergetic efficiency is to provide a chain of cofactors for uncompromised electron flux between the catalytic sites, while the details of protein scaffold are secondary.« less

X-ray and cryo-EM structures of inhibitor-bound cytochrome bc 1 complexes for structure-based drug discovery

PubMed Central

Amporndanai, Kangsa; O’Neill, Paul M.

2018-01-01

Cytochrome bc 1, a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. Structural studies of cytochrome bc 1 from mammalian homologues co-crystallized with lead compounds have underpinned structure-based drug design to develop compounds with higher potency and selectivity. However, owing to the limited amount of cytochrome bc 1 that may be available from parasites, all efforts have been focused on homologous cytochrome bc 1 complexes from mammalian species, which has resulted in the failure of some drug candidates owing to toxicity in the host. Crystallographic studies of the native parasite proteins are not feasible owing to limited availability of the proteins. Here, it is demonstrated that cytochrome bc 1 is highly amenable to single-particle cryo-EM (which uses significantly less protein) by solving the apo and two inhibitor-bound structures to ∼4.1 Å resolution, revealing clear inhibitor density at the binding site. Therefore, cryo-EM is proposed as a viable alternative method for structure-based drug discovery using both host and parasite enzymes. PMID:29765610

Nanoparticle string formation on self-assembled copolymer films

NASA Astrophysics Data System (ADS)

Jenczyk, J.; Woźniak-Budych, M.; Jarek, M.; Grzeszkowiak, M.; Nowaczyk, G.; Jurga, S.

2017-06-01

Nanoparticles (NP) string formations on self-assembled copolymeric substrates has been observed. These "thread of beads" like structures develop via simple colloidal droplet evaporation during meniscus rim withdrawal on polystyrene-block-poly(ethylene oxide) (PS-PEO) copolymer surfaces. It is shown that the process is triggered by the presence of the substrate impurities, which lead to NP aggregate formations serving as string initiation sites. The growth mechanism of these linear structures seems to be capillarity-driven. Moreover, there is an exceptional alignment coupling between NP strips and the block copolymer (BC) domains observed. BC directed NP assembly stems from a gold nanocrystal surface functionalization, which introduces selective affinity for one particular type of BC domain. The presented results reveal a potential fabrication method of NP wires characterized by remarkably low width and thickness comparable with the size of the individual constituent NP.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiarello, Carmelina; Bortoloso, Elena; Carpi, Andrea

2013-07-15

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α{sub 1}-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1 h, and no up-regulation of Homer 1b/c, as judged bymore » Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy. -- Highlights: • Homer 1a is constitutively expressed in cardiac tissue. • In HL-1 cells, norepinephrine activates signaling pathways leading to hypertrophy. • Homer 1a up-regulation is an early event of norepinephrine-induced hypertrophy. • Homer 1a plays a negative feedback regulation modulating pathological hypertrophy. • Over-expression of Homer 1a per se does not induce hypertrophy.« less

Preparation and Characterization of PVA Alkaline Solid Polymer Electrolyte with Addition of Bamboo Charcoal.

PubMed

Fan, Lidan; Wang, Mengyue; Zhang, Zhen; Qin, Gang; Hu, Xiaoyi; Chen, Qiang

2018-04-26

Natural bamboo charcoal (BC) powder has been developed as a novel filler in order to further improve performances of the polyvinyl alcohol (PVA)-based alkaline solid polymer electrolyte (ASPE) by solution casting method. X-ray diffraction patterns of composite polymer electrolyte with BC revealed the decrease in the degree of crystallinity with increasing content of BC. Scanning electron microscopy images showed pores on a micrometer scale (average diameter about 2 μm) distributed inside and on the surface of the membranes, indicating a three-dimension network formed in the polymer framework. The ionic conductivity was measured by the alternating-current (AC) impedance method, and the highest conductivity value of 6.63 × 10 −2 S·cm −1 was obtained with 16 wt % of BC content and m KOH : m PVA = 2:1.5 at 30 °C. The contents of BC and KOH could significantly influence the conductivity. The temperature dependence of the bulk electrical conductivity displayed a combination of Arrhenius nature, and the activation energy for the ion in polymer electrolyte has been calculated. The electrochemical stability window of the electrolyte membrane was over 1.6 V. The thermogravimetric analysis curves showed that the degradation temperatures of PVA-BC-KOH ASPE membranes shifted toward higher with adding BC. A simple nickel-hydrogen battery containing PVA-BC-KOH electrolyte membrane was assembled with a maximum discharge capacity of 193 mAh·g −1 .

The role of TcdB and TccC subunits in secretion of the Photorhabdus Tcd toxin complex.

PubMed

Yang, Guowei; Waterfield, Nicholas R

2013-01-01

The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of bacterial pathogens. The best-characterized examples are from the insect pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large protein subunits, designated A, B and C that assemble in a 5∶1∶1 stoichiometry. Oral toxicity to a range of insects means that some have the potential to be developed as pest control technology. The three subunit proteins do not encode any recognisable export sequences and as such little progress has been made in understanding their secretion. We have developed heterologous TC production and secretion models in E. coli and used them to ascribe functions to different domains of the crucial B+C sub-complex. We have determined that the B and C subunits use a secretion mechanism that is either encoded by the proteins themselves or employ an as yet undefined system common to laboratory strains of E. coli. We demonstrate that both the N-terminal domains of the B and C subunits are required for secretion of the whole complex. We propose a model whereby the N-terminus of the C-subunit toxin exports the B+C sub-complex across the inner membrane while that of the B-subunit allows passage across the outer membrane. We also demonstrate that even in the absence of the B-subunit, that the C-subunit can also facilitate secretion of the larger A-subunit. The recognition of this novel export system is likely to be of importance to future protein secretion studies. Finally, the identification of homologues of B and C subunits in diverse bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these toxins are likely to be important in a range of different hosts, including man.

Structural Basis of Resistance to Anti-Cytochrome bc1 Complex Inhibitors: Implication for Drug Improvement

PubMed Central

Esser, Lothar; Yu, Chang-An; Xia, Di

2016-01-01

The emergence of drug resistance has devastating economic and social consequences, a testimonial of which is the rise and fall of inhibitors against the respiratory component cytochrome bc1 complex, a time tested and highly effective target for disease control. Unfortunately, the mechanism of resistance is a multivariate problem, including primarily mutations in the gene of the cytochrome b subunit but also activation of alternative pathways of ubiquinol oxidation and pharmacokinetic effects. There is a considerable interest in designing new bc1 inhibitors with novel modes of binding and lower propensity to induce the development of resistance. The accumulation of crystallographic data of bc1 complexes with and without inhibitors bound provides the structural basis for rational drug design. In particular, the cytochrome b subunit offers two distinct active sites that can be targeted for inhibition - the quinol oxidation site and the quinone reduction site. This review brings together available structural information of inhibited bc1 by various quinol oxidation- and reduction-site inhibitors, the inhibitor binding modes, conformational changes upon inhibitor binding of side chains in the active site and large scale domain movements of the iron-sulfur protein subunit. Structural data analysis provides a clear understanding of where and why existing inhibitors fail and points towards promising alternatives. PMID:23688079

Electronic and magnetic properties of Fe-, Co-, and Ni-decorated BC3: A first-principles study

NASA Astrophysics Data System (ADS)

Zhu, Jingzhong; Zhao, Yinchang; Zulfiqar, Muhammad; Zeng, Shuming; Ni, Jun

2018-05-01

The electronic and magnetic properties of Fe-, Co-, and Ni-decorated two dimensional (2D) BC3 are systematically investigated by first-principles calculations. We find that the Fe, Co, and Ni atoms can be strongly adsorbed on the hollow sites of 2D BC3. Fe and Co adatoms are more stable when adsorbed on the hollow sites of the carbon rings in the 2D BC3, while the hollow sites of boron-carbon rings in the 2D BC3 are the most stable sites for the adsorption of Ni adatoms. These proposed metal-BC3 complexes exhibit interesting electronic and magnetic behaviors. In particular, the Fe-BC3 and Co-BC3 complexes are metals with magnetic ground states , while the Ni-BC3 complex behaves as a nonmagnetic semiconductor with a direct bandgap. Furthermore, our magnetic analysis reveals that induced magnetism in the Fe-BC3 and Co-BC3 complexes arises from their local magnetic moments. Functionalization of 2D BC3 through these metal-adatom adsorption appears to be a promising way to extend its applications.

Draft Genome Assembly of a Filamentous Euendolithic (True Boring) Cyanobacterium, Mastigocoleus testarum Strain BC008.

PubMed

Guida, Brandon S; Garcia-Pichel, Ferran

2016-01-28

Mastigocoleus testarum strain BC008 is a model organism used to study marine photoautotrophic carbonate dissolution. It is a multicellular, filamentous, diazotrophic, euendolithic cyanobacterium ubiquitously found in marine benthic environments. We present an accurate draft genome assembly of 172 contigs spanning 12,700,239 bp with 9,131 annotated genes with an average G+C% of 37.3. Copyright © 2016 Guida and Garcia-Pichel.

Substituting leucine for alanine-86 in the tether region of the iron-sulfur protein of the cytochrome bc1 complex affects the mobility of the [2Fe2S] domain.

PubMed

Ghosh, M; Wang, Y; Ebert, C E; Vadlamuri, S; Beattie, D S

2001-01-16

Mutating three conserved alanine residues in the tether region of the iron-sulfur protein of the yeast cytochrome bc(1) complex resulted in 22-56% decreases in enzymatic activity [Obungu et al. (2000) Biochim. Biophys. Acta 1457, 36-44]. The activity of the cytochrome bc(1) complex isolated from A86L was decreased 60% compared to the wild-type without loss of heme or protein and without changes in the 2Fe2S cluster or proton-pumping ability. The activity of the bc(1) complex from mutant A92R was identical to the wild-type, while loss of both heme and activity was observed in the bc(1) complex isolated from mutant A90I. Computer simulations indicated that neither mutation A86L nor mutation A92R affects the alpha-helical backbone in the tether region; however, the side chain of the leucine substituted for Ala-86 interacts with the side chain of Leu-89. The Arrhenius plot for mutant A86L was apparently biphasic with a transition observed at 17-19 degrees C and an activation energy of 279.9 kJ/mol below 17 degrees C and 125.1 kJ/mol above 17 degrees C. The initial rate of cytochrome c(1) reduction was lowered 33% in mutant A86L; however, the initial rate of cytochrome b reduction was unaffected, suggesting that movement of the tether region of the iron-sulfur protein is necessary for maximum rates of enzymatic activity. Substituting a leucine for Ala-86 impedes the unwinding of the alpha-helix and hence movement of the tether.

Bacterial Cellulose: A Robust Platform for Design of Three Dimensional Carbon-Based Functional Nanomaterials.

PubMed

Wu, Zhen-Yu; Liang, Hai-Wei; Chen, Li-Feng; Hu, Bi-Cheng; Yu, Shu-Hong

2016-01-19

Three dimensional (3D) carbon nanomaterials exhibit great application potential in environmental protection, electrochemical energy storage and conversion, catalysis, polymer science, and advanced sensors fields. Current methods for preparing 3D carbon nanomaterials, for example, carbonization of organogels, chemical vapor deposition, and self-assembly of nanocarbon building blocks, inevitably involve some drawbacks, such as expensive and toxic precursors, complex equipment and technological requirements, and low production ability. From the viewpoint of practical application, it is highly desirable to develop a simple, cheap, and environmentally friendly way for fabricating 3D carbon nanomaterials in large scale. On the other hand, in order to extend the application scope and improve the performance of 3D carbon nanomaterials, we should explore efficient strategies to prepare diverse functional nanomaterials based on their 3D carbon structure. Recently, many researchers tend to fabricate high-performance 3D carbon-based nanomaterials from biomass, which is low cost, easy to obtain, and nontoxic to humans. Bacterial cellulose (BC), a typical biomass material, has long been used as the raw material of nata-de-coco (an indigenous dessert food of the Philippines). It consists of a polysaccharide with a β-1,4-glycosidic linkage and has a interconnected 3D porous network structure. Interestingly, the network is made up of a random assembly of cellulose nanofibers, which have a high aspect ratio with a diameter of 20-100 nm. As a result, BC has a high specific surface area. Additionally, BC hydrogels can be produced on an industrial scale via a microbial fermentation process at a very low price. Thus, it can be an ideal platform for design of 3D carbon-based functional nanomaterials. Before our work, no systematic work and summary on this topic had been reported. This Account presents the concepts and strategies of our studies on BC in the past few years, that is, converting cheap biomass into high value-added 3D carbon nanomaterials and designing diverse functional materials on 3D carbon structure. We first briefly introduce the history, constituent, and microstructure features of BC and discuss its advantages as a raw material for preparing the CNF aerogels. Then, we summarize the methods and strategies for preparing various 3D carbon-based nanomaterials from BC. In addition, the potential applications of the developed CNF aerogel based functional materials are also highlighted in this Account, including stretchable conductors, oxygen reduction reaction catalysts, supercapacitors, lithium-ion battery, and oil cleanup. Finally, we give some prospects on the future challenges in this emerging research area of designing CNF aerogel based functional nanomaterials from BC.

A Biomimetic Approach to Discrimination Between Sequential and Concerted Models for the Oxidation of Ubiquinol at the Qo­ site of the Cyt bc1 Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cape, Jonathan L.; Forquer, Isaac P.; Bowman, Michael K.

2005-09-26

The cytochrome bc complexes function as quinol:cytochrome c oxidoreductases in the energy conserving membranes of nearly all organisms, where they couple the oxidation of a quinol substrate (QH2) to the pumping of protons across the bioenergetic membrane, resulting in the establishment of a proton motive force, which is used to drive the (C)F0/(C)F1 ATP synthase (Trumpower and Gennis 1994). Among the variety of biological quinols characterized, ubiquinol is the substrate used by most bc-type complexes, and its reactions are of great interest concerning diseases related to oxidative stress and the fundamentals of biological energy transduction.

Functional Analysis of BcBem1 and Its Interaction Partners in Botrytis cinerea: Impact on Differentiation and Virulence

PubMed Central

Schumacher, Julia; Kokkelink, Leonie; Tudzynski, Paul

2014-01-01

In phytopathogenic fungi the establishment and maintenance of polarity is not only essential for vegetative growth and differentiation, but also for penetration and colonization of host tissues. We investigated orthologs of members of the yeast polarity complex in the grey mould fungus Botrytis cinerea: the scaffold proteins Bem1 and Far1, the GEF (guanine nucleotide exchange factor) Cdc24, and the formin Bni1 (named Sep1 in B. cinerea). BcBem1 does not play an important role in regular hyphal growth, but has significant impact on spore formation and germination, on the establishment of conidial anastomosis tubes (CATs) and on virulence. As in other fungi, BcBem1 interacts with the GEF BcCdc24 and the formin BcSep1, indicating that in B. cinerea the apical complex has a similar structure as in yeast. A functional analysis of BcCdc24 suggests that it is essential for growth, since it was not possible to obtain homokaryotic deletion mutants. Heterokaryons of Δcdc24 (supposed to exhibit reduced bccdc24 transcript levels) already show a strong phenotype: an inability to penetrate the host tissue, a significantly reduced growth rate and malformation of conidia, which tend to burst as observed for Δbcbem1. Also the formin BcSep1 has significant impact on hyphal growth and development, whereas the role of the putative ortholog of the yeast scaffold protein Far1 remains open: Δbcfar1 mutants have no obvious phenotypes. PMID:24797931

Synthetic chromanol derivatives and their interaction with complex III in mitochondria from bovine, yeast, and Leishmania.

PubMed

Monzote, L; Stamberg, W; Patel, A; Rosenau, T; Maes, L; Cos, P; Gille, L

2011-10-17

Synthetic chromanol derivatives (TMC4O, 6-hydroxy-2,2,7,8-tetramethyl-chroman-4-one; TMC2O, 6-hydroxy-4,4,7,8-tetramethyl-chroman-2-one; and Twin, 1,3,4,8,9,11-hexamethyl-6,12-methano-12H-dibenzo[d,g][1,3]dioxocin-2,10-diol) share structural elements with the potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex stigmatellin. Studies with isolated bovine cyt bc(1) complex demonstrated that these compounds partially inhibit the mammalian enzyme. The aim of this work was to comparatively investigate these toxicological aspects of synthetic vitamin E derivatives in mitochondria of different species. The chromanols and atovaquone as reference compound were evaluated for their inhibition of the cyt bc(1) activity in mitochondrial fractions from bovine hearts, yeast, and Leishmania. In addition, compounds were evaluated in vitro for their inhibitory activity against whole-cell Leishmania and mouse peritoneal macrophages. In these organisms, the chromanols showed a species-selective inhibition of the cyt bc(1) activity different from that of atovaquone. While in atovaquone the side chain mediates species-selectivity, the marked differences for TMC2O and TMC4O in cyt bc(1) inhibition suggests that direct substitution of the chromanol headgroup will control selectivity in these compounds. Low micromolar concentrations of TMC2O (IC(50) = 9.5 ± 0.5 μM) inhibited the growth of Leishmania, and an esterified TMC2CO derivative inhibited the cyt bc(1) activity with an IC(50) of 4.9 ± 0.9 μM. These findings suggest that certain chromanols also exhibit beyond their antioxidative properties antileishmanial activities and that TMC2O derivatives could be useful toward the development of highly active antiprotozoal compounds.

Assembling the Tat protein translocase

PubMed Central

Alcock, Felicity; Stansfeld, Phillip J; Basit, Hajra; Habersetzer, Johann; Baker, Matthew AB; Palmer, Tracy; Wallace, Mark I; Berks, Ben C

2016-01-01

The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, molecular simulations, and experimentation to define the interactions between the Tat proteins of Escherichia coli at molecular-level resolution. In the TatBC receptor complex the transmembrane helix of each TatB molecule is sandwiched between two TatC molecules, with one of the inter-subunit interfaces incorporating a functionally important cluster of interacting polar residues. Unexpectedly, we find that TatA also associates with TatC at the polar cluster site. Our data provide a structural model for assembly of the active Tat translocase in which substrate binding triggers replacement of TatB by TatA at the polar cluster site. Our work demonstrates the power of co-evolution analysis to predict protein interfaces in multi-subunit complexes. DOI: http://dx.doi.org/10.7554/eLife.20718.001 PMID:27914200

Reconstructing the Qo Site of Plasmodium falciparum bc 1 Complex in the Yeast Enzyme

PubMed Central

Vallières, Cindy; Fisher, Nicholas; Meunier, Brigitte

2013-01-01

The bc 1 complex of the mitochondrial respiratory chain is essential for Plasmodium falciparum proliferation, the causative agent of human malaria. Therefore, this enzyme is an attractive target for antimalarials. However, biochemical investigations of the parasite enzyme needed for the study of new drugs are challenging. In order to facilitate the study of new compounds targeting the enzyme, we are modifying the inhibitor binding sites of the yeast Saccharomyces cerevisiae to generate a complex that mimics the P. falciparum enzyme. In this study we focused on its Qo pocket, the site of atovaquone binding which is a leading antimalarial drug used in treatment and causal prophylaxis. We constructed and studied a series of mutants with modified Qo sites where yeast residues have been replaced by P. falciparum equivalents, or, for comparison, by human equivalents. Mitochondria were prepared from the yeast Plasmodium-like and human-like Qo mutants. We measured the bc 1 complex sensitivity to atovaquone, azoxystrobin, a Qo site targeting fungicide active against P. falciparum and RCQ06, a quinolone-derivative inhibitor of P. falciparum bc 1 complex.The data obtained highlighted variations in the Qo site that could explain the differences in inhibitor sensitivity between yeast, plasmodial and human enzymes. We showed that the yeast Plasmodium-like Qo mutants could be useful and easy-to-use tools for the study of that class of antimalarials. PMID:23951230

Photo-Initiated Electron Transfer Within the P. denitrificans Cytochrome bc1 Complex: The mobility of the Iron Sulfur Protein is modulated by the occupant of the Qo site†

PubMed Central

Havens, Jeffrey; Castellani, Michela; Kleinschroth, Thomas; Ludwig, Bernd; Durham, Bill; Millett, Francis

2011-01-01

Domain rotation of the Rieske iron-sulfur protein (ISP) between the cytochrome (cyt) b and cyt c1 redox centers plays a key role in the mechanism of the cyt bc1 complex. Electron transfer within the cyt bc1 complex of P. denitrificans was studied using a ruthenium dimer to rapidly photo-oxidize cyt c1 within 1 μs and initiate the reaction. In the absence of any added quinol or inhibitor of the bc1 complex at pH 8.0, electron transfer from reduced ISP to cyt c1 was biphasic with rate constants of k1f = 6300 ± 3000 s−1 and k1s = 640 ± 300 s−1 and amplitudes of 10 ± 3% and 16 ± 4 % of the total amount of cyt c1 photooxidized. Upon addition of any of the Pm type inhibitors MOA-stilbene, myxothiazol, or azoxystrobin to cyt bc1 in the absence of quinol, the total amplitude increased 2-fold, consistent with a decrease in redox potential of the ISP. In addition, the relative amplitude of the fast phase increased significantly, consistent with a change in the dynamics of the ISP domain rotation. In contrast, addition of the Pf type inhibitors JG-144 and famoxadone decreased the rate constant k1f by 5 to 10-fold, and increased the amplitude over 2-fold. Addition of quinol substrate in the absence of inhibitors led to a two-fold increase in the amplitude of the k1f phase. The effect of QH2 on the kinetics of electron transfer from reduced ISP to cyt c1 was thus similar to that of the Pm inhibitors and very different from that of the Pf inhibitors. The current results indicate that the species occupying the Qo site has a significant conformational influence on the dynamics of the ISP domain rotation. PMID:22026826

Reaction Intermediates of Quinol Oxidation in a Photoactivatable System that Mimics Electron Transfer in the Cytochrome bc1 Complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cape, Jonathan L.; Bowman, Michael K.; Kramer, David M.

2005-03-30

Current competing models for the two-electron oxidation of quinol (QH{sub 2}) at the cytochrome bc{sub 1} complex and related complexes have different requirements for the reaction intermediate. At present, the intermediate species of the enzymatic oxidation process have not been observed or characterized, probably due to their transient nature. Here, we use a biomimetic oxidant, Ru(bpy){sub 2}(pbim)(PF6)2 (bpy = 2,2'-dipyridyl, pbim = 2-(2-benzimidazolate)pyridine) in an aprotic medium to probe the oxidation of the ubiquinol analogue, 2,3-dimethoxy-5-methyl-1,4-benzoquinol (UQH{sub 2}-0), an the plastoquinol analogue, trimethyl-1,4-benzoquinol (TMQH{sub 2}-0), using time-resolved and steady state spectroscopic techniques. This system qualitatively reproduces key features observed duringmore » ubiquinol oxidation by the mitochondrial cytochrome bc1 complex. Comparison of isotope dependent activation properties in the native and synthetic systems, as well as, analysis of the time-resolved direct-detection electron para magnetic resonance signals in the synthetic system allows us to conclude that: (1) the initial and rate-limiting step in quinol oxidation, both in the biological and biomimetic systems, involves electron and proton transfer, probably via a proton coupled electron transfer mechanism; (2) a neutral semiquinone intermediate is formed in the biomimetic system; and (3) oxidation of the QH*/QH{sub 2} couple for UQH{sub 2}-0, but not TMQH{sub 2}-0, exhibits a non-classical primary deuterium kinetic isotope effect on its Arrhenius activation energy ({Delta}G{sup TS}), where {Delta}G{sup TS} for the protiated form is larger than for the deuterated form. The same behavior is observed during steady state turnover of the cyt bc{sub 1} complex using ubiquinol, but not plastoquinol, as a substrate, leading to the conclusion that similar chemical pathways are involved in both systems. The synthetic system is an unambiguous n=1 electron acceptor and it is thus inferred that sequential oxidation of ubiquinol (by two sequential n=1 processes) is more rapid than a truly concerted (n=2) oxidation in the cyt bc{sub 1} complex.« less

Studies of molecular species of the human androgen receptor (AR): comparison of the physicochemical properties of the (/sup 3/H)methyltrienolone-AR complex formed in cytosol to the complex produced in intact genital skin fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keenan, B.S.; Greger, N.C.; Hedge, A.M.

1986-07-01

Two forms of the human genital skin fibroblast (GSF) androgen receptor (AR) complexed with (/sup 3/H)17 alpha-methyltrienolone were compared: 1) the intact complex formed in cytosol at 4 C (broken cell or B/C complex); and 2) the complex formed in the whole cell at 37 C (W/C complex). The intact form of the B/C complex was distinguished from partly degraded forms by the gel filtration profile in 0.5 M KCl. The W/C complex was considered to represent the transformed state of the receptor. The W/C complex had a smaller molecular radius than the B/C complex by gel filtration (Kav =more » 0.26-0.28 vs. 0.11-0.18). By low salt density gradient centrifugation, the B/C complex sedimented at 8.8S and the W/C complex at 6.6S. However, in 0.5 M KCl, each sedimented at 5.1S, and they were homogeneous, indicating that the monomeric forms differed markedly in molecular radius, but by only about 20,000 daltons in calculated mol wt (134,500 vs. 114,300 daltons). The complexes were separated from DNA, desalted, and compared by chromatography on DEAE-Sephacel and hydroxylapatite (HAP). The B/C complex bound readily to both column matrices and eluted from each as a sharp homogeneous peak: from DEAE at 172-190 mM KCl and from HAP at 123 mM phosphate. The W/C complex, however, was heterogeneous. One component did not bind to DEAE, and one eluted at 22-40 mM KCl. The W/C complex eluted from HAP as a peak at 42 mM, with a shoulder at 102 mM phosphate. Thus, transformation of the human genital skin fibroblast androgen receptor involves a major decrease in molecular radius and loss of negative charge with a possible loss of a 20,000-dalton macromolecular component.« less

Detection of intra-brain cytoplasmic 1 (BC1) long noncoding RNA using graphene oxide-fluorescence beacon detector.

PubMed

Kim, Mee Young; Hwang, Do Won; Li, Fangyuan; Choi, Yoori; Byun, Jung Woo; Kim, Dongho; Kim, Jee-Eun; Char, Kookheon; Lee, Dong Soo

2016-03-21

Detection of cellular expression of long noncoding RNAs (lncRNAs) was elusive due to the ambiguity of exposure of their reactive sequences associated with their secondary/tertiary structures and dynamic binding of proteins around lncRNAs. Herein, we developed graphene-based detection techniques exploiting the quenching capability of graphene oxide (GO) flakes for fluorescent dye (FAM)-labeled single-stranded siRNAs and consequent un-quenching by their detachment from GO by matching lncRNAs. A brain cytoplasmic 1 (BC1) lncRNA expression was significantly decreased by a siRNA, siBC1-1. GO quenched the FAM-labeled siBC1-1 peptide nucleic acid (PNA) probe, and this quenching was recovered by BC1. While FAM-siBC1-1-PNA-GO complex transfected spontaneously mouse or human neural stem cells, fluorescence was recovered only in mouse cells having high BC1 expression. Fluorescent dye-labeled single-stranded RNA-GO probe could detect the reactive exposed nucleic acid sequence of a cytoplasmic lncRNA expressing in the cytoplasm, which strategy can be used as a detection method of lncRNA expression.

Quantum Computational Studies of Electron Transfer in Respiratory Complex III and its Application for Designing New Mitocan Drugs

NASA Astrophysics Data System (ADS)

Hagras, Muhammad Ahmed

Electron transfer occurs in many biological systems which are imperative to sustain life; oxidative phosphorylation in prokaryotes and eukaryotes, and photophosphorylation in photosynthetic and plant cells are well-balanced and complementary processes. Investigating electron transfer in those natural systems provides detailed knowledge of the atomistic events that lead eventually to production of ATP, or harvesting light energy. Ubiquinol:cytochrome c oxidoreductase complex (also known as bc 1 complex, or respiratory complex III) is a middle player in the electron transport proton pumping orchestra, located in the inner-mitochondrial membrane in eukaryotes or plasma membrane in prokaryotes, which converts the free energy of redox reactions to electrochemical proton gradient across the membrane, following the fundamental chemiosmotic principle discovered by Peter Mitchell 1. In humans, the malfunctioned bc1 complex plays a major role in many neurodegenerative diseases, stress-induced aging, and cancer development, because it produces most of the reactive oxygen species, which are also involved in cellular signaling 2. The mitochondrial bc1 complex has an intertwined dimeric structure comprised of 11 subunits in each monomer, but only three of them have catalytic function, and those are the only domains found in bacterial bc1 complex. The core subunits include: Rieske domain, which incorporates iron-sulfur cluster [2Fe-2S]; trans-membrane cytochrome b domain, incorporating low-potential heme group (heme b L) and high-potential heme group (heme b H); and cytochrome c1 domain, containing heme c1 group and two separate binding sites, Qo (or QP) site where the hydrophobic electron carrier ubihydroquinol QH2 is oxidized, and Qi (or QN) site where ubiquinone molecule Q is reduced 3. Electrons and protons in the bc1 complex flow according to the proton-motive Q-cycle proposed by Mitchell, which includes a unique electron flow bifurcation at the Qo site. At this site, one electron of a bound QH2 molecule transfers to [2Fe-2S] cluster of the Rieske domain, docked at the proximal docking site, and another electron transfers to heme b L , which subsequently passes it to heme bH , and finally to Q or SQ molecule bound at the Qi-site 4. Rieske domain undergoes a domain movement 22 A to bind at the distal docking site, where [2Fe-2S] cluster passes its electron to heme c1, which in turn passes it to heme c of the water-soluble cytochrome c carrier 3c, 5 (which shuttles it to cytochrome c oxidase, complex IV). In the current compiled work presented in the subsequent chapters, we deployed a stacking tiers hierarchy where each chapter's work presents a foundation for the next one. In chapter 1, we first present different methods to calculate tunneling currents in proteins including a new derivation method for the inter-atomic tunneling current method. In addition, we show the results of the inter-atomic tunneling current theory on models based on heme bL-heme bH redox pair system in bc1 complex. Afterwards, in chapter 2, we examine the electron tunneling pathways 6 between different intra-monomeric and inter-monomeric redox centers of bc1 complex, including its electron carriers - ubiquinol, ubiquinone, and cytochrome c molecules, using the well-studied coarse-grained interatomic method of the tunneling current theory 7. Going through the different tunneling pathways in bc1 complex, we discovered a pair of internal switches that modulate the electron transfer rate which we discuss in full details in chapter 3. Motivated by the discovery of those internal switches, we discuss in chapter 4 the discovery of a new binding pocket (designated as NonQ-site or NQ-site for short) in bc 1 complex which is located at the opposite side of the enzyme with respect to Qo site. In contrast to Qo site, however, the NQ-site penetrates deeply in the cytochrome b domain and reaches very closely the LH region. Hence the NQ-site provides a suitable binding pocket for ligands that can influence the orientation of Phe90 residue, and hence modulate the corresponding ET rate between heme b L and heme bH. Finally we present in chapter 5 our unique integrated software package (called Electron Tunneling in Proteins Program or ETP) which provides an environment with different capabilities such as tunneling current calculation, semi-empirical quantum mechanical calculation and molecular modeling simulation for calculation and analysis of electron transfer reactions in proteins.

The absorption Ångström exponent of black carbon: from numerical aspects

NASA Astrophysics Data System (ADS)

Liu, Chao; Eddy Chung, Chul; Yin, Yan; Schnaiter, Martin

2018-05-01

The absorption Ångström exponent (AAE) is an important aerosol optical parameter used for aerosol characterization and apportionment studies. The AAE of black carbon (BC) particles is widely accepted to be 1.0, although observational estimates give quite a wide range of 0.6-1.3. With considerable uncertainties related to observations, a numerical study is a powerful method, if not the only one, to provide a better and more accurate understanding on BC AAE. This study calculates BC AAE using realistic particle geometries based on fractal aggregate and an accurate numerical optical model (namely the multiple-sphere T-matrix method), and considers bulk properties of an ensemble of BC particles following lognormal size distributions. At odds with the expectations, BC AAE is not 1.0, even when BC is assumed to have small sizes and a wavelength-independent refractive index. With a wavelength-independent refractive index, the AAE of fresh BC is approximately 1.05 and relatively insensitive to particle size. For BC with geometric mean diameters larger than 0.12 µm, BC AAE becomes smaller when BC particles are aged (compact structures or coated by other non-absorptive materials). For coated BC, we prescribe the coating fraction variation based on a laboratory study, where smaller BC cores are shown to develop larger coating fractions than those of bigger BC cores. For both compact and coated BC, the AAE is highly sensitive to particle size distribution, ranging from approximately 0.8 to even over 1.4 with wavelength-independent refractive index. When the refractive index is allowed to vary with wavelength, a feature with observational backing, the BC AAE may show an even wider range. For different BC morphologies, we derive simple empirical equations on BC AAE based on our numerical results, which can serve as a guide for the response of BC AAE to BC size and refractive index. Due to its complex influences, the effects of BC geometry is better to be discussed at certain BC properties, i.e., known size and refractive index.

The Expression Alteration of BC1 RNA and its Interaction with Eukaryotic Translation Initiation Factor eIF4A Post-Status Epilepticus.

PubMed

Zeng, Xiangchang; Zong, Wenjing; Gao, Qing; Chen, Siyu; Chen, Lulu; Zeng, Guirong; Huang, Weihua; Li, Zhenyu; Zeng, Chang; Xie, Yuanyuan; Li, Xiaohui; Xiao, Bo; Dongsheng-Ouyang; Hu, Kai

2018-05-17

Abnormal dendritic sprouting and synaptic remodelling are important pathological features of temporal lobe epilepsy. BC1 RNA is a translation repressor involved in the regulation of the dendritic protein synthesis and mRNA transport, which is essential for dendritic development and plasticity. The expression alteration of BC1 RNA in the pilocarpine induced epilepsy model remains unknown. It is unclear if the interactions between BC1 RNA and eukaryotic initiation factor 4A (eIF4A) exists in this model. The purpose of this study was to investigate the expression changes of BC1 RNA and its interactions with eIF4A post-status epilepticus (SE). Chloride lithium and pilocarpine were used to induce the SE rat model. Either a whole brain or hippocampus tissues were collected at different time points after SE. The expression patterns of BC1 was detected by qPCR and in situ hybridization. The levels of eIF4AI/II protein expression were analyzed via western blotting and immunohistochemistry. The BC1 RNA-eIF4AI/II interaction was determined by electrophoretic mobility shift assay (EMSA). We found that the BC1 RNA levels decreased in hippocampus 3d, 1w and 2w post-SE before the levels recovered. The eIF4AI/II began to rise 3d post-SE and reached the maximum level 1w post-SE. After 1w post-SE the levels decreased in the hippocampal CA1, CA3 and DG subregions. EMSA analysis showed that BC1 RNA specifically interacted with the eIF4AI/II. The BC1 RNA-eIF4AI/II complex reduced to the lowest level 1w post-SE. Our results suggested that BC1 has a negative regulatory correlation with eIF4AI/II, where BC1 RNA could be involved in epileptogenesis by regulating dendritic protein synthesis.

Rheological performance of bacterial cellulose based nonmineralized and mineralized hydrogel scaffolds

NASA Astrophysics Data System (ADS)

Basu, Probal; Saha, Nabanita; Bandyopadhyay, Smarak; Saha, Petr

2017-05-01

Bacterial cellulose (BC) based hydrogels (BC-PVP and BC-CMC) are modified with β-tri-calcium phosphate (β-TCP) and hydroxyapatite (HA) to improve the structural and functional properties of the existing hydrogel scaffolds. The modified hydrogels are then biomineralized with CaCO3 following liquid diffusion technique, where salt solutions of Na2CO3 (5.25 g/100 mL) and CaCl2 (7.35 g/100 mL) were involved. The BC-PVP and BC-CMC are being compared with the non-mineralized (BC-PVP-β-TCP/HA and BC-CMC-β-TCP/HA) and biomineralized (BC-PVP-β-TCP/HA-CaCO3 and BC-CMC-β-TCP/HA-CaCO3) hydrogels on the basis of their structural and rheological properties. The Fourier Transform Infrared (FTIR) spectral analysis demonstrated the presence of BC, CMC, PVP, β-TCP, HA in the non-mineralized and BC, CMC, PVP, β-TCP, HA and CaCO3 in the biomineralized samples. Interestingly, the morphological property of non-mineralized and biomineralized, hydrogels are different than that of BC-PVP and BC-CMC based novel biomaterials. The Scanning Electron Microscopic (SEM) images of the before mentioned samples reveal the denser structures than BC-PVP and BC-CMC, which exhibits the changes in their pore sizes. Concerning rheological analysis point of view, all the non-mineralized and biomineralized hydrogel scaffolds have shown significant elastic property. Additionally, the complex viscosity (η*) values have also found in decreasing order with the increase of angular frequency (ω) 0.1 rad.sec-1 to 100 rad.sec-1. All these BC based hydrogel scaffolds are elastic in nature, can be recommended for their application as an implant for bone tissue engineering.

Immobilization of heavy metals in electroplating sludge by biochar and iron sulfide.

PubMed

Lyu, Honghong; Gong, Yanyan; Tang, Jingcshun; Huang, Yao; Wang, Qilin

2016-07-01

Electroplating sludge (ES) containing large quantities of heavy metals is regarded as a hazardous waste in China. This paper introduced a simple method of treating ES using environmentally friendly fixatives biochar (BC) and iron sulfide (FeS), respectively. After 3 days of treatment with FeS at a FeS-to-ES mass ratio of 1:5, the toxicity characteristic leaching procedure (TCLP)-based leachability of total Cr (TCr), Cu(II), Ni(II), Pb(II), and Zn(II) was decreased by 59.6, 100, 63.8, 73.5, and 90.5 %, respectively. After 5 days of treatment with BC at a BC-to-ES mass ratio of 1:2, the TCLP-based leachability was declined by 35.1, 30.6, 22.3, 23.1, and 22.4 %, respectively. Pseudo first-order kinetic model adequately simulated the sorption kinetic data. Structure and morphology analysis showed that adsorption, electrostatic attraction, surface complexation, and chemical precipitation were dominant mechanisms for heavy metals immobilization by BC, and that chemical precipitation (formation of metal sulfide and hydroxide precipitates), iron exchange (formation of CuFeS2), and surface complexation were mainly responsible for heavy metals removal by FeS. Economic costs of BC and FeS were 500 and 768 CNY/t, lower than that of Na2S (940 CNY/t). The results suggest that BC and FeS are effective, economic, and environmentally friendly fixatives for immobilization of heavy metals in ES before landfill disposal.

Lipid functions in cytochrome bc complexes: an odd evolutionary transition in a membrane protein structure

PubMed Central

Hasan, S. Saif; Cramer, William A.

2012-01-01

Lipid-binding sites and properties were compared in the hetero-oligomeric cytochrome (cyt) b6f and the yeast bc1 complexes that function, respectively, in photosynthetic and respiratory electron transport. Seven lipid-binding sites in the monomeric unit of the dimeric cyanobacterial b6f complex overlap four sites in the Chlamydomonas reinhardtii algal b6f complex and four in the yeast bc1 complex. The proposed lipid functions include: (i) interfacial–interhelix mediation between (a) the two 8-subunit monomers of the dimeric complex, (b) between the core domain (cyt b, subunit IV) and the six trans membrane helices of the peripheral domain (cyt f, iron–sulphur protein (ISP), and four small subunits in the boundary ‘picket fence’); (ii) stabilization of the ISP domain-swapped trans-membrane helix; (iii) neutralization of basic residues in the single helix of cyt f and of the ISP; (iv) a ‘latch’ to photosystem I provided by the β-carotene chain protruding through the ‘picket fence’; (v) presence of a lipid and chlorophyll a chlorin ring in b6f in place of the eighth helix in the bc1 cyt b polypeptide. The question is posed of the function of the lipid substitution in relation to the evolutionary change between the eight and seven helix structures of the cyt b polypeptide. On the basis of the known n-side activation of light harvesting complex II (LHCII) kinase by the p-side level of plastoquinol, one possibility is that the change was directed by the selective advantage of p- to n-side trans membrane signalling functions in b6f, with the lipid either mediating this function or substituting for the trans membrane helix of a signalling protein lost in crystallization. PMID:23148267

Imaging protein complex formation in the autophagy pathway: analysis of the interaction of LC3 and Atg4BC74A in live cells using Förster resonance energy transfer and fluorescence recovery after photobleaching

NASA Astrophysics Data System (ADS)

Kraft, Lewis J.; Kenworthy, Anne K.

2012-01-01

The protein microtubule-associated protein 1, light chain 3 (LC3) functions in autophagosome formation and plays a central role in the autophagy pathway. Previously, we found LC3 diffuses more slowly in cells than is expected for a freely diffusing monomer, suggesting it may constitutively associate with a macromolecular complex containing other protein components of the pathway. In the current study, we used Förster resonance energy transfer (FRET) microscopy and fluorescence recovery after photobleaching (FRAP) to investigate the interactions of LC3 with Atg4BC74A, a catalytically inactive mutant of the cysteine protease involved in lipidation and de-lipidation of LC3, as a model system to probe protein complex formation in the autophagy pathway. We show Atg4BC74A is in FRET proximity with LC3 in both the cytoplasm and nucleus of living cells, consistent with previous biochemical evidence that suggests these proteins directly interact. In addition, overexpressed Atg4BC74A diffuses significantly more slowly than predicted based on its molecular weight, and its translational diffusion coefficient is significantly slowed upon coexpression with LC3 to match that of LC3 itself. Taken together, these results suggest Atg4BC74A and LC3 are contained within the same multiprotein complex and that this complex exists in both the cytoplasm and nucleoplasm of living cells.

Preface.

PubMed

Villarreal-Garza, Cynthia; Castro-Sánchez, Andrea

2017-01-01

Young women with breast cancer (BC) are a special population with distinctive genetic, clinical, and psychosocial features and requirements based on at least three considerations: (1) Cancer presentation at young age is often diagnosed at advanced stages, hence its prognosis is worse compared to their older counterparts1,2; (2) young BC patients often receive aggressive and prolonged systemic treatments that can be associated with significant long-term morbidity3; and (3) young women with BC experience substantial psychosocial vulnerability resulting from high levels of distress and depression associated with oncological interventions4. These factors pose complex issues for young patients with BC, particularly in regard to their family dynamics, social and professional lives, and self-development, thereby substantially undermining their quality of life.

Complex Landscape of Germline Variants in Brazilian Patients With Hereditary and Early Onset Breast Cancer.

PubMed

Torrezan, Giovana T; de Almeida, Fernanda G Dos Santos R; Figueiredo, Márcia C P; Barros, Bruna D de Figueiredo; de Paula, Cláudia A A; Valieris, Renan; de Souza, Jorge E S; Ramalho, Rodrigo F; da Silva, Felipe C C; Ferreira, Elisa N; de Nóbrega, Amanda F; Felicio, Paula S; Achatz, Maria I; de Souza, Sandro J; Palmero, Edenir I; Carraro, Dirce M

2018-01-01

Pathogenic variants in known breast cancer (BC) predisposing genes explain only about 30% of Hereditary Breast Cancer (HBC) cases, whereas the underlying genetic factors for most families remain unknown. Here, we used whole-exome sequencing (WES) to identify genetic variants associated to HBC in 17 patients of Brazil with familial BC and negative for causal variants in major BC risk genes ( BRCA1/2, TP53 , and CHEK2 c.1100delC). First, we searched for rare variants in 27 known HBC genes and identified two patients harboring truncating pathogenic variants in ATM and BARD1 . For the remaining 15 negative patients, we found a substantial vast number of rare genetic variants. Thus, for selecting the most promising variants we used functional-based variant prioritization, followed by NGS validation, analysis in a control group, cosegregation analysis in one family and comparison with previous WES studies, shrinking our list to 23 novel BC candidate genes, which were evaluated in an independent cohort of 42 high-risk BC patients. Rare and possibly damaging variants were identified in 12 candidate genes in this cohort, including variants in DNA repair genes ( ERCC1 and SXL4 ) and other cancer-related genes ( NOTCH2, ERBB2, MST1R , and RAF1 ). Overall, this is the first WES study applied for identifying novel genes associated to HBC in Brazilian patients, in which we provide a set of putative BC predisposing genes. We also underpin the value of using WES for assessing the complex landscape of HBC susceptibility, especially in less characterized populations.

Cyanide Ligand Assembly by Carbon Atom Transfer to an Iron Nitride

DOE PAGES

Martinez, Jorge L.; Lin, Hsiu-Jung; Lee, Wei-Tsung; ...

2017-09-21

The new iron(IV) nitride complex PhB( iPr 2Im) 3Fe≡N reacts with two equivalents of bis(diisopropylamino)cyclopropenylidene (BAC) to provide PhB( iPr 2Im) 3Fe(CN)(N 2)(BAC). This unusual example of a four-electron reaction involves carbon atom transfer from BAC to create a cyanide ligand along with the alkyne iPr 2N-C≡C-N iPr 2. The iron complex is in equilibrium with an N 2- free species. Further reaction with CO leads to formation of a CO analogue, which can be independently prepared using NaCN as the cyanide source, while reaction with B(C 6F 5) 3 provides the cyanoborane derivative.

In situ synthesis of silver-nanoparticles/bacterial cellulose composites for slow-released antimicrobial wound dressing.

PubMed

Wu, Jian; Zheng, Yudong; Song, Wenhui; Luan, Jiabin; Wen, Xiaoxiao; Wu, Zhigu; Chen, Xiaohua; Wang, Qi; Guo, Shaolin

2014-02-15

Bacterial cellulose has attracted increasing attention as a novel wound dressing material, but it has no antimicrobial activity, which is one of critical skin-barrier functions in wound healing. To overcome such deficiency, we developed a novel method to synthesize and impregnate silver nanoparticles on to bacterial cellulose nanofibres (AgNP-BC). Uniform spherical silver nano-particles (10-30 nm) were generated and self-assembled on the surface of BC nano-fibers, forming a stable and evenly distributed Ag nanoparticles coated BC nanofiber. Such hybrid nanostructure prevented Ag nanoparticles from dropping off BC network and thus minimized the toxicity of nanoparticles. Regardless the slow Ag(+) release, AgNP-BC still exhibited significant antibacterial activities with more than 99% reductions in Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, AgNP-BC allowed attachment and growth of epidermal cells with no cytotoxicity emerged. The results demonstrated that AgNP-BC could reduce inflammation and promote wound healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer.

PubMed

Khalid, Samra; Hanif, Rumeza; Tareen, Samar H K; Siddiqa, Amnah; Bibi, Zurah; Ahmad, Jamil

2016-01-01

Breast cancer (BC) is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s). It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER- α ) associated Biological Regulatory Network (BRN) for a small part of complex events that leads to BC metastasis. A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN) to analyze the logical parameters of the involved entities. In-silico based discrete and continuous modeling of ER- α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER- α , IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs) such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER- α , IGF-1R and EGFR) for wet lab experiments as well as provided valuable insights in the treatment of cancers such as BC.

Recent progress in heteronuclear long-range NMR of complex carbohydrates: 3D H2BC and clean HMBC.

PubMed

Meier, Sebastian; Petersen, Bent O; Duus, Jens Ø; Sørensen, Ole W

2009-11-02

The new NMR experiments 3D H2BC and clean HMBC are explored for challenging applications to a complex carbohydrate at natural abundance of (13)C. The 3D H2BC experiment is crucial for sequential assignment as it yields heteronuclear one- and two-bond together with COSY correlations for the (1)H spins, all in a single spectrum with good resolution and non-informative diagonal-type peaks suppressed. Clean HMBC is a remedy for the ubiquitous problem of strong coupling induced one-bond correlation artifacts in HMBC spectra of carbohydrates. Both experiments work well for one of the largest carbohydrates whose structure has been determined by NMR, not least due to the enhanced resolution offered by the third dimension in 3D H2BC and the improved spectral quality due to artifact suppression in clean HMBC. Hence these new experiments set the scene to take advantage of the sensitivity boost achieved by the latest generation of cold probes for NMR structure determination of even larger and more complex carbohydrates in solution.

Arsenic removal by perilla leaf biochar in aqueous solutions and groundwater: An integrated spectroscopic and microscopic examination.

PubMed

Niazi, Nabeel Khan; Bibi, Irshad; Shahid, Muhammad; Ok, Yong Sik; Burton, Edward D; Wang, Hailong; Shaheen, Sabry M; Rinklebe, Jörg; Lüttge, Andreas

2018-01-01

In this study, we examined the removal of arsenite (As(III)) and arsenate (As(V)) by perilla leaf-derived biochars produced at 300 and 700 °C (referred as BC300 and BC700) in aqueous environments. Results revealed that the Langmuir isotherm model provided the best fit for As(III) and As(V) sorption, with the sorption affinity following the order: BC700-As(III) > BC700-As(V) > BC300-As(III) > BC300-As(V) (Q L  = 3.85-11.01 mg g -1 ). In general, As removal decreased (76-60%) with increasing pH from 7 to 10 except for the BC700-As(III) system, where notably higher As removal (88-90%) occurred at pH from 7 to 9. Surface functional moieties contributed to As sequestration by the biochars examined here. However, significantly higher surface area and aromaticity of BC700 favored a greater As removal compared to BC300, suggesting that surface complexation/precipitation dominated As removal by BC700. Arsenic K-edge X-ray absorption near edge structure (XANES) spectroscopy demonstrated that up to 64% of the added As(V) was reduced to As(III) in BC700- and BC300-As(V) sorption experiments, and in As(III) sorption experiments, partial oxidation of As(III) to As(V) occurred (37-39%). However, XANES spectroscopy was limited to precisely quantify As binding with sulfur species as As 2 S 3 -like phase. Both biochars efficiently removed As from natural As-contaminated groundwater (As: 23-190 μg L -1 ; n = 12) despite in the presence of co-occurring anions (e.g., CO 3 2- , PO 4 3- , SO 4 2- ) with the highest levels of As removal observed for BC700 (97-100%). Overall, this study highlights that perilla leaf biochars, notably BC700, possessed the greatest ability to remove As from solution and groundwater (drinking water). Significantly, the integrated spectroscopic techniques advanced our understanding to examine complex redox transformation of As(III)/As(V) with biochar, which are crucial to determine fate of As on biochar in aquatic environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relation Between the Molopo Farms and Bushveld Complexes: An Analysis of Pyroxene Exsolution Lamellae

NASA Astrophysics Data System (ADS)

Moore, I.; Feineman, M. D.; Nyblade, A.

2017-12-01

The Molopo Farms Complex (MFC) is a layered igneous intrusion in Botswana, considered to be related to the nearby South African Bushveld Complex (BC) due to their similarities. The BC has been researched in depth for its economic deposits of platinum group elements (PGEs), while the under-researched MFC has no PGEs and is under 200 m of sediment. This study aims to increase knowledge about the MFC regarding the theory that the BC and MFC come from the same parental magma body by showing similar cooling history in the exsolution of pyroxenes. Using optical microscopy and scanning electron microscopy (SEM) paired with an energy-dispersive detector (EDS), thin sections of pyroxenes with exsolution lamellae from both complexes were observed in terms of chemical composition and microtextures. MFC pyroxenes were then compared to literature data of BC pyroxenes. The pyroxenes are closely related, indicating that the MFC and the BC cooled at a similar rate and come from the same parental magma body. Further research can expand on these findings to prove that the MFC and BC are from the same magma.

N-doping effectively enhances the adsorption capacity of biochar for heavy metal ions from aqueous solution.

PubMed

Yu, Wenchao; Lian, Fei; Cui, Guannan; Liu, Zhongqi

2018-02-01

N-doping was successfully employed to improve the adsorption capacity of biochar (BC) for Cu 2+ and Cd 2+ by direct annealing of crop straws in NH 3 . The surface N content of BC increased more than 20 times by N-doping; meanwhile the content of oxidized-N was gradually diminished but graphitic-N was formed and increased with increasing annealing temperature and duration time. After N-doping, a high graphitic-N percentage (46.4%) and S BET (418.7 m 2 /g) can be achieved for BC. As a result, the N-doped BC exhibited an excellent adsorption capacity for Cu 2+ (1.63 mmol g -1 ) and Cd 2+ (1.76 mmol g -1 ), which was up to 4.0 times higher than that of the original BC. Furthermore, the adsorption performance of the N-doped BC remained stable even at acidic conditions. A positive correlation can be found between adsorption capacity with the graphitic N content on BC surface. The surface chemistry of N-doped BC before and after the heavy metal ions adsorption was carefully examined by XPS and FTIR techniques, which indicated that the adsorption mechanisms mainly included cation-π bonding and complexation with graphitic-N and hydroxyl groups of carbon surfaces. Copyright © 2017 Elsevier Ltd. All rights reserved.

Noncovalent fabrication and tunable fusion of block copolymer-giant polyoxometalate hybrid micelles.

PubMed

Zhang, Liying; Li, Haolong; Wu, Lixin

2014-09-21

The block copolymers (BCs), as structure-directing agents, co-assembling with nanoscale inorganic additives is an important route to fabricate nanostructured hybrid materials. In this work, we present a facile approach to fabricate hybrid micelles composed of BCs and polyoxometalates (POMs), in which the POM clusters are premodified with the groups that can specifically interact with a certain BC block. A representative POM (NH4)42[Mo(132)O(372)(CH(3)COO)(30)(H2O)72] (Mo(132)) is chosen as the example and encapsulated with cationic molecules containing carboxyphenyl groups through electrostatic interactions, and then the resulting hybrid complex can further co-assemble with poly(styrene-block-4-vinylpyridine) (PS-b-P4VP) through hydrogen bonding with the pyridine groups, which leads to the formation of hybrid micelles and the localization of Mo(132) in the micelle cores. The micelles exhibit a high stability despite time and dilution. Furthermore, the fusion of the micelles can be readily adjusted by varying the length of PS blocks, which is promising to be used in constructing polymer-POM hybrid materials with discrete or continuous hybrid domains. This work is based on the electrostatic premodification of POMs and thus its concept is generally suitable for the whole anionic POM system, which may create a large class of BC-POM nanocomposites with tunable structures.

Activation of EVI1 transcription by the LEF1/β-catenin complex with p53-alteration in myeloid blast crisis of chronic myeloid leukemia.

PubMed

Manachai, Nawin; Saito, Yusuke; Nakahata, Shingo; Bahirvani, Avinash Govind; Osato, Motomi; Morishita, Kazuhiro

2017-01-22

The presence of a BCR-ABL1 fusion gene is necessary for the pathogenesis of chronic myeloid leukemia (CML) through t(9;22)(q34;q11) translocation. Imatinib, an ABL tyrosine kinase inhibitor, is dramatically effective in CML patients; however, 30% of CML patients will need further treatment due to progression of CML to blast crisis (BC). Aberrant high expression of ecotropic viral integration site 1 (EVI1) is frequently observed in CML during myeloid-BC as a potent driver with a CML stem cell signature; however, the precise molecular mechanism of EVI1 transcriptional regulation during CML progression is poorly defined. Here, we demonstrate the transcriptional activity of EVI1 is dependent on activation of lymphoid enhancer-binding factor 1 (LEF1)/β-catenin complex by BCR-ABL with loss of p53 function during CML-BC. The activation of β-catenin is partly dependent on BCR-ABL expression through enhanced GSK3β phosphorylation, and EVI1 expression is directly enhanced by the LEF1/β-catenin complex bound to the EVI1 promoter region. Moreover, the loss of p53 expression is inversely correlated with high expression of EVI1 in CML leukemia cells with an aggressive phase of CML, and a portion of the activation mechanism of EVI1 expression is dependent on β-catenin activation through GSK3β phosphorylation by loss of p53. Therefore, we found that the EVI1 activation in CML-BC is dependent on LEF1/β-catenin activation by BCR-ABL expression with loss of p53 function, representing a novel selective therapeutic approach targeting myeloid blast crisis progression. Copyright © 2016 Elsevier Inc. All rights reserved.

The biguanides metformin and phenformin inhibit angiogenesis, local and metastatic growth of breast cancer by targeting both neoplastic and microenvironment cells.

PubMed

Orecchioni, Stefania; Reggiani, Francesca; Talarico, Giovanna; Mancuso, Patrizia; Calleri, Angelica; Gregato, Giuliana; Labanca, Valentina; Noonan, Douglas M; Dallaglio, Katiuscia; Albini, Adriana; Bertolini, Francesco

2015-03-15

The human white adipose tissue (WAT) contains progenitors with cooperative roles in breast cancer (BC) angiogenesis, local and metastatic progression. The biguanide Metformin (Met), commonly used for Type 2 diabetes, might have activity against BC and was found to inhibit angiogenesis in vivo. We studied Met and another biguanide, phenformin (Phe), in vitro and in vivo in BC models. In vitro, biguanides activated AMPK, inhibited Complex 1 of the respiratory chain and induced apoptosis of BC and WAT endothelial cells. In coculture, biguanides inhibited the production of several angiogenic proteins. In vivo, biguanides inhibited local and metastatic growth of triple negative and HER2+ BC in immune-competent and immune-deficient mice orthotopically injected with BC. Biguanides inhibited local and metastatic BC growth in a genetically engineered murine model model of HER2+ BC. In vivo, biguanides increased pimonidazole binding (but not HIF-1 expression) of WAT progenitors, reduced tumor microvessel density and altered the vascular pericyte/endothelial cell ratio, so that cancer vessels displayed a dysplastic phenotype. Phe was significantly more active than Met both in vitro and in vivo. Considering their safety profile, biguanides deserve to be further investigated for BC prevention in high-risk subjects, in combination with chemo and/or targeted therapy and/or as post-therapy consolidation or maintenance therapy for the prevention of BC recurrence. © 2014 UICC.

Structure of the Zymomonas mobilis respiratory chain: oxygen affinity of electron transport and the role of cytochrome c peroxidase.

PubMed

Balodite, Elina; Strazdina, Inese; Galinina, Nina; McLean, Samantha; Rutkis, Reinis; Poole, Robert K; Kalnenieks, Uldis

2014-09-01

The genome of the ethanol-producing bacterium Zymomonas mobilis encodes a bd-type terminal oxidase, cytochrome bc1 complex and several c-type cytochromes, yet lacks sequences homologous to any of the known bacterial cytochrome c oxidase genes. Recently, it was suggested that a putative respiratory cytochrome c peroxidase, receiving electrons from the cytochrome bc1 complex via cytochrome c552, might function as a peroxidase and/or an alternative oxidase. The present study was designed to test this hypothesis, by construction of a cytochrome c peroxidase mutant (Zm6-perC), and comparison of its properties with those of a mutant defective in the cytochrome b subunit of the bc1 complex (Zm6-cytB). Disruption of the cytochrome c peroxidase gene (ZZ60192) caused a decrease of the membrane NADH peroxidase activity, impaired the resistance of growing culture to exogenous hydrogen peroxide and hampered aerobic growth. However, this mutation did not affect the activity or oxygen affinity of the respiratory chain, or the kinetics of cytochrome d reduction. Furthermore, the peroxide resistance and membrane NADH peroxidase activity of strain Zm6-cytB had not decreased, but both the oxygen affinity of electron transport and the kinetics of cytochrome d reduction were affected. It is therefore concluded that the cytochrome c peroxidase does not terminate the cytochrome bc1 branch of Z. mobilis, and that it is functioning as a quinol peroxidase. © 2014 The Authors.

An Evaluation of Selected Communications Assemblies and Hearing Protection Systems: A Field Study Conducted for the Future Force Warrior Integrated Headgear Integrated Process Team

DTIC Science & Technology

2005-04-01

Hearing restoration was provided via binaural hear-through microphones on the 1Communications & Ear...second question asked was “which of the systems provided the best speech intelligibility?” The BC system beat the TAC by half a vote (because one

Crystal Structure of Biotin Carboxylase in Complex with Substrates and Implications for Its Catalytic Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, C.; Yu, L; Tong, L

2009-01-01

Biotin-dependent carboxylases are widely distributed in nature and have important functions in many cellular processes. These enzymes share a conserved biotin carboxylase (BC) component, which catalyzes the ATP-dependent carboxylation of biotin using bicarbonate as the donor. Despite the availability of a large amount of biochemical and structural information on BC, the molecular basis for its catalysis is currently still poorly understood. We report here the crystal structure at 2.0 {angstrom} resolution of wild-type Escherichia coli BC in complex with its substrates biotin, bicarbonate, and Mg-ADP. The structure suggests that Glu{sup 296} is the general base that extracts the proton frommore » bicarbonate, and Arg{sup 338} is the residue that stabilizes the enolate biotin intermediate in the carboxylation reaction. The B domain of BC is positioned closer to the active site, leading to a 2-{angstrom} shift in the bound position of the adenine nucleotide and bringing it near the bicarbonate for catalysis. One of the oxygen atoms of bicarbonate is located in the correct position to initiate the nucleophilic attack on ATP to form the carboxyphosphate intermediate. This oxygen is also located close to the N1' atom of biotin, providing strong evidence that the phosphate group, derived from decomposition of carboxyphosphate, is the general base that extracts the proton on this N1' atom. The structural observations are supported by mutagenesis and kinetic studies. Overall, this first structure of BC in complex with substrates offers unprecedented insights into the molecular mechanism for the catalysis by this family of enzymes.« less

Computational discovery of picomolar Q(o) site inhibitors of cytochrome bc1 complex.

PubMed

Hao, Ge-Fei; Wang, Fu; Li, Hui; Zhu, Xiao-Lei; Yang, Wen-Chao; Huang, Li-Shar; Wu, Jia-Wei; Berry, Edward A; Yang, Guang-Fu

2012-07-11

A critical challenge to the fragment-based drug discovery (FBDD) is its low-throughput nature due to the necessity of biophysical method-based fragment screening. Herein, a method of pharmacophore-linked fragment virtual screening (PFVS) was successfully developed. Its application yielded the first picomolar-range Q(o) site inhibitors of the cytochrome bc(1) complex, an important membrane protein for drug and fungicide discovery. Compared with the original hit compound 4 (K(i) = 881.80 nM, porcine bc(1)), the most potent compound 4f displayed 20 507-fold improved binding affinity (K(i) = 43.00 pM). Compound 4f was proved to be a noncompetitive inhibitor with respect to the substrate cytochrome c, but a competitive inhibitor with respect to the substrate ubiquinol. Additionally, we determined the crystal structure of compound 4e (K(i) = 83.00 pM) bound to the chicken bc(1) at 2.70 Å resolution, providing a molecular basis for understanding its ultrapotency. To our knowledge, this study is the first application of the FBDD method in the discovery of picomolar inhibitors of a membrane protein. This work demonstrates that the novel PFVS approach is a high-throughput drug discovery method, independent of biophysical screening techniques.

Modeling the molecular basis of atovaquone resistance in parasites and pathogenic fungi.

PubMed

Kessl, Jacques J; Meshnick, Steven R; Trumpower, Bernard L

2007-10-01

Atovaquone is a substituted hydroxynaphthoquinone that is used therapeutically for treating Plasmodium falciparum malaria, Pneumocystis jirovecii pneumonia and Toxoplasma gondii toxoplasmosis. It is thought to act on these organisms by inhibiting parasite and fungal respiration by binding to the cytochrome bc1 complex. The recent, growing failure of atovaquone treatment and increased mortality of patients with malaria or Pneumocystis pneumonia has been linked to the appearance of mutations in the cytochrome b gene. To better understand the molecular basis of drug resistance, we have developed the yeast and bovine bc1 complexes as surrogates to model the molecular interaction of atovaquone with human and resistant pathogen enzymes.

Regulatory interactions in the dimeric cytochrome bc(1) complex: the advantages of being a twin.

PubMed

Covian, Raul; Trumpower, Bernard L

2008-09-01

The dimeric cytochrome bc(1) complex catalyzes the oxidation-reduction of quinol and quinone at sites located in opposite sides of the membrane in which it resides. We review the kinetics of electron transfer and inhibitor binding that reveal functional interactions between the quinol oxidation site at center P and quinone reduction site at center N in opposite monomers in conjunction with electron equilibration between the cytochrome b subunits of the dimer. A model for the mechanism of the bc(1) complex has emerged from these studies in which binding of ligands that mimic semiquinone at center N regulates half-of-the-sites reactivity at center P and binding of ligands that mimic catalytically competent binding of ubiquinol at center P regulates half-of-the-sites reactivity at center N. An additional feature of this model is that inhibition of quinol oxidation at the quinone reduction site is avoided by allowing catalysis in only one monomer at a time, which maximizes the number of redox acceptor centers available in cytochrome b for electrons coming from quinol oxidation reactions at center P and minimizes the leakage of electrons that would result in the generation of damaging oxygen radicals.

Isolation and characterization of an Arabidopsis biotin carboxylase gene and its promoter.

PubMed

Bao, X; Shorrosh, B S; Ohlrogge, J B

1997-11-01

In the plastids of most plants, acetyl-CoA carboxylase (ACCase; EC 6.4.1.2) is a multisubunit complex consisting of biotin carboxylase (BC), biotin-carboxyl carrier protien (BCCP), and carboxytransferase (alpha-CT, beta-CT) subunits. To better understand the regulation of this enzyme, we have isolated and sequenced a BC genomic clone from Arabidopsis and partially characterized its promoter. Fifteen introns were identified. The deduced amino acid sequence of the mature BC protein is highly conserved between Arabidopsis and tobacco (92.6% identity). BC expression was evaluated using northern blots and BC/GUS fusion constructs in transgenic Arabidopsis. GUS activity in the BC/GUS transgenics as well as transcript level of the native gene were both found to be higher in silique and flower than in root and leaf. Analysis of tobacco suspension cells transformed with truncated BC promoter/GUS gene fusions indicated the region from -140 to +147 contained necessary promoter elements which supported basal gene expression. A positive regulatory region was found to be located between -2100 and -140, whereas a negative element was possibly located in the first intron. In addition, several conserved regulatory elements were identified in the BC promoter. Surprisingly, although BC is a low-abundance protein, the expression of BC/GUS fusion constructs was similar to 35S/GUS constructs.

Redox pathways of the mitochondrion.

PubMed

Koehler, Carla M; Beverly, Kristen N; Leverich, Edward P

2006-01-01

The mitochondrion houses a variety of redox pathways, utilized for protection from oxidative damage and assembly of the organelle. The glutathione/glutaredoxin and thioredoxin systems function in the mitochondrial matrix. The intermembrane space is protected from oxidative damage via superoxide dismutase and glutathione. Subunits in the cytochrome bc (1) complex utilize disulfide bonds for enzymatic activity, whereas cytochrome oxidase relies on disulfide linkages for copper acquisition. A redox pathway (Mia40p and Erv1p) mediates the import of intermembrane space proteins such as the small Tim proteins, Cox17p, and Cox19p, which have disulfide bonds. Many of the candidate proteins with disulfide bridges possess a twin CX3C motif or CX9C motif and utilize both metal binding and disulfide linkages for function. It may seem surprising that the intermembrane space has developed redox pathways, considering that the buffered environment should be reducing like the cytosol. However, the prokaryotic origin of the mitochondrion suggests that the intermembrane space may be akin to the oxidative environment of the bacterial periplasm. Although the players forming disulfide bonds are not conserved between mitochondria and prokaryotes, the mitochondrion may have maintained redox chemistry as an assembly mechanism in the intermembrane space for the import of proteins and metals and enzymatic activity.

Effect of vitamin supplements on HIV shedding in breast milk.

PubMed

Villamor, Eduardo; Koulinska, Irene N; Aboud, Said; Murrin, Clare; Bosch, Ronald J; Manji, Karim P; Fawzi, Wafaie W

2010-10-01

Supplementation in lactating HIV-1-infected women with preformed vitamin A and β-carotene (VA/BC) increases the risk of mother-to-child transmission of HIV through breastfeeding. Identifying a biological mechanism to explain this unexpected finding would lend support to a causal effect. The aim of the study was to evaluate the effect of VA/BC or multivitamin (B complex, vitamin C, and vitamin E) supplementation of HIV-infected women on HIV shedding in breast milk during the first 2 y postpartum. We quantified viral (cell-free) and proviral (cell-associated) HIV loads in breast-milk samples collected ≤15 d after delivery and every 3 mo thereafter from 594 Tanzanian HIV-1-infected women who participated in a randomized trial. Women received 1 of the following 4 daily oral regimens in a 2 × 2 factorial fashion during pregnancy and throughout the first 2 y postpartum: multivitamin, VA/BC, multivitamin including VA/BC, or placebo. The proportion of breast-milk samples with detectable viral load was significantly higher in women who received VA/BC (51.3%) than in women who were not assigned to VA/BC (44.8%; P = 0.02). The effect was apparent ≥6 mo postpartum (relative risk: 1.34; 95% CI: 1.04, 1.73). No associations with proviral load were observed. The multivitamin had no effects. In observational analyses, β-carotene but not retinol breast-milk concentrations were significantly associated with an increased viral load in milk. VA/BC supplementation in lactating women increases the HIV load in breast milk. This finding contributes to explaining the adverse effect of VA/BC on mother-to-child transmission. β-Carotene appears to have an effect on breast-milk viral load, independent of preformed vitamin A. This trial was registered at clinicaltrials.gov as NCT00197756.

Complement Activation in Relation to Capillary Leakage in Children with Septic Shock and Purpura

PubMed Central

Hazelzet, Jan A.; de Groot, Ronald; van Mierlo, Gerard; Joosten, Koen F. M.; van der Voort, Edwin; Eerenberg, Anke; Suur, Marja H.; Hop, Wim C. J.; Hack, C. Erik

1998-01-01

To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease. PMID:9784543

The effects of protein crowding in bacterial photosynthetic membranes on the flow of quinone redox species between the photochemical reaction center and the ubiquinol-cytochrome c2 oxidoreductase.

PubMed

Woronowicz, Kamil; Sha, Daniel; Frese, Raoul N; Sturgis, James N; Nanda, Vikas; Niederman, Robert A

2011-08-01

Atomic force microscopy (AFM) of the native architecture of the intracytoplasmic membrane (ICM) of a variety of species of purple photosynthetic bacteria, obtained at submolecular resolution, shows a tightly packed arrangement of light harvesting (LH) and reaction center (RC) complexes. Since there are no unattributed structures or gaps with space sufficient for the cytochrome bc(1) or ATPase complexes, they are localized in membrane domains distinct from the flat regions imaged by AFM. This has generated a renewed interest in possible long-range pathways for lateral diffusion of UQ redox species that functionally link the RC and the bc(1) complexes. Recent proposals to account for UQ flow in the membrane bilayer are reviewed, along with new experimental evidence provided from an analysis of intrinsic near-IR fluorescence emission that has served to test these hypotheses. The results suggest that different mechanism of UQ flow exist between species such as Rhodobacter sphaeroides, with a highly organized arrangement of LH and RC complexes and fast RC electron transfer turnover, and Phaeospirillum molischianum with a more random organization and slower RC turnover. It is concluded that packing density of the peripheral LH2 antenna in the Rba. sphaeroides ICM imposes constraints that significantly slow the diffusion of UQ redox species between the RC and cytochrome bc(1) complex, while in Phs. molischianum, the crowding of the ICM with LH3 has little effect upon UQ diffusion. This supports the proposal that in this type of ICM, a network of RC-LH1 core complexes observed in AFM provides a pathway for long-range quinone diffusion that is unaffected by differences in LH complex composition or organization.

Crystal structure of a β-aminopeptidase from an Australian Burkholderia sp.

PubMed

John-White, Marietta; Dumsday, Geoff J; Johanesen, Priscilla; Lyras, Dena; Drinkwater, Nyssa; McGowan, Sheena

2017-07-01

β-Aminopeptidases are a unique group of enzymes that have the unusual capability to hydrolyze N-terminal β-amino acids from synthetic β-peptides. β-Peptides can form secondary structures mimicking α-peptide-like structures that are resistant to degradation by most known proteases and peptidases. These characteristics of β-peptides give them great potential as peptidomimetics. Here, the X-ray crystal structure of BcA5-BapA, a β-aminopeptidase from a Gram-negative Burkholderia sp. that was isolated from activated sludge from a wastewater-treatment plant in Australia, is reported. The crystal structure of BcA5-BapA was determined to a resolution of 2.0 Å and showed a tetrameric assembly typical of the β-aminopeptidases. Each monomer consists of an α-subunit (residues 1-238) and a β-subunit (residues 239-367). Comparison of the structure of BcA5-BapA with those of other known β-aminopeptidases shows a highly conserved structure and suggests a similar proteolytic mechanism of action.

Fractal scaling laws of black carbon aerosol and their influence on spectral radiative properties

NASA Astrophysics Data System (ADS)

Tiwari, S.; Chakrabarty, R. K.; Heinson, W.

2016-12-01

Current estimates of the direct radiative forcing for Black Carbon (BC) aerosol span over a poorly constrained range between 0.2 and 1 W.m-2. To improve this large uncertainty, tighter constraints need to be placed on BC's key wavelength-dependent optical properties, namely, the absorption (MAC) and scattering (MSC) cross sections per unit mass and hemispherical upscatter fraction (β; a dimensionless scattering directionality parameter). These parameters are very sensitive to changes in particle morphology and complex refractive index nindex. Their interplay determines the magnitude of net positive or negative radiative forcing efficiencies. The current approach among climate modelers for estimating MAC and MSC values of BC is from their optical cross-sections calculated assuming spherical particle morphology with homogeneous, constant-valued refractive index in the visible solar spectrum. The β values are typically assumed to be a constant across this spectrum. This approach, while being computationally inexpensive and convenient, ignores the inherent fractal morphology of BC and its scaling behaviors, and resulting optical properties. In this talk, I will present recent results from my laboratory on determination of the fractal scaling laws of BC aggregate packing density and its complex refractive index for size spanning across three orders of magnitude, and their effects on spectral (Visible-infrared wavelength) scaling of MAC, MSC, and β values. Our experiments synergistically combined novel BC generation techniques, aggregation models, contact-free multi-wavelength optical measurements, and electron microscopy analysis. The scale dependence of nindex on aggregate size followed power-law exponents of -1.4 and -0.5 for sub- and super-micron size aggregates, respectively. The spherical Rayleigh-optics approximation limits, used by climate models for spectral extrapolation of BC optical cross-sections and deconvolution of multi-species mixing ratios, are redefined using the concept of phase shift parameter. I will highlight the importance of size-dependent β values and its role in offsetting the strong light absorbing nature of BC. Finally, the errors introduced in forcing efficiency calculations of BC by assuming spherical homogeneous morphology will be evaluated.

H2BC: a new technique for NMR analysis of complex carbohydrates.

PubMed

Petersen, Bent O; Vinogradov, Evguenii; Kay, William; Würtz, Peter; Nyberg, Nils T; Duus, Jens Ø; Sørensen, Ole W

2006-03-20

It is demonstrated that the H2BC NMR pulse sequence (J. Am. Chem. Soc.2005, 127, 6154, Magn. Reson. Chem.2005, 43, 971-974) offers unambiguous assignments and significant simplification of NMR spectra of large and complex carbohydrates compared to other techniques for the establishment of correlations over more than one bond. H2BC almost exclusively correlates protons and proton-bearing carbon spins separated by two covalent bonds and is independent of occasionally vanishing (2)J(CH) coupling constants, which alleviates the problem of missing two-bond correlations in HMBC spectra. H2BC also solves the problem of distinguishing two- and three-bond correlations in HSQC-TOCSY or HMBC. It is a further asset of H2BC that the experiment is significantly shorter than HMBC and HSQC-TOCSY, and hence less sensitive to transverse relaxation. The H2BC experiment is demonstrated on an approximately 30-residue oligosaccharide from Francisella victoria.

From chemolithoautotrophs to electrolithoautotrophs: CO2 fixation by Fe(II)-oxidizing bacteria coupled with direct uptake of electrons from solid electron sources.

PubMed

Ishii, Takumi; Kawaichi, Satoshi; Nakagawa, Hirotaka; Hashimoto, Kazuhito; Nakamura, Ryuhei

2015-01-01

At deep-sea vent systems, hydrothermal emissions rich in reductive chemicals replace solar energy as fuels to support microbial carbon assimilation. Until recently, all the microbial components at vent systems have been assumed to be fostered by the primary production of chemolithoautotrophs; however, both the laboratory and on-site studies demonstrated electrical current generation at vent systems and have suggested that a portion of microbial carbon assimilation is stimulated by the direct uptake of electrons from electrically conductive minerals. Here we show that chemolithoautotrophic Fe(II)-oxidizing bacterium, Acidithiobacillus ferrooxidans, switches the electron source for carbon assimilation from diffusible Fe(2+) ions to an electrode under the condition that electrical current is the only source of energy and electrons. Site-specific marking of a cytochrome aa3 complex (aa3 complex) and a cytochrome bc1 complex (bc1 complex) in viable cells demonstrated that the electrons taken directly from an electrode are used for O2 reduction via a down-hill pathway, which generates proton motive force that is used for pushing the electrons to NAD(+) through a bc1 complex. Activation of carbon dioxide fixation by a direct electron uptake was also confirmed by the clear potential dependency of cell growth. These results reveal a previously unknown bioenergetic versatility of Fe(II)-oxidizing bacteria to use solid electron sources and will help with understanding carbon assimilation of microbial components living in electronically conductive chimney habitats.

From chemolithoautotrophs to electrolithoautotrophs: CO2 fixation by Fe(II)-oxidizing bacteria coupled with direct uptake of electrons from solid electron sources

PubMed Central

Ishii, Takumi; Kawaichi, Satoshi; Nakagawa, Hirotaka; Hashimoto, Kazuhito; Nakamura, Ryuhei

2015-01-01

At deep-sea vent systems, hydrothermal emissions rich in reductive chemicals replace solar energy as fuels to support microbial carbon assimilation. Until recently, all the microbial components at vent systems have been assumed to be fostered by the primary production of chemolithoautotrophs; however, both the laboratory and on-site studies demonstrated electrical current generation at vent systems and have suggested that a portion of microbial carbon assimilation is stimulated by the direct uptake of electrons from electrically conductive minerals. Here we show that chemolithoautotrophic Fe(II)-oxidizing bacterium, Acidithiobacillus ferrooxidans, switches the electron source for carbon assimilation from diffusible Fe2+ ions to an electrode under the condition that electrical current is the only source of energy and electrons. Site-specific marking of a cytochrome aa3 complex (aa3 complex) and a cytochrome bc1 complex (bc1 complex) in viable cells demonstrated that the electrons taken directly from an electrode are used for O2 reduction via a down-hill pathway, which generates proton motive force that is used for pushing the electrons to NAD+ through a bc1 complex. Activation of carbon dioxide fixation by a direct electron uptake was also confirmed by the clear potential dependency of cell growth. These results reveal a previously unknown bioenergetic versatility of Fe(II)-oxidizing bacteria to use solid electron sources and will help with understanding carbon assimilation of microbial components living in electronically conductive chimney habitats. PMID:26500609

Structural and Biochemical Studies on the Regulation of Biotin Carboxylase by Substrate Inhibition and Dimerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

C Chou; L Tong

2011-12-31

Biotin carboxylase (BC) activity is shared among biotin-dependent carboxylases and catalyzes the Mg-ATP-dependent carboxylation of biotin using bicarbonate as the CO{sub 2} donor. BC has been studied extensively over the years by structural, kinetic, and mutagenesis analyses. Here we report three new crystal structures of Escherichia coli BC at up to 1.9 {angstrom} resolution, complexed with different ligands. Two structures are wild-type BC in complex with two ADP molecules and two Ca{sup 2+} ions or two ADP molecules and one Mg{sup 2+} ion. One ADP molecule is in the position normally taken by the ATP substrate, whereas the other ADPmore » molecule occupies the binding sites of bicarbonate and biotin. One Ca{sup 2+} ion and the Mg{sup 2+} ion are associated with the ADP molecule in the active site, and the other Ca{sup 2+} ion is coordinated by Glu-87, Glu-288, and Asn-290. Our kinetic studies confirm that ATP shows substrate inhibition and that this inhibition is competitive against bicarbonate. The third structure is on the R16E mutant in complex with bicarbonate and Mg-ADP. Arg-16 is located near the dimer interface. The R16E mutant has only a 2-fold loss in catalytic activity compared with the wild-type enzyme. Analytical ultracentrifugation experiments showed that the mutation significantly destabilized the dimer, although the presence of substrates can induce dimer formation. The binding modes of bicarbonate and Mg-ADP are essentially the same as those to the wild-type enzyme. However, the mutation greatly disrupted the dimer interface and caused a large re-organization of the dimer. The structures of these new complexes have implications for the catalysis by BC.« less

Structural and Biochemical Studies on the Regulation of Biotin Carboxylase by Substrate Inhibition and Dimerization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, Chi-Yuan; Tong, Liang

2012-06-19

Biotin carboxylase (BC) activity is shared among biotin-dependent carboxylases and catalyzes the Mg-ATP-dependent carboxylation of biotin using bicarbonate as the CO{sub 2} donor. BC has been studied extensively over the years by structural, kinetic, and mutagenesis analyses. Here we report three new crystal structures of Escherichia coli BC at up to 1.9 {angstrom} resolution, complexed with different ligands. Two structures are wild-type BC in complex with two ADP molecules and two Ca{sup 2+} ions or two ADP molecules and one Mg{sup 2+} ion. One ADP molecule is in the position normally taken by the ATP substrate, whereas the other ADPmore » molecule occupies the binding sites of bicarbonate and biotin. One Ca{sup 2+} ion and the Mg{sup 2+} ion are associated with the ADP molecule in the active site, and the other Ca{sup 2+} ion is coordinated by Glu-87, Glu-288, and Asn-290. Our kinetic studies confirm that ATP shows substrate inhibition and that this inhibition is competitive against bicarbonate. The third structure is on the R16E mutant in complex with bicarbonate and Mg-ADP. Arg-16 is located near the dimer interface. The R16E mutant has only a 2-fold loss in catalytic activity compared with the wild-type enzyme. Analytical ultracentrifugation experiments showed that the mutation significantly destabilized the dimer, although the presence of substrates can induce dimer formation. The binding modes of bicarbonate and Mg-ADP are essentially the same as those to the wild-type enzyme. However, the mutation greatly disrupted the dimer interface and caused a large re-organization of the dimer. The structures of these new complexes have implications for the catalysis by BC.« less

Limitation of using Angstrom exponent for source apportionment of black carbon in complex environments - A case study from the North West Indo- Gangetic plain

NASA Astrophysics Data System (ADS)

Garg, S.; Sinha, B.; Sinha, V.; Chandra, P.; Sarda Esteve, R.; Gros, V.

2015-12-01

Determining the contribution of different sources to the total BC is necessary for targeted mitigation. Absorption Angstrom exponent (αabs) measurements of black carbon (BC) have recently been introduced as a novel tool to apportion the contribution of biomass burning sources to BC. Two-component Aethalometer model for apportioning BC to biomass burning sources and fossil fuel combustion sources, which uses αabs as a generic indicator of the source type, is widely used for determining the contribution of the two types of sources to the total BC. Our work studies BC emissions in the highly-populated, anthropogenic emissions-dominated Indo-Gangetic Plain and demonstrates that the αabs cannot be used as a generic tracer for biomass burning emissions in a complex environment. Simultaneously collected high time resolution data from a 7-wavelength Aethalometer (AE 42, Magee Scientific, USA) and a high sensitivity Proton Transfer Reaction- Quadrupole Mass Spectrometer (PTR-MS) installed at a sub-urban site in Mohali (Punjab), India, were used to identify a number of biomass combustion plumes during which BC enhancements correlated strongly with an increase in acetonitrile (a well-established biomass burning tracer) mixing ratio. Each type of biomass combustion is classified and characterized by distinct emission ratios of aromatic compounds and oxygenated VOCs to acetonitrile. The identified types of biomass combustion include two different types of crop residue burning (paddy and wheat), burning of leaf-litter, and garbage burning. Traffic (fossil-fuel burning) plumes were also selected for comparison. We find that the two-component Aethalometer source-apportionment method cannot be extrapolated to all types of biomass combustion and αabs of traffic plumes can be >1 in developing countries like India, where use of adulterated fuel in vehicles is common. Thus in a complex environment, where multiple anthropogenic BC sources and air masses of variable photochemical age impact a receptor site, the angstrom exponent is not representative of the combustion type and therefore, cannot be used as a generic tracer to constrain source contributions.

TP53 mutation-correlated genes predict the risk of tumor relapse and identify MPS1 as a potential therapeutic kinase in TP53-mutated breast cancers.

PubMed

Győrffy, Balázs; Bottai, Giulia; Lehmann-Che, Jacqueline; Kéri, György; Orfi, László; Iwamoto, Takayuki; Desmedt, Christine; Bianchini, Giampaolo; Turner, Nicholas C; de Thè, Hugues; André, Fabrice; Sotiriou, Christos; Hortobagyi, Gabriel N; Di Leo, Angelo; Pusztai, Lajos; Santarpia, Libero

2014-05-01

Breast cancers (BC) carry a complex set of gene mutations that can influence their gene expression and clinical behavior. We aimed to identify genes driven by the TP53 mutation status and assess their clinical relevance in estrogen receptor (ER)-positive and ER-negative BC, and their potential as targets for patients with TP53 mutated tumors. Separate ROC analyses of each gene expression according to TP53 mutation status were performed. The prognostic value of genes with the highest AUC were assessed in a large dataset of untreated, and neoadjuvant chemotherapy treated patients. The mitotic checkpoint gene MPS1 was the most significant gene correlated with TP53 status, and the most significant prognostic marker in all ER-positive BC datasets. MPS1 retained its prognostic value independently from the type of treatment administered. The biological functions of MPS1 were investigated in different BC cell lines. We also assessed the effects of a potent small molecule inhibitor of MPS1, SP600125, alone and in combination with chemotherapy. Consistent with the gene expression profiling and siRNA assays, the inhibition of MPS1 by SP600125 led to a reduction in cell viability and a significant increase in cell death, selectively in TP53-mutated BC cells. Furthermore, the chemical inhibition of MPS1 sensitized BC cells to conventional chemotherapy, particularly taxanes. Our results collectively demonstrate that TP53-correlated kinase MPS1, is a potential therapeutic target in BC patients with TP53 mutated tumors, and that SP600125 warrant further development in future clinical trials. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Bonding-restricted structure search for novel 2D materials with dispersed C2 dimers.

PubMed

Zhang, Cunzhi; Zhang, Shunhong; Wang, Qian

2016-07-12

Currently, the available algorithms for unbiased structure searches are primarily atom-based, where atoms are manipulated as the elementary units, and energy is used as the target function without any restrictions on the bonding of atoms. In fact, in many cases such as nanostructure-assembled materials, the structural units are nanoclusters. We report a study of a bonding-restricted structure search method based on the particle swarm optimization (PSO) for finding the stable structures of two-dimensional (2D) materials containing dispersed C2 dimers rather than individual C atoms. The C2 dimer can be considered as a prototype of nanoclusters. Taking Si-C, B-C and Ti-C systems as test cases, our method combined with density functional theory and phonon calculations uncover new ground state geometrical structures for SiC2, Si2C2, BC2, B2C2, TiC2, and Ti2C2 sheets and their low-lying energy allotropes, as well as their electronic structures. Equally important, this method can be applied to other complex systems even containing f elements and other molecular dimers such as S2, N2, B2 and Si2, where the complex orbital orientations require extensive search for finding the optimal orientations to maximize the bonding with the dimers, predicting new 2D materials beyond MXenes (a family of transition metal carbides or nitrides) and dichalcogenide monolayers.

Characterisation of Black Carbon (BC) mixing state and flux in Beijing using single particle measurements.

NASA Astrophysics Data System (ADS)

Joshi, Rutambhara; Liu, Dantong; Allan, James; Coe, Hugh; Flynn, Michael; Broda, Kurtis; Olfert, Jason; Irwin, Martin; Sun, Yele; Fu, Pingqing; Wang, Junfeng; Ge, Xinlei; Langford, Ben; Nemitz, Eiko; Mullinger, Neil

2017-04-01

BC is generated by the incomplete combustion of carbonaceous fuels and it is an important component of fine PM2.5. In the atmosphere BC particles have a complex structure and its mixing state has crucial impact on optical properties. Quantifying the sources and emissions of black carbon in urban environments is important and presently uncertain, particularly in megacities undergoing rapid growth and change in emissions. During the winter of 2016 (10th Nov-10th Dec) the BC was characterised as part of a large joint UK-China field experiment in Beijing. This paper focuses on understanding the mixing state of BC as well as identification and quantification of BC sources. We used a combination of a Centrifugal Particle Mass Analyser (CPMA) and a Single Particle Soot Photometer (SP2) to uniquely quantify the morphology independent mass of single refractory BC particles and their coating content. The CPMA allows us to select pre-charged aerosol particles according to their mass to charge ratio and the SP2 provides information on the mass of refractory BC through a laser-induced incandescence method. Furthermore, another SP2 was used to measure the BC flux at 100m height using the Eddy Covariance method. We have successfully gathered 4 weeks of continuous measurements which include several severe pollution events in Beijing. Here we present preliminary results, characterising the distribution of coating mass on BC particles in Beijing and linking this to the main sources of BC in the city. We will provide initial estimates of the BC flux over a several kilometre footprint. Such analysis will provide important information for the further investigation of source distribution, emission, lifetime and optical properties of BC under complex environments in Beijing.

Biochar composites with nano zerovalent iron and eggshell powder for nitrate removal from aqueous solution with coexisting chloride ions.

PubMed

Ahmad, Munir; Ahmad, Mahtab; Usman, Adel R A; Al-Faraj, Abdullah S; Abduljabbar, Adel S; Al-Wabel, Mohammad I

2017-09-18

Biochar (BC) was produced from date palm tree leaves and its composites were prepared with nano zerovalent iron (nZVI-BC) and hen eggshell powder (EP-BC). The produced BC and its composites were characterized by SEM, XRD, BET, and FTIR for surface structural, mineralogical, and chemical groups and tested for their efficiency for nitrate removal from aqueous solutions in the presence and absence of chloride ions. The incidence of graphene and nano zerovalent iron (Fe 0 ) in the nZVI-BC composite was confirmed by XRD. The nZVI-BC composite possessed highest surface area (220.92 m 2  g -1 ), carbon (80.55%), nitrogen (3.78%), and hydrogen (11.09%) contents compared to other materials. Nitrate sorption data was fitted well to the Langmuir (R 2  = 0.93-0.98) and Freundlich (R 2  = 0.90-0.99) isotherms. The sorption kinetics was adequately explained by the pseudo-second-order, power function, and Elovich models. The nZVI-BC composite showed highest Langmuir predicted sorption capacity (148.10 mg g -1 ) followed by EP-BC composite (72.77 mg g -1 ). In addition to the high surface area, the higher nitrate removal capacity of nZVI-BC composite could be attributed to the combination of two processes, i.e., chemisorption (outer-sphere complexation) and reduction of nitrate to ammonia or nitrogen by Fe 0 . The appearance of Fe-O stretching and N-H bonds in post-sorption FTIR spectra of nZVI-BC composite suggested the occurrence of redox reaction and formation of Fe compound with N, such as ferric nitrate (Fe(NO 3 ) 3 ·9H 2 O). Coexistence of chloride ions negatively influenced the nitrate sorption. The decrease in nitrate sorption with increasing chloride ion concentration was observed, which could be due to the competition of free active sites on the sorbents between nitrate and chloride ions. The nZVI-BC composite exhibited higher nitrate removal efficiency compared to other materials even in the presence of highest concentration (100 mg L -1 ) of coexisting chloride ion.

Arsenic sorption by red mud-modified biochar produced from rice straw.

PubMed

Wu, Chuan; Huang, Liu; Xue, Sheng-Guo; Huang, Yu-Ying; Hartley, William; Cui, Meng-Qian; Wong, Ming-Hung

2017-08-01

Red mud-modified biochar (RM-BC) has been produced to be utilized as a novel adsorbent to remove As because it can effectively combine the beneficial features of red mud (rich metal oxide composition and porous structure) and biochar (large surface area and porous structure properties). SEM-EDS and XRD analyses demonstrated that red mud had loaded successfully on the surface of biochar. With the increasing of pH in solution, arsenate (As(V)) adsorption on RM-BC decreased while arsenite (As(III)) increased. Arsenate adsorption kinetics process on RM-BC fitted the pseudo-second-order model, while that of As(III) favored the Elovich model. All sorption isotherms produced superior fits with the Langmuir model. RM-BC exhibited improved As removal capabilities, with a maximum adsorption capacity (Q max ) for As(V) of 5923 μg g -1 , approximately ten times greater than that of the untreated BC (552.0 μg g -1 ). Furthermore, it has been indicated that the adsorption of As(V) on RM-BC may be strongly associated with iron oxides (hematite and magnetite) and aluminum oxides (gibbsite) by X-ray absorption near-edge spectroscopy (XANES), which was possibly because of surface complexation and electrostatic interactions. RM-BC may be used as a valuable adsorbent for removing As in the environment due to the waste materials being relatively abundant.

T-matrix modeling of linear depolarization by morphologically complex soot and soot-containing aerosols

NASA Astrophysics Data System (ADS)

Mishchenko, Michael I.; Liu, Li; Mackowski, Daniel W.

2013-07-01

We use state-of-the-art public-domain Fortran codes based on the T-matrix method to calculate orientation and ensemble averaged scattering matrix elements for a variety of morphologically complex black carbon (BC) and BC-containing aerosol particles, with a special emphasis on the linear depolarization ratio (LDR). We explain theoretically the quasi-Rayleigh LDR peak at side-scattering angles typical of low-density soot fractals and conclude that the measurement of this feature enables one to evaluate the compactness state of BC clusters and trace the evolution of low-density fluffy fractals into densely packed aggregates. We show that small backscattering LDRs measured with ground-based, airborne, and spaceborne lidars for fresh smoke generally agree with the values predicted theoretically for fluffy BC fractals and densely packed near-spheroidal BC aggregates. To reproduce higher lidar LDRs observed for aged smoke, one needs alternative particle models such as shape mixtures of BC spheroids or cylinders.

T-Matrix Modeling of Linear Depolarization by Morphologically Complex Soot and Soot-Containing Aerosols

NASA Technical Reports Server (NTRS)

Mishchenko, Michael I.; Liu, Li; Mackowski, Daniel W.

2013-01-01

We use state-of-the-art public-domain Fortran codes based on the T-matrix method to calculate orientation and ensemble averaged scattering matrix elements for a variety of morphologically complex black carbon (BC) and BC-containing aerosol particles, with a special emphasis on the linear depolarization ratio (LDR). We explain theoretically the quasi-Rayleigh LDR peak at side-scattering angles typical of low-density soot fractals and conclude that the measurement of this feature enables one to evaluate the compactness state of BC clusters and trace the evolution of low-density fluffy fractals into densely packed aggregates. We show that small backscattering LDRs measured with groundbased, airborne, and spaceborne lidars for fresh smoke generally agree with the values predicted theoretically for fluffy BC fractals and densely packed near-spheroidal BC aggregates. To reproduce higher lidar LDRs observed for aged smoke, one needs alternative particle models such as shape mixtures of BC spheroids or cylinders.

Arsenic removal by Japanese oak wood biochar in aqueous solutions and well water: Investigating arsenic fate using integrated spectroscopic and microscopic techniques.

PubMed

Niazi, Nabeel Khan; Bibi, Irshad; Shahid, Muhammad; Ok, Yong Sik; Shaheen, Sabry M; Rinklebe, Jörg; Wang, Hailong; Murtaza, Behzad; Islam, Ejazul; Farrakh Nawaz, M; Lüttge, Andreas

2018-04-15

In this study, we examined the sorption of arsenite (As(III)) and arsenate (As(V)) to Japanese oak wood-derived biochar (OW-BC) in aqueous solutions, and determined its efficiency to remove As from As-contaminated well water. Results revealed that, among the four sorption isotherm models, Langmuir model showed the best fit to describe As(III) and As(V) sorption on OW-BC, with slightly greater sorption affinity for As(V) compared to As(III) (Q L =3.89 and 3.16mgg -1 ; R 2 =0.91 and 0.85, respectively). Sorption edge experiments indicated that the maximum As removal was 81% and 84% for As(III)- and As(V)-OW-BC systems at pH7 and 6, respectively, which decreased above these pH values (76-69% and 80-58%). Surface functional groups, notably OH, COOH, CO, CH 3 , were involved in As sequestration by OW-BC, suggesting the surface complexation/precipitation and/or electrostatic interaction of As on OW-BC surface. Arsenic K-edge X-ray absorption near edge structure (XANES) spectroscopy indicated that 36% of the added As(III) was partially oxidized to As(V) in the As(III) sorption experiment, and in As(V) sorption experiment, 48% of As(V) was, albeit incompletely, reduced to As(III) on OW-BC surface. Application of OW-BC to As-contaminated well water (As: 27-144μgL -1 ; n=10) displayed that 92 to 100% of As was depleted despite in the presence of co-occurring competing anions (e.g., SO 4 2- , CO 3 2- , PO 4 3- ). This study shows that OW-BC has a great potential to remove As from solution and drinking (well) water. Overall, the combination of macroscopic sorption data and integrated spectroscopic and microscopic techniques highlight that the fate of As on biochar involves complex redox transformation and association with surface functional moieties in aquatic systems, thereby providing crucial information required for implication of biochar in environmental remediation programs. Copyright © 2017 Elsevier B.V. All rights reserved.

Black Carbon and Precipitation: An Energetics Perspective

NASA Astrophysics Data System (ADS)

Sand, M.; Samset, B. H.; Stjern, C.; Tsigaridis, K.; Myhre, G.

2017-12-01

Airborne Black Carbon (BC) can affect precipitation rates, both globally and regionally, through a number of mechanisms. Many studies have investigated the impact of the direct radiative effect, indirect modification of cloud properties and rapid adjustments (the semidirect effect), individually or in combination, but the net climate impacts of anthropogenic and natural BC are still highly uncertain. A particular problem is the complex behavior of BC-climate interactions with altitude. Since the atmospheric residence time, ageing and removal processes for BC are also poorly known, differences in vertical BC concentration profiles between models and intercomparison experiments greatly complicate the picture. Recently, precipitation changes predicted by climate models have been studied in the framework of changes to the global and regional energy balance. Here, we employ such an energetics perspective to simulations of BC inserted at isolated altitudes, in two major climate models (NCAR CESM1, NASA GISS). We show the resulting regional and global changes to precipitation, and analyze it in both in terms of individual components of radiative forcing, and the atmospheric energy balance. The results are presented in the context of recent literature.

Effects of humic acid and heavy metals on the sorption of polar and apolar organic pollutants onto biochars.

PubMed

Wang, Fei; Sun, Hongwen; Ren, Xinhao; Liu, Yarui; Zhu, Hongkai; Zhang, Peng; Ren, Chao

2017-12-01

The effects of humic acid (HA) and heavy metals (Cu 2+ and Ag + ) on the sorption of polar and apolar organic pollutants onto biochars that were produced at temperatures of 200 °C (BC200) and 700 °C (BC700) were studied. Due to the plentiful polar functional groups on BC200, cationic propranolol exhibited higher levels of sorption than naphthalene on BC200 while naphthalene and propranolol showed similar sorption capacities on BC700. HA changed the characteristics of biochars and generally inhibited the sorption of target organic pollutants on biochars; however, enhancement occurred in some cases depending on the pollutants involved and their concentrations, biochars used and the addition sequences and concentrations of HA. On BC200, HA modifications mainly influenced sorption by decreasing its polarity and increasing its aromaticity, while on BC700, the surface area and pore volume greatly decreased due to the pore-blocking effects of HA. Residue dissolved HA in solution may also contribute to sorption inhibition. Complexation between polar functional groups on BC200 and heavy metals slightly enhanced the sorption of neutral naphthalene and significantly enhanced that of anionic 4-nitro-1-naphtol, while limited the sorption of cationic propranolol. Heavy metals together with their associated water molecules decreased the sorption of target chemicals on BC700 via pore-filling or pore-mouth-covering. Inhibition of heavy metals for 4-nitro-1-naphthol was found to be the weakest due to the bridge effects of heavy metals between 4-nitro-1-naphtol and BC700. The higher polarizability of Ag + led to the increase of its sorption on biochars in the presence of organic aromatic pollutants. The results of the present study shed light on the sorption mechanisms of bi-solute systems and enable us to select suitable biochar sorbents when chemicals co-exist. Copyright © 2017. Published by Elsevier Ltd.

Rational Design of Highly Potent and Slow-Binding Cytochrome bc1 Inhibitor as Fungicide by Computational Substitution Optimization

PubMed Central

Hao, Ge-Fei; Yang, Sheng-Gang; Huang, Wei; Wang, Le; Shen, Yan-Qing; Tu, Wen-Long; Li, Hui; Huang, Li-Shar; Wu, Jia-Wei; Berry, Edward A.; Yang, Guang-Fu

2015-01-01

Hit to lead (H2L) optimization is a key step for drug and agrochemical discovery. A critical challenge for H2L optimization is the low efficiency due to the lack of predictive method with high accuracy. We described a new computational method called Computational Substitution Optimization (CSO) that has allowed us to rapidly identify compounds with cytochrome bc1 complex inhibitory activity in the nanomolar and subnanomolar range. The comprehensively optimized candidate has proved to be a slow binding inhibitor of bc1 complex, ~73-fold more potent (Ki = 4.1 nM) than the best commercial fungicide azoxystrobin (AZ; Ki = 297.6 nM) and shows excellent in vivo fungicidal activity against downy mildew and powdery mildew disease. The excellent correlation between experimental and calculated binding free-energy shifts together with further crystallographic analysis confirmed the prediction accuracy of CSO method. To the best of our knowledge, CSO is a new computational approach to substitution-scanning mutagenesis of ligand and could be used as a general strategy of H2L optimisation in drug and agrochemical design.

TaABC1, a member of the activity of bc1 complex protein kinase family from common wheat, confers enhanced tolerance to abiotic stresses in Arabidopsis

PubMed Central

Wang, Caixiang; Jing, Ruilian; Mao, Xinguo; Chang, Xiaoping; Li, Ang

2011-01-01

Abiotic stresses such as drought, salinity, and low temperature have drastic effects on plant growth and development. However, the molecular mechanisms regulating biochemical and physiological changes in response to stresses are not well understood. Protein kinases are major signal transduction factors among the reported molecular mechanisms mediating acclimation to environmental changes. Protein kinase ABC1 (activity of bc1 complex) is involved in regulating coenzyme Q biosynthesis in mitochondria in yeast (Saccharomyces cersvisiae), and in balancing oxidative stress in chloroplasts in Arabidopsis thaliana. In the current study, TaABC1 (Triticum aestivum L. activity of bc1 complex) protein kinase was localized to the cell membrane, cytoplasm, and nucleus. The effects of overexpressing TaABC1 in transgenic Arabidopsis plants on responses to drought, salt, and cold stress were further investigated. Transgenic Arabidopsis overexpressing the TaABC1 protein showed lower water loss and higher osmotic potential, photochemistry efficiency, and chlorophyll content, while cell membrane stability and controlled reactive oxygen species homeostasis were maintained. In addition, overexpression of TaABC1 increased the expression of stress-responsive genes, such as DREB1A, DREB2A, RD29A, ABF3, KIN1, CBF1, LEA, and P5CS, detected by real-time PCR analysis. The results suggest that TaABC1 overexpression enhances drought, salt, and cold stress tolerance in Arabidopsis, and imply that TaABC1 may act as a regulatory factor involved in a multiple stress response pathways. PMID:21115661

Effect of vitamin supplements on HIV shedding in breast milk123

PubMed Central

Koulinska, Irene N; Aboud, Said; Murrin, Clare; Bosch, Ronald J; Manji, Karim P; Fawzi, Wafaie W

2010-01-01

Background: Supplementation in lactating HIV-1–infected women with preformed vitamin A and β-carotene (VA/BC) increases the risk of mother-to-child transmission of HIV through breastfeeding. Identifying a biological mechanism to explain this unexpected finding would lend support to a causal effect. Objective: The aim of the study was to evaluate the effect of VA/BC or multivitamin (B complex, vitamin C, and vitamin E) supplementation of HIV-infected women on HIV shedding in breast milk during the first 2 y postpartum. Design: We quantified viral (cell-free) and proviral (cell-associated) HIV loads in breast-milk samples collected ≤15 d after delivery and every 3 mo thereafter from 594 Tanzanian HIV-1–infected women who participated in a randomized trial. Women received 1 of the following 4 daily oral regimens in a 2 × 2 factorial fashion during pregnancy and throughout the first 2 y postpartum: multivitamin, VA/BC, multivitamin including VA/BC, or placebo. Results: The proportion of breast-milk samples with detectable viral load was significantly higher in women who received VA/BC (51.3%) than in women who were not assigned to VA/BC (44.8%; P = 0.02). The effect was apparent ≥6 mo postpartum (relative risk: 1.34; 95% CI: 1.04, 1.73). No associations with proviral load were observed. The multivitamin had no effects. In observational analyses, β-carotene but not retinol breast-milk concentrations were significantly associated with an increased viral load in milk. Conclusions: VA/BC supplementation in lactating women increases the HIV load in breast milk. This finding contributes to explaining the adverse effect of VA/BC on mother-to-child transmission. β-Carotene appears to have an effect on breast-milk viral load, independent of preformed vitamin A. This trial was registered at clinicaltrials.gov as NCT00197756. PMID:20739426

Communication: Microsecond dynamics of the protein and water affect electron transfer in a bacterial bc1 complex

NASA Astrophysics Data System (ADS)

Martin, Daniel R.; Matyushov, Dmitry V.

2015-04-01

Cross-membrane electron transport between cofactors localized in proteins of mitochondrial respiration and bacterial photosynthesis is the source of all biological energy. The statistics and dynamics of nuclear fluctuations in these protein/membrane/water heterogeneous systems are critical for their energetic efficiency. The results of 13 μs of atomistic molecular dynamics simulations of the membrane-bound bc1 bacterial complex are analyzed here. The reaction is affected by a broad spectrum of nuclear modes, with the slowest dynamics in the range of time-scales ˜0.1-1.6 μs contributing half of the reaction reorganization energy. Two reorganization energies are required to describe protein electron transfer due to dynamical arrest of protein conformations on the observation window. This mechanistic distinction allows significant lowering of activation barriers for reactions in proteins.

Dimerization of the Bacterial Biotin Carboxylase Subunit Is Required for Acetyl Coenzyme A Carboxylase Activity In Vivo

PubMed Central

Smith, Alexander C.

2012-01-01

Acetyl coenzyme A (acteyl-CoA) carboxylase (ACC) is the first committed enzyme of the fatty acid synthesis pathway. Escherichia coli ACC is composed of four different proteins. The first enzymatic activity of the ACC complex, biotin carboxylase (BC), catalyzes the carboxylation of the protein-bound biotin moiety of another subunit with bicarbonate in an ATP-dependent reaction. Although BC is found as a dimer in cell extracts and the carboxylase activities of the two subunits of the dimer are interdependent, mutant BC proteins deficient in dimerization are reported to retain appreciable activity in vitro (Y. Shen, C. Y. Chou, G. G. Chang, and L. Tong, Mol. Cell 22:807–818, 2006). However, in vivo BC must interact with the other proteins of the complex, and thus studies of the isolated BC may not reflect the intracellular function of the enzyme. We have tested the abilities of three BC mutant proteins deficient in dimerization to support growth and report that the two BC proteins most deficient in dimerization fail to support growth unless expressed at high levels. In contrast, the wild-type protein supports growth at low expression levels. We conclude that BC must be dimeric to fulfill its physiological function. PMID:22037404

Efficiency and mechanisms of Cd removal from aqueous solution by biochar derived from water hyacinth (Eichornia crassipes).

PubMed

Zhang, Feng; Wang, Xin; Yin, Daixia; Peng, Bo; Tan, Changyin; Liu, Yunguo; Tan, Xiaofei; Wu, Shixue

2015-04-15

This study investigated the efficiency and mechanisms of Cd removal by biochar pyrolyzed from water hyacinth (BC) at 250-550 °C. BC450 out-performed the other BCs at varying Cd concentrations and can remove nearly 100% Cd from aqueous solution within 1 h at initial Cd ≤ 50 mg l(-1). The process of Cd sorption by BC450 followed the pseudo-second order kinetics with the equilibrium being achieved after 24 h with initial Cd ranging from 100 to 500 mg l(-1). The maximum Cd sorption capacity of BC450 was estimated to be 70.3 mg g(-1) based on Langmuir model, which is prominent among a range of low-cost sorbents. Based on the balance analysis between cations released and Cd sorbed onto BC450 in combination with SEM-EDX and XPS data, ion-exchange followed by surface complexation is proposed as the dominant mechanism responsible for Cd immobilization by BC450. In parallel, XRD analysis also suggested the formation of insoluble Cd minerals (CdCO3, Cd3P2, Cd3(PO4)2 and K4CdCl6) from either (co)-precipitation or ion exchange. Results from this study highlighted that the conversion of water hyacinth into biochar is a promising method to achieve effective Cd immobilization and improved management of this highly problematic invasive species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Complex Relationships between Occupation, Environment, DNA Adducts, Genetic Polymorphisms and Bladder Cancer in a Case-Control Study Using a Structural Equation Modeling

PubMed Central

Porru, Stefano; Pavanello, Sofia; Carta, Angela; Arici, Cecilia; Simeone, Claudio; Izzotti, Alberto; Mastrangelo, Giuseppe

2014-01-01

DNA adducts are considered an integrate measure of carcinogen exposure and the initial step of carcinogenesis. Their levels in more accessible peripheral blood lymphocytes (PBLs) mirror that in the bladder tissue. In this study we explore whether the formation of PBL DNA adducts may be associated with bladder cancer (BC) risk, and how this relationship is modulated by genetic polymorphisms, environmental and occupational risk factors for BC. These complex interrelationships, including direct and indirect effects of each variable, were appraised using the structural equation modeling (SEM) analysis. Within the framework of a hospital-based case/control study, study population included 199 BC cases and 213 non-cancer controls, all Caucasian males. Data were collected on lifetime smoking, coffee drinking, dietary habits and lifetime occupation, with particular reference to exposure to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs). No indirect paths were found, disproving hypothesis on association between PBL DNA adducts and BC risk. DNA adducts were instead positively associated with occupational cumulative exposure to AAs (p = 0.028), whereas XRCC1 Arg 399 (p<0.006) was related with a decreased adduct levels, but with no impact on BC risk. Previous findings on increased BC risk by packyears (p<0.001), coffee (p<0.001), cumulative AAs exposure (p = 0.041) and MnSOD (p = 0.009) and a decreased risk by MPO (p<0.008) were also confirmed by SEM analysis. Our results for the first time make evident an association between occupational cumulative exposure to AAs with DNA adducts and BC risk, strengthening the central role of AAs in bladder carcinogenesis. However the lack of an association between PBL DNA adducts and BC risk advises that these snapshot measurements are not representative of relevant exposures. This would envisage new scenarios for biomarker discovery and new challenges such as repeated measurements at different critical life stages. PMID:24722645

Bacterial community shift and incurred performance in response to in situ microbial self-assembly graphene and polarity reversion in microbial fuel cell.

PubMed

Chen, Junfeng; Zhang, Lihua; Hu, Yongyou; Huang, Wantang; Niu, Zhuyu; Sun, Jian

2017-10-01

In this work, bacterial community shift and incurred performance of graphene modified bioelectrode (GM-BE) in microbial fuel cell (MFC) were illustrated by high throughput sequencing technology and electrochemical analysis. The results showed that Firmicutes occupied 48.75% in graphene modified bioanode (GM-BA), while Proteobacteria occupied 62.99% in graphene modified biocathode (GM-BC), both were dominant bacteria in phylum level respectively. Typical exoelectrogens, including Geobacter, Clostridium, Pseudomonas, Geothrix and Hydrogenophaga, were counted 26.66% and 17.53% in GM-BA and GM-BC. GM-BE was tended to decrease the bacterial diversity and enrich the dominant species. Because of the enrichment of exoelectrogens and excellent electrical conductivity of graphene, the maximum power density of MFC with GM-BA and GM-BC increased 33.1% and 21.6% respectively, and the transfer resistance decreased 83.8% and 73.6% compared with blank bioelectrode. This study aimed to enrich the microbial study in MFC and broaden the development and application for bioelectrode. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atomistic determinants of co-enzyme Q reduction at the Qi-site of the cytochrome bc1 complex

NASA Astrophysics Data System (ADS)

Postila, Pekka A.; Kaszuba, Karol; Kuleta, Patryk; Vattulainen, Ilpo; Sarewicz, Marcin; Osyczka, Artur; Róg, Tomasz

2016-09-01

The cytochrome (cyt) bc1 complex is an integral component of the respiratory electron transfer chain sustaining the energy needs of organisms ranging from humans to bacteria. Due to its ubiquitous role in the energy metabolism, both the oxidation and reduction of the enzyme’s substrate co-enzyme Q has been studied vigorously. Here, this vast amount of data is reassessed after probing the substrate reduction steps at the Qi-site of the cyt bc1 complex of Rhodobacter capsulatus using atomistic molecular dynamics simulations. The simulations suggest that the Lys251 side chain could rotate into the Qi-site to facilitate binding of half-protonated semiquinone - a reaction intermediate that is potentially formed during substrate reduction. At this bent pose, the Lys251 forms a salt bridge with the Asp252, thus making direct proton transfer possible. In the neutral state, the lysine side chain stays close to the conserved binding location of cardiolipin (CL). This back-and-forth motion between the CL and Asp252 indicates that Lys251 functions as a proton shuttle controlled by pH-dependent negative feedback. The CL/K/D switching, which represents a refinement to the previously described CL/K pathway, fine-tunes the proton transfer process. Lastly, the simulation data was used to formulate a mechanism for reducing the substrate at the Qi-site.

Spatiotemporal Association of Real-Time Concentrations of Black Carbon (BC) with Fine Particulate Matters (PM2.5) in Urban Hotspots of South Korea.

PubMed

Kim, Sungroul; Yu, Sol; Yun, Dongmin

2017-11-06

We evaluated the spatiotemporal distributions of black carbon (BC) and particulate matters with aerodynamic diameters of less than 2.5 m (PM 2.5 ) concentrations at urban diesel engine emission (DEE) hotspots of South Korea. Concentrations of BC and PM 2.5 were measured at the entrance gate of two diesel bus terminals and a train station, in 2014. Measurements were conducted simultaneously at the hotspot (Site 1) and at its adjacent, randomly selected, residential areas, apartment complex near major roadways, located with the same direction of 300 m (Site 2) and 500 m (Site 3) away from Site 1 on 4 different days over the season, thrice per day; morning ( n = 120 measurements for each day and site), evening ( n = 120), and noon ( n = 120). The median (interquartile range) PM 2.5 ranged from 12.6 (11.3-14.3) to 60.1 (47.0-76.0) μg/m³ while those of BC concentrations ranged from 2.6 (1.9-3.7) to 6.3 (4.2-10.3) μg/m³. We observed a strong relationship of PM 2.5 concentrations between sites (slopes 0.89-0.9, the coefficient of determination 0.89-0.96) while the relationship for BC concentrations between sites was relatively weak (slopes 0.76-0.85, the coefficient of determination 0.54-0.72). PM 2.5 concentrations were changed from 4% to 140% by unit increase of BC concentration, depending on site and time while likely supporting the necessity of monitoring of BC as well as PM 2.5 , especially at urban DEE related hotspot areas.

Camptothecin prodrug nanomicelle based on a boronate ester-linked diblock copolymer as the carrier of doxorubicin with enhanced cellular uptake.

PubMed

Gao, Ya; Xiao, Yi; Liu, Shiyuan; Yu, Jiahui

2018-02-01

A novel pH-sensitive polymeric prodrug of camptothecin (CPT) by polymerizing γ-camptothecin-glutamate N-carboxyanhydride (Glu (CPT)-NCA) on boronate ester-linked poly (ethyleneglycol) (PEG) directly via the amine-initiated ring open polymerization (ROP) has been developed. The resulting amphiphilic prodrug (mPEG-BC-PGluCPT) could self-assemble into nanoparticles and encapsulate doxorubicin (Dox) simultaneously in aqueous solution for dual-drug delivery. The formation of polymeric prodrug micelles (mPEG-BC@PGluCPT) was confirmed by the measurements of critical aggregation concentration (CAC), particle size, and morphology observations. The mPEG-BC@PGluCPT micelles were colloidally stable in solutions for two weeks. Polymeric prodrug micelles mPEG-BC@PGluCPT and Dox-loaded micelles mPEG-BC@PGluCPT⋅Dox showed sustained drug release profiles over 48 h. As expected, drug release was accelerated by the decreasement of pH value from 7.4 to 6.0, which demonstrated pH-dependent manner of drug release. Additionally, it was found that cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles on HepG2 cells was higher than that on HL-7702 cells, especially in culture medium at pH 6.0. The enhanced cellular uptake of mPEG-BC@PGluCPT⋅Dox micelles under acidic condition on HepG2 cells resulted in the higher cytotoxicity of mPEG-BC@PGluCPT⋅Dox micelles at acidic pH than that at pH 7.4.

Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria.

PubMed

Stickles, Allison M; Smilkstein, Martin J; Morrisey, Joanne M; Li, Yuexin; Forquer, Isaac P; Kelly, Jane X; Pou, Sovitj; Winter, Rolf W; Nilsen, Aaron; Vaidya, Akhil B; Riscoe, Michael K

2016-08-01

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV-resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria

PubMed Central

Smilkstein, Martin J.; Morrisey, Joanne M.; Li, Yuexin; Forquer, Isaac P.; Kelly, Jane X.; Pou, Sovitj; Winter, Rolf W.; Nilsen, Aaron; Vaidya, Akhil B.

2016-01-01

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV-resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV. PMID:27270285

SufD and SufC ATPase activity are required for iron acquisition during in vivo Fe-S cluster formation on SufB.

PubMed

Saini, Avneesh; Mapolelo, Daphne T; Chahal, Harsimranjit K; Johnson, Michael K; Outten, F Wayne

2010-11-02

In vivo biogenesis of Fe-S cluster cofactors requires complex biosynthetic machinery to limit release of iron and sulfide, to protect the Fe-S cluster from oxidation, and to target the Fe-S cluster to the correct apoenzyme. The SufABCDSE pathway for Fe-S cluster assembly in Escherichia coli accomplishes these tasks under iron starvation and oxidative stress conditions that disrupt Fe-S cluster metabolism. Although SufB, SufC, and SufD are all required for in vivo Suf function, their exact roles are unclear. Here we show that SufB, SufC, and SufD, coexpressed with the SufS-SufE sulfur transfer pair, purify as two distinct complexes (SufBC(2)D and SufB(2)C(2)) that contain Fe-S clusters and FADH(2). These studies also show that SufC and SufD are required for in vivo Fe-S cluster formation on SufB. Furthermore, while SufD is dispensable for in vivo sulfur transfer, it is absolutely required for in vivo iron acquisition. Finally, we demonstrate for the first time that the ATPase activity of SufC is necessary for in vivo iron acquisition during Fe-S cluster assembly.

Recessive resistance to Bean common mosaic virus conferred by the bc-1 and bc-2 genes in common bean (Phaseolus vulgaris L.) affects long distance movement of the virus.

PubMed

Feng, Xue; Orellana, Gardenia; Myers, James; Karasev, Alexander V

2018-04-12

Recessive resistance to Bean common mosaic virus (BCMV) in common bean (Phaseolus vulgaris L.) is governed by four genes that include one strain-nonspecific helper gene bc-u, and three strain-specific genes bc-1, bc-2, and bc-3. The bc-3 gene was identified as an eIF4E translation initiation factor gene mediating resistance through disruption of the interaction between this protein and the VPg protein of the virus. The mode of action of bc-1 and bc-2 in expression of BCMV resistance is unknown, although bc-1 gene was found to affect systemic spread of a related potyvirus, Bean common mosaic necrosis virus. To investigate the possible role of both bc-1 and bc-2 genes in replication, cell-to-cell, and long distance movement of BCMV in P. vulgaris, we tested virus spread of eight BCMV isolates representing pathogroups I, IV, VI, VII, and VIII, in a set of bean differentials expressing different combinations of six resistance alleles including bc-u, bc-1, bc-1 2 , bc-2, bc-2 2 , and bc-3. All studied BCMV isolates were able to replicate and spread in inoculated leaves of bean cultivars harboring bc-u, bc-1, bc-1 2 , bc-2, and bc-2 2 alleles and their combinations, while no BCMV replication was found in inoculated leaves of 'IVT7214' carrying the bc-u, bc-2 and bc-3 genes, except for isolate 1755a capable of overcoming the resistance conferred by bc-2 and bc-3. In contrast, the systemic spread of all BCMV isolates from pathogroups I, IV,VI, VII, and VIII was impaired in common bean cultivars carrying bc-1, bc-1 2 , bc-2, and bc-2 2 alleles. The data suggest that bc-1 and bc-2 recessive resistance genes have no effect on the replication and cell-to-cell movement of BCMV, but affect systemic spread of BCMV in common bean. The BCMV resistance conferred by bc-1 and bc-2 and affecting systemic spread was found only partially effective when these two genes were expressed singly. The efficiency of the restriction of the systemic spread of the virus was greatly enhanced when the alleles of bc-1 and bc-2 genes were combined together.

Four Closely Related HIV-1 CRF01_AE/CRF07_BC Recombinant Forms Identified in East China.

PubMed

Li, Fan; Li, Yuxueyun; Feng, Yi; Hu, Jing; Ruan, Yuhua; Xing, Hui; Shao, Yiming

2017-07-01

Five near full-length genomes of novel second-generation HIV-1 recombinant virus (JS150021, JS150029, JS150129, JS150132, and AH150183) were identified from five HIV-positive people in Jiangsu and Anhui province, east China. Phylogenic analyses showed that these five sequences are all composed of two well-established circulating recombinant forms (CRFs) CRF07_BC and CRF01_AE, grouped into four new discovered recombinant forms, which show several very similar but not identical recombinant breakpoints. The four recombinant forms are also identified to be a sort of family or related viruses, seems to be the results of different recombination events. The emergence of a serious new closely related CRF07_BC/CRF01_AE recombinant strain indicates the increasing complexity of sexual transmission of the HIV-1 epidemic in China.

Targeting the Cytochrome bc1 Complex of Leishmania Parasites for Discovery of Novel Drugs.

PubMed

Ortiz, Diana; Forquer, Isaac; Boitz, Jan; Soysa, Radika; Elya, Carolyn; Fulwiler, Audrey; Nilsen, Aaron; Polley, Tamsen; Riscoe, Michael K; Ullman, Buddy; Landfear, Scott M

2016-08-01

Endochin-like quinolones (ELQs) are potent and specific inhibitors of cytochrome bc1 from Plasmodium falciparum and Toxoplasma gondii and show promise for novel antiparasitic drug development. To determine whether the mitochondrial electron transport chain of Leishmania parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse ELQs. A cohort of ELQs was selectively toxic to amastigotes of Leishmania mexicana and L. donovani, with 50% inhibitory concentrations (IC50s) in the low micromolar range, but the structurally similar hydroxynaphthoquinone buparvaquone was by far the most potent inhibitor of electron transport, ATP production, and intracellular amastigote growth. Cytochrome bc1 is thus a promising target for novel antileishmanial drugs, and further improvements on the buparvaquone scaffold are warranted for development of enhanced therapeutics. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Bonding-restricted structure search for novel 2D materials with dispersed C2 dimers

PubMed Central

Zhang, Cunzhi; Zhang, Shunhong; Wang, Qian

2016-01-01

Currently, the available algorithms for unbiased structure searches are primarily atom-based, where atoms are manipulated as the elementary units, and energy is used as the target function without any restrictions on the bonding of atoms. In fact, in many cases such as nanostructure-assembled materials, the structural units are nanoclusters. We report a study of a bonding-restricted structure search method based on the particle swarm optimization (PSO) for finding the stable structures of two-dimensional (2D) materials containing dispersed C2 dimers rather than individual C atoms. The C2 dimer can be considered as a prototype of nanoclusters. Taking Si-C, B-C and Ti-C systems as test cases, our method combined with density functional theory and phonon calculations uncover new ground state geometrical structures for SiC2, Si2C2, BC2, B2C2, TiC2, and Ti2C2 sheets and their low-lying energy allotropes, as well as their electronic structures. Equally important, this method can be applied to other complex systems even containing f elements and other molecular dimers such as S2, N2, B2 and Si2, where the complex orbital orientations require extensive search for finding the optimal orientations to maximize the bonding with the dimers, predicting new 2D materials beyond MXenes (a family of transition metal carbides or nitrides) and dichalcogenide monolayers. PMID:27403589

Requirement of histidine 217 for ubiquinone reductase activity (Qi site) in the cytochrome bc1 complex.

PubMed

Gray, K A; Dutton, P L; Daldal, F

1994-01-25

Folding models suggest that the highly conserved histidine 217 of the cytochrome b subunit from the cytochrome bc1 complex is close to the quinone reductase (Qi) site. This histidine (bH217) in the cytochrome b polypeptide of the photosynthetic bacterium Rhodobacter capsulatus has been replaced with three other residues, aspartate (D), arginine (R), and leucine (L). bH217D and bH217R are able to grow photoheterotrophically and contain active cytochrome bc1 complexes (60% of wild-type activity), whereas the bH217L mutant is photosynthetically incompetent and contains a cytochrome bc1 complex that has only 10% of the wild-type activity. Single-turnover flash-activated electron transfer experiments show that cytochrome bH is reduced via the Qo site with near native rates in the mutant strains but that electron transfer between cytochrome bH and quinone bound at the Qi site is greatly slowed. These results are consistent with redox midpoint potential (Em) measurements of the cytochrome b subunit hemes and the Qi site quinone. The Em values of cyt bL and bH are approximately the same in the mutants and wild type, although the mutant strains have a larger relative concentration of what may be the high-potential form of cytochrome bH, called cytochrome b150. However, the redox properties of the semiquinone at the Qi site are altered significantly. The Qi site semiquinone stability constant of bH217R is 10 times higher than in the wild type, while in the other two strains (bH217D and bH217L) the stability constant is much lower than in the wild type. Thus H217 appears to have major effects on the redox properties of the quinone bound at the Qi site. These data are incorporated into a suggestion that H217 forms part of the binding pocket of the Qi site in a manner reminiscent of the interaction between quinone bound at the Qb site and H190 of the L subunit of the bacterial photosynthetic reaction center.

Magnetic dipole transitions of Bc and Bc* mesons in the relativistic independent quark model

NASA Astrophysics Data System (ADS)

Patnaik, Sonali; Dash, P. C.; Kar, Susmita; Patra, Sweta P.; Barik, N.

2017-12-01

We study M1-transitions involving mesons: Bc(1 s ), Bc*(1 s ), Bc(2 s ), Bc*(2 s ), Bc(3 s ), and Bc*(3 s ) in the relativistic independent quark (RIQ) model based on a flavor independent average potential in the scalar-vector harmonic form. The transition form factor for Bc*→Bcγ is found to have analytical continuation from spacelike to physical timelike region. Our predicted coupling constant gBc*Bc=0.34 GeV-1 and decay width Γ (Bc*→Bcγ )=23 eV agree with other model predictions. In view of possible observation of Bc and Bc* s-wave states at LHC and Z-factory and potential use of theoretical estimate on M1-transitions, we investigate the allowed as well as hindered transitions of orbitally excited Bc-meson states and predict their decay widths in overall agreement with other model predictions. We consider the typical case of Bc*(1 s )→Bc(1 s )γ , where our predicted decay width which is found quite sensitive to the mass difference between Bc* and Bc mesons may help in determining the mass of Bc* experimentally.

Nasal Bone Shape Is under Complex Epistatic Genetic Control in Mouse Interspecific Recombinant Congenic Strains

PubMed Central

Burgio, Gaétan; Baylac, Michel; Heyer, Evelyne; Montagutelli, Xavier

2012-01-01

Background Genetic determinism of cranial morphology in the mouse is still largely unknown, despite the localization of putative QTLs and the identification of genes associated with Mendelian skull malformations. To approach the dissection of this multigenic control, we have used a set of interspecific recombinant congenic strains (IRCS) produced between C57BL/6 and mice of the distant species Mus spretus (SEG/Pas). Each strain has inherited 1.3% of its genome from SEG/Pas under the form of few, small-sized, chromosomal segments. Results The shape of the nasal bone was studied using outline analysis combined with Fourier descriptors, and differential features were identified between IRCS BcG-66H and C57BL/6. An F2 cross between BcG-66H and C57BL/6 revealed that, out of the three SEG/Pas-derived chromosomal regions present in BcG-66H, two were involved. Segments on chromosomes 1 (∼32 Mb) and 18 (∼13 Mb) showed additive effect on nasal bone shape. The three chromosomal regions present in BcG-66H were isolated in congenic strains to study their individual effect. Epistatic interactions were assessed in bicongenic strains. Conclusions Our results show that, besides a strong individual effect, the QTL on chromosome 1 interacts with genes on chromosomes 13 and 18. This study demonstrates that nasal bone shape is under complex genetic control but can be efficiently dissected in the mouse using appropriate genetic tools and shape descriptors. PMID:22662199

Synthesis and structure of the first discrete dinuclear cationic aluminum complexes.

PubMed

Wang, Xingbao; Dorcet, Vincent; Luo, Yi; Carpentier, Jean-Francois; Kirillov, Evgueni

2016-08-02

The reactions of the charge neutral dinuclear aluminum tetraalkyl complexes of di-Schiff base ligands, i.e. [AlMe2{ON}-R-{ON}AlMe2] (1a, R = 1,3-propylene; 1b, R = 1,3-cyclohexylene) with B(C6F5)3 and [H(Et2O)2](+)[H2N{B(C6F5)3}2](-) were investigated. When B(C6F5)3 was used as the cationizing agent (1 or 2 equiv. vs. Al), only monocationic dinuclear complexes [2a,b]+[MeB(C6F5)3]- were obtained. In contrast, with [H(Et2O)2](+)[H2N{B(C6F5)3}2](-), both mixed-dicationic [3a,b·(OEt2)2]2+[MeB(C6F5)3]-[H2N{B(C6F5)3}2]- and homo-dicationic [3a,b·(OEt2)2]2+[H2N{B(C6F5)3}2]-2 ion-pairs were prepared. All cationic complexes were characterized by (1)H, (13)C, (19)F and (11)B NMR spectroscopy, and an X-ray diffraction study was performed for [3b·(OEt2)2]2+[H2N{B(C6F5)3}2]-2.

High-valent manganese–oxo valence tautomers and the influence of Lewis/Brönsted acids on C–H bond cleavage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baglia, Regina A.; Krest, Courtney M.; Yang, Tzuhsiung

The addition of Lewis or Brönsted acids (LA = Zn(OTf) 2, B(C 6F 5) 3, HBAr F, TFA) to the high-valent manganese–oxo complex Mn V(O)(TBP 8Cz) results in the stabilization of a valence tautomer Mn IV(O-LA)(TBP 8Cz •+). The Zn II and B(C 6F 5) 3 complexes were characterized by manganese K-edge X-ray absorption spectroscopy (XAS). The position of the edge energies and the intensities of the pre-edge (1s to 3d) peaks confirm that the Mn ion is in the +4 oxidation state. Fitting of the extended X-ray absorption fine structure (EXAFS) region reveals 4 N/O ligands at Mn–N avemore » = 1.89 Å and a fifth N/O ligand at 1.61 Å, corresponding to the terminal oxo ligand. This Mn–O bond length is elongated compared to the Mn V(O) starting material (Mn–O = 1.55 Å). The reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H substrates was examined, and it was found that H • abstraction from C–H bonds occurs in a 1:1 stoichiometry, giving a Mn IV complex and the dehydrogenated organic product. The rates of C–H cleavage are accelerated for the Mn IV(O-LA)(TBP 8Cz •+) valence tautomer as compared to the MnV(O) valence tautomer when LA = Zn II, B(C 6F 5) 3, and HBArF, whereas for LA = TFA, the C–H cleavage rate is slightly slower than when compared to MnV(O). A large, nonclassical kinetic isotope effect of k H/ k D = 25–27 was observed for LA = B(C 6F 5) 3 and HBAr F, indicating that H-atom transfer (HAT) is the rate-limiting step in the C–H cleavage reaction and implicating a potential tunneling mechanism for HAT. Furthermore, the reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H bonds depends on the strength of the Lewis acid. The HAT reactivity is compared with the analogous corrole complex Mn IV(O–H)(tpfc •+) recently reported.« less

High-valent manganese–oxo valence tautomers and the influence of Lewis/Brönsted acids on C–H bond cleavage

DOE PAGES

Baglia, Regina A.; Krest, Courtney M.; Yang, Tzuhsiung; ...

2016-09-30

The addition of Lewis or Brönsted acids (LA = Zn(OTf) 2, B(C 6F 5) 3, HBAr F, TFA) to the high-valent manganese–oxo complex Mn V(O)(TBP 8Cz) results in the stabilization of a valence tautomer Mn IV(O-LA)(TBP 8Cz •+). The Zn II and B(C 6F 5) 3 complexes were characterized by manganese K-edge X-ray absorption spectroscopy (XAS). The position of the edge energies and the intensities of the pre-edge (1s to 3d) peaks confirm that the Mn ion is in the +4 oxidation state. Fitting of the extended X-ray absorption fine structure (EXAFS) region reveals 4 N/O ligands at Mn–N avemore » = 1.89 Å and a fifth N/O ligand at 1.61 Å, corresponding to the terminal oxo ligand. This Mn–O bond length is elongated compared to the Mn V(O) starting material (Mn–O = 1.55 Å). The reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H substrates was examined, and it was found that H • abstraction from C–H bonds occurs in a 1:1 stoichiometry, giving a Mn IV complex and the dehydrogenated organic product. The rates of C–H cleavage are accelerated for the Mn IV(O-LA)(TBP 8Cz •+) valence tautomer as compared to the MnV(O) valence tautomer when LA = Zn II, B(C 6F 5) 3, and HBArF, whereas for LA = TFA, the C–H cleavage rate is slightly slower than when compared to MnV(O). A large, nonclassical kinetic isotope effect of k H/ k D = 25–27 was observed for LA = B(C 6F 5) 3 and HBAr F, indicating that H-atom transfer (HAT) is the rate-limiting step in the C–H cleavage reaction and implicating a potential tunneling mechanism for HAT. Furthermore, the reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H bonds depends on the strength of the Lewis acid. The HAT reactivity is compared with the analogous corrole complex Mn IV(O–H)(tpfc •+) recently reported.« less

Isolation and Functional Characterization of a Floral Repressor, BcMAF1, From Pak-choi (Brassica rapa ssp. Chinensis).

PubMed

Huang, Feiyi; Liu, Tongkun; Hou, Xilin

2018-01-01

MADS-box genes form a large gene family in plants and are involved in multiple biological processes, such as flowering. However, the regulation mechanism of MADS-box genes in flowering remains unresolved, especially under short-term cold conditions. In the present study, we isolated BcMAF1 , a Pak-choi ( Brassica rapa ssp. Chinensis ) MADS AFFECTING FLOWERING ( MAF ), as a floral repressor and functionally characterized BcMAF1 in Arabidopsis and Pak-choi. Subcellular localization and sequence analysis indicated that BcMAF1 was a nuclear protein and contained a conserved MADS-box domain. Expression analysis revealed that BcMAF1 had higher expression levels in leaves, stems, and petals, and could be induced by short-term cold conditions in Pak-choi. Overexpressing BcMAF1 in Arabidopsis showed that BcMAF1 had a negative function in regulating flowering, which was further confirmed by silencing endogenous BcMAF1 in Pak-choi. In addition, qPCR results showed that AtAP3 expression was reduced and AtMAF2 expression was induced in BcMAF1 -overexpressing Arabidopsis . Meanwhile, BcAP3 transcript was up-regulated and BcMAF2 transcript was down-regulated in BcMAF1 -silencing Pak-choi. Yeast one-hybrid and dual luciferase transient assays showed that BcMAF1 could bind to the promoters of BcAP3 and BcMAF2 . These results indicated that BcAP3 and BcMAF2 might be the targets of BcMAF1. Taken together, our results suggested that BcMAF1 could negatively regulate flowering by directly activating BcMAF2 and repressing BcAP3 .

The C. elegans RSA complex localizes protein phosphatase 2A to centrosomes and regulates mitotic spindle assembly.

PubMed

Schlaitz, Anne-Lore; Srayko, Martin; Dammermann, Alexander; Quintin, Sophie; Wielsch, Natalie; MacLeod, Ian; de Robillard, Quentin; Zinke, Andrea; Yates, John R; Müller-Reichert, Thomas; Shevchenko, Andrei; Oegema, Karen; Hyman, Anthony A

2007-01-12

Microtubule behavior changes during the cell cycle and during spindle assembly. However, it remains unclear how these changes are regulated and coordinated. We describe a complex that targets the Protein Phosphatase 2A holoenzyme (PP2A) to centrosomes in C. elegans embryos. This complex includes Regulator of Spindle Assembly 1 (RSA-1), a targeting subunit for PP2A, and RSA-2, a protein that binds and recruits RSA-1 to centrosomes. In contrast to the multiple functions of the PP2A catalytic subunit, RSA-1 and RSA-2 are specifically required for microtubule outgrowth from centrosomes and for spindle assembly. The centrosomally localized RSA-PP2A complex mediates these functions in part by regulating two critical mitotic effectors: the microtubule destabilizer KLP-7 and the C. elegans regulator of spindle assembly TPXL-1. By regulating a subset of PP2A functions at the centrosome, the RSA complex could therefore provide a means of coordinating microtubule outgrowth from centrosomes and kinetochore microtubule stability during mitotic spindle assembly.

Immunogenicity of Newcastle Disease Virus Vectors Expressing Norwalk Virus Capsid Protein in the Presence or Absence of VP2 Protein

PubMed Central

Kim, Shin-Hee; Chen, Shun; Jiang, Xi; Green, Kim Y.; Samal, Siba K.

2015-01-01

Noroviruses are the most common cause of acute gastroenteritis in humans. Development of an effective vaccine is required for reducing their outbreaks. In order to develop a GI norovirus vaccine, Newcastle disease virus vectors, rLaSota and modified rBC, were used to express VP1 protein of Norwalk virus. Co-expression of VP1 and VP2 proteins by Newcastle disease virus vectors resulted in enhanced expression of Norwalk virus VP1 protein and self-assembly of VP1 protein into virus-like particles. Furthermore, the Norwalk virus-specific IgG response induced in mice by Newcastle disease virus vectors was similar to that induced by baculovirs-expressed virus-like particles in mice. However, the modified rBC vector in the presence of VP2 protein induced significantly higher levels of cellular and mucosal immune responses than those induced by baculovirus-expressed VLPs. These results indicate that Newcastle disease virus has great potential for developing a live Norwalk virus vaccine by inducing humoral, cellular and mucosal immune responses in humans. PMID:26099695

Ecosystem features determine seagrass community response to sea otter foraging

USGS Publications Warehouse

Hessing-Lewis, Margot; Rechsteiner, Erin U.; Hughes, Brent B.; Tinker, M. Tim; Monteith, Zachary L.; Olson, Angeleen M.; Henderson, Matthew Morgan; Watson, Jane C.

2017-01-01

Comparing sea otter recovery in California (CA) and British Columbia (BC) reveals key ecosystem properties that shape top-down effects in seagrass communities. We review potential ecosystem drivers of sea otter foraging in CA and BC seagrass beds, including the role of coastline complexity and environmental stress on sea otter effects. In BC, we find greater species richness across seagrass trophic assemblages. Furthermore, Cancer spp. crabs, an important link in the seagrass trophic cascade observed in CA, are less common. Additionally, the more recent reintroduction of sea otters, more complex coastline, and reduced environmental stress in BC seagrass habitats supports the hypotheses that sea otter foraging pressure is currently reduced there. In order to manage the ecosystem features that lead to regional differences in top predator effects in seagrass communities, we review our findings, their spatial and temporal constraints, and present a social-ecological framework for future research.

Superhard BC(3) in cubic diamond structure.

PubMed

Zhang, Miao; Liu, Hanyu; Li, Quan; Gao, Bo; Wang, Yanchao; Li, Hongdong; Chen, Changfeng; Ma, Yanming

2015-01-09

We solve the crystal structure of recently synthesized cubic BC(3) using an unbiased swarm structure search, which identifies a highly symmetric BC(3) phase in the cubic diamond structure (d-BC(3)) that contains a distinct B-B bonding network along the body diagonals of a large 64-atom unit cell. Simulated x-ray diffraction and Raman peaks of d-BC(3) are in excellent agreement with experimental data. Calculated stress-strain relations of d-BC(3) demonstrate its intrinsic superhard nature and reveal intriguing sequential bond-breaking modes that produce superior ductility and extended elasticity, which are unique among superhard solids. The present results establish the first boron carbide in the cubic diamond structure with remarkable properties, and these new findings also provide insights for exploring other covalent solids with complex bonding configurations.

A non-canonical mechanism for Crm1-export cargo complex assembly.

PubMed

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Faza, Marius Boulos; Panse, Vikram Govind

2015-04-21

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export.

C1orf163/RESA1 is a novel mitochondrial intermembrane space protein connected to respiratory chain assembly.

PubMed

Kozjak-Pavlovic, Vera; Prell, Florian; Thiede, Bernd; Götz, Monika; Wosiek, Dominik; Ott, Christine; Rudel, Thomas

2014-02-20

Oxidative phosphorylation (OXPHOS) in mitochondria takes place at the inner membrane, which folds into numerous cristae. The stability of cristae depends, among other things, on the mitochondrial intermembrane space bridging complex. Its components include inner mitochondrial membrane protein mitofilin and outer membrane protein Sam50. We identified a conserved, uncharacterized protein, C1orf163 [SEL1 repeat containing 1 protein (SELRC1)], as one of the proteins significantly reduced after the knockdown of Sam50 and mitofilin. We show that C1orf163 is a mitochondrial soluble intermembrane space protein. Sam50 depletion affects moderately the import and assembly of C1orf163 into two protein complexes of approximately 60kDa and 150kDa. We observe that the knockdown of C1orf163 leads to reduction of levels of proteins belonging to the OXPHOS complexes. The activity of complexes I and IV is reduced in C1orf163-depleted cells, and we observe the strongest defects in the assembly of complex IV. Therefore, we propose C1orf163 to be a novel factor important for the assembly of respiratory chain complexes in human mitochondria and suggest to name it RESA1 (for RESpiratory chain Assembly 1). Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of a New HIV-1 CRF01_AE/ CRF07_BC recombinant virus in Tianjin, China.

PubMed

Zhou, Zhehua; Ma, Ping; Feng, Yi; Ou, Weidong; Qian, Jing; Gao, Liying; Zhang, Defa; Shao, Yiming; Wei, Min

2018-05-04

Human immunodeficiency virus (HIV) is notorious for its rapid evolving since its transmissions from money to human. Currently, HIV contains multiple subtypes, circulating recombinant forms (CRFs) and unique recombinant forms (URFs). Here, from an HIV-positive mother and her child in Tianjin, China, we identified a novel HIV-1 second-generation recombinant virus (TJ20170316 and TJ20170317) between CRF01_AE and CRF07_BC. Near full-length genomes were obtained from both samples, and they shared very close sequences, except some point mutations. Phylogenetic analyses of the near full-length genomes showed that they consist of CRF01_AE backbone and part CRF07_BC sequences. Recombinant Identification Program (RIP) and Simplot software identified four breakpoints in gag, pol, vif, tat genes in TJ20170316, totally different from other reported CRFs and URFs. The emergence of such URF in Tianjin, China, highlights the complexity of HIV-1 epidemic and more measures should be taken to prevent HIV transmissions.

Exploiting the synthetic lethality between terminal respiratory oxidases to kill Mycobacterium tuberculosis and clear host infection

PubMed Central

Kalia, Nitin P.; Hasenoehrl, Erik J.; Ab Rahman, Nurlilah B.; Koh, Vanessa H.; Ang, Michelle L. T.; Sajorda, Dannah R.; Hards, Kiel; Grüber, Gerhard; Alonso, Sylvie; Cook, Gregory M.; Berney, Michael; Pethe, Kevin

2017-01-01

The recent discovery of small molecules targeting the cytochrome bc1:aa3 in Mycobacterium tuberculosis triggered interest in the terminal respiratory oxidases for antituberculosis drug development. The mycobacterial cytochrome bc1:aa3 consists of a menaquinone:cytochrome c reductase (bc1) and a cytochrome aa3-type oxidase. The clinical-stage drug candidate Q203 interferes with the function of the subunit b of the menaquinone:cytochrome c reductase. Despite the affinity of Q203 for the bc1:aa3 complex, the drug is only bacteriostatic and does not kill drug-tolerant persisters. This raises the possibility that the alternate terminal bd-type oxidase (cytochrome bd oxidase) is capable of maintaining a membrane potential and menaquinol oxidation in the presence of Q203. Here, we show that the electron flow through the cytochrome bd oxidase is sufficient to maintain respiration and ATP synthesis at a level high enough to protect M. tuberculosis from Q203-induced bacterial death. Upon genetic deletion of the cytochrome bd oxidase-encoding genes cydAB, Q203 inhibited mycobacterial respiration completely, became bactericidal, killed drug-tolerant mycobacterial persisters, and rapidly cleared M. tuberculosis infection in vivo. These results indicate a synthetic lethal interaction between the two terminal respiratory oxidases that can be exploited for anti-TB drug development. Our findings should be considered in the clinical development of drugs targeting the cytochrome bc1:aa3, as well as for the development of a drug combination targeting oxidative phosphorylation in M. tuberculosis. PMID:28652330

A study of H-alpha velocities in NGC 1499, NGC 7000, and IC 1318B/C

NASA Technical Reports Server (NTRS)

Fountain, W. F.; Gary, G. A.; Odell, C. R.

1983-01-01

Multiple slit echelle spectrograph observations of the H-alpha emission line are used to map the radial velocities of the California Nebula (NGC 1499), the North American Nebula complex (NGC 7000 and IC 5070), and IC 1318B/C. The California Nebula is singularly constant in velocity, considering its geometry. The North American Nebula complex reflects a very simple, classical dynamical picture. The expansion discovered earlier in IC 1318B/C is confirmed, detailed, and the model refined. The new data, along with that in earlier papers of this series, show that stellar wind acceleration and champagne flow mechanisms both play important roles in determining the evolution of H II regions.

Bioceramic/poly (glycolic)-poly (lactic acid) composite induces mineralized barrier after direct capping of rat tooth pulp tissue.

PubMed

Gala-Garcia, Alfonso; Teixeira, Karina Imaculada Rosa; Wykrota, Francisco Henrique Lana; Sinisterra, Rubén Dario; Cortés, Maria Esperanza

2010-01-01

The aim of this study was to observe the histopathological pulp response following direct pulp capping of mechanically exposed teeth in rats with a composite of beta-tricalcium phosphate-hydroxyapatite bioceramic (BC) and poly (glycolic)-poly (lactic acid) (PLGA) material or a calcium hydroxide [Ca(OH)2] material, compared to BC alone and a negative control of water. Pulp of the maxillary molars was exposed, followed by capping with the experimental material. The pulpal tissue response was assessed post-operatively at 1, 7, 14 and 30 d, followed by histological analysis. The Ca(OH)2 group exhibited severe acute inflammatory cell infiltration at day 14. However after 30 d, a new hard tissue with macro porous obliteration of the pulp chamber and a characteristic necrotic area had appeared. BC and Ca(OH)2 capping were associated with moderate inflammation and dentinal bridge similar. Meanwhile, in the BC/PLGA composite group, there was moderate inflammatory infiltrate and formation of a dense and complete dentinal bridge. In conclusion, the BC/PLGA composite material showed a large zone of tertiary dentin, and effectively reorganized the dentin-pulp complex.

[Molecular epidemiology and transmission of HIV-1 infection in Zhejiang province, 2015].

PubMed

Yang, J Z; Chen, W J; Zhang, W J; He, L; Zhang, J F; Pan, X H

2017-11-10

Objective: To understand the distribution of HIV-1 subtype diversity and its transmission characteristics in Zhejiang province. Methods: A total of 302 newly diagnosed HIV-1 positive patients were selected through stratified random sampling in Zhejiang in 2015. HIV-1 pol genes were sequenced successfully with reverse transcription PCR/nested PCR and phylogenetic analysis was conducted for 276 patients. Then a molecular epidemiologic study was performed combined with field epidemiological investigation. Results: Of 276 sequence samples analyzed, 122 CRF07_BC strains (44.2%), 103 CRF01_AE strains (37.3%), 17 CRF08_BC strains (6.1%), 9 B strains (3.2%), 6 CRF55_01B strains (2.2%), 5 C strains (1.8%), 1 CRF59_01B strain (0.4%), 1 CRF67_01B strain (0.4%), 1 A1 strain (0.4%), and 11 URFs strains (4.0%) were identified. Phylogenetic analysis revealed 16 clusters with only 15.1% (34/225) sequences involved among CRF07_BC and CRF01_AE strains. The clustered cases in MSM were higher than that in populations with other transmission routes. And clusters existed between the populations with different transmission routes. Conclusion: The major strains of HIV-1 in Zhejiang are CRF07_BC and CRF01_AE. The HIV subtypes showed more complexity in Zhejiang. It is necessary to strengthen the surveillance for HIV subtypes, carry out classified management and conduct effective prevention and control in the population at high risk.

Superhard BC 3 in cubic diamond structure

DOE PAGES

Zhang, Miao; Liu, Hanyu; Li, Quan; ...

2015-01-06

We solve the crystal structure of recently synthesized cubic BC 3 using an unbiased swarm structure search, which identifies a highly symmetric BC 3 phase in the cubic diamond structure (d–BC3) that contains a distinct B-B bonding network along the body diagonals of a large 64-atom unit cell. Simulated x-ray diffraction and Raman peaks of d–BC 3 are in excellent agreement with experimental data. Calculated stress-strain relations of d–BC 3 demonstrate its intrinsic superhard nature and reveal intriguing sequential bond-breaking modes that produce superior ductility and extended elasticity, which are unique among superhard solids. Here, the present results establish themore » first boron carbide in the cubic diamond structure with remarkable properties, and these new findings also provide insights for exploring other covalent solids with complex bonding configurations.« less

Haloacyl complexes of boron, [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br, I).

PubMed

Finze, Maik; Bernhardt, Eduard; Willner, Helge; Lehmann, Christian W

2005-11-04

The haloacyltris(trifluoromethyl)borate anions [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br, I) have been synthesized by reacting (CF3)3BCO with either MHal (M=K, Cs; Hal=F) in SO2 or MHal (M=[nBu4N]+, [Et4N]+, [Ph4P]+; Hal=Cl, Br, I) in dichloromethane. Metathesis reactions of the fluoroacyl complex with Me3SiHal (Hal=Cl, Br, I) led to the formation of its higher homologues. The thermal stabilities of the haloacyltris(trifluoromethyl)borates decrease from the fluorine to the iodine derivative. The chemical reactivities decrease in the same order as demonstrated by a series of selected reactions. The new [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br) salts are used as starting materials in the syntheses of novel compounds that contain the (CF3)3B-C fragment. All borate anions [(CF3)3BC(O)Hal]- (Hal=F, Cl, Br, I) have been characterized by multinuclear NMR spectroscopy (11B, 13C, 17O, 19F) and vibrational spectroscopy. [PPh4][(CF3)3BC(O)Br] crystallizes in the monoclinic space group P2/c (no. 13) and the bond parameters are compared with those of (CF3)3BCO and K[(CF3)3BC(O)F]. The interpretation of the spectroscopic and structural data are supported by DFT calculations [B3LYP/6-311+G(d)].

Adsorption of Cd(II) from aqueous solutions by rape straw biochar derived from different modification processes.

PubMed

Li, Bing; Yang, Lan; Wang, Chang-Quan; Zhang, Qing-Pei; Liu, Qing-Cheng; Li, Yi-Ding; Xiao, Rui

2017-05-01

In order to deal with cadmium (Cd(II)) pollution, three modified biochar materials: alkaline treatment of biochar (BC-NaOH), KMnO 4 impregnation of biochar (BC-MnO x ) and FeCl 3 magnetic treatment of biochar (BC-FeO x ), were investigated. Nitrogen adsorption-desorption isotherms, Fourier transform infrared spectroscopy (FTIR), Boehm titration, and scanning electron microscopy (SEM) were used to determine the characteristics of adsorbents and explore the main adsorption mechanism. The results show that manganese oxide particles are carried successfully within the biochar, contributing to micropore creation, boosting specific surface area and forming innersphere complexes with oxygen-containing groups, while also increasing the number of oxygen-containing groups. The adsorption sites created by the loaded manganese oxide, rather than specific surface areas, play the most important roles in cadmium adsorption. Batch adsorption experiments demonstrate a Langmuir model fit for Cd(II), and BC-MnO x provided the highest sorption capacity (81.10 mg g -1 ). The sorption kinetics of Cd(II) on adsorbents follows pseudo-second-order kinetics and the adsorption rate of the BC-MnO x material was the highest (14.46 g (mg·h) -1 ). Therefore, biochar modification methods involving KMnO 4 impregnation may provide effective ways of enhancing Cd(II) removal from aqueous solutions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Monomeric RC-LH1 core complexes retard LH2 assembly and intracytoplasmic membrane formation in PufX-minus mutants of Rhodobacter sphaeroides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, Peter G.; Mothersole, David J.; Ng, Irene W.

2011-01-01

In the model photosynthetic bacterium Rhodobacter sphaeroides domains of light-harvesting 2 (LH2) complexes surround and interconnect dimeric reaction centre–light-harvesting 1–PufX (RC–LH1–PufX) ‘core’ complexes, forming extensive networks for energy transfer and trapping. These complexes are housed in spherical intracytoplasmic membranes (ICMs), which are assembled in a stepwise process where biosynthesis of core complexes tends to dominate the early stages of membrane invagination. The kinetics of LH2 assembly were measured in PufX mutants that assemble monomeric core complexes, as a consequence of either a twelve-residue N-terminal truncation of PufX (PufXΔ12) or the complete removal of PufX (PufX -). Lower rates of LH2more » assembly and retarded maturation of membrane invagination were observed for the larger and less curved ICM from the PufX - mutant, consistent with the proposition that local membrane curvature, initiated by arrays of bent RC–LH1–PufX dimers, creates a favourable environment for stable assembly of LH2 complexes. Transmission electron microscopy and high-resolution atomic force microscopy were used to examine ICM morphology and membrane protein organisation in these mutants. Some partitioning of core and LH2 complexes was observed in PufX - membranes, resulting in locally ordered clusters of monomeric RC–LH1 complexes. The distribution of core and LH2 complexes in the three types of membrane examined is consistent with previous models of membrane curvature and domain formation (Frese et al., 2008), which demonstrated that a combination of crowding and asymmetries in sizes and shapes of membrane protein complexes drives membrane organisation.« less

Monomeric RC-LH1 core complexes retard LH2 assembly and intracytoplasmic membrane formation in PufX-minus mutants of Rhodobacter sphaeroides.

PubMed

Adams, Peter G; Mothersole, David J; Ng, Irene W; Olsen, John D; Hunter, C Neil

2011-09-01

In the model photosynthetic bacterium Rhodobacter sphaeroides domains of light-harvesting 2 (LH2) complexes surround and interconnect dimeric reaction centre-light-harvesting 1-PufX (RC-LH1-PufX) 'core' complexes, forming extensive networks for energy transfer and trapping. These complexes are housed in spherical intracytoplasmic membranes (ICMs), which are assembled in a stepwise process where biosynthesis of core complexes tends to dominate the early stages of membrane invagination. The kinetics of LH2 assembly were measured in PufX mutants that assemble monomeric core complexes, as a consequence of either a twelve-residue N-terminal truncation of PufX (PufXΔ12) or the complete removal of PufX (PufX(-)). Lower rates of LH2 assembly and retarded maturation of membrane invagination were observed for the larger and less curved ICM from the PufX(-) mutant, consistent with the proposition that local membrane curvature, initiated by arrays of bent RC-LH1-PufX dimers, creates a favourable environment for stable assembly of LH2 complexes. Transmission electron microscopy and high-resolution atomic force microscopy were used to examine ICM morphology and membrane protein organisation in these mutants. Some partitioning of core and LH2 complexes was observed in PufX(-) membranes, resulting in locally ordered clusters of monomeric RC-LH1 complexes. The distribution of core and LH2 complexes in the three types of membrane examined is consistent with previous models of membrane curvature and domain formation (Frese et al., 2008), which demonstrated that a combination of crowding and asymmetries in sizes and shapes of membrane protein complexes drives membrane organisation. 2011 Elsevier B.V. All rights reserved.

Degradation of dimethyl disulphide in soil with or without biochar amendment.

PubMed

Han, Dawei; Yan, Dongdong; Cao, Aocheng; Fang, Wensheng; Liu, Pengfei; Li, Yuan; Ouyang, Canbin; Wang, Qiuxia

2017-09-01

Dimethyl disulphide (DMDS) is a new and effective alternative to methyl bromide for soil fumigation. The effect of biochar on the fate of DMDS in soil is not fully understood. The objective of this study was to determine the degradation kinetics of DMDS in different soils and evaluate the effect of biochar amendment on DMDS degradation using incubation experiments. The degradation half-life of DMDS was between 1.05 and 6.66 days under non-sterile conditions, and 12.63 to 22.67 days under sterile conditions in five types of soil. Seven out of the eight tested biochar amendments (BC-2 to BC-8) delayed the degradation of DMDS in soil, increasing the half-life of DMDS in Fangshan soil from 1.05 to 1.16-5.87 days following amendment with 1% (w/w) biochar. The degradation rate of DMDS in Fangshan soil accelerated as the amendment rate of BC-1 increased, and decreased as the amendment rate of BC-7 increased. Biodegradation is an important degradation route for DMDS in soil, and DMDS degraded faster in alkaline soil. The effects of biochar amendments on DMDS degradation in soil are determined by complex multiple factors (such as surface area, pH and physicochemical composition), rather than by any single property of biochar. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

A non-canonical mechanism for Crm1-export cargo complex assembly

PubMed Central

Fischer, Ute; Schäuble, Nico; Schütz, Sabina; Altvater, Martin; Chang, Yiming; Boulos Faza, Marius; Panse, Vikram Govind

2015-01-01

The transport receptor Crm1 mediates the export of diverse cargos containing leucine-rich nuclear export signals (NESs) through complex formation with RanGTP. To ensure efficient cargo release in the cytoplasm, NESs have evolved to display low affinity for Crm1. However, mechanisms that overcome low affinity to assemble Crm1-export complexes in the nucleus remain poorly understood. In this study, we reveal a new type of RanGTP-binding protein, Slx9, which facilitates Crm1 recruitment to the 40S pre-ribosome-associated NES-containing adaptor Rio2. In vitro, Slx9 binds Rio2 and RanGTP, forming a complex. This complex directly loads Crm1, unveiling a non-canonical stepwise mechanism to assemble a Crm1-export complex. A mutation in Slx9 that impairs Crm1-export complex assembly inhibits 40S pre-ribosome export. Thus, Slx9 functions as a scaffold to optimally present RanGTP and the NES to Crm1, therefore, triggering 40S pre-ribosome export. This mechanism could represent one solution to the paradox of weak binding events underlying rapid Crm1-mediated export. DOI: http://dx.doi.org/10.7554/eLife.05745.001 PMID:25895666

Measuring persistence to hormonal therapy in patients with breast cancer: accounting for temporary treatment discontinuation.

PubMed

Huiart, Laetitia; Ferdynus, Cyril; Dell'Aniello, Sophie; Bakiri, Naciba; Giorgi, Roch; Suissa, Samy

2014-08-01

Several studies have been conducted to estimate persistence to hormonal therapy among women with breast cancer (BC). Most studies focus on first treatment discontinuation. Patients, however, can have numerous periods of treatment discontinuation or treatment exposure. Our objective is to estimate persistence to tamoxifen in patients with BC while accounting for temporary treatment discontinuations and this by using multi-state (MS) models. A cohort of 10,806 women with BC having received at least one prescription of tamoxifen between 1998 and 2008 was constituted from the UK General Practice Research Database. We fitted a semi-Markov model with three states to estimate the probability of being off treatment over a 5-year period while accounting for temporary treatment discontinuations (transition between on treatment and off treatment) and competing risks (recurrence of BC or death). Non-persistence, as estimated from the MS model, ranged from 12.1% (95% confidence interval [95%CI]: 9.2-15.1) at 1 year to 14.9% (95%CI: 11.7-18.1) at 5 years. Estimations of non-persistence based on the Kaplan-Meier model were higher, i.e., 29.3% (95%CI: 28.1-30.6) at 5 years, as well as those obtained from a competing risk model, i.e., 24.0% (95%CI: 22.9-25.1). Most temporary discontinuations (94.7%) lasted less than 6 months. Temporary treatment discontinuations are frequent and should be accounted for when measuring adherence to treatment. MS models can provide a useful framework for this sort of analysis insofar as they help describe patients' complex behavior. This may help tailor interventions that improve persistence to hormonal therapy among women with BC. Copyright © 2014 John Wiley & Sons, Ltd.

Patient-Centered Care in Breast Cancer Genetic Clinics

PubMed Central

Brédart, Anne; Anota, Amélie; Kuboth, Violetta; Lareyre, Olivier; Cano, Alejandra; Stoppa-Lyonnet, Dominique; Schmutzler, Rita; Dolbeault, Sylvie

2018-01-01

With advances in breast cancer (BC) gene panel testing, risk counseling has become increasingly complex, potentially leading to unmet psychosocial needs. We assessed psychosocial needs and correlates in women initiating testing for high genetic BC risk in clinics in France and Germany, and compared these results with data from a literature review. Among the 442 counselees consecutively approached, 212 (83%) in France and 180 (97%) in Germany, mostly BC patients (81% and 92%, respectively), returned the ‘Psychosocial Assessment in Hereditary Cancer’ questionnaire. Based on the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) BC risk estimation model, the mean BC lifetime risk estimates were 19% and 18% in France and Germany, respectively. In both countries, the most prevalent needs clustered around the “living with cancer” and “children-related issues” domains. In multivariate analyses, a higher number of psychosocial needs were significantly associated with younger age (b = −0.05), higher anxiety (b = 0.78), and having children (b = 1.51), but not with country, educational level, marital status, depression, or loss of a family member due to hereditary cancer. These results are in line with the literature review data. However, this review identified only seven studies that quantitatively addressed psychosocial needs in the BC genetic counseling setting. Current data lack understandings of how cancer risk counseling affects psychosocial needs, and improves patient-centered care in that setting. PMID:29439543

Patient-Centered Care in Breast Cancer Genetic Clinics.

PubMed

Brédart, Anne; Anota, Amélie; Dick, Julia; Kuboth, Violetta; Lareyre, Olivier; De Pauw, Antoine; Cano, Alejandra; Stoppa-Lyonnet, Dominique; Schmutzler, Rita; Dolbeault, Sylvie; Kop, Jean-Luc

2018-02-12

With advances in breast cancer (BC) gene panel testing, risk counseling has become increasingly complex, potentially leading to unmet psychosocial needs. We assessed psychosocial needs and correlates in women initiating testing for high genetic BC risk in clinics in France and Germany, and compared these results with data from a literature review. Among the 442 counselees consecutively approached, 212 (83%) in France and 180 (97%) in Germany, mostly BC patients (81% and 92%, respectively), returned the 'Psychosocial Assessment in Hereditary Cancer' questionnaire. Based on the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) BC risk estimation model, the mean BC lifetime risk estimates were 19% and 18% in France and Germany, respectively. In both countries, the most prevalent needs clustered around the "living with cancer" and "children-related issues" domains. In multivariate analyses, a higher number of psychosocial needs were significantly associated with younger age (b = -0.05), higher anxiety (b = 0.78), and having children (b = 1.51), but not with country, educational level, marital status, depression, or loss of a family member due to hereditary cancer. These results are in line with the literature review data. However, this review identified only seven studies that quantitatively addressed psychosocial needs in the BC genetic counseling setting. Current data lack understandings of how cancer risk counseling affects psychosocial needs, and improves patient-centered care in that setting.

TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex.

PubMed

Guarani, Virginia; Paulo, Joao; Zhai, Bo; Huttlin, Edward L; Gygi, Steven P; Harper, J Wade

2014-03-01

Complex I (CI) of the electron transport chain, a large membrane-embedded NADH dehydrogenase, couples electron transfer to the release of protons into the mitochondrial inner membrane space to promote ATP production through ATP synthase. In addition to being a central conduit for ATP production, CI activity has been linked to neurodegenerative disorders, including Parkinson's disease. CI is built in a stepwise fashion through the actions of several assembly factors. We employed interaction proteomics to interrogate the molecular associations of 15 core subunits and assembly factors previously linked to human CI deficiency, resulting in a network of 101 proteins and 335 interactions (edges). TIMMDC1, a predicted 4-pass membrane protein, reciprocally associated with multiple members of the MCIA CI assembly factor complex and core CI subunits and was localized in the mitochondrial inner membrane, and its depletion resulted in reduced CI activity and cellular respiration. Quantitative proteomics demonstrated a role for TIMMDC1 in assembly of membrane-embedded and soluble arms of the complex. This study defines a new membrane-embedded CI assembly factor and provides a resource for further analysis of CI biology.

Fumonisins, Tortillas and Neural Tube Defects: Untangling a Complex Issue

USDA-ARS?s Scientific Manuscript database

Fumonisin mycotoxins are found in corn and corn-based foods. Fumonisin B1 (FB1), the most common, disrupts sphingolipid metabolism thereby causing species-specific diseases in animals that include cancer in rodents and (birth) neural tube defects (NTD) in LM/Bc mice. Fumonisins’ affect on human heal...

Development of Lead Free Energy Absorber for Space Shuttle Blast Container

NASA Technical Reports Server (NTRS)

Ingram, T.; Balles, D.; Schricker, A.; Novak, H.

1998-01-01

The Space Shuttle vehicle (SSV) is connected to the mobile launch platform (MLP) by four aft skirt hold down studs on each solid rocket booster (SRB). Prior to lift-off, the frangible nuts inside the aft skirt blast containers (BC) are severed into two nut halves by two pyrotechnic booster cartridges. This action releases the SSV and allows the hold down studs to eject through the aft skirt bore and then down into the MLP. USBI has been tasked to upgrade the BC for two specific reasons; 1. to eliminate lead for environmental concerns, and 2. to reduce the chance of nut recontact with the holddown stud. Nut recontact with the stud has been identified as a likely contributor to stud hangups. This upgrade will replace the lead liner with an aluminum foam material. The aluminum foam used as a energy absorber is a proven design in many other aerospace/defense applications. Additional benefits of using the open cell, energy absorbent aluminum foam in place of the solid lead liner are: A. Lead handling/ exposure, and possible contamination, along with hazardous waste disposal will be eliminated; B. Approximately 200 lbs. weight savings will be contributed to each Space Shuttle flight by using aluminum foam over lead; C. The new aluminum liner is designed to catch all shrapnel from frangible nuts thus virtually eliminating chance of foreign object debris (FOD) exiting the HDP, and causing potential damage to the vehicle; D. Potential of using the lighter aluminum liner over lead, allows for easier assembly and disassembly of blast container elements, also allowing for improvements in safety, operator handling, and efficiency of operations. Six BC firing tests will be required to determine if the new liner material will perform in a way to decrease the chance of stud hangups and enhance the ability of the BC to retain blast debris. Testing will be performed at the Kennedy Space Center (KSC) facility known as the Launch Equipment Test Facility (LETF), and will simulate the SRB hold- down post, with actual BC hardware and pyrotechnics assembled, and then test fired. Initial testing was performed in 1997 using a frangible nut in a static drop test over lead and aluminum foam sheet materials. The aluminum foam showed a dramatic improvement of energy absorption over the lead liner material. Proof-of-Principle testing at the KSC-LETF commenced in May, 1998, and is expected to be completed by June, 1998.

Facile synthesis of Cu(II) impregnated biochar with enhanced adsorption activity for the removal of doxycycline hydrochloride from water.

PubMed

Liu, Su; Xu, Wei-Hua; Liu, Yun-Guo; Tan, Xiao-Fei; Zeng, Guang-Ming; Li, Xin; Liang, Jie; Zhou, Zan; Yan, Zhi-Li; Cai, Xiao-Xi

2017-08-15

In this study, the effect factors and mechanisms of doxycycline hydrochloride (DOX) adsorption on copper nitrate modified biochar (Cu-BC) was investigated. Cu-BC absorbent was synthesized through calcination of peanut shells biomass at 450°C and then impregnation with copper nitrate. The Cu-BC has exhibited excellent sorption efficiency about 93.22% of doxycycline hydrochloride from aqueous solution, which was double higher than that of the unmodified biochar. The experimental results suggest that the adsorption efficiency of DOX on the Cu-BC is dominated by the strong complexation, electrostatic interactions between DOX molecules and the Cu-BC samples. Comprehensively considering the cost, efficiency and the application to realistic water, the Cu-BC hold the significant potential for enhancing the effectiveness to remove DOX from water. Copyright © 2017 Elsevier B.V. All rights reserved.

PucC and LhaA direct efficient assembly of the light‐harvesting complexes in Rhodobacter sphaeroides

PubMed Central

Mothersole, David J.; Jackson, Philip J.; Vasilev, Cvetelin; Tucker, Jaimey D.; Brindley, Amanda A.; Dickman, Mark J.

2015-01-01

Summary The mature architecture of the photosynthetic membrane of the purple phototroph R hodobacter sphaeroides has been characterised to a level where an atomic‐level membrane model is available, but the roles of the putative assembly proteins LhaA and PucC in establishing this architecture are unknown. Here we investigate the assembly of light‐harvesting LH2 and reaction centre‐light‐harvesting1‐PufX (RC‐LH1‐PufX) photosystem complexes using spectroscopy, pull‐downs, native gel electrophoresis, quantitative mass spectrometry and fluorescence lifetime microscopy to characterise a series of lha A and puc C mutants. LhaA and PucC are important for specific assembly of LH1 or LH2 complexes, respectively, but they are not essential; the few LH1 subunits found in Δlha A mutants assemble to form normal RC‐LH1‐PufX core complexes showing that, once initiated, LH1 assembly round the RC is cooperative and proceeds to completion. LhaA and PucC form oligomers at sites of initiation of membrane invagination; LhaA associates with RCs, bacteriochlorophyll synthase (BchG), the protein translocase subunit YajC and the YidC membrane protein insertase. These associations within membrane nanodomains likely maximise interactions between pigments newly arriving from BchG and nascent proteins within the SecYEG‐SecDF‐YajC‐YidC assembly machinery, thereby co‐ordinating pigment delivery, the co‐translational insertion of LH polypeptides and their folding and assembly to form photosynthetic complexes. PMID:26419219

Atomic force microscopy reveals multiple patterns of antenna organization in purple bacteria: implications for energy transduction mechanisms and membrane modeling.

PubMed

Sturgis, James N; Niederman, Robert A

2008-01-01

Recent topographs of the intracytoplasmic membrane (ICM) of purple bacteria obtained by atomic force microscopy (AFM) have provided the first surface views of the native architecture of a multicomponent biological membrane at submolecular resolution, representing an important landmark in structural biology. A variety of species-dependent, closely packed arrangements of light-harvesting (LH) complexes was revealed: the most highly organized was found in Rhodobacter sphaeroides in which the peripheral LH2 antenna was seen either in large clusters or in fixed rows interspersed among ordered arrays of dimeric LH1-reaction center (RC) core complexes. A more random organization was observed in other species containing both the LH1 and LH2 complexes, as typified by Rhododspirillum photometricum with randomly packed monomeric LH1-RC core complexes intermingled with large, paracrystalline domains of LH2 antenna. Surprisingly, no structures that could be identified as the ATP synthase or cytochrome bc (1) complexes were observed, which may reflect their localization at ICM vesicle poles or in curved membrane areas, out of view from the flat regions imaged by AFM. This possible arrangement of energy transducing complexes has required a reassessment of energy tranduction mechanisms which place the cytochrome bc (1) complex in close association with the RC. Instead, more plausible proposals must account for the movement of quinone redox species over considerable membrane distances on appropriate time scales. AFM, together with atomic resolution structures are also providing the basis for molecular modeling of the ICM that is leading to an improved picture of the supramolecular organization of photosynthetic complexes, as well as the forces that drive their segregation into distinct domains.

Measured Wavelength-Dependent Absorption Enhancement of Internally Mixed Black Carbon with Absorbing and Nonabsorbing Materials.

PubMed

You, Rian; Radney, James G; Zachariah, Michael R; Zangmeister, Christopher D

2016-08-02

Optical absorption spectra of laboratory generated aerosols consisting of black carbon (BC) internally mixed with nonabsorbing materials (ammonium sulfate, AS, and sodium chloride, NaCl) and BC with a weakly absorbing brown carbon surrogate derived from humic acid (HA) were measured across the visible to near-IR (550 to 840 nm). Spectra were measured in situ using a photoacoustic spectrometer and step-scanning a supercontinuum laser source with a tunable wavelength and bandwidth filter. BC had a mass-specific absorption cross section (MAC) of 7.89 ± 0.25 m(2) g(-1) at λ = 550 nm and an absorption Ångström exponent (AAE) of 1.03 ± 0.09 (2σ). For internally mixed BC, the ratio of BC mass to the total mass of the mixture was chosen as 0.13 to mimic particles observed in the terrestrial atmosphere. The manner in which BC mixed with each material was determined from transmission electron microscopy (TEM). AS/BC and HA/BC particles were fully internally mixed, and the BC was both internally and externally mixed for NaCl/BC particles. The AS/BC, NaCl/BC, and HA/BC particles had AAEs of 1.43 ± 0.05, 1.34 ± 0.06, and 1.91 ± 0.05, respectively. The observed absorption enhancement of mixed BC relative to the pure BC was wavelength dependent for AS/BC and decreased from 1.5 at λ = 550 nm with increasing wavelength while the NaCl/BC enhancement was essentially wavelength independent. For HA/BC, the enhancement ranged from 2 to 3 and was strongly wavelength dependent. Removal of the HA absorption contribution to enhancement revealed that the enhancement was ≈1.5 and independent of wavelength.

Plasma and Electro-energetic Physics

DTIC Science & Technology

2012-03-07

Dynamical Equations (with complex surfaces ): Relativistic Lorentz Force Law for relativistic momentum p and velocity u: tDcJcH tBcE   /)/1()/4...0.1-1 s • 3D, high-fidelity, parallel modeling of high energy density fields and particles in complex geometry with some surface effects...cathodes (500 µm separation) Tang, AFRL/RD 12 DISTRIBUTION A: Approved for public release; distribution is unlimited. ICEPIC simulations Equipotential

Immunogenicity of Newcastle disease virus vectors expressing Norwalk virus capsid protein in the presence or absence of VP2 protein.

PubMed

Kim, Shin-Hee; Chen, Shun; Jiang, Xi; Green, Kim Y; Samal, Siba K

2015-10-01

Noroviruses are the most common cause of acute gastroenteritis in humans. Development of an effective vaccine is required for reducing their outbreaks. In order to develop a GI norovirus vaccine, Newcastle disease virus vectors, rLaSota and modified rBC, were used to express VP1 protein of Norwalk virus. Co-expression of VP1 and VP2 proteins by Newcastle disease virus vectors resulted in enhanced expression of Norwalk virus VP1 protein and self-assembly of VP1 protein into virus-like particles. Furthermore, the Norwalk virus-specific IgG response induced in mice by Newcastle disease virus vectors was similar to that induced by baculovirus-expressed virus-like particles in mice. However, the modified rBC vector in the presence of VP2 protein induced significantly higher levels of cellular and mucosal immune responses than those induced by baculovirus-expressed VLPs. These results indicate that Newcastle disease virus has great potential for developing a live Norwalk virus vaccine by inducing humoral, cellular and mucosal immune responses in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

The Ca2+/Calcineurin-Dependent Signaling Pathway in the Gray Mold Botrytis cinerea: The Role of Calcipressin in Modulating Calcineurin Activity

PubMed Central

Harren, Karin; Schumacher, Julia; Tudzynski, Bettina

2012-01-01

In the gray mold fungus Botrytis cinerea the Gα subunit Bcg1 of a heterotrimeric G protein is an upstream activator of the Ca2+/calmodulin-dependent phosphatase calcineurin. In this study we focused on the functional characterization of the catalytic subunit of calcineurin (BcCnA) and its putative regulator calcipressin (BcRcn1). We deleted the genes encoding both proteins to examine their role concerning growth, differentiation and virulence. The ΔbccnA mutant shows a severe growth defect, does not produce conidia and is avirulent, while the loss of BcRcn1 caused retardation of hyphal growth and delayed infection of host plants, but had no impact on conidiation and sclerotia formation. Expression of several calcineurin-dependent genes and bccnA itself is positively affected by BcRcn1. Complementation of the Δbcrcn1 mutant with a GFP-BcRcn1 fusion construct revealed that BcRcn1 is localized in the cytoplasm and accumulates around the nuclei. Furthermore, we showed that BcCnA physically interacts with BcRcn1 and the regulatory subunit of calcineurin, BcCnB. We investigated the impact of several protein domains characteristic for modulation and activation of BcCnA via BcRcn1, such as the phosphorylation sites and the calcineurin-docking site, by physical interaction studies between BcCnA and wild-type and mutated copies of BcRcn1. Based on the observed phenotypes we conclude that BcRcn1 acts as a positive modulator of BcCnA and the Ca2+/calcineurin-mediated signal transduction in B. cinerea, and that both proteins regulate fungal development and virulence. PMID:22844520

The relationship between black carbon concentration and black smoke: A more general approach

NASA Astrophysics Data System (ADS)

Heal, Mathew R.; Quincey, Paul

2012-07-01

The black carbon (BC) component of ambient particulate matter is an important marker for combustion sources and for its impact on human health and radiative forcing. Extensive data archives exist for the black smoke metric, the historic measure of ambient particle darkness. An expression presented in earlier publications (Quincey, 2007; Quincey et al., 2011) for estimating BC concentrations from traditional black smoke measurements is shown to have limitations that can be addressed by using a more systematic approach to the issue of corrections for increasing darkening of the filter. The form of the more general relationship is shown to be an off-axis parabola rather than the on-axis parabola of the earlier work. Existing data from co-located black smoke and aethalometer measurements at 5 UK sites are reanalysed in this context. At very low concentrations of dark particles (British Black Smoke index < ˜10 μg m-3) a simple linear relationship BC (/μg m-3) ≈ 0.27·BSIBRITISH will suffice. A parabolic relationship, [BC/μgm]=√{5.2-1.1+1.5×BSI+62-13+19}-7.9-0.9+1.1, quantitatively similar to the previously published relationship will be more reliable for BSIBRITISH values up to 20-25 μg m-3. The full set of data available was fitted empirically to the off-axis parabola over the range 0-80 μg m-3 as the quadratic: [BC/μg m-3] = (0.27 ± 0.03) · BSIBRITISH - (4.0 ± 0.2) × 10-4(BSIBRITISH)2, but this curve is highly dependent on the variations between the individual data sets. Adding the extra complexity of the full off-axis parabolic relationship is unlikely to be justified in practical situations. All expressions apply also to the OECD definition of black smoke with the substitution BSIBRITISH = 0.85·BSIOECD. However, in common with the previous approach, they apply only to black smoke values obtained from standard black smoke samplers with 25 mm diameter filters and ˜2 m3 day-1 volumetric flow rate, and presume a value 16.6 m2 g-1 for the specific absorption of BC in ambient particulate matter measured by aethalometry. Fitting uncertainties correspond to imprecision in estimated BC of ±5%, ±12% and ±18% at BSIBRITISH of 5, 20 and 80 μg m-3, respectively. Spatial and temporal variation in particle ensemble optical properties contributes to uncertainty in BC quantification.

Drug-resistant pulmonary tuberculosis in the Baja California-San Diego County border population.

PubMed Central

Peter, C R; Schultz, E; Moser, K; Cox, M; Freeman, R; Ramirez-Zetina, M; Lomeli, M R

1998-01-01

A study was conducted to determine the frequency of, and risk factors for, drug-resistant pulmonary tuberculosis (TB) among Baja California (BC) and San Diego County (SDC) residents. Another purpose was to document the amount of contact between pulmonary TB patients and residents of the opposite side of the the border. During the period from February 1995 to May 1996, pulmonary TB patients from BC (n = 427) and SDC (n = 331) were evaluated with cultures, drug susceptibility tests, and questionnaires. Drug resistance was found in 41% of the BC Mycobacterium tuberculosis complex (MTB) isolates and 20% of the SDC isolates. Resistance to both isoniazid (INH) and rifampin (RIF) varied from 1% of isolates from SDC patients to 17% of isolates from BC patients. Patients with a history of previous treatment had increased odds of drug-resistant disease. Older BC patients were more likely to have INH- or RIF-resistant TB. Although 42% of Tijuana TB patients reported recent contact with residents from SDC, travel to Mexico and contact with residents from Mexico were not significant risk factors for drug-resistant TB among SDC residents. However, the demonstrated contact between TB patients and residents on opposite sides of the border indicates the importance of coordinating efforts internationally to control TB. PMID:9795580

Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

PubMed

Papaioannou, Anastasios; Kuyucak, Serdar; Kuncic, Zdenka

2015-01-01

A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT) as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1) The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2) The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin) is initiated. 3) The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

Electronic connection between the quinone and cytochrome C redox pools and its role in regulation of mitochondrial electron transport and redox signaling.

PubMed

Sarewicz, Marcin; Osyczka, Artur

2015-01-01

Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc1 or ubiquinol:cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria. Copyright © 2015 the American Physiological Society.

Electronic Connection Between the Quinone and Cytochrome c Redox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

PubMed Central

Sarewicz, Marcin; Osyczka, Artur

2015-01-01

Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc1 or ubiquinol:cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria. PMID:25540143

The roles of USH1 proteins and PDZ domain-containing USH proteins in USH2 complex integrity in cochlear hair cells.

PubMed

Zou, Junhuang; Chen, Qian; Almishaal, Ali; Mathur, Pranav Dinesh; Zheng, Tihua; Tian, Cong; Zheng, Qing Y; Yang, Jun

2017-02-01

Usher syndrome (USH) is the most common cause of inherited deaf-blindness, manifested as USH1, USH2 and USH3 clinical types. The protein products of USH2 causative and modifier genes, USH2A, ADGRV1, WHRN and PDZD7, interact to assemble a multiprotein complex at the ankle link region of the mechanosensitive stereociliary bundle in hair cells. Defects in this complex cause stereociliary bundle disorganization and hearing loss. The four USH2 proteins also interact in vitro with USH1 proteins including myosin VIIa, USH1G (SANS), CIB2 and harmonin. However, it is unclear whether the interactions between USH1 and USH2 proteins occur in vivo and whether USH1 proteins play a role in USH2 complex assembly in hair cells. In this study, we identified a novel interaction between myosin VIIa and PDZD7 by FLAG pull-down assay. We further investigated the role of the above-mentioned four USH1 proteins in the cochlear USH2 complex assembly using USH1 mutant mice. We showed that only myosin VIIa is indispensable for USH2 complex assembly at ankle links, indicating the potential transport and/or anchoring role of myosin VIIa for USH2 proteins in hair cells. However, myosin VIIa is not required for USH2 complex assembly in photoreceptors. We further showed that, while PDZ protein harmonin is not involved, its paralogous USH2 proteins, PDZD7 and whirlin, function synergistically in USH2 complex assembly in cochlear hair cells. In summary, our studies provide novel insight into the functional relationship between USH1 and USH2 proteins in the cochlea and the retina as well as the disease mechanisms underlying USH1 and USH2. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Large-scale remodeling of a repressed exon ribonucleoprotein to an exon definition complex active for splicing

PubMed Central

Wongpalee, Somsakul Pop; Vashisht, Ajay; Sharma, Shalini; Chui, Darryl; Wohlschlegel, James A; Black, Douglas L

2016-01-01

Polypyrimidine-tract binding protein PTBP1 can repress splicing during the exon definition phase of spliceosome assembly, but the assembly steps leading to an exon definition complex (EDC) and how PTBP1 might modulate them are not clear. We found that PTBP1 binding in the flanking introns allowed normal U2AF and U1 snRNP binding to the target exon splice sites but blocked U2 snRNP assembly in HeLa nuclear extract. Characterizing a purified PTBP1-repressed complex, as well as an active early complex and the final EDC by SILAC-MS, we identified extensive PTBP1-modulated changes in exon RNP composition. The active early complex formed in the absence of PTBP1 proceeded to assemble an EDC with the eviction of hnRNP proteins, the late recruitment of SR proteins, and binding of the U2 snRNP. These results demonstrate that during early stages of splicing, exon RNP complexes are highly dynamic with many proteins failing to bind during PTBP1 arrest. DOI: http://dx.doi.org/10.7554/eLife.19743.001 PMID:27882870

Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors.

PubMed

Becker, Thomas; Pfannschmidt, Sylvia; Guiard, Bernard; Stojanovski, Diana; Milenkovic, Dusanka; Kutik, Stephan; Pfanner, Nikolaus; Meisinger, Chris; Wiedemann, Nils

2008-01-04

The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane alpha-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM(core) components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the beta-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex.

Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit.

PubMed

Rohrmoser, Michaela; Hölzel, Michael; Grimm, Thomas; Malamoussi, Anastassia; Harasim, Thomas; Orban, Mathias; Pfisterer, Iris; Gruber-Eber, Anita; Kremmer, Elisabeth; Eick, Dirk

2007-05-01

The PeBoW complex is essential for cell proliferation and maturation of the large ribosomal subunit in mammalian cells. Here we examined the role of PeBoW-specific proteins Pes1, Bop1, and WDR12 in complex assembly and stability, nucleolar transport, and pre-ribosome association. Recombinant expression of the three subunits is sufficient for complex formation. The stability of all three subunits strongly increases upon incorporation into the complex. Only overexpression of Bop1 inhibits cell proliferation and rRNA processing, and its negative effects could be rescued by coexpression of WDR12, but not Pes1. Elevated levels of Bop1 induce Bop1/WDR12 and Bop1/Pes1 subcomplexes. Knockdown of Bop1 abolishes the copurification of Pes1 with WDR12, demonstrating Bop1 as the integral component of the complex. Overexpressed Bop1 substitutes for endogenous Bop1 in PeBoW complex assembly, leading to the instability of endogenous Bop1. Finally, indirect immunofluorescence, cell fractionation, and sucrose gradient centrifugation experiments indicate that transport of Bop1 from the cytoplasm to the nucleolus is Pes1 dependent, while Pes1 can migrate to the nucleolus and bind to preribosomal particles independently of Bop1. We conclude that the assembly and integrity of the PeBoW complex are highly sensitive to changes in Bop1 protein levels.

An alternative ionospheric correction model for global navigation satellite systems

NASA Astrophysics Data System (ADS)

Hoque, M. M.; Jakowski, N.

2015-04-01

The ionosphere is recognized as a major error source for single-frequency operations of global navigation satellite systems (GNSS). To enhance single-frequency operations the global positioning system (GPS) uses an ionospheric correction algorithm (ICA) driven by 8 coefficients broadcasted in the navigation message every 24 h. Similarly, the global navigation satellite system Galileo uses the electron density NeQuick model for ionospheric correction. The Galileo satellite vehicles (SVs) transmit 3 ionospheric correction coefficients as driver parameters of the NeQuick model. In the present work, we propose an alternative ionospheric correction algorithm called Neustrelitz TEC broadcast model NTCM-BC that is also applicable for global satellite navigation systems. Like the GPS ICA or Galileo NeQuick, the NTCM-BC can be optimized on a daily basis by utilizing GNSS data obtained at the previous day at monitor stations. To drive the NTCM-BC, 9 ionospheric correction coefficients need to be uploaded to the SVs for broadcasting in the navigation message. Our investigation using GPS data of about 200 worldwide ground stations shows that the 24-h-ahead prediction performance of the NTCM-BC is better than the GPS ICA and comparable to the Galileo NeQuick model. We have found that the 95 percentiles of the prediction error are about 16.1, 16.1 and 13.4 TECU for the GPS ICA, Galileo NeQuick and NTCM-BC, respectively, during a selected quiet ionospheric period, whereas the corresponding numbers are found about 40.5, 28.2 and 26.5 TECU during a selected geomagnetic perturbed period. However, in terms of complexity the NTCM-BC is easier to handle than the Galileo NeQuick and in this respect comparable to the GPS ICA.

Anionic lipids and the cytoskeletal proteins MreB and RodZ define the spatio-temporal distribution and function of membrane stress controller PspA in Escherichia coli.

PubMed

Jovanovic, Goran; Mehta, Parul; Ying, Liming; Buck, Martin

2014-11-01

All cell types must maintain the integrity of their membranes. The conserved bacterial membrane-associated protein PspA is a major effector acting upon extracytoplasmic stress and is implicated in protection of the inner membrane of pathogens, formation of biofilms and multi-drug-resistant persister cells. PspA and its homologues in Gram-positive bacteria and archaea protect the cell envelope whilst also supporting thylakoid biogenesis in cyanobacteria and higher plants. In enterobacteria, PspA is a dual function protein negatively regulating the Psp system in the absence of stress and acting as an effector of membrane integrity upon stress. We show that in Escherichia coli the low-order oligomeric PspA regulatory complex associates with cardiolipin-rich, curved polar inner membrane regions. There, cardiolipin and the flotillin 1 homologue YqiK support the PspBC sensors in transducing a membrane stress signal to the PspA-PspF inhibitory complex. After stress perception, PspA high-order oligomeric effector complexes initially assemble in polar membrane regions. Subsequently, the discrete spatial distribution and dynamics of PspA effector(s) in lateral membrane regions depend on the actin homologue MreB and the peptidoglycan machinery protein RodZ. The consequences of loss of cytoplasmic membrane anionic lipids, MreB, RodZ and/or YqiK suggest that the mode of action of the PspA effector is closely associated with cell envelope organization. © 2014 The Authors.

Dual Nature of Translational Control by Regulatory BC RNAs ▿

PubMed Central

Eom, Taesun; Berardi, Valerio; Zhong, Jun; Risuleo, Gianfranco; Tiedge, Henri

2011-01-01

In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3′ stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems. PMID:21930783

Acute toxicity and associated mechanisms of four strobilurins in algae.

PubMed

Liu, Xiaoxu; Wang, Yu; Chen, Hao; Zhang, Junli; Wang, Chengju; Li, Xuefeng; Pang, Sen

2018-06-01

Strobilurins have been reported highly toxic to non-target aquatic organisms but few illustrated how they cause toxic effects on algae. This study investigated the acute toxicity of Kresoxim-methy (KRE), Pyraclostrobin (PYR), Trifloxystrobin (TRI) and Picoxystrobin (PIC) on two algae and their toxicity mechanisms. Four strobilurins showed lower toxic effects on Chlorella pyrenoidsa but higher on Chlorella vulgaris. bc1 complex activities in C. vulgaris were significantly inhibited by all strobilurins, suggesting bc 1 complex might be the target of strobilurin toxicity in algae. Moreover, SOD, CAT and POD activities were significantly up-regulated by all doses of KRE, PYR and PIC. In contrast, low concentrations of TRI stimulated SOD and POD activities but highest concentration significantly inhibited those activities. Comet assays showed damaged DNA in C. vulgaris by four strobulirins, suggesting their potential genotoxic threats to algae. The results illustrated acute toxicity by strobulirins on algae and their possible toxicity mechanisms. Copyright © 2018 Elsevier B.V. All rights reserved.

KPNA2 is a nuclear export protein that contributes to aberrant localisation of key proteins and poor prognosis of breast cancer.

PubMed

Alshareeda, A T; Negm, O H; Green, A R; Nolan, C C; Tighe, P; Albarakati, N; Sultana, R; Madhusudan, S; Ellis, I O; Rakha, E A

2015-06-09

It is recognised that modulations of the nuclear import of macromolecules have a role in changing cellular phenotypes and carcinogenesis. We and others have noticed that aberrant subcellular localisation of DNA damage response (DDR) proteins in breast cancer (BC) is associated with loss-of-function phenotype. This study aims to investigate the biological and clinical significance of the nucleocytoplasmic transport protein karyopherin α-2 (KPNA2), and its role in controlling DDR proteins subcellular localisation in BC. A large (n=1494) and well-characterised series of early-stage invasive BC with a long-term follow-up was assessed for KPNA2 protein by using immunohistochemistry. KPNA2 expression was associated with the subcellular localisation of key DDR proteins that showed cytoplasmic expression including BRCA1, RAD51, SMC6L1, γH2AX, BARD1, UBC9, PIAS1 and CHK1. High level of KPNA2 was associated not only with cytoplasmic localisation of these proteins but also with their low/negative nuclear expression. Positive KPNA2 expression was associated with negative oestrogen receptor and triple-negative phenotype. Survival analysis showed that KPNA2 was associated with poor outcome (P<0.0001), but this effect was not independent of other prognostic variables. This study provides further evidence for the complexity of DDR mechanism in BC, and that KNPA2 has a role in the aberrant subcellular localisation of DDR proteins with subsequent impaired function.

Proton pumping in the bc1 complex: a new gating mechanism that prevents short circuits.

PubMed

Crofts, Antony R; Lhee, Sangmoon; Crofts, Stephanie B; Cheng, Jerry; Rose, Stuart

2006-08-01

The Q-cycle mechanism of the bc1 complex explains how the electron transfer from ubihydroquinone (quinol, QH2) to cytochrome (cyt) c (or c2 in bacteria) is coupled to the pumping of protons across the membrane. The efficiency of proton pumping depends on the effectiveness of the bifurcated reaction at the Q(o)-site of the complex. This directs the two electrons from QH2 down two different pathways, one to the high potential chain for delivery to an electron acceptor, and the other across the membrane through a chain containing heme bL and bH to the Qi-site, to provide the vectorial charge transfer contributing to the proton gradient. In this review, we discuss problems associated with the turnover of the bc1 complex that center around rates calculated for the normal forward and reverse reactions, and for bypass (or short-circuit) reactions. Based on rate constants given by distances between redox centers in known structures, these appeared to preclude conventional electron transfer mechanisms involving an intermediate semiquinone (SQ) in the Q(o)-site reaction. However, previous research has strongly suggested that SQ is the reductant for O2 in generation of superoxide at the Q(o)-site, introducing an apparent paradox. A simple gating mechanism, in which an intermediate SQ mobile in the volume of the Q(o)-site is a necessary component, can readily account for the observed data through a coulombic interaction that prevents SQ anion from close approach to heme bL when the latter is reduced. This allows rapid and reversible QH2 oxidation, but prevents rapid bypass reactions. The mechanism is quite natural, and is well supported by experiments in which the role of a key residue, Glu-295, which facilitates proton transfer from the site through a rotational displacement, has been tested by mutation.

DNA-mediated association of two histone-bound complexes of yeast Chromatin Assembly Factor-1 (CAF-1) drives tetrasome assembly in the wake of DNA replication.

PubMed

Mattiroli, Francesca; Gu, Yajie; Yadav, Tejas; Balsbaugh, Jeremy L; Harris, Michael R; Findlay, Eileen S; Liu, Yang; Radebaugh, Catherine A; Stargell, Laurie A; Ahn, Natalie G; Whitehouse, Iestyn; Luger, Karolin

2017-03-18

Nucleosome assembly in the wake of DNA replication is a key process that regulates cell identity and survival. Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that associates with the replisome and orchestrates chromatin assembly following DNA synthesis. Little is known about the mechanism and structure of this key complex. Here we investigate the CAF-1•H3-H4 binding mode and the mechanism of nucleosome assembly. We show that yeast CAF-1 binding to a H3-H4 dimer activates the Cac1 winged helix domain interaction with DNA. This drives the formation of a transient CAF-1•histone•DNA intermediate containing two CAF-1 complexes, each associated with one H3-H4 dimer. Here, the (H3-H4) 2 tetramer is formed and deposited onto DNA. Our work elucidates the molecular mechanism for histone deposition by CAF-1, a reaction that has remained elusive for other histone chaperones, and it advances our understanding of how nucleosomes and their epigenetic information are maintained through DNA replication.

Interactions within the yeast t-SNARE Sso1p that control SNARE complex assembly.

PubMed

Munson, M; Chen, X; Cocina, A E; Schultz, S M; Hughson, F M

2000-10-01

In the eukaryotic secretory and endocytic pathways, transport vesicles shuttle cargo among intracellular organelles and to and from the plasma membrane. Cargo delivery entails fusion of the transport vesicle with its target, a process thought to be mediated by membrane bridging SNARE protein complexes. Temporal and spatial control of intracellular trafficking depends in part on regulating the assembly of these complexes. In vitro, SNARE assembly is inhibited by the closed conformation adopted by the syntaxin family of SNAREs. To visualize this closed conformation directly, the X-ray crystal structure of a yeast syntaxin, Sso1p, has been determined and refined to 2.1 A resolution. Mutants designed to destabilize the closed conformation exhibit accelerated rates of SNARE assembly. Our results provide insight into the mechanism of SNARE assembly and its intramolecular and intermolecular regulation.

Two Novel Hypovirulence-Associated Mycoviruses in the Phytopathogenic Fungus Botrytis cinerea: Molecular Characterization and Suppression of Infection Cushion Formation

PubMed Central

Hao, Fangmin; Ding, Ting; Wu, Mingde; Zhang, Jing; Yang, Long; Chen, Weidong; Li, Guoqing

2018-01-01

Botrytis cinerea is a necrotrophic fungus causing disease on many important agricultural crops. Two novel mycoviruses, namely Botrytis cinerea hypovirus 1 (BcHV1) and Botrytis cinerea fusarivirus 1 (BcFV1), were fully sequenced. The genome of BcHV1 is 10,214 nt long excluding a poly-A tail and possesses one large open reading frame (ORF) encoding a polyprotein possessing several conserved domains including RNA-dependent RNA polymerase (RdRp), showing homology to hypovirus-encoded polyproteins. Phylogenetic analysis indicated that BcHV1 may belong to the proposed genus Betahypovirus in the viral family Hypoviridae. The genome of BcFV1 is 8411 nt in length excluding the poly A tail and theoretically processes two major ORFs, namely ORF1 and ORF2. The larger ORF1 encoded polypeptide contains protein domains of an RdRp and a viral helicase, whereas the function of smaller ORF2 remains unknown. The BcFV1 was phylogenetically clustered with other fusariviruses forming an independent branch, indicating BcFV1 was a member in Fusariviridae. Both BcHV1 and BcFV1 were capable of being transmitted horizontally through hyphal anastomosis. Infection by BcHV1 alone caused attenuated virulence without affecting mycelial growth, significantly inhibited infection cushion (IC) formation, and altered expression of several IC-formation-associated genes. However, wound inoculation could fully rescue the virulence phenotype of the BcHV1 infected isolate. These results indicate the BcHV1-associated hypovirulence is caused by the viral influence on IC-formation-associated pathways. PMID:29757259

Enhanced light absorptivity of black carbon with air pollution development in urban Beijing, China

NASA Astrophysics Data System (ADS)

Zhang, Y.; Zhang, Q.; Cheng, Y.; Su, H.; He, K.

2017-12-01

The impacts of black carbon (BC) aerosols on air quality and climate are dependent on BC light absorptivity. However, the light absorptivity of ambient BC-containing particles remains conflicting. In this work, we investigated the evolution of BC light absorptivity with pollution development in urban Beijing, China. We found that the mass absorption cross-section (MAC) of ambient BC-containing particles measured during the campaign increased with BC mass concentration, which can be attributed to more coating materials on BC surface with pollution development. A single-particle soot photometer (SP2) measurement showed that the coating thickness (CT) of BC-containing particles increased by 48% with PM1 and BC mass concentration increasing from 10 μg m-3 and 0.3 μg m-3 to 230 μg m-3 and 12 μg m-3. Based on Mie calculation, the CT increase could led to light absorption enhancement (Eab) of BC-containing particles increasing by 22%, consistent with the increase of measured MAC. The relationship between growth rate of BC light absorptivity (kEab) and that of PM1 or rBC concentration (kPM1 or krBC) showed that kEab ≈ 4.8% kPM1 or kEab ≈ 2.5% krBC. The analysis of effective emission intensity (EEI) for BC revealed that the enhancement of BC light absorptivity with increasing pollution levels was dominated by regional transport. During the pollution period, 63% of BC over Beijing originated from regional sources. The aging of these regional BC during atmospheric transport controlled the increase of coating materials for BC-containing particles observed in Beijing. As a result of enhanced light absorptivity with pollution development, BC forcing efficiency could increase by 20% during polluted period. Our work identified the importance of BC on radiative forcing under polluted environment, which is determined by not only the increase of BC mass concentration, but also the enhancement of BC forcing efficiency due to more coating materials.

mTORC1 and CK2 coordinate ternary and eIF4F complex assembly

PubMed Central

Gandin, Valentina; Masvidal, Laia; Cargnello, Marie; Gyenis, Laszlo; McLaughlan, Shannon; Cai, Yutian; Tenkerian, Clara; Morita, Masahiro; Balanathan, Preetika; Jean-Jean, Olivier; Stambolic, Vuk; Trost, Matthias; Furic, Luc; Larose, Louise; Koromilas, Antonis E.; Asano, Katsura; Litchfield, David; Larsson, Ola; Topisirovic, Ivan

2016-01-01

Ternary complex (TC) and eIF4F complex assembly are the two major rate-limiting steps in translation initiation regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway, respectively. How TC and eIF4F assembly are coordinated, however, remains largely unknown. We show that mTOR suppresses translation of mRNAs activated under short-term stress wherein TC recycling is attenuated by eIF2α phosphorylation. During acute nutrient or growth factor stimulation, mTORC1 induces eIF2β phosphorylation and recruitment of NCK1 to eIF2, decreases eIF2α phosphorylation and bolsters TC recycling. Accordingly, eIF2β mediates the effect of mTORC1 on protein synthesis and proliferation. In addition, we demonstrate a formerly undocumented role for CK2 in regulation of translation initiation, whereby CK2 stimulates phosphorylation of eIF2β and simultaneously bolsters eIF4F complex assembly via the mTORC1/4E-BP pathway. These findings imply a previously unrecognized mode of translation regulation, whereby mTORC1 and CK2 coordinate TC and eIF4F complex assembly to stimulate cell proliferation. PMID:27040916

Lignin metabolism involves Botrytis cinerea BcGs1- induced defense response in tomato.

PubMed

Yang, Chenyu; Liang, Yingbo; Qiu, Dewen; Zeng, Hongmei; Yuan, Jingjing; Yang, Xiufen

2018-06-04

BcGs1, a cell wall-degrading enzyme (CWDE), was originally derived from Botrytis cinerea. Our previous study revealed that BcGs1 could trigger defense responses and protect plants against various pathogens. We researched the defense response mechanism underlying this BcGs1 elicitation in tomato. We revealed that the two domains were required for BcGs1's full necrosis activity. According to analysis and quantitative real-time PCR of the up-regulated proteins and genes filtered by iTRAQ-based quantitative proteome approach, oxidative metabolism and phenylpropanoid metabolism were speculated to be involved in BcGs1-triggered defense response in tomato. Furthermore, experimental evidence showed that BcGs1 triggered reactive oxygen species (ROS) burst and increased the level of phenylalanine-ammonia lyase (PAL) and peroxidase (POD) enzyme activity, as well as lignin accumulation. Moreover, histochemical analysis revealed that infiltration of BcGs1 in tomato leaves exhibited cell wall thickening compared with untreated plants. The results suggested that BcGs1 activated the basal defense response included lignin metabolism contributed to BcGs1-induced resistance to Botrytis. cinerea infection in tomato.

Genetic variants in ATM, H2AFX and MRE11 genes and susceptibility to breast cancer in the polish population.

PubMed

Podralska, Marta; Ziółkowska-Suchanek, Iwona; Żurawek, Magdalena; Dzikiewicz-Krawczyk, Agnieszka; Słomski, Ryszard; Nowak, Jerzy; Stembalska, Agnieszka; Pesz, Karolina; Mosor, Maria

2018-04-20

DNA damage repair is a complex process, which can trigger the development of cancer if disturbed. In this study, we hypothesize a role of variants in the ATM, H2AFX and MRE11 genes in determining breast cancer (BC) susceptibility. We examined the whole sequence of the ATM kinase domain and estimated the frequency of founder mutations in the ATM gene (c.5932G > T, c.6095G > A, and c.7630-2A > C) and single nucleotide polymorphisms (SNPs) in H2AFX (rs643788, rs8551, rs7759, and rs2509049) and MRE11 (rs1061956 and rs2155209) among 315 breast cancer patients and 515 controls. The analysis was performed using high-resolution melting for new variants and the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for recurrent ATM mutations. H2AFX and MRE11 polymorphisms were analyzed using TaqMan assays. The cumulative genetic risk scores (CGRS) were calculated using unweighted and weighted approaches. We identified four mutations (c.6067G > A, c.8314G > A, c.8187A > T, and c.6095G > A) in the ATM gene in three BC cases and two control subjects. We observed a statistically significant association of H2AFX variants with BC. Risk alleles (the G of rs7759 and the T of rs8551 and rs2509049) were observed more frequently in BC cases compared to the control group, with P values, odds ratios (OR) and 95% confidence intervals (CIs) of 0.0018, 1.47 (1.19 to 1.82); 0.018, 1.33 (1.09 to 1.64); and 0.024, 1.3 (1.06 to 1.59), respectively. Haplotype-based tests identified a significant association of the H2AFX CACT haplotype with BC (P <  0.0001, OR = 27.29, 95% CI 3.56 to 209.5). The risk of BC increased with the growing number of risk alleles. The OR (95% CI) for carriers of ≥ four risk alleles was 1.71 (1.11 to 2.62) for the CGRS. This study confirms that H2AFX variants are associated with an increased risk of BC. The above-reported sequence variants of MRE11 genes may not constitute a risk factor of breast cancer in the Polish population. The contribution of mutations detected in the ATM gene to the development of breast cancer needs further detailed study.

Light Absorption Enhancement of Black Carbon Aerosol Constrained by Particle Morphology.

PubMed

Wu, Yu; Cheng, Tianhai; Liu, Dantong; Allan, James D; Zheng, Lijuan; Chen, Hao

2018-06-19

The radiative forcing of black carbon aerosol (BC) is one of the largest sources of uncertainty in climate change assessments. Contrasting results of BC absorption enhancement ( E abs ) after aging are estimated by field measurements and modeling studies, causing ambiguous parametrizations of BC solar absorption in climate models. Here we quantify E abs using a theoretical model parametrized by the complex particle morphology of BC in different aging scales. We show that E abs continuously increases with aging and stabilizes with a maximum of ∼3.5, suggesting that previous seemingly contrast results of E abs can be explicitly described by BC aging with corresponding particle morphology. We also report that current climate models using Mie Core-Shell model may overestimate E abs at a certain aging stage with a rapid rise of E abs , which is commonly observed in the ambient. A correction coefficient for this overestimation is suggested to improve model predictions of BC climate impact.

Four unexpected lanthanide coordination polymers involving in situ reaction of solvent N, N-Dimethylformamide

NASA Astrophysics Data System (ADS)

Jin, Jun-Cheng; Tong, Wen-Quan; Fu, Ai-Yun; Xie, Cheng-Gen; Chang, Wen-Gui; Wu, Ju; Xu, Guang-Nian; Zhang, Ya-Nan; Li, Jun; Li, Yong; Yang, Peng-Qi

2015-05-01

Four unexpected 2D lanthanide coordination polymers have been synthesized through in situ reactions of DMF solvent under solvothermal conditions. The isostructural complexes 1-3 contain four types of 21 helical chains. While the Nd(III) ions are bridged through μ2-HIDC2- and oxalate to form a 2D sheet along the bc plane without helical character in 4. Therefore, complex 1 exhibits bright red solid-state phosphorescence upon exposure to UV radiation at room temperature.

Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly

PubMed Central

Cook, Jeremy D.; Kondapalli, Kalyan C.; Rawat, Swati; Childs, William C.; Murugesan, Yogapriya; Dancis, Andrew; Stemmler, Timothy L.

2010-01-01

Frataxin, a conserved nuclear encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich’s ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two: Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone n the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to better understand the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry (ITC). Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into a Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly. PMID:20815377

Molecular Details of the Yeast Frataxin-Isu1 Interaction during Mitochondrial Fe-S Cluster Assembly

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, J.; Kondapalli, K; Rawat, S

2010-01-01

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural modulemore » to improve our understanding of the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry. Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into an Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly.« less

Molecular details of the yeast frataxin-Isu1 interaction during mitochondrial Fe-S cluster assembly.

PubMed

Cook, Jeremy D; Kondapalli, Kalyan C; Rawat, Swati; Childs, William C; Murugesan, Yogapriya; Dancis, Andrew; Stemmler, Timothy L

2010-10-12

Frataxin, a conserved nuclear-encoded mitochondrial protein, plays a direct role in iron-sulfur cluster biosynthesis within the ISC assembly pathway. Humans with frataxin deficiency have Friedreich's ataxia, a neurodegenerative disorder characterized by mitochondrial iron overload and disruption in Fe-S cluster synthesis. Biochemical and genetic studies have shown frataxin interacts with the iron-sulfur cluster assembly scaffold protein (in yeast, there are two, Isu1 and Isu2), indicating frataxin plays a direct role in cluster assembly, possibly by serving as an iron chaperone in the assembly pathway. Here we provide molecular details of how yeast frataxin (Yfh1) interacts with Isu1 as a structural module to improve our understanding of the multiprotein complex assembly that completes Fe-S cluster assembly; this complex also includes the cysteine desulfurase (Nfs1 in yeast) and the accessory protein (Isd11), together in the mitochondria. Thermodynamic binding parameters for protein partner and iron binding were measured for the yeast orthologs using isothermal titration calorimetry. Nuclear magnetic resonance spectroscopy was used to provide the molecular details to understand how Yfh1 interacts with Isu1. X-ray absorption studies were used to electronically and structurally characterize how iron is transferred to Isu1 and then incorporated into an Fe-S cluster. These results were combined with previously published data to generate a structural model for how the Fe-S cluster protein assembly complex can come together to accomplish Fe-S cluster assembly.

Radiation Nanomedicine for EGFR-Positive Breast Cancer: Panitumumab-Modified Gold Nanoparticles Complexed to the β-Particle-Emitter, (177)Lu.

PubMed

Yook, Simmyung; Cai, Zhongli; Lu, Yijie; Winnik, Mitchell A; Pignol, Jean-Philippe; Reilly, Raymond M

2015-11-02

Our objective was to construct a novel radiation nanomedicine for treatment of breast cancer (BC) expressing epidermal growth factor receptors (EGFR), particularly triple-negative tumors (TNBC). Gold nanoparticles (AuNP; 30 nm) were modified with polyethylene glycol (PEG) chains (4 kDa) derivatized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators for complexing the β-emitter, (177)Lu and with PEG chains (5 kDa) linked to panitumumab for targeting BC cells expressing EGFR. The AuNP were further coated with PEG chains (2 kDa) to stabilize the particles to aggregation. The binding and internalization of EGFR-targeted AuNP ((177)Lu-T-AuNP) into BC cells was studied and compared to nontargeted (177)Lu-NT-AuNP. The cytotoxicity of (177)Lu-T-AuNP and (177)Lu-NT-AuNP was measured in clonogenic assays using BC cells with widely different EGFR densities: MDA-MB-468 (10(6) receptors/cell), MDA-MB-231 (10(5) receptors/cell), and MCF-7 cells (10(4) receptors/cell). Radiation absorbed doses to the cell nucleus of MDA-MB-468 cells were estimated based on subcellular distribution. Darkfield and fluorescence microscopy as well as radioligand binding assays revealed that (177)Lu-T-AuNP were specifically bound by BC cells dependent on their EGFR density whereas the binding and internalization of (177)Lu-NT-AuNP was significantly lower. The affinity of binding of (177)Lu-T-AuNP to MDA-MB-468 cells was reduced by 2-fold compared to (123)I-labeled panitumumab (KD = 1.3 ± 0.2 nM vs 0.7 ± 0.4 nM, respectively). The cytotoxicity of (177)Lu-T-AuNP was dependent on the amount of radioactivity incubated with BC cells, their EGFR density and the radiosensitivity of the cells. The clonogenic survival (CS) of MDA-MB-468 cells overexpressing EGFR was reduced to <0.001% at the highest amount of (177)Lu-T-AuNP tested (4.5 MBq; 6 × 10(11) AuNP per 2.5 × 10(4)-1.2 × 10(5) cells). (177)Lu-T-AuNP were less effective for killing MDA-MB-231 cells or MCF-7 cells with moderate or low EGFR density (CS = 33.8 ± 1.6% and 25.8 ± 1.2%, respectively). Because the β-particles emitted by (177)Lu have a 2 mm range, (177)Lu-NT-AuNP were also cytotoxic to BC cells due to a cross-fire effect but (177)Lu-T-AuNP were significantly more potent for killing MDA-MB-468 cells overexpressing EGFR than (177)Lu-NT-AuNP at all amounts tested. The cross-fire effect of the β-particles emitted by (177)Lu may be valuable for eradicating BC cells in tumors that have low or moderate EGFR expression or cells that are not targeted by (177)Lu-T-AuNP as a consequence of heterogeneous intratumoral distribution. The radiation dose to the nucleus of a single MDA-MB-468 cell was 73.2 ± 6.7 Gy, whereas (177)Lu-NT-AuNP delivered 5.6 ± 0.6 Gy. We conclude that (177)Lu-T-AuNP is a promising novel radiation nanomedicine with potential application for treatment of TNBC, in which EGFR are often overexpressed.

Production of Cow's Milk Free from Beta-Casein A1 and Its Application in the Manufacturing of Specialized Foods for Early Infant Nutrition.

PubMed

Duarte-Vázquez, Miguel Á; García-Ugalde, Carlos; Villegas-Gutiérrez, Laura M; García-Almendárez, Blanca E; Rosado, Jorge L

2017-07-12

Beta-casein (BC) is frequently expressed as BC A2 and BC A1 in cow's milk. Gastrointestinal digestion of BC A1 results in the release of the opioid peptide beta-casomorphin 7 (BCM7) which is less likely to occur from BC A2. This work was aimed to produce milk containing BC A2 with no BC A1 (BC A2 milk) using genetically selected CSN2 A2A2 Jersey cows. Additionally, we aimed to develop an infant formula (IF) suitable for healthy full-term infants during the first six months of life based on BC A2 milk. The concentration of BCM7 released from BC A2 IF, from commercially available IFs as well as from human milk and raw cow's milk was evaluated after simulated gastrointestinal digestion (SGID). BC A2 IF presented the lowest mean relative abundance of BC A1 (IF 1 = 0.136 ± 0.010), compared with three commercially available IFs (IF 2 = 0.597 ± 0.020; IF 3 = 0.441 ± 0.014; IF 4 = 0.503 ± 0.011). Accordingly, SGID of whole casein fraction from BC A2 IF resulted in a significantly lower release of BCM7 (IF 1 = 0.860 ± 0.014 µg/100 mL) compared to commercially available IFs (IF 2 = 2.625 ± 0.042 µg/100 mL; IF 3 = 1.693 ± 0.012 µg/100 mL; IF 4 = 1.962 ± 0.067 µg/100 mL). Nevertheless, BCM7 levels from BC A2 IF were significantly higher than those found in SGID hydrolysates of BC A2 raw milk (0.742 ± 0.008 µg/100 mL). Interestingly, results showed that BCM7 was also present in human milk in significantly lower amounts (0.697 ± 0.007 µg/100 mL) than those observed in IF 1 and BC A2 milk. This work demonstrates that using BC A2 milk in IF formulation significantly reduces BCM7 formation during SGID. Clinical implications of BC A2 IF on early infant health and development need further investigations.

Production of Cow’s Milk Free from Beta-Casein A1 and Its Application in the Manufacturing of Specialized Foods for Early Infant Nutrition

PubMed Central

Duarte-Vázquez, Miguel Á.; García-Ugalde, Carlos; Villegas-Gutiérrez, Laura M.; García-Almendárez, Blanca E.; Rosado, Jorge L.

2017-01-01

Beta-casein (BC) is frequently expressed as BC A2 and BC A1 in cow’s milk. Gastrointestinal digestion of BC A1 results in the release of the opioid peptide beta-casomorphin 7 (BCM7) which is less likely to occur from BC A2. This work was aimed to produce milk containing BC A2 with no BC A1 (BC A2 milk) using genetically selected CSN2 A2A2 Jersey cows. Additionally, we aimed to develop an infant formula (IF) suitable for healthy full-term infants during the first six months of life based on BC A2 milk. The concentration of BCM7 released from BC A2 IF, from commercially available IFs as well as from human milk and raw cow’s milk was evaluated after simulated gastrointestinal digestion (SGID). BC A2 IF presented the lowest mean relative abundance of BC A1 (IF 1 = 0.136 ± 0.010), compared with three commercially available IFs (IF 2 = 0.597 ± 0.020; IF 3 = 0.441 ± 0.014; IF 4 = 0.503 ± 0.011). Accordingly, SGID of whole casein fraction from BC A2 IF resulted in a significantly lower release of BCM7 (IF 1 = 0.860 ± 0.014 µg/100 mL) compared to commercially available IFs (IF 2 = 2.625 ± 0.042 µg/100 mL; IF 3 = 1.693 ± 0.012 µg/100 mL; IF 4 = 1.962 ± 0.067 µg/100 mL). Nevertheless, BCM7 levels from BC A2 IF were significantly higher than those found in SGID hydrolysates of BC A2 raw milk (0.742 ± 0.008 µg/100 mL). Interestingly, results showed that BCM7 was also present in human milk in significantly lower amounts (0.697 ± 0.007 µg/100 mL) than those observed in IF 1 and BC A2 milk. This work demonstrates that using BC A2 milk in IF formulation significantly reduces BCM7 formation during SGID. Clinical implications of BC A2 IF on early infant health and development need further investigations. PMID:28704923

Changes in Fire-Derived Soil Black Carbon Storage in a Sub-humid Woodland

NASA Astrophysics Data System (ADS)

White, J. D.; Yao, J.; Murray, D. B.; Hockaday, W. C.

2014-12-01

Fire-derived black carbon (BC) in soil, including charcoal, represents a potentially important fraction of terrestrial carbon cycling due to its presumed long persistence in soil. Interpretation of site BC retention is important for assessing feedbacks to ecosystem processes including nutrient and water cycling. However, interaction between vegetation disturbance, BC formation, and off site transport may exist that complicate interpretation of BC addition to soils from wildfire or prescribed burns directly. To investigate the relationship between disturbance and site retention on soil BC, we determined BC concentrations for a woodland in central Texas, USA, from study plots in hilly terrain with a fire scar dendrochronology spanning 100 years. BC values were determined from 13C nuclear magnetic resonance (NMR) spectroscopy. Estimated values showed mean BC concentration of 2.73 ± 3.06 g BC kg-1 (0.91 ± 0.51 kg BC m-2) for sites with fire occurrence within the last 40 years compared with BC values of1.21 ± 1.70 g BC kg-1 soil (0.18 ± 0.14 kg BC m-2) for sites with fire 40 - 100 years ago. Sites with no tree ring evidence of fire during the last 100 years had the lowest mean soil BC concentration of 0.05 ± 0.11 g BC kg-1 (0.02 ± 0.03 kg BC m-2). Molecular proxies of stability (lignin/N) and decomposition (Alkyl C/O-Alky C) showed no differences across the sites, indicating that low potential for BC mineralization. Modeled soil erosion and time since fire from fire scar data showed that soil BC concentrations were inversely correlated. A modified the ecosystem process model, Biome-BGC, was also used simulate the effects of fire disturbance with different severities and seasonality on C cycling related to the BC production, effect on soil water availability, and off-site transport. Results showed that BC impacts on ecosystem processes, including net ecosystem exchange and leaf area development, were predominantly related to fire frequency. Site BC loss rates were affected by initial slope-affected erosion, fire severity, vegetation type, and rate of vegetation recovery. The simulation results showed that fire types, such as high severity, was generally associated with low site BC retention related to low vertical transfer of BC into soils, buoyancy of BC particles, and surface runoff from unvegetated soils.

Formation of RNA Granule-Derived Capsid Assembly Intermediates Appears To Be Conserved between Human Immunodeficiency Virus Type 1 and the Nonprimate Lentivirus Feline Immunodeficiency Virus.

PubMed

Reed, Jonathan C; Westergreen, Nick; Barajas, Brook C; Ressler, Dylan T B; Phuong, Daryl J; Swain, John V; Lingappa, Vishwanath R; Lingappa, Jaisri R

2018-05-01

During immature capsid assembly in cells, human immunodeficiency virus type 1 (HIV-1) Gag co-opts a host RNA granule, forming a pathway of intracellular assembly intermediates containing host components, including two cellular facilitators of assembly, ABCE1 and DDX6. A similar assembly pathway has been observed for other primate lentiviruses. Here we asked whether feline immunodeficiency virus (FIV), a nonprimate lentivirus, also forms RNA granule-derived capsid assembly intermediates. First, we showed that the released FIV immature capsid and a large FIV Gag-containing intracellular complex are unstable during analysis, unlike for HIV-1. We identified harvest conditions, including in situ cross-linking, that overcame this problem, revealing a series of FIV Gag-containing complexes corresponding in size to HIV-1 assembly intermediates. Previously, we showed that assembly-defective HIV-1 Gag mutants are arrested at specific assembly intermediates; here we identified four assembly-defective FIV Gag mutants, including three not previously studied, and demonstrated that they appear to be arrested at the same intermediate as the cognate HIV-1 mutants. Further evidence that these FIV Gag-containing complexes correspond to assembly intermediates came from coimmunoprecipitations demonstrating that endogenous ABCE1 and the RNA granule protein DDX6 are associated with FIV Gag, as shown previously for HIV-1 Gag, but are not associated with a ribosomal protein, at steady state. Additionally, we showed that FIV Gag associates with another RNA granule protein, DCP2. Finally, we validated the FIV Gag-ABCE1 and FIV Gag-DCP2 interactions with proximity ligation assays demonstrating colocalization in situ Together, these data support a model in which primate and nonprimate lentiviruses form intracellular capsid assembly intermediates derived from nontranslating host RNA granules. IMPORTANCE Like HIV-1 Gag, FIV Gag assembles into immature capsids; however, it is not known whether FIV Gag progresses through a pathway of immature capsid assembly intermediates derived from host RNA granules, as shown for HIV-1 Gag. Here we showed that FIV Gag forms complexes that resemble HIV-1 capsid assembly intermediates in size and in their association with ABCE1 and DDX6, two host facilitators of HIV-1 immature capsid assembly that are found in HIV-1 assembly intermediates. Our studies also showed that known and novel assembly-defective FIV Gag mutants fail to progress past putative intermediates in a pattern resembling that observed for HIV-1 Gag mutants. Finally, we used imaging to demonstrate colocalization of FIV Gag with ABCE1 and with the RNA granule protein DCP2. Thus, we conclude that formation of assembly intermediates derived from host RNA granules is likely conserved between primate and nonprimate lentiviruses and could provide targets for future antiviral strategies. Copyright © 2018 American Society for Microbiology.

Black carbon, a 'hidden' player in the global C cycle

NASA Astrophysics Data System (ADS)

Santín, C.; Doerr, S. H.

2012-04-01

During the 2011 alone more than 600 scientific papers about black carbon (BC) were published, half of them dealing with soils (ISI Web of Knowledge, accessed 15/01/2012). If the search is extended to the other terms by which BC is commonly named (i.e. biochar, charcoal, pyrogenic C or soot), the number of 2011 publications increases to >2400, 20% of them also related to soils. These figures confirm BC as a well-known feature in the scientific literature and, thus, in our research community. In fact, there is a wide variety of research topics where BC is currently studied: from its potential as long-term C reservoir in soils (man-made biochar), to its effects on the Earth's radiation balance (soot-BC), including its value as indicator in paleoenvironmental studies (charcoal) or, even surprisingly, its use in suicide attempts. BC is thus relevant to many aspects of our environment, making it a very far-reaching, but also very complex topic. When focusing 'only' on the role of BC in the global C cycle, numerous questions arise. For example: (i) how much BC is produced by different sources (i.e. vegetation fires, fossil fuel and biofuel combustion); (ii) what are the main BC forms and their respective proportions generated (i.e. proportion of atmospheric BC [BC-soot] and the solid residues [char-BC]); (iii) where does this BC go (i.e. main mobilization pathways and sinks); (iv) how long does BC stay in the different systems (i.e. residence times in soils, sediments, water and atmosphere); (v) which are the BC stocks and its main transformations within and between the different systems (i.e. BC preservation, alteration and mineralization); (vi) what is the interaction of BC with other elements and how does this influence BC half-life (i.e. physical protection, interaction with pollutants, priming effects in other organic materials)? These questions, and some suggestions about how to tackle these, will be discussed in this contribution. It will focus in particular on the role of black carbon within soil system sciences, but will also consider it from an integrated atmosphere-marine-terrestrial perspective.

Flux, Budget and Sources of Black Carbon (BC) in the Continental Shelf of the Bohai and Yellow Seas, China

NASA Astrophysics Data System (ADS)

Fang, Y.; Chen, Y.; Tian, C.

2015-12-01

Black carbon (BC) derived from incomplete combustion of fossil fuels and biomass has received increasing attention due to their potential importance in a wide range of biogeochemical processes. China has been generally considered as the world's largest BC emitter. Due to a combination of the prevailing East Asia monsoon and large amounts of riverine outflow, BC released from China can be transported to the adjacent continental shelf seas, the Bohai Sea (BS) and Yellow Sea (YS). Based on measurements of BC in 191 surface sediments, 36 riverine water, and 2 seawater samples, as well as the reported BC data set of the aerosol samples in the Bohai Rim, the concentration, flux, and budget of BC in the BS and YS were investigated. The spatial distribution of the BC concentration in surface sediments was largely influenced by the regional hydrodynamic conditions, with high values mainly occurring in the central mud areas. The BC burial flux in the BS and YS ranged from 4 to 1100 μg/cm2/yr, and averaged 166 ± 200 μg/cm2/yr. The area-integrated sedimentary BC sink flux in the entire BS and YS was ~325 Gg/yr. The BC budget calculated in the BS showed that atmospheric deposition and riverine discharge played comparable importance in delivering BC to the BS, and sequestration to bottom sediments was the major BC output pattern, accounting for ~88% of the total input BC. Besides, we attempted to apportion the BC sources in the BS and YS surface sediments using PAHs (organic molecular proxies cogenerated with BC) and BC as an input data to the Positive Matrix Factorization (PMF) receptor model. Results showed that ~83% of the sediment BC was attributed to the combustion of fossil fuels, and the remaining ~17% was from biomass burning. Due to the differences in their production mechanisms and therefore physicochemical properties, the above distinction and quantification would help us better understand their different environmental behaviors in the complex continental shelf regimes.

Evaluation of cotton leaf curl virus resistance in BC1, BC2, and BC3 progenies from an interspecific cross between Gossypium arboreum and Gossypium hirsutum.

PubMed

Nazeer, Wajad; Tipu, Abdul Latif; Ahmad, Saghir; Mahmood, Khalid; Mahmood, Abid; Zhou, Baoliang

2014-01-01

Cotton leaf curl virus disease (CLCuD) is an important constraint to cotton production. The resistance of G. arboreum to this devastating disease is well documented. In the present investigation, we explored the possibility of transferring genes for resistance to CLCuD from G. arboreum (2n = 26) cv 15-Mollisoni into G. hirsutum (2n = 52) cv CRSM-38 through conventional breeding. We investigated the cytology of the BC1 to BC3 progenies of direct and reciprocal crosses of G. arboreum and G. hirsutum and evaluated their resistance to CLCuD. The F1 progenies were completely resistant to this disease, while a decrease in resistance was observed in all backcross generations. As backcrossing progressed, the disease incidence increased in BC1 (1.7-2.0%), BC2 (1.8-4.0%), and BC3 (4.2-7.0%). However, the disease incidence was much lower than that of the check variety CIM-496, with a CLCuD incidence of 96%. Additionally, the disease incidence percentage was lower in the direct cross 2(G. arboreum)×G. hirsutum than in that of G. hirsutum×G. arboreum. Phenotypic resemblance of BC1 ∼BC3 progenies to G. arboreum confirmed the success of cross between the two species. Cytological studies of CLCuD-resistant plants revealed that the frequency of univalents and multivalents was high in BC1, with sterile or partially fertile plants, but low in BC2 (in both combinations), with shy bearing plants. In BC3, most of the plants exhibited normal bearing ability due to the high frequency of chromosome associations (bivalents). The assessment of CLCuD through grafting showed that the BC1 to BC3 progenies were highly resistant to this disease. Thus, this study successfully demonstrates the possibility of introgressing CLCuD resistance genes from G. arboreum to G. hirsutum.

New archaeomagnetic data from three roman kilns in northeast Spain: a contribution to the Iberian palaeosecular variation curve

NASA Astrophysics Data System (ADS)

Beamud, E.; Gómez-Paccard, M.; McIntosh, G.; Larrasoaña, J. C.

2012-04-01

New archaeomagnetic results from three kilns recovered from a roman age archaeological site in Badalona (northeast Spain) are reported. Archaeological evidences constrain the abandonment of kilns BC1 and BC2 between 0 and 50 yrs AD, whereas the abandonment of kiln BC3 is established between 50 and 150 yrs AD. In order to perform the archaeomagnetic study 12 to 14 samples per kiln were collected using a portable electrical drill with a water-cooled diamond bit, following standard palaeomagnetic sampling methods. Samples were distributed all around the combustion chambers, being obtained in different orientations from the burnt walls and central pillars. Rock magnetic measurements revealed a dominance of low titanium titanomagnetite or substituted magnetite as the main carrier of the magnetic signal and a minor contribution of maghemite. The presence of single domain material, along with the thermal stability of the samples, means that they are suitable candidates for archaeomagnetic studies, and in particular intensity determinations. Archaeomagnetic experiments were attempted on 32 specimens characterised by NRM intensities between 0.5 and 8.3 A/m. Mean archaeomagnetic directions and archaeointensities have been obtained from the original Thellier method with regular partial thermoremanent magnetisation (pTRM) checks being used to estimate archaeointensities. Mean intensities of 68.3 ± 4.2 µT, 72.4 ± 5.0 µT and 72.9 ± 3.7 µT were obtained for kilns BC1, BC2 and BC3, respectively. A cooling rate correction factor of 5% has been applied to mean intensities and the values obtained have been relocated to Paris and Madrid through the virtual dipole moment VDM. The mean directions of the characteristic magnetization of each kiln and their associated statistical parameters were derived from principal component analysis and Fisher statistics. Very similar directions were obtained for BC1 and BC2 with the circle of confidence (α95) of the BC2 direction falling within that of BC1. This is in agreement with archaeological evidence that proposed the same age interval for the abandonment of kilns BC1 and BC2. On the contrary, there is only a small overlapping between the circles of confidence of BC1-BC2 and the BC3 circle of confidence. Moreover, the inclination obtained for the mean BC3 direction is lower than those obtained for kilns BC1-BC2, suggesting that kiln BC3 was abandoned latter than kilns BC1 and BC2. This is in agreement with archaeological evidence that proposed that kiln BC3 was abandoned about 60 years later than kilns BC1 and BC2. The new data are also consistent with previous archaeomagnetic data for the Iberian Peninsula. They add to and improve the description of palaeosecular variation during Roman times in Iberia.

Bio-Inspired Assembly of Artificial Photosynthetic Antenna Complexes for Development of Nanobiodevices

DTIC Science & Technology

2011-06-24

extensively studied by ultrafast laser spectroscopy. More recently the structures of the LH2 complexes has revealed the nonameric and octameric arrangement of...Scheme 1). 4 Scheme 1. Compartimentalization of light harvesting and charge separation. The antenna complexes( LH2 ,LH1-RC) efficiently...realize various photosynthetic functions using cofactors (BChl a and carotenoid) assembled into the apoproteins (LH1 and LH2 ). The light-harvesting

Cdt1p, through its interaction with Mcm6p, is required for the formation, nuclear accumulation and chromatin loading of the MCM complex.

PubMed

Wu, Rentian; Wang, Jiafeng; Liang, Chun

2012-01-01

Regulation of DNA replication initiation is essential for the faithful inheritance of genetic information. Replication initiation is a multi-step process involving many factors including ORC, Cdt1p, Mcm2-7p and other proteins that bind to replication origins to form a pre-replicative complex (pre-RC). As a prerequisite for pre-RC assembly, Cdt1p and the Mcm2-7p heterohexameric complex accumulate in the nucleus in G1 phase in an interdependent manner in budding yeast. However, the nature of this interdependence is not clear, nor is it known whether Cdt1p is required for the assembly of the MCM complex. In this study, we provide the first evidence that Cdt1p, through its interaction with Mcm6p with the C-terminal regions of the two proteins, is crucial for the formation of the MCM complex in both the cytoplasm and nucleoplasm. We demonstrate that disruption of the interaction between Cdt1p and Mcm6p prevents the formation of the MCM complex, excludes Mcm2-7p from the nucleus, and inhibits pre-RC assembly and DNA replication. Our findings suggest a function for Cdt1p in promoting the assembly of the MCM complex and maintaining its integrity by interacting with Mcm6p.

Gene expression patterns combined with network analysis identify hub genes associated with bladder cancer.

PubMed

Bi, Dongbin; Ning, Hao; Liu, Shuai; Que, Xinxiang; Ding, Kejia

2015-06-01

To explore molecular mechanisms of bladder cancer (BC), network strategy was used to find biomarkers for early detection and diagnosis. The differentially expressed genes (DEGs) between bladder carcinoma patients and normal subjects were screened using empirical Bayes method of the linear models for microarray data package. Co-expression networks were constructed by differentially co-expressed genes and links. Regulatory impact factors (RIF) metric was used to identify critical transcription factors (TFs). The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and clusters were obtained through molecular complex detection (MCODE) algorithm. Centralities analyses for complex networks were performed based on degree, stress and betweenness. Enrichment analyses were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Co-expression networks and TFs (based on expression data of global DEGs and DEGs in different stages and grades) were identified. Hub genes of complex networks, such as UBE2C, ACTA2, FABP4, CKS2, FN1 and TOP2A, were also obtained according to analysis of degree. In gene enrichment analyses of global DEGs, cell adhesion, proteinaceous extracellular matrix and extracellular matrix structural constituent were top three GO terms. ECM-receptor interaction, focal adhesion, and cell cycle were significant pathways. Our results provide some potential underlying biomarkers of BC. However, further validation is required and deep studies are needed to elucidate the pathogenesis of BC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural and immunochemical relatedness suggests a conserved pathogenicity motif for secondary cell wall polysaccharides in Bacillus anthracis and infection-associated Bacillus cereus

PubMed Central

Saile, Elke; Klee, Silke R.; Hoffmaster, Alex; Kannenberg, Elmar L.

2017-01-01

Bacillus anthracis (Ba) and human infection-associated Bacillus cereus (Bc) strains Bc G9241 and Bc 03BB87 have secondary cell wall polysaccharides (SCWPs) comprising an aminoglycosyl trisaccharide repeat: →4)-β-d-ManpNAc-(1→4)-β-d-GlcpNAc-(1→6)-α-d-GlcpNAc-(1→, substituted at GlcNAc residues with both α- and β-Galp. In Bc G9241 and Bc 03BB87, an additional α-Galp is attached to O-3 of ManNAc. Using NMR spectroscopy, mass spectrometry and immunochemical methods, we compared these structures to SCWPs from Bc biovar anthracis strains isolated from great apes displaying “anthrax-like” symptoms in Cameroon (Bc CA) and Côte d’Ivoire (Bc CI). The SCWPs of Bc CA/CI contained the identical HexNAc trisaccharide backbone and Gal modifications found in Ba, together with the α-Gal-(1→3) substitution observed previously at ManNAc residues only in Bc G9241/03BB87. Interestingly, the great ape derived strains displayed a unique α-Gal-(1→3)-α-Gal-(1→3) disaccharide substitution at some ManNAc residues, a modification not found in any previously examined Ba or Bc strain. Immuno-analysis with specific polyclonal anti-Ba SCWP antiserum demonstrated a reactivity hierarchy: high reactivity with SCWPs from Ba 7702 and Ba Sterne 34F2, and Bc G9241 and Bc 03BB87; intermediate reactivity with SCWPs from Bc CI/CA; and low reactivity with the SCWPs from structurally distinct Ba CDC684 (a unique strain producing an SCWP lacking all Gal substitutions) and non-infection-associated Bc ATCC10987 and Bc 14579 SCWPs. Ba-specific monoclonal antibody EAII-6G6-2-3 demonstrated a 10–20 fold reduced reactivity to Bc G9241 and Bc 03BB87 SCWPs compared to Ba 7702/34F2, and low/undetectable reactivity to SCWPs from Bc CI, Bc CA, Ba CDC684, and non-infection-associated Bc strains. Our data indicate that the HexNAc motif is conserved among infection-associated Ba and Bc isolates (regardless of human or great ape origin), and that the number, positions and structures of Gal substitutions confer unique antigenic properties. The conservation of this structural motif could open a new diagnostic route in detection of pathogenic Bc strains. PMID:28832613

Structural and immunochemical relatedness suggests a conserved pathogenicity motif for secondary cell wall polysaccharides in Bacillus anthracis and infection-associated Bacillus cereus.

PubMed

Kamal, Nazia; Ganguly, Jhuma; Saile, Elke; Klee, Silke R; Hoffmaster, Alex; Carlson, Russell W; Forsberg, Lennart S; Kannenberg, Elmar L; Quinn, Conrad P

2017-01-01

Bacillus anthracis (Ba) and human infection-associated Bacillus cereus (Bc) strains Bc G9241 and Bc 03BB87 have secondary cell wall polysaccharides (SCWPs) comprising an aminoglycosyl trisaccharide repeat: →4)-β-d-ManpNAc-(1→4)-β-d-GlcpNAc-(1→6)-α-d-GlcpNAc-(1→, substituted at GlcNAc residues with both α- and β-Galp. In Bc G9241 and Bc 03BB87, an additional α-Galp is attached to O-3 of ManNAc. Using NMR spectroscopy, mass spectrometry and immunochemical methods, we compared these structures to SCWPs from Bc biovar anthracis strains isolated from great apes displaying "anthrax-like" symptoms in Cameroon (Bc CA) and Côte d'Ivoire (Bc CI). The SCWPs of Bc CA/CI contained the identical HexNAc trisaccharide backbone and Gal modifications found in Ba, together with the α-Gal-(1→3) substitution observed previously at ManNAc residues only in Bc G9241/03BB87. Interestingly, the great ape derived strains displayed a unique α-Gal-(1→3)-α-Gal-(1→3) disaccharide substitution at some ManNAc residues, a modification not found in any previously examined Ba or Bc strain. Immuno-analysis with specific polyclonal anti-Ba SCWP antiserum demonstrated a reactivity hierarchy: high reactivity with SCWPs from Ba 7702 and Ba Sterne 34F2, and Bc G9241 and Bc 03BB87; intermediate reactivity with SCWPs from Bc CI/CA; and low reactivity with the SCWPs from structurally distinct Ba CDC684 (a unique strain producing an SCWP lacking all Gal substitutions) and non-infection-associated Bc ATCC10987 and Bc 14579 SCWPs. Ba-specific monoclonal antibody EAII-6G6-2-3 demonstrated a 10-20 fold reduced reactivity to Bc G9241 and Bc 03BB87 SCWPs compared to Ba 7702/34F2, and low/undetectable reactivity to SCWPs from Bc CI, Bc CA, Ba CDC684, and non-infection-associated Bc strains. Our data indicate that the HexNAc motif is conserved among infection-associated Ba and Bc isolates (regardless of human or great ape origin), and that the number, positions and structures of Gal substitutions confer unique antigenic properties. The conservation of this structural motif could open a new diagnostic route in detection of pathogenic Bc strains.

Rocket launcher mechanism of collaborative actin assembly defined by single-molecule imaging.

PubMed

Breitsprecher, Dennis; Jaiswal, Richa; Bombardier, Jeffrey P; Gould, Christopher J; Gelles, Jeff; Goode, Bruce L

2012-06-01

Interacting sets of actin assembly factors work together in cells, but the underlying mechanisms have remained obscure. We used triple-color single-molecule fluorescence microscopy to image the tumor suppressor adenomatous polyposis coli (APC) and the formin mDia1 during filament assembly. Complexes consisting of APC, mDia1, and actin monomers initiated actin filament formation, overcoming inhibition by capping protein and profilin. Upon filament polymerization, the complexes separated, with mDia1 moving processively on growing barbed ends while APC remained at the site of nucleation. Thus, the two assembly factors directly interact to initiate filament assembly and then separate but retain independent associations with either end of the growing filament.

Rocket launcher mechanism of collaborative actin assembly defined by single-molecule imaging

PubMed Central

Breitsprecher, Dennis; Jaiswal, Richa; Bombardier, Jeffrey P.; Gould, Christopher J.; Gelles, Jeff; Goode, Bruce L.

2013-01-01

Interacting sets of actin assembly factors work together in cells, but the underlying mechanisms have remained obscure. We used triple-color single molecule fluorescence microscopy to image the tumor-suppressor Adenomateous polyposis coli (APC) and the formin mDia1 during filament assembly. Complexes consisting of APC, mDia1, and actin monomers intiated actin filament formation, overcoming inhibition by capping protein and profilin. Upon filament polymerization, the complexes separated, with mDia1 moving processively on growing barbed ends while APC remained at the site of nucleation. Thus, the two assembly factors directly interact to initiate filament assembly, and then separate but retain independent associations with either end of the growing filament. PMID:22654058

[Inheritance of bc1 gene in intersubspecific hybrids of rice (Oryza sativa L.)].

PubMed

Lü, Chuan-Gen; Zong, Shou-Yu; Zhao, Ling; Qi, Qing-Ming; Zou, Jiang-Shi; Ikehashi, Hiroshi

2004-10-01

Distorted segregation of the brittle culm-1 gene (bc1) on rice chromosome 3 was found with greatly increased or decreased frequency of bc1 bc1 genotype in inter-subspecific hybrids, although the gene normally transmitted to its offspring following the Mendelian Law in intra-subspecific hybrids. In a combination of Kamairazu//Ketan Nangka/Kamairazu,an increased frequency of bc1 bc1 in F1, normal segregation in F2, and increased and decreased frequency in a few F3 and F4 lines were observed. In a cross of IR36/Kamairazu, decreased frequency in F2, both normal and decreased segregations in F3 and F4, and a few lines of increased ratio in F4 were found. In F2 of Ketan Nangka/IR36//Kamairazu, increased and decreased and normal segregations were all observed. There was no significant correlation between the frequency of bc1 bc1 and pollen fertility. It implied that distorted segregation of bc1 was caused by selective fertilization of male gametes, which were governed by gametophyte genes of ga2, ga3 and ga14 on chromosome 3.

A murine retrovirus co-Opts YB-1, a translational regulator and stress granule-associated protein, to facilitate virus assembly.

PubMed

Bann, Darrin V; Beyer, Andrea R; Parent, Leslie J

2014-04-01

The Gag protein of the murine retrovirus mouse mammary tumor virus (MMTV) orchestrates the assembly of immature virus particles in the cytoplasm which are subsequently transported to the plasma membrane for release from the cell. The morphogenetic pathway of MMTV assembly is similar to that of Saccharomyces cerevisiae retrotransposons Ty1 and Ty3, which assemble virus-like particles (VLPs) in intracytoplasmic ribonucleoprotein (RNP) complexes. Assembly of Ty1 and Ty3 VLPs depends upon cellular mRNA processing factors, prompting us to examine whether MMTV utilizes a similar set of host proteins to facilitate viral capsid assembly. Our data revealed that MMTV Gag colocalized with YB-1, a translational regulator found in stress granules and P bodies, in intracytoplasmic foci. The association of MMTV Gag and YB-1 in cytoplasmic granules was not disrupted by cycloheximide treatment, suggesting that these sites were not typical stress granules. However, the association of MMTV Gag and YB-1 was RNA dependent, and an MMTV RNA reporter construct colocalized with Gag and YB-1 in cytoplasmic RNP complexes. Knockdown of YB-1 resulted in a significant decrease in MMTV particle production, indicating that YB-1 plays a role in MMTV capsid formation. Analysis by live-cell imaging with fluorescence recovery after photobleaching (FRAP) revealed that the population of Gag proteins localized within YB-1 complexes was relatively immobile, suggesting that Gag forms stable complexes in association with YB-1. Together, our data imply that the formation of intracytoplasmic Gag-RNA complexes is facilitated by YB-1, which promotes MMTV virus assembly. Cellular mRNA processing factors regulate the posttranscriptional fates of mRNAs, affecting localization and utilization of mRNAs under normal conditions and in response to stress. RNA viruses such as retroviruses interact with cellular mRNA processing factors that accumulate in ribonucleoprotein complexes known as P bodies and stress granules. This report shows for the first time that mouse mammary tumor virus (MMTV), a mammalian retrovirus that assembles intracytoplasmic virus particles, commandeers the cellular factor YB-1, a key regulator of translation involved in the cellular stress response. YB-1 is essential for the efficient production of MMTV particles, a process directed by the viral Gag protein. We found that Gag and YB-1 localize together in cytoplasmic granules. Functional studies of Gag/YB-1 granules suggest that they may be sites where virus particles assemble. These studies provide significant insights into the interplay between mRNA processing factors and retroviruses.

Silylene extrusion from organosilanes via double geminal Si-H bond activation by a Cp*Ru(kappa2-P,N)+ complex: observation of a key stoichiometric step in the glaser-tilley alkene hydrosilylation mechanism.

PubMed

Rankin, Matthew A; MacLean, Darren F; Schatte, Gabriele; McDonald, Robert; Stradiotto, Mark

2007-12-26

Treatment of Cp*RuCl(kappa2-P,N-2b) (2b = 2-NMe2-3-PiPr2-indene) with TlSO3CF3 produced the cyclometalated complex [4]+SO3CF3- in 94% isolated yield. Exposure of [4]+X- (X = B(C6F5)4 or SO3CF3) to Ph2SiH2 (10 equiv) or PhSiH3 afforded the corresponding [Cp*(mu-P,N-2b)(H)2Ru=SiRPh]+X- complexes, [5]+X- (R = Ph; X = B(C6F5)4, 82%; X = SO3CF3, 39%) and [6]+X- (R = H; X = B(C6F5)4, 94%; X = SO3CF3, 95%). Notably, these transformations represent the first documented examples of Ru-mediated silylene extrusion via double geminal Si-H bond activation of an organosilane-a key step in the recently proposed Glaser-Tilley (G-T) alkene hydrosilylation mechanism. Treatment of [5]+B(C6F5)4- with KN(SiMe3)2 or [6]+SO3CF3- with NaN(SiMe3)2 afforded the corresponding zwitterionic Cp*(mu-2-NMe2-3-PiPr2-indenide)(H)2Ru=SiRPh complex in 69% (R = Ph, 7) or 86% (R = H, 8) isolated yield. Both [6]+X- and 8 proved unreactive toward 1-hexene and styrene and provided negligible catalytic turnover in the attempted metal-mediated hydrosilylation of these substrates with PhSiH3, thereby providing further empirical evidence for the required intermediacy of base-free Ru=Si species in the G-T mechanism. Isomerization of the P,N-indene ligand backbone in [6]+X-, giving rise to [Cp*(mu-1-PiPr2-2-NMe2-indene)(H)2Ru=SiHPh]+X- ([9]+X-), was observed. In the case of [9]+SO3CF3-, net intramolecular addition of the Ru=Si-H group across the styrene-like C=C unit within the ligand backbone to give 10 (96% isolated yield) was observed. Crystallographic characterization data are provided for [4]+X-, [5]+X-, [6]+X-, 8, and 10.

On the role of the chaperonin CCT in the just-in-time assembly process of APC/CCdc20.

PubMed

Dekker, Carien

2010-02-05

The just-in-time hypothesis relates to the assembly of large multi-protein complexes and their regulation of activation in the cell. Here I postulate that chaperonins may contribute to the timely assembly and activation of such complexes. For the case of anaphase promoting complex/cyclosome(Cdc20) assembly by the eukaryotic chaperonin chaperonin containing Tcp1 it is shown that just-in-time synthesis and chaperone-assisted folding can synergise to generate a highly regulated assembly process of a protein complex that is vital for cell cycle progression. Once dependency has been established transcriptional regulation and chaperonin-dependency may have co-evolved to safeguard the timely activation of important multi-protein complexes. 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Fatigue Investigation of the E-2B/C Nose Landing Gear

DTIC Science & Technology

1975-12-31

Specimen - Outer Cylinder and Caster Barrel 9 3 E-2B NLG Test Specimen - Drag Brace 10 4 E-2B NLG Drag Brace Attachment Lugs Modification . . 11 5...Attachment Lug Fracture Surface . . 23 ■■■■ ? 16 Tow Link Modification 30 17 Tow Link #2 Failur 31 18 Tow Link #2 Fracture Face 32 19...34-" ’’- .-.„.,.,„...^ ,.., M1| lf^^~i*>-^^-^^ "u- II li ’ 7«™.™»«*" ■ NADC-75369-30 Bach «hock «true assembly consist« of the «xle- caster barrel, outer cylinder

Short-term exposure to traffic-related air pollution and daily mortality in London, UK.

PubMed

Atkinson, Richard W; Analitis, Antonis; Samoli, Evangelia; Fuller, Gary W; Green, David C; Mudway, Ian S; Anderson, Hugh R; Kelly, Frank J

2016-01-01

Epidemiological studies have linked daily concentrations of urban air pollution to mortality, but few have investigated specific traffic sources that can inform abatement policies. We assembled a database of >100 daily, measured and modelled pollutant concentrations characterizing air pollution in London between 2011 and 2012. Based on the analyses of temporal patterns and correlations between the metrics, knowledge of local emission sources and reference to the existing literature, we selected, a priori, markers of traffic pollution: oxides of nitrogen (general traffic); elemental and black carbon (EC/BC) (diesel exhaust); carbon monoxide (petrol exhaust); copper (tyre), zinc (brake) and aluminium (mineral dust). Poisson regression accounting for seasonality and meteorology was used to estimate the percentage change in risk of death associated with an interquartile increment of each pollutant. Associations were generally small with confidence intervals that spanned 0% and tended to be negative for cardiovascular mortality and positive for respiratory mortality. The strongest positive associations were for EC and BC adjusted for particle mass and respiratory mortality, 2.66% (95% confidence interval: 0.11, 5.28) and 2.72% (0.09, 5.42) per 0.8 and 1.0 μg/m(3), respectively. These associations were robust to adjustment for other traffic metrics and regional pollutants, suggesting a degree of specificity with respiratory mortality and diesel exhaust containing EC/BC.

Down-regulation of Homer1b/c protects against chemically induced seizures through inhibition of mTOR signaling.

PubMed

Cao, Lei; Tian, Ye; Jiang, Yi; Zhang, Ge-Juan; Lei, Hui; Di, Zheng-Li

2015-01-01

Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. Reducing Homer1b/c expression has been shown in previous studies to be protective against excitotoxic insults, implicating Homer1b/c in the physiological regulation of aberrant neuronal excitability. To test the efficacy of a Homer1b/c reducing therapy for disorders with a detrimental hyperexcitability profile in mice, we used small interfere RNA (siRNA) to decrease endogenous Homer1b/c expression in mouse hippocampus. The baseline motor and cognitive behavior was measured by sensorimotor tests, Morris water maze and elevated plus maze tasks. The anti-epileptic effects of Homer1b/c knockdown were determined in two chemically induced seizure models induced by Picrotoxin (PTX) or pentylenetetrazole (PTZ) administration. The results of sensorimotor tests, Morris water maze and elevated plus maze tasks showed that Homer1b/c reduction had no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced Homerb/c protein had less severe seizures than control mice. Total Homer1b/c protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of Homer1b/c. In addition, the phosphorylation of mammalian target of rapamycin (mTOR) and its target protein S6 was significantly inhibited in Homer1b/c down-regulated mice. Homer1b/c knockdown-induced inhibition of mTOR pathway was partially ablated by the metabotropic glutamate receptor 5 (mGluR5) agonist CHPG. Our results demonstrate that endogenous Homer1b/c is integral for regulating neuronal hyperexcitability in adult animals and suggest that reduction of Homer1b/c could protect against chemically induced seizures through inhibition mTOR pathway. © 2015 S. Karger AG, Basel.

--No Title--

Science.gov Websites

/ARW1 : IC/BC from 6-h old GFS Alaska ARW2 : IC from current NAM, BC from 6-h old NAM CONUS NMMB/ARW1 : IC from current RAP, BC from 6-h old GFS CONUS ARW2 ; IC from current NAM, BC from 6-h old NAM Hawaii NMMB/ARW1: IC/BC from 6-h old GFS Hawaii ARW2 : IC from current NAM, BC from 6-h old NAM Puerto Rico

Screening for bovine leukocyte adhesion deficiency, deficiency of uridine monophosphate synthase, complex vertebral malformation, bovine citrullinaemia, and factor XI deficiency in Holstein cows reared in Turkey.

PubMed

Meydan, Hasan; Yildiz, Mehmet A; Agerholm, Jørgen S

2010-10-07

Bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), complex vertebral malformation (CVM), bovine citrullinaemia (BC) and factor XI deficiency (FXID) are autosomal recessive hereditary disorders, which have had significant economic impact on dairy cattle breeding worldwide. In this study, 350 Holstein cows reared in Turkey were screened for BLAD, DUMPS, CVM, BC and FXID genotypes to obtain an indication on the importance of these defects in Turkish Holsteins. Genomic DNA was obtained from blood and the amplicons of BLAD, DUMPS, CVM, BC and FXID were obtained by using PCR. PCR products were digested with TaqI, AvaI and AvaII restriction enzymes for BLAD, DUMPS, and BC, respectively. These digested products and PCR product of FXID were analyzed by agarose gel electrophoresis stained with ethidium bromide. CVM genotypes were detected by DNA sequencing. Additionally, all genotypes were confirmed by DNA sequencing to determine whether there was a mutant allele or not. Fourteen BLAD, twelve CVM and four FXID carriers were found among the 350 Holstein cows examined, while carriers of DUMPS and BC were not detected. The mutant allele frequencies were calculated as 0.02, 0.017, and 0.006 for BLAD, CVM and FXID, respectively with corresponding carrier prevalence of 4.0% (BLAD), 3.4% (CVM) and 1.2% (FXID). This study demonstrates that carriers of BLAD, CVM and FXID are present in the Turkish Holstein population, although at a low frequency. The actual number of clinical cases is unknown, but sporadic cases may appear. As artificial insemination is widely used in dairy cattle breeding, carriers of BLAD, CVM and FXID are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population.

Screening for bovine leukocyte adhesion deficiency, deficiency of uridine monophosphate synthase, complex vertebral malformation, bovine citrullinaemia, and factor XI deficiency in Holstein cows reared in Turkey

PubMed Central

2010-01-01

Background Bovine leukocyte adhesion deficiency (BLAD), deficiency of uridine monophosphate synthase (DUMPS), complex vertebral malformation (CVM), bovine citrullinaemia (BC) and factor XI deficiency (FXID) are autosomal recessive hereditary disorders, which have had significant economic impact on dairy cattle breeding worldwide. In this study, 350 Holstein cows reared in Turkey were screened for BLAD, DUMPS, CVM, BC and FXID genotypes to obtain an indication on the importance of these defects in Turkish Holsteins. Methods Genomic DNA was obtained from blood and the amplicons of BLAD, DUMPS, CVM, BC and FXID were obtained by using PCR. PCR products were digested with TaqI, AvaI and AvaII restriction enzymes for BLAD, DUMPS, and BC, respectively. These digested products and PCR product of FXID were analyzed by agarose gel electrophoresis stained with ethidium bromide. CVM genotypes were detected by DNA sequencing. Additionally, all genotypes were confirmed by DNA sequencing to determine whether there was a mutant allele or not. Results Fourteen BLAD, twelve CVM and four FXID carriers were found among the 350 Holstein cows examined, while carriers of DUMPS and BC were not detected. The mutant allele frequencies were calculated as 0.02, 0.017, and 0.006 for BLAD, CVM and FXID, respectively with corresponding carrier prevalence of 4.0% (BLAD), 3.4% (CVM) and 1.2% (FXID). Conclusion This study demonstrates that carriers of BLAD, CVM and FXID are present in the Turkish Holstein population, although at a low frequency. The actual number of clinical cases is unknown, but sporadic cases may appear. As artificial insemination is widely used in dairy cattle breeding, carriers of BLAD, CVM and FXID are likely present within the population of breeding sires. It is recommended to screen breeding sires for these defective genes in order to avoid an unwanted spread within the population. PMID:20929557

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.

PubMed

Cervelli, Manuela; Bellavia, Gabriella; Fratini, Emiliano; Amendola, Roberto; Polticelli, Fabio; Barba, Marco; Federico, Rodolfo; Signore, Fabrizio; Gucciardo, Giacomo; Grillo, Rosalba; Woster, Patrick M; Casero, Robert A; Mariottini, Paolo

2010-10-14

Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

PubMed Central

2010-01-01

Background Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. Methods BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Results Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. Conclusions This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials. PMID:20946629

Abi1 is essential for the formation and activation of a WAVE2 signalling complex.

PubMed

Innocenti, Metello; Zucconi, Adriana; Disanza, Andrea; Frittoli, Emanuela; Areces, Liliana B; Steffen, Anika; Stradal, Theresia E B; Di Fiore, Pier Paolo; Carlier, Marie-France; Scita, Giorgio

2004-04-01

WAVE2 belongs to a family of proteins that mediates actin reorganization by relaying signals from Rac to the Arp2/3 complex, resulting in lamellipodia protrusion. WAVE2 displays Arp2/3-dependent actin nucleation activity in vitro, and does not bind directly to Rac. Instead, it forms macromolecular complexes that have been reported to exert both positive and negative modes of regulation. How these complexes are assembled, localized and activated in vivo remains to be established. Here we use tandem mass spectrometry to identify an Abi1-based complex containing WAVE2, Nap1 (Nck-associated protein) and PIR121. Abi1 interacts directly with the WHD domain of WAVE2, increases WAVE2 actin polymerization activity and mediates the assembly of a WAVE2-Abi1-Nap1-PIR121 complex. The WAVE2-Abi1-Nap1-PIR121 complex is as active as the WAVE2-Abi1 sub-complex in stimulating Arp2/3, and after Rac activation it is re-localized to the leading edge of ruffles in vivo. Consistently, inhibition of Abi1 by RNA interference (RNAi) abrogates Rac-dependent lamellipodia protrusion. Thus, Abi1 orchestrates the proper assembly of the WAVE2 complex and mediates its activation at the leading edge in vivo.

Regulatory BC1 RNA in Cognitive Control

ERIC Educational Resources Information Center

Iacoangeli, Anna; Dosunmu, Aderemi; Eom, Taesun; Stefanov, Dimitre G.; Tiedge, Henri

2017-01-01

Dendritic regulatory BC1 RNA is a non-protein-coding (npc) RNA that operates in the translational control of gene expression. The absence of BC1 RNA in BC1 knockout (KO) animals causes translational dysregulation that entails neuronal phenotypic alterations including prolonged epileptiform discharges, audiogenic seizure activity in vivo, and…

Assembly of Photosynthetic Antenna Protein / Pigments Complexes from Algae and Plants for Development of Nanobiodevices

DTIC Science & Technology

2012-07-10

recently the structures of the LH2 complexes has revealed the nonameric and octameric arrangement of repeating units consisting of two apoproteins and...Compartimentalization of light -harvesting and charge separation. The antenna complexes( LH2 ,LH1-RC) efficiently realize various photosynthetic functions using...cofactors (BChl a and carotenoid) assembled into the apoproteins (LH1 and LH2 ). The light-harvesting mechanisms in these light-harvesting complexes have

Sources and burial fluxes of soot black carbon in sediments on the Mackenzie, Chukchi, and Bering Shelves

NASA Astrophysics Data System (ADS)

Yang, Weifeng; Guo, Laodong

2018-03-01

Black carbon (BC) has been recognized as a climate forcing and a major component in the global carbon budget. However, studies on BC in the Arctic Ocean remain scarce. We report here variations in the abundance, sources and burial fluxes of sedimentary soot black carbon (soot-BC) in the western Arctic Ocean. The soot-BC contents averaged 1.6 ± 0.3, 0.46 ± 0.04 and 0.56 ± 0.10 mg-C g-1 on the Mackenzie, Chukchi and Bering Shelves, respectively, accounting for 16.6%, 10.2% and 10.4% of the total organic carbon in surface sediment. Temporally, contents of soot-BC remained fairly stable before 1910, but increased rapidly after the 1970s on the Mackenzie Shelf, indicating enhanced source input related to warming. Comparable δ13C signatures of soot-BC (- 24.95‰ to - 24.57‰) to C3 plants pointed to a major biomass source of soot-BC to the Beaufort Sea. Soot-BC showed similar temporal patterns with large fluctuations in the Chukchi/Bering shelf regions, implying the same source terms for soot-BC in these areas. Two events with elevated soot-BC corresponded to a simultaneous increase in biomass combustion and fossil fuel (coal and oil) consumption in Asia. The similar temporal variability in sedimentary soot-BC between the Arctic shelves and Asian lakes and the comparable δ13C values manifested that anthropogenic emission from East Asia was an important source of soot-BC in the western Arctic and subarctic regions. The burial fluxes of soot-BC, estimated from both 137Cs- and 210Pb-derived sedimentation rates, were 2.43 ± 0.42 g-C m-2 yr-1 on the Mackenzie Shelf, representing an efficient soot-BC sink. Soot-BC showed an increase in buried fluxes from 0.56 ± 0.02 g-C m-2 yr-1 during 1963-1986 to 0.88 ± 0.05 g-C m-2 yr-1 after 1986 on the Chukchi Shelf, and from 1.00 ± 0.18 g-C m-2 yr-1 to 2.58 ± 1.70 g-C m-2 yr-1 on the Bering Shelf, which were consistent with recent anthropogenically enhanced BC input observed especially in Asia. Overall, the three Arctic shelves could bury more than 3000 Gg soot-BC each year, attesting to an important role of the Arctic and subarctic shelves in global BC budget and carbon cycle.

The crystal structure of the Rv0301-Rv0300 VapBC-3 toxin-antitoxin complex from M. tuberculosis reveals a Mg 2+ ion in the active site and a putative RNA-binding site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Min, Andrew B; Miallau, Linda; Sawaya, Michael R

VapBC pairs account for 45 out of 88 identified toxin-antitoxin (TA) pairs in the Mycobacterium tuberculosis (Mtb) H37Rv genome. A working model suggests that under times of stress, antitoxin molecules are degraded, releasing the toxins to slow the metabolism of the cell, which in the case of VapC toxins is via their RNase activity. Otherwise the TA pairs remain bound to their promoters, autoinhibiting transcription. The crystal structure of Rv0301-Rv0300, an Mtb VapBC TA complex determined at 1.49 Å resolution, suggests a mechanism for these three functions: RNase activity, its inhibition by antitoxin, and its ability to bind promoter DNA.more » The Rv0301 toxin consists of a core of five parallel beta strands flanked by alpha helices. Three proximal aspartates coordinate a Mg2+ ion forming the putative RNase active site. The Rv0300 antitoxin monomer is extended in structure, consisting of an N-terminal beta strand followed by four helices. The last two helices wrap around the toxin and terminate near the putative RNase active site, but with different conformations. In one conformation, the C-terminal arginine interferes with Mg2+ ion coordination, suggesting a mechanism by which the antitoxin can inhibit toxin activity. At the N-terminus of the antitoxin, two pairs of Ribbon-Helix-Helix (RHH) motifs are related by crystallographic twofold symmetry. The resulting hetero-octameric complex is similar to the FitAB system, but the two RHH motifs are about 30 Å closer together in the Rv0301-Rv0300 complex, suggesting either a different span of the DNA recognition sequence or a conformational change.« less

Identification of a novel mitochondrial complex I assembly factor ACDH-12 in Caenorhabditis elegans.

PubMed

Chuaijit, Sirithip; Boonyatistan, Worawit; Boonchuay, Pichsinee; Metheetrairut, Chanatip; Suthammarak, Wichit

2018-03-11

Assembly of complex I of the mitochondrial respiratory chain (MRC) requires not only structural subunits for electron transport, but also assembly factors. In the nematode Caenorhabditis elegans, NUAF-1 and NUAF-3 are the only two assembly factors that have been characterized. In this study, we identify ACDH-12 as an assembly factor of the respiratory complex I. We demonstrate for the first time that a deficiency of ACDH-12 affects the formation and function of complex I. RNAi knockdown of acdh-12 also shortens lifespan and decreases fecundity. Although ACDH-12 has long been recognized as a very long-chain acyl-CoA dehydrogenase (VLCAD), the knockdown nematodes did not exhibit any change in body fat content. We suggested that in Caenorhabditis elegans, ACDH-12 is required for the assembly of the respiratory complex I, but may not be crucial to fatty acid oxidation. Interestingly, sequence analysis shows high homology between ACDH-12 and the human ACAD9, a protein that has initially been identified as a VLCAD, but later found to also be involved in the assembly of complex I in human. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

P-wave excited {B}_{c}^{* * } meson photoproduction at the LHeC

NASA Astrophysics Data System (ADS)

Kai, He; Huan-Yu, Bi; Ren-You, Zhang; Xiao-Zhou, Li; Wen-Gan, Ma

2018-05-01

As an important sequential work of the S-wave {B}c(* ) ({}1{S}0({}3{S}1) ) meson production at the large hadron electron collider (LHeC), we investigate the production of the P-wave excited {B}c* * states (1 P 1 and 3 P J with J = 0, 1, 2) via photoproduction mechanism within the framework of nonrelativistic QCD at the LHeC. Generally, the {e}-+P\\to γ +g\\to {B}c* * +b+\\bar{c} process is considered as the main production mechanism at an electron–proton collider due to the large luminosity of the gluon. However, according to our experience on the S-wave {B}c(* ) meson production at the LHeC, the extrinsic production mechanism, i.e., {e}-+P\\to γ +c\\to {B}c* * +b and {e}-+P\\to γ +\\bar{b} \\to {B}c* * +\\bar{c}, could also provide dominating contributions at low p T region. A careful treatment between these channels is performed and the results on total and differential cross sections, together with main uncertainties are discussed. Taking the quark masses m b = 4.90 ± 0.40 GeV and m c = 1.50 ± 0.20 GeV into account and summing up all the production channels, we expect to accumulate ({2.48}-1.75+3.55)× {10}4 {B}c* * ({}1{P}1), ({1.14}-0.82+1.49)× {10}4 {B}c* * ({}3{P}0),({2.38}-1.74+3.39)× {10}4 {B}c* * ({}3{P}1) and ({5.59}-3.93+7.84)× {10}4 {B}c* * ({}3{P}2) events at the \\sqrt{S}=1.30 {{T}}{{e}}{{V}} LHeC in one operation year with luminosity { \\mathcal L }={10}33 cm‑2 s‑1. With such sizable events, it is worth studying the properties of excited P-wave {B}c* * states at the LHeC.

BcXYG1, a Secreted Xyloglucanase from Botrytis cinerea, Triggers Both Cell Death and Plant Immune Responses.

PubMed

Zhu, Wenjun; Ronen, Mordechi; Gur, Yonatan; Minz-Dub, Anna; Masrati, Gal; Ben-Tal, Nir; Savidor, Alon; Sharon, Itai; Eizner, Elad; Valerius, Oliver; Braus, Gerhard H; Bowler, Kyle; Bar-Peled, Maor; Sharon, Amir

2017-09-01

In search of Botrytis cinerea cell death-inducing proteins, we found a xyloglucanase (BcXYG1) that induced strong necrosis and a resistance response in dicot plants. Expression of the BcXYG1 gene was strongly induced during the first 12 h post inoculation, and analysis of disease dynamics using PathTrack showed that a B. cinerea strain overexpressing BcXYG1 produced early local necrosis, supporting a role of BcXYG1 as an early cell death-inducing factor. The xyloglucanase activity of BcXYG1 was not necessary for the induction of necrosis and plant resistance, as a mutant of BcXYG1 lacking the xyloglucanase enzymatic activity retained both functions. Residues in two exposed loops on the surface of BcXYG1 were found to be necessary for the induction of cell death but not to induce plant resistance. Further analyses showed that BcXYG1 is apoplastic and possibly interacts with the proteins of the plant cell membrane and also that the BcXYG1 cell death-promoting signal is mediated by the leucine-rich repeat receptor-like kinases BAK1 and SOBIR1. Our findings support the role of cell death-inducing proteins in establishing the infection of necrotrophic pathogens and highlight the recognition of fungal apoplastic proteins by the plant immune system as an important mechanism of resistance against this class of pathogens. © 2017 American Society of Plant Biologists. All Rights Reserved.

Structural Study of the RIPoptosome Core Reveals a Helical Assembly for Kinase Recruitment

PubMed Central

2015-01-01

Receptor interaction protein kinase 1 (RIP1) is a molecular cell-fate switch. RIP1, together with Fas-associated protein with death domain (FADD) and caspase-8, forms the RIPoptosome that activates apoptosis. RIP1 also associates with RIP3 to form the necrosome that triggers necroptosis. The RIPoptosome assembles through interactions between the death domains (DDs) of RIP1 and FADD and between death effector domains (DEDs) of FADD and caspase-8. In this study, we analyzed the overall structure of the RIP1 DD/FADD DD complex, the core of the RIPoptosome, by negative-stain electron microscopy and modeling. The results show that RIP1 DD and FADD DD form a stable complex in vitro similar to the previously described Fas DD/FADD DD complex, suggesting that the RIPoptosome and the Fas death-inducing signaling complex share a common assembly mechanism. Both complexes adopt a helical conformation that requires type I, II, and III interactions between the death domains. PMID:25119434

Molecular requirements for RNA-induced silencing complex assembly in the Drosophila RNA interference pathway.

PubMed

Pham, John W; Sontheimer, Erik J

2005-11-25

Complexes in the Drosophila RNA-induced silencing complex (RISC) assembly pathway can be resolved using native gel electrophoresis, revealing an initiator called R1, an intermediate called R2, and an effector called R3 (now referred to as holo-RISC). Here we show that R1 forms when the Dicer-2/R2D2 heterodimer binds short interfering RNA (siRNA) duplexes. The heterodimer alone can initiate RISC assembly, indicating that other factors are dispensable for initiation. During assembly, R2 requires Argonaute 2 to convert into holo-RISC. This requirement is reminiscent of the RISC-loading complex, which also requires Argonaute 2 for assembly into RISC. We have compared R2 to the RISC-loading complex and show that the two complexes are similar in their sensitivities to ATP and to chemical modifications on siRNA duplexes, indicating that they are likely to be identical. We have examined the requirements for RISC formation and show that the siRNA 5'-termini are repeatedly monitored during RISC assembly, first by the Dcr-2/R2D2 heterodimer and again after R2 formation, before siRNA unwinding. The 2'-position of the 5'-terminal nucleotide also affects RISC assembly, because an siRNA strand bearing a 2'-deoxyribose at this position can inhibit the cognate strand from entering holo-RISC; in contrast, the 2'-deoxyribose-modified strand has enhanced activity in the RNA interference pathway.

Genome characterization of a breeding line derived from a cross between Oryza sativa and Oryza rufipogon.

PubMed

Keong, B P; Harikrishna, J A

2012-02-01

A preliminary screening was conducted on BC3F1 and BC4F1 backcross families developed from crossing Oryza sativa (MR219) and O. rufipogon (IRGC105491). Despite earlier results showing that O. rufipogon alleles (wild introgression) contributed to both number of panicles (qPPL-2) and tillers (qTPL-2) at loci RM250, RM208, and RM48 in line A20 of the BC2F2 population, we observed that wild introgression was lost at loci RM250 and RM208 but retained at locus RM48 in BC3F1 and BC4F1. Progeny tests conducted utilizing genotype and phenotype data on both BC4F1 and a reference population, BC2F7 (A20 line), did not show significant differences between groups having the MR219 allele and wild introgression at locus RM48. This suggests that there is no additive and transgressive effect of wild introgression in the BC3F1 and BC4F1 generated. The presence of wild introgression was largely due to gene contamination by cross-pollination during field breeding practices.

X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3

PubMed Central

Olcese, Chiara; Patel, Mitali P.; Shoemark, Amelia; Kiviluoto, Santeri; Legendre, Marie; Williams, Hywel J.; Vaughan, Cara K.; Hayward, Jane; Goldenberg, Alice; Emes, Richard D.; Munye, Mustafa M.; Dyer, Laura; Cahill, Thomas; Bevillard, Jeremy; Gehrig, Corinne; Guipponi, Michel; Chantot, Sandra; Duquesnoy, Philippe; Thomas, Lucie; Jeanson, Ludovic; Copin, Bruno; Tamalet, Aline; Thauvin-Robinet, Christel; Papon, Jean- François; Garin, Antoine; Pin, Isabelle; Vera, Gabriella; Aurora, Paul; Fassad, Mahmoud R.; Jenkins, Lucy; Boustred, Christopher; Cullup, Thomas; Dixon, Mellisa; Onoufriadis, Alexandros; Bush, Andrew; Chung, Eddie M. K.; Antonarakis, Stylianos E.; Loebinger, Michael R.; Wilson, Robert; Armengot, Miguel; Escudier, Estelle; Hogg, Claire; Al-Turki, Saeed; Anderson, Carl; Antony, Dinu; Barroso, Inês; Beales, Philip L.; Bentham, Jamie; Bhattacharya, Shoumo; Carss, Keren; Chatterjee, Krishna; Cirak, Sebahattin; Cosgrove, Catherine; Allan, Daly; Durbin, Richard; Fitzpatrick, David; Floyd, Jamie; Foley, A. Reghan; Franklin, Chris; Futema, Marta; Humphries, Steve E.; Hurles, Matt; McCarthy, Shane; Muddyman, Dawn; Muntoni, Francesco; Parker, Victoria; Payne, Felicity; Plagnol, Vincent; Raymond, Lucy; Savage, David B.; Scambler, Peter J.; Schmidts, Miriam; Semple, Robert; Serra, Eva; Stalker, Jim; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Walter, Klaudia; Amselem, Serge; Sun, Zhaoxia; Bartoloni, Lucia; Blouin, Jean-Louis; Mitchison, Hannah M.

2017-01-01

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2–DNAAF4–HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins. PMID:28176794

X-linked primary ciliary dyskinesia due to mutations in the cytoplasmic axonemal dynein assembly factor PIH1D3.

PubMed

Olcese, Chiara; Patel, Mitali P; Shoemark, Amelia; Kiviluoto, Santeri; Legendre, Marie; Williams, Hywel J; Vaughan, Cara K; Hayward, Jane; Goldenberg, Alice; Emes, Richard D; Munye, Mustafa M; Dyer, Laura; Cahill, Thomas; Bevillard, Jeremy; Gehrig, Corinne; Guipponi, Michel; Chantot, Sandra; Duquesnoy, Philippe; Thomas, Lucie; Jeanson, Ludovic; Copin, Bruno; Tamalet, Aline; Thauvin-Robinet, Christel; Papon, Jean-François; Garin, Antoine; Pin, Isabelle; Vera, Gabriella; Aurora, Paul; Fassad, Mahmoud R; Jenkins, Lucy; Boustred, Christopher; Cullup, Thomas; Dixon, Mellisa; Onoufriadis, Alexandros; Bush, Andrew; Chung, Eddie M K; Antonarakis, Stylianos E; Loebinger, Michael R; Wilson, Robert; Armengot, Miguel; Escudier, Estelle; Hogg, Claire; Amselem, Serge; Sun, Zhaoxia; Bartoloni, Lucia; Blouin, Jean-Louis; Mitchison, Hannah M

2017-02-08

By moving essential body fluids and molecules, motile cilia and flagella govern respiratory mucociliary clearance, laterality determination and the transport of gametes and cerebrospinal fluid. Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder frequently caused by non-assembly of dynein arm motors into cilia and flagella axonemes. Before their import into cilia and flagella, multi-subunit axonemal dynein arms are thought to be stabilized and pre-assembled in the cytoplasm through a DNAAF2-DNAAF4-HSP90 complex akin to the HSP90 co-chaperone R2TP complex. Here, we demonstrate that large genomic deletions as well as point mutations involving PIH1D3 are responsible for an X-linked form of PCD causing disruption of early axonemal dynein assembly. We propose that PIH1D3, a protein that emerges as a new player of the cytoplasmic pre-assembly pathway, is part of a complementary conserved R2TP-like HSP90 co-chaperone complex, the loss of which affects assembly of a subset of inner arm dyneins.

Knockdown of synaptic scaffolding protein Homer 1b/c attenuates secondary hyperalgesia induced by complete Freund's adjuvant in rats.

PubMed

Yao, Yong-Xing; Jiang, Zhen; Zhao, Zhi-Qi

2011-12-01

Previous studies have demonstrated that Homer 1b/c, a postsynaptic molecular scaffolding protein that binds and clusters metabotropic glutamate receptors at neuronal synapses, has an important role in the metabotropic glutamate receptor signaling process. In the current study, we investigated the possible involvement of Homer 1b/c in secondary hyperalgesia induced by complete Freund's adjuvant (CFA). Chronic inflammation was induced by injecting CFA into the left hind ankle of Wistar rats. Homer 1b/c antisense or missense oligonucleotides were intrathecally administrated (antisense, 10 μg/10 μL, 5 μg/10 μL, or 2.5 μg/10 μL, once a day; missense, 10 μg/10 μL) from 5 to 8 days after the onset of inflammation. The withdrawal threshold and withdrawal latency to mechanical or thermal stimuli were determined before and after the intrathecal administration. The expression and distribution of Homer 1b/c were examined in the spinal cord using immunological techniques. Mechanical allodynia and thermal hyperalgesia were induced within 24 hours and maintained for >2 weeks after the CFA injection. The expression of Homer 1b/c reached the highest level 7 days after inflammation and returned to baseline at day 28. Intrathecal administration of Homer 1b/c antisense oligonucleotides markedly reduced the expression of Homer 1b/c protein in the spinal cord. Additionally, administration of Homer 1b/c antisense oligonucleotides attenuated secondary mechanical hypersensitization on days 2 to 5 and reduced thermal hypersensitization on days 3 to 4. There were no effects of missense oligonucleotides on hypersensitization and the expression of Homer 1b/c. In the naïve rats, Homer 1b/c antisense oligonucleotides did not affect the mechanical and thermal responses or locomotor activity. These novel results demonstrate that Homer 1b/c in the spinal cord contributes to the maintenance of secondary hyperalgesia induced by CFA and suggest that Homer 1b/c may be a novel target for pain therapy.

Historical record of black carbon in urban soils and its environmental implications.

PubMed

He, Yue; Zhang, Gan-Lin

2009-10-01

Energy use in urbanization has fundamentally changed the pattern and fluxes of carbon cycling, which has global and local environmental impacts. Here we have investigated organic carbon (OC) and black carbon (BC) in six soil profiles from two contrast zones in an ancient city (Nanjing) in China. BC in soils was widely variable, from 0.22 to 32.19 g kg(-1). Its average concentration in an ancient residential area (Zone 1) was, 0.91 g kg(-1), whereas in Zone 2, an industrial and commercial area, the figure was 8.62 g kg(-1). The ratio of BC/OC ranged from 0.06 to 1.29 in soil profiles, with an average of 0.29. The vertical distribution of BC in soil is suggested to reflect the history of BC formation from burning of biomass and/or fossil fuel. BC in the surface layer of soils was mainly from traffic emission (especially from diesel vehicles). In contrast, in cultural layers BC was formed from historical coal use. The contents of BC and the ratio of BC/OC may reflect different human activities and pollution sources in the contrasting urban zones. In addition, the significant correlation of heavy metals (Cu, Pb, and Zn) with BC contents in some culture layers suggests the sorption of the metals by BC or their coexistence resulted from the coal-involved smelting.

Tissue kallikrein protects neurons from hypoxia/reoxygenation-induced cell injury through Homer1b/c.

PubMed

Su, Jingjing; Tang, Yuping; Zhou, Houguang; Liu, Ling; Dong, Qiang

2012-11-01

Previous studies have demonstrated that human tissue kallikrein (TK) gene delivery protects against mouse cerebral ischemia/reperfusion (I/R) injury through bradykinin B2 receptor (B2R) activation. We have also reported that exogenous TK administration can suppress glutamate- or acidosis-induced neurotoxicity through the extracellular signal-regulated kinase1/2 (ERK1/2) pathway. To further explore the neuroprotection mechanisms of TK, in the present study we performed immunoprecipitation analysis and identified a scaffolding protein Homer1b/c using MALDI-TOF MS analysis. Here, we tested the hypothesis that TK reduces cell injury induced by oxygen and glucose deprivation/reoxygenation (OGD/R) through activating Homer1b/c. We found that TK increased the expression of Homer1b/c in a concentration- and time-dependent manner. Moreover, TK facilitated the translocation of Homer1b/c to the plasma membrane under OGD/R condition by confocal microscope assays. We also observed that overexpression of Homer1b/c showed the neuroprotection against OGD/R-induced cell injury by enhancing cell survival, reducing LDH release, caspase-3 activity and cell apoptosis. However, the knockdown of Homer1b/c by small interfering RNA showed the opposite effects, indicating that Homer1b/c had protective effects against OGD/R-induced neuronal injury. More interestingly, TK exerted its much more significantly neuroprotective effects after Homer1b/c overexpression, whereas it exerted its reduced effects after Homer1b/c knockdown. In addition, TK pretreatment increased the phosphorylation of the ERK1/2 and Akt-GSK3β through Homer1b/c activation. The beneficial effects of Homer1b/c were abolished by the ERK1/2 or PI3K antagonist. Therefore, we propose novel signaling mechanisms involved in the anti-hypoxic function of TK through activation of Homer1b/c-ERK1/2 and Homer1b/c-PI3K-Akt signaling pathways. Copyright © 2012 Elsevier Inc. All rights reserved.

Natural oxidation of a temperature series of biochars: opposite effect on the sorption of aromatic cationic herbicides.

PubMed

Shi, Kaishun; Xie, Ya; Qiu, Yuping

2015-04-01

The natural oxidation of biochar in the environment has been widely observed. However, its influence on the sorption of organic contaminants remains poorly understood. In the present study, a series of wood-based biochars prepared between 300 and 600°C (referred to as BC300-BC600) was abiotically incubated for one year to examine the aging effect of the temperature series of biochars on their sorption of aromatic cationic herbicides (ACHs, paraquat and diquat) as well as a nonpolar reference adsorbate (naphthalene). One year of oxidation showed no obvious effect on the surface area, but distinct increases in the O/C elemental ratio, density of the surface groups and cation exchange capacity (CEC) were observed. Therefore, these properties were significantly affected by the charring temperature. After incubation, high-temperature biochars (BC500 and BC600) displayed a 14.1-36.3% decrease in the sorption (qm) of ACHs. The alteration of their sorption tendency was similar to the reduced sorption of naphthalene on oxidized biochars, in which the increased surface groups lowered the surface area accessible to adsorbates because of blockage by adsorbed water molecule clusters. Conversely, a pronounced increase of ACHs sorption by 121.7-201.1% on the low-temperature biochar (BC300) was observed, presumably due to the increase of CEC values after oxidation. This result was further demonstrated by a significant linear relationship between the paraquat sorption (qm) and CEC values (R(2)=0.9895) of oxidized biochars. Interestingly, one year of oxidation simultaneously resulted in an enhanced sorption of paraquat and a reduced sorption of diquat on BC400, which indicated that the oxidation-induced sorption change of ACHs is a complex function of changes in the surface properties of the biochars as well as the molecular structure of the solute. Copyright © 2015 Elsevier Inc. All rights reserved.

Macroscopic behavior and microscopic magnetic properties of nanocarbon

NASA Astrophysics Data System (ADS)

Lähderanta, E.; Ryzhov, V. A.; Lashkul, A. V.; Galimov, D. M.; Titkov, A. N.; Matveev, V. V.; Mokeev, M. V.; Kurbakov, A. I.; Lisunov, K. G.

2015-06-01

Here are presented investigations of powder and glass-like samples containing carbon nanoparticles, not intentionally doped and doped with Ag, Au and Co. The neutron diffraction study reveals an amorphous structure of the samples doped with Au and Co, as well as the magnetic scattering due to a long-range FM order in the Co-doped sample. The composition and molecular structure of the sample doped with Au is clarified with the NMR investigations. The temperature dependence of the magnetization, M (T), exhibits large irreversibility in low fields of B=1-7 mT. M (B) saturates already above 2 T at high temperatures, but deviates from the saturation behavior below 50 (150 K). Magnetic hysteresis is observed already at 300 K and exhibits a power-law temperature decay of the coercive field, Bc (T). The macroscopic behavior above is typical of an assembly of partially blocked magnetic nanoparticles. The values of the saturation magnetization, Ms, and the blocking temperature, Tb, are obtained as well. However, the hysteresis loop in the Co-doped sample differs from that in other samples, and the values of Bc and Ms are noticeably increased.

Characterization of carbonaceous aerosols during the MINOS campaign in Crete, July August 2001: a multi-analytical approach

NASA Astrophysics Data System (ADS)

Sciare, J.; Cachier, H.; Oikonomou, K.; Ausset, P.; Sarda-Estève, R.; Mihalopoulos, N.

2003-10-01

During the major part of the Mediterranean Intensive Oxidant Study (MINOS) campaign (summer 2001, Crete Isl.), the Marine Boundary Layer (MBL) air was influenced by long range transport of biomass burning from the northern and western part of the Black Sea. During this campaign, carbonaceous aerosols were collected on quartz filters at a Free Tropospheric (FT) site, and at a MBL site together with size-resolved distribution of aerosols. Three Evolution Gas Analysis (EGA) protocols have been tested in order to better characterize the collected aged biomass burning smoke: A 2-step thermal method (Cachier et al., 1989) and a thermo-optical technique using two different temperature programs. The later temperature programs are those used for IMPROVE (Interagency Monitoring of Protected Visual Environments) and NIOSH 5040 (National Institute of Occupational Safety and Health). Artifacts were observed using the NIOSH temperature program and identified as interactions between carbon and dust deposited on the filter matrix at high temperature (T>550ºC) under the pure helium step of the analysis. During the MINOS campaign, Black Carbon (BC) and Organic Carbon (OC) mass concentrations were on average respectively 1.19±0.56 and 3.62±1.08 mgC/m3 for the IMPROVE temperature program, and 1.09±0.36 and 3.75±1.24 mgC/m3 for the thermal method. Though these values compare well on average and the agreement between the Total Carbon (TC) measurements sample to sample was excellent (slope=1.00, r2=0.93, n=56), important discrepancies were observed in determining BC concentrations from these two methods (average error of 33±22%). BC from the IMPROVE temperature program compared well with non-sea-salt potassium (nss-K) pointing out an optical sensitivity to biomass burning. On the other hand, BC from the thermal method showed a better agreement with non-sea-salt sulfate (nss-SO4), considered as a tracer for fossil fuel combustion during the MINOS campaign. The coupling between these two methods for determining BC brings here new insights on the origin of carbonaceous aerosols in a complex mixture of different sources. It brings also to our attention that important deviations in BC levels are observed using three widely used EGA's techniques and most probably none of the EGA tested here are well adapted to fully characterize this aerosol mixture. Spherical, smooth and silico-aluminated fly-ash observed by an Analytical Scanning Electron Microscope (ASEM) confirm the influence of coal combustion on the carbonaceous aerosol load throughout the campaign. A rough calculation based on a BC/nss-SO4 mass ratio suggests that biomass burning could be responsible for half of the BC concentration recorded during the MINOS campaign. From the plot of BC as a function of TC, two linear correlations were observed corresponding to 2 times series (before and after 12 August). Such good correlations suggest, from a first look, that both BC and OC have similar origin and atmospheric transport. On the other hand, the plot of BC as a function of TC obtained from the 2-step thermal method applied to DEKATI Low Pressure Cascade Impactor samples does not show a similar correlation and points out a non conservative distribution of this ratio with 2 super micron modes enriched in OC, correlated with sea salt aerosols and probably originating from gas-to-particle conversion.

Characterization of carbonaceous aerosols during the MINOS campaign in Crete, July-August 2001: a multi-analytical approach

NASA Astrophysics Data System (ADS)

Sciare, J.; Cachier, H.; Oikonomou, K.; Ausset, P.; Sarda-Estève, R.; Mihalopoulos, N.

2003-07-01

During the major part of the Mediterranean Intensive Oxidant Study (MINOS) campaign (summer 2001, Crete Isl.), the Marine Boundary Layer (MBL) air was influenced by long range transport of biomass burning from the northern and western part of the Black Sea. During this campaign, carbonaceous aerosols were collected on quartz filters at a Free Tropospheric (FT) site, and at a MBL site together with size-resolved distribution of aerosols. Three Evolution Gas Analysis (EGA) protocols have been tested in order to better characterize the collected aged biomass burning smoke: A 2-step thermal method (Cachier et al., 1989) and a thermo-optical technique using two different temperature programs. The later temperature programs are those used for IMPROVE (Interagency Monitoring of Protected Visual Environments) and NIOSH 5040 (National Institute of Occupational Safety and Health). Artifacts were observed using the NIOSH temperature program and identified as interactions between carbon and dust deposited on the filter matrix at high temperature (T=550°C) under the pure helium step of the analysis. During the MINOS campaign, Black Carbon (BC) and Organic Carbon (OC) concentrations were on average respectively 1.19±0.56 and 3.62±1.08 μgC/m3 for the IMPROVE temperature program, and 1.09±0.36 and 3.75±1.24 μgC/m3 for the thermal method. Though these values compare well on average and the agreement between the Total Carbon (TC) measurements sample to sample was excellent (slope = 1.00, r2=0.93, n=56), important discrepancies were observed in determining BC concentrations from these two methods (average error of 33±22%). BC from the IMPROVE temperature program compared well with non-sea-salt potassium (nss-K) pointing out an optical sensitivity to biomass burning. On the other hand, BC from the thermal method showed a better agreement with non-sea-salt sulfate (nss-SO4), considered as a tracer for fossil fuel combustion during the MINOS campaign. The coupling between these two methods for determining BC brings here new insights on the origin of carbonaceous aerosols in a complex mixture of different sources. It brings also to our attention that important deviations in BC levels are observed using three widely used EGA techniques and most probably none of the EGA tested here are well adapted to fully characterize this aerosol mixture. Spherical, smooth and silico-aluminated fly-ash observed by Analytical Scanning Electron Microscope (ASEM) confirm the influence of coal combustion on the carbonaceous aerosol load throughout the campaign. A raw calculation based on BC/nss-SO4 mass ratio suggests that biomass burning could be responsible for half of the BC concentration recorded during the MINOS campaign. From the plot of BC as a function of TC, two linear correlations were observed corresponding to 2 times series (before and after 12 August). Such good correlations suggest, from a first look, that both BC and OC have similar origin and atmospheric transport. On the other hand, the plot of BC as a function of TC obtained from the 2-step thermal method applied to DEKATI Low Pressure Cascade Impactor samples does not show a similar correlation and points out a non conservative distribution of this ratio with 2 super micron modes enriched in OC, correlated with sea salt aerosols and probably originating from gas-to-particle conversion.

Chaperoning 5S RNA assembly

PubMed Central

Madru, Clément; Lebaron, Simon; Blaud, Magali; Delbos, Lila; Pipoli, Juliana; Pasmant, Eric; Réty, Stéphane; Leulliot, Nicolas

2015-01-01

In eukaryotes, three of the four ribosomal RNAs (rRNAs)—the 5.8S, 18S, and 25S/28S rRNAs—are processed from a single pre-rRNA transcript and assembled into ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S ribonucleoprotein particle (RNP), containing ribosomal proteins Rpl5/uL18 and Rpl11/uL5, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53. The nucleolar localization of the 5S RNP and its assembly into preribosomes are performed by a specialized complex composed of Rpf2 and Rrs1 in yeast or Bxdc1 and hRrs1 in humans. Here we report the structural and functional characterization of the Rpf2–Rrs1 complex alone, in complex with the 5S RNA, and within pre-60S ribosomes. We show that the Rpf2–Rrs1 complex contains a specialized 5S RNA E-loop-binding module, contacts the Rpl5 protein, and also contacts the ribosome assembly factor Rsa4 and the 25S RNA. We propose that the Rpf2–Rrs1 complex establishes a network of interactions that guide the incorporation of the 5S RNP in preribosomes in the initial conformation prior to its rotation to form the central protuberance found in the mature large ribosomal subunit. PMID:26159998

Distinct oxidative stabilities of char versus soot black carbon: Implications for quantification and environmental recalcitrance

NASA Astrophysics Data System (ADS)

Elmquist, Marie; Cornelissen, Gerard; Kukulska, Zofia; Gustafsson, Örjan

2006-06-01

Sequestration in sediments of black carbon (BC) from vegetation fires and fuel combustion may constitute a significant sink of otherwise rapidly cycling carbon from the atmosphere-biosphere cycle. It also has the potential to provide a historical record of atmospheric BC loadings. Previous treatments of BC as one homogeneous entity are being replaced with the growing awareness of a BC combustion continuum, a range spanning from slightly charred biomass to soot and graphite. Here the relative recalcitrance of different BC forms is evaluated, and implications for both BC quantification and environmental stability are considered. The stabilities of four BC reference materials against thermal oxidation in air were quite distinct with T50%BC values (i.e., the temperature where 50% BC remained in the residue) of 444°C (diesel soot-BC), 388°C (n-hexane soot-BC), 338°C (wood char-BC), and 266°C (grass char-BC). The implications for BC quantification have been illustrated for a thermal oxidation (the CTO-375) method commonly applied to study BC in sediments. This technique measured BC:TOC ratios of 78.3 ± 1.3% for the diesel soot-BC and 45.3 ± 6.1% for n-hexane soot-BC, whereas no CTO375-BC was detected for the two analyzed char-BC materials. The greater lability of char-BC compared to soot-BC likely reflects higher accessibility to internal microporosity in char-BC, facilitating internal O2 transfer. Decreasing the temperature cutoff below 375°C to also include char-BC is not possible as thermograms of nonpyrogenic reference materials indicated that such material would then be artifactually quantified as BC. The presence of mineral oxides in the sediment matrix may lead to a catalytically mediated lowering of the activation energy for soot-BC oxidation but not for char-BC or nonpyrogenic organic material. Several recent studies combine to challenge the proposition of complete recalcitrance of BC. Particularly, the thermal lability of char-BC from grassland fires deserves further attention in order to improve the understanding of BC in the global carbon cycle.

Neighborhood socioeconomic deprivation, tumor subtypes, and causes of death after non-metastatic invasive breast cancer diagnosis: a multilevel competing-risk analysis.

PubMed

Lian, Min; Pérez, Maria; Liu, Ying; Schootman, Mario; Frisse, Ann; Foldes, Ellen; Jeffe, Donna B

2014-10-01

The purpose of this study is to examine the associations of neighborhood socioeconomic deprivation and triple-negative breast cancer (TNBC) subtype with causes of death [breast cancer (BC)-specific and non-BC-specific] among non-metastatic invasive BC patients. We identified 3,312 patients younger than 75 years (mean age 53.5 years; 621 [18.8 %] TNBC) with first primary BC treated at an academic medical center from 1999 to 2010. We constructed a census-tract-level socioeconomic deprivation index using the 2000 U.S. Census data and performed a multilevel competing-risk analysis to estimate the hazard ratios (HR) and 95 % confidence intervals (CI) of BC-specific and non-BC-specific mortality associated with neighborhood socioeconomic deprivation and TNBC subtype. The adjusted models controlled for patient sociodemographics, health behaviors, tumor characteristics, comorbidity, and cancer treatment. With a median 62-month follow-up, 349 (10.5 %) patients died; 233 died from BC. In the multivariate models, neighborhood socioeconomic deprivation was independently associated with non-BC-specific mortality (the most- vs. the least-deprived quartile: HR = 2.98, 95 % CI = 1.33-6.66); in contrast, its association with BC-specific mortality was explained by the aforementioned patient-level covariates, particularly sociodemographic factors (HR = 1.15, 95 % CI = 0.71-1.87). TNBC subtype was independently associated with non-BC-specific mortality (HR = 2.15; 95 % CI = 1.20-3.84), while the association between TNBC and BC-specific mortality approached significance (HR = 1.42; 95 % CI = 0.99-2.03, P = 0.057). Non-metastatic invasive BC patients who lived in more socioeconomically deprived neighborhoods were more likely to die as a result of causes other than BC compared with those living in the least socioeconomically deprived neighborhoods. TNBC was associated with non-BC-specific mortality but not BC-specific mortality.

HSP90 and its R2TP/Prefoldin-like cochaperone are involved in the cytoplasmic assembly of RNA polymerase II.

PubMed

Boulon, Séverine; Pradet-Balade, Bérengère; Verheggen, Céline; Molle, Dorothée; Boireau, Stéphanie; Georgieva, Marya; Azzag, Karim; Robert, Marie-Cécile; Ahmad, Yasmeen; Neel, Henry; Lamond, Angus I; Bertrand, Edouard

2010-09-24

RNA polymerases are key multisubunit cellular enzymes. Microscopy studies indicated that RNA polymerase I assembles near its promoter. However, the mechanism by which RNA polymerase II is assembled from its 12 subunits remains unclear. We show here that RNA polymerase II subunits Rpb1 and Rpb3 accumulate in the cytoplasm when assembly is prevented and that nuclear import of Rpb1 requires the presence of all subunits. Using MS-based quantitative proteomics, we characterized assembly intermediates. These included a cytoplasmic complex containing subunits Rpb1 and Rpb8 associated with the HSP90 cochaperone hSpagh (RPAP3) and the R2TP/Prefoldin-like complex. Remarkably, HSP90 activity stabilized incompletely assembled Rpb1 in the cytoplasm. Our data indicate that RNA polymerase II is built in the cytoplasm and reveal quality-control mechanisms that link HSP90 to the nuclear import of fully assembled enzymes. hSpagh also bound the free RPA194 subunit of RNA polymerase I, suggesting a general role in assembling RNA polymerases. Copyright © 2010 Elsevier Inc. All rights reserved.

HSP90 and Its R2TP/Prefoldin-like Cochaperone Are Involved in the Cytoplasmic Assembly of RNA Polymerase II

PubMed Central

Boireau, Stéphanie; Georgieva, Marya; Azzag, Karim; Robert, Marie-Cécile; Ahmad, Yasmeen; Neel, Henry; Lamond, Angus I.; Bertrand, Edouard

2015-01-01

SUMMARY RNA polymerases are key multisubunit cellular enzymes. Microscopy studies indicated that RNA polymerase I assembles near its promoter. However, the mechanism by which RNA polymerase II is assembled from its 12 subunits remains unclear. We show here that RNA polymerase II subunits Rpb1 and Rpb3 accumulate in the cytoplasm when assembly is prevented and that nuclear import of Rpb1 requires the presence of all subunits. Using MS-based quantitative proteomics, we characterized assembly intermediates. These included a cytoplasmic complex containing subunits Rpb1 and Rpb8 associated with the HSP90 cochaperone hSpagh (RPAP3) and the R2TP/Prefoldin-like complex. Remarkably, HSP90 activity stabilized incompletely assembled Rpb1 in the cytoplasm. Our data indicate that RNA polymerase II is built in the cytoplasm and reveal quality-control mechanisms that link HSP90 to the nuclear import of fully assembled enzymes. hSpagh also bound the free RPA194 subunit of RNA polymerase I, suggesting a general role in assembling RNA polymerases. PMID:20864038

Identifying the assembly intermediate in which Gag first associates with unspliced HIV-1 RNA suggests a novel model for HIV-1 RNA packaging.

PubMed

Barajas, Brook C; Tanaka, Motoko; Robinson, Bridget A; Phuong, Daryl J; Chutiraka, Kasana; Reed, Jonathan C; Lingappa, Jaisri R

2018-04-01

During immature capsid assembly, HIV-1 genome packaging is initiated when Gag first associates with unspliced HIV-1 RNA by a poorly understood process. Previously, we defined a pathway of sequential intracellular HIV-1 capsid assembly intermediates; here we sought to identify the intermediate in which HIV-1 Gag first associates with unspliced HIV-1 RNA. In provirus-expressing cells, unspliced HIV-1 RNA was not found in the soluble fraction of the cytosol, but instead was largely in complexes ≥30S. We did not detect unspliced HIV-1 RNA associated with Gag in the first assembly intermediate, which consists of soluble Gag. Instead, the earliest assembly intermediate in which we detected Gag associated with unspliced HIV-1 RNA was the second assembly intermediate (~80S intermediate), which is derived from a host RNA granule containing two cellular facilitators of assembly, ABCE1 and the RNA granule protein DDX6. At steady-state, this RNA-granule-derived ~80S complex was the smallest assembly intermediate that contained Gag associated with unspliced viral RNA, regardless of whether lysates contained intact or disrupted ribosomes, or expressed WT or assembly-defective Gag. A similar complex was identified in HIV-1-infected T cells. RNA-granule-derived assembly intermediates were detected in situ as sites of Gag colocalization with ABCE1 and DDX6; moreover these granules were far more numerous and smaller than well-studied RNA granules termed P bodies. Finally, we identified two steps that lead to association of assembling Gag with unspliced HIV-1 RNA. Independent of viral-RNA-binding, Gag associates with a broad class of RNA granules that largely lacks unspliced viral RNA (step 1). If a viral-RNA-binding domain is present, Gag further localizes to a subset of these granules that contains unspliced viral RNA (step 2). Thus, our data raise the possibility that HIV-1 packaging is initiated not by soluble Gag, but by Gag targeted to a subset of host RNA granules containing unspliced HIV-1 RNA.

Identifying the assembly intermediate in which Gag first associates with unspliced HIV-1 RNA suggests a novel model for HIV-1 RNA packaging

PubMed Central

Barajas, Brook C.; Tanaka, Motoko; Robinson, Bridget A.; Phuong, Daryl J.; Reed, Jonathan C.

2018-01-01

During immature capsid assembly, HIV-1 genome packaging is initiated when Gag first associates with unspliced HIV-1 RNA by a poorly understood process. Previously, we defined a pathway of sequential intracellular HIV-1 capsid assembly intermediates; here we sought to identify the intermediate in which HIV-1 Gag first associates with unspliced HIV-1 RNA. In provirus-expressing cells, unspliced HIV-1 RNA was not found in the soluble fraction of the cytosol, but instead was largely in complexes ≥30S. We did not detect unspliced HIV-1 RNA associated with Gag in the first assembly intermediate, which consists of soluble Gag. Instead, the earliest assembly intermediate in which we detected Gag associated with unspliced HIV-1 RNA was the second assembly intermediate (~80S intermediate), which is derived from a host RNA granule containing two cellular facilitators of assembly, ABCE1 and the RNA granule protein DDX6. At steady-state, this RNA-granule-derived ~80S complex was the smallest assembly intermediate that contained Gag associated with unspliced viral RNA, regardless of whether lysates contained intact or disrupted ribosomes, or expressed WT or assembly-defective Gag. A similar complex was identified in HIV-1-infected T cells. RNA-granule-derived assembly intermediates were detected in situ as sites of Gag colocalization with ABCE1 and DDX6; moreover these granules were far more numerous and smaller than well-studied RNA granules termed P bodies. Finally, we identified two steps that lead to association of assembling Gag with unspliced HIV-1 RNA. Independent of viral-RNA-binding, Gag associates with a broad class of RNA granules that largely lacks unspliced viral RNA (step 1). If a viral-RNA-binding domain is present, Gag further localizes to a subset of these granules that contains unspliced viral RNA (step 2). Thus, our data raise the possibility that HIV-1 packaging is initiated not by soluble Gag, but by Gag targeted to a subset of host RNA granules containing unspliced HIV-1 RNA. PMID:29664940

Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex.

PubMed

Tipton, Aaron R; Ji, Wenbin; Sturt-Gillespie, Brianne; Bekier, Michael E; Wang, Kexi; Taylor, William R; Liu, Song-Tao

2013-12-06

MPS1 kinase is an essential component of the spindle assembly checkpoint (SAC), but its functioning mechanisms are not fully understood. We have shown recently that direct interaction between BUBR1 and MAD2 is critical for assembly and function of the human mitotic checkpoint complex (MCC), the SAC effector. Here we report that inhibition of MPS1 kinase activity by reversine disrupts BUBR1-MAD2 as well as CDC20-MAD2 interactions, causing premature activation of the anaphase-promoting complex/cyclosome. The effect of MPS1 inhibition is likely due to reduction of closed MAD2 (C-MAD2), as expressing a MAD2 mutant (MAD2(L13A)) that is locked in the C conformation rescued the checkpoint defects. In the presence of reversine, exogenous C-MAD2 does not localize to unattached kinetochores but is still incorporated into the MCC. Contrary to a previous report, we found that sustained MPS1 activity is required for maintaining both the MAD1·C-MAD2 complex and open MAD2 (O-MAD2) at unattached kinetochores to facilitate C-MAD2 production. Additionally, mitotic phosphorylation of BUBR1 is also affected by MPS1 inhibition but seems dispensable for MCC assembly. Our results support the notion that MPS1 kinase promotes C-MAD2 production and subsequent MCC assembly to activate the SAC.

Living supramolecular polymerization achieved by collaborative assembly of platinum(II) complexes and block copolymers

PubMed Central

Zhang, Kaka; Yeung, Margaret Ching-Lam; Leung, Sammual Yu-Lut; Yam, Vivian Wing-Wah

2017-01-01

An important feature of biological systems to achieve complexity and precision is the involvement of multiple components where each component plays its own role and collaborates with other components. Mimicking this, we report living supramolecular polymerization achieved by collaborative assembly of two structurally dissimilar components, that is, platinum(II) complexes and poly(ethylene glycol)-b-poly(acrylic acid) (PEG-b-PAA). The PAA blocks neutralize the charges of the platinum(II) complexes, with the noncovalent metal–metal and π–π interactions directing the longitudinal growth of the platinum(II) complexes into 1D crystalline nanostructures, and the PEG blocks inhibiting the transverse growth of the platinum(II) complexes and providing the whole system with excellent solubility. The ends of the 1D crystalline nanostructures have been found to be active during the assembly and remain active after the assembly. One-dimensional segmented nanostructures with heterojunctions have been produced by sequential growth of two types of platinum(II) complexes. The PAA blocks act as adapters at the heterojunctions for lattice matching between chemically and crystallographically different platinum(II) complexes, achieving heterojunctions with a lattice mismatch as large as 21%. PMID:29078381

Fuel regulation in inland navigation: Reduced soil black carbon deposition in river valleys in Germany

NASA Astrophysics Data System (ADS)

Bläsing, M.; Shao, Y.; Lehndorff, E.

2015-11-01

Inland navigation is of increasing economic and ecological interest, however its contribution to environmental quality is hardly known. We hypothesized that i) inland navigation emits considerable amounts of soot-Black Carbon (BC) as a product of incomplete combustion of diesel fuel, which is then deposited on soils along river valleys, that ii) improvement of fuel quality by sulfur reduction in 2011 decreased BC inputs to soil, and that iii) this provides a tracer for the spatial impact of inland navigation emissions. The spatial and temporal patterns of soil BC deposits from inland navigation were investigated yearly (2010-2013) working within transects perpendicular to the rivers Rhine, Moselle and Ahr, Germany (the Ahr Valley is free of shipping and served as a reference). In rural areas at inland waterways navigation likely represented the dominant BC emitter. Topsoils (0-10 cm depth) were sampled in vineyards. Their BC content and composition was determined via oxidation of bulk soil organic matter to benzene polycarboxylic acids (BPCAs). The highly trafficked Rhine Valley yielded only little more BC (64.7 ± 12 g BC kg-1 soil organic carbon (SOC) compared to 51.7 ± 9 at the Moselle, and 53.6 ± 6 at the reference Ahr Valley). At both inland waterways soil BC increased towards the river, following the simulated dispersal of ship-derived BC using a Lagrangian model. In the course of ship fuel regulation, soil BC deposits at the Rhine and Moselle waterways decreased significantly from 70.2 ± 3.2 to 47.9 ± 1.1 and 57.6 ± 1.3 to 41.7 ± 0.9 g BC kg-1 SOC within 3 years. Even more pronounced was the change in BC composition, i.e., the ratio of pentacarboxylated to mellitic acid increased from 0.75 to 1.3 (Rhine) and 1 to 1.4 (Moselle) during this time span. From this we calculated that ∼30% less BC was deposited by inland navigation likely due to reduced BC emissions after sulfur regulation in ship diesel.

Activated carbon and biochar from agricultural by-products in the adorption of Cd, Pb and Zn under laboratory conditions

NASA Astrophysics Data System (ADS)

Coscione, Aline; Zini, Barbara

2015-04-01

The immobilization of inorganic contaminants by using biochar in soils has played an increasingly important role and it is seen as an attractive alternative for the remediation of heavy metals. Although, the production of activated carbon (CA) from agricultural by-products has received special attention, the activation of the the organic source has been studied in order to increase its porposity, surface area and chemical polarity, resulting in higher adsorption of metals. Therefore, this study aimed to evaluate the effectiveness of BC and CA samples, obtained from a eucalyptus husks and cane sugar bagasse after activation with 20% phosphoric acid and pyrolyzed at 450oC in the retention of Zn, Cd and Pb using contaminated individual solutions. The experiment was performed using samples of activated carbon of eucalyptus husk (CCA), eucalyptus husk biochar (BC), activated carbon of sugar cane bagasse (CBA) and sugar cane bagasse biochar (BB), treated with Zn, Cd (range of tested solution from 0.1 up to 12 mmol L-1) and Pb (from 0.1 up 50 mmol L-1) and the adjustemento of Langmuir adsorption isotherms. Samples obtained from bagasse presented higher adsoprtion of the metals tested then eucalyptus. Also the activation process had not the expected effect on either eucalyptus and bagasse samples The maxmum adsorption capacyty of samples were as follws, in mmol g-1: for Cd - 0.36 for BC; 0.32 for CCA; 0.40 for BB; 0.31 for CBA. For Zn- 0.14 for BC; no adsorbed by CCA; 0.35 5 for BB; 0.06 for CBA. For Pb - 1.24 for BC; 0.40 for CCA; 0,45 for BB; 0,03 for CBA. However, it was also observed that due to the activation with phosphoric acid, the pH of the activated carbon (CCA and CBA) were 2.4 and 2.5 in comparison with the biochars not activated (BC and BB) 9.7 and 7.0 respectively. Thus, it is yet not possible to state if the calculate capacity is due exclusively to the complexation of chemical groups in the surface of samples or to which extent there is a contribution of precipitation caused by the basic pH (non-activated) biochar samples, as shown for Zn and Pb.

In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic

PubMed Central

Huang, Hsiao-Yun

2015-01-01

Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1–RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. PMID:25838545

Ecophysiological differences in tree carbon gain and water use for two fast growing loblolly pine ideotypes that differ in carbon allocation

NASA Astrophysics Data System (ADS)

Maier, C. A.; Johnsen, K. H.; Dougherty, P.; Albaugh, T.; Patterson, S.

2013-12-01

We examined the ecophysiological basis for differences in growth efficiency and water-use for two contrasting Pinus taeda (L.) ideotypes: a ';broad-crown' (BC) and a ';narrow crown' (NC) clone, which allocate more growth to leaves and wood, respectively. Tree growth, above and belowground biomass production, fine root turnover, light use efficiency (LUE), and transpiration on a ground (Et) and leaf (EL) basis were measured periodically over eight years. Silviculture treatments were a control consisting of shearing and bedding following local commercial operations and a mulch treatment where chipped logging residue (C/N≈700) was incorporated into the soil during bedding at a rate of 25 Mg ha-1. We hypothesized that: 1) the NC and BC clone would display similar aboveground productivity in the control treatment, but because of lower leaf area and thus lower nitrogen demand, the NC would display higher productivity than BC on the mulch treatment, 2) the NC would have higher LUE, and 3) the NC clone would have lower Et and EL. There were no treatment, clone, or interaction effects on stemwood production. At age eight, standing stem biomass was 80.7 and 86.0 Mg ha-1 (p=0.33), for the NC and BC, respectively. However, there were significant clone effects on carbon allocation. The BC had greater foliage (BC: 8.1, NC: 6.6 Mg ha-1, se=0.2, p=0.01) and branch (BC: 15.0, NC: 12.4 Mg ha-1, se=0.4, p<0.001) biomass, while the NC clone had greater taproot (BC: 14.8, NC: 17.1, Mg ha-1, se=0.4, p=0.003) and coarse root (>2mm) (BC: 9.7, NC: 11.23 Mg ha-1, se=0.2, P<0.001) biomass. In addition, the NC clone averaged on a monthly basis 30% more fine root biomass (<2mm) (BC: 42.4, NC: 61.0 g m-2, se=4.0, p=0.011). The BC clone had 16% more LAI (BC: 3.52×0.12, NC: 2.94×0.14 m2 m-2) at peak foliage biomass and had more leaf area to conducting sapwood area (AL/AS) (BC: 0.175 m2 cm-2, NC: 0.150 m2 cm-2) than the NC clone. Growth efficiency, defined as annual stem increment per unit leaf area was 5.36 and 4.70 Mg ha-1 yr-1 LAI-1 in the NC and BC, respectively (p<0.0001). There were no clone differences in LUE (NC: 1.41, BC 1.35 g MJ-1, p=0.48). Et of the BC clone was 22% (403 mm year-1) greater than the NC (315 mm year-1); however, most of this difference was due to greater water use by the BC clone during the winter and spring. There were no differences in Et during the summer months. For example, EL averaged 1.03×0.07 and 0.69×0.04 mm day-1 in March compared to 0.72×.07 and 0.61×0.05 mm day-1in August for the BC and NC, respectively. Our results show that the contrasting ideotypes had similar stem biomass production, but the NC ideotype produced more stemwood per unit leaf area, which confers greater nutrient use efficiency. In addition, the NC had significantly greater belowground carbon allocation, which could have long-term implications for soil carbon sequestration.

Visceral Crisis Means Short Survival Among Patients With Luminal A Metastatic Breast Cancer: A Retrospective Cohort Study.

PubMed

Sbitti, Yassir; Slimani, Khaoula; Debbagh, Adil; Mokhlis, Anouar; Kadiri, Habiba; Laraqui, Abdelilah; Errihani, Hassan; Ichou, Mohamed

2017-08-01

Patients with visceral crisis from luminal metastatic breast cancer (mBC) are often treated with palliative chemotherapy. No studies have analyzed the aggressiveness of the care in visceral crisis from luminal mBC patients. The objective of this study was to assess practices in this setting in a university medical oncology department. This retrospective study included all patients who were managed for luminal mBC between January 2013 and April 2016. The analysis focused on the characteristics of the patients, the modalities of cancer treatment and delays between visceral crisis and death. Thirty-five patients pre-treated with two hormonal therapy lines were enrolled retrospectively. Worse performance status and a higher proportion of severe organ dysfunction for luminal mBC were observed among patients with visceral crisis. Sixty-five percent of patients received cytotoxic treatment. One cycle of chemotherapy was administrated in the majority of patients. Palliative care was performed in 35% of patients. Chemotherapy did not have any significant effect on patient outcome in the present study. The mean time between visceral crisis and death was 4.7 weeks (standard deviation = 1.9). Our study showed that visceral crisis in patients with luminal mBC is a complex problem. We need more comprehension of molecular pathogenesis to visceral crisis disease to propose efficacious treatments for these patients and to identify subgroup of patients who need chemotherapy followed by maintenance endocrine therapy.

Mobility of black carbon in drained peatland soils

NASA Astrophysics Data System (ADS)

Leifeld, J.; Fenner, S.; Müller, M.

2007-06-01

Amount, stability, and distribution of black carbon (BC) were studied at four sites of a large peatland ("Witzwil") formerly used as a disposal for combustion residues from households to derive BC displacement rates in the profile. Possible artefacts from thermal oxidation with Differential Scanning Calorimetry (DSC) on BC quantification of C-rich deposits were inferred by choosing three sites from a second peatland with no historical record of waste disposal as a reference ("Seebodenalp"). All sites were under grassland at time of sampling, but were partially cropped in the past at Witzwil. Mean BC contents in topsoils of Witzwil ranged from 10.7 to 91.5 (0-30 cm) and from 0.44 to 51.3 (30-140 cm) mg BC g-1 soil, corresponding to BC/OC ratios of 0.04 to 0.3 (topsoil) and 0.02 to 0.18 (deeper soil). At three sites of Seebodenalp, BC was below the detection limit of 0.4 mg g-1 organic soil, indicating negligible formation of BC during thermal oxidation of peat. 13C NMR spectra corroborated the high BC contents at Witzwil. The data support a considerable vertical transport of BC given that soils were ploughed not deeper than 30 cm since abandonment of waste application about 50 years ago. The total amount of BC in the Witzwil profiles ranged from 3.2 to 7.5 kg BC m-2, with 21 to 69 percent of it stemming from below the former ploughing depth. Under the premise of negligible rates of BC consumption since abandonment of waste application, minimum BC transport rates in these peats are 0.6 to 1.2 cm a-1. The high mobility of BC might be explained by high macro-pore volumes in combination with occasional water saturation. By means of DSC peak temperatures, different types of BC could be distinguished, with deeper horizons containing BC of higher thermal stability. Application of combustion residues likely involved a mixture of various BC types, of which thermally more stable ones, most likely soots, were preferentially transported downwards.

Mobility of black carbon in drained peatland soils

NASA Astrophysics Data System (ADS)

Leifeld, J.; Fenner, S.; Müller, M.

2007-03-01

Amount, stability, and distribution of black carbon BC were studied at four sites of a large peatland ("Witzwil") formerly used as a disposal for combustion residues from households to derive BC displacement rates in the profile. Possible artefacts from thermal oxidation with Differential Scanning Calorimetry (DSC) on BC quantification of C-rich deposits were inferred by choosing three sites from a second peatland with no historical record of waste disposal as a reference ("Seebodenalp"). All sites were under grassland at time of sampling, but were partially cropped in the past at Witzwil. Mean BC contents in topsoils of Witzwil ranged from 10.7 to 91.5 (0-30 cm) and from 0.44 to 51.3 (30-140 cm) mg BC g-1 soil, corresponding to BC/OC ratios of 0.04 to 0.3 (topsoil) and 0.02 to 0.18 (deeper soil). At three sites of Seebodenalp, BC was below the detection limit of 0.4 mg g-1 organic soil, indicating negligible formation of BC during thermal oxidation of peat. 13C NMR spectra corroborated the high BC contents at Witzwil. The data refer to a considerable vertical transport of BC given that soils were ploughed not deeper than 30 cm since abandonment of waste application about 50 years ago. The total amount of BC in the Witzwil profiles ranged from 3.2 to 7.5 kg BC m-2, with 21 to 69 percent of it stemming from below the former ploughing depth. Under the premise of negligible rates of BC consumption since abandonment of waste application, minimum BC transport rates in these peats are 0.6 to 1.2 cm a-1. The high mobility of BC might be explained by high macro-pore volumes in combination with occasional water saturation. By means of DSC peak temperatures, different types of BC could be distinguished, with deeper horizons containing BC of higher thermal stability. Application of combustion residues likely involved a mixture of various BC types, of which thermally more stable ones, most likely soots, were preferentially transported downwards.

On BC1 RNA and the fragile X mental retardation protein

PubMed Central

Iacoangeli, Anna; Rozhdestvensky, Timofey S.; Dolzhanskaya, Natalia; Tournier, Barthélémy; Schütt, Janin; Brosius, Jürgen; Denman, Robert B.; Khandjian, Edouard W.; Kindler, Stefan; Tiedge, Henri

2008-01-01

The fragile X mental retardation protein (FMRP), the functional absence of which causes fragile X syndrome, is an RNA-binding protein that has been implicated in the regulation of local protein synthesis at the synapse. The mechanism of FMRP's interaction with its target mRNAs, however, has remained controversial. In one model, it has been proposed that BC1 RNA, a small non-protein-coding RNA that localizes to synaptodendritic domains, operates as a requisite adaptor by specifically binding to both FMRP and, via direct base-pairing, to FMRP target mRNAs. Other models posit that FMRP interacts with its target mRNAs directly, i.e., in a BC1-independent manner. Here five laboratories independently set out to test the BC1–FMRP model. We report that specific BC1–FMRP interactions could be documented neither in vitro nor in vivo. Interactions between BC1 RNA and FMRP target mRNAs were determined to be of a nonspecific nature. Significantly, the association of FMRP with bona fide target mRNAs was independent of the presence of BC1 RNA in vivo. The combined experimental evidence is discordant with a proposed scenario in which BC1 RNA acts as a bridge between FMRP and its target mRNAs and rather supports a model in which BC1 RNA and FMRP are translational repressors that operate independently. PMID:18184799

Light-triggered self-assembly of triarylamine-based nanospheres

NASA Astrophysics Data System (ADS)

Moulin, Emilie; Niess, Frédéric; Fuks, Gad; Jouault, Nicolas; Buhler, Eric; Giuseppone, Nicolas

2012-10-01

Tailored triarylamine units modified with terpyridine ligands were coordinated to Zn2+ ions and characterized as discrete dimeric entities. Interestingly, when these complexes were subsequently irradiated with simple visible light in chloroform, they readily self-assembled into monodisperse spheres with a mean diameter of 160 nm.Tailored triarylamine units modified with terpyridine ligands were coordinated to Zn2+ ions and characterized as discrete dimeric entities. Interestingly, when these complexes were subsequently irradiated with simple visible light in chloroform, they readily self-assembled into monodisperse spheres with a mean diameter of 160 nm. Electronic supplementary information (ESI) available: Synthetic procedures and products' characterization (2-4 and 6-9). 1H NMR titration of compound 6 by Zn(OTf)2 to form complex 7. Kinetic measurements by UV-Vis-NIR spectroscopy. Transmission electron microscopy imaging for complexes 8 and 9. UV-Vis-NIR for an Fe2+ analogue of complex 7. Dynamic light scattering and time autocorrelation function for self-assembly of complexes 7-9. Copies of 1H and 13C NMR spectra for compounds 2-4 and 6. See DOI: 10.1039/c2nr32168h

Dietary glycemic index and glycemic load and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC).

PubMed

Romieu, Isabelle; Ferrari, Pietro; Rinaldi, Sabina; Slimani, Nadia; Jenab, Mazda; Olsen, Anja; Tjonneland, Anne; Overvad, Kim; Boutron-Ruault, Marie-Christine; Lajous, Martin; Kaaks, Rudolf; Teucher, Birgit; Boeing, Heiner; Trichopoulou, Antonia; Naska, Androniki; Vasilopoulo, Effie; Sacerdote, Carlotta; Tumino, Rosario; Masala, Giovanna; Sieri, Sabina; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Van-der-A, Daphne; van Gils, Carla H; Peeters, Petra H M; Lund, Eiliv; Skeie, Guri; Asli, Lene Angell; Rodriguez, Laudina; Navarro, Carmen; Amiano, Pilar; Sanchez, Maria-José; Barricarte, Aurelio; Buckland, Genevieve; Sonestedt, Emily; Wirfält, Elisabet; Hallmans, Göran; Johansson, Ingegerd; Key, Timothy J; Allen, Naomi E; Khaw, Kay-Tee; Wareham, Nicholas J; Norat, Teresa; Riboli, Elio; Clavel-Chapelon, Françoise

2012-08-01

The glycemic potential of a diet is associated with chronically elevated insulin concentrations, which may augment breast cancer (BC) risk by stimulating insulin receptor or by affecting insulin-like growth factor I (IGF-I)-mediated mitogenesis. It is unclear whether this effect differs by BC phenotype. The objective was to investigate the relation between glycemic index (GI), glycemic load (GL), and total carbohydrate intake with BC by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). We identified 11,576 women with invasive BC among 334,849 EPIC women aged 34-66 y (5th to 95th percentiles) at baseline over a median follow-up of 11.5 y. Dietary GI and GL were calculated from country-specific dietary questionnaires. We used multivariable Cox proportional hazards models to quantify the association between GI, GL, and carbohydrate intake and BC risk. BC tumors were classified by receptor status. Overall GI, GL, and carbohydrates were not related to BC. Among postmenopausal women, GL and carbohydate intake were significantly associated with an increased risk of estrogen receptor-negative (ER(-)) BC when extreme quintiles (Q) were compared [multivariable HR(Q5-Q1) (95% CI) = 1.36 (1.02, 1.82; P-trend = 0.010) and HR(Q5-Q1) = 1.41 (1.05, 1.89; P-trend = 0.009), respectively]. Further stratification by progesterone receptor (PR) status showed slightly stronger associations with ER(-)/PR(-) BC [HR(Q5-Q1) (95% CI) = 1.48 (1.07, 2.05; P-trend = 0.010) for GL and HR(Q5-Q1) = 1.62 (1.15, 2.30; P-trend = 0.005) for carbohydrates]. No significant association with ER-positive BC was observed. Our results indicate that a diet with a high GL and carbohydrate intake is positively associated with an increased risk of developing ER(-) and ER(-)/PR(-) BC among postmenopausal women.

Development of sedentary communities in the Maya lowlands: coexisting mobile groups and public ceremonies at Ceibal, Guatemala.

PubMed

Inomata, Takeshi; MacLellan, Jessica; Triadan, Daniela; Munson, Jessica; Burham, Melissa; Aoyama, Kazuo; Nasu, Hiroo; Pinzón, Flory; Yonenobu, Hitoshi

2015-04-07

Our archaeological investigations at Ceibal, a lowland Maya site located in the Pasión region, documented that a formal ceremonial complex was built around 950 B.C. at the onset of the Middle Preclassic period, when ceramics began to be used in the Maya lowlands. Our refined chronology allowed us to trace the subsequent social changes in a resolution that had not been possible before. Many residents of Ceibal appear to have remained relatively mobile during the following centuries, living in ephemeral post-in-ground structures and frequently changing their residential localities. In other parts of the Pasión region, there may have existed more mobile populations who maintained the traditional lifestyle of the preceramic period. Although the emerging elite of Ceibal began to live in a substantial residential complex by 700 B.C., advanced sedentism with durable residences rebuilt in the same locations and burials placed under house floors was not adopted in most residential areas until 500 B.C., and did not become common until 300 B.C. or the Late Preclassic period. During the Middle Preclassic period, substantial formal ceremonial complexes appear to have been built only at a small number of important communities in the Maya lowlands, and groups with different levels of sedentism probably gathered for their constructions and for public rituals held in them. These collaborative activities likely played a central role in socially integrating diverse groups with different lifestyles and, eventually, in developing fully established sedentary communities.

Factors Controlling Black Carbon Deposition in Snow in the Arctic

NASA Astrophysics Data System (ADS)

Qi, L.; Li, Q.; He, C.; Li, Y.

2015-12-01

This study evaluates the sensitivity of black carbon (BC) concentration in snow in the Arctic to BC emissions, dry deposition and wet scavenging efficiency using a 3D global chemical transport model GEOS-Chem driven by meteorological field GEOS-5. With all improvements, simulated median BC concentration in snow agrees with observation (19.2 ng g-1) within 10%, down from -40% in the default GEOS-Chem. When the previously missed gas flaring emissions (mainly located in Russia) are included, the total BC emission in the Arctic increases by 70%. The simulated BC in snow increases by 1-7 ng g-1, with the largest improvement in Russia. The discrepancy of median BC in snow in the whole Arctic reduces from -40% to -20%. In addition, recent measurements of BC dry deposition velocity suggest that the constant deposition velocity of 0.03 cm s-1 over snow and ice used in the GEOS-Chem is too low. So we apply resistance-in-series method to calculate the dry deposition velocity over snow and ice and the resulted dry deposition velocity ranges from 0.03 to 0.24 cm s-1. However, the simulated total BC deposition flux in the Arctic and BC in snow does not change, because the increased dry deposition flux has been compensated by decreased wet deposition flux. However, the fraction of dry deposition to total deposition increases from 16% to 25%. This may affect the mixing of BC and snow particles and further affect the radative forcing of BC deposited in snow. Finally, we reduced the scavenging efficiency of BC in mixed-phase clouds to account for the effect of Wegener-Bergeron-Findeisen (WBF) process based on recent observations. The simulated BC concentration in snow increases by 10-100%, with the largest increase in Greenland (100%), Tromsø (50%), Alaska (40%), and Canadian Arctic (30%). Annual BC loading in the Arctic increases from 0.25 to 0.43 mg m-2 and the lifetime of BC increases from 9.2 to 16.3 days. This indicates that BC simulation in the Arctic is really sensitive to the representation of BC scavenging efficiency. More measurements are needed to better understand the BC-cloud interaction and to constrain the model.

TIMSS Advanced 2015 and Advanced Placement Calculus & Physics. A Framework Analysis. Research in Review 2016-1

ERIC Educational Resources Information Center

Lazzaro, Christopher; Jones, Lee; Webb, David C.; Grover, Ryan; Di Giacomo, F. Tony; Marino, Katherine Adele

2016-01-01

This report will determine to what degree the AP Physics 1 and 2 and AP Calculus AB and BC frameworks are aligned with the Trends in International Mathematics and Science Study (TIMSS) Advanced Physics and Mathematics frameworks. This will enable an exploration of any differences in content coverage and levels of complexity, and will set the stage…

Characteristics and source apportionment of black carbon aerosols over an urban site.

PubMed

Rajesh, T A; Ramachandran, S

2017-03-01

Aethalometer based source apportionment model using the measured aerosol absorption coefficients at different wavelengths is used to apportion the contribution of fossil fuel and wood burning sources to the total black carbon (BC) mass concentration. Temporal and seasonal variabilities in BC mass concentrations, equivalent BC from fossil fuel (BC f f ), and wood burning (BC w b ) are investigated over an urban location in western India during January 2014 to December 2015. BC, BC f f , and BC w b mass concentrations exhibit strong diurnal variation and are mainly influenced by atmospheric dynamics. BC f f was higher by a factor of 2-4 than BC w b and contributes maximum to BC mass throughout the day, confirming consistent anthropogenic activities. Diurnal contribution of BC f f and BC w b exhibits opposite variation due to differences in emission sources over Ahmedabad. Night time BC values are about a factor of 1.4 higher than day time BC values. The annual mean percentage contributions of day time and night time are 42 and 58 %, respectively. BC, BC f f , and BC w b mass concentrations exhibit large and significant variations during morning, afternoon, evening, and night time. During afternoon, mass concentration values are minimum throughout the year because of the fully evolved boundary layer and reduced anthropogenic activities. BC exhibits a strong seasonal variability with postmonsoon high (8.3 μg m -3 ) and monsoon low (1.9 μg m -3 ). Annual mean BC f f and BC w b contributions are 80 and 20 %, respectively, to total BC, which suggests that major contribution of BC in Ahmedabad comes from fossil fuel emissions. The results show that the study location is dominated by fossil fuel combustion as compared to the emissions from wood burning. The results obtained represent a regional value over an urban regime which can be used as inputs on source apportionment to model BC emissions in regional and global climate models.

Marker-assisted breeding for introgression of opaque-2 allele into elite maize inbred line BML-7.

PubMed

Krishna, M S R; Sokka Reddy, S; Satyanarayana, Sadam D V

2017-07-01

Improvement of quality protein maize (QPM) along with high content of lysine and tryptophan had foremost importance in maize breeding program. The efficient and easiest way of developing QPM hybrids was by backcross breeding in marker aided selection. Hence, the present investigation aimed at conversion of elite maize inbred line BML-7 into QPM line. CML-186 was identified to be a donor variety as it revealed high-quality polymorphism with BML-7 for opaque-2 gene specific marker umc1066. Non-QPM inbred line BML-7 was crossed with QPM donor CML-186 and produced F 1 followed by the development of BC 1 F 1 and BC 2 F 1 population. Foreground selection was carried out with umc1066 in F 1 , and selected plants were used for BC 1 F 1 and BC 2 F 1 populations. Two hundred plants were screened in both BC 1 F 1 and BC 2 F 1 population with umc1066 for foreground selection amino acid modifiers. Foreground selected plants for both opaque-2 and amino acid modifiers were screened for background selection for BML-7 genome. Recurrent parent genome (RPG) was calculated for BC 2 F 1 population plants. Two plants have shown with RPG 90-93% in two generation with back cross population. Two BC 2 F 2 populations resulted from marker recognized BC 2 F 1 individuals subjected toward foreground selection followed by tryptophan estimation. The tryptophan and lysine concentration was improved in all the plants. BC 2 F 2 lines developed from hard endosperm kernels were selfed for BC 2 F 2 lines and finest line was selected to illustrate the QPM version of BML-7, with 0.97% of tryptophan and 4.04% of lysine concentration in protein. Therefore, the QPM version of BML-7 line can be used for the development of single cross hybrid QPM maize version.

First Observation of a Baryonic Bc+ Decay

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Chefdeville, M.; Chen, S.; Cheung, S.-F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cojocariu, L.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Counts, I.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dreimanis, K.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, H.-M.; Evans, T.; Falabella, A.; Färber, C.; Farinelli, C.; Farley, N.; Farry, S.; Fay, RF; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; García Pardiñas, J.; Garofoli, J.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gavrilov, G.; Geraci, A.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianelle, A.; Giani', S.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gotti, C.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Hernando Morata, J. A.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Karodia, S.; Kelsey, M.; Kenyon, I. R.; Ketel, T.; Khanji, B.; Khurewathanakul, C.; Klaver, S.; Klimaszewski, K.; Kochebina, O.; Kolpin, M.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Likhomanenko, T.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lowdon, P.; Lu, H.; Lucchesi, D.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Malinin, A.; Manca, G.; Mancinelli, G.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marino, P.; Märki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martín Sánchez, A.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M.-N.; Moggi, N.; Molina Rodriguez, J.; Monteil, S.; Morandin, M.; Morawski, P.; Mordà, A.; Morello, M. J.; Moron, J.; Morris, A.-B.; Mountain, R.; Muheim, F.; Müller, K.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, G.; Orlandea, M.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrignani, C.; Pazos Alvarez, A.; Pearce, A.; Pellegrino, A.; Pepe Altarelli, M.; Perazzini, S.; Perez Trigo, E.; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Petridis, K.; Petrolini, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Pistone, A.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Price, E.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Rachwal, B.; Rademacker, J. H.; Rakotomiaramanana, B.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Roa Romero, D. A.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruiz, H.; Ruiz Valls, P.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrie, M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Sepp, I.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, E.; Smith, J.; Smith, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Stroili, R.; Subbiah, V. K.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szilard, D.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; Voss, H.; de Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiedner, D.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.; LHCb Collaboration

2014-10-01

A baryonic decay of the Bc+ meson, Bc+→J/ψpp ¯π+, is observed for the first time, with a significance of 7.3 standard deviations, in pp collision data collected with the LHCb detector and corresponding to an integrated luminosity of 3.0 fb-1 taken at center-of-mass energies of 7 and 8 TeV. With the Bc+→J/ψπ+ decay as the normalization channel, the ratio of branching fractions is measured to be B(Bc+→J/ψpp ¯π+)/B(Bc+→J/ψπ+)=0.143-0.034+0.039(stat)±0.013(syst). The mass of the Bc+ meson is determined as M(Bc+)=6274.0±1.8(stat)±0.4(syst) MeV/c2, using the Bc+→J/ψpp ¯π+ channel.

The brain cytoplasmic RNA BC1 regulates dopamine D2 receptor-mediated transmission in the striatum.

PubMed

Centonze, Diego; Rossi, Silvia; Napoli, Ilaria; Mercaldo, Valentina; Lacoux, Caroline; Ferrari, Francesca; Ciotti, Maria Teresa; De Chiara, Valentina; Prosperetti, Chiara; Maccarrone, Mauro; Fezza, Filomena; Calabresi, Paolo; Bernardi, Giorgio; Bagni, Claudia

2007-08-15

Dopamine D(2) receptor (D(2)DR)-mediated transmission in the striatum is remarkably flexible, and changes in its efficacy have been heavily implicated in a variety of physiological and pathological conditions. Although receptor-associated proteins are clearly involved in specific forms of synaptic plasticity, the molecular mechanisms regulating the sensitivity of D(2) receptors in this brain area are essentially obscure. We have studied the physiological responses of the D(2)DR stimulations in mice lacking the brain cytoplasmic RNA BC1, a small noncoding dendritically localized RNA that is supposed to play a role in mRNA translation. We show that the efficiency of D(2)-mediated transmission regulating striatal GABA synapses is under the control of BC1 RNA, through a negative influence on D(2) receptor protein level affecting the functional pool of receptors. Ablation of the BC1 gene did not result in widespread dysregulation of synaptic transmission, because the sensitivity of cannabinoid CB(1) receptors was intact in the striatum of BC1 knock-out (KO) mice despite D(2) and CB(1) receptors mediated similar electrophysiological actions. Interestingly, the fragile X mental retardation protein FMRP, one of the multiple BC1 partners, is not involved in the BC1 effects on the D(2)-mediated transmission. Because D(2)DR mRNA is apparently equally translated in the BC1-KO and wild-type mice, whereas the protein level is higher in BC1-KO mice, we suggest that BC1 RNA controls D(2)DR indirectly, probably regulating translation of molecules involved in D(2)DR turnover and/or stability.

Joint measurements of black carbon and particle mass for heavy-duty diesel vehicles using a portable emission measurement system

NASA Astrophysics Data System (ADS)

Zheng, Xuan; Wu, Ye; Zhang, Shaojun; Baldauf, Richard W.; Zhang, K. Max; Hu, Jingnan; Li, Zhenhua; Fu, Lixin; Hao, Jiming

2016-09-01

The black carbon (BC) emitted from heavy-duty diesel vehicles (HDDVs) is an important source of urban atmospheric pollution and creates strong climate-forcing impacts. The emission ratio of BC to total particle mass (PM) (i.e., BC/PM ratio) is an essential variable used to estimate total BC emissions from historical PM data; however, these ratios have not been measured using portable emission measurement systems (PEMS) in order to obtain real-world measurements over a wide range of driving conditions. In this study, we developed a PEMS platform by integrating two Aethalometers and an electric low pressure impactor to realize the joint measurement of real-world BC and PM emissions for ten HDDVs in China. Test results showed that the average BC/PM ratio for five HDDVs equipped with mechanical fuel injection (MI) engines was 0.43 ± 0.06, significantly lower (P < 0.05) than another five HDDVs equipped with electronically-controlled fuel injection (EI) engines (0.56 ± 0.12). Traffic conditions also affected the BC/PM ratios with higher ratios on freeway routes than on local roads. Furthermore, higher ratios were observed for HDDVs equipped with EI engines than for the MI engines for the highway and local road routes. With an operating mode binning approach, we observed that the instantaneous BC/PM ratios of EI engine vehicles were above those of the MI engine vehicles in all operating modes except for the braking mode (i.e., Bin 0). Therefore, the complex impacts from engine technology and traffic conditions on BC/PM ratios should be carefully considered when estimating real-world BC emissions from HDDVs based on overall PM emissions data.

"Best Case/Worst Case": Training Surgeons to Use a Novel Communication Tool for High-Risk Acute Surgical Problems.

PubMed

Kruser, Jacqueline M; Taylor, Lauren J; Campbell, Toby C; Zelenski, Amy; Johnson, Sara K; Nabozny, Michael J; Steffens, Nicole M; Tucholka, Jennifer L; Kwekkeboom, Kris L; Schwarze, Margaret L

2017-04-01

Older adults often have surgery in the months preceding death, which can initiate postoperative treatments inconsistent with end-of-life values. "Best Case/Worst Case" (BC/WC) is a communication tool designed to promote goal-concordant care during discussions about high-risk surgery. The objective of this study was to evaluate a structured training program designed to teach surgeons how to use BC/WC. Twenty-five surgeons from one tertiary care hospital completed a two-hour training session followed by individual coaching. We audio-recorded surgeons using BC/WC with standardized patients and 20 hospitalized patients. Hospitalized patients and their families participated in an open-ended interview 30 to 120 days after enrollment. We used a checklist of 11 BC/WC elements to measure tool fidelity and surgeons completed the Practitioner Opinion Survey to measure acceptability of the tool. We used qualitative analysis to evaluate variability in tool content and to characterize patient and family perceptions of the tool. Surgeons completed a median of 10 of 11 BC/WC elements with both standardized and hospitalized patients (range 5-11). We found moderate variability in presentation of treatment options and description of outcomes. Three months after training, 79% of surgeons reported BC/WC is better than their usual approach and 71% endorsed active use of BC/WC in clinical practice. Patients and families found that BC/WC established expectations, provided clarity, and facilitated deliberation. Surgeons can learn to use BC/WC with older patients considering acute high-risk surgical interventions. Surgeons, patients, and family members endorse BC/WC as a strategy to support complex decision making. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

RNA recognition by a human antibody against brain cytoplasmic 200 RNA

PubMed Central

Jung, Euihan; Lee, Jungmin; Hong, Hyo Jeong; Park, Insoo; Lee, Younghoon

2014-01-01

Diverse functional RNAs participate in a wide range of cellular processes. The RNA structure is critical for function, either on its own or as a complex form with proteins and other ligands. Therefore, analysis of the RNA conformation in cells is essential for understanding their functional mechanisms. However, no appropriate methods have been established as yet. Here, we developed an efficient strategy for panning and affinity maturation of anti-RNA human monoclonal antibodies from a naïve antigen binding fragment (Fab) combinatorial phage library. Brain cytoplasmic 200 (BC200) RNA, which is also highly expressed in some tumors, was used as an RNA antigen. We identified MabBC200-A3 as the optimal binding antibody. Mutagenesis and SELEX experiments showed that the antibody recognized a domain of BC200 in a structure- and sequence-dependent manner. Various breast cancer cell lines were further examined for BC200 RNA expression using conventional hybridization and immunoanalysis with MabBC200-A3 to see whether the antibody specifically recognizes BC200 RNA among the total purified RNAs. The amounts of antibody-recognizable BC200 RNA were consistent with hybridization signals among the cell lines. Furthermore, the antibody was able to discriminate BC200 RNA from other RNAs, supporting the utility of this antibody as a specific RNA structure-recognizing probe. Intriguingly, however, when permeabilized cells were subjected to immunoanalysis instead of purified total RNA, the amount of antibody-recognizable RNA was not correlated with the cellular level of BC200 RNA, indicating that BC200 RNA exists as two distinct forms (antibody-recognizable and nonrecognizable) in breast cancer cells and that their distribution depends on the cell type. Our results clearly demonstrate that anti-RNA antibodies provide an effective novel tool for detecting and analyzing RNA conformation. PMID:24759090

Cyclophilin 40 facilitates HSP90-mediated RISC assembly in plants.

PubMed

Iki, Taichiro; Yoshikawa, Manabu; Meshi, Tetsuo; Ishikawa, Masayuki

2012-01-18

Posttranscriptional gene silencing is mediated by RNA-induced silencing complexes (RISCs) that contain AGO proteins and single-stranded small RNAs. The assembly of plant AGO1-containing RISCs depends on the molecular chaperone HSP90. Here, we demonstrate that cyclophilin 40 (CYP40), protein phosphatase 5 (PP5), and several other proteins with the tetratricopeptide repeat (TPR) domain associates with AGO1 in an HSP90-dependent manner in extracts of evacuolated tobacco protoplasts (BYL). Intriguingly, CYP40, but not the other TPR proteins, could form a complex with small RNA duplex-bound AGO1. Moreover, CYP40 that was synthesized by in-vitro translation using BYL uniquely facilitated binding of small RNA duplexes to AGO1, and as a result, increased the amount of mature RISCs that could cleave target RNAs. CYP40 was not contained in mature RISCs, indicating that the association is transient. Addition of PP5 or cyclophilin-binding drug cyclosporine A prevented the association of endogenous CYP40 with HSP90-AGO1 complex and inhibited RISC assembly. These results suggest that a complex of AGO1, HSP90, CYP40, and a small RNA duplex is a key intermediate of RISC assembly in plants.

Effects of photochemical oxidation on the mixing state and light absorption of black carbon in the urban atmosphere of China

NASA Astrophysics Data System (ADS)

Wang, Qiyuan; Huang, Rujin; Zhao, Zhuzi; Cao, Junji; Ni, Haiyan; Tie, Xuexi; Zhu, Chongshu; Shen, Zhenxing; Wang, Meng; Dai, Wenting; Han, Yongming; Zhang, Ningning; Prévôt, André S. H.

2017-04-01

The relationship between the refractory black carbon (rBC) aerosol mixing state and the atmospheric oxidation capacity was investigated to assess the possible influence of oxidants on the particles’ light absorption effects at two large cities in China. The number fraction of thickly-coated rBC particles (F rBC) was positively correlated with a measure of the oxidant concentrations (OX = O3 + NO2), indicating an enhancement of coated rBC particles under more oxidizing conditions. The slope of a linear regression of F rBC versus OX was 0.58% ppb-1 for Beijing and 0.84% ppb-1 for Xi’an, and these relationships provide some insights into the evolution of rBC mixing state in relation to atmospheric oxidation processes. The mass absorption cross-section of rBC (MACrBC) increased with OX during the daytime at Xi’an, at a rate of 0.26 m2 g-1 ppb-1, suggesting that more oxidizing conditions lead to internal mixing that enhances the light-absorbing capacity of rBC particles. Understanding the dependence of the increasing rates of F rBC and MACrBC as a function of OX may lead to improvements of climate models that deal with the warming effects, but more studies in different cities and seasons are needed to gauge the broader implications of these findings.

H-Bonding Assisted Self-Assembly of Anionic and Neutral Ligand on Metal: A Comprehensive Strategy To Mimic Ditopic Ligands in Olefin Polymerization.

PubMed

Mote, Nilesh R; Patel, Ketan; Shinde, Dinesh R; Gaikwad, Shahaji R; Koshti, Vijay S; Gonnade, Rajesh G; Chikkali, Samir H

2017-10-16

Self-assembly of two neutral ligands on a metal to mimic bidentate ligand coordination has been frequently encountered in the recent past, but self-assembly of an anionic ligand on a metal template alongside a neutral ligand remains an elusive target. Such a self-assembly is hampered by additional complexity, wherein a highly negatively charged anion can form intermolecular hydrogen bonding with the supramolecular motif, leaving no scope for self-assembly with neutral ligand. Presented here is the self-association of anionic ligand 3-ureidobenzoic acid (2a) and neutral ligand 1-(3-(diphenylphosphanyl)phenyl)urea (1a) on a metal template to yield metal complex [{COOC 6 H 4 NH(CO)NH 2 }{Ph 2 PC 6 H 4 NH(CO)NH 2 }PdMeDMSO] (4a). The identity of 4a was established by NMR and mass spectroscopy. Along the same lines, 3-(3-phenylureido)benzoic acid (2b) and 1-(3-(diphenylphosphanyl)phenyl)-3-phenylurea (1b) self-assemble on a metal template to produce palladium complex [{COOC 6 H 4 NH(CO)NHPh}{Ph 2 PC 6 H 4 NH(CO)NHPh}PdMePy] (5c). The existence of 5c was confirmed by Job plot, 1-2D NMR spectroscopy, deuterium labeling, IR spectroscopy, UV-vis spectroscopy, model complex synthesis, and DFT calculations. These solution and gas phase investigations authenticated the presence of intramolecular hydrogen bonding between hydrogen's of 1b and carbonyl oxygen of 2b. The generality of the supramolecular approach has been validated by preparing six complexes from four monodentate ligands, and their synthetic utility was demonstrated in ethylene polymerization. Complex 4a was found to be the most active, leading to the production of highly branched polyethylene with a molecular weight of 55700 g/mol and melting temperature of 112 °C.

Neighborhood Socioeconomic Deprivation, Tumor Subtypes, and Causes of Death after Non-Metastatic Invasive Breast Cancer Diagnosis: A Multilevel Competing-Risk Analysis

PubMed Central

Lian, Min; Pérez, Maria; Liu, Ying; Schootman, Mario; Frisse, Ann; Foldes, Ellen; Jeffe, Donna B.

2014-01-01

Purpose To examine the associations of neighborhood socioeconomic deprivation and triple-negative breast cancer (TNBC) subtype with causes of death (breast cancer [BC]-specific and non-BC-specific) among non-metastatic invasive BC patients. Methods We identified 3,312 patients younger than 75 years (mean age 53.5 years; 621 [18.8%] TNBC) with first primary BC treated at an academic medical center from 1999–2010. We constructed a census-tract-level socioeconomic deprivation index using the 2000 U.S. Census data and performed a multilevel competing-risk analysis to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of BC-specific and non-BC-specific mortality associated with neighborhood socioeconomic deprivation and TNBC subtype. The adjusted models controlled for patient sociodemographics, health behaviors, tumor characteristics, comorbidity, and cancer treatment. Results With a median 62-month follow-up, 349 (10.5%) patients died; 233 died from BC. In the multivariate models, neighborhood socioeconomic deprivation was independently associated with non-BC-specific mortality (the most- vs. the least-deprived quartile: HR=2.98, 95% CI=1.33–6.66); in contrast, its association with BC-specific mortality was explained by the aforementioned patient-level covariates, particularly sociodemographic factors (HR=1.15, 95% CI=0.71–1.87). TNBC subtype was independently associated with non-BC-specific mortality (HR=2.15; 95% CI=1.20–3.84), while the association between TNBC and BC-specific mortality approached significance (HR=1.42; 95% CI=0.99–2.03, P=0.057). Conclusions Non-metastatic invasive BC patients who lived in more socioeconomically deprived neighborhoods were more likely to die as a result of causes other than breast cancer compared with those living in the least socioeconomically deprived neighborhoods. TNBC was associated with non-BC-specific mortality but not BC-specific mortality. PMID:25234843

Assembly and disassembly of the nucleolus during the cell cycle.

PubMed

Hernandez-Verdun, Danièle

2011-01-01

The nucleolus is a large nuclear domain in which transcription, maturation and assembly of ribosomes take place. In higher eukaryotes, nucleolar organization in three sub-domains reflects the compartmentation of the machineries related to active or inactive transcription of the ribosomal DNA, ribosomal RNA processing and assembly with ribosomal proteins of the two (40S and 60S) ribosomal subunits. The assembly of the nucleoli during telophase/early G(1) depends on pre-existing machineries inactivated during prophase (the transcription machinery and RNP processing complexes) and on partially processed 45S rRNAs inherited throughout mitosis. In telophase, the 45S rRNAs nucleate the prenucleolar bodies and order the dynamics of nucleolar assembly. The assembly/disassembly processes of the nucleolus depend on the equilibrium between phosphorylation/dephosphorylation of the transcription machinery and on the RNP processing complexes under the control of the CDK1-cyclin B kinase and PP1 phosphatases. The dynamics of assembly/disassembly of the nucleolus is time and space regulated.

Citrus Epicarp-Derived Biochar Reduced Cd Uptake and Ameliorates Oxidative Stress in Young Abelmoschus esculentus (L.) Moench (okra) Under Low Cd Stress.

PubMed

Ogunkunle, Clement O; Varun, Mayank; Ogundele, Iyanuoluwa G; Olorunmaiye, Kehinde S; Paul, Manoj S

2018-06-01

Due to the important role of biochar (BC) in reducing metal-toxicity in plants, this study was aimed at assessing the potential of citrus epicarp-derived BC in ameliorating Cd toxicity in young Abelmoschus esculentus (okra) under low Cd toxicity. Okra was grown in soil amended with BC at four treatment levels for 49 days as follows: control (A), sole 1.4 mg Cd/kg-spiked soil (B), 1.4 mg Cd/kg-spiked soil + 1% BC (C) and 1.4 mg Cd/kg-spiked soil + 3% BC (D). The results showed a dose-dependent reduction in shoot accumulation of Cd due to the BC application. In addition, compared to control and sole Cd-amended soil, BC treatments (both at 1% and 3% w/w) decreased the oxidative stress, and enhanced activities of enzymatic and non-enzymatic antioxidants in the young okra. Generally, the application of BC to the soil was effective in ameliorating the Cd-induced oxidative stress in okra with limited shoot bioaccumulation of Cd.

A New Method to Obtain the Black Carbon Mixing State of Biomass and Combustion Aerosols

NASA Astrophysics Data System (ADS)

Irwin, M.; Liu, D.; Joshi, R.; Allan, J. D.; Coe, H.; Flynn, M.; Olfert, J. S.; Broda, K.; Fu, P.; Sun, Y.; Ge, X.; Wang, J.

2017-12-01

Black carbon particles (BC) significantly contribute to warming effects in the atmosphere, altering weather systems, and pose significant health risks. These impacts are especially efficient at regional hotspots with high emissions of pollutants, such as in fast-developing megacities. These urban environments have the most population exposure, and improving the understanding of the sources and the processing of pollutants in these environments is critical in guiding policy making. Here we present the results of BC characterization in Beijing during the winter of 2016 (10th Nov-10th Dec), as part of a large joint UK-China field experiment. During this experiment, we successfully gathered 4 weeks of continuous measurements, including several severe pollution events in Beijing. MethodologyThe mixing state of BC, which is how BC is associated with non-BC material (its coating) within a particle, is crucial to determine its lifetime in the atmosphere and also its optical properties. However precisely quantifying the BC mixing state has posed a challenge, in part due to complex particle morphology. We have applied morphology-independent measurements of BC mixing state on a single-particle basis throughout this experiment: mono-dispersed particle mass (MP) is selected using a Centrifugal Particle Mass Analyser (CPMA, Cambustion Ltd) and a single particle soot photometer (SP2, DMT inc.) was used downstream of the CPMA to measure the refractory BC mass (MrBC). The full scan of CPMA masses (21 mass bins covering most of MP) are performed every half hour, following polydispersed particles measured without running CPMA.

Assembly of Photosynthetic Antenna Protein Complexes from Algae for Development of Nano-biodevice and Its Fuelization

DTIC Science & Technology

2013-05-20

More recently the structures of the LH2 complexes has revealed the nonameric and octameric arrangement of repeating units consisting of two...Compartimentalization of light -harvesting and charge separation. The antenna complexes( LH2 ,LH1-RC) efficiently realize various photosynthetic functions...using cofactors (BChl a and carotenoid) assembled into the apoproteins (LH1 and LH2 ). The light-harvesting mechanisms in these light-harvesting

Characterization of the quantitative trait locus OilA1 for oil content in Brassica napus.

PubMed

Chen, Yubo; Qi, Lu; Zhang, Xiaoyu; Huang, Jixiang; Wang, Jibian; Chen, Hongcheng; Ni, Xiyuan; Xu, Fei; Dong, Yanjun; Xu, Haiming; Zhao, Jianyi

2013-10-01

Increasing seed oil content has become one of the most important breeding criteria in rapeseed (Brassica napus). However, oil content is a complex quantitative trait. QTL mapping in a double haploid population (SG population) emerging from a cross between a German (Sollux) and Chinese (Gaoyou) cultivars revealed one QTL for oil content on linkage group A1 (OilA1), which was mapped to a 17 cM genetic interval. To further validate and characterize the OilA1, we constructed a high-resolution map using B. rapa sequence resources and developed a set of near-isogenic lines (NILs) by employing a DH line SG-DH267 as donor and Chinese parent Gaoyou as recurrent background. The results showed highly conserved synteny order between B. rapa and B. napus within the linkage group A1 and revealed a possible centromere region between two markers ZAASA1-38 and NTP3 (2.5 cM). OilA1 was firstly validated by 250 BC5F2 plants and was confirmed in a 10.6 cM interval between the markers ZAASA1-47 and ZAASA1-77. Further substitution mapping was conducted by using two generations of QTL-NILs, 283 lines from eight BC5F3:4 families and 428 plants from six BC5F4 sub-NILs and thus narrowed the OilA1 interval to 6.9 cM and 4.3 cM (1.4 Mb), respectively. Field investigations with two replications using homozygous BC5F3:4 sister sub-NILs indicated that NILs, which carry a Sollux chromosome segment across the target region showed significant higher oil content (1.26 %, p < 0.001) than their sister NILs containing Gaoyou chromosome. The OilA1 locus is of particular interest for breeding purpose in China because 80 % of Chinese cultivars do not carry this desirable allele.

G.I. Joe Meets Barbie, Software Engineer Meets Caregiver: Males and Females in B.C.'s Public Schools and Beyond. BCTF Research Report.

ERIC Educational Resources Information Center

Schaefer, Anne C.

Following a referral from the March 2000 Annual General Meeting of the British Columbia (B.C.) Teachers' Federation, the Spring 2000 Representative Assembly passed a motion that recommended research be collected, conducted, and disseminated on the current status of students in the province. This research report identifies current information on…

Increased metabolic activity detected by FLIM in human breast cancer cells with desmoplastic reaction: a pilot study

NASA Astrophysics Data System (ADS)

Natal, Rodrigo de Andrade; Pelegati, Vitor B.; Bondarik, Caroline; Mendonça, Guilherme R.; Derchain, Sophie F.; Lima, Carmen P.; Cesar, Carlos L.; Sarian, Luís. O.; Vassallo, José

2015-07-01

Introduction: In breast cancer (BC), desmoplastic reaction, assembled primarily by fibroblasts, is associated with unfavorable prognosis, but the reason of this fact remains still unclear. In this context, nonlinear optics microscopy, including Fluorescence Lifetime Imaging Microscopy (FLIM), has provided advancement in cellular metabolism research. In this paper, our purpose is to differentiate BC cells metabolism with or without contact to desmoplastic reaction. Formalin fixed, paraffin embedded samples were used at different points of hematoxylin stained sections. Methodology: Sections from 14 patients with invasive ductal breast carcinoma were analyzed with FLIM methodology to NAD(P)H and FAD fluorescence lifetime on a Confocal Upright LSM780 NLO device (Carl Zeiss AG, Germany). Quantification of the fluorescence lifetime and fluorescence intensity was evaluated by SPC Image software (Becker &Hickl) and ImageJ (NIH), respectively. Optical redox ratio was calculated by dividing the FAD fluorescence intensity by NAD(P)H fluorescence intensity. Data value for FLIM measurements and fluorescence intensities were calculated using Wilcoxon test; p< 0.05 was considered significant. Results: BC cells in contact with desmoplastic reaction presented a significantly lower NAD(P)H and FAD fluorescence lifetime. Furthermore, optical redox ratio was also lower in these tumor cells. Conclusion: Our results suggest that contact of BC cells with desmoplastic reaction increase their metabolic activity, which might explain the adverse prognosis of cases associated with higher peritumoral desmoplastic reaction.

New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients.

PubMed

Rodríguez-Iglesias, Beatriz; Novella-Maestre, Edurne; Herraiz, Sonia; Díaz-García, César; Pellicer, Nuria; Pellicer, Antonio

2015-12-01

To develop a novel molecular panel of markers to detect breast cancer (BC) disseminated malignant cells in ovarian tissue, and to improve the safety of ovarian tissue transplantation. Experimental study. University hospital. Ten ovarian biopsies from healthy patients, 13 biopsies with diagnosed BC metastasis, and 4 biopsies from primary BC tumor for designing a diagnostic panel of BC cell contamination; 60 ovarian biopsies from BC patients undergoing fertility preservation for validating the panel. Female nude mice. A novel panel for BC malignant cell detection by reverse-transcription polymerase chain reaction (RT-PCR), inmmunohistochemical analysis, in vitro invasion assay and xenotransplantation assayed in ovarian tissue from BC patients. Expression of GCDFP15, MGB1, SBEM, MUC1, WT-1, and NY-BR-01, selected as markers, assessed by quantitative RT-PCR in samples with confirmed BC metastasis. The most sensitive markers were confirmed by immunohistochemistry, and tested in vitro and in vivo. GCDFP15, MGB1, and SBEM were the most sensitive and specific markers to detect BC metastatic cells when at least one was expressed by quantitative RT-PCR. The panel was validated in 60 patients and confirmed in an in vitro invasion assay, where no invasive cells were observed. Samples negative for BC cells cannot develop disease when xenografted. GCDFP15, MGB1, and SBEM were the most sensitive molecules to create a diagnostic panel for BC malignant cell contamination, which may make ovarian tissue cryopreservation and transplantation a safe technique for fertility preservation in BC patients. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Assessing the chemical and biological accessibility of the herbicide isoproturon in soil amended with biochar.

PubMed

Sopeña, Fatima; Semple, Kirk; Sohi, Saran; Bending, Gary

2012-06-01

There is considerable current interest in using biochar (BC) as a soil amendment to sequester carbon to mitigate climate change. However, the implications of adding BC to agricultural soil for the environmental fate of pesticides remain unclear. In particular, the effect of biochars on desorption behavior of compounds is poorly understood. This study examined the influence of BC on pesticide chemical and biological accessibility using the herbicide isoproturon (IPU). Soils amended with 1% and 2% BC showed enhanced sorption, slower desorption, and reduced biodegradation of IPU. Addition of 0.1% BC had no effect on sorption, desorption or biodegradation of IPU. However, the mineralization of (14)C-IPU was reduced by all BC concentrations, reducing by 13.6%, 40.1% and 49.8% at BC concentrations of 0.1%, 1% and 2% respectively. Further, the ratio of the toxic metabolite 4-isopropyl-aniline to intact IPU was substantially reduced by higher BC concentrations. Hydroxypropyl-β-cyclodextrin (HPCD) extractions were used to estimate the IPU bioaccessibility in the BC-amended soil. Significant correlations were found between HPCD-extracted (14)C-IPU and the IPU desorbed (%) (r(2)=0.8518, p<0.01), and also the (14)C-IPU mineralized (%) (r(2)=0.733; p<0.01) for all BC-amended soils. This study clearly demonstrates how desorption in the presence of BC is intimately related to pesticide biodegradation by the indigenous soil microbiota. BC application to agricultural soils can affect the persistence of pesticides as well as the fate of their degradation products. This has important implications for the effectiveness of pesticides as well as the sequestration of contaminants in soils. Copyright © 2012 Elsevier Ltd. All rights reserved.

Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site

PubMed Central

Calviño, Fabiola R.; Kharde, Satyavati; Ori, Alessandro; Hendricks, Astrid; Wild, Klemens; Kressler, Dieter; Bange, Gert; Hurt, Ed; Beck, Martin; Sinning, Irmgard

2015-01-01

During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11, assembles into a pre-60S particle, where docking relies on RpL11 interacting with helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the pre-60S is not known. Here we report the crystal structure of a ternary symportin Syo1–RpL5-N–RpL11 complex and provide biochemical and structural insights into 5S RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with H84 for binding. Pull-down experiments show that H84 releases RpL11 from the ternary complex, but not in the presence of 5S RNA. Crosslinking mass spectrometry visualizes structural rearrangements on incorporation of 5S RNA into the Syo1–RpL5–RpL11 complex supporting the formation of a pre-5S RNP. Our data underline the dual role of Syo1 in ribosomal protein transport and as an assembly platform for 5S RNP. PMID:25849277

Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site.

PubMed

Calviño, Fabiola R; Kharde, Satyavati; Ori, Alessandro; Hendricks, Astrid; Wild, Klemens; Kressler, Dieter; Bange, Gert; Hurt, Ed; Beck, Martin; Sinning, Irmgard

2015-04-07

During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11, assembles into a pre-60S particle, where docking relies on RpL11 interacting with helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the pre-60S is not known. Here we report the crystal structure of a ternary symportin Syo1-RpL5-N-RpL11 complex and provide biochemical and structural insights into 5S RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with H84 for binding. Pull-down experiments show that H84 releases RpL11 from the ternary complex, but not in the presence of 5S RNA. Crosslinking mass spectrometry visualizes structural rearrangements on incorporation of 5S RNA into the Syo1-RpL5-RpL11 complex supporting the formation of a pre-5S RNP. Our data underline the dual role of Syo1 in ribosomal protein transport and as an assembly platform for 5S RNP.

Identification of ovule transcripts from the Apospory-Specific Genomic Region (ASGR)-carrier chromosome

PubMed Central

2011-01-01

Background Apomixis, asexual seed production in plants, holds great potential for agriculture as a means to fix hybrid vigor. Apospory is a form of apomixis where the embryo develops from an unreduced egg that is derived from a somatic nucellar cell, the aposporous initial, via mitosis. Understanding the molecular mechanism regulating aposporous initial specification will be a critical step toward elucidation of apomixis and also provide insight into developmental regulation and downstream signaling that results in apomixis. To discover candidate transcripts for regulating aposporous initial specification in P. squamulatum, we compared two transcriptomes derived from microdissected ovules at the stage of aposporous initial formation between the apomictic donor parent, P. squamulatum (accession PS26), and an apomictic derived backcross 8 (BC8) line containing only the Apospory-Specific Genomic Region (ASGR)-carrier chromosome from P. squamulatum. Toward this end, two transcriptomes derived from ovules of an apomictic donor parent and its apomictic backcross derivative at the stage of apospory initiation, were sequenced using 454-FLX technology. Results Using 454-FLX technology, we generated 332,567 reads with an average read length of 147 base pairs (bp) for the PS26 ovule transcriptome library and 363,637 reads with an average read length of 142 bp for the BC8 ovule transcriptome library. A total of 33,977 contigs from the PS26 ovule transcriptome library and 26,576 contigs from the BC8 ovule transcriptome library were assembled using the Multifunctional Inertial Reference Assembly program. Using stringent in silico parameters, 61 transcripts were predicted to map to the ASGR-carrier chromosome, of which 49 transcripts were verified as ASGR-carrier chromosome specific. One of the alien expressed genes could be assigned as tightly linked to the ASGR by screening of apomictic and sexual F1s. Only one transcript, which did not map to the ASGR, showed expression primarily in reproductive tissue. Conclusions Our results suggest that a strategy of comparative sequencing of transcriptomes between donor parent and backcross lines containing an alien chromosome of interest can be an efficient method of identifying transcripts derived from an alien chromosome in a chromosome addition line. PMID:21521529

Multi-Mode Binding of Cellobiohydrolase Cel7A from Trichoderma reesei to Cellulose

PubMed Central

Jalak, Jürgen; Väljamäe, Priit

2014-01-01

Enzymatic hydrolysis of recalcitrant polysaccharides like cellulose takes place on the solid-liquid interface. Therefore the adsorption of enzymes to the solid surface is a pre-requisite for catalysis. Here we used enzymatic activity measurements with fluorescent model-substrate 4-methyl-umbelliferyl-β-D-lactoside for sensitive monitoring of the binding of cellobiohydrolase TrCel7A from Trichoderma reesei to bacterial cellulose (BC). The binding at low nanomolar free TrCel7A concentrations was exclusively active site mediated and was consistent with Langmuir's one binding site model with K d and A max values of 2.9 nM and 126 nmol/g BC, respectively. This is the strongest binding observed with non-complexed cellulases and apparently represents the productive binding of TrCel7A to cellulose chain ends on the hydrophobic face of BC microfibril. With increasing free TrCel7A concentrations the isotherm gradually deviated from the Langmuir's one binding site model. This was caused by the increasing contribution of lower affinity binding modes that included both active site mediated binding and non-productive binding with active site free from cellulose chain. The binding of TrCel7A to BC was found to be only partially reversible. Furthermore, the isotherm was dependent on the concentration of BC with more efficient binding observed at lower BC concentrations. The phenomenon can be ascribed to the BC concentration dependent aggregation of BC microfibrils with concomitant reduction of specific surface area. PMID:25265511

Inflammasome Assembly in the Chorioamniotic Membranes during Spontaneous Labor at Term

PubMed Central

Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Garcia-Flores, Valeria; Leng, Yaozhu; Panaitescu, Bogdan; Miller, Derek; Abrahams, Vikki M.; Hassan, Sonia S.

2017-01-01

Problem Inflammasome activation requires two steps: priming and assembly of the multimeric complex. The second step includes assembly of the sensor molecule and adaptor protein ASC (an apoptosis-associated speck-like protein containing a CARD), which results in ASC speck formation and the recruitment of caspase (CASP)-1. Herein, we investigated whether there is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes from women who underwent spontaneous labor at term. Method of Study Using in situ proximity ligation assays, ASC/CASP-1 complexes were determined in the chorioamniotic membranes from women who delivered at term without labor or underwent spontaneous labor at term with or without acute histologic chorioamnionitis (n=10–11 each). Also, ASC speck formation was determined by flow cytometry in the choriodecidual leukocytes isolated from women who delivered at term with or without spontaneous labor (n=9–12 each). Results 1) ASC/CASP-1 complexes were detected in the chorioamniotic membranes; 2) ASC/CASP-1 complexes were greater in the chorioamniotic membranes from women who underwent spontaneous labor at term than in those without labor; 3) ASC/CASP-1 complexes were even more abundant in the chorioamniotic membranes from women who underwent spontaneous labor at term with acute histologic chorioamnionitis than in those without this placental lesion; 4) ASC speck formation was detected in the choriodecidual leukocytes; and 5) ASC speck formation was greater in the choriodecidual leukocytes isolated from women who underwent spontaneous labor at term than in those without labor. Conclusion There is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes during spontaneous labor at term. PMID:28233423

Chaperoning 5S RNA assembly.

PubMed

Madru, Clément; Lebaron, Simon; Blaud, Magali; Delbos, Lila; Pipoli, Juliana; Pasmant, Eric; Réty, Stéphane; Leulliot, Nicolas

2015-07-01

In eukaryotes, three of the four ribosomal RNAs (rRNAs)—the 5.8S, 18S, and 25S/28S rRNAs—are processed from a single pre-rRNA transcript and assembled into ribosomes. The fourth rRNA, the 5S rRNA, is transcribed by RNA polymerase III and is assembled into the 5S ribonucleoprotein particle (RNP), containing ribosomal proteins Rpl5/uL18 and Rpl11/uL5, prior to its incorporation into preribosomes. In mammals, the 5S RNP is also a central regulator of the homeostasis of the tumor suppressor p53. The nucleolar localization of the 5S RNP and its assembly into preribosomes are performed by a specialized complex composed of Rpf2 and Rrs1 in yeast or Bxdc1 and hRrs1 in humans. Here we report the structural and functional characterization of the Rpf2-Rrs1 complex alone, in complex with the 5S RNA, and within pre-60S ribosomes. We show that the Rpf2-Rrs1 complex contains a specialized 5S RNA E-loop-binding module, contacts the Rpl5 protein, and also contacts the ribosome assembly factor Rsa4 and the 25S RNA. We propose that the Rpf2-Rrs1 complex establishes a network of interactions that guide the incorporation of the 5S RNP in preribosomes in the initial conformation prior to its rotation to form the central protuberance found in the mature large ribosomal subunit. © 2015 Madru et al.; Published by Cold Spring Harbor Laboratory Press.

Structural Insights into DD-Fold Assembly and Caspase-9 Activation by the Apaf-1 Apoptosome.

PubMed

Su, Tsung-Wei; Yang, Chao-Yu; Kao, Wen-Pin; Kuo, Bai-Jiun; Lin, Shan-Meng; Lin, Jung-Yaw; Lo, Yu-Chih; Lin, Su-Chang

2017-03-07

Death domain (DD)-fold assemblies play a crucial role in regulating the signaling to cell survival or death. Here we report the crystal structure of the caspase recruitment domain (CARD)-CARD disk of the human apoptosome. The structure surprisingly reveals that three 1:1 Apaf-1:procaspase-9 CARD protomers form a novel helical DD-fold assembly on the heptameric wheel-like platform of the apoptosome. The small-angle X-ray scattering and multi-angle light scattering data also support that three protomers could form an oligomeric complex similar to the crystal structure. Interestingly, the quasi-equivalent environment of CARDs could generate different quaternary CARD assemblies. We also found that the type II interaction is conserved in all DD-fold complexes, whereas the type I interaction is found only in the helical DD-fold assemblies. This study provides crucial insights into the caspase activation mechanism, which is tightly controlled by a sophisticated and highly evolved CARD assembly on the apoptosome, and also enables better understanding of the intricate DD-fold assembly. Copyright © 2017 Elsevier Ltd. All rights reserved.

The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression.

PubMed

Silva, Nicola; Ferrandiz, Nuria; Barroso, Consuelo; Tognetti, Silvia; Lightfoot, James; Telecan, Oana; Encheva, Vesela; Faull, Peter; Hanni, Simon; Furger, Andre; Snijders, Ambrosius P; Speck, Christian; Martinez-Perez, Enrique

2014-11-24

Proper chromosome segregation during meiosis requires the assembly of the synaptonemal complex (SC) between homologous chromosomes. However, the SC structure itself is indifferent to homology, and poorly understood mechanisms that depend on conserved HORMA-domain proteins prevent ectopic SC assembly. Although HORMA-domain proteins are thought to regulate SC assembly as intrinsic components of meiotic chromosomes, here we uncover a key role for nuclear soluble HORMA-domain protein HTP-1 in the quality control of SC assembly. We show that a mutant form of HTP-1 impaired in chromosome loading provides functionality of an HTP-1-dependent checkpoint that delays exit from homology search-competent stages until all homolog pairs are linked by the SC. Bypassing of this regulatory mechanism results in premature meiotic progression and licensing of homology-independent SC assembly. These findings identify nuclear soluble HTP-1 as a regulator of early meiotic progression, suggesting parallels with the mode of action of Mad2 in the spindle assembly checkpoint. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Regulatory BC1 RNA Deletion on Synaptic Plasticity, Learning, and Memory

ERIC Educational Resources Information Center

Chung, Ain; Dahan, Nessy; Alarcon, Juan Marcos; Fenton, André A.

2017-01-01

Nonprotein coding dendritic BC1 RNA regulates translation of mRNAs in neurons. We examined two lines of BC1 knockout mice and report that loss of BC1 RNA exaggerates group I mGluR-stimulated LTD of the Schaffer collateral synapse, with one of the lines showing a much more enhanced DHPG-induced LTD than the other. When the animals were given the…

Assessing predicted age-specific breast cancer mortality rates in 27 European countries by 2020.

PubMed

Clèries, R; Rooney, R M; Vilardell, M; Espinàs, J A; Dyba, T; Borras, J M

2018-03-01

We assessed differences in predicted breast cancer (BC) mortality rates, across Europe, by 2020, taking into account changes in the time trends of BC mortality rates during the period 2000-2010. BC mortality data, for 27 European Union (EU) countries, were extracted from the World Health Organization mortality database. First, we compared BC mortality data between time periods 2000-2004 and 2006-2010 through standardized mortality ratios (SMRs) and carrying out a graphical assessment of the age-specific rates. Second, making use of the base period 2006-2012, we predicted BC mortality rates by 2020. Finally, making use of the SMRs and the predicted data, we identified a clustering of countries, assessing differences in the time trends between the areas defined in this clustering. The clustering approach identified two clusters of countries: the first cluster were countries where BC predicted mortality rates, in 2020, might slightly increase among women aged 69 and older compared with 2010 [Greece (SMR 1.01), Croatia (SMR 1.02), Latvia (SMR 1.15), Poland (SMR 1.14), Estonia (SMR 1.16), Bulgaria (SMR 1.13), Lithuania (SMR 1.03), Romania (SMR 1.13) and Slovakia (SMR 1.06)]. The second cluster was those countries where BC mortality rates level off or decrease in all age groups (remaining countries). However, BC mortality rates between these clusters might diminish and converge to similar figures by 2020. For the year 2020, our predictions have shown a converging pattern of BC mortality rates between European regions. Reducing disparities, in access to screening and treatment, could have a substantial effect in countries where a non-decreasing trend in age-specific BC mortality rates has been predicted.

Anthropogenic Black Carbon Emission Increase during the Last 150 Years at Coastal Jiangsu, China

PubMed Central

Bao, Kunshan; Shen, Ji; Wang, Guoping; Gao, Chuanyu

2015-01-01

Black carbon (BC) is one of the major drivers of climate change and a useful indicator of environmental pollution from industrialization, and thus it is essential to reconstruct the historical trend in BC flux to better understand its impact. The Yancheng coastal wetland reserve in Jiangsu province is an area sensitive to global sea level change and is also located in the most developed as well as most polluted region of China. We investigated the concentration and historical flux of BC over the past 150 years through geochemical analysis of two 210Pb-dated sediment cores from Yancheng coastal wetland. Measured BC contents ranged from 0.24 mg g-1 to 1.41 mg g-1 with average values of 0.51mg g-1-0.69 mg g-1, and BC fluxes ranged from 0.69 g m-2 yr-1 to 11.80 g m-2 yr-1 with averages of 2.94g m-2 yr-1-3.79 g m-2 yr-1. These values are consistent with other records worldwide. Both BC content and flux show a gradual and continuous increase over time and clearly reflect increased emissions from anthropogenic activities. The BC records have a significant peak in recent years (from 2000 to 2007), which is accompanied by the sharp increase of energy consumption and total carbon emission in the region. It is reasonable to conclude that changes in BC from increasing human activities have controlled BC fluxes during the last 150 years. Industrial contamination, especially BC emission, in the coastal region of eastern China should be taken into account when developing management strategies for protecting the natural environment. PMID:26200665

Proteins from Multiple Metabolic Pathways Associate with Starch Biosynthetic Enzymes in High Molecular Weight Complexes: A Model for Regulation of Carbon Allocation in Maize Amyloplasts1[C][W][OA

PubMed Central

Hennen-Bierwagen, Tracie A.; Lin, Qiaohui; Grimaud, Florent; Planchot, Véronique; Keeling, Peter L.; James, Martha G.; Myers, Alan M.

2009-01-01

Starch biosynthetic enzymes from maize (Zea mays) and wheat (Triticum aestivum) amyloplasts exist in cell extracts in high molecular weight complexes; however, the nature of those assemblies remains to be defined. This study tested the interdependence of the maize enzymes starch synthase IIa (SSIIa), SSIII, starch branching enzyme IIb (SBEIIb), and SBEIIa for assembly into multisubunit complexes. Mutations that eliminated any one of those proteins also prevented the others from assembling into a high molecular mass form of approximately 670 kD, so that SSIII, SSIIa, SBEIIa, and SBEIIb most likely all exist together in the same complex. SSIIa, SBEIIb, and SBEIIa, but not SSIII, were also interdependent for assembly into a complex of approximately 300 kD. SSIII, SSIIa, SBEIIa, and SBEIIb copurified through successive chromatography steps, and SBEIIa, SBEIIb, and SSIIa coimmunoprecipitated with SSIII in a phosphorylation-dependent manner. SBEIIa and SBEIIb also were retained on an affinity column bearing a specific conserved fragment of SSIII located outside of the SS catalytic domain. Additional proteins that copurified with SSIII in multiple biochemical methods included the two known isoforms of pyruvate orthophosphate dikinase (PPDK), large and small subunits of ADP-glucose pyrophosphorylase, and the sucrose synthase isoform SUS-SH1. PPDK and SUS-SH1 required SSIII, SSIIa, SBEIIa, and SBEIIb for assembly into the 670-kD complex. These complexes may function in global regulation of carbon partitioning between metabolic pathways in developing seeds. PMID:19168640

The prevalence of BRCA mutations among familial breast cancer patients in Korea: results of the Korean Hereditary Breast Cancer study.

PubMed

Han, Sang-Ah; Kim, Sung-Won; Kang, Eunyoung; Park, Sue K; Ahn, Sei-Hyun; Lee, Min Hyuk; Nam, Seok-Jin; Han, Wonshik; Bae, Young Tae; Kim, Hyun-Ah; Cho, Young Up; Chang, Myung Chul; Paik, Nam Sun; Hwang, Ki-Tae; Kim, Sei Joong; Noh, Dong-Young; Choi, Doo Ho; Noh, Woo-Chul; Kim, Lee Su; Kim, Ku Sang; Suh, Young Jin; Lee, Jeong Eon; Jung, Yongsik; Moon, Byung-In; Yang, Jung-Hyun; Son, Byung Ho; Yom, Cha Kyong; Kim, Sung Yong; Lee, Hyde; Jung, Sung Hoo

2013-03-01

The primary aim of this study was to estimate the prevalence of BRCA1/2 mutations among familial breast cancer (BC) patients in Korea. We analyzed 775 familial BC patients who were enrolled in the Korean Hereditary Breast Cancer (KOHBRA) study and treated at 36 institutions between May 2007 and May 2010. Patients with familial BC were defined as BC patients with family histories of BC or ovarian cancer (OC) in any relatives. All probands received genetic counseling and BRCA genetic testing was performed after obtaining informed consent. The mean age of BC diagnosis was 43.6 years. The numbers of probands with family histories of BC only and OC only were 682 and 93, respectively. The overall prevalence of the BRCA mutation among familial BC patients was 21.7 % (BRCA1 9.3 % and BRCA2 12.4 %). Subgroup analyses observed prevalences of the BRCA mutation as follows: 19.6 % among patients with BC family history only (BRCA1 7.6 % and BRCA2 12.0 %) and 36.6 % among patients with OC family history only (BRCA1 21.5 % and BRCA2 15.1 %). Most of the subgroups satisfied the 10 % probability criteria to undergo BRCA testing. However, the prevalence of the BRCA mutations among subgroups that had 2 BC patients in a family with both age at diagnosis of more than 50 years old did not reach the 10 % criteria (4.1 %). Korean familial BC patients are good candidates for BRCA testing even when they have family histories of single breast cancers. However, proband age at diagnosis should be carefully considered when selecting patients for testing.

Rewriting the Central European Early Bronze Age Chronology: Evidence from Large-Scale Radiocarbon Dating

PubMed Central

Knipper, Corina; Friedrich, Ronny; Kromer, Bernd; Lindauer, Susanne; Radosavljević, Jelena; Wittenborn, Fabian; Krause, Johannes

2015-01-01

The transition from the Neolithic to the Early Bronze Age in Central Europe has often been considered as a supra-regional uniform process, which led to the growing mastery of the new bronze technology. Since the 1920s, archaeologists have divided the Early Bronze Age into two chronological phases (Bronze A1 and A2), which were also seen as stages of technical progress. On the basis of the early radiocarbon dates from the cemetery of Singen, southern Germany, the beginning of the Early Bronze Age in Central Europe was originally dated around 2300/2200 BC and the transition to more complex casting techniques (i.e., Bronze A2) around 2000 BC. On the basis of 140 newly radiocarbon dated human remains from Final Neolithic, Early and Middle Bronze Age cemeteries south of Augsburg (Bavaria) and a re-dating of ten graves from the cemetery of Singen, we propose a significantly different dating range, which forces us to re-think the traditional relative and absolute chronologies as well as the narrative of technical development. We are now able to date the beginning of the Early Bronze Age to around 2150 BC and its end to around 1700 BC. Moreover, there is no transition between Bronze (Bz) A1 and Bronze (Bz) A2, but a complete overlap between the type objects of the two phases from 1900–1700 BC. We thus present a revised chronology of the assumed diagnostic type objects of the Early Bronze Age and recommend a radiocarbon-based view on the development of the material culture. Finally, we propose that the traditional phases Bz A1 and Bz A2 do not represent a chronological sequence, but regionally different social phenomena connected to the willingness of local actors to appropriate the new bronze technology. PMID:26488413

BcGs1, a glycoprotein from Botrytis cinerea, elicits defence response and improves disease resistance in host plants.

PubMed

Zhang, Yi; Zhang, Yunhua; Qiu, Dewen; Zeng, Hongmei; Guo, Lihua; Yang, Xiufen

2015-02-20

In this study, a necrosis-inducing protein was purified from the culture filtrate of the necrotrophic fungus Botrytis cinerea BC-98 strain. Secreted proteins were collected and fractionated by liquid chromatography. The fraction with the highest necrosis-inducing activity was further purified. A glycoprotein named BcGs1 was identified by 2D electrophoresis and mass spectrometry. The BcGs1 protein consisted of 672 amino acids with a theoretical molecular weight of 70.487 kDa. Functional domain analysis indicated that BcGs1 was a glucan 1,4-alpha-glucosidase, a cell wall-degrading enzyme, with a Glyco_hydro_15 domain and a CBM20_glucoamylase domain. The BcGs1 protein caused necrotic lesions that mimicked a typical hypersensitive response and H2O2 production in tomato and tobacco leaves. BcGs1-treated plants exhibited resistance to B. cinerea, Pseudomonas syringae pv. tomato DC3000 and tobacco mosaic virus in systemic leaves. In addition, BcGs1 triggered elevation of the transcript levels of the defence-related genes PR-1a, TPK1b and Prosystemin. This is the first report of a Botrytis glucan 1,4-alpha-glucosidase triggering host plant immunity as an elicitor. These results lay a foundation for further study of the comprehensive interaction between plants and necrotrophic fungi. Copyright © 2015 Elsevier Inc. All rights reserved.

The risk of bladder cancer in patients with urinary calculi: a meta-analysis.

PubMed

Yu, Zhang; Yue, Wu; Jiuzhi, Li; Youtao, Jiang; Guofei, Zhang; Wenbin, Guo

2018-01-05

The objective of this meta-analysis was to evaluate the association between a history of urinary calculi (UC) and the risk of bladder cancer (BC). A literature search was performed from inception until July 2017. Studies that reported odds ratios (OR), relative risks or hazard ratios comparing the risk of BC in patients with the history of UC vs those without the history of UC were included. Pooled odds ratios and 95% confidence interval (CI) were calculated using a random-effect or fixed-effect method. Thirteen studies were included in our analysis to assess the association between a history of UC and risk of BC. The pooled OR of BC in patients with UC was 1.87 (95% CI, 1.45-2.41). Bladder calculi [OR, 2.17 (95% CI, 1.52-3.08)] had a higher risk of BC than kidney calculi [OR, 1.39 (95% CI, 1.06-1.82)]. The subjects had a history of UC that was associated with increased BC risk both in males [OR, 2.04 (95% CI, 1.41-2.96)] and in females [OR, 2.99 (95% CI, 2.37-3.76)]. The subgroup analysis demonstrated that UC increasing risk of BC both in case-control studies [OR, 1.75 (95% CI, 1.25-2.45)] and cohort studies [OR, 2.27 (95% CI, 1.55-3.32)]. The pooled OR of BC risk in patients with UC were 1.60 (95% CI, 1.15-2.24) in America, 1.36 (95% CI, 1.14-1.64) in Europe and 3.05 (95% CI, 2.21-4.21) in Asia, respectively. Our study demonstrates a significant increased risk of BC in patients with prior UC. This finding suggests that a history of UC is associated with BC and may impact clinical management and cancer surveillance. Further studies still needed to confirm the findings.

In vivo biochemical analyses reveal distinct roles of β-importins and eEF1A in tRNA subcellular traffic.

PubMed

Huang, Hsiao-Yun; Hopper, Anita K

2015-04-01

Bidirectional tRNA movement between the nucleus and the cytoplasm serves multiple biological functions. To gain a biochemical understanding of the mechanisms for tRNA subcellular dynamics, we developed in vivo β-importin complex coimmunoprecipitation (co-IP) assays using budding yeast. Our studies provide the first in vivo biochemical evidence that two β-importin family members, Los1 (exportin-t) and Msn5 (exportin-5), serve overlapping but distinct roles in tRNA nuclear export. Los1 assembles complexes with RanGTP and tRNA. Both intron-containing pre-tRNAs and spliced tRNAs, regardless of whether they are aminoacylated, assemble into Los1-RanGTP complexes, documenting that Los1 participates in both primary nuclear export and re-export of tRNAs to the cytoplasm. In contrast, β-importin Msn5 preferentially assembles with RanGTP and spliced, aminoacylated tRNAs, documenting its role in tRNA nuclear re-export. Tef1/2 (the yeast form of translation elongation factor 1α [eEF1A]) aids the specificity of Msn5 for aminoacylated tRNAs to form a quaternary complex consisting of Msn5, RanGTP, aminoacylated tRNA, and Tef1/2. Assembly and/or stability of this quaternary complex requires Tef1/2, thereby facilitating efficient re-export of aminoacylated tRNAs to the cytoplasm. © 2015 Huang and Hopper; Published by Cold Spring Harbor Laboratory Press.

An Assembly Funnel Makes Biomolecular Complex Assembly Efficient

PubMed Central

Zenk, John; Schulman, Rebecca

2014-01-01

Like protein folding and crystallization, the self-assembly of complexes is a fundamental form of biomolecular organization. While the number of methods for creating synthetic complexes is growing rapidly, most require empirical tuning of assembly conditions and/or produce low yields. We use coarse-grained simulations of the assembly kinetics of complexes to identify generic limitations on yields that arise because of the many simultaneous interactions allowed between the components and intermediates of a complex. Efficient assembly occurs when nucleation is fast and growth pathways are few, i.e. when there is an assembly “funnel”. For typical complexes, an assembly funnel occurs in a narrow window of conditions whose location is highly complex specific. However, by redesigning the components this window can be drastically broadened, so that complexes can form quickly across many conditions. The generality of this approach suggests assembly funnel design as a foundational strategy for robust biomolecular complex synthesis. PMID:25360818

Selective Complexation of Cyanide and Fluoride Ions with Ammonium Boranes: A Theoretical Study on Sensing Mechanism Involving Intramolecular Charge Transfer and Configurational Changes.

PubMed

Bhat, Haamid R; Jha, Prakash C

2017-05-18

The anion binding selectivity and the recognition mechanism of two isomeric boranes, namely, 4-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N-trimethylaniline ([p-(Mes 2 B)C 6 H 4 (NMe 3 )] + , 1, where "Mes" represents mesitylene and "Me" represents methyl) and 2-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N-trimethylaniline ([o-(Mes 2 B)C 6 H 4 (NMe 3 )] + , 2) has been investigated using density functional theory (DFT) and time dependent-density functional theory (TD-DFT) methods. Natural population analysis indicates that the central boron atoms in 1 and 2 are the most active centers for nucleophilic addition of anions. The negative magnitude of free energy changes (ΔG) reveals that out of CN - , F - , Cl - , Br - , NO 3 - , and HSO 4 - only the binding of CN - and F - with 1 and 2 is thermodynamically feasible and spontaneous. In addition, the calculated binding energies reveal that the CN - is showing lesser binding affinity than F - both with 1 and 2, while other ions, viz. NO 3 - , HSO 4 - , Br - , and Cl - , either do not bind at all or show very insignificant binding energy. The first excited states (S 1 ) of 1 and 2 are shown to be the local excited states with π → σ* transition by frontier molecular orbital analysis, whereas fourth excited states (S 4 ) of 4-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N-trimethylaniline cyanide ([p-(Mes 2 B)C 6 H 4 (NMe 3 )] CN, 1CN, the cyano form of 1) and 4-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N-trimethylaniline fluoride ([p-(Mes 2 B)C 6 H 4 (NMe 3 )] F, 1F, the fluoro form of 1) and fifth excited state (S 5 ) of 2-[bis(2,4,6-trimethylphenyl)boranyl]-N,N,N-trimethylaniline fluoride ([o-(Mes 2 B)C 6 H 4 (NMe 3 )] F, 2F, the fluoro form of 2) are charge separation states that are found to be responsible for the intramolecular charge transfer (ICT) process. The synergistic effect of ICT and partial configuration changes induce fluorescence quenching in 1CN, 1F, and 2F after a significant internal conversion (IC) from S 4 and S 5 to S 1.

Effect of integral membrane proteins on the lateral mobility of plastoquinone in phosphatidylcholine proteoliposomes.

PubMed

Blackwell, M F; Whitmarsh, J

1990-11-01

PYRENE FLUORESCENCE QUENCHING BY PLASTOQUINONE WAS USED TO ESTIMATE THE RATE OF PLASTOQUINONE LATERAL DIFFUSION IN SOYBEAN PHOSPHATIDYLCHOLINE PROTEOLIPOSOMES CONTAINING THE FOLLOWING INTEGRAL MEMBRANE PROTEINS: gramicidin D, spinach cytochrome bf complex, spinach cytochrome f, reaction centers from Rhodobacter sphaeroides, beef heart mitochondrial cytochrome bc(1), and beef heart mitochondrial cytochrome oxidase. The measured plastoquinone lateral diffusion coefficient varied between 1 and 3 . 10(-7) cm(2) s(-1) in control liposomes that lacked protein. When proteins were added, these values decreased: a 10-fold decrease was observed when 16-26% of the membrane surface area was occupied by protein for all the proteins but gramicidin. The larger protein complexes (cytochrome bf, Rhodobacter sphaeroides reaction centers, cytochrome bc(1), and cytochrome oxidase), whose hydrophobic volumes were 15-20 times as large as that of cytochrome f and the gramicidin transmembrane dimer, were 15-20 times as effective in decreasing the lateral-diffusion coefficient over the range of concentrations studied. These proteins had a much stronger effect than that observed for bacteriorhodopsin in fluorescence photobleaching recovery measurements. The effect of high-protein concentrations in gramicidin proteoliposomes was in close agreement with fluorescence photobleaching measurements. The results are compared with the predictions of several theoretical models of lateral mobility as a function of integral membrane concentration.

Effect of integral membrane proteins on the lateral mobility of plastoquinone in phosphatidylcholine proteoliposomes

PubMed Central

Blackwell, Mary F.; Whitmarsh, John

1990-01-01

Pyrene fluorescence quenching by plastoquinone was used to estimate the rate of plastoquinone lateral diffusion in soybean phosphatidylcholine proteoliposomes containing the following integral membrane proteins: gramicidin D, spinach cytochrome bf complex, spinach cytochrome f, reaction centers from Rhodobacter sphaeroides, beef heart mitochondrial cytochrome bc1, and beef heart mitochondrial cytochrome oxidase. The measured plastoquinone lateral diffusion coefficient varied between 1 and 3 · 10-7 cm2 s-1 in control liposomes that lacked protein. When proteins were added, these values decreased: a 10-fold decrease was observed when 16-26% of the membrane surface area was occupied by protein for all the proteins but gramicidin. The larger protein complexes (cytochrome bf, Rhodobacter sphaeroides reaction centers, cytochrome bc1, and cytochrome oxidase), whose hydrophobic volumes were 15-20 times as large as that of cytochrome f and the gramicidin transmembrane dimer, were 15-20 times as effective in decreasing the lateral-diffusion coefficient over the range of concentrations studied. These proteins had a much stronger effect than that observed for bacteriorhodopsin in fluorescence photobleaching recovery measurements. The effect of high-protein concentrations in gramicidin proteoliposomes was in close agreement with fluorescence photobleaching measurements. The results are compared with the predictions of several theoretical models of lateral mobility as a function of integral membrane concentration. PMID:19431774

Predictors of Breast Cancer Worry in a Hispanic and Predominantly Immigrant Mammography Screening Population.

PubMed

April-Sanders, Ayana; Oskar, Sabine; Shelton, Rachel C; Schmitt, Karen M; Desperito, Elise; Protacio, Angeline; Tehranifar, Parisa

Worry about developing breast cancer (BC) has been associated with participation in screening and genetic testing and with follow-up of abnormal screening results. Little is known about the scope and predictors of BC worry in Hispanic and immigrant populations. We collected in-person interview data from 250 self-identified Hispanic women recruited from an urban mammography facility (average age 50.4 years; 82% foreign-born). Women reported whether they worried about developing breast cancer rarely/never (low worry), sometimes (moderate worry), or often/all the time (high worry). We examined whether sociocultural and psychological factors (e.g., acculturation, education, perceived risk), and risk factors and objective risk for BC (e.g., family history, Gail model 5-year risk estimates, parity) predicted BC worry using multinomial and logistic regression. In multivariable models, women who perceived higher absolute BC risk (odds ratio, 1.66 [95% confidence interval, 1.28-2.14] for a one-unit increase in perceived lifetime risk) and comparative BC risk (e.g., odds ratio, 2.73, 95% confidence interval, 1.23-6.06) were more likely to report high BC worry than moderate or low BC worry. There were no associations between BC worry and indicators of objective risk or acculturation. In Hispanic women undergoing screening mammography, higher perceptions of BC risk, in both absolute and comparative terms, were associated independently with high BC worry, and were stronger predictors of BC worry than indicators of objective BC risk, including family history, mammographic density, and personal BC risk estimates. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

CryoEM and Molecular Dynamics of the Circadian KaiB-KaiC Complex Indicates That KaiB Monomers Interact with KaiC and Block ATP Binding Clefts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villarreal, Seth A.; Pattanayek, Rekha; Williams, Dewight R.

The circadian control of cellular processes in cyanobacteria is regulated by a posttranslational oscillator formed by three Kai proteins. During the oscillator cycle, KaiA serves to promote autophosphorylation of KaiC while KaiB counteracts this effect. Here, we present a crystallographic structure of the wild-type Synechococcus elongatus KaiB and a cryo-electron microscopy (cryoEM) structure of a KaiBC complex. The crystal structure shows the expected dimer core structure and significant conformational variations of the KaiB C-terminal region, which is functionally important in maintaining rhythmicity. The KaiBC sample was formed with a C-terminally truncated form of KaiC, KaiC-Δ489, which is persistently phosphorylated. Themore » KaiB–KaiC-Δ489 structure reveals that the KaiC hexamer can bind six monomers of KaiB, which form a continuous ring of density in the KaiBC complex. We performed cryoEM-guided molecular dynamics flexible fitting simulations with crystal structures of KaiB and KaiC to probe the KaiBC protein–protein interface. This analysis indicated a favorable binding mode for the KaiB monomer on the CII end of KaiC, involving two adjacent KaiC subunits and spanning an ATP binding cleft. A KaiC mutation, R468C, which has been shown to affect the affinity of KaiB for KaiC and lengthen the period in a bioluminescence rhythm assay, is found within the middle of the predicted KaiBC interface. The proposed KaiB binding mode blocks access to the ATP binding cleft in the CII ring of KaiC, which provides insight into how KaiB might influence the phosphorylation status of KaiC.« less

Climatic Effects of Black Carbon Aerosols Over the Tibetan Plateau

NASA Astrophysics Data System (ADS)

He, Cenlin

Black carbon (BC), also known as soot, has been identified as the second most important anthropogenic emissions in terms of global climate forcing in the current atmosphere. Ample evidence has shown that BC deposition is an important driver of rapid snow melting and glacier retreat over the Tibetan Plateau, which holds the largest snow/ice mass outside polar regions. However, the climatic effects of BC over the Tibetan Plateau have not been thoroughly investigated in such a manner as to understand, quantify, and reduce large uncertainties in the estimate of radiative and hydrological effects. Thus, this Ph.D. study seeks to understand and improve key processes controlling BC life cycle in global and regional models and to quantify BC radiative effects over the Tibetan Plateau. First, the capability of a state-of-the-art global chemical transport model (CTM), GEOS-Chem, and the associated model uncertainties are systematically evaluated in simulating BC over the Tibetan Plateau, using in situ measurements of BC in surface air, BC in snow, and BC absorption optical depth. The effects of three key factors on the simulation are also delineated, including Asian anthropogenic emissions, BC aging process, and model resolution. Subsequently, a microphysics-based BC aging scheme that accounts for condensation, coagulation, and heterogeneous chemical oxidation processes is developed and examined in GEOS-Chem by comparing with aircraft measurements. Compared to the default aging scheme, the microphysical scheme reduces model-observation discrepancies by a factor of 3, particularly in the middle and upper troposphere. In addition, a theoretical BC aging-optics model is developed to account for three typical evolution stages, namely, freshly emitted aggregates, coated BC by soluble material, and BC particles undergoing further hygroscopic growth. The geometric-optics surface-wave (GOS) approach is employed to compute the BC single-scattering properties at each aging stage, which are subsequently compared with laboratory measurements. Results show large variations in BC optical properties caused by coating morphology and aging stages. Furthermore, a comprehensive intercomparison of the GOS approach, the superposition T-matrix method, and laboratory measurements is performed for optical properties of BC with complex structures during aging. Moreover, a new snow albedo model is developed for widely-observed close-packed snow grains internally mixed with BC. Results indicate that albedo simulations that account for snow close packing match closer to observations. Close packing enhances BC-induced snow albedo reduction and associated surface radiative forcing by up to 15% (20%) for fresh (old) snow, which suggests that BC-snow albedo forcing is underestimated in previous modeling studies without accounting for close packing. Finally, the snow albedo forcing and direct radiative forcing (DRF) of BC in the Tibetan Plateau are estimated using GEOS-Chem in conjunction with a stochastic snow model and a radiative transfer model. This, for the first time, accounts for realistic non-spherical snow grain shape and stochastic multiple inclusions of BC within snow in assessing BC-snow interactions. The annual mean BC snow albedo forcing is 2.9 W m-2 over snow-covered Plateau regions. BC-snow internal mixing increases the albedo forcing by 40-60% compared with external mixing, whereas Koch snowflakes reduce the forcing by 20-40% relative to spherical snow grains. BC DRF at the top of the atmosphere is 2.3 W m-2 with uncertainties of -70% - +85% in the Plateau. The BC forcings are further attributed to emissions from different regions.

Optimization and proficiency testing of a pseudovirus-based assay for detection of HIV-1 neutralizing antibody in China.

PubMed

Nie, Jianhui; Wang, Wenbo; Wen, Zhiheng; Song, Aijing; Hong, Kunxue; Lu, Shan; Zhong, Ping; Xu, Jianqing; Kong, Wei; Li, Jingyun; Shang, Hong; Ling, Hong; Ruan, Li; Wang, Youchun

2012-11-01

Among the neutralizing antibody evaluation assays, the single-cycle pseudovirus infection assay is high-throughput and can provide rapid, sensitive and reproducible measurements after a single cycle of infection. Cell counts, pseudovirus inoculation levels, amount of diethylaminoethyl-dextran (DEAE-dextran), and the nonspecific effects of serum and plasma were tested to identify the optimal conditions for a neutralizing antibody assay based on pseudoviruses. Optimal conditions for cell counts, pseudovirus inoculation, and amount of DEAE-dextran were 1 × 10(4)cells/well, 200TCID(50)/well, and 15 μg/ml, respectively. Compared with serum samples, high-concentration anticoagulants reduced the relative light unit (RLU) value. The RLU value increased sharply initially but then decreased slowly with dilution of the plasma sample. Test kits containing 10 HIV-1 CRF07/08_BC pseudovirus strains and 10 plasma samples from individuals infected with HIV-1 CRF07/08_BC were assembled into two packages and distributed to nine laboratories with a standard operating procedure included. For the 10 laboratories that evaluated the test, 17 of 44 (37%) laboratory pairs were considered equivalent. A statistical qualification rule was developed based on the testing results from 5 experienced laboratories, where a laboratory qualified if at least 83% of values lied within the acceptable range. Copyright © 2012 Elsevier B.V. All rights reserved.

Role of water-soluble polysaccharides in bacterial cellulose production.

PubMed

Ishida, Takehiko; Mitarai, Makoto; Sugano, Yasushi; Shoda, Makoto

2003-08-20

Acetobacter xylinum BPR2001 produces water-insoluble bacterial cellulose (BC) and a water-soluble polysaccharide called acetan in corn steep liquor-fructose medium. Acetobacter xylinum EP1, which is incapable of acetan production was derived by disrupting the aceA gene of BPR2001. The BC production by EP1 (2.88 g/L) was lower than that by BPR2001 (4.6 g/L) in baffled-flask culture. When purified acetan or agar was added to the medium from the start of cultivation, the BC production by EP1 was enhanced and the final BC yield of EP1 was almost the same as that of BPR2001. A similar improvement of BC production by EP1 by the addition of agar was also confirmed by cultivation in a 50-L airlift reactor. From these results, the role of acetan in BC production is associated with the increase in the viscosity of the culture medium which may hinder coagulation of BC and cells in the culture, thereby accelerating the growth of BPR2001 and BC production by BPR2001. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 474-478, 2003.

Modeling the assembly order of multimeric heteroprotein complexes

PubMed Central

Esquivel-Rodriguez, Juan; Terashi, Genki; Christoffer, Charles; Shin, Woong-Hee

2018-01-01

Protein-protein interactions are the cornerstone of numerous biological processes. Although an increasing number of protein complex structures have been determined using experimental methods, relatively fewer studies have been performed to determine the assembly order of complexes. In addition to the insights into the molecular mechanisms of biological function provided by the structure of a complex, knowing the assembly order is important for understanding the process of complex formation. Assembly order is also practically useful for constructing subcomplexes as a step toward solving the entire complex experimentally, designing artificial protein complexes, and developing drugs that interrupt a critical step in the complex assembly. There are several experimental methods for determining the assembly order of complexes; however, these techniques are resource-intensive. Here, we present a computational method that predicts the assembly order of protein complexes by building the complex structure. The method, named Path-LzerD, uses a multimeric protein docking algorithm that assembles a protein complex structure from individual subunit structures and predicts assembly order by observing the simulated assembly process of the complex. Benchmarked on a dataset of complexes with experimental evidence of assembly order, Path-LZerD was successful in predicting the assembly pathway for the majority of the cases. Moreover, when compared with a simple approach that infers the assembly path from the buried surface area of subunits in the native complex, Path-LZerD has the strong advantage that it can be used for cases where the complex structure is not known. The path prediction accuracy decreased when starting from unbound monomers, particularly for larger complexes of five or more subunits, for which only a part of the assembly path was correctly identified. As the first method of its kind, Path-LZerD opens a new area of computational protein structure modeling and will be an indispensable approach for studying protein complexes. PMID:29329283

Modeling the assembly order of multimeric heteroprotein complexes.

PubMed

Peterson, Lenna X; Togawa, Yoichiro; Esquivel-Rodriguez, Juan; Terashi, Genki; Christoffer, Charles; Roy, Amitava; Shin, Woong-Hee; Kihara, Daisuke

2018-01-01

Protein-protein interactions are the cornerstone of numerous biological processes. Although an increasing number of protein complex structures have been determined using experimental methods, relatively fewer studies have been performed to determine the assembly order of complexes. In addition to the insights into the molecular mechanisms of biological function provided by the structure of a complex, knowing the assembly order is important for understanding the process of complex formation. Assembly order is also practically useful for constructing subcomplexes as a step toward solving the entire complex experimentally, designing artificial protein complexes, and developing drugs that interrupt a critical step in the complex assembly. There are several experimental methods for determining the assembly order of complexes; however, these techniques are resource-intensive. Here, we present a computational method that predicts the assembly order of protein complexes by building the complex structure. The method, named Path-LzerD, uses a multimeric protein docking algorithm that assembles a protein complex structure from individual subunit structures and predicts assembly order by observing the simulated assembly process of the complex. Benchmarked on a dataset of complexes with experimental evidence of assembly order, Path-LZerD was successful in predicting the assembly pathway for the majority of the cases. Moreover, when compared with a simple approach that infers the assembly path from the buried surface area of subunits in the native complex, Path-LZerD has the strong advantage that it can be used for cases where the complex structure is not known. The path prediction accuracy decreased when starting from unbound monomers, particularly for larger complexes of five or more subunits, for which only a part of the assembly path was correctly identified. As the first method of its kind, Path-LZerD opens a new area of computational protein structure modeling and will be an indispensable approach for studying protein complexes.

Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers

PubMed Central

Kuchenbaecker, Karoline B.; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Soucy, Penny; Healey, Sue; Dennis, Joe; Lush, Michael; Robson, Mark; Spurdle, Amanda B.; Ramus, Susan J.; Mavaddat, Nasim; Terry, Mary Beth; Neuhausen, Susan L.; Hamann, Ute; Southey, Melissa; John, Esther M.; Chung, Wendy K.; Daly, Mary B.; Buys, Saundra S.; Goldgar, David E.; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Ding, Yuan Chun; Ejlertsen, Bent; Gerdes, Anne-Marie; Hansen, Thomas V. O.; Slager, Susan; Hallberg, Emily; Benitez, Javier; Osorio, Ana; Cohen, Nancy; Lawler, William; Weitzel, Jeffrey N.; Peterlongo, Paolo; Pensotti, Valeria; Dolcetti, Riccardo; Barile, Monica; Bonanni, Bernardo; Azzollini, Jacopo; Manoukian, Siranoush; Peissel, Bernard; Radice, Paolo; Savarese, Antonella; Papi, Laura; Giannini, Giuseppe; Fostira, Florentia; Konstantopoulou, Irene; Adlard, Julian; Brewer, Carole; Cook, Jackie; Davidson, Rosemarie; Eccles, Diana; Eeles, Ros; Ellis, Steve; Frost, Debra; Hodgson, Shirley; Izatt, Louise; Lalloo, Fiona; Ong, Kai-ren; Godwin, Andrew K.; Arnold, Norbert; Dworniczak, Bernd; Engel, Christoph; Gehrig, Andrea; Hahnen, Eric; Hauke, Jan; Kast, Karin; Meindl, Alfons; Niederacher, Dieter; Schmutzler, Rita Katharina; Varon-Mateeva, Raymonda; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Barjhoux, Laure; Collonge-Rame, Marie-Agnès; Elan, Camille; Golmard, Lisa; Barouk-Simonet, Emmanuelle; Lesueur, Fabienne; Mazoyer, Sylvie; Sokolowska, Joanna; Stoppa-Lyonnet, Dominique; Isaacs, Claudine; Claes, Kathleen B. M.; Poppe, Bruce; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Aittomäki, Kristiina; Nevanlinna, Heli; Ausems, Margreet G. E. M.; de Lange, J. L.; Gómez Garcia, Encarna B.; Hogervorst, Frans B. L.; Kets, Carolien M.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; Rookus, Matti A.; van Asperen, Christi J.; van den Ouweland, Ans M. W.; van Doorn, Helena C.; van Os, Theo A. M.; Kwong, Ava; Olah, Edith; Diez, Orland; Brunet, Joan; Lazaro, Conxi; Teulé, Alex; Gronwald, Jacek; Jakubowska, Anna; Kaczmarek, Katarzyna; Lubinski, Jan; Sukiennicki, Grzegorz; Barkardottir, Rosa B.; Chiquette, Jocelyne; Agata, Simona; Montagna, Marco; Teixeira, Manuel R.; Park, Sue Kyung; Olswold, Curtis; Tischkowitz, Marc; Foretova, Lenka; Gaddam, Pragna; Vijai, Joseph; Pfeiler, Georg; Rappaport-Fuerhauser, Christine; Singer, Christian F.; Tea, Muy-Kheng M.; Greene, Mark H.; Loud, Jennifer T.; Rennert, Gad; Imyanitov, Evgeny N.; Hulick, Peter J.; Hays, John L.; Piedmonte, Marion; Rodriguez, Gustavo C.; Martyn, Julie; Glendon, Gord; Mulligan, Anna Marie; Andrulis, Irene L.; Toland, Amanda Ewart; Jensen, Uffe Birk; Kruse, Torben A.; Pedersen, Inge Sokilde; Thomassen, Mads; Caligo, Maria A.; Teo, Soo-Hwang; Berger, Raanan; Friedman, Eitan; Laitman, Yael; Arver, Brita; Borg, Ake; Ehrencrona, Hans; Rantala, Johanna; Olopade, Olufunmilayo I.; Ganz, Patricia A.; Nussbaum, Robert L.; Bradbury, Angela R.; Domchek, Susan M.; Nathanson, Katherine L.; Arun, Banu K.; James, Paul; Karlan, Beth Y.; Lester, Jenny; Simard, Jacques; Pharoah, Paul D. P.; Offit, Kenneth; Couch, Fergus J.; Chenevix-Trench, Georgia; Easton, Douglas F.

2017-01-01

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]–positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2×10−53). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2×10−20). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management. PMID:28376175

Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers.

PubMed

Kuchenbaecker, Karoline B; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Soucy, Penny; Dennis, Joe; Domchek, Susan M; Robson, Mark; Spurdle, Amanda B; Ramus, Susan J; Mavaddat, Nasim; Terry, Mary Beth; Neuhausen, Susan L; Schmutzler, Rita Katharina; Simard, Jacques; Pharoah, Paul D P; Offit, Kenneth; Couch, Fergus J; Chenevix-Trench, Georgia; Easton, Douglas F; Antoniou, Antonis C

2017-07-01

Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P =  8.2×10 -53 ). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P =  7.2×10 -20 ). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management. © The Author 2017. Published by Oxford University Press.

Developing leadership in nurse managers: the British Columbia Nursing Leadership Institute.

PubMed

MacPhee, Maura; Bouthillette, France

2008-01-01

The British Columbia Nursing Administrative Leadership Institute for First Line Nurse Leaders (BC NLI) is a collaborative partnership among British Columbia's Chief Nursing Officers, the Ministry of Health Nursing Directorate and the University of British Columbia School of Nursing. This initiative consists of a four-day residential program and a year-long leadership project between BC NLI participants and their organizational mentors. The evidence-based curriculum covers universal leadership and management concepts, but it also addresses leadership issues of relevance to nurse leaders in today's complex healthcare environments. The BC NLI is part of a provincial health human resources endeavour to ensure sufficient nursing leaders - for now and in the future. This paper will discuss the development, implementation and evaluation of the BC NLI. Unique aspects of the program, such as its online networking component, will be described, and its role in nursing leadership research will be briefly examined.

EZH2 in Bladder Cancer, a Promising Therapeutic Target

PubMed Central

Martínez-Fernández, Mónica; Rubio, Carolina; Segovia, Cristina; López-Calderón, Fernando F.; Dueñas, Marta; Paramio, Jesús M.

2015-01-01

Bladder Cancer (BC) represents a current clinical and social challenge. The recent studies aimed to describe the genomic landscape of BC have underscored the relevance of epigenetic alterations in the pathogenesis of these tumors. Among the epigenetic alterations, histone modifications occupied a central role not only in cancer, but also in normal organism homeostasis and development. EZH2 (Enhancer of Zeste Homolog 2) belongs to the Polycomb repressive complex 2 as its catalytic subunit, which through the trimethylation of H3 (Histone 3) on K27 (Lysine 27), produces gene silencing. EZH2 is frequently overexpressed in multiple tumor types, including BC, and plays multiple roles besides the well-recognized histone mark generation. In this review, we summarize the present knowledge on the oncogenic roles of EZH2 and its potential use as a therapeutic target, with special emphasis on BC pathogenesis and management. PMID:26580594

Black Carbon in Estuarine and Coastal Ocean Dissolved Organic Matter

NASA Technical Reports Server (NTRS)

Mannino, Antonio; Harvey, H. Rodger

2003-01-01

Black carbon (BC) in ultrafiltered high-molecular-weight DOM (UDOM) was measured in surface waters of Delaware Bay, Chesapeake Bay and the adjacent Atlantic Ocean (USA) to ascertain the importance of riverine and estuarine DOM as a source of BC to the ocean. BC comprised 5-72% of UDOM-C (27+/-l7%) and on average 8.9+/-6.5% of dissolved organic carbon (DOC) with higher values in the turbid region of the Delaware Estuary and lower yields in the river and coastal ocean. The spatial and seasonal distributions of BC along the salinity gradient of Delaware Bay suggest that the higher levels of BC in surface water UDOM originated from localized sources, possibly from atmospheric deposition or released from resuspended sediments. Black carbon comprised 4 to 7% of the DOC in the coastal Atlantic Ocean, revealing that river-estuary systems are important exporters of colloidal BC to the ocean. The annual flux of BC from Delaware Bay UDOM to the Atlantic Ocean was estimated at 2.4x10(exp 10) g BC yr(exp -1). The global river flux of BC through DOM to the ocean could be on the order of 5.5x1O(exp 12)g BC yr (exp -1). These results support the hypothesis that the DOC pool is the intermediate reservoir in which BC ages prior to sedimentary deposition.

Reference quality assembly of the 3.5-Gb genome of Capsicum annuum from a single linked-read library.

PubMed

Hulse-Kemp, Amanda M; Maheshwari, Shamoni; Stoffel, Kevin; Hill, Theresa A; Jaffe, David; Williams, Stephen R; Weisenfeld, Neil; Ramakrishnan, Srividya; Kumar, Vijay; Shah, Preyas; Schatz, Michael C; Church, Deanna M; Van Deynze, Allen

2018-01-01

Linked-Read sequencing technology has recently been employed successfully for de novo assembly of human genomes, however, the utility of this technology for complex plant genomes is unproven. We evaluated the technology for this purpose by sequencing the 3.5-gigabase (Gb) diploid pepper ( Capsicum annuum ) genome with a single Linked-Read library. Plant genomes, including pepper, are characterized by long, highly similar repetitive sequences. Accordingly, significant effort is used to ensure that the sequenced plant is highly homozygous and the resulting assembly is a haploid consensus. With a phased assembly approach, we targeted a heterozygous F 1 derived from a wide cross to assess the ability to derive both haplotypes and characterize a pungency gene with a large insertion/deletion. The Supernova software generated a highly ordered, more contiguous sequence assembly than all currently available C. annuum reference genomes. Over 83% of the final assembly was anchored and oriented using four publicly available  de novo linkage maps. A comparison of the annotation of conserved eukaryotic genes indicated the completeness of assembly. The validity of the phased assembly is further demonstrated with the complete recovery of both 2.5-Kb insertion/deletion haplotypes of the PUN1 locus in the F 1 sample that represents pungent and nonpungent peppers, as well as nearly full recovery of the BUSCO2 gene set within each of the two haplotypes. The most contiguous pepper genome assembly to date has been generated which demonstrates that Linked-Read library technology provides a tool to de novo assemble complex highly repetitive heterozygous plant genomes. This technology can provide an opportunity to cost-effectively develop high-quality genome assemblies for other complex plants and compare structural and gene differences through accurate haplotype reconstruction.

Numerical Investigation on Absorption Enhancement of Black Carbon Aerosols Partially Coated With Nonabsorbing Organics

NASA Astrophysics Data System (ADS)

Zhang, Xiaolin; Mao, Mao; Yin, Yan; Wang, Bin

2018-01-01

This study numerically evaluates the effects of aerosol microphysics, including coated volume fraction of black carbon (BC), shell/core ratio, and size distribution, on the absorption enhancement (Eab) of polydisperse BC aggregates partially coated by organics, which is calculated by the exact multiple-sphere T-matrix method. The coated volume fraction of BC plays a substantial role in determining the absorption enhancement of partially coated BC aggregates, which typically have an Eab in the range of 1.0-2.0 with a larger value for larger coated volume fraction of BC as the shell/core ratio, BC geometry, and size distribution are fixed. The shell/core ratio, BC geometry, and size distribution have little impact on the Eab of coated BC with small coated volume fraction of BC, while they become significant for large coated volume fraction of BC. The Eab of partially coated BC particles can be slightly less than 1.0 for the large BC in the accumulation mode exhibiting large shell/core ratio and small coated volume fraction of BC, indicating that the absorption shows even slight decrease relative to uncoated BC particles. For partially coated BC aggregates in the accumulation and coarse modes, the refractive index uncertainties of BC result in the Eab differences of less than 9% and 2%, respectively, while those of organics can induce larger variations with the maximum differences up to 22% and 18%, respectively. Our study indicates that accounting for particle coating microphysics, particularly the coated volume fraction of BC, can potentially help to understand the differences in observations of largely variable absorption enhancements over various regions.

Glucose and lipoprotein biomarkers and breast cancer severity using data from the Swedish AMORIS cohort.

PubMed

Melvin, Jennifer C; Garmo, Hans; Holmberg, Lars; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Lambe, Mats; Van Hemelrijck, Mieke

2017-04-04

The lipid and glucose metabolisms are postulated as possible intermediary mechanisms in linking obesity and breast cancer (BC). Links between serum lipid and glucose biomarkers and BC risk has been observed in the Swedish Apolipoprotein MORtality RISk (AMORIS) cohort. We conducted a follow-up analysis including information on tumour characteristics. One thousand eight hundred twenty-four women diagnosed with BC, with serum biomarker levels of glucose, triglycerides, cholesterol (total, HDL, and LDL), and apolipoproteins A-1 and B recorded in a routine health check at baseline were included. BC severity was split into categories (good, moderate, and poor prognosis) based on ER status, TNM stage, and age at diagnosis. Proportional odds models were used to obtain odds ratios (ORs) and 95% confidence intervals (CI), with the interval time between baseline measurement and BC diagnosis accounted for. Serum glucose and the ApoB/ApoA-1 ratio showed a non-statistically significant positive association with BC severity (proportional OR: 1.25 (95%CI: 0.92-1.70) for glucose (

A Toxoplasma MORN1 Null Mutant Undergoes Repeated Divisions but Is Defective in Basal Assembly, Apicoplast Division and Cytokinesis

PubMed Central

Lorestani, Alexander; Sheiner, Lilach; Yang, Kevin; Robertson, Seth D.; Sahoo, Nivedita; Brooks, Carrie F.; Ferguson, David J. P.; Striepen, Boris; Gubbels, Marc-Jan

2010-01-01

The membrane occupation and recognition nexus protein 1 (MORN1) is highly conserved among apicomplexan parasites and is associated with several structures that have a role in cell division. Here we dissected the role of MORN1 using the relatively simple budding process of Toxoplasma gondii as a model. Ablation of MORN1 in a conditional null mutant resulted in pronounced defects suggesting a central role for MORN1 in apicoplast segregation and in daughter cell budding. Lack of MORN1 resulted in double-headed parasites. These Janus-headed parasites form two complete apical complexes but fail to assemble a basal complex. Moreover, these parasites were capable of undergoing several more budding rounds resulting in the formation of up to 16-headed parasites conjoined at the basal end. Despite this segregation defect, the mother's cytoskeleton was completely disassembled in every budding round. Overall this argues that successful completion of the budding is not required for cell cycle progression. None of the known basal complex components, including a set of recently identified inner membrane complex (IMC) proteins, localized correctly in these multi-headed parasites. These data suggest that MORN1 is essential for assembly of the basal complex, and that lack of the basal complex abolishes the contractile capacity assigned to the basal complex late in daughter formation. Consistent with this hypothesis we observe that MORN1 mutants fail to efficiently constrict and divide the apicoplast. We used the null background provided by the mutant to dissect the function of subdomains of the MORN1 protein. This demonstrated that deletion of a single MORN domain already prevented the function of MORN1 whereas a critical role for the short linker between MORN domains 6 and 7 was identified. In conclusion, MORN1 is required for basal complex assembly and loss of MORN1 results in defects in apicoplast division and daughter segregation. PMID:20808817

ASF1 is required to load histones on the HIRA complex in preparation of paternal chromatin assembly at fertilization.

PubMed

Horard, Béatrice; Sapey-Triomphe, Laure; Bonnefoy, Emilie; Loppin, Benjamin

2018-05-11

Anti-Silencing Factor 1 (ASF1) is a conserved H3-H4 histone chaperone involved in both Replication-Coupled and Replication-Independent (RI) nucleosome assembly pathways. At DNA replication forks, ASF1 plays an important role in regulating the supply of H3.1/2 and H4 to the CAF-1 chromatin assembly complex. ASF1 also provides H3.3-H4 dimers to HIRA and DAXX chaperones for RI nucleosome assembly. The early Drosophila embryo is an attractive system to study chromatin assembly in a developmental context. The formation of a diploid zygote begins with the unique, genome-wide RI assembly of paternal chromatin following sperm protamine eviction. Then, within the same cytoplasm, syncytial embryonic nuclei undergo a series of rapid, synchronous S and M phases to form the blastoderm embryo. Here, we have investigated the implication of ASF1 in these two distinct assembly processes. We show that depletion of the maternal pool of ASF1 with a specific shRNA induces a fully penetrant, maternal effect embryo lethal phenotype. Unexpectedly, despite the depletion of ASF1 protein to undetectable levels, we show that asf1 knocked-down (KD) embryos can develop to various stages, thus demonstrating that ASF1 is not absolutely required for the amplification of cleavage nuclei. Remarkably, we found that ASF1 is required for the formation of the male pronucleus, although ASF1 protein does not reside in the decondensing sperm nucleus. In asf1 KD embryos, HIRA localizes to the male nucleus but is only capable of limited and insufficient chromatin assembly. Finally, we show that the conserved HIRA B domain, which is involved in ASF1-HIRA interaction, is dispensable for female fertility. We conclude that ASF1 is critically required to load H3.3-H4 dimers on the HIRA complex prior to histone deposition on paternal DNA. This separation of tasks could optimize the rapid assembly of paternal chromatin within the gigantic volume of the egg cell. In contrast, ASF1 is surprisingly dispensable for the amplification of cleavage nuclei, although chromatin integrity is likely compromised in KD embryos.

Development of sedentary communities in the Maya lowlands: Coexisting mobile groups and public ceremonies at Ceibal, Guatemala

PubMed Central

Inomata, Takeshi; MacLellan, Jessica; Triadan, Daniela; Munson, Jessica; Burham, Melissa; Aoyama, Kazuo; Nasu, Hiroo; Pinzón, Flory; Yonenobu, Hitoshi

2015-01-01

Our archaeological investigations at Ceibal, a lowland Maya site located in the Pasión region, documented that a formal ceremonial complex was built around 950 B.C. at the onset of the Middle Preclassic period, when ceramics began to be used in the Maya lowlands. Our refined chronology allowed us to trace the subsequent social changes in a resolution that had not been possible before. Many residents of Ceibal appear to have remained relatively mobile during the following centuries, living in ephemeral post-in-ground structures and frequently changing their residential localities. In other parts of the Pasión region, there may have existed more mobile populations who maintained the traditional lifestyle of the preceramic period. Although the emerging elite of Ceibal began to live in a substantial residential complex by 700 B.C., advanced sedentism with durable residences rebuilt in the same locations and burials placed under house floors was not adopted in most residential areas until 500 B.C., and did not become common until 300 B.C. or the Late Preclassic period. During the Middle Preclassic period, substantial formal ceremonial complexes appear to have been built only at a small number of important communities in the Maya lowlands, and groups with different levels of sedentism probably gathered for their constructions and for public rituals held in them. These collaborative activities likely played a central role in socially integrating diverse groups with different lifestyles and, eventually, in developing fully established sedentary communities. PMID:25831523

Ramifications of kinetic partitioning on usher-mediated pilus biogenesis.

PubMed Central

Saulino, E T; Thanassi, D G; Pinkner, J S; Hultgren, S J

1998-01-01

The biogenesis of diverse adhesive structures in a variety of Gram-negative bacterial species is dependent on the chaperone/usher pathway. Very little is known about how the usher protein translocates protein subunits across the outer membrane or how assembly of these adhesive structures occurs. We have discovered several mechanisms by which the usher protein acts to regulate the ordered assembly of type 1 pili, specifically through critical interactions of the chaperone-adhesin complex with the usher. A study of association and dissociation events of chaperone-subunit complexes with the usher in real time using surface plasmon resonance revealed that the chaperone-adhesin complex has the tightest and fastest association with the usher. This suggests that kinetic partitioning of chaperone-adhesin complexes to the usher is a defining factor in tip localization of the adhesin in the pilus. Furthermore, we identified and purified a chaperone-adhesin-usher assembly intermediate that was formed in vivo. Trypsin digestion assays showed that the usher in this complex was in an altered conformation, which was maintained during pilus assembly. The data support a model in which binding of the chaperone-adhesin complex to the usher stabilizes the usher in an assembly-competent conformation and allows initiation of pilus assembly. PMID:9545231

Bacterial cellulose may provide the microbial-life biosignature in the rock records

NASA Astrophysics Data System (ADS)

Zaets, I.; Podolich, O.; Kukharenko, O.; Reshetnyak, G.; Shpylova, S.; Sosnin, M.; Khirunenko, L.; Kozyrovska, N.; de Vera, J.-P.

2014-03-01

Bacterial cellulose (BC) is a matrix for a biofilm formation, which is critical for survival and persistence of microbes in harsh environments. BC could play a significant role in the formation of microbial mats in pristine ecosystems on Earth. The prime objective of this study was to measure to what extent spectral and other characteristics of BC were changed under the performance of BC interaction with the earthly rock - anorthosite - via microorganisms. The spectral analyses (Fourier Transform Infrared FT-IR, spectroscopy, and atomic absorption spectroscopy) showed unprecedented accumulation of chemical elements in the BC-based biofilm. The absorption capacity of IR by BC was shielded a little by mineral crust formed by microorganisms on the BC-based biofilm surface, especially clearly seen in the range of 1200-900 cm-1 in FT-IR spectra. Confocal scanning laser microscopy analysis revealed that elements bioleached from anorthosite created surface coats on the BC nanofibril web. At the same time, the vibrational spectra bands showed the presence of the characteristic region of anomeric carbons (960-730 cm-1), wherein a band at 897 cm-1 confirmed the presence of β-1, 4-linkages, which may serve as the cellulose fingerprint region. Results show that BC may be a biosignature for search signs of living organisms in rock records.

JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium.

PubMed

Gomi, Kazunori; Staudt, Michelle R; Salit, Jacqueline; Kaner, Robert J; Heldrich, Jonna; Rogalski, Allison M; Arbelaez, Vanessa; Crystal, Ronald G; Walters, Matthew S

2016-08-01

Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process in the human airway epithelium is largely unknown. The objective of this study was to define the role of the Notch ligand JAG1 in regulating human BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. These data demonstrate JAG1-mediated Notch signaling regulates differentiation of BC into secretory cells.

A Novel Approach for Determining Source-Receptor Relationships of Aerosols in Model Simulations

NASA Astrophysics Data System (ADS)

Ma, P.; Gattiker, J.; Liu, X.; Rasch, P. J.

2013-12-01

The climate modeling community usually performs sensitivity studies in the 'one-factor-at-a-time' fashion. However, owing to the a-priori unknown complexity and nonlinearity of the climate system and simulation response, it is computationally expensive to systematically identify the cause-and-effect of multiple factors in climate models. In this study, we use a Gaussian Process emulator, based on a small number of Community Atmosphere Model Version 5.1 (CAM5) simulations (constrained by meteorological reanalyses) using a Latin Hypercube experimental design, to demonstrate that it is possible to characterize model behavior accurately and very efficiently without any modifications to the model itself. We use the emulator to characterize the source-receptor relationships of black carbon (BC), focusing specifically on describing the constituent burden and surface deposition rates from emissions in various regions. Our results show that the emulator is capable of quantifying the contribution of aerosol burden and surface deposition from different source regions, finding that most of current Arctic BC comes from remote sources. We also demonstrate that the sensitivity of the BC burdens to emission perturbations differs for various source regions. For example, the emission growth in Africa where dry convections are strong results in a moderate increase of BC burden over the globe while the same emission growth in the Arctic leads to a significant increase of local BC burdens and surface deposition rates. These results provide insights into the dynamical, physical, and chemical processes of the climate model, and the conclusions may have policy implications for making cost-effective global and regional pollution management strategies.

Biochar may physically entrap nitrate during field aging or co-composting which become plant available under controlled conditions

NASA Astrophysics Data System (ADS)

Haider, Ghulam; Steffens, Diedrich; Müller, Christoph; Kammann, Claudia

2017-04-01

Conversion of organic biomass (agriculture/forestry residues) to biochar (BC) for carbon sequestration in soil to abate global warming has received much attention in recent years. However, apart from carbon sequestration, the incorporation of freshly produced biochars in agricultural soils have shown varying effects on soil-plant-moisture and nutrient interactions. It has been frequently reported that BC amendment may accelerate soil N transformations, reduce nitrate leaching, increase nutrient availability and soil fertility thereby increase crop yields by 10-15%. In addition, recent meta-studies suggested that BC-nitrogen (N) interactions in agricultural soils have the potential to reduce nitrous oxide (N2O) emissions by 50% with the underlying mechanisms not well understood. Also, mechanisms of BC-N sorption and desorption or plant availability of captured N in BC remain poorly understood. In this study we conducted two different experiments aiming (a) to understand the mechanism of nitrate capture by field aged (>3 years) BC (wood chip, pruning, bark and leaves (550-600°C)) and (b) to test the availability of captured nitrate by field-aged and composted BC to plants (quinoa, ryegrass) in a pot study under controlled conditions. Experiment (A): We hypothesized that N captured in the pores of BC may remain inaccessible to extraction solutions due to clogging of BC pores by the development of hydrophobic layer on BC surface following oxidation under field conditions. Therefore (i) physically breaking the structure or (ii) exerting under-pressure to water-immersed aged BC particles may allow extracting greater nitrate with the standard 2 M KCl method compared to intact particles. Study (A) encompassed 1) extraction from intact field-aged BC particles, 2) extraction after immersion in water and evacuation in vacutainers, 3) extraction after grinding of BC to powder and 4) prolonged shaking (48 hours at 80°C) of intact field aged BC particles and then extraction. Surprisingly, the ground BC particles released more than two times the amount of nitrate than standard-extracted intact BC particles (2 M KCl 1 hour shaking). Evacuation of intact BC particles did not result in a significant difference from the control either, while the prolonged shaking in hot water resulted in the maximum extracted amount of nitrate. Experiment (B): The availability of N from three different sources (nitrate supplied via field-aged BC, composted BC or Ca(NO3)) applied at increasing rate of addition (control, 44, 88, 177 and 355 kg N ha-1) was tested by growing Quinoa (Chenopodium quinoa) and ryegrass (Lolium perenne L.). Interestingly, the captured N by field aged and composted BC was largely plant available and supported plant biomass production comparable to the synthetic N fertilizer. In conclusion, we argue that the BC N capture is more likely due to physical entrapment (in pores) rather than to chemical bonding. Moreover, N loading of BC may provide an option to use biochar for crop production and climate change mitigation. Acknowledgements: CK acknowledges funding by DFG-grant KA3442/1-1 and GH was funded by DAAD and the higher education commission of Pakistan.

Biochar supported nanoscale zerovalent iron composite used as persulfate activator for removing trichloroethylene.

PubMed

Yan, Jingchun; Han, Lu; Gao, Weiguo; Xue, Song; Chen, Mengfang

2015-01-01

Biochar (BC) supported nanoscale zerovalent iron (nZVI) composite was synthesized and used as an activator for persulfate to enhance the trichloroethylene (TCE) removal in aqueous solutions. The degradation efficiency of TCE (0.15mmolL(-1)) was 99.4% in the presence of nZVI/BC (4.5mmolL(-1), nZVI to BC mass ratio was 1:5) and persulfate (4.5mmolL(-1)) within 5min, which was significantly higher than that (56.6%) in nZVI-persulfate system under the same conditions. Owing to large specific surface area and oxygen-containing functional groups of BC, nZVI/BC enhanced the SO4(-) generation and accelerated TCE degradation. On the basis of the characterization and analysis data, possible activation mechanisms of the Fe(2+)/Fe(3+) (Fe(II)/Fe(III)) redox action and the electron-transfer mediator of the BC oxygen functional groups promoting the generation of SO4(-) in nZVI/BC-persulfate system were clarified. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of soil biochar aging on sorption of the herbicides MCPA, nicosulfuron, terbuthylazine, indaziflam, and fluoroethyldiaminotriazine.

PubMed

Trigo, Carmen; Spokas, Kurt A; Cox, Lucia; Koskinen, William C

2014-11-12

Sorption of four herbicides and a metabolite of indaziflam on a fresh macadamia nut biochar and biochars aged one or two years in soil was characterized. On fresh biochar, the sorption was terbuthylazine (Kd = 595) > indaziflam (Kd = 162) > MCPA (Kd = 7.5) > fluoroethyldiaminotriazine (Kd = 0.26) and nicosulfuron (Kd = 0). Biochar surface area increased with aging attributed to the loss of a surface film. This was also manifested in a decline in water extractable organic carbon with aging. Correspondingly, an increase in the aromaticity was observed. The higher surface area and porosity in aged biochar increased sorption of indaziflam (KdBC-2yr = 237) and fluoroethyldiaminotriazine (KdBC-1yr = 1.2 and KdBC-2yr = 3.0), but interestingly decreased sorption of terbuthylazine (KdBC-1yr = 312 and KdBC-2yr = 221) and MCPA (KdBC-1yr = 2 and KdBC-2yr = 2). These results will facilitate development of biochars for specific remediation purposes.

Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery.

PubMed

Gakh, Oleksandr; Ranatunga, Wasantha; Smith, Douglas Y; Ahlgren, Eva-Christina; Al-Karadaghi, Salam; Thompson, James R; Isaya, Grazia

2016-09-30

Fe-S clusters, essential cofactors needed for the activity of many different enzymes, are assembled by conserved protein machineries inside bacteria and mitochondria. As the architecture of the human machinery remains undefined, we co-expressed in Escherichia coli the following four proteins involved in the initial step of Fe-S cluster synthesis: FXN 42-210 (iron donor); [NFS1]·[ISD11] (sulfur donor); and ISCU (scaffold upon which new clusters are assembled). We purified a stable, active complex consisting of all four proteins with 1:1:1:1 stoichiometry. Using negative staining transmission EM and single particle analysis, we obtained a three-dimensional model of the complex with ∼14 Å resolution. Molecular dynamics flexible fitting of protein structures docked into the EM map of the model revealed a [FXN 42-210 ] 24 ·[NFS1] 24 ·[ISD11] 24 ·[ISCU] 24 complex, consistent with the measured 1:1:1:1 stoichiometry of its four components. The complex structure fulfills distance constraints obtained from chemical cross-linking of the complex at multiple recurring interfaces, involving hydrogen bonds, salt bridges, or hydrophobic interactions between conserved residues. The complex consists of a central roughly cubic [FXN 42-210 ] 24 ·[ISCU] 24 sub-complex with one symmetric ISCU trimer bound on top of one symmetric FXN 42-210 trimer at each of its eight vertices. Binding of 12 [NFS1] 2 ·[ISD11] 2 sub-complexes to the surface results in a globular macromolecule with a diameter of ∼15 nm and creates 24 Fe-S cluster assembly centers. The organization of each center recapitulates a previously proposed conserved mechanism for sulfur donation from NFS1 to ISCU and reveals, for the first time, a path for iron donation from FXN 42-210 to ISCU. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery*

PubMed Central

Gakh, Oleksandr; Ranatunga, Wasantha; Smith, Douglas Y.; Ahlgren, Eva-Christina; Al-Karadaghi, Salam; Thompson, James R.; Isaya, Grazia

2016-01-01

Fe-S clusters, essential cofactors needed for the activity of many different enzymes, are assembled by conserved protein machineries inside bacteria and mitochondria. As the architecture of the human machinery remains undefined, we co-expressed in Escherichia coli the following four proteins involved in the initial step of Fe-S cluster synthesis: FXN42–210 (iron donor); [NFS1]·[ISD11] (sulfur donor); and ISCU (scaffold upon which new clusters are assembled). We purified a stable, active complex consisting of all four proteins with 1:1:1:1 stoichiometry. Using negative staining transmission EM and single particle analysis, we obtained a three-dimensional model of the complex with ∼14 Å resolution. Molecular dynamics flexible fitting of protein structures docked into the EM map of the model revealed a [FXN42–210]24·[NFS1]24·[ISD11]24·[ISCU]24 complex, consistent with the measured 1:1:1:1 stoichiometry of its four components. The complex structure fulfills distance constraints obtained from chemical cross-linking of the complex at multiple recurring interfaces, involving hydrogen bonds, salt bridges, or hydrophobic interactions between conserved residues. The complex consists of a central roughly cubic [FXN42–210]24·[ISCU]24 sub-complex with one symmetric ISCU trimer bound on top of one symmetric FXN42–210 trimer at each of its eight vertices. Binding of 12 [NFS1]2·[ISD11]2 sub-complexes to the surface results in a globular macromolecule with a diameter of ∼15 nm and creates 24 Fe-S cluster assembly centers. The organization of each center recapitulates a previously proposed conserved mechanism for sulfur donation from NFS1 to ISCU and reveals, for the first time, a path for iron donation from FXN42–210 to ISCU. PMID:27519411

Patterns and processes in the genetic differentiation of the Brachionus calyciflorus complex, a passively dispersing freshwater zooplankton.

PubMed

Xiang, Xian-ling; Xi, Yi-long; Wen, Xin-li; Zhang, Gen; Wang, Jin-xia; Hu, Ke

2011-05-01

Elucidating the evolutionary patterns and processes of extant species is an important objective of any research program that seeks to understand population divergence and, ultimately, speciation. The island-like nature and temporal fluctuation of limnetic habitats create opportunities for genetic differentiation in rotifers through space and time. To gain further understanding of spatio-temporal patterns of genetic differentiation in rotifers other than the well-studied Brachionus plicatilis complex in brackish water, a total of 318 nrDNA ITS sequences from the B. calyciflorus complex in freshwater were analysed using phylogenetic and phylogeographic methods. DNA taxonomy conducted by both the sequence divergence and the GMYC model suggested the occurrence of six potential cryptic species, supported also by reproductive isolation among the tested lineages. The significant genetic differentiation and non-significant correlation between geographic and genetic distances existed in the most abundant cryptic species, BcI-W and Bc-SW. The large proportion of genetic variability for cryptic species Bc-SW was due to differences between sampling localities within seasons, rather than between different seasons. Nested Clade Analysis suggested allopatric or past fragmentation, contiguous range expansion and long-distance colonization possibly coupled with subsequent fragmentation as the probable main forces shaping the present-day phylogeographic structure of the B. calyciflorus species complex. Copyright © 2011 Elsevier Inc. All rights reserved.

Ancient palace complex (300–100 BC) discovered in the Valley of Oaxaca, Mexico

PubMed Central

Redmond, Elsa M.; Spencer, Charles S.

2017-01-01

Recently completed excavations at the site of El Palenque in Mexico’s Valley of Oaxaca have recovered the well-preserved remains of a palace complex dated by associated radiocarbon samples and ceramics to the Late Formative period or Late Monte Albán I phase (300–100 BC), the period of archaic state emergence in the region. The El Palenque palace exhibits certain architectural and organizational features similar to the royal palaces of much later Mesoamerican states described by Colonial-period sources. The excavation data document a multifunctional palace complex covering a maximum estimated area of 2,790 m2 on the north side of the site’s plaza and consisting of both governmental and residential components. The data indicate that the palace complex was designed and built as a single construction. The palace complex at El Palenque is the oldest multifunctional palace excavated thus far in the Valley of Oaxaca. PMID:28348218

Demonstration and implications when 50% beam combiners can behave as 0% or 100% reflector/transmitter inside some interferometers

NASA Astrophysics Data System (ADS)

Roychoudhuri, ChandraSekhar

2017-08-01

The purpose of this paper is to embolden students to raise basic questions regarding the feasibility of "indivisible single photon interference". We do this by presenting experimental results of well-known classical Mach-Zehnder interferometer (MZI) under two different conditions of beam alignment. We routinely do such experiments in our laboratories. In the first case, we align the light beams on the beam combiner (BC) with their Poynting vectors as perfectly collinear. The 50% dielectric boundary can now transmit 100% of the energy of both the beams into either one of the two MZI output ports, depending upon the relative phase between the two beams combined on the BC from the opposite directions. The dielectric boundary layer actively re-directs the energy from one beam to the other. This is pure classical superposition effect. In the second case, we combine the two beams on the BC with a small intersecting angle. Now the BC functions as a 50% beam splitter to both the beams. One can see spatial fringes as the relative phase varies with spatial distance by placing a photo detector array after the BC. At very low intensity, the quantum properties of the photo detector will become apparent because the photo electrons are discrete and are always bound quantum mechanically to its host molecular assembly; and not because light is definitely quantized. Students can learn to distinguish the pedagogical difference between the Superposition Principle (linear sum of wave amplitudes) and the Superposition Effect (square modulus of the sum of all the wave-induced stimulations) as observable intensity variations due to interaction with materials, classical or quantum.

Interactions of photosystem II with bicarbonate, formate and acetate.

PubMed

Shevela, Dmitriy; Klimov, Vyacheslav; Messinger, Johannes

2007-01-01

In this study, we probe the effects of bicarbonate (hydrogencarbonate), BC, removal from photosystem II in spinach thylakoids by measuring flash-induced oxygen evolution patterns (FIOPs) with a Joliot-type electrode. For this we compared three commonly employed methods: (1) washing in BC-free medium, (2) formate addition, and (3) acetate addition. Washing of the samples with buffers depleted of BC and CO2 by bubbling with argon (Method 1) under our conditions leads to an increase in the double hit parameter of the first flash (beta 1), while the miss parameter and the overall activity remain unchanged. In contrast, addition of 40-50 mM formate or acetate results in a significant increase in the miss parameter and to an approximately 50% (formate) and approximately 10% (acetate) inhibition of the overall oxygen evolution activity, but not to an increased beta 1 parameter. All described effects could be reversed by washing with formate/acetate free buffer and/or addition of 2-10 mM bicarbonate. The redox potential of the water-oxidizing complex (WOC) in samples treated by Method 1 is compared to samples containing 2 mM bicarbonate in two ways: (1) The lifetimes of the S0, S2, and S3 states were measured, and no differences were found between the two sample types. (2) The S1, S0, S(-1), and S(-2) states were probed by incubation with small concentrations of NH2OH. These experiments displayed a subtle, yet highly reproducible difference in the apparent Si/S(-i) state distribution which is shown to arise from the interaction of BC with PSII in the already reduced states of the WOC. These data are discussed in detail by also taking into account the CO2 concentrations present in the buffers after argon bubbling and during the measurements. These values were measured by membrane-inlet mass spectrometry (MIMS).

Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study.

PubMed

Brouckaert, Olivier; Rudolph, Anja; Laenen, Annouschka; Keeman, Renske; Bolla, Manjeet K; Wang, Qin; Soubry, Adelheid; Wildiers, Hans; Andrulis, Irene L; Arndt, Volker; Beckmann, Matthias W; Benitez, Javier; Blomqvist, Carl; Bojesen, Stig E; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Chenevix-Trench, Georgia; Choi, Ji-Yeob; Cornelissen, Sten; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Eriksson, Mikael; Fasching, Peter A; Figueroa, Jonine; Flyger, Henrik; Giles, Graham G; González-Neira, Anna; Guénel, Pascal; Hall, Per; Hollestelle, Antoinette; Hopper, John L; Ito, Hidemi; Jones, Michael; Kang, Daehee; Knight, Julia A; Kosma, Veli-Matti; Li, Jingmei; Lindblom, Annika; Lilyquist, Jenna; Lophatananon, Artitaya; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Muir, Kenneth; Nevanlinna, Heli; Peterlongo, Paolo; Pylkäs, Katri; Saajrang, Suleeporn; Seynaeve, Caroline; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Swerdlow, Anthony; Teo, Soo-Hwang; Tollenaar, Rob A E M; Truong, Thérèse; Tseng, Chiu-Chen; van den Broek, Alexandra J; van Deurzen, Carolien H M; Winqvist, Robert; Wu, Anna H; Yip, Cheng Har; Yu, Jyh-Cherng; Zheng, Wei; Milne, Roger L; Pharoah, Paul D P; Easton, Douglas F; Schmidt, Marjanka K; Garcia-Closas, Montserrat; Chang-Claude, Jenny; Lambrechts, Diether; Neven, Patrick

2017-11-07

Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p < 0.0001), but this effect was not apparent at a later FFTP. Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.

TssA forms a gp6-like ring attached to the type VI secretion sheath.

PubMed

Planamente, Sara; Salih, Osman; Manoli, Eleni; Albesa-Jové, David; Freemont, Paul S; Filloux, Alain

2016-08-01

The type VI secretion system (T6SS) is a supra-molecular bacterial complex that resembles phage tails. It is a killing machine which fires toxins into target cells upon contraction of its TssBC sheath. Here, we show that TssA1 is a T6SS component forming dodecameric ring structures whose dimensions match those of the TssBC sheath and which can accommodate the inner Hcp tube. The TssA1 ring complex binds the T6SS sheath and impacts its behaviour in vivo In the phage, the first disc of the gp18 sheath sits on a baseplate wherein gp6 is a dodecameric ring. We found remarkable sequence and structural similarities between TssA1 and gp6 C-termini, and propose that TssA1 could be a baseplate component of the T6SS Furthermore, we identified similarities between TssK1 and gp8, the former interacting with TssA1 while the latter is found in the outer radius of the gp6 ring. These observations, combined with similarities between TssF and gp6N-terminus or TssG and gp53, lead us to propose a comparative model between the phage baseplate and the T6SS. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Risk of bladder cancer by disease severity in relation to metabolic factors and smoking; a prospective pooled cohort study of 800,000 men and women.

PubMed

Teleka, Stanley; Häggström, Christel; Nagel, Gabriele; Bjørge, Tone; Manjer, Jonas; Ulmer, Hanno; Liedberg, Fredrik; Ghaderi, Sara; Lang, Alois; Jonsson, Håkan; Jahnson, Staffan; Orho-Melander, Marju; Tretli, Steinar; Stattin, Pär; Stocks, Tanja

2018-05-14

Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811 633 participants in six European cohorts, we investigated sex-specific associations between body mass index (BMI), mid-blood pressure (BP, [systolic+diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow-up, 2 983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% CI 1.06-1.27] and 1.09 [1.02-1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82-0.99]). The associations for BMI and BP differed between men and women (P interaction ≤0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01-1.18], 1.14 [1.02-1.25], and 1.30 [1.12-1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02-1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04-3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. This study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub-groups, there were generally no significant differences in associations by smoking or tumor invasiveness. This article is protected by copyright. All rights reserved. © 2018 UICC.

Regulatory BC1 RNA in cognitive control.

PubMed

Iacoangeli, Anna; Dosunmu, Aderemi; Eom, Taesun; Stefanov, Dimitre G; Tiedge, Henri

2017-07-01

Dendritic regulatory BC1 RNA is a non-protein-coding (npc) RNA that operates in the translational control of gene expression. The absence of BC1 RNA in BC1 knockout (KO) animals causes translational dysregulation that entails neuronal phenotypic alterations including prolonged epileptiform discharges, audiogenic seizure activity in vivo, and excessive cortical oscillations in the γ frequency band. Here we asked whether BC1 RNA control is also required for higher brain functions such as learning, memory, or cognition. To address this question, we used odor/object attentional set shifting tasks in which prefrontal cortical performance was assessed in a series of discrimination and conflict learning sessions. Results obtained in these behavioral trials indicate that BC1 KO animals were significantly impaired in their cognitive flexibility. When faced with conflicting information sources, BC1 KO animals committed regressive errors as they were compromised in their ability to disengage from recently acquired memories even though recall of such memories was in conflict with new situational context. The observed cognitive deficits are reminiscent of those previously described in subtypes of human autism spectrum disorders. © 2017 Iacoangeli et al.; Published by Cold Spring Harbor Laboratory Press.

[Genotyping of BRCA1, BRCA2 and CHEK2 germline mutations in Russian breast cancer patients using diagnostic biochips].

PubMed

Nasedkina, T V; Gromyko, O E; Emel'ianova, M A; Ignatova, E O; Kazubskaia, T P; Portnoĭ, S M; Zasedatelev, A S; Liubchenko, L N

2014-01-01

Germline mutations of BRCA1/2 genes cause the predisposition of their carriers to breast or/and ovary cancers (BC or/and OC) during the lifetime. Identification of these mutations is a basis of molecular diagnosis for BC susceptibility. Rapid genotyping technique using microarrays for identification of BRCA1 185delAG, 300T>G, 4153delA, 5382insC mutations and 4158 A>G sequence variant; BRCA2 695insT and 6174delT mutations; 1100delC mutation in CHEK2 gene was applied for 412 randomly collected breast cancer samples from the central region of European area of Russia. In 25 (6.0%) patients (6.0%) BC was associated with other tumours: OC, cervical cancer, colorectal cancer etc. BRCA1/2 and CHEK2 mutations were found in 33 (8.0%) BC patients. The most frequent mutation was BRCA1 5382insC, occurred in 16 (3.9%) BC patients, and CHEK2 1100delC, revealed in 7 (1.7%) BC patients. An application of diagnostic BC-microarray for genetic testing of BRCA1/2 and CHEK2 founder mutations has been discussed.

Assembly of Multi-tRNA Synthetase Complex via Heterotetrameric Glutathione Transferase-homology Domains.

PubMed

Cho, Ha Yeon; Maeng, Seo Jin; Cho, Hyo Je; Choi, Yoon Seo; Chung, Jeong Min; Lee, Sangmin; Kim, Hoi Kyoung; Kim, Jong Hyun; Eom, Chi-Yong; Kim, Yeon-Gil; Guo, Min; Jung, Hyun Suk; Kang, Beom Sik; Kim, Sunghoon

2015-12-04

Many multicomponent protein complexes mediating diverse cellular processes are assembled through scaffolds with specialized protein interaction modules. The multi-tRNA synthetase complex (MSC), consisting of nine different aminoacyl-tRNA synthetases and three non-enzymatic factors (AIMP1-3), serves as a hub for many signaling pathways in addition to its role in protein synthesis. However, the assembly process and structural arrangement of the MSC components are not well understood. Here we show the heterotetrameric complex structure of the glutathione transferase (GST) domains shared among the four MSC components, methionyl-tRNA synthetase (MRS), glutaminyl-prolyl-tRNA synthetase (EPRS), AIMP2 and AIMP3. The MRS-AIMP3 and EPRS-AIMP2 using interface 1 are bridged via interface 2 of AIMP3 and EPRS to generate a unique linear complex of MRS-AIMP3:EPRS-AIMP2 at the molar ratio of (1:1):(1:1). Interestingly, the affinity at interface 2 of AIMP3:EPRS can be varied depending on the occupancy of interface 1, suggesting the dynamic nature of the linear GST tetramer. The four components are optimally arranged for maximal accommodation of additional domains and proteins. These characteristics suggest the GST tetramer as a unique and dynamic structural platform from which the MSC components are assembled. Considering prevalence of the GST-like domains, this tetramer can also provide a tool for the communication of the MSC with other GST-containing cellular factors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Modeling of the Nitric Oxide Transport in the Human Lungs.

PubMed

Karamaoun, Cyril; Van Muylem, Alain; Haut, Benoît

2016-01-01

In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might provide an interesting way to characterize the extent of BC in unhealthy patients.

Interaction of vaginal Lactobacillus strains with HeLa cells plasma membrane.

PubMed

Calonghi, N; Parolin, C; Sartor, G; Verardi, L; Giordani, B; Frisco, G; Marangoni, A; Vitali, B

2017-08-24

Vaginal lactobacilli offer protection against recurrent urinary and vaginal infections. The precise mechanisms underlying the interaction between lactobacilli and the host epithelium remain poorly understood at the molecular level. Deciphering such events can provide valuable information on the mode of action of commensal and probiotic bacteria in the vaginal environment. We investigated the effects exerted by five Lactobacillus strains of vaginal origin (Lactobacillus crispatus BC1 and BC2, Lactobacillus gasseri BC9 and BC11 and Lactobacillus vaginalis BC15) on the physical properties of the plasma membrane in a cervical cell line (HeLa). The interaction of the vaginal lactobacilli with the cervical cells determined two kinds of effects on plasma membrane: (1) modification of the membrane polar lipid organisation and the physical properties (L. crispatus BC1 and L. gasseri BC9); (2) modification of α5β1 integrin organisation (L. crispatus BC2, L. gasseri BC11 and L. vaginalis BC15). These two mechanisms can be at the basis of the protective role of lactobacilli against Candida albicans adhesion. Upon stimulation with all Lactobacillus strains, we observed a reduction of the basal oxidative stress in HeLa cells that could be related to modifications in physical properties and organisation of the plasma membrane. These results confirm the strictly strain-specific peculiarities of Lactobacillus and deepen the understanding of the mechanisms underlying the health-promoting role of this genus within the vaginal ecosystem.

Introgression of heat shock protein (Hsp70 and sHsp) genes into the Malaysian elite chilli variety Kulai (Capsicum annuum L.) through the application of marker-assisted backcrossing (MAB).

PubMed

Usman, Magaji G; Rafii, Mohd Y; Martini, Mohammad Y; Yusuff, Oladosu A; Ismail, Mohd R; Miah, Gous

2018-03-01

Backcrossing together with simple sequence repeat marker strategy was adopted to improve popular Malaysian chilli Kulai (Capsicum annuum L.) for heat tolerance. The use of molecular markers in backcross breeding and selection contributes significantly to overcoming the main drawbacks such as increase linkage drag and time consumption, in the ancient manual breeding approach (conventional), and speeds up the genome recovery of the recurrent parent. The strategy was adopted to introgress heat shock protein gene(s) from AVPP0702 (C. annuum L.), which are heat-tolerant, into the genetic profile of Kulai, a popular high-yielding chilli but which is heat sensitive. The parents were grown on seed trays, and parental screening was carried out with 252 simple sequence repeat markers. The selected parents were crossed and backcrossed to generate F 1 hybrids and backcross generations. Sixty-eight markers appeared to be polymorphic and were used to assess the backcross generation; BC 1 F 1 , BC 2 F 1 and BC 3 F 1 . The average recipient allele of the selected four BC 1 F 1 plants was 80.75% which were used to produce the BC 2 F 1 generation. BC 1 -P 7 was the best BC 1 F 1 plant because it had the highest recovery at 83.40% and was positive to Hsp-linked markers (Hsp70-u2 and AGi42). After three successive generations of backcrossing, the average genome recovery of the recurrent parent in the selected plants in BC 3 F 1 was 95.37%. Hsp gene expression analysis was carried out on BC 1 F 1 , BC 2 F 1 and BC 3 F 1 selected lines. The Hsp genes were found to be up-regulated when exposed to heat treatment. The pattern of Hsp expression in the backcross generations was similar to that of the donor parent. This confirms the successful introgression of a stress-responsive gene (Hsp) into a Kulai chilli pepper variety. Furthermore, the yield performance viz. plant height, number of fruits, fruit length and weight and total yield of the improved plant were similar with the recurrent parent except that the plant height was significantly lower than the Kulai (recurrent) parent.

Single haplotype assembly of the human genome from a hydatidiform mole.

PubMed

Steinberg, Karyn Meltz; Schneider, Valerie A; Graves-Lindsay, Tina A; Fulton, Robert S; Agarwala, Richa; Huddleston, John; Shiryev, Sergey A; Morgulis, Aleksandr; Surti, Urvashi; Warren, Wesley C; Church, Deanna M; Eichler, Evan E; Wilson, Richard K

2014-12-01

A complete reference assembly is essential for accurately interpreting individual genomes and associating variation with phenotypes. While the current human reference genome sequence is of very high quality, gaps and misassemblies remain due to biological and technical complexities. Large repetitive sequences and complex allelic diversity are the two main drivers of assembly error. Although increasing the length of sequence reads and library fragments can improve assembly, even the longest available reads do not resolve all regions. In order to overcome the issue of allelic diversity, we used genomic DNA from an essentially haploid hydatidiform mole, CHM1. We utilized several resources from this DNA including a set of end-sequenced and indexed BAC clones and 100× Illumina whole-genome shotgun (WGS) sequence coverage. We used the WGS sequence and the GRCh37 reference assembly to create an assembly of the CHM1 genome. We subsequently incorporated 382 finished BAC clone sequences to generate a draft assembly, CHM1_1.1 (NCBI AssemblyDB GCA_000306695.2). Analysis of gene, repetitive element, and segmental duplication content show this assembly to be of excellent quality and contiguity. However, comparison to assembly-independent resources, such as BAC clone end sequences and PacBio long reads, indicate misassembled regions. Most of these regions are enriched for structural variation and segmental duplication, and can be resolved in the future. This publicly available assembly will be integrated into the Genome Reference Consortium curation framework for further improvement, with the ultimate goal being a completely finished gap-free assembly. © 2014 Steinberg et al.; Published by Cold Spring Harbor Laboratory Press.

Single haplotype assembly of the human genome from a hydatidiform mole

PubMed Central

Steinberg, Karyn Meltz; Schneider, Valerie A.; Graves-Lindsay, Tina A.; Fulton, Robert S.; Agarwala, Richa; Huddleston, John; Shiryev, Sergey A.; Morgulis, Aleksandr; Surti, Urvashi; Warren, Wesley C.; Church, Deanna M.; Eichler, Evan E.; Wilson, Richard K.

2014-01-01

A complete reference assembly is essential for accurately interpreting individual genomes and associating variation with phenotypes. While the current human reference genome sequence is of very high quality, gaps and misassemblies remain due to biological and technical complexities. Large repetitive sequences and complex allelic diversity are the two main drivers of assembly error. Although increasing the length of sequence reads and library fragments can improve assembly, even the longest available reads do not resolve all regions. In order to overcome the issue of allelic diversity, we used genomic DNA from an essentially haploid hydatidiform mole, CHM1. We utilized several resources from this DNA including a set of end-sequenced and indexed BAC clones and 100× Illumina whole-genome shotgun (WGS) sequence coverage. We used the WGS sequence and the GRCh37 reference assembly to create an assembly of the CHM1 genome. We subsequently incorporated 382 finished BAC clone sequences to generate a draft assembly, CHM1_1.1 (NCBI AssemblyDB GCA_000306695.2). Analysis of gene, repetitive element, and segmental duplication content show this assembly to be of excellent quality and contiguity. However, comparison to assembly-independent resources, such as BAC clone end sequences and PacBio long reads, indicate misassembled regions. Most of these regions are enriched for structural variation and segmental duplication, and can be resolved in the future. This publicly available assembly will be integrated into the Genome Reference Consortium curation framework for further improvement, with the ultimate goal being a completely finished gap-free assembly. PMID:25373144

High-speed superresolution imaging of the proteins in fission yeast clathrin-mediated endocytic actin patches

PubMed Central

Arasada, Rajesh; Sayyad, Wasim A.; Berro, Julien; Pollard, Thomas D.

2018-01-01

To internalize nutrients and cell surface receptors via clathrin-mediated endocytosis, cells assemble at least 50 proteins, including clathrin, clathrin-interacting proteins, actin filaments, and actin binding proteins, in a highly ordered and regulated manner. The molecular mechanism by which actin filament polymerization deforms the cell membrane is unknown, largely due to lack of knowledge about the organization of the regulatory proteins and actin filaments. We used high-speed superresolution localization microscopy of live fission yeast cells to improve the spatial resolution to ∼35 nm with 1-s temporal resolution. The nucleation promoting factors Wsp1p (WASp) and Myo1p (myosin-I) define two independent pathways that recruit Arp2/3 complex, which assembles two zones of actin filaments. Myo1p concentrates at the site of endocytosis and initiates a zone of actin filaments assembled by Arp2/3 complex. Wsp1p appears simultaneously at this site but subsequently moves away from the cell surface as it stimulates Arp2/3 complex to assemble a second zone of actin filaments. Cells lacking either nucleation-promoting factor assemble only one, stationary, zone of actin filaments. These observations support our two-zone hypothesis to explain endocytic tubule elongation and vesicle scission in fission yeast. PMID:29212877

Promoting the productivity and quality of brinjal aligned with heavy metals immobilization in a wastewater irrigated heavy metal polluted soil with biochar and chitosan.

PubMed

Turan, Veysel; Khan, Shahbaz Ali; Mahmood-Ur-Rahman; Iqbal, Muhammad; Ramzani, Pia Muhammad Adnan; Fatima, Maryam

2018-06-12

Depleting aquifers, lack of planning and low socioeconomic status of Pakistani farmers have led them to use wastewater (WW) for irrigating their crops causing food contamination with heavy metals and ultimately negative effects on human health. This study evaluates the effects of chitosan (CH) and biochar (BC) on growth and nutritional quality of brinjal plant together with in situ immobilization of heavy metals in a soil polluted with heavy metals due to irrigation with wastewater (SPHIW) and further irrigated with the same WW. Both CH and BC were applied at three different rates i.e. low rate [(LR), BC0.5%, CH0.5% and BC0.25%+CH0.25%], medium rate [(MR), BC1%, CH1% and BC0.5%+CH0.5%] and high rate [(HR), BC1.5%, CH1.5% and BC0.75%+CH0.75%]. Result revealed that brinjal growth, antioxidant enzymes, and fruit nutritional quality significantly improved from LR to HR for each amendment, relative to control. However, these results were more prominent with BC alone and BC+CH, compared with CH alone at each rate. Similarly, with few exceptions, significant reduction in Ni, Cd, Co, Cr and Pb concentrations in the root, shoot and fruit were found in sole CH treatment both at LR and MR but in both CH and BC+CH treatments at HR, relative to control. Interestingly, the concentrations of Fe in the roots, shoots and fruit were more pronounced at BC treatments relative to CH and BC+CH treatments at each rate, compared to control. Overall, the BC+CH treatment at HR was the most effective treatment for in situ immobilization of heavy metals in SPHIW and further irrigated with the same WW, compared to rest of the treatments. This study indicates that BC0.75%+CH0.75% treatment can be used to reduce mobility and bioavailability of heavy metals in SPHIW and facilitates plant growth by improving the antioxidant system. However, the feasibility of BC0.75%+CH0.75% treatment should also be tested at the field scale. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantifying cadherin mechanotransduction machinery assembly/disassembly dynamics using fluorescence covariance analysis.

PubMed

Vedula, Pavan; Cruz, Lissette A; Gutierrez, Natasha; Davis, Justin; Ayee, Brian; Abramczyk, Rachel; Rodriguez, Alexis J

2016-06-30

Quantifying multi-molecular complex assembly in specific cytoplasmic compartments is crucial to understand how cells use assembly/disassembly of these complexes to control function. Currently, biophysical methods like Fluorescence Resonance Energy Transfer and Fluorescence Correlation Spectroscopy provide quantitative measurements of direct protein-protein interactions, while traditional biochemical approaches such as sub-cellular fractionation and immunoprecipitation remain the main approaches used to study multi-protein complex assembly/disassembly dynamics. In this article, we validate and quantify multi-protein adherens junction complex assembly in situ using light microscopy and Fluorescence Covariance Analysis. Utilizing specific fluorescently-labeled protein pairs, we quantified various stages of adherens junction complex assembly, the multiprotein complex regulating epithelial tissue structure and function following de novo cell-cell contact. We demonstrate: minimal cadherin-catenin complex assembly in the perinuclear cytoplasm and subsequent localization to the cell-cell contact zone, assembly of adherens junction complexes, acto-myosin tension-mediated anchoring, and adherens junction maturation following de novo cell-cell contact. Finally applying Fluorescence Covariance Analysis in live cells expressing fluorescently tagged adherens junction complex proteins, we also quantified adherens junction complex assembly dynamics during epithelial monolayer formation.

Perinatal and childhood factors and risk of breast cancer subtypes in adulthood.

PubMed

Lope, Virginia; García-Esquinas, Esther; Pérez-Gómez, Beatriz; Altzibar, Jone M; Gracia-Lavedan, Esther; Ederra, María; Molina de la Torre, Antonio José; LLorca, Francisco Javier; Tardón, Adonina; Moreno, Víctor; Bayo, Juan; Salas-Trejo, Dolores; Marcos-Gragera, Rafael; Pumarega, José; Dierssen-Sotos, Trinidad; Lera, Juan Pablo Barrio; de Miguel Medina, M A Concepción; Tusquets, Ignasi; Amiano, Pilar; Boldo, Elena; Kogevinas, Manolis; Aragonés, Nuria; Castaño-Vinyals, Gemma; Pollán, Marina

2016-02-01

Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes. This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors. Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93). These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

Analysis of transpacific transport of black carbon during HIPPO-3: implications for black carbon aging

NASA Astrophysics Data System (ADS)

Shen, Z.; Liu, J.; Horowitz, L. W.; Henze, D. K.; Fan, S.; Levy, H., II; Mauzerall, D. L.; Lin, J.-T.; Tao, S.

2014-06-01

Long-range transport of black carbon (BC) is a growing concern as a result of the efficiency of BC in warming the climate and its adverse impact on human health. We study transpacific transport of BC during HIPPO-3 using a combination of inverse modeling and sensitivity analysis. We use the GEOS-Chem chemical transport model and its adjoint to constrain Asian BC emissions and estimate the source of BC over the North Pacific. We find that different sources of BC dominate the transport to the North Pacific during the southbound (29 March 2010) and northbound (13 April 2010) measurements in HIPPO-3. While biomass burning in Southeast Asia (SE) contributes about 60% of BC in March, more than 90% of BC comes from fossil fuel and biofuel combustion in East Asia (EA) during the April mission. GEOS-Chem simulations generally resolve the spatial and temporal variation of BC concentrations over the North Pacific, but are unable to reproduce the low and high tails of the observed BC distribution. We find that the optimized BC emissions derived from inverse modeling fail to improve model simulations significantly. This failure indicates that uncertainties in BC removal as well as transport, rather than in emissions, account for the major biases in GEOS-Chem simulations of BC over the North Pacific. The aging process, transforming BC from hydrophobic into hydrophilic form, is one of the key factors controlling wet scavenging and remote concentrations of BC. Sensitivity tests on BC aging (ignoring uncertainties of other factors controlling BC long range transport) suggest that in order to fit HIPPO-3 observations, the aging timescale of anthropogenic BC from EA may be several hours (faster than assumed in most global models), while the aging process of biomass burning BC from SE may occur much slower, with a timescale of a few days. To evaluate the effects of BC aging and wet deposition on transpacific transport of BC, we develop an idealized model of BC transport. We find that the mid-latitude air masses sampled during HIPPO-3 may have experienced a series of precipitation events, particularly near the EA and SE source region. Transpacific transport of BC is sensitive to BC aging when the aging rate is fast; this sensitivity peaks when the aging timescale is in the range of 1-1.5 d. Our findings indicate that BC aging close to the source must be simulated accurately at a process level in order to simulate better the global abundance and climate forcing of BC.

Enhanced Solar Energy Absorption by Internally-mixed Black Carbon in Snow Grains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flanner, M. G.; Liu, Xiaohong; Zhou, Cheng

2012-05-30

Here we explore light absorption by snowpack containing black carbon (BC) particles residing within ice grains. Basic considerations of particle volumes and BC/snow mass concentrations show that there are generally 0:05-109 BC particles for each ice grain. This suggests that internal BC is likely distributed as multiple inclusions within ice grains, and thus the dynamic effective medium approximation (DEMA) (Chylek and Srivastava, 1983) is a more appropriate optical representation for BC/ice composites than coated-sphere or standard mixing approximations. DEMA calculations show that the 460 nm absorption cross-section of BC/ice composites, normalized to the mass of BC, is typically enhanced bymore » factors of 1.8-2.1 relative to interstitial BC. BC effective radius is the dominant cause of variation in this enhancement, compared with ice grain size and BC volume fraction. We apply two atmospheric aerosol models that simulate interstitial and within-hydrometeor BC lifecycles. Although only {approx}2% of the atmospheric BC burden is cloud-borne, 71-83% of the BC deposited to global snow and sea-ice surfaces occurs within hydrometeors. Key processes responsible for within-snow BC deposition are development of hydrophilic coatings on BC, activation of liquid droplets, and subsequent snow formation through riming or ice nucleation by other species and aggregation/accretion of ice particles. Applying deposition fields from these aerosol models in offline snow and sea-ice simulations, we calculate that 32-73% of BC in global surface snow resides within ice grains. This fraction is smaller than the within-hydrometeor deposition fraction because meltwater flux preferentially removes internal BC, while sublimation and freezing within snowpack expose internal BC. Incorporating the DEMA into a global climate model, we simulate increases in BC/snow radiative forcing of 43-86%, relative to scenarios that apply external optical properties to all BC. We show that snow metamorphism driven by diffusive vapor transfer likely proceeds too slowly to alter the mass of internal BC while it is radiatively active, but neglected processes like wind pumping and convection may play much larger roles. These results suggest that a large portion of BC in surface snowpack may reside within ice grains and increase BC/snow radiative forcing, although measurements to evaluate this are lacking. Finally, previous studies of BC/snow forcing that neglected this absorption enhancement are not necessarily biased low, because of application of absorption-enhancing sulfate coatings to hydrophilic BC, neglect of coincident absorption by dust in snow, and implicit treatment of cloud-borne BC resulting in longer-range transport.« less

Long non-coding RNA-CTD-2108O9.1 represses breast cancer metastasis by influencing leukemia inhibitory factor receptor.

PubMed

Wang, Mozhi; Wang, Mengshen; Wang, Zhenning; Yu, Xueting; Song, Yongxi; Wang, Chong; Xu, Yujie; Wei, Fengheng; Zhao, Yi; Xu, Yingying

2018-06-01

Breast cancer (BC) is an aggressive malignant disease in women worldwide with a high tendency to metastasize. However, important biomarkers for BC metastasis remain largely undefined. In the present study, we identified that long non-coding RNA-CTD-2108O9.1 is downregulated in BC tissues and cells and acts as a metastatic inhibitor of BC. Mechanistic investigation determined that lncRNA-CTD-2108O9.1 represses metastasis by targeting leukemia inhibitory factor receptor (LIFR), which is designated as a metastasis suppressor in BC. Our study characterizes a significant tumor suppressor active in BC metastasis repression through the known metastasis inhibitor LIFR. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Regulated assembly and disassembly of the yeast telomerase quaternary complex

PubMed Central

Tucey, Timothy M.

2014-01-01

The enzyme telomerase, which elongates chromosome termini, is a critical factor in determining long-term cellular proliferation and tissue renewal. Hence, even small differences in telomerase levels can have substantial consequences for human health. In budding yeast, telomerase consists of the catalytic Est2 protein and two regulatory subunits (Est1 and Est3) in association with the TLC1 RNA, with each of the four subunits essential for in vivo telomerase function. We show here that a hierarchy of assembly and disassembly results in limiting amounts of the quaternary complex late in the cell cycle, following completion of DNA replication. The assembly pathway, which is driven by interaction of the Est3 telomerase subunit with a previously formed Est1–TLC1–Est2 preassembly complex, is highly regulated, involving Est3-binding sites on both Est2 and Est1 as well as an interface on Est3 itself that functions as a toggle switch. Telomerase subsequently disassembles by a mechanistically distinct pathway due to dissociation of the catalytic subunit from the complex in every cell cycle. The balance between the assembly and disassembly pathways, which dictate the levels of the active holoenzyme in the cell, reveals a novel mechanism by which telomerase (and hence telomere homeostasis) is regulated. PMID:25240060

β-Arrestin1 regulates γ-secretase complex assembly and modulates amyloid-β pathology

PubMed Central

Liu, Xiaosong; Zhao, Xiaohui; Zeng, Xianglu; Bossers, Koen; Swaab, Dick F; Zhao, Jian; Pei, Gang

2013-01-01

Alzheimer's disease (AD) is a progressive and complex neurodegenerative disease in which the γ-secretase-mediated amyloid-β (Aβ) pathology plays an important role. We found that a multifunctional protein, β-arrestin1, facilitated the formation of NCT/APH-1 (anterior pharynx-defective phenotype 1) precomplex and mature γ-secretase complex through its functional interaction with APH-1. Deficiency of β-arrestin1 or inhibition of binding of β-arrestin1 with APH-1 by small peptides reduced Aβ production without affecting Notch processing. Genetic ablation of β-arrestin1 diminished Aβ pathology and behavioral deficits in transgenic AD mice. Moreover, in brains of sporadic AD patients and transgenic AD mice, the expression of β-arrestin1 was upregulated and correlated well with neuropathological severity and senile Aβ plaques. Thus, our study identifies a regulatory mechanism underlying both γ-secretase assembly and AD pathogenesis, and indicates that specific reduction of Aβ pathology can be achieved by regulation of the γ-secretase assembly. PMID:23208420

Near-Surface Refractory Black Carbon Observations in the Atmosphere and Snow in the McMurdo Dry Valleys, Antarctica, and Potential Impacts of Foehn Winds

NASA Astrophysics Data System (ADS)

Khan, Alia L.; McMeeking, Gavin R.; Schwarz, Joshua P.; Xian, Peng; Welch, Kathleen A.; Berry Lyons, W.; McKnight, Diane M.

2018-03-01

Measurements of light-absorbing particles in the boundary layer of the high southern latitudes are scarce, particularly in the McMurdo Dry Valleys (MDV), Antarctica. During the 2013-2014 austral summer near-surface boundary layer refractory black carbon (rBC) aerosols were measured in air by a single-particle soot photometer (SP2) at multiple locations in the MDV. Near-continuous rBC atmospheric measurements were collected at Lake Hoare Camp (LH) over 2 months and for several hours at more remote locations away from established field camps. We investigated periods dominated by both upvalley and downvalley winds to explore the causes of differences in rBC concentrations and size distributions. Snow samples were also collected in a 1 m pit on a glacier near the camp. The range of concentrations rBC in snow was 0.3-1.2 ± 0.3 μg-rBC/L-H2O, and total organic carbon was 0.3-1.4 ± 0.3 mg/L. The rBC concentrations measured in this snow pit are not sufficient to reduce surface albedo; however, there is potential for accumulation of rBC on snow and ice surfaces at low elevation throughout the MDV, which were not measured as part of this study. At LH, the average background rBC mass aerosol concentrations were 1.3 ng/m3. rBC aerosol mass concentrations were slightly lower, 0.09-1.3 ng/m3, at the most remote sites in the MDV. Concentration spikes as high as 200 ng/m3 were observed at LH, associated with local activities. During a foehn wind event, the average rBC mass concentration increased to 30-50 ng/m3. Here we show that the rBC increase could be due to resuspension of locally produced BC from generators, rocket toilets, and helicopters, which may remain on the soil surface until redistributed during high wind events. Quantification of local production and long-range atmospheric transport of rBC to the MDV is necessary for understanding the impacts of this species on regional climate.

Incidence, risk factors and ERCP outcome for biliary complications after cadaveric OLT.

PubMed

Martins, Fernanda Prata; De Paulo, Gustavo Andrade; Conceição, Raquel Dilgerian; Zurstrassen, Maria Paula; Thomé, Tadeu; Ferraz-Neto, Ben-Hur; Ferrari, Angelo Paulo

2011-01-01

Biliary complications (BC) occur in up to 39.5% of patients after orthotopic liver transplantation (OLT), being an important source of post-transplant morbidity. The aim is to evaluate the incidence of BC after OLT, associated risk factors and outcome after endoscopic treatment. A retrospective case series between June 2005 and December 2008, including 195 patients that underwent 216 OLT from deceased donors. Thirty-one patients (14.3%) presented at least 1 BC, anastomotic stricture being the most frequent (83.8%). Non-anastomotic stricture was present in 1 (3.2%) and anastomotic fistula in 1. One patient presented anastomotic disconnection at ERCP. BC occurred 94.6 (7-487) days after OLT. Twenty-seven patients underwent endoscopic treatment, on average 2.6 ERCPs were performed per patient. Global endoscopic treatment success rate was 77.3%; being 73.7% for stenosis and 100% (3/3) for anastomotic fistula with stenosis. Recurrence of biliary stricture was observed in 3 patients, all referred to endoscopic re-treatment. ERCP complications: 2 (2.8%) stent migrations, 1 (1.4%) early stent occlusion, 1 (1.4%) respiratory distress and 1(1.4%) severe acute pancreatitis and death. There was no correlation between studied risk factors and BC's occurrence. ERCP was effective for the treatment of BC after OLT. Studied risk factors had no correlation with BC.

The efficacy of bamboo charcoal in comparison with smectite to reduce the detrimental effect of aflatoxin B1 on in vitro rumen fermentation of a hay-rich feed mixture.

PubMed

Jiang, Ya-Hui; Wang, Ping; Yang, Hong-Jian; Chen, Ying

2014-07-10

Two commercial materials, a bamboo charcoal (BC) and a smectite clay (SC), were assessed in vitro with aflatoxin B1 (AFB1) in an equilibrium adsorption test. The adsorption capacity and proportion adsorbed (0.381 μg/mg, 0.955) for BC were greater than for SC (0.372 μg/mg, 0.931). The effects of in vitro ruminal fermentation of hay-rich feed incubated with 1.0 μg/mL AFB1 for 0-10 g/L doses of BC and SC were measured at 39 °C for 72 h. The BC and SC binders increased AFB1 loss at dosages ≥1.0 g/L (p < 0.0001). Average AFB1 loss (p < 0.0001) was greater for SC (0.904) than BC (0.881). Both SC and SC addition increased in vitro dry matter loss, and the average dry matter losses were similar. Asymptotic gas volume and volatile fatty acid production were greater for BC than for SC (p < 0.0001). Thus, BC may be as effective as SC in removing aflatoxin B1's detrimental effects on rumen degradability and fermentation under the occurrence of microbial aflatoxin degradation.

The Efficacy of Bamboo Charcoal in Comparison with Smectite to Reduce the Detrimental Effect of Aflatoxin B1 on In Vitro Rumen Fermentation of a Hay-Rich Feed Mixture

PubMed Central

Jiang, Ya-Hui; Wang, Ping; Yang, Hong-Jian; Chen, Ying

2014-01-01

Two commercial materials, a bamboo charcoal (BC) and a smectite clay (SC), were assessed in vitro with aflatoxin B1 (AFB1) in an equilibrium adsorption test. The adsorption capacity and proportion adsorbed (0.381 μg/mg, 0.955) for BC were greater than for SC (0.372 μg/mg, 0.931). The effects of in vitro ruminal fermentation of hay-rich feed incubated with 1.0 μg/mL AFB1 for 0–10 g/L doses of BC and SC were measured at 39 °C for 72 h. The BC and SC binders increased AFB1 loss at dosages ≥1.0 g/L (p < 0.0001). Average AFB1 loss (p < 0.0001) was greater for SC (0.904) than BC (0.881). Both SC and SC addition increased in vitro dry matter loss, and the average dry matter losses were similar. Asymptotic gas volume and volatile fatty acid production were greater for BC than for SC (p < 0.0001). Thus, BC may be as effective as SC in removing aflatoxin B1’s detrimental effects on rumen degradability and fermentation under the occurrence of microbial aflatoxin degradation. PMID:25014194

Variation of the radiative properties during black carbon aging: theoretical and experimental intercomparison

DOE PAGES

He, C.; Liou, K.-N.; Takano, Y.; ...

2015-07-20

A theoretical black carbon (BC) aging model is developed to account for three typical evolution stages, namely, freshly emitted aggregates, coated BC by soluble material, and BC particles undergoing further hygroscopic growth. The geometric-optics surface-wave (GOS) approach is employed to compute the BC single-scattering properties at each aging stage, which are subsequently compared with laboratory measurements. Theoretical calculations are consistent with measurements in extinction and absorption cross sections for fresh BC aggregates, but overestimate the scattering cross sections for BC mobility diameters of 155, 245, and 320 nm, because of uncertainties associated with theoretical calculations for small particles as wellmore » as laboratory scattering measurements. The measured optical cross sections for coated BC by sulfuric acid and for those undergoing further hygroscopic growth are captured by theoretical calculations using a concentric core-shell structure, with differences of less than 20 %. This suggests that the core-shell shape represents the realistic BC coating morphology reasonably well in this case, which is consistent with the observed strong structure compaction during aging. We find that the absorption and scattering properties of fresh BC aggregates vary by up to 60 % due to uncertainty in the BC refractive index, which, however, is a factor of two smaller in the case of coated BC particles. Sensitivity analyses on the BC morphology show that the optical properties of fresh BC aggregates are more sensitive to fractal dimension than primary spherule size. The absorption and scattering cross sections of coated BC particles vary by more than a factor of two due to different coating structures. We find an increase of 20–250 % in absorption and a factor of 3–15 in scattering during aging, significantly depending on coating morphology and aging stages. Applying the aging model to CalNex 2010 field measurements, we show that the resulting BC direct radiative forcing (DRF) first increases from 1.5 to 1.7 W m -2 and subsequently decreases to 1.0 W m -2 during the transport from the Los Angeles Basin to downwind regions, as a result of the competition between absorption enhancement due to coating and dilution of BC concentration. The BC DRF can vary by up to a factor of two due to differences in BC coating morphology. Thus, an accurate estimate of BC DRF requires the incorporation of a dynamic BC aging process that accounts for realistic morphology in climate models, particularly for the regional analysis with high atmospheric heterogeneity.« less

Variation of the radiative properties during black carbon aging: theoretical and experimental intercomparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, C.; Liou, K.-N.; Takano, Y.

A theoretical black carbon (BC) aging model is developed to account for three typical evolution stages, namely, freshly emitted aggregates, coated BC by soluble material, and BC particles undergoing further hygroscopic growth. The geometric-optics surface-wave (GOS) approach is employed to compute the BC single-scattering properties at each aging stage, which are subsequently compared with laboratory measurements. Theoretical calculations are consistent with measurements in extinction and absorption cross sections for fresh BC aggregates, but overestimate the scattering cross sections for BC mobility diameters of 155, 245, and 320 nm, because of uncertainties associated with theoretical calculations for small particles as wellmore » as laboratory scattering measurements. The measured optical cross sections for coated BC by sulfuric acid and for those undergoing further hygroscopic growth are captured by theoretical calculations using a concentric core-shell structure, with differences of less than 20 %. This suggests that the core-shell shape represents the realistic BC coating morphology reasonably well in this case, which is consistent with the observed strong structure compaction during aging. We find that the absorption and scattering properties of fresh BC aggregates vary by up to 60 % due to uncertainty in the BC refractive index, which, however, is a factor of two smaller in the case of coated BC particles. Sensitivity analyses on the BC morphology show that the optical properties of fresh BC aggregates are more sensitive to fractal dimension than primary spherule size. The absorption and scattering cross sections of coated BC particles vary by more than a factor of two due to different coating structures. We find an increase of 20–250 % in absorption and a factor of 3–15 in scattering during aging, significantly depending on coating morphology and aging stages. Applying the aging model to CalNex 2010 field measurements, we show that the resulting BC direct radiative forcing (DRF) first increases from 1.5 to 1.7 W m -2 and subsequently decreases to 1.0 W m -2 during the transport from the Los Angeles Basin to downwind regions, as a result of the competition between absorption enhancement due to coating and dilution of BC concentration. The BC DRF can vary by up to a factor of two due to differences in BC coating morphology. Thus, an accurate estimate of BC DRF requires the incorporation of a dynamic BC aging process that accounts for realistic morphology in climate models, particularly for the regional analysis with high atmospheric heterogeneity.« less

Free fatty acids electronically bridge the self-assembly of a three-component nanocomplex consisting of amylose, protein, and free fatty acids.

PubMed

Zhang, Genyi; Maladen, Michelle; Campanella, Osvaldo H; Hamaker, Bruce R

2010-08-25

The self-assembly of a ternary complex, which is formed through heating and cooling of a mixture of amylose (1.0 mg/mL), whey protein isolate (50 μg/mL), and free fatty acids (FFAs, 250 μg/mL) was investigated. High-performance size-exclusion chromatography-multi-angle laser light scattering (HPSEC-MALLS) analysis showed that the complex is a water-soluble supramolecule (Mw = 6-7 × 10(6)), with a radius of gyration of 20-100 nm, indicating a nanoscale complex. Experimental results using 1-monostearyl-rac-glycerol (MSG) or cetyl alcohol that is similar to FFA in structure (except the headgroup) indicate that FFAs are the bridge between thermodynamically incompatible amylose and protein molecules and their functional carboxyl group is essential to the formation of the complex. Additionally, the effects of pH and salt treatments suggest that electrostatic interactions between negatively charged carboxyl groups of FFAs and polyionic protein are the foundation for the self-assembly of the complex. The fact that FFA is one important component in the self-assembled complex with an estimated molar ratio of 6:1:192 (amylose/protein/FFA, ∼4-5% FFA) demonstrates that it might be used as a nanocarrier for the controlled release of lipophilic functional materials to maintain their stability, bioactivity, and more importantly water solubility.

Black carbon cookstove emissions: A field assessment of 19 stove/fuel combinations

NASA Astrophysics Data System (ADS)

Garland, Charity; Delapena, Samantha; Prasad, Rajendra; L'Orange, Christian; Alexander, Donee; Johnson, Michael

2017-11-01

Black carbon (BC) emissions from household cookstoves consuming solid fuel produce approximately 25 percent of total anthropogenic BC emissions. The short atmospheric lifetime of BC means that reducing BC emissions would result in a faster climate response than mitigating CO2 and other long-lived greenhouse gases. This study presents the results of optical BC measurements of two new cookstove emissions field assessments and 17 archived cookstove datasets. BC was determined from attenuation of 880 nm light, which is strongly absorbed by BC, and linearly related between 1 and 125 attenuation units. A relationship was experimentally determined correlating BC mass deposition on quartz filters determined via thermal optical analysis (TOA) and on PTFE and quartz filters using transmissometry, yielding an attenuation cross-section (σATN) for both filter media types. σATN relates TOA measurements to optical measurements on PTFE and quartz (σATN(PTFE) = 13.7 cm-2 μg, R2 = 0.87, σATN(Quartz) = 15.6 cm-2 μg, R2 = 0.87). These filter-specific σATN, optical measurements of archived filters were used to determine BC emission factors and the fraction of particulate matter (PM) in the form of black carbon (BC/PM). The 19 stoves measured fell into five stove classes; simple wood, rocket, advanced biomass, simple charcoal, and advanced charcoal. Advanced biomass stoves include forced- and natural-draft gasifiers which use wood or biomass pellets as fuel. Of these classes, the simple wood and rocket stoves demonstrated the highest median BC emission factors, ranging from 0.051 to 0.14 g MJ-1. The lowest BC emission factors were seen in charcoal stoves, which corresponds to the generally low PM emission factors observed during charcoal combustion, ranging from 0.0084 to 0.014 g MJ-1. The advanced biomass stoves generally showed an improvement in BC emissions factors compared to simple wood and rocket stoves, ranging from 0.0031 to 0.071 g MJ-1. BC/PM ratios were highest for the advanced and rocket stoves. Potential relative climate impacts were estimated by converting aerosol emissions to CO2-equivalent, and suggest that some advanced stove/fuel combinations could provide substantial climate benefits.

The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1

PubMed Central

Osada, Shigehiro; Sutton, Ann; Muster, Nemone; Brown, Christine E.; Yates, John R.; Sternglanz, Rolf; Workman, Jerry L.

2001-01-01

It is well established that acetylation of histone and nonhistone proteins is intimately linked to transcriptional activation. However, loss of acetyltransferase activity has also been shown to cause silencing defects, implicating acetylation in gene silencing. The something about silencing (Sas) 2 protein of Saccharomyces cerevisiae, a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family, promotes silencing at HML and telomeres. Here we identify a ∼450-kD SAS complex containing Sas2p, Sas4p, and the tf2f-related Sas5 protein. Mutations in the conserved acetyl-CoA binding motif of Sas2p are shown to disrupt the ability of Sas2p to mediate the silencing at HML and telomeres, providing evidence for an important role for the acetyltransferase activity of the SAS complex in silencing. Furthermore, the SAS complex is found to interact with chromatin assembly factor Asf1p, and asf1 mutants show silencing defects similar to mutants in the SAS complex. Thus, ASF1-dependent chromatin assembly may mediate the role of the SAS complex in silencing. PMID:11731479

BRCA1 and TP53 Gene-Mutations: Family Predisposition and Radioecological Risk of Developing Breast Cancer.

PubMed

Apsalikov, Bakytbek; Manambaeva, Zukhra; Ospanov, Erlan; Massabayeva, Meruyert; Zhabagin, Kuantkan; Zhagiparova, Zhanar; Maximov, Vladymir; Voropaeva, Elena; Apsalikov, Kazbek; Belikhina, Tatiana; Abdrahmanov, Ramil; Cherepkova, Elena; Tanatarov, Sayat; Massadykov, Adilzhan; Urazalina, Naylia

2016-01-01

Frequencies of polymorphisms of genes BRCA1 and TP53 in breast cancer (BC) patients with a BC family history and radiation history were assessed and compared in the Semey region of Kazakhstan. The study included 60 women directly irradiated by the activities of the Semipalatinsk test site with a calculated effective equivalent dose of 500 mSv and their first generation descendants (group BC+Her+Exp); 65 women with family BC and absence of radiological history - the effective equivalent dose due to anthropogenic sources not exceeding 50 mSv (group BC+Her-Exp). The comparison group consisted of 65 women patients with breast cancer without family and radiological history (BC-Her-Exp). The control group comprised 60 women without breast cancer and without family and radiological history (nonBC). We carried out the genotyping of the polymorphisms c.2311T>C, c.4308T>C and 5382insC of the BRCA1 gene and rs1042522 of the TP53 gene. The frequency of the polymorphism c.2311T>C was significantly higher in patients of the group BC+Her+Exp than in healthy women, and of the polymorphism 5382insC in BC+Her+Exp compared to all other groups. The frequency of the rs1042522 polymorphism of TP53 was significantly higher in all groups of patients with breast cancer compared with the control group. Differences between groups of women with breast cancer were significant only in BC+Her+Exp vs. BC+Her-Exp. Combinations of polymorphisms of the genes BRCA1 and TP53 predominated in women with a family and radiological history.

Abiotic reduction of trifluralin and pendimethalin by sulfides in black-carbon-amended coastal sediments.

PubMed

Gong, Wenwen; Liu, Xinhui; Xia, Shuhua; Liang, Baocui; Zhang, Wei

2016-06-05

Dinitroaniline herbicides such as trifluralin and pendimethalin are persistent bioaccumulative toxins to aquatic organisms. Thus, in-situ remediation of contaminated sediments is desired. This study investigated whether black carbons (BCs), including apple wood charcoal (BC1), rice straw biochar (BC2), and activated carbon (BC3), could facilitate abiotic reduction of trifluralin and pendimethalin by sulfides of environmentally-relevant concentrations in anoxic coastal sediments. The reduction rates of trifluralin and pendimethalin increased substantially with increasing BC dosages in the sediments. This enhancing effect was dependent on BC type with the greatest for BC3 followed by BC1 and BC2, which well correlated with their specific surface area. The pseudo-first order reduction rate constants (kobs) for BC3-amended sediment (2%) were 13- and 14 times the rate constants in the BC-free sediment. The reduction rates increased with increasing temperature from 8 to 25°C in the BC-amended sediment, following the Arrhenius relationship. Finally, through molecular modeling by density functional theory and reaction species identification from mass spectra, molecular pathways of trifluralin and pendimethalin reduction were elucidated. In contrary to the separate sequential reduction of each nitro group to amine group, both nitro groups, first reduced to nitroso, then eventually to amine groups. Copyright © 2016 Elsevier B.V. All rights reserved.

Red meat, poultry, and fish intake and breast cancer risk among Hispanic and Non-Hispanic white women: The Breast Cancer Health Disparities Study

PubMed Central

Kim, Andre; Lundgreen, Abbie; Wolff, Roger K.; Fejerman, Laura; John, Esther M.; Torres-Mejía, Gabriela; Ingles, Sue A.; Boone, Stephanie D.; Connor, Avonne E.; Hines, Lisa M.; Baumgartner, Kathy B.; Giuliano, Anna; Joshi, Amit D.; Slattery, Martha L.; Stern, Mariana C.

2016-01-01

Purpose There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women. Methods The study included NHW (1,982 cases and 2,218 controls) and US Hispanics (1,777 cases and 2,218 controls) from 2 population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study and race/ethnicity specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels. Results When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR = 1.25; 95% CI = 1.05–1.50; trend p = 0.006),. Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR = 1.42; 95% CI 1.18–1.71; trend p < 0.001), and between white meat (OR = 0.80; 95% CI 0.67–0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models, and were restricted to estrogen receptor positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups. Conclusions Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities. PMID:26898200

Impact of DNA repair genes polymorphism (XPD and XRCC1) on the risk of breast cancer in Egyptian female patients.

PubMed

Hussien, Yousry Mostafa; Gharib, Amal F; Awad, Hanan A; Karam, Rehab A; Elsawy, Wael H

2012-02-01

The genes involved in DNA repair system play a crucial role in the protection against mutations. It has been hypothesized that functional deficiencies in highly conserved DNA repair processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer (BC). The aim of the present study was to evaluate the association of genetic polymorphisms in 2 DNA repair genes, XPD (Asp312Asn) and XRCC1 (A399G), with BC susceptibility. We further investigated the potential combined effect of these DNA repair variants on BC risk. Both XPD (xeroderma pigmentosum group D) and XRCC1 (X-ray repair cross-complementing group 1) polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method and PCR with confronting two-pair primers (PCR-CTPP), using DNA from peripheral blood in a case control study. Our results revealed that the frequencies of AA genotype of XPD codon 312 polymorphism were significantly higher in the BC patients than in the normal individuals (P ≤ 0.003), and did not observe any association between the XRCC1 Arg399Gln polymorphism and risk of developing BC. Also, no association between both XPD Asp312Asn and XRCC1 A399G polymorphisms and the clinical characteristics of disease. Finally, the combination of AA(XPD) + AG(XRCC1) were significantly associated with BC risk. Our results suggested that, XPD gene is an important candidate gene for susceptibility to BC. Also, gene-gene interaction between XPD(AA) + XRCC1(AG) polymorphism may be associated with increased risk of BC in Egyptian women.

Inflammasome assembly in the chorioamniotic membranes during spontaneous labor at term.

PubMed

Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Garcia-Flores, Valeria; Leng, Yaozhu; Panaitescu, Bogdan; Miller, Derek; Abrahams, Vikki M; Hassan, Sonia S

2017-05-01

Inflammasome activation requires two steps: priming and assembly of the multimeric complex. The second step includes assembly of the sensor molecule and adaptor protein ASC (an apoptosis-associated speck-like protein containing a CARD), which results in ASC speck formation and the recruitment of caspase (CASP)-1. Herein, we investigated whether there is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes from women who underwent spontaneous labor at term. Using in situ proximity ligation assays, ASC/CASP-1 complexes were determined in the chorioamniotic membranes from women who delivered at term without labor or underwent spontaneous labor at term with or without acute histologic chorioamnionitis (n=10-11 each). Also, ASC speck formation was determined by flow cytometry in the choriodecidual leukocytes isolated from women who delivered at term with or without spontaneous labor (n=9-12 each). (i) ASC/CASP-1 complexes were detected in the chorioamniotic membranes; (ii) ASC/CASP-1 complexes were greater in the chorioamniotic membranes from women who underwent spontaneous labor at term than in those without labor; (iii) ASC/CASP-1 complexes were even more abundant in the chorioamniotic membranes from women who underwent spontaneous labor at term with acute histologic chorioamnionitis than in those without this placental lesion; (iv) ASC speck formation was detected in the choriodecidual leukocytes; and (v) ASC speck formation was greater in the choriodecidual leukocytes isolated from women who underwent spontaneous labor at term than in those without labor. There is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes during spontaneous labor at term. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Orai1 as New Therapeutic Target for Inhibiting Breast Tumor Metastasis

DTIC Science & Technology

2009-09-01

includes focal adhesion assembly (formation of focal complex) and focal adhesion disassembly, we used live - cell imaging to quantify the rates of assembly...A and B) Live cell imaging of paxillin-GFP transfected MEF cells in the absence (A) or presence (B) of SKF96365. Scale bar: 10 µm. (C and D...includes focal adhesion assembly (formation of focal complexes) and focal adhesion disassembly, we used live - cell imaging to quantify the rates of focal

Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Su-Chang; Lo, Yu-Chih; Wu, Hao

2010-08-23

MyD88, IRAK4 and IRAK2 are critical signalling mediators of the TLR/IL1-R superfamily. Here we report the crystal structure of the MyD88-IRAK4-IRAK2 death domain (DD) complex, which surprisingly reveals a left-handed helical oligomer that consists of 6 MyD88, 4 IRAK4 and 4 IRAK2 DDs. Assembly of this helical signalling tower is hierarchical, in which MyD88 recruits IRAK4 and the MyD88-IRAK4 complex recruits the IRAK4 substrates IRAK2 or the related IRAK1. Formation of these Myddosome complexes brings the kinase domains of IRAKs into proximity for phosphorylation and activation. Composite binding sites are required for recruitment of the individual DDs in the complex,more » which are confirmed by mutagenesis and previously identified signalling mutations. Specificities in Myddosome formation are dictated by both molecular complementarity and correspondence of surface electrostatics. The MyD88-IRAK4-IRAK2 complex provides a template for Toll signalling in Drosophila and an elegant mechanism for versatile assembly and regulation of DD complexes in signal transduction.« less

Wildfires in northern Eurasia affect the budget of black carbon in the Arctic - a 12-year retrospective synopsis (2002-2013)

NASA Astrophysics Data System (ADS)

Evangeliou, N.; Balkanski, Y.; Hao, W. M.; Petkov, A.; Silverstein, R. P.; Corley, R.; Nordgren, B. L.; Urbanski, S. P.; Eckhardt, S.; Stohl, A.; Tunved, P.; Crepinsek, S.; Jefferson, A.; Sharma, S.; Nøjgaard, J. K.; Skov, H.

2016-06-01

In recent decades much attention has been given to the Arctic environment, where climate change is happening rapidly. Black carbon (BC) has been shown to be a major component of Arctic pollution that also affects the radiative balance. In the present study, we focused on how vegetation fires that occurred in northern Eurasia during the period of 2002-2013 influenced the budget of BC in the Arctic. For simulating the transport of fire emissions from northern Eurasia to the Arctic, we adopted BC fire emission estimates developed independently by GFED3 (Global Fire Emissions Database) and FEI-NE (Fire Emission Inventory - northern Eurasia). Both datasets were based on fire locations and burned areas detected by MODIS (Moderate resolution Imaging Spectroradiometer) instruments on NASA's (National Aeronautics and Space Administration) Terra and Aqua satellites. Anthropogenic sources of BC were adopted from the MACCity (Monitoring Atmospheric Composition and Climate and megacity Zoom for the Environment) emission inventory.During the 12-year period, an average area of 250 000 km2 yr-1 was burned in northern Eurasia (FEI-NE) and the global emissions of BC ranged between 8.0 and 9.5 Tg yr-1 (FEI-NE+MACCity). For the BC emitted in the Northern Hemisphere (based on FEI-NE+MACCity), about 70 % originated from anthropogenic sources and the rest from biomass burning (BB). Using the FEI-NE+MACCity inventory, we found that 102 ± 29 kt yr-1 BC was deposited in the Arctic (defined here as the area north of 67° N) during the 12 years simulated, which was twice as much as when using the MACCity inventory (56 ± 8 kt yr-1). The annual mass of BC deposited in the Arctic from all sources (FEI-NE in northern Eurasia, MACCity elsewhere) is significantly higher by about 37 % in 2009 (78 vs. 57 kt yr-1) to 181 % in 2012 (153 vs. 54 kt yr-1), compared to the BC deposited using just the MACCity emission inventory. Deposition of BC in the Arctic from BB sources in the Northern Hemisphere thus represents 68 % of the BC deposited from all BC sources (the remaining being due to anthropogenic sources). Northern Eurasian vegetation fires (FEI-NE) contributed 85 % (79-91 %) to the BC deposited over the Arctic from all BB sources in the Northern Hemisphere.We estimate that about 46 % of the BC deposited over the Arctic from vegetation fires in northern Eurasia originated from Siberia, 6 % from Kazakhstan, 5 % from Europe, and about 1 % from Mongolia. The remaining 42 % originated from other areas in northern Eurasia. About 42 % of the BC released from northern Eurasian vegetation fires was deposited over the Arctic (annual average: 17 %) during spring and summer.

Applicability of bacterial cellulose as an alternative to paper points in endodontic treatment.

PubMed

Yoshino, Aya; Tabuchi, Mari; Uo, Motohiro; Tatsumi, Hiroto; Hideshima, Katsumi; Kondo, Seiji; Sekine, Joji

2013-04-01

Dental root canal treatment is required when dental caries progress to infection of the dental pulp. A major goal of this treatment is to provide complete decontamination of the dental root canal system. However, the morphology of dental root canal systems is complex, and many human dental roots have inaccessible areas. In addition, dental reinfection is fairly common. In conventional treatment, a cotton pellet and paper point made from plant cellulose is used to dry and sterilize the dental root canal. Such sterilization requires a treatment material with high absorbency to remove any residue, the ability to improve the efficacy of intracanal medication and high biocompatibility. Bacterial cellulose (BC) is produced by certain strains of bacteria. In this study, we developed BC in a pointed form and evaluated its applicability as a novel material for dental canal treatment with regard to solution absorption, expansion, tensile strength, drug release and biocompatibility. We found that BC has excellent material and biological characteristics compared with conventional materials, such as paper points (plant cellulose). BC showed noticeably higher absorption and expansion than paper points, and maintained a high tensile strength even when wet. The cumulative release of a model drug was significantly greater from BC than from paper points, and BC showed greater compatibility than paper points. Taken together, BC has great potential for use in dental root canal treatment. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Decoding the usefulness of non-coding RNAs as breast cancer markers.

PubMed

Amorim, Maria; Salta, Sofia; Henrique, Rui; Jerónimo, Carmen

2016-09-15

Although important advances in the management of breast cancer (BC) have been recently accomplished, it still constitutes the leading cause of cancer death in women worldwide. BC is a heterogeneous and complex disease, making clinical prediction of outcome a very challenging task. In recent years, gene expression profiling emerged as a tool to assist in clinical decision, enabling the identification of genetic signatures that better predict prognosis and response to therapy. Nevertheless, translation to routine practice has been limited by economical and technical reasons and, thus, novel biomarkers, especially those requiring non-invasive or minimally invasive collection procedures, while retaining high sensitivity and specificity might represent a significant development in this field. An increasing amount of evidence demonstrates that non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are aberrantly expressed in several cancers, including BC. miRNAs are of particular interest as new, easily accessible, cost-effective and non-invasive tools for precise management of BC patients because they circulate in bodily fluids (e.g., serum and plasma) in a very stable manner, enabling BC assessment and monitoring through liquid biopsies. This review focus on how ncRNAs have the potential to answer present clinical needs in the personalized management of patients with BC and comprehensively describes the state of the art on the role of ncRNAs in the diagnosis, prognosis and prediction of response to therapy in BC.

Variation of the radiative properties during black carbon aging: theoretical and experimental intercomparison

DOE PAGES

He, C.; Liou, K.-N.; Takano, Y.; ...

2015-10-28

A theoretical black carbon (BC) aging model is developed to account for three typical evolution stages, namely, freshly emitted aggregates, BC coated by soluble material, and BC particles undergoing further hygroscopic growth. The geometric-optics surface-wave (GOS) approach is employed to compute the BC single-scattering properties at each aging stage, which are subsequently compared with laboratory measurements. Theoretical calculations are consistent with measurements in extinction and absorption cross sections for fresh BC aggregates with different BC sizes (i.e., mobility diameters of 155, 245, and 320 nm), with differences of ≤ 25 %. The measured optical cross sections for BC coated bymore » sulfuric acid and for that undergoing further hygroscopic growth are generally captured (differences < 30 %) by theoretical calculations using a concentric core-shell structure, with an overestimate in extinction and absorption of the smallest BC size and an underestimate in scattering of the largest BC size. We find that the absorption and scattering cross sections of fresh BC aggregates vary by 20–40 and 50–65 %, respectively, due to the use of upper (1.95–0.79 i) and lower (1.75–0.63 i) bounds of BC refractive index, while the variations are < 20 % in absorption and < 50 % in scattering in the case of coated BC particles. Sensitivity analyses of the BC morphology show that the optical properties of fresh BC aggregates are more sensitive to fractal dimension than primary spherule size. The absorption and scattering cross sections of coated BC particles vary by more than a factor of 2 due to different coating structures. We find an increase of 20–250 % in absorption and a factor of 3–15 in scattering during aging, significantly depending on coating morphology and aging stages. This study suggests that an accurate estimate of BC radiative effects requires the incorporation of a dynamic BC aging process that accounts for realistic coating structures in climate models.« less

Variation of the radiative properties during black carbon aging: theoretical and experimental intercomparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, C.; Liou, K.-N.; Takano, Y.

A theoretical black carbon (BC) aging model is developed to account for three typical evolution stages, namely, freshly emitted aggregates, BC coated by soluble material, and BC particles undergoing further hygroscopic growth. The geometric-optics surface-wave (GOS) approach is employed to compute the BC single-scattering properties at each aging stage, which are subsequently compared with laboratory measurements. Theoretical calculations are consistent with measurements in extinction and absorption cross sections for fresh BC aggregates with different BC sizes (i.e., mobility diameters of 155, 245, and 320 nm), with differences of ≤ 25 %. The measured optical cross sections for BC coated bymore » sulfuric acid and for that undergoing further hygroscopic growth are generally captured (differences < 30 %) by theoretical calculations using a concentric core-shell structure, with an overestimate in extinction and absorption of the smallest BC size and an underestimate in scattering of the largest BC size. We find that the absorption and scattering cross sections of fresh BC aggregates vary by 20–40 and 50–65 %, respectively, due to the use of upper (1.95–0.79 i) and lower (1.75–0.63 i) bounds of BC refractive index, while the variations are < 20 % in absorption and < 50 % in scattering in the case of coated BC particles. Sensitivity analyses of the BC morphology show that the optical properties of fresh BC aggregates are more sensitive to fractal dimension than primary spherule size. The absorption and scattering cross sections of coated BC particles vary by more than a factor of 2 due to different coating structures. We find an increase of 20–250 % in absorption and a factor of 3–15 in scattering during aging, significantly depending on coating morphology and aging stages. This study suggests that an accurate estimate of BC radiative effects requires the incorporation of a dynamic BC aging process that accounts for realistic coating structures in climate models.« less

Amino Acid Availability Modulates Vacuolar H+-ATPase Assembly*

PubMed Central

Stransky, Laura A.; Forgac, Michael

2015-01-01

The vacuolar H+-ATPase (V-ATPase) is an ATP-dependent proton pump composed of a peripheral ATPase domain (V1) and a membrane-integral proton-translocating domain (V0) and is involved in many normal and disease processes. An important mechanism of regulating V-ATPase activity is reversible assembly of the V1 and V0 domains. Increased assembly in mammalian cells occurs under various conditions and has been shown to involve PI3K. The V-ATPase is necessary for amino acid-induced activation of mechanistic target of rapamycin complex 1 (mTORC1), which is important in controlling cell growth in response to nutrient availability and growth signals. The V-ATPase undergoes amino acid-dependent interactions with the Ragulator complex, which is involved in recruitment of mTORC1 to the lysosomal membrane during amino acid sensing. We hypothesized that changes in the V-ATPase/Ragulator interaction might involve amino acid-dependent changes in V-ATPase assembly. To test this, we measured V-ATPase assembly by cell fractionation in HEK293T cells treated with and without amino acids. V-ATPase assembly increases upon amino acid starvation, and this effect is reversed upon readdition of amino acids. Lysosomes from amino acid-starved cells possess greater V-ATPase-dependent proton transport, indicating that assembled pumps are catalytically active. Amino acid-dependent changes in both V-ATPase assembly and activity are independent of PI3K and mTORC1 activity, indicating the involvement of signaling pathways distinct from those implicated previously in controlling assembly. By contrast, lysosomal neutralization blocks the amino acid-dependent change in assembly and reactivation of mTORC1 after amino acid starvation. These results identify an important new stimulus for controlling V-ATPase assembly. PMID:26378229

Archaeo-directional and -intensity data from burnt structures at the Thracian site of Halka Bunar (Bulgaria): The effect of magnetic mineralogy, temperature and atmosphere of heating in antiquity

NASA Astrophysics Data System (ADS)

Herries, A. I. R.; Kovacheva, M.; Kostadinova, M.; Shaw, J.

2007-07-01

Archaeomagnetic results are presented from a series of burnt structures at the Thracian site of Halka Bunar. Archaeointensity and archaeodirectional studies were undertaken on three kilns from a pottery production complex. This has been dated to the late 4th and early 3rd century B.C. (325-280 B.C.) based on coins found associated with the kilns [Tonkova, M., 2003. Newly discovered Thracian Centre of the Early Hellenistic Age at the Spring "Halka Bunar" in the Land of C. Gorno Belevo. Annuary of the Institute of Archaeology with Museum. Bulgarian Academy Sci. 2, 148-196 (in Bulgarian)]. This data provides a new point for the Bulgarian archaeomagnetic curve (Dec: 348.70 ± 5.79, Inc: 62.20 ± 2.70, and Fa: 77.23 ± 2.17 μT). The kilns are thought to have been used for producing different types of pottery in a range of heating atmospheres and at different temperatures. Therefore, special attention was paid to the magnetic mineralogy of the samples and its effect on the palaeodata. Kiln 3, orange clay samples were dominated by fine to ultra-fine grained single domain and superparamagnetic magnetite, with a small proportion of haematite. The samples were heated in a high temperature oxidising environment. Kiln 2 was probably used to make grey ware pottery. The samples are light grey and were dominated by stable single domain magnetite formed by high temperature heating in a more reducing environment. Kiln 4, mottled samples consisted of a variable mineralogy showing characteristics of both Kiln 2 and Kiln 3 samples. It was probably used to make traditional, mottled, Thracian ware pottery and was heated to lower temperatures in a mixed environment of heating. Samples heated in an oxidising environment gave more reliable Thellier results than samples heated in a reducing environment in antiquity, as the latter altered heavily on re-heating. A fourth kiln and a destruction feature from different trenches than the kiln complex were also investigated to establish their age. Archaeodirectional data was not recoverable from these two structures due to post-burning disturbance. The mean archaeointensity from Kiln 5 (mean 78.0 ± 1.7 μT) is consistent with that from the main kiln complex (mean 77.23 ± 2.17 μT) and is therefore considered to be contemporary. It was probably not used to make pottery. The destruction feature records much lower archaeointensity values (mean 65.1 ± 1.1 μT). When this value is compared to the existing reference points of the Bulgarian database it suggests this feature is younger than the kilns (250-140 B.C.). Multiple age use of the site is therefore confirmed with a main period of occupation in the late 4th and early 3rd century B.C. and another phase of occupation in the mid 3rd to mid 2nd century B.C.

Ammonium boranes for the selective complexation of cyanide or fluoride ions in water.

PubMed

Hudnall, Todd W; Gabbaï, François P

2007-10-03

With the recognition of aqueous fluoride and cyanide ions as an objective, we have investigated the anion binding properties of two isomeric ammonium boranes, namely [p-(Mes2B)C6H4(NMe3)]+ ([1]+) and [o-(Mes2B)C6H4(NMe3)]+ ([2]+). These cationic boranes, which could be obtained by reaction of the known 4- and 2-dimesitylboryl-N,N-dimethylaniline with MeOTf, have been investigated both experimentally and computationally. They both react with fluoride and cyanide ions in organic solvents to afford the corresponding fluoroborate/ or cyanoborate/ammonium zwitterions 1F, 1CN, 2F, and 2CN. In aqueous solution, however, these cationic boranes behave as remarkably selective receptors. Indeed, [1]+ only complexes cyanide ions while [2]+ only complexes fluoride ions. In H2O/DMSO 60:40 vol (HEPES 6 mM, pH 7), the cyanide binding constant of [1]+ and the fluoride binding constant of [2]+ are respectively equal to 3.9 (+/-0.1) x 108 and 910 (+/-50) M-1. Structural and computational studies indicate that both steric and electronic effects contribute to the unusual selectivity displayed by these cationic boranes. Owing to favorable Coulombic effects, the para-derivative [1]+ has a very high affinity for cyanide; yet these effects are not sufficiently intense to allow complexation of the more efficiently hydrated and less basic fluoride anion. In the case of the ortho-derivative [2]+, the proximity of the ammonium moiety leads to an increase in the Lewis acidity of the boron center thus making fluoride binding possible. However, steric effects prevent cyanide coordination to the boron center of [2]+. Finally, cation [1]+ and [2]+ bind their dedicated anions reversibly and show a negligible response in the presence of other common anions including Cl-, Br-, I-, NO3-, OAc-, H2PO4-, and HSO4-.

Hadronic production of the doubly heavy baryon {Xi}{sub bc} at the LHC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang Jiawei; Wu Xinggang; Zhong Tao

We investigate the hadronic production of the doubly heavy baryon {Xi}{sub bc} at the Large Hadron Collider (LHC), where contributions from the four (bc)-diquark states (bc){sub 3,6}[{sup 1}S{sub 0}] and (bc){sub 3,6}[{sup 3}S{sub 1}] have been taken into consideration. Numerical results show that under the condition of p{sub T}>4 GeV and |y|<1.5, sizable {Xi}{sub bc} events about 1.7x10{sup 7} and 3.5x10{sup 9} per year can be produced for the center-of-mass energy {radical}(S)=7 TeV and {radical}(S)=14 TeV, respectively. For experimental usage, the total and the interested differential cross sections are estimated under some typical p{sub T} and y cuts for themore » LHC detectors CMS, ATLAS, and LHCb. The main uncertainties are discussed and a comparative study on the hadronic production of {Xi}{sub cc}, {Xi}{sub bc}, and {Xi}{sub bb} at the LHC are also presented.« less

Bovine colostrum supplementation does not affect plasma I-FABP concentrations following exercise in a hot and humid environment.

PubMed

McKenna, Zachary; Berkemeier, Quint; Naylor, Ashley; Kleint, Austin; Gorini, Felipe; Ng, Jason; Kim, Jong-Kyung; Sullivan, Sean; Gillum, Trevor

2017-12-01

To quantify the impact of a 14-day bovine colostrum (BC) supplementation on intestinal cell damage following exercise in a hot and humid environment. Ten male participants (20 ± 2 years, VO 2max 55.80 ± 3.79 mL kg -1  min -1 , 11.81 ± 2.71% body fat) ran for 46 ± 7.75 min at 95% of ventiliatory threshold in 40 °C and 50% RH following a 14-day double-blinded supplementation with either BC or placebo (Plac). Core temperature, skin temperature, heart rate, and rating of perceived exertion were recorded every 5 min during exercise. Blood was taken pre, post, 1 h, and 4 h post exercise. Intestinal cell damage was assessed via intestinal fatty acid binding protein (I-FABP). I-FABP concentrations were similar between conditions at all time points [pre 989.39 ± 490.88 pg ml -1 (BC) 851.35 ± 450.71 pg ml -1 (Plac) post 1505.10 ± 788.63 pg ml -1 (BC) 1267.12 ± 521.51 pg ml -1 (Plac) 1-h, 1087.77 ± 397.06 pg ml -1 (BC) 997.25 ± 524.74 pg ml -1 (Plac) 4-h, 511.35 ± 243.10 pg ml -1 (BC) 501.46 ± 222.54 pg ml -1 (Plac)]. I-FABP was elevated pre to post exercise for both BC (162 ± 50%) and Plac (162 ± 56%) (p < 0.05). BC had no effect on mean body temperature [beginning 36.11 ± 0.30 °C, ending: 39.52 ± 0.28 °C (BC); beginning:35.96 ± 0.43 °C, ending:39.42 ± 0.38 °C (Plac)]. While BC supplementation may protect against enterocyte damage during exercise in thermonuetral environments, our data suggest that BC supplementation may not be an effective technique for preventing enterocyte damage during exercise when core temperature exceeds 39 °C.

Molecular Epidemiology of HIV-1 in Jilin Province, Northeastern China: Emergence of a New CRF07_BC Transmission Cluster and Intersubtype Recombinants

PubMed Central

Ning, Chuanyi; Feng, Yi; Xie, Cunxin; He, Xiang; Takebe, Yutaka; Sun, Liuyan; Guo, Qi; Xing, Hui; Kalish, Marcia L.; Shao, Yiming

2014-01-01

Objective To investigate the HIV-1 molecular epidemiology among newly diagnosed HIV-1 infected persons living in the Jilin province of northeastern China. Methods Plasma samples from 189 newly diagnosed HIV-1 infected patients were collected between June 2010 and August 2011 from all nine cities of Jilin province. HIV-1 nucleotide sequences of gag P17–P24 and env C2–C4 gene regions were amplified using a multiplex RT-PCR method and sequenced. Phylogenetic and recombination analyses were used to determine the HIV-1 genotypes. Results Based on all sequences generated, the subtype/CFR distribution was as follows: CRF01_AE (58.1%), CRF07_BC (13.2%), subtype B’ (13.2%), recombinant viruses (8.1%), subtype B (3.7%), CRF02_AG (2.9%), subtype C (0.7%). In addition to finding CRF01_AE strains from previously reported transmission clusters 1, 4 and 5, a new transmission cluster was described within the CRF07_BC radiation. Among 11 different recombinants identified, 10 contained portions of gene regions from the CRF01_AE lineage. CRF02_AG was found to form a transmission cluster of 4 in local Jilin residents. Conclusions Our study presents a molecular epidemiologic investigation describing the complex structure of HIV-1 strains co-circulating in Jilin province. The results highlight the critical importance of continuous monitoring of HIV-infections, along with detailed socio-demographic data, in order to design appropriate prevention measures to limit the spread of new HIV infections. PMID:25356726

Using Combustion Tracers to Estimate Surface Black Carbon Distributions in WRF-Chem

NASA Astrophysics Data System (ADS)

Raman, A.; Arellano, A. F.

2015-12-01

Black Carbon (BC) emissions significantly affect the global and regional climate, air quality, and human health. However, BC observations are currently limited in space and time; leading to considerable uncertainties in the estimates of BC distribution from regional and global models. Here, we investigate the usefulness of carbon monoxide (CO) in quantifying BC across continental United States (CONUS). We use high resolution EPA AQS observations of CO and IMPROVE BC to estimate BC/CO ratios. We model the BC and CO distribution using the community Weather Research and Forecasting model with Chemistry (WRF-Chem). We configured WRF-Chem using MOZART chemistry, NEI 2005, MEGAN, and FINNv1.5 for anthropogenic, biogenic and fire emissions, respectively. In this work, we address the following three key questions: 1) What are the discrepancies in the estimates of BC and CO distributions across CONUS during summer and winter periods?, 2) How do BC/CO ratios change for different spatial and temporal regimes?, 3) Can we get better estimates of BC from WRF-Chem if we use BC/CO ratios along with optimizing CO concentrations? We compare ratios derived from the model and observations and develop characteristic ratios for several geographical and temporal regimes. We use an independent set of measurements of BC and CO to evaluate these ratios. Finally, we use a Bayesian synthesis inversion to optimize CO from WRF-Chem using regionally tagged CO tracers. We multiply the characteristic ratios we derived with the optimized CO to obtain BC distributions. Our initial results suggest that the maximum ratios of BC versus CO occur in the western US during the summer (average: 4 ng/m3/ppbv) and in the southeast during the winter (average: 5 ng/m3/ppbv). However, we find that these relationships vary in space and time and are highly dependent on fuel usage and meteorology. We find that optimizing CO using EPA-AQS provides improvements in BC but only over areas where BC/CO ratios are close to observed values.Black Carbon (BC) emissions significantly affect the global and regional climate, air quality, and human health. However, BC observations are currently limited in space and time; leading to considerable uncertainties in the estimates of BC distribution from regional and global models. Here, we investigate the usefulness of carbon monoxide (CO) in quantifying BC across continental United States (CONUS). We use high resolution EPA AQS observations of CO and IMPROVE BC to estimate BC/CO ratios. We model the BC and CO distribution using the community Weather Research and Forecasting model with Chemistry (WRF-Chem). We configured WRF-Chem using MOZART chemistry, NEI 2005, MEGAN, and FINNv1.5 for anthropogenic, biogenic and fire emissions, respectively. In this work, we address the following three key questions: 1) What are the discrepancies in the estimates of BC and CO distributions across CONUS during summer and winter periods?, 2) How do BC/CO ratios change for different spatial and temporal regimes?, 3) Can we get better estimates of BC from WRF-Chem if we use BC/CO ratios along with optimizing CO concentrations? We compare ratios derived from the model and observations and develop characteristic ratios for several geographical and temporal regimes. We use an independent set of measurements of BC and CO to evaluate these ratios. Finally, we use a Bayesian synthesis inversion to optimize CO from WRF-Chem using regionally tagged CO tracers. We multiply the characteristic ratios we derived with the optimized CO to obtain BC distributions. Our initial results suggest that the maximum ratios of BC versus CO occur in the western US during the summer (average: 4 ng/m3/ppbv) and in the southeast during the winter (average: 5 ng/m3/ppbv). However, we find that these relationships vary in space and time and are highly dependent on fuel usage and meteorology. We find that optimizing CO using EPA-AQS provides improvements in BC but only over areas where BC/CO ratios are close to observed values.

Antihuman factor VIII C2 domain antibodies in hemophilia A mice recognize a functionally complex continuous spectrum of epitopes dominated by inhibitors of factor VIII activation

PubMed Central

Meeks, Shannon L.; Healey, John F.; Parker, Ernest T.; Barrow, Rachel T.

2007-01-01

The diversity of factor VIII (fVIII) C2 domain antibody epitopes was investigated by competition enzyme-linked immunosorbent assay (ELISA) using a panel of 56 antibodies. The overlap patterns produced 5 groups of monoclonal antibodies (MAbs), designated A, AB, B, BC, and C, and yielded a set of 18 distinct epitopes. Group-specific loss of antigenicity was associated with mutations at the Met2199/Phe2200 phospholipid binding β-hairpin (group AB MAbs) and at Lys2227 (group BC MAbs), which allowed orientation of the epitope structure as a continuum that covers one face of the C2 β-sandwich. MAbs from groups A, AB, and B inhibit the binding of fVIIIa to phospholipid membranes. Group BC was the most common group and displayed the highest specific fVIII inhibitor activities. MAbs in this group are type II inhibitors that inhibit the activation of fVIII by either thrombin or factor Xa and poorly inhibit the binding of fVIII to phospholipid membranes or von Willebrand factor (VWF). Group BC MAbs are epitopically and mechanistically distinct from the extensively studied group C MAb, ESH8. These results reveal the structural and functional complexity of the anti-C2 domain antibody response and indicate that interference with fVIII activation is a major attribute of the inhibitor landscape. PMID:17848617

Long and spatially variable Neolithic Demographic Transition in the North American Southwest

PubMed Central

Kohler, Timothy A.; Reese, Kelsey M.

2014-01-01

In many places of the world, a Neolithic Demographic Transition (NDT) is visible as a several-hundred-year period of increased birth rates coupled with stable mortality rates, resulting in dramatic population growth that is eventually curtailed by increased mortality. Similar processes can be reconstructed in particular detail for the North American Southwest, revealing an anomalously long and spatially variable NDT. Irrigation-dependent societies experienced relatively low birth rates but were quick to achieve a high degree of sociopolitical complexity, whereas societies dependent on dry or rainfed farming experienced higher birth rates but less initial sociopolitical complexity. Low birth rates after A.D. 1200 mark the beginning of the decline of the Hohokam. Overall in the Southwest, birth rates increased slowly from 1100 B.C. to A.D. 500, and remained at high levels with some fluctuation until decreasing rapidly beginning A.D. 1300. Life expectancy at 15 increased slowly from 900 B.C. to A.D. 700, and then increased rapidly for 200 y before fluctuating and then declining after A.D. 1400. Life expectancy at birth, on the other hand, generally declined from 1100 B.C. to A.D. 1100/1200, before rebounding. Farmers took two millennia (∼1100 B.C. to ∼A.D. 1000) to reach the carrying capacity of the agricultural niche in the Southwest. PMID:24982134

Smoking increases risks of all-cause and breast cancer specific mortality in breast cancer individuals: a dose-response meta-analysis of prospective cohort studies involving 39725 breast cancer cases

PubMed Central

Wang, Kang; Li, Feng; Zhang, Xiang; Li, Zhuyue; Li, Hongyuan

2016-01-01

Smoking is associated with the risks of mortality from breast cancer (BC) or all causes in BC survivors. Two-stage dose-response meta-analysis was conducted. A search of PubMed and Embase was performed, and a random-effect model was used to yield summary hazard ratios (HRs). Eleven prospective cohort studies were included. The summary HR per 10 cigarettes/day, 10 pack-years, 10 years increase were 1.10 (95% confidence interval (CI) = 1.04–1.16), 1.09 (95% CI = 1.06–1.12), 1.10 (95% CI = 1.06–1.14) for BC specific mortality, and 1.15 (95% CI = 1.10–1.19), 1.15 (95% CI = 1.10–1.20), 1.17 (95% CI = 1.11–1.23) for all-cause mortality, respectively. The linear or non-linear associations between smoking and risks of mortality from BC or all causes were revealed. Subgroup analyses suggested a positive association between ever or former smoking and the risk of all-cause mortality in BC patients, especially in high doses consumption. In conclusion, higher smoking intensity, more cumulative amount of cigarettes consumption and longer time for smoking is associated with elevated risk of mortality from BC and all causes in BC individuals. The results regarding smoking cessation and “ever or former” smokers should be treated with caution due to limited studies. PMID:27863414

RISC assembly: Coordination between small RNAs and Argonaute proteins.

PubMed

Kobayashi, Hotaka; Tomari, Yukihide

2016-01-01

Non-coding RNAs generally form ribonucleoprotein (RNP) complexes with their partner proteins to exert their functions. Small RNAs, including microRNAs, small interfering RNAs, and PIWI-interacting RNAs, assemble with Argonaute (Ago) family proteins into the effector complex called RNA-induced silencing complex (RISC), which mediates sequence-specific target gene silencing. RISC assembly is not a simple binding between a small RNA and Ago; rather, it follows an ordered multi-step pathway that requires specific accessory factors. Some steps of RISC assembly and RISC-mediated gene silencing are dependent on or facilitated by particular intracellular platforms, suggesting their spatial regulation. In this review, we summarize the currently known mechanisms for RISC assembly of each small RNA class and propose a revised model for the role of the chaperone machinery in the duplex-initiated RISC assembly pathway. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. Copyright © 2015 Elsevier B.V. All rights reserved.

Traffic-Related Air Pollution, Blood Pressure, and Adaptive Response of Mitochondrial Abundance.

PubMed

Zhong, Jia; Cayir, Akin; Trevisi, Letizia; Sanchez-Guerra, Marco; Lin, Xinyi; Peng, Cheng; Bind, Marie-Abèle; Prada, Diddier; Laue, Hannah; Brennan, Kasey J M; Dereix, Alexandra; Sparrow, David; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A

2016-01-26

Exposure to black carbon (BC), a tracer of vehicular-traffic pollution, is associated with increased blood pressure (BP). Identifying biological factors that attenuate BC effects on BP can inform prevention. We evaluated the role of mitochondrial abundance, an adaptive mechanism compensating for cellular-redox imbalance, in the BC-BP relationship. At ≥ 1 visits among 675 older men from the Normative Aging Study (observations=1252), we assessed daily BP and ambient BC levels from a stationary monitor. To determine blood mitochondrial abundance, we used whole blood to analyze mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA) using quantitative polymerase chain reaction. Every standard deviation increase in the 28-day BC moving average was associated with 1.97 mm Hg (95% confidence interval [CI], 1.23-2.72; P<0.0001) and 3.46 mm Hg (95% CI, 2.06-4.87; P<0.0001) higher diastolic and systolic BP, respectively. Positive BC-BP associations existed throughout all time windows. BC moving averages (5-day to 28-day) were associated with increased mtDNA/nDNA; every standard deviation increase in 28-day BC moving average was associated with 0.12 standard deviation (95% CI, 0.03-0.20; P=0.007) higher mtDNA/nDNA. High mtDNA/nDNA significantly attenuated the BC-systolic BP association throughout all time windows. The estimated effect of 28-day BC moving average on systolic BP was 1.95-fold larger for individuals at the lowest mtDNA/nDNA quartile midpoint (4.68 mm Hg; 95% CI, 3.03-6.33; P<0.0001), in comparison with the top quartile midpoint (2.40 mm Hg; 95% CI, 0.81-3.99; P=0.003). In older adults, short-term to moderate-term ambient BC levels were associated with increased BP and blood mitochondrial abundance. Our findings indicate that increased blood mitochondrial abundance is a compensatory response and attenuates the cardiac effects of BC. © 2015 American Heart Association, Inc.

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE PAGES

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; ...

2017-02-23

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel Phase Formation in Dilute Triblock Copolyelectrolyte Complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Prabhu, Vivek; de Pablo, Juan; Tirrell, Matthew

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at extremely low polymer concentrations (<1 % by mass) has been observed in scattering experiments and molecular dynamics simulations. In contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing polymer concentrations, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assemblies of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously upon solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of triblock copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries not only contribute to our fundamental understanding of the structure and pathways of complexation driven assemblies, but also raise intriguing prospects for formation of gel structures at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

Gel phase formation in dilute triblock copolyelectrolyte complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; Goldfeld, David J.; Mao, Jun; Heller, William T.; Prabhu, Vivek M.; de Pablo, Juan J.; Tirrell, Matthew V.

2017-02-01

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

Age at diagnosis of female breast cancer in Oman: Issues and implications.

PubMed

Mehdi, Itrat; Monem, Essam Abdul; Al Bahrani, Bassim Jaffar; Al Kharusi, Suad; Nada, Ayman Mohammad; Al Lawati, Jawad; Al Lawati, Najla

2014-04-01

Female breast cancer (BC) is the most frequent malignancy diagnosed globally, about 23% of the diagnosed cancers. BC incidence varies geographically, highest in Western Europe and lowest in Africa. BC in females is strongly correlated to age, the highest incidence rate amongst older women reinforcing the importance of hormonal status. BC in young females has an aggressive phenotype. There is a shared observation amongst practicing oncologists that BC in Middle East and the developing world presents at an earlier age. The aims of this study are to evaluate the age at presentation of female BC in Oman, and to compare our data with international and regional published data. It discusses the impact of young age Breast Cancer. All diagnosed female BC cases registered from 1996-2010 all over the country, were retrieved from the National Cancer Registry, Ministry of Health. BC cases were analyzed with respect to age at presentation. The data were compared with regional and international data. A total of 14,109 cancer cases were recorded during the period of study. BC was the leading malignancy as 1,294 cases (9.1%). Female BC patients were 1,230; denoting 19.2% of all female cancers. 53.5% of female BC presented below 50 years of age. Male BC constituted 5% of total, with 67% of male BC occurring over 50 years of age. Compared with data from Oman, the highest rates in UK and other Western countries are above 50 years of age. These rates are four to 10 times higher than local in different age groups. Interestingly, these rates increase with increasing age in UK from 40-45 to up to 85+, keep on increasing and go up to four times higher with higher age. This phenomenon, of increasing incidence rates with age, is not observed in our local population. BC is significantly correlated to age as reported from Western population. BC is reported at a younger age from developing and Arab World, which need to be further studied and validated. This phenomenon of BC in younger age may have significant implications and effects ranging from screening, diagnosis, management, prognosis, and cost of treatment. The impact on young women diagnosed with BC is enormous, ranging from psychosocial to healthcare services and economics. There is a need to study it further in depth in developing World.

Isolation and identification of cellulose-producing strain Komagataeibacter intermedius from fermented fruit juice.

PubMed

Lin, Shin-Ping; Huang, Yin-Hsuan; Hsu, Kai-Di; Lai, Ying-Jang; Chen, Yu-Kuo; Cheng, Kuan-Chen

2016-10-20

A bacterial cellulose (BC) producing strain isolated from fermented fruit juice was identified as Komagataeibacter intermedius (K. intermedius) FST213-1 by 16s rDNA sequencing analysis and biochemical characteristics test. K. intermedius FST213-1 can produce BC within pH 4-9 and exhibit maximum BC production (1.2g/L) at pH 8 in short-term (4-day) cultivation. Results of Fourier transform infrared spectroscopy, X-ray diffraction, water content, thermogravimetric analysis and mechanical property indicated that BC produced from K. intermedius FST213-1 exhibits higher water content ability (99.5%), lower thermostability (315°C), lower crystallinity (79.3%) and similar mechanical properties in comparison with the specimen from model BC producer, Gluconacetobacter xylinus 23769. Based on these analyses, the novel based-resistant strain K. intermedius FST213-1 can efficiently produce BC, which can be applied for industrial manufacturing with potential features. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk of depression, anxiety, and adjustment disorders in women with a suspected but unconfirmed diagnosis of breast or genital organ cancer in Germany.

PubMed

Kostev, Karel; Jacob, Louis; Kalder, Matthias

2017-10-01

Breast cancer (BC) and genital organ cancers (GOC) are known to have a major impact on the quality of life of patients. The aim of this study was to analyze the risk of depression, anxiety, and adjustment disorders in women in Germany with a suspected but unconfirmed diagnosis of BC or GOC in their medical history. This study included women who received a suspected diagnosis of BC or GOC and were followed between 2007 and 2015 (index date). These women were matched (1:1:1) by age to women with a confirmed diagnosis of BC or GOC and women without a cancer diagnosis. The main outcome measure of the study was the rate of depression, anxiety, and adjustment disorder diagnoses within 3 years of the index date. The present analysis included a total of 4,842 patients (mean age = 49.3 years). Within 3 years of the index date, 23.5% of women with a confirmed diagnosis of BC or GOC, 14.1% of those with a suspected diagnosis of BC or GOC, and 10.5% of those without a cancer diagnosis developed depression, anxiety, or an adjustment disorder (log-rank p value <0.001). Women with a suspected diagnosis of cancer were at a higher risk for these psychiatric conditions than those without a cancer diagnosis (BC and GOC: HR 1.32; BC: HR 1.21; GOC: HR 1.50). A suspected diagnosis of BC or GOC in a woman's medical history is associated with an increased risk of developing depression, anxiety, and adjustment disorders.

The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

PubMed

Booth, David S; Cheng, Yifan; Frankel, Alan D

2014-12-08

The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

Cell type–dependent mechanisms for formin-mediated assembly of filopodia

PubMed Central

Young, Lorna E.; Heimsath, Ernest G.; Higgs, Henry N.

2015-01-01

Filopodia are finger-like protrusions from the plasma membrane and are of fundamental importance to cellular physiology, but the mechanisms governing their assembly are still in question. One model, called convergent elongation, proposes that filopodia arise from Arp2/3 complex–nucleated dendritic actin networks, with factors such as formins elongating these filaments into filopodia. We test this model using constitutively active constructs of two formins, FMNL3 and mDia2. Surprisingly, filopodial assembly requirements differ between suspension and adherent cells. In suspension cells, Arp2/3 complex is required for filopodial assembly through either formin. In contrast, a subset of filopodia remains after Arp2/3 complex inhibition in adherent cells. In adherent cells only, mDia1 and VASP also contribute to filopodial assembly, and filopodia are disproportionately associated with focal adhesions. We propose an extension of the existing models for filopodial assembly in which any cluster of actin filament barbed ends in proximity to the plasma membrane, either Arp2/3 complex dependent or independent, can initiate filopodial assembly by specific formins. PMID:26446836

Fiber intake modulates the association of alcohol intake with breast cancer.

PubMed

Romieu, Isabelle; Ferrari, Pietro; Chajès, Veronique; de Batlle, Jordi; Biessy, Carine; Scoccianti, Chiara; Dossus, Laure; Christine Boutron, Marie; Bastide, Nadia; Overvad, Kim; Olsen, Anja; Tjønneland, Anne; Kaaks, Rudolf; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Bueno-de-Mesquita, H B As; Gils, Carla H; Peeters, Petra H; Lund, Eiliv; Skeie, Guri; Weiderpass, Elisabete; Ramón Quirós, J; Chirlaque, María-Dolores; Ardanaz, Eva; Sánchez, María-José; Duell, Eric J; Amiano Etxezarreta, Pilar; Borgquist, Signe; Hallmans, Göran; Johansson, Ingegerd; Maria Nilsson, Lena; Khaw, Kay-Tee; Wareham, Nick; Key, Timothy J; Travis, Ruth C; Murphy, Neil; Wark, Petra A; Riboli, Elio

2017-01-15

Alcohol intake has been related to an increased risk of breast cancer (BC) while dietary fiber intake has been inversely associated to BC risk. A beneficial effect of fibers on ethanol carcinogenesis through their impact on estrogen levels is still controversial. We investigated the role of dietary fiber as a modifying factor of the association of alcohol and BC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). This study included 334,850 women aged 35-70 years at baseline enrolled in the ten countries of the EPIC study and followed up for 11.0 years on average. Information on fiber and alcohol intake at baseline and average lifetime alcohol intake were calculated from country-specific dietary and lifestyle questionnaires. Hazard ratios (HR) of developing invasive BC according to different levels of alcohol and fiber intake were computed. During 3,670,439 person-years, 11,576 incident BC cases were diagnosed. For subjects with low intake of fiber (<18.5 g/day), the risk of BC per 10 g/day of alcohol intake was 1.06 (1.03-1.08) while among subjects with high intake of fiber (>24.2 g/day) the risk of BC was 1.02 (0.99-1.05) (test for interaction p = 0.011). This modulating effect was stronger for fiber from vegetables. Our results suggest that fiber intake may modulate the positive association of alcohol intake and BC. Alcohol is well known to increase the risk for BC, while a fiber-rich diet has the opposite effect. Here the authors find a significant interaction between both lifestyle factors indicating that high fiber intake can ease the adverse effects associated with alcohol consumption. Consequently, women with high alcohol intake and low fiber intake (<18.5 g/day) had the highest risk for BC. Specific benefits were associated with fibers from vegetable, warranting further investigations into specific fiber sources and their mechanistic interactions with alcohol-induced BC risk. © 2016 UICC.

Translation and Assembly of Radiolabeled Mitochondrial DNA-Encoded Protein Subunits from Cultured Cells and Isolated Mitochondria.

PubMed

Formosa, Luke E; Hofer, Annette; Tischner, Christin; Wenz, Tina; Ryan, Michael T

2016-01-01

In higher eukaryotes, the mitochondrial electron transport chain consists of five multi-subunit membrane complexes responsible for the generation of cellular ATP. Of these, four complexes are under dual genetic control as they contain subunits encoded by both the mitochondrial and nuclear genomes, thereby adding another layer of complexity to the puzzle of respiratory complex biogenesis. These subunits must be synthesized and assembled in a coordinated manner in order to ensure correct biogenesis of different respiratory complexes. Here, we describe techniques to (1) specifically radiolabel proteins encoded by mtDNA to monitor the rate of synthesis using pulse labeling methods, and (2) analyze the stability, assembly, and turnover of subunits using pulse-chase methods in cultured cells and isolated mitochondria.

Effect of Wegener-Bergeron-Findeisen Process to Black Carbon Simulation

NASA Astrophysics Data System (ADS)

Qi, Ling; Li, Qinbin; He, Cenlin; Wang, Xin; Huang, Jianping

2016-04-01

We systematically investigated the effect of Wegener-Bergeron-Findeisen (WBF) process to black carbon (BC) simulation by a global 3D chemical transport model GEOS-Chem constrained by measurements of BC scavenging efficiencies, concentration in air, deposition fluxes, concentration in snow and washout ratios. Including effect of WBF process reduces the annual mean BC scavenging efficiencies (the ratio of BC in cloud droplets to total BC) at all altitudes by 43-76% in the Arctic. For mid latitude BC scavenging efficiencies decrease by 8-22%, 23-39%, and 41-50% in lower (0-2 km), middle (2-5 km) and upper troposphere (5-10 km), respectively. Simulated BC in air in the Arctic and at mid altitude (˜4 km) in mid latitude increases by ˜40%, and the discrepancy reduces from -65% to -30%. Simulated median BC in snow decreases from 25.7 to 22.4 ng g-1, by 15% in mid latitude and increases from 8.7 to 11.0 ng g-1, by 26% in the Arctic and the comparison with observations improves. The model overestimates washout ratios (ratio of BC in fresh snow/rain to BC in surface air) at most of the sites by up to a factor of 165. With effect of WBF process included, the discrepancy decreases to a factor of 72. The simulated BC burden increases from 0.22 to 0.35 mg m-2 yr-1 when effect of WBF process is included, partly explains the scaled up of BC burden in Bond et al., 2013. Moreover, burden above 5 km increases from 22% to 27% when WBF process is included, indicating a higher forcing efficiency. We also found that BC simulation is insensitive to the temperature criteria between mixed phase clouds and ice clouds. The simulated BC burden is the same when the temperature is set as -15° C and -25° C. This study also suggests that more observations are needed to better distinguish riming dominated and WBF dominated conditions and better parameterize BC scavenging efficiency under the two conditions.

Role of the PufX protein in photosynthetic growth of Rhodobacter sphaeroides. 2. PufX is required for efficient ubiquinone/ubiquinol exchange between the reaction center QB site and the cytochrome bc1 complex.

PubMed

Barz, W P; Verméglio, A; Francia, F; Venturoli, G; Melandri, B A; Oesterhelt, D

1995-11-21

The PufX membrane protein is essential for photosynthetic growth of Rhodobacter sphaeroides because it is required for multiple-turnover electron transfer under anaerobic conditions [see accompanying article; Barz, W. P., Francia, F., Venturoli, G., Melandri, B. A., Verméglio, A., & Oesterhelt, D. (1995) Biochemistry 34, 15235-15247]. In order to understand the molecular role of PufX, light-induced absorption spectroscopy was performed using a pufX- mutant, a pufX+ strain, and two suppressor mutants. We show that the reaction center (RC) requires PufX for its functionality under different redox conditions than the cytochrome bc1 complex: When the kinetics of flash-induced reduction of cytochrome b561 were monitored in chromatophores, we observed a requirement of PufX for turnover of the cytochrome bc1 complex only at high redox potential (Eh > 140 mV), suggesting a function of PufX in lateral ubiquinol transfer from the RC. In contrast, PufX is required for multiple turnover of the RC only under reducing conditions: When the Q pool was partially oxidized in vivo using oxygen or electron acceptors like dimethyl sulfoxide or trimethylamine N-oxide, the deletion of PufX had no effect on light-driven electron flow through the RC. Flash train experiments under anaerobic in vivo conditions revealed that RC photochemistry does not depend on PufX for the first two flash excitations. Following the third and subsequent flashes, however, efficient charge separation requires PufX, indicating an important role of PufX for fast Q/QH2 exchange at the QB site of the RC. We show that the Q/QH2 exchange rate is reduced approximately 500-fold by the deletion of PufX when the Q pool is nearly completely reduced, demonstrating an essential role of PufX for the access of ubiquinone to the QB site. The fast ubiquinone/ubiquinol exchange is partially restored by suppressor mutations altering the macromolecular antenna structure. These results suggest an indirect role of PufX in structurally organizing a functional photosynthetic apparatus.

Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities.

PubMed

Didychuk, Allison L; Montemayor, Eric J; Carrocci, Tucker J; DeLaitsch, Andrew T; Lucarelli, Stefani E; Westler, William M; Brow, David A; Hoskins, Aaron A; Butcher, Samuel E

2017-09-08

U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3' phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2-8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome.The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.

Biophysical Characterization of the Strong Stabilization of the RNA Triplex poly(U)•poly(A)*poly(U) by 9-O-(ω-amino) Alkyl Ether Berberine Analogs

PubMed Central

Hossain, Maidul; Haq, Lucy; Suresh Kumar, Gopinatha

2012-01-01

Background Binding of two 9-O-(ω-amino) alkyl ether berberine analogs BC1 and BC2 to the RNA triplex poly(U)•poly(A)*poly(U) was studied by various biophysical techniques. Methodology/Principal Findings Berberine analogs bind to the RNA triplex non-cooperatively. The affinity of binding was remarkably high by about 5 and 15 times, respectively, for BC1 and BC2 compared to berberine. The site size for the binding was around 4.3 for all. Based on ferrocyanide quenching, fluorescence polarization, quantum yield values and viscosity results a strong intercalative binding of BC1 and BC2 to the RNA triplex has been demonstrated. BC1 and BC2 stabilized the Hoogsteen base paired third strand by about 18.1 and 20.5°C compared to a 17.5°C stabilization by berberine. The binding was entropy driven compared to the enthalpy driven binding of berbeine, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by the alkyl side chain. Conclusions/Significance Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berberine. The length of the alkyl side chain influence in the triplex stabilization phenomena. PMID:22666416

Granular biochar compared with activated carbon for wastewater treatment and resource recovery.

PubMed

Huggins, Tyler M; Haeger, Alexander; Biffinger, Justin C; Ren, Zhiyong Jason

2016-05-01

Granular wood-derived biochar (BC) was compared to granular activated carbon (GAC) for the treatment and nutrient recovery of real wastewater in both batch and column studies. Batch adsorption studies showed that BC material had a greater adsorption capacity at the high initial concentrations of total chemical oxygen demand (COD-T) (1200 mg L(-1)), PO4 (18 mg L(-1)), and NH4 (50 mg L(-1)) compared to GAC. Conversely the BC material showed a lower adsorption capacity for all concentrations of dissolved chemical oxygen demand (COD-D) and the lower concentrations of PO4 (5 mg L(-1)) and NH4 (10 mg L(-1)). Packed bed column studies showed similar average COD-T removal rate for BC with 0.27 ± 0.01 kg m(-3) d(-1) and GAC with 0.24 ± 0.01 kg m(-3) d(-1), but BC had nearly twice the average removal rate (0.41 ± 0.08 kg m(-3) d(-3)) compared to GAC during high COD-T concentrations (>500 mg L(-1)). Elemental analysis showed that both materials accumulated phosphorous during wastewater treatment (2.6 ± 0.4 g kg(-1) and 1.9 ± 0.1 g kg(-1) for BC and GAC respectively). They also contained high concentrations of other macronutrients (K, Ca, and Mg) and low concentrations of metals (As, Cd, Cr, Pb, Zn, and Cu). The good performance of BC is attributed to its macroporous structure compared with the microporous GAC. These favorable treatment data for high strength wastewater, coupled with additional life-cycle benefits, helps support the use of BC in packed bed column filters for enhanced wastewater treatment and nutrient recovery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Space beam combiner for long-baseline interferometry

NASA Astrophysics Data System (ADS)

Lin, Yao; Bartos, Randall D.; Korechoff, Robert P.; Shaklan, Stuart B.

1999-04-01

An experimental beam combiner (BC) is being developed to support the space interferometry program at the JPL. The beam combine forms the part of an interferometer where star light collected by the sidestats or telescopes is brought together to produce white light fringes, and to provide wavefront tilt information via guiding spots and beam walk information via shear spots. The assembly and alignment of the BC has been completed. The characterization test were performed under laboratory conditions with an artificial star and optical delay line. Part of each input beam was used to perform star tracking. The white light interference fringes were obtained over the selected wavelength range from 450 nm to 850 nm. A least-square fit process was used to analyze the fringe initial phase, fringe visibilities and shift errors of the optical path difference in the delay line using the dispersed white-light fringes at different OPD positions.

A comparative DFT study on CO oxidation reaction over Si-doped BC2N nanosheet and nanotube

NASA Astrophysics Data System (ADS)

Nematollahi, Parisa; Neyts, Erik C.

2018-05-01

In this study, we performed density functional theory (DFT) calculations to investigate different reaction mechanisms of CO oxidation catalyzed by the Si atom embedded defective BC2N nanostructures as well as the analysis of the structural and electronic properties. The structures of all the complexes are optimized and characterized by frequency calculations at the M062X/6-31G∗ computational level. Also, The electronic structures and thermodynamic parameters of adsorbed CO and O2 molecules over Si-doped BC2N nanostructures are examined in detail. Moreover, to investigate the curvature effect on the CO oxidation reaction, all the adsorption and CO oxidation reactions on a finite-sized armchair (6,6) Si-BC2NNT are also studied. Our results indicate that there can be two possible pathways for the CO oxidation with O2 molecule: O2(g) + CO(g) → O2(ads) + CO(ads) → CO2(g) + O(ads) and O(ads) + CO(g) → CO2(g). The first reaction proceeds via the Langmuir-Hinshelwood (LH) mechanism while the second goes through the Eley-Rideal (ER) mechanism. On the other hand, by increasing the tube diameter, the energy barrier increases due to the strong adsorption energy of the O2 molecule which is related to its dissociation over the tube surface. Our calculations indicate that the two step energy barrier of the oxidation reaction over Si-BC2NNS is less than that over the Si-BC2NNT. Hence, Si-BC2NNS may serve as an efficient and highly activated substrate to CO oxidation rather than (4,4) Si-BC2NNT.

Significant cooling effect on the surface due to soot particles over Brahmaputra River Valley region, India: An impact on regional climate.

PubMed

Tiwari, S; Kumar, R; Tunved, P; Singh, S; Panicker, A S

2016-08-15

Black carbon (BC) is an important atmospheric aerosol constituent that affects the climate by absorbing (directly) the sunlight and modifying cloud characteristics (indirectly). Here, we present first time yearlong measurements of BC and carbon monoxide (CO) from an urban location of Guwahati located in the Brahmaputra River valley (BRV) in the northeast region of India from 1st July 2013 to 30th June 2014. Daily BC concentrations varied within the range of 2.86 to 11.56μgm(-3) with an annual average of 7.17±1.89μgm(-3), while, CO varied from 0.19 to 1.20ppm with a mean value of 0.51±0.19ppm during the study period. The concentrations of BC (8.37μgm(-3)) and CO (0.67ppm) were ~39% and ~55% higher during the dry months (October to March) than the wet months (April to September) suggesting that seasonal changes in meteorology and emission sources play an important role in controlling these species. The seasonal ΔBC/ΔCO ratios were highest (lowest) in the pre-monsoon (winter) 18.1±1.4μgm(-3)ppmv(-1) (12.6±2.2μgm(-3)ppmv(-1)) which indicate the combustion of biofuel/biomass as well as direct emissions from fossil fuel during the pre-monsoon season. The annual BC emission was estimated to be 2.72Gg in and around Guwahati which is about 44% lower than the mega city 'Delhi' (4.86Gg). During the study period, the annual mean radiative forcing (RF) at the top of the atmosphere (TOA) for clear skies of BC was +9.5Wm(-2), however, the RF value at the surface (SFC) was -21.1Wm(-2) which indicates the net warming and cooling effects, respectively. The highest RF at SFC was in the month of April (-30Wm(-2)) which is coincident with the highest BC mass level. The BC atmospheric radiative forcing (ARF) was +30.16 (annual mean) Wm(-2) varying from +23.1 to +43.8Wm(-2). The annual mean atmospheric heating rate (AHR) due to the BC aerosols was 0.86Kday(-1) indicates the enhancement in radiation effect over the study region. The Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) captured the seasonal cycle of observed BC fairly well but underestimated the observed BC during the month of May-August. Model results show that BC at Guwahati is controlled mainly by anthropogenic emissions except during the pre-monsoon season when open biomass burning also makes a similar contribution. Copyright © 2016 Elsevier B.V. All rights reserved.

Black carbon radiative forcing derived from AERONET measurements and models over an urban location in the southeastern Iberian Peninsula

NASA Astrophysics Data System (ADS)

Valenzuela, A.; Arola, A.; Antón, M.; Quirantes, A.; Alados-Arboledas, L.

2017-07-01

This paper provides an account of observed variations in Black carbon (BC) aerosol concentrations and their induced radiative forcing for the first time over Granada a measurement site in Southeastern Iberian Peninsula. Column-integrated BC concentrations were retrieved for the period 2005-2012. Monthly averages of BC concentrations (± one standard deviation) ranged from higher values in January and December with 4.0 ± 2.5 and 4 ± 3 mg/m2, respectively, to lower values in July and August with 1.6 ± 1.2 and 2.0 ± 0.5 mg/m2, respectively. This reduction is not only observed in the average values, but also in the median, third and first quartiles. The average BC concentration in winter (3.8 ± 0.6 mg/m2) was substantially higher than in summer (1.9 ± 0.3 mg/m2), being the eight-year average of 2.9 ± 0.9 mg/m2. The reduction in the use of fossil fuels during the economic crisis contributed significantly to reduced atmospheric loadings of BC. According to our analysis this situation persisted until 2010. BC concentration values were analyzed in terms of air mass influence using cluster analysis. BC concentrations for cluster 1 (local and regional areas) showed high correlations with air masses frequency in winter and autumn. In these seasons BC sources were related to the intense road traffic and increased BC emissions from domestic heating. High BC concentrations were found in autumn just when air mass frequencies for cluster 3 (Mediterranean region) were more elevated, suggesting that air masses coming from that area transport biomass burning particles towards Granada. BC aerosol optical properties were retrieved from BC fraction using aerosol AERONET size volume distribution and Mie theory. A radiative transfer model (SBDART) was used to estimate the aerosol radiative forcing separately for composite aerosol (total aerosols) and exclusively for BC aerosols. The mean radiative forcing for composite aerosol was + 23 ± 6 W/m2 (heating rate of + 0.21 ± 0.06 K/day) and + 15 ± 6 W/m2 for BC aerosol (heating rate of + 0.15 ± 0.06 K/day). These values of radiative forcing and heating rate for BC aerosol represent about 70% of their values for composite aerosol, which highlights the crucial role that BC aerosols play in modifying the radiation budget and climate.

Evaluation of thermal optical analysis method of elemental carbon for marine fuel exhaust.

PubMed

Lappi, Maija K; Ristimäki, Jyrki M

2017-12-01

The awareness of black carbon (BC) as the second largest anthropogenic contributor in global warming and an ice melting enhancer has increased. Due to prospected increase in shipping especially in the Arctic reliability of BC emissions and their invented amounts from ships is gaining more attention. The International Maritime Organization (IMO) is actively working toward estimation of quantities and effects of BC especially in the Arctic. IMO has launched work toward constituting a definition for BC and agreeing appropriate methods for its determination from shipping emission sources. In our study we evaluated the suitability of elemental carbon (EC) analysis by a thermal-optical transmittance (TOT) method to marine exhausts and possible measures to overcome the analysis interferences related to the chemically complex emissions. The measures included drying with CaSO 4, evaporation at 40-180ºC, H 2 O treatment, and variation of the sampling method (in-stack and diluted) and its parameters (e.g., dilution ratio, Dr). A reevaluation of the nominal organic carbon (OC)/EC split point was made. Measurement of residual carbon after solvent extraction (TC-C SOF ) was used as a reference, and later also filter smoke number (FSN) measurement, which is dealt with in a forthcoming paper by the authors. Exhaust sources used for collecting the particle sample were mainly four-stroke marine engines operated with variable loads and marine fuels ranging from light to heavy fuel oils (LFO and HFO) with a sulfur content range of <0.1-2.4% S. The results were found to be dependent on many factors, namely, sampling, preparation and analysis method, and fuel quality. It was found that the condensed H 2 SO 4 + H 2 O on the particulate matter (PM) filter had an effect on the measured EC content, and also promoted the formation of pyrolytic carbon (PyC) from OC, affecting the accuracy of EC determination. Thus, uncertainty remained regarding the EC results from HFO fuels. The work supports one part of the decision making in black carbon (BC) determination methodology. If regulations regarding BC emissions from marine engines will be implemented in the future, a well-defined and at best unequivocal method of BC determination is required for coherent and comparable emission inventories and estimating BC effects. As the aerosol from marine emission sources may be very heterogeneous and low in BC, special attention to the effects of sampling conditions and sample pretreatments on the validity of the results was paid in developing the thermal-optical analysis methodology (TOT).

A cellphone based system for large-scale monitoring of black carbon

NASA Astrophysics Data System (ADS)

Ramanathan, N.; Lukac, M.; Ahmed, T.; Kar, A.; Praveen, P. S.; Honles, T.; Leong, I.; Rehman, I. H.; Schauer, J. J.; Ramanathan, V.

2011-08-01

Black carbon aerosols are a major component of soot and are also a major contributor to global and regional climate change. Reliable and cost-effective systems to measure near-surface black carbon (BC) mass concentrations (hereafter denoted as [BC]) globally are necessary to validate air pollution and climate models and to evaluate the effectiveness of BC mitigation actions. Toward this goal we describe a new wireless, low-cost, ultra low-power, BC cellphone based monitoring system (BC_CBM). BC_CBM integrates a Miniaturized Aerosol filter Sampler (MAS) with a cellphone for filter image collection, transmission and image analysis for determining [BC] in real time. The BC aerosols in the air accumulate on the MAS quartz filter, resulting in a coloration of the filter. A photograph of the filter is captured by the cellphone camera and transmitted by the cellphone to the analytics component of BC_CBM. The analytics component compares the image with a calibrated reference scale (also included in the photograph) to estimate [BC]. We demonstrate with field data collected from vastly differing environments, ranging from southern California to rural regions in the Indo-Gangetic plains of Northern India, that the total BC deposited on the filter is directly and uniquely related to the reflectance of the filter in the red wavelength, irrespective of its source or how the particles were deposited. [BC] varied from 0.1 to 1 μg m -3 in Southern California and from 10 to 200 μg m -3 in rural India in our field studies. In spite of the 3 orders of magnitude variation in [BC], the BC_CBM system was able to determine the [BC] well within the experimental error of two independent reference instruments for both indoor air and outdoor ambient air. Accurate, global-scale measurements of [BC] in urban and remote rural locations, enabled by the wireless, low-cost, ultra low-power operation of BC_CBM, will make it possible to better capture the large spatial and temporal variations in [BC], informing climate science, health, and policy.

Structural and functional characterization of a cell cycle associated HDAC1/2 complex reveals the structural basis for complex assembly and nucleosome targeting

PubMed Central

Itoh, Toshimasa; Fairall, Louise; Muskett, Frederick W.; Milano, Charles P.; Watson, Peter J.; Arnaudo, Nadia; Saleh, Almutasem; Millard, Christopher J.; El-Mezgueldi, Mohammed; Martino, Fabrizio; Schwabe, John W.R.

2015-01-01

Recent proteomic studies have identified a novel histone deacetylase complex that is upregulated during mitosis and is associated with cyclin A. This complex is conserved from nematodes to man and contains histone deacetylases 1 and 2, the MIDEAS corepressor protein and a protein called DNTTIP1 whose function was hitherto poorly understood. Here, we report the structures of two domains from DNTTIP1. The amino-terminal region forms a tight dimerization domain with a novel structural fold that interacts with and mediates assembly of the HDAC1:MIDEAS complex. The carboxy-terminal domain of DNTTIP1 has a structure related to the SKI/SNO/DAC domain, despite lacking obvious sequence homology. We show that this domain in DNTTIP1 mediates interaction with both DNA and nucleosomes. Thus, DNTTIP1 acts as a dimeric chromatin binding module in the HDAC1:MIDEAS corepressor complex. PMID:25653165

Observation of an excited Bc(±) meson state with the ATLAS detector.

PubMed

Aad, G; Abbott, B; Abdallah, J; Abdel Khalek, S; Abdinov, O; Aben, R; Abi, B; Abolins, M; AbouZeid, O S; Abramowicz, H; Abreu, H; Abreu, R; Abulaiti, Y; Acharya, B S; Adamczyk, L; Adams, D L; Adelman, J; Adomeit, S; Adye, T; Agatonovic-Jovin, T; Aguilar-Saavedra, J A; Agustoni, M; Ahlen, S P; Ahmadov, F; Aielli, G; Akerstedt, H; Åkesson, T P A; Akimoto, G; Akimov, A V; Alberghi, G L; Albert, J; Albrand, S; Alconada Verzini, M J; Aleksa, M; Aleksandrov, I N; Alexa, C; Alexander, G; Alexandre, G; Alexopoulos, T; Alhroob, M; Alimonti, G; Alio, L; Alison, J; Allbrooke, B M M; Allison, L J; Allport, P P; Almond, J; Aloisio, A; Alonso, A; Alonso, F; Alpigiani, C; Altheimer, A; Alvarez Gonzalez, B; Alviggi, M G; Amako, K; Amaral Coutinho, Y; Amelung, C; Amidei, D; Amor Dos Santos, S P; Amorim, A; Amoroso, S; Amram, N; Amundsen, G; Anastopoulos, C; Ancu, L S; Andari, N; Andeen, T; Anders, C F; Anders, G; Anderson, K J; Andreazza, A; Andrei, V; Anduaga, X S; Angelidakis, S; Angelozzi, I; Anger, P; Angerami, A; Anghinolfi, F; Anisenkov, A V; Anjos, N; Annovi, A; Antonaki, A; Antonelli, M; Antonov, A; Antos, J; Anulli, F; Aoki, M; Aperio Bella, L; Apolle, R; Arabidze, G; Aracena, I; Arai, Y; Araque, J P; Arce, A T H; Arguin, J-F; Argyropoulos, S; Arik, M; Armbruster, A J; Arnaez, O; Arnal, V; Arnold, H; Arratia, M; Arslan, O; Artamonov, A; Artoni, G; Asai, S; Asbah, N; Ashkenazi, A; Åsman, B; Asquith, L; Assamagan, K; Astalos, R; Atkinson, M; Atlay, N B; Auerbach, B; Augsten, K; Aurousseau, M; Avolio, G; Azuelos, G; Azuma, Y; Baak, M A; Baas, A; Bacci, C; Bachacou, H; Bachas, K; Backes, M; Backhaus, M; Backus Mayes, J; Badescu, E; Bagiacchi, P; Bagnaia, P; Bai, Y; Bain, T; Baines, J T; Baker, O K; Balek, P; Balli, F; Banas, E; Banerjee, Sw; Bannoura, A A E; Bansal, V; Bansil, H S; Barak, L; Baranov, S P; Barberio, E L; Barberis, D; Barbero, M; Barillari, T; Barisonzi, M; Barklow, T; Barlow, N; Barnett, B M; Barnett, R M; Barnovska, Z; Baroncelli, A; Barone, G; Barr, A J; Barreiro, F; Barreiro Guimarães da Costa, J; Bartoldus, R; Barton, A E; Bartos, P; Bartsch, V; Bassalat, A; Basye, A; Bates, R L; Batkova, L; Batley, J R; Battaglia, M; Battistin, M; Bauer, F; Bawa, H S; Beau, T; Beauchemin, P H; Beccherle, R; Bechtle, P; Beck, H P; Becker, K; Becker, S; Beckingham, M; Becot, C; Beddall, A J; Beddall, A; Bedikian, S; Bednyakov, V A; Bee, C P; Beemster, L J; Beermann, T A; Begel, M; Behr, K; Belanger-Champagne, C; Bell, P J; Bell, W H; Bella, G; Bellagamba, L; Bellerive, A; Bellomo, M; Belotskiy, K; Beltramello, O; Benary, O; Benchekroun, D; Bendtz, K; Benekos, N; Benhammou, Y; Benhar Noccioli, E; Benitez Garcia, J A; Benjamin, D P; Bensinger, J R; Benslama, K; Bentvelsen, S; Berge, D; Bergeaas Kuutmann, E; Berger, N; Berghaus, F; Beringer, J; Bernard, C; Bernat, P; Bernius, C; Bernlochner, F U; Berry, T; Berta, P; Bertella, C; Bertoli, G; Bertolucci, F; Bertsche, D; Besana, M I; Besjes, G J; Bessidskaia, O; Bessner, M; Besson, N; Betancourt, C; Bethke, S; Bhimji, W; 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Yu, J M; Yu, J; Yuan, L; Yurkewicz, A; Yusuff, I; Zabinski, B; Zaidan, R; Zaitsev, A M; Zaman, A; Zambito, S; Zanello, L; Zanzi, D; Zeitnitz, C; Zeman, M; Zemla, A; Zengel, K; Zenin, O; Ženiš, T; Zerwas, D; Zevi della Porta, G; Zhang, D; Zhang, F; Zhang, H; Zhang, J; Zhang, L; Zhang, X; Zhang, Z; Zhao, Z; Zhemchugov, A; Zhong, J; Zhou, B; Zhou, L; Zhou, N; Zhu, C G; Zhu, H; Zhu, J; Zhu, Y; Zhuang, X; Zhukov, K; Zibell, A; Zieminska, D; Zimine, N I; Zimmermann, C; Zimmermann, R; Zimmermann, S; Zimmermann, S; Zinonos, Z; Ziolkowski, M; Zobernig, G; Zoccoli, A; zur Nedden, M; Zurzolo, G; Zutshi, V; Zwalinski, L

2014-11-21

A search for excited states of the Bc(±) meson is performed using 4.9  fb(-1) of 7 TeV and 19.2  fb(-1) of 8 TeV pp collision data collected by the ATLAS experiment at the LHC. A new state is observed through its hadronic transition to the ground state, with the latter detected in the decay Bc(±)→J/ψπ(±). The state appears in the m(Bc(±)π(+)π(-))-m(Bc(±))-2m(π(±)) mass difference distribution with a significance of 5.2 standard deviations. The mass of the observed state is 6842±4±5  MeV, where the first error is statistical and the second is systematic. The mass and decay of this state are consistent with expectations for the second S-wave state of the Bc(±) meson, Bc(±)(2S).

Luffa sponge offsets the negative effects of aeration on bacterial cellulose production.

PubMed

Krusong, W; Kerdpiboon, S; Pornpukdeewattana, S; Jindaprasert, A

2016-12-01

To offset the negative effects of aeration on bacterial cellulose (BC) production by acetic acid bacteria using enmeshed cellulose microfibrils (CM) on luffa sponge matrices (LSM). The CM were enmeshed on LSM (LSM-CM). The optimal amount of LSM-CM was determined for BC production under aerated conditions. Without LSM-CM, no BC was produced in seven out of nine production cycles at the highest aeration rate (9 l min -1 ). However, with 0·5% LSM-CM and an aeration rate of 3 l min -1 , a satisfactory oxygen transfer coefficient was achieved, and also a good yield of BC (5·24 g l -1 ). Moreover, the LSM-CM was able to be recycled through nine consecutive BC production cycles. The highest BC yields (from 5·8 ± 0·4 to 6·6 ± 0·4 g l -1 ) were associated with high bacterial biomass and this was confirmed by scanning electron microscopy. We confirm that LSM-CM works well as a starter. Microenvironments low in dissolved oxygen within the matrices of LSM-CM are important for BC production under aeration conditions. The LSM-CM provides a microenvironment which offsets the negative effects of aeration on BC production. A sustainable, economic process for mass BC production is described using recycled LSM-CM with aeration. © 2016 The Society for Applied Microbiology.

Insight into Oxide-Bridged Heterobimetallic Al/Zr Olefin Polymerization Catalysts.

PubMed

Boulho, Cédric; Zijlstra, Harmen S; Hofmann, Alexander; Budzelaar, Peter H M; Harder, Sjoerd

2016-11-21

Reaction of (TBBP)AlMe⋅THF with [Cp* 2 Zr(Me)OH] gave [(TBBP)Al(THF)-O-Zr(Me)Cp* 2 ] (TBBP=3,3',5,5'-tetra-tBu-2,2'-biphenolato). Reaction of [DIPPnacnacAl(Me)-O-Zr(Me)Cp 2 ] with [PhMe 2 NH] + [B(C 6 F 5 ) 4 ] - gave a cationic Al/Zr complex that could be structurally characterized as its THF adduct [(DIPPnacnac)Al(Me)-O-Zr(THF)Cp 2 ] + [B(C 6 F 5 ) 4 ] - (DIPPnacnac=HC[(Me)C=N(2,6-iPr 2 -C 6 H 3 )] 2 ). The first complex polymerizes ethene in the presence of an alkylaluminum scavenger but in the absence of methylalumoxane (MAO). The adduct cation is inactive under these conditions. Theoretical calculations show very high energy barriers (ΔG=40-47 kcal mol -1 ) for ethene insertion with a bridged AlOZr catalyst. This is due to an unfavorable six-membered-ring transition state, in which the methyl group bridges the metal and ethene with an obtuse metal-Me-C angle that prevents synchronized bond-breaking and making. A more-likely pathway is dissociation of the Al-O-Zr complex into an aluminate and the active polymerization catalyst [Cp* 2 ZrMe] + . © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sources and physicochemical characteristics of black carbon aerosol from the southeastern Tibetan Plateau: internal mixing enhances light absorption

NASA Astrophysics Data System (ADS)

Wang, Qiyuan; Cao, Junji; Han, Yongming; Tian, Jie; Zhu, Chongshu; Zhang, Yonggang; Zhang, Ningning; Shen, Zhenxing; Ni, Haiyan; Zhao, Shuyu; Wu, Jiarui

2018-04-01

Black carbon (BC) aerosol has important effects on the climate and hydrology of the Tibetan Plateau (TP). An intensive measurement campaign was conducted at Lulang (˜ 3300 m a.s.l. - above sea level), southeastern TP, from September to October 2015, to investigate the sources and physicochemical characteristics of refractory BC (rBC) aerosol. The average rBC mass concentration was 0.31 ± 0.55 µg m-3, which is higher than most prior results for BC on the TP. A clear diurnal cycle in rBC showed high values in the morning and low values in the afternoon. A bivariate polar plot showed that rBC loadings varied with wind speed and direction, which also reflected the dominant transport direction. The estimated net surface rBC transport intensity was +0.05 ± 0.29 µg s-1 m-2, indicating stronger transport from outside the TP compared with its interior. Cluster analysis and a concentration-weighted trajectory model connected emissions from north India to the high rBC loadings, but the effects of internal TP sources should not be overlooked. The average mass median diameter (MMD) of rBC was 160 ± 23 nm, with smaller MMDs on rainy days (145 nm) compared with non-rainy days (164 nm). The average number fraction of thickly coated rBC (FrBC) was 39 ± 8 %, and it increased with the O3 mixing ratios from 10:00 to 14:00 LT, indicating that photochemical oxidation played a role in forming rBC coatings. The average rBC absorption enhancement (Eabs) was estimated to be 1.9, suggesting that light absorption by coated rBC particles was greater than for uncoated ones. The Eabs was strongly positively correlated with the FrBC, indicating an amplification of light absorption for internally mixed rBC. For rBC cores < 170 nm, Eabs was negatively correlated with MMD, but it was nearly constant for rBC cores > 170 nm. Our study provides insight into the sources and evolution of rBC aerosol on the TP, and the results should be useful for improving models of the radiative effects of carbonaceous aerosols in this area.

Generation of a human airway epithelium derived basal cell line with multipotent differentiation capacity

PubMed Central

2013-01-01

Background As the multipotent progenitor population of the airway epithelium, human airway basal cells (BC) replenish the specialized differentiated cell populations of the mucociliated airway epithelium during physiological turnover and repair. Cultured primary BC divide a limited number of times before entering a state of replicative senescence, preventing the establishment of long-term replicating cultures of airway BC that maintain their original phenotype. Methods To generate an immortalized human airway BC cell line, primary human airway BC obtained by brushing the airway epithelium of healthy nonsmokers were infected with a retrovirus expressing human telomerase (hTERT). The resulting immortalized cell line was then characterized under non-differentiating and differentiating air-liquid interface (ALI) culture conditions using ELISA, TaqMan quantitative PCR, Western analysis, and immunofluorescent and immunohistochemical staining analysis for cell type specific markers. In addition, the ability of the cell line to respond to environmental stimuli under differentiating ALI culture was assessed. Results We successfully generated an immortalized human airway BC cell line termed BCi-NS1 via expression of hTERT. A single cell derived clone from the parental BCi-NS1 cells, BCi-NS1.1, retains characteristics of the original primary cells for over 40 passages and demonstrates a multipotent differentiation capacity into secretory (MUC5AC, MUC5B), goblet (TFF3), Clara (CC10) and ciliated (DNAI1, FOXJ1) cells on ALI culture. The cells can respond to external stimuli such as IL-13, resulting in alteration of the normal differentiation process. Conclusion Development of immortalized human airway BC that retain multipotent differentiation capacity over long-term culture should be useful in understanding the biology of BC, the response of BC to environmental stress, and as a target for assessment of pharmacologic agents. PMID:24298994

Preparation and characterization of a novel graphene/biochar composite for aqueous phenanthrene and mercury removal.

PubMed

Tang, Jingchun; Lv, Honghong; Gong, Yanyan; Huang, Yao

2015-11-01

A graphene/biochar composite (G/BC) was synthesized via slow pyrolysis of graphene (G) pretreated wheat straw, and tested for the sorption characteristics and mechanisms of representative aqueous contaminants (phenanthrene and mercury). Structure and morphology analysis showed that G was coated on the surface of biochar (BC) mainly through π-π interactions, resulting in a larger surface area, more functional groups, greater thermal stability, and higher removal efficiency of phenanthrene and mercury compared to BC. Pseudo second-order model adequately simulated sorption kinetics, and sorption isotherms of phenanthrene and mercury were simulated well by dual-mode and BET models, respectively. FTIR and SEM analysis suggested that partitioning and surface sorption were dominant mechanisms for phenanthrene sorption, and that surface complexation between mercury and C-O, CC, -OH, and OC-O functional groups was responsible for mercury removal. The results suggested that the G/BC composite is an efficient, economic, and environmentally friendly multifunctional adsorbent for environmental remediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Assessing the Climate Trade-Offs of Gasoline Direct Injection Engines.

PubMed

Zimmerman, Naomi; Wang, Jonathan M; Jeong, Cheol-Heon; Wallace, James S; Evans, Greg J

2016-08-02

Compared to port fuel injection (PFI) engine exhaust, gasoline direct injection (GDI) engine exhaust has higher emissions of black carbon (BC), a climate-warming pollutant. However, the relative increase in BC emissions and climate trade-offs of replacing PFI vehicles with more fuel efficient GDI vehicles remain uncertain. In this study, BC emissions from GDI and PFI vehicles were compiled and BC emissions scenarios were developed to evaluate the climate impact of GDI vehicles using global warming potential (GWP) and global temperature potential (GTP) metrics. From a 20 year time horizon GWP analysis, average fuel economy improvements ranging from 0.14 to 14% with GDI vehicles are required to offset BC-induced warming. For all but the lowest BC scenario, installing a gasoline particulate filter with an 80% BC removal efficiency and <1% fuel penalty is climate beneficial. From the GTP-based analysis, it was also determined that GDI vehicles are climate beneficial within <1-20 years; longer time horizons were associated with higher BC scenarios. The GDI BC emissions spanned 2 orders of magnitude and varied by ambient temperature, engine operation, and fuel composition. More work is needed to understand BC formation mechanisms in GDI engines to ensure that the climate impacts of this engine technology are minimal.

Geomicrobiology of the Ocean Crust: The Phylogenetic Diversity, Abundance, and Distribution of Microbial Communities Inhabiting Basalt and Implications for Rock Alteration Processes

DTIC Science & Technology

2007-06-01

AF317741) 93 EPR3970- MOlA -Bc32 gamma-Proteobacteria Uncultured gamma proteobacterium clone AT-s80 (AY225635) 99 FPR3970-MO IA-Bc33 Actinobacteria...bacterium partial I AJ966584) 99 1iPR3970- MOlA -Bc65 Unidentified Uncultured bacterium clone CV90 (DQ499320) 89 1iPR3970- MOlA -Bc66 Unidentified Uncultured

Probabilistic Geoacoustic Inversion in Complex Environments

DTIC Science & Technology

2015-09-30

Probabilistic Geoacoustic Inversion in Complex Environments Jan Dettmer School of Earth and Ocean Sciences, University of Victoria, Victoria BC...long-range inversion methods can fail to provide sufficient resolution. For proper quantitative examination of variability, parameter uncertainty must...project aims to advance probabilistic geoacoustic inversion methods for complex ocean environments for a range of geoacoustic data types. The work is

The potential of biochar in improving drainage, aeration and maize yields in heavy clay soils

PubMed Central

Mulder, Jan; Hale, Sarah Elizabeth; Nurida, Neneng Laela; Cornelissen, Gerard

2018-01-01

Heavy clay soils are globally widespread but their poor drainage and poor aeration limit their use for agriculture. This study was designed to test the effect of the amendment of biochar (BC) from woody shrubs on drainage/saturated hydraulic conductivity (Ksat), soil aeration/air capacity, available water capacity and biomass and grain yields of maize. In a field experiment, BC from Gliricidia sepium was applied in planting basins or rip lines at 2.5% and 5% w/w in addition to a control without BC. The maize biomass and grain yields were higher in BC treated plots compared to control (p<0.05) during the 2012 and 2013 seasons. There was no significant difference in the yields between 2.5% and 5% BC treatments (e.g. grain yield were 6.6 and 8.1 t ha-1 in 2012 and 9.3 and 10.3 t ha-1 in 2013 compared to control with 4.2 and 6.7 t ha-1 in 2012 and 2013, respectively). Soil from the same field site was also mixed with a similar woody shrub BC from Eupatorium adenophorum in the laboratory at rates of 2.5%, 5% and 10% BC w/w and a control without BC. The mixtures were then incubated and subjected to two wet-dry cycles for two weeks. Core samples were taken from the incubated soil and tested for bulk density, Ksat and pF measurements. Total porosity and moisture at field capacity and wilting point were 72.3%, 43.7% and 23.7%, respectively, and not affected by BC amendment (p>0.05). In contrast, bulk density decreased linearly by 0.011±0.002 g cm-3 per percent BC added (p<0.001). Ksat and air capacity of the soil were 288 cm day-1 and 30.9%, respectively falling within the generally accepted optimal range. Both Ksat and air capacity followed a significant quadratic relation (p<0.05) upon BC addition, decreasing at low BC doses, reaching a minimum at 3–5% BC and increasing at higher doses. Results allowed a partial attribution of the yield increases to changes in soil physical properties such as changes in bulk density and not clearly to Ksat and air capacity. PMID:29750796

The potential of biochar in improving drainage, aeration and maize yields in heavy clay soils.

PubMed

Obia, Alfred; Mulder, Jan; Hale, Sarah Elizabeth; Nurida, Neneng Laela; Cornelissen, Gerard

2018-01-01

Heavy clay soils are globally widespread but their poor drainage and poor aeration limit their use for agriculture. This study was designed to test the effect of the amendment of biochar (BC) from woody shrubs on drainage/saturated hydraulic conductivity (Ksat), soil aeration/air capacity, available water capacity and biomass and grain yields of maize. In a field experiment, BC from Gliricidia sepium was applied in planting basins or rip lines at 2.5% and 5% w/w in addition to a control without BC. The maize biomass and grain yields were higher in BC treated plots compared to control (p<0.05) during the 2012 and 2013 seasons. There was no significant difference in the yields between 2.5% and 5% BC treatments (e.g. grain yield were 6.6 and 8.1 t ha-1 in 2012 and 9.3 and 10.3 t ha-1 in 2013 compared to control with 4.2 and 6.7 t ha-1 in 2012 and 2013, respectively). Soil from the same field site was also mixed with a similar woody shrub BC from Eupatorium adenophorum in the laboratory at rates of 2.5%, 5% and 10% BC w/w and a control without BC. The mixtures were then incubated and subjected to two wet-dry cycles for two weeks. Core samples were taken from the incubated soil and tested for bulk density, Ksat and pF measurements. Total porosity and moisture at field capacity and wilting point were 72.3%, 43.7% and 23.7%, respectively, and not affected by BC amendment (p>0.05). In contrast, bulk density decreased linearly by 0.011±0.002 g cm-3 per percent BC added (p<0.001). Ksat and air capacity of the soil were 288 cm day-1 and 30.9%, respectively falling within the generally accepted optimal range. Both Ksat and air capacity followed a significant quadratic relation (p<0.05) upon BC addition, decreasing at low BC doses, reaching a minimum at 3-5% BC and increasing at higher doses. Results allowed a partial attribution of the yield increases to changes in soil physical properties such as changes in bulk density and not clearly to Ksat and air capacity.

Risk Differences Between Prediabetes And Diabetes According To Breast Cancer Molecular Subtypes.

PubMed

Crispo, A; Augustin, L S A; Grimaldi, M; Nocerino, F; Giudice, A; Cavalcanti, E; Di Bonito, M; Botti, G; De Laurentiis, M; Rinaldo, M; Esposito, E; Riccardi, G; Amore, A; Libra, M; Ciliberto, G; Jenkins, D J A; Montella, M

2017-05-01

Hyperglycemia and hyperinsulinemia may play a role in breast carcinogenesis and prediabetes and diabetes have been associated with increased breast cancer (BC) risk. However, whether BC molecular subtypes may modify these associations is less clear. We therefore investigated these associations in all cases and by BC molecular subtypes among women living in Southern Italy. Cases were 557 patients with non-metastatic incident BC and controls were 592 outpatients enrolled during the same period as cases and in the same hospital for skin-related non-malignant conditions. Adjusted multivariate logistic regression models were built to assess the risks of developing BC in the presence of prediabetes or diabetes. The analyses were repeated by strata of BC molecular subtypes: Luminal A, Luminal B, HER2+, and Triple Negative (TN). Prediabetes and diabetes were significantly associated with higher BC incidence after controlling for known risk factors (OR = 1.94, 95% CI 1.32-2.87 and OR = 2.46, 95% CI 1.38-4.37, respectively). Similar results were seen in Luminal A and B while in the TN subtype only prediabetes was associated with BC (OR = 2.43, 95% CI 1.11-5.32). Among HER2+ patients, only diabetes was significantly associated with BC risk (OR = 3.04, 95% CI 1.24-7.47). Furthermore, when postmenopausal HER2+ was split into hormone receptor positive versus negative, the association with diabetes remained significant only in the former (OR = 5.13, 95% CI 1.53-17.22). These results suggest that prediabetes and diabetes are strongly associated with BC incidence and that these metabolic conditions may be more relevant in the presence of breast cancer molecular subtypes with positive hormone receptors. J. Cell. Physiol. 232: 1144-1150, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Fission yeast MOZART1/Mzt1 is an essential γ-tubulin complex component required for complex recruitment to the microtubule organizing center, but not its assembly

PubMed Central

Masuda, Hirohisa; Mori, Risa; Yukawa, Masashi; Toda, Takashi

2013-01-01

γ-Tubulin plays a universal role in microtubule nucleation from microtubule organizing centers (MTOCs) such as the animal centrosome and fungal spindle pole body (SPB). γ-Tubulin functions as a multiprotein complex called the γ-tubulin complex (γ-TuC), consisting of GCP1–6 (GCP1 is γ-tubulin). In fungi and flies, it has been shown that GCP1–3 are core components, as they are indispensable for γ-TuC complex assembly and cell division, whereas the other three GCPs are not. Recently a novel conserved component, MOZART1, was identified in humans and plants, but its precise functions remain to be determined. In this paper, we characterize the fission yeast homologue Mzt1, showing that it is essential for cell viability. Mzt1 is present in approximately equal stoichiometry with Alp4/GCP2 and localizes to all the MTOCs, including the SPB and interphase and equatorial MTOCs. Temperature-sensitive mzt1 mutants display varying degrees of compromised microtubule organization, exhibiting multiple defects during both interphase and mitosis. Mzt1 is required for γ-TuC recruitment, but not sufficient to localize to the SPB, which depends on γ-TuC integrity. Intriguingly, the core γ-TuC assembles in the absence of Mzt1. Mzt1 therefore plays a unique role within the γ-TuC components in attachment of this complex to the major MTOC site. PMID:23885124

Relationship between Telomere Length, Genetic Traits and Environmental/Occupational Exposures in Bladder Cancer Risk by Structural Equation Modelling.

PubMed

Pavanello, Sofia; Carta, Angela; Mastrangelo, Giuseppe; Campisi, Manuela; Arici, Cecilia; Porru, Stefano

2017-12-21

Background : Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods : Within the framework of a hospital-based case ( n = 96)/control ( n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results : The SEM analysis indicates negative direct links ( p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk ( p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects ( p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link). Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention.

Relationship between Telomere Length, Genetic Traits and Environmental/Occupational Exposures in Bladder Cancer Risk by Structural Equation Modelling

PubMed Central

Pavanello, Sofia; Carta, Angela; Mastrangelo, Giuseppe; Campisi, Manuela; Porru, Stefano

2017-01-01

Background: Telomere length (TL) maintenance plays an important role in bladder cancer (BC) and prognosis. However the manifold influence of everyday life exposures and genetic traits on leucocyte TL (LTL), is not fully elucidated. Methods: Within the framework of a hospital-based case (n = 96)/control (n = 94) study (all Caucasian males), we investigated the extent to which LTL and BC risk were modulated by genetic polymorphisms and environmental and occupational exposures. Data on lifetime smoking, alcohol and coffee drinking, dietary habits and occupational exposures, pointing to aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) were collected. Structural equation modelling (SEM) analysis appraised this complex relationships. Results: The SEM analysis indicates negative direct links (p < 0.05) between LTL with age, DNA adducts, alcohol and NAT2, and positive ones with coffee, MPO and XRCC3; and between BC risk (p < 0.01) with cigarettes, cumulative exposure to AAs and coffee, while are negative with LTL and age. There was evidence of indirect effects (p < 0.05) on BC risk, probably via LTL reduction, by age and NAT2 (positive link), MPO and XRCC3 (negative link). Conclusions: Our study supports evidence that LTL attrition is a critical event in BC. The new finding that LTL erosion depends on some preventable everyday life exposures genetically modulated, opens new perspectives in BC prevention. PMID:29267235

Cooperative Lewis pairs based on late transition metals: activation of small molecules by platinum(0) and B(C6 F5 )3.

PubMed

Forrest, Sebastian J K; Clifton, Jamie; Fey, Natalie; Pringle, Paul G; Sparkes, Hazel A; Wass, Duncan F

2015-02-09

A Lewis basic platinum(0)-CO complex supported by a diphosphine ligand and B(C6 F5 )3 act cooperatively, in a manner reminiscent of a frustrated Lewis pair, to activate small molecules such as hydrogen, CO2 , and ethene. This cooperative Lewis pair facilitates the coupling of CO and ethene in a new way. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Expression profile of BRCA1 and BRCA2 genes in premenopausal Mexican women with breast cancer: clinical and immunohistochemical correlates.

PubMed

Loredo-Pozos, Gloria; Chiquete, Erwin; Oceguera-Villanueva, Antonio; Panduro, Arturo; Siller-López, Fernando; Ramos-Márquez, Martha E

2009-01-01

Low BRCA1 gene expression is associated with increased invasiveness and influences the response of breast carcinoma (BC) to chemotherapeutics. However, expression of BRCA1 and BRCA2 genes has not been completely characterized in premenopausal BC. We analyzed the clinical and immunohistochemical correlates of BRCA1 and BRCA2 expression in young BC women. We studied 62 women (mean age 38.8 years) who developed BC before the age of 45 years. BRCA1 and BRCA2 mRNA expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and that of HER-2 and p53 proteins by immunohistochemistry. Body mass index (BMI) > or = 27 (52%) and a declared family history of BC (26%) were the main risk factors. Ductal infiltrative adenocarcinoma was found in 86% of the cases (tumor size >5 cm in 48%). Disease stages I-IV occurred in 2, 40, 55, and 3%, respectively (73% implicating lymph nodes). Women aged < or = 35 years (24%) had more family history of cervical cancer, stage III/IV disease, HER-2 positivity, and lower BRCA1 expression than older women (P < 0.05). BRCA1 and BRCA2 expression correlated in healthy, but not in tumor tissues (TT). Neither BRCA1 nor BRCA2 expression was associated with tumor histology, differentiation, nodal metastasis or p53 and HER-2 expression. After multivariate analysis, only disease stage explained BRCA1 mRNA levels in the lowest quartile. Premenopausal BC has aggressive clinical and molecular characteristics. Low BRCA1 mRNA expression is associated mainly with younger ages and advanced clinical stage of premenopausal BC. BRCA2 expression is not associated with disease severity in young BC women.

Temporal and Spatial Changes in Black Carbon Sedimentary Processes in Wetlands of Songnen Plain, Northeast of China

PubMed Central

He, Jiabao; Gao, Chuanyu; Lin, Qianxin; Zhang, Shaoqing; Zhao, Winston; Lu, Xianguo; Wang, Guoping

2015-01-01

Black carbon (BC), an important component of organic carbon (OC) produced from incomplete combustion of carbon compounds, is widespread and affects the global carbon storage. The objectives of this study were to analyze the BC contents and fluxes in the last 150 years to determine the causes of differences in the three profiles of the Songnen Plain of Northeast China and to estimate the BC storage in the wetlands of the Songnen Plain. In the three sampling sites, BC fluxes in the period between 1950 and the present time increased by the ratios of 1.3, 31.1 and 1.4, respectively, compared to their own baseline between 1850 and 1900. Furthermore, the BC fluxes varying from 0.76 to 5.63 g m-2 y-1 in the three profiles had an opposite trend with the sand percentages with mean values changing from 78.9% to 19.6%, suggesting that sand desertification might additionally affect the BC processes in the region. PMID:26469981

Reduction of uncertainty in global black carbon direct radiative forcing constrained by observations

NASA Astrophysics Data System (ADS)

Wang, R.; Balkanski, Y.; Boucher, O.; Ciais, P.; Schuster, G. L.; Chevallier, F.; Samset, B. H.; Valari, M.; Liu, J.; Tao, S.

2017-12-01

Black carbon (BC) absorbs sunlight and contributes to global warming. However, the size of this effect, namely the direct radiative forcing (DRF), ranges from +0.1 to +1.0 W m-2, largely due to discrepancies between modeled and observed BC radiation absorption. Studies that adjusted emissions to correct biases of models resulted in a revised upward estimate of the BC DRF. However, the observation-based BC RF was not optimized against observations in a rigorous mathematical manner, because uncertainties in emissions and the representativeness errors due to use of coarse-resolution models were not fully assessed. Here we simulated the absorption of solar radiation by BC from all sources at the 10-km resolution by combining a nested aerosol model with a downscaling method. The normalized mean bias in BC radiation absorption was reduced from -51% to -24% in Asia and from -57% to -50% elsewhere. We applied a Bayesian method that account for model, representativeness and observational uncertainties to estimate the BC RF and its uncertainty. Using the high-resolution model reduces uncertainty in BC DRF from -101%/+152% to -70%/+71% over Asia and from -83%/+108% to -64%/+68% over other continental regions. We derived an observation-based BC DRF of 0.61 Wm-2 (0.16 to 1.40 as 90% confidence) as our best estimate.

MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells

PubMed Central

Ying, Xuexiang; Sun, Yunpo; He, Pingqing

2017-01-01

Bone morphogenetic protein-7 (BMP7) is known to antagonize transforming growth factor β 1 (TGFβ1)-mediated fibrosis through suppressing epithelial-mesenchymal transition (EMT). We recently reported that BMP7 also antagonizes the effects of TGFβ1 in breast cancer (BC) tumorigenesis-related EMT. Nevertheless, the control of BMP7 expression in BC remains ill-defined. Here, we detected significantly lower levels of BMP7 and significantly higher levels of microRNA-137 (miR-137) in the BC specimens, relative to paired adjacent non-tumor breast tissue. BMP7 and miR-137 levels were correlated inversely. Additionally, the high miR-137 levels in BC specimens were correlated with reduced patient survival. In vitro, overexpression of miR-137 significantly increased cell EMT and invasion, while depletion of miR-137 significantly decreased cell EMT and invasion in BC cells. The increases in BC cell invasiveness by miR-137 appeared to result from its suppression of BMP7, through direct binding of miR-137 to the 3'-UTR of BMP7 mRNA, thereby blocking its protein translation in BC cells. This study sheds light on miR-137 as a crucial factor that enhances BC cell EMT and invasiveness, and points to miR-137 as a promising innovative therapeutic target for BC treatment. PMID:28407692

The MIA complex is a conserved and novel dynein regulator essential for normal ciliary motility

PubMed Central

Yamamoto, Ryosuke; Song, Kangkang; Yanagisawa, Haru-aki; Fox, Laura; Yagi, Toshiki; Wirschell, Maureen; Hirono, Masafumi; Kamiya, Ritsu; Nicastro, Daniela

2013-01-01

Axonemal dyneins must be precisely regulated and coordinated to produce ordered ciliary/flagellar motility, but how this is achieved is not understood. We analyzed two Chlamydomonas reinhardtii mutants, mia1 and mia2, which display slow swimming and low flagellar beat frequency. We found that the MIA1 and MIA2 genes encode conserved coiled-coil proteins, FAP100 and FAP73, respectively, which form the modifier of inner arms (MIA) complex in flagella. Cryo–electron tomography of mia mutant axonemes revealed that the MIA complex was located immediately distal to the intermediate/light chain complex of I1 dynein and structurally appeared to connect with the nexin–dynein regulatory complex. In axonemes from mutants that lack both the outer dynein arms and the MIA complex, I1 dynein failed to assemble, suggesting physical interactions between these three axonemal complexes and a role for the MIA complex in the stable assembly of I1 dynein. The MIA complex appears to regulate I1 dynein and possibly outer arm dyneins, which are both essential for normal motility. PMID:23569216

Light-Induced Conversion of Chemical Permeability to Enhance Electron and Molecular Transfer in Nanoscale Assemblies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balgley, Renata; de Ruiter, Graham; Evmenenko, Guennadi

In this paper, we demonstrate how photochemically enhancing the permeability of metal–organic assemblies results in a significant enhancement of the electrochemical activity of metal complexes located within the assembly. The molecular assemblies consist of different layers of redox-active metal complexes ([M(mbpy-py)3][PF6]2; M = Ru or Os) that are separated by redox-inactive spacers consisting of 1,4-bis[2-(4-pyridyl)ethenyl]benzene (BPEB) and PdCl2 of variable thicknesses (0–13.4 nm). UV-irradiation (λ = 254 nm) of our assemblies induces a photochemical reaction in the redox-inactive spacer increasing the permeability of the assembly. The observed increase was evident by trapping organic (nBu4NBF4) and inorganic (NiCl2) salts inside themore » assemblies, and by evaluating the electrochemical response of quinones absorbed inside the molecular assemblies before and after UV irradiation. The increase in permeability is reflected by higher currents and a change in the directionality of electron transfer, i.e., from mono- to bidirectional, between the redox-active metal complexes and the electrode surface. The supramolecular structure of the assemblies dominates the overall electron transfer properties and overrules possible electron transfer mediated by the extensive π-conjugation of its individual organic components.« less

Self-assembled containers based on extended tetrathiafulvalene.

PubMed

Bivaud, Sébastien; Goeb, Sébastien; Croué, Vincent; Dron, Paul I; Allain, Magali; Sallé, Marc

2013-07-10

Two original self-assembled containers constituted each by six electroactive subunits are described. They are synthesized from a concave tetratopic π-extended tetrathiafulvalene ligand bearing four pyridyl units and cis-M(dppf)(OTf)2 (M = Pd or Pt; dppf = 1,1'-bis(diphenylphosphino)ferrocene; OTf = trifluoromethane-sulfonate) complexes. Both fully characterized assemblies present an oblate spheroidal cavity that can incorporate one perylene molecule.

Characterization of Atg38 and NRBF2, a fifth subunit of the autophagic Vps34/PIK3C3 complex

PubMed Central

Ohashi, Yohei; Soler, Nicolas; García Ortegón, Miguel; Zhang, Lufei; Kirsten, Marie L.; Perisic, Olga; Masson, Glenn R.; Burke, John E.; Jakobi, Arjen J.; Apostolakis, Apostolos A.; Johnson, Christopher M.; Ohashi, Maki; Ktistakis, Nicholas T.; Sachse, Carsten; Williams, Roger L.

2016-01-01

ABSTRACT The phosphatidylinositol 3-kinase Vps34 is part of several protein complexes. The structural organization of heterotetrameric complexes is starting to emerge, but little is known about organization of additional accessory subunits that interact with these assemblies. Combining hydrogen-deuterium exchange mass spectrometry (HDX-MS), X-ray crystallography and electron microscopy (EM), we have characterized Atg38 and its human ortholog NRBF2, accessory components of complex I consisting of Vps15-Vps34-Vps30/Atg6-Atg14 (yeast) and PIK3R4/VPS15-PIK3C3/VPS34-BECN1/Beclin 1-ATG14 (human). HDX-MS shows that Atg38 binds the Vps30-Atg14 subcomplex of complex I, using mainly its N-terminal MIT domain and bridges the coiled-coil I regions of Atg14 and Vps30 in the base of complex I. The Atg38 C-terminal domain is important for localization to the phagophore assembly site (PAS) and homodimerization. Our 2.2 Å resolution crystal structure of the Atg38 C-terminal homodimerization domain shows 2 segments of α-helices assembling into a mushroom-like asymmetric homodimer with a 4-helix cap and a parallel coiled-coil stalk. One Atg38 homodimer engages a single complex I. This is in sharp contrast to human NRBF2, which also forms a homodimer, but this homodimer can bridge 2 complex I assemblies. PMID:27630019

Inhibition of autophagy as a new means of improving chemotherapy efficiency in high-LC3B triple-negative breast cancers

PubMed Central

Lefort, Sylvain; Joffre, Carine; Kieffer, Yann; Givel, Anne-Marie; Bourachot, Brigitte; Zago, Giulia; Bieche, Ivan; Dubois, Thierry; Meseure, Didier; Vincent-Salomon, Anne; Camonis, Jacques; Mechta-Grigoriou, Fatima

2015-01-01

The triple-negative breast cancer (TN BC) subtype is the most aggressive form of invasive BC. Despite intensive efforts to improve BC treatments, patients with TN BC continue to exhibit poor survival, with half developing resistance to chemotherapy. Here we identify autophagy as a key mechanism in the progression and chemoresistance of a subset of TN tumors. We demonstrate that LC3B, a protein involved in autophagosome formation, is a reliable marker of poor prognosis in TN BC, validating this prognostic value at both the mRNA and protein levels in several independent cohorts. We also show that LC3B has no prognostic value for other BC subtypes (Luminal or HER2 BC), thus revealing a specific impact of autophagy on TN tumors. Autophagy is essential for the proliferative and invasive properties in 3D of TN BC cells characterized by high LC3B levels. Interestingly, the activity of the transcriptional co-activator YAP1 (Yes-associated protein 1) is regulated by the autophagy process and we identify YAP1 as a new actor in the autophagy-dependent proliferative and invasive properties of high-LC3B TN BC. Finally, inhibiting autophagy by silencing ATG5 or ATG7 significantly impaired high-LC3B TN tumor growth in vivo. Moreover, using a patient-derived TN tumor transplanted into mice, we show that an autophagy inhibitor, chloroquine, potentiates the effects of chemotherapeutic agents. Overall, our data identify LC3B as a new prognostic marker for TN BC and the inhibition of autophagy as a promising therapeutic strategy for TN BC patients. PMID:25427136

Short-Term Responses of Soil Respiration and C-Cycle Enzyme Activities to Additions of Biochar and Urea in a Calcareous Soil

PubMed Central

Song, Dali; Xi, Xiangyin; Huang, Shaomin; Liang, Guoqing; Sun, Jingwen; Zhou, Wei; Wang, Xiubin

2016-01-01

Biochar (BC) addition to soil is a proposed strategy to enhance soil fertility and crop productivity. However, there is limited knowledge regarding responses of soil respiration and C-cycle enzyme activities to BC and nitrogen (N) additions in a calcareous soil. A 56-day incubation experiment was conducted to investigate the combined effects of BC addition rates (0, 0.5, 1.0, 2.5 and 5.0% by mass) and urea (U) application on soil nutrients, soil respiration and C-cycle enzyme activities in a calcareous soil in the North China Plain. Our results showed soil pH values in both U-only and U plus BC treatments significantly decreased within the first 14 days and then stabilized, and CO2emission rate in all U plus BC soils decreased exponentially, while there was no significant difference in the contents of soil total organic carbon (TOC), dissolved organic carbon (DOC), total nitrogen (TN), and C/N ratio in each treatment over time. At each incubation time, soil pH, electrical conductivity (EC), TOC, TN, C/N ratio, DOC and cumulative CO2 emission significantly increased with increasing BC addition rate, while soil potential activities of the four hydrolytic enzymes increased first and then decreased with increasing BC addition rate, with the largest values in the U + 1.0%BC treatment. However, phenol oxidase activity in all U plus BC soils showed a decreasing trend with the increase of BC addition rate. Our results suggest that U plus BC application at a rate of 1% promotes increases in hydrolytic enzymes, does not highly increase C/N and C mineralization, and can improve in soil fertility. PMID:27589265

Loss of the Mammalian DREAM Complex Deregulates Chondrocyte Proliferation

PubMed Central

Forristal, Chantal; Henley, Shauna A.; MacDonald, James I.; Bush, Jason R.; Ort, Carley; Passos, Daniel T.; Talluri, Srikanth; Ishak, Charles A.; Thwaites, Michael J.; Norley, Chris J.; Litovchick, Larisa; DeCaprio, James A.; DiMattia, Gabriel; Holdsworth, David W.; Beier, Frank

2014-01-01

Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes. PMID:24710275

Effect of in-situ aged and fresh biochar on soil hydraulic conditions and microbial C use under drought conditions.

PubMed

Paetsch, Lydia; Mueller, Carsten W; Kögel-Knabner, Ingrid; von Lützow, Margit; Girardin, Cyril; Rumpel, Cornelia

2018-05-01

Biochar (BC) amendments may be suitable to increase the ecosystems resistance to drought due to their positive effects on soil water retention and availability. We investigated the effect of BC in situ ageing on water availability and microbial parameters of a grassland soil. We used soil containing 13 C labeled BC and determined its water holding capacity, microbial biomass and activity during a 3 months incubation under optimum and drought conditions. Our incubation experiment comprised three treatments: soil without BC (Control), soil containing aged BC (BC aged ) and soil containing fresh BC (BC fresh ), under optimum soil water (pF 1.8) and drought conditions (pF 3.5). Under optimum water as well as drought conditions, soils containing BC showed higher soil organic carbon (SOC) mineralization as compared to control soil. Moreover, BC effects on the soil water regime increase upon in situ aging. Native SOC mineralization increased most for soils containing BC aged . The BC aged led to improved C use under drought as compared to the other treatments. We conclude that BC addition to soils can ameliorate their water regime, especially under drought conditions. This beneficial effect of BC increases upon its aging, which also improved native substrate availability.

The potential effect of temperature-humidity index on productive and reproductive performance of buffaloes with different genotypes under hot conditions.

PubMed

Nasr, Mohammed A F

2017-08-01

The current study was aimed to investigate the impact of THI on productive and reproductive indices of PE and F 1 crosses (50% PE and 50% Italian buffaloes) and back crosses (BC) (75% PE and 25% Italian buffaloes) under hot conditions. In this study, 8385 records used PE (1914, 1518, and 1737), F 1 (387, 447, and 657), and BC (495, 585, and 645) for low, medium, and high THI, respectively. The high THI reduced the conception rate after first insemination in PE, F 1 , and BC ((odds ratio, OR) = 1.187, P = 0.007; 2.361, <0.0001 and 1.603, <0.0001, respectively) when compared with low THI. But, stillbirth and calving condition were not significantly influenced by different THI levels in BC and F 1 . BC was more bearable to the harsh environment; they possessed the highest incidence of conception after first insemination (72.70, 72.60, and 62.40%), producing live calves (98.50, 100, and 99.40%) with easy calving condition (98.50, 100, and 99.40%) when compared to PE and F 1 at different levels of THI, respectively. The average daily milk yield and peak of milk production were decreased in PE (4.02 and 5.12%), BC (13.33 and 10.95%), and F 1 (25.29 and 12.20%) from low to high THI. However, BC revealed no significant changes in days open, dry period, calving interval, gestation length, service per conception, and the first service post-partum at different levels of THI when compared with PE and F 1 . Therefore, rearing BC is recommended for improving buffalo productive and reproductive performance under hot conditions.

Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis.

PubMed

Ma, Lu; Rebane, Aleksander A; Yang, Guangcan; Xi, Zhiqun; Kang, Yuhao; Gao, Ying; Zhang, Yongli

2015-12-23

Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD, and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

Next-generation sequencing in familial breast cancer patients from Lebanon.

PubMed

Jalkh, Nadine; Chouery, Eliane; Haidar, Zahraa; Khater, Christina; Atallah, David; Ali, Hamad; Marafie, Makia J; Al-Mulla, Mohamed R; Al-Mulla, Fahd; Megarbane, Andre

2017-02-15

Familial breast cancer (BC) represents 5 to 10% of all BC cases. Mutations in two high susceptibility BRCA1 and BRCA2 genes explain 16-40% of familial BC, while other high, moderate and low susceptibility genes explain up to 20% more of BC families. The Lebanese reported prevalence of BRCA1 and BRCA2 deleterious mutations (5.6% and 12.5%) were lower than those reported in the literature. In the presented study, 45 Lebanese patients with a reported family history of BC were tested using Whole Exome Sequencing (WES) technique followed by Sanger sequencing validation. Nineteen pathogenic mutations were identified in this study. These 19 mutations were found in 13 different genes such as: ABCC12, APC, ATM, BRCA1, BRCA2, CDH1, ERCC6, MSH2, POLH, PRF1, SLX4, STK11 and TP53. In this first application of WES on BC in Lebanon, we detected six BRCA1 and BRCA2 deleterious mutations in seven patients, with a total prevalence of 15.5%, a figure that is lower than those reported in the Western literature. The p.C44F mutation in the BRCA1 gene appeared twice in this study, suggesting a founder effect. Importantly, the overall mutation prevalence was equal to 40%, justifying the urgent need to deploy WES for the identification of genetic variants responsible for familial BC in the Lebanese population.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sunahori, Fumie X.; Nagarajan, Ramya; Clouthier, Dennis J., E-mail: dclaser@uky.edu

The cold boron carbide free radical (BC X {sup 4}Σ{sup −}) has been produced in a pulsed discharge free jet expansion using a precursor mixture of trimethylborane in high pressure argon. High resolution laser induced fluorescence spectra have been obtained for the B {sup 4}Σ{sup −}–X {sup 4}Σ{sup −} and E {sup 4}Π–X {sup 4}Σ{sup −} band systems of both {sup 11}BC and {sup 10}BC. An optical-optical double resonance (OODR) scheme was implemented to study the finer details of both band systems. This involved pumping a single rotational level of the B state with one laser and then recording the various allowed transitions from themore » intermediate B state to the final E state with a second laser by monitoring the subsequent E–X ultraviolet fluorescence. In this fashion, we were able to prove unambiguously that, contrary to previous studies, the spin-spin constant λ is negative in the ground state and positive in the B {sup 4}Σ{sup −} excited state. It has been shown that λ″ < 0 is in fact expected based on a semiempirical second order perturbation theory calculation of the magnitude of the spin-spin constant. The OODR spectra have also been used to validate our assignments of the complex and badly overlapped E {sup 4}Π–X {sup 4}Σ{sup −} 0-0 and 1-0 bands of {sup 11}BC. The E–X 0-0 band of {sup 10}BC was found to be severely perturbed. The ground state main electron configuration is …3σ{sup 2}4σ{sup 2}5σ{sup 1}1π{sup 2}2π{sup 0} and the derived bond lengths show that there is a 0.03 Å contraction in the B state, due to the promotion of an electron from the 4σ antibonding orbital to the 5σ bonding orbital. In contrast, the bond length elongates by 0.15 Å in the E state, a result of promoting an electron from the 5σ bonding orbital to the 2π antibonding orbitals.« less

PTK 7 Is a Transforming Gene and Prognostic Marker for Breast Cancer and Nodal Metastasis Involvement

PubMed Central

Knyazeva, Tatiana; Wolf, Petra; Högel, Bernhard; Eiermann, Wolfgang; Ullrich, Axel; Knyazev, Pjotr; Ataseven, Beyhan

2014-01-01

Protein Tyrosin Kinase 7 (PTK7) is upregulated in several human cancers; however, its clinical implication in breast cancer (BC) and lymph node (LN) is still unclear. In order to investigate the function of PTK7 in mediating BC cell motility and invasivity, PTK7 expression in BC cell lines was determined. PTK7 signaling in highly invasive breast cancer cells was inhibited by a dominant-negative PTK7 mutant, an antibody against the extracellular domain of PTK7, and siRNA knockdown of PTK7. This resulted in decreased motility and invasivity of BC cells. We further examined PTK7 expression in BC and LN tissue of 128 BC patients by RT-PCR and its correlation with BC related genes like HER2, HER3, PAI1, MMP1, K19, and CD44. Expression profiling in BC cell lines and primary tumors showed association of PTK7 with ER/PR/HER2-negative (TNBC-triple negative BC) cancer. Oncomine data analysis confirmed this observation and classified PTK7 in a cluster with genes associated with agressive behavior of primary BC. Furthermore PTK7 expression was significantly different with respect to tumor size (ANOVA, p = 0.033) in BC and nodal involvement (ANOVA, p = 0.007) in LN. PTK7 expression in metastatic LN was related to shorter DFS (Cox Regression, p = 0.041). Our observations confirmed the transforming potential of PTK7, as well as its involvement in motility and invasivity of BC cells. PTK7 is highly expressed in TNBC cell lines. It represents a novel prognostic marker for BC patients and has potential therapeutic significance. PMID:24409301

The human immunodeficiency virus type 1 long terminal repeat specifies two different transcription complexes, only one of which is regulated by Tat.

PubMed Central

Lu, X; Welsh, T M; Peterlin, B M

1993-01-01

The human immunodeficiency virus type 1 long terminal repeat sets up two different transcription complexes, which have been called processive and nonprocessive complexes. By mutating and substituting cis-acting sequences, we mapped elements of the human immunodeficiency virus long terminal repeat that are responsible for creating each transcription complex. Whereas processive complexes are efficiently assembled by upstream promoter elements in the absence of the TATA box, nonprocessive complexes absolutely require the TATA box. Moreover, the TATA box alone can set up these nonprocessive complexes, and nonprocessive but not processive complexes are trans activated by Tat. Finally, a strong DNA-binding site between the TATA box and trans-activation-responsive region interferes with either the assembly or movement of these nonprocessive complexes and diminishes the effects of Tat. Thus, Tat affects a critical step in the formation of elongation-competent transcription complexes. Images PMID:8445708

The variability in the relationship between black carbon and carbon monoxide over the eastern coast of China: BC aging during transport

NASA Astrophysics Data System (ADS)

Guo, Qingfeng; Hu, Min; Guo, Song; Wu, Zhijun; Peng, Jianfei; Wu, Yusheng

2017-09-01

East Asia is a densely populated region with a myriad of primary emissions of pollutants such as black carbon (BC) and carbon monoxide (CO). To characterize primary emissions over the eastern coast of China, a series of field campaigns were conducted in 2011, including measurements from a ship cruise, island, and coastal receptor sites. The relationship between BC and CO is presented here for the first ship cruise (C1), the second ship cruise (C2), an island site (Changdao Island, CD), and a coastal site (Wenling, WL). The average BC mass concentrations were 2.43, 2.73, 1.09, 0.94, and 0.77 µg m-3 for CD, WL, C1-YS (Yellow Sea), C1-ES (East China Sea), and C2-ES, respectively. For those locations, the average CO mixing ratios were 0.55, 0.48, 0.31, 0.36, and 0.27 ppm. The high loadings of both BC and CO imply severe anthropogenic pollution over the eastern coast of China. Additionally, the linear correlation between BC and CO was regressed for each location. The slopes, i.e., the ratios of ΔBC to ΔCO derived from their relationship, correlated well with the ratios of diesel consumption to gasoline consumption in each province/city, which reveals vehicular emission to be the common source for BC and CO and that there are distinct fuel structures between North and South China. The ΔBC/ΔCO values at coastal sites (Changdao Island and Wenling) were much higher than those over the Yellow Sea and East China Sea, and the correlation coefficients also showed a decreasing trend from the coast to the sea. Therefore, the quantity of ΔBC/ΔCO and the correlation coefficients are possible indicators for the aging and removal of BC.

The Assembly Pathway of Mitochondrial Respiratory Chain Complex I.

PubMed

Guerrero-Castillo, Sergio; Baertling, Fabian; Kownatzki, Daniel; Wessels, Hans J; Arnold, Susanne; Brandt, Ulrich; Nijtmans, Leo

2017-01-10

Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes. We delineate the stepwise incorporation of all but one subunit into a series of distinct assembly intermediates and their association with known and putative assembly factors, which had not been implicated in this process before. The resulting detailed and comprehensive model of complex I assembly is fully consistent with recent structural data and the remarkable modular architecture of this multiprotein complex. Copyright © 2017 Elsevier Inc. All rights reserved.

Electron microscopic analysis of rotavirus assembly-replication intermediates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boudreaux, Crystal E.; Kelly, Deborah F.; McDonald, Sarah M., E-mail: mcdonaldsa@vtc.vt.edu

2015-03-15

Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally,more » using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process. - Highlights: • Rotaviruses replicate their genomes in tandem with early virion assembly. • Little is known about rotavirus assembly-replication intermediates. • Assembly-replication intermediates were imaged using electron microscopy.« less

Assembly and function of the major histocompatibility complex (MHC) I peptide-loading complex are conserved across higher vertebrates.

PubMed

Hinz, Andreas; Jedamzick, Johanna; Herbring, Valentina; Fischbach, Hanna; Hartmann, Jessica; Parcej, David; Koch, Joachim; Tampé, Robert

2014-11-28

Antigen presentation to cytotoxic T lymphocytes via major histocompatibility complex class I (MHC I) molecules depends on the heterodimeric transporter associated with antigen processing (TAP). For efficient antigen supply to MHC I molecules in the ER, TAP assembles a macromolecular peptide-loading complex (PLC) by recruiting tapasin. In evolution, TAP appeared together with effector cells of adaptive immunity at the transition from jawless to jawed vertebrates and diversified further within the jawed vertebrates. Here, we compared TAP function and interaction with tapasin of a range of species within two classes of jawed vertebrates. We found that avian and mammalian TAP1 and TAP2 form heterodimeric complexes across taxa. Moreover, the extra N-terminal domain TMD0 of mammalian TAP1 and TAP2 as well as avian TAP2 recruits tapasin. Strikingly, however, only TAP1 and TAP2 from the same taxon can form a functional heterodimeric translocation complex. These data demonstrate that the dimerization interface between TAP1 and TAP2 and the tapasin docking sites for PLC assembly are conserved in evolution, whereas elements of antigen translocation diverged later in evolution and are thus taxon specific. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Subcellular distribution of swine vesicular disease virus proteins and alterations induced in infected cells: A comparative study with foot-and-mouth disease virus and vesicular stomatitis virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin-Acebes, Miguel A.; Gonzalez-Magaldi, Monica; Rosas, Maria F.

2008-05-10

The intracellular distribution of swine vesicular disease virus (SVDV) proteins and the induced reorganization of endomembranes in IBRS-2 cells were analyzed. Fluorescence to new SVDV capsids appeared first upon infection, concentrated in perinuclear circular structures and colocalized to dsRNA. As in foot-and-mouth disease virus (FMDV)-infected cells, a vesicular pattern was predominantly found in later stages of SVDV capsid morphogenesis that colocalized with those of non-structural proteins 2C, 2BC and 3A. These results suggest that assembly of capsid proteins is associated to the replication complex. Confocal microscopy showed a decreased fluorescence to ER markers (calreticulin and protein disulfide isomerase), and disorganizationmore » of cis-Golgi gp74 and trans-Golgi caveolin-1 markers in SVDV- and FMDV-, but not in vesicular stomatitis virus (VSV)-infected cells. Electron microscopy of SVDV-infected cells at an early stage of infection revealed fragmented ER cisternae with expanded lumen and accumulation of large Golgi vesicles, suggesting alterations of vesicle traffic through Golgi compartments. At this early stage, FMDV induced different patterns of ER fragmentation and Golgi alterations. At later stages of SVDV cytopathology, cells showed a completely vacuolated cytoplasm containing vesicles of different sizes. Cell treatment with brefeldin A, which disrupts the Golgi complex, reduced SVDV ({approx} 5 log) and VSV ({approx} 4 log) titers, but did not affect FMDV growth. Thus, three viruses, which share target tissues and clinical signs in natural hosts, induce different intracellular effects in cultured cells.« less

Age at diagnosis of female breast cancer in Oman: Issues and implications

PubMed Central

Mehdi, Itrat; Monem, Essam Abdul; Al Bahrani, Bassim Jaffar; Al Kharusi, Suad; Nada, Ayman Mohammad; Al Lawati, Jawad; Al Lawati, Najla

2014-01-01

Introduction: Female breast cancer (BC) is the most frequent malignancy diagnosed globally, about 23% of the diagnosed cancers. BC incidence varies geographically, highest in Western Europe and lowest in Africa. BC in females is strongly correlated to age, the highest incidence rate amongst older women reinforcing the importance of hormonal status. BC in young females has an aggressive phenotype. There is a shared observation amongst practicing oncologists that BC in Middle East and the developing world presents at an earlier age. Aim and Objective: The aims of this study are to evaluate the age at presentation of female BC in Oman, and to compare our data with international and regional published data. It discusses the impact of young age Breast Cancer. Materials and Methods: All diagnosed female BC cases registered from 1996-2010 all over the country, were retrieved from the National Cancer Registry, Ministry of Health. BC cases were analyzed with respect to age at presentation. The data were compared with regional and international data. Results: A total of 14,109 cancer cases were recorded during the period of study. BC was the leading malignancy as 1,294 cases (9.1%). Female BC patients were 1,230; denoting 19.2% of all female cancers. 53.5% of female BC presented below 50 years of age. Male BC constituted 5% of total, with 67% of male BC occurring over 50 years of age. Compared with data from Oman, the highest rates in UK and other Western countries are above 50 years of age. These rates are four to 10 times higher than local in different age groups. Interestingly, these rates increase with increasing age in UK from 40-45 to up to 85+, keep on increasing and go up to four times higher with higher age. This phenomenon, of increasing incidence rates with age, is not observed in our local population. Discussion: BC is significantly correlated to age as reported from Western population. BC is reported at a younger age from developing and Arab World, which need to be further studied and validated. This phenomenon of BC in younger age may have significant implications and effects ranging from screening, diagnosis, management, prognosis, and cost of treatment. Conclusion: The impact on young women diagnosed with BC is enormous, ranging from psychosocial to healthcare services and economics. There is a need to study it further in depth in developing World. PMID:24818104

The Two Cryptochrome/Photolyase Family Proteins Fulfill Distinct Roles in DNA Photorepair and Regulation of Conidiation in the Gray Mold Fungus Botrytis cinerea

PubMed Central

Cohrs, Kim C.

2017-01-01

ABSTRACT The plant-pathogenic leotiomycete Botrytis cinerea is known for the strict regulation of its asexual differentiation programs by environmental light conditions. Sclerotia are formed in constant darkness; black/near-UV (NUV) light induces conidiation; and blue light represses both differentiation programs. Sensing of black/NUV light is attributed to proteins of the cryptochrome/photolyase family (CPF). To elucidate the molecular basis of the photoinduction of conidiation, we functionally characterized the two CPF proteins encoded in the genome of B. cinerea as putative positive-acting components. B. cinerea CRY1 (BcCRY1), a cyclobutane pyrimidine dimer (CPD) photolyase, acts as the major enzyme of light-driven DNA repair (photoreactivation) and has no obvious role in signaling. In contrast, BcCRY2, belonging to the cry-DASH proteins, is dispensable for photorepair but performs regulatory functions by repressing conidiation in white and especially black/NUV light. The transcription of bccry1 and bccry2 is induced by light in a White Collar complex (WCC)-dependent manner, but neither light nor the WCC is essential for the repression of conidiation through BcCRY2 when bccry2 is constitutively expressed. Further, BcCRY2 affects the transcript levels of both WCC-induced and WCC-repressed genes, suggesting a signaling function downstream of the WCC. Since both CPF proteins are dispensable for photoinduction by black/NUV light, the origin of this effect remains elusive and may be connected to a yet unknown UV-light-responsive system. IMPORTANCE Botrytis cinerea is an economically important plant pathogen that causes gray mold diseases in a wide variety of plant species, including high-value crops and ornamental flowers. The spread of disease in the field relies on the formation of conidia, a process that is regulated by different light qualities. While this feature has been known for a long time, we are just starting to understand the underlying molecular mechanisms. Conidiation in B. cinerea is induced by black/near-UV light, whose sensing is attributed to the action of cryptochrome/photolyase family (CPF) proteins. Here we report on the distinct functions of two CPF proteins in the photoresponse of B. cinerea. While BcCRY1 acts as the major photolyase in photoprotection, BcCRY2 acts as a cryptochrome with a signaling function in regulating photomorphogenesis (repression of conidiation). PMID:28667107

Scaffold Protein Connector Enhancer of Kinase Suppressor of Ras Isoform 3 (CNK3) Coordinates Assembly of a Multiprotein Epithelial Sodium Channel (ENaC)-regulatory Complex*

PubMed Central

Soundararajan, Rama; Ziera, Tim; Koo, Eric; Ling, Karen; Wang, Jian; Borden, Steffen A.; Pearce, David

2012-01-01

Hormone regulation of ion transport in the kidney tubules is essential for fluid and electrolyte homeostasis in vertebrates. A large body of evidence has suggested that transporters and channels exist in multiprotein regulatory complexes; however, relatively little is known about the composition of these complexes or their assembly. The epithelial sodium channel (ENaC) in particular is tightly regulated by the salt-regulatory hormone aldosterone, which acts at least in part by increasing expression of the serine-threonine kinase SGK1. Here we show that aldosterone induces the formation of a 1.0–1.2-MDa plasma membrane complex, which includes ENaC, SGK1, and the ENaC inhibitor Nedd4-2, a key target of SGK1. We further show that this complex contains the PDZ domain-containing protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3). CNK3 physically interacts with ENaC, Nedd4-2, and SGK1; enhances the interactions among them; and stimulates ENaC function in a PDZ domain-dependent, aldosterone-induced manner. These results strongly suggest that CNK3 is a molecular scaffold, which coordinates the assembly of a multiprotein ENaC-regulatory complex and hence plays a central role in Na+ homeostasis. PMID:22851176

Unveiling the Semicoherent Interface with Definite Orientation Relationships between Reinforcements and Matrix in Novel Al3BC/Al Composites.

PubMed

Zhao, Yongfeng; Qian, Zhao; Ma, Xia; Chen, Houwen; Gao, Tong; Wu, Yuying; Liu, Xiangfa

2016-10-05

High-strength lightweight Al-based composites are promising materials for a wide range of applications. To provide high performance, a strong bonding interface for effective load transfer from the matrix to the reinforcement is essential. In this work, the novel Al 3 BC reinforced Al composites have been in situ fabricated through a liquid-solid reaction method and the bonding interface between Al 3 BC and Al matrix has been unveiled. The HRTEM characterizations on the Al 3 BC/Al interface verify it to be a semicoherent bonding structure with definite orientation relationships: (0001) Al 3 BC //(11̅1) Al ;[112̅0] Al 3 BC //[011] Al . Periodic arrays of geometrical misfit dislocations are also observed along the interface at each (0001) Al 3 BC plane or every five (11̅1) Al planes. This kind of interface between the reinforcement and the matrix is strong enough for effective load transfer, which would lead to the evidently improved strength and stiffness of the introduced new Al 3 BC/Al composites.

Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions.

PubMed

Cory, Seth A; Van Vranken, Jonathan G; Brignole, Edward J; Patra, Shachin; Winge, Dennis R; Drennan, Catherine L; Rutter, Jared; Barondeau, David P

2017-07-03

In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1-ISD11-ACP (SDA) complex forms the core of the iron-sulfur (Fe-S) assembly complex and associates with assembly proteins ISCU2, frataxin (FXN), and ferredoxin to synthesize Fe-S clusters. Here we present crystallographic and electron microscopic structures of the SDA complex coupled to enzyme kinetic and cell-based studies to provide structure-function properties of a mitochondrial cysteine desulfurase. Unlike prokaryotic cysteine desulfurases, the SDA structure adopts an unexpected architecture in which a pair of ISD11 subunits form the dimeric core of the SDA complex, which clarifies the critical role of ISD11 in eukaryotic assemblies. The different quaternary structure results in an incompletely formed substrate channel and solvent-exposed pyridoxal 5'-phosphate cofactor and provides a rationale for the allosteric activator function of FXN in eukaryotic systems. The structure also reveals the 4'-phosphopantetheine-conjugated acyl-group of ACP occupies the hydrophobic core of ISD11, explaining the basis of ACP stabilization. The unexpected architecture for the SDA complex provides a framework for understanding interactions with acceptor proteins for sulfur-containing biosynthetic pathways, elucidating mechanistic details of eukaryotic Fe-S cluster biosynthesis, and clarifying how defects in Fe-S cluster assembly lead to diseases such as Friedreich's ataxia. Moreover, our results support a lock-and-key model in which LYR proteins associate with acyl-ACP as a mechanism for fatty acid biosynthesis to coordinate the expression, Fe-S cofactor maturation, and activity of the respiratory complexes.

Examining the Influence of Beta Blockers and ACE Inhibitors on the Risk for Breast Cancer Recurrence: Results from the LACE Cohort

PubMed Central

Ganz, Patricia A.; Habel, Laurel A.; Weltzien, Erin K.; Caan, Bette J.; Cole, Steven W.

2011-01-01

There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta-blockers (BB) and/or angiotensin converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality. Among 1,779 women, there were 292 BC recurrences, 174 BC deaths, and 323 total deaths. 23% were exposed to either a BB and/or an ACEi. These drugs were associated with older age, postmenopausal status, tamoxifen therapy, greater pre-diagnosis BMI, hypertension, and diabetes. In Cox proportional hazards models, ACEi exposure was associated with BC recurrence (HR 1.56, 95% CI 1.02, 2.39, p=0.04), but not cause-specific mortality or overall mortality. Combined ACEi and BB was associated with overall mortality (HR 1.94, 95% CI 1.22, 3.10, p=0.01). BB exposure was associated with lower hazard of recurrence and cause-specific mortality. However, there was no evidence of a dose response with either medication. For recurrence and cause-specific mortality, BB combined with ACEi was associated with a lower HR for the outcome than when ACEi alone was used. These hypothesis generating findings suggest that BC recurrence and survival were associated with exposure to two commonly used classes of anti-hypertensive medications. These observations need to be confirmed and suggest that greater attention should focus on the potential role of these commonly used medications in BC outcomes. PMID:21479924

The role of the dynein light intermediate chain in retrograde IFT and flagellar function in Chlamydomonas

PubMed Central

Reck, Jaimee; Schauer, Alexandria M.; VanderWaal Mills, Kristyn; Bower, Raqual; Tritschler, Douglas; Perrone, Catherine A.; Porter, Mary E.

2016-01-01

The assembly of cilia and flagella depends on the activity of two microtubule motor complexes, kinesin-2 and dynein-2/1b, but the specific functions of the different subunits are poorly defined. Here we analyze Chlamydomonas strains expressing different amounts of the dynein 1b light intermediate chain (D1bLIC). Disruption of D1bLIC alters the stability of the dynein 1b complex and reduces both the frequency and velocity of retrograde intraflagellar transport (IFT), but it does not eliminate retrograde IFT. Flagellar assembly, motility, gliding, and mating are altered in a dose-dependent manner. iTRAQ-based proteomics identifies a small subset of proteins that are significantly reduced or elevated in d1blic flagella. Transformation with D1bLIC-GFP rescues the mutant phenotypes, and D1bLIC-GFP assembles into the dynein 1b complex at wild-type levels. D1bLIC-GFP is transported with anterograde IFT particles to the flagellar tip, dissociates into smaller particles, and begins processive retrograde IFT in <2 s. These studies demonstrate the role of D1bLIC in facilitating the recycling of IFT subunits and other proteins, identify new components potentially involved in the regulation of IFT, flagellar assembly, and flagellar signaling, and provide insight into the role of D1bLIC and retrograde IFT in other organisms. PMID:27251063

Coffee consumption and bladder cancer: a meta-analysis of observational studies

PubMed Central

Wu, Weixiang; Tong, Yeqing; Zhao, Qiang; Yu, Guangxia; Wei, Xiaoyun; Lu, Qing

2015-01-01

Controversial results of the association between coffee consumption and bladder cancer (BC) risk were reported among epidemiological studies. Therefore, we conducted this meta-analysis to clarify the association. Relevant studies were identified according to the inclusion criteria. Totally, 34 case-control studies and 6 cohort studies were included in our meta-analysis. The overall odds ratio (OR) with 95% confidence interval (CI) between coffee consumption and BC risk was 1.33 (95% CI 1.19 to 1.48). The summary ORs of BC for an increase of 1 cup of coffee per day were 1.05 (95% CI 1.03 to 1.06) for case-control studies and 1.03 (95% CI 0.99 to 1.06) for cohort studies. The overall ORs for male coffee drinkers, female coffee drinkers and coffee drinkers of both gender were 1.31 (95% CI: 1.08 to 1.59), 1.30 (95% CI: 0.87 to 1.96) and 1.35 (95% CI: 1.20 to 1.51). Compared with smokers (OR = 1.24, 95% CI: 0.91 to 1.70), non-smokers had a higher risk (OR = 1.72, 95% CI: 1.25 to 2.35) for BC. Results of this meta-analysis suggested that there was an increased risk between coffee consumption and BC. Male coffee drinkers and non-smoking coffee drinkers were more likely to develop BC. PMID:25761588

Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly.

PubMed

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C; Nogales, Eva; Taatjes, Dylan J

2011-03-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator-pol II interface is not well-characterized, whereas attempts to structurally define the Mediator-pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator-pol II-TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator-pol II-TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator-pol II-TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator-CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator-pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly.

Molecular Architecture of the Human Mediator–RNA Polymerase II–TFIIF Assembly

PubMed Central

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C.; Nogales, Eva; Taatjes, Dylan J.

2011-01-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator–pol II interface is not well-characterized, whereas attempts to structurally define the Mediator–pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator–pol II–TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator–pol II–TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator–pol II–TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator–CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator–pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly. PMID:21468301

Hydrogenation of Carbon Dioxide Catalyzed by Ruthenium Trimethylphosphine Complexes: A Mechanistic Investigation using High-Pressure NMR Spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Getty, April D.; Tai, Chih-Cheng; Linehan, John C.

2009-08-26

The previously reported complex, cis-(PMe3)4RuCl(OAc) (1) acts as a catalyst for CO2 hydrogenation into formic acid in the presence of a base and an alcohol co-catalyst. NMR spectroscopy has revealed that 1 exists in solution in equilibrium with fac-(PMe3)3RuCl(h2-OAc) (2), [(PMe3)4Ru(h2-OAc)]Cl (3a), and free PMe3. Complex 2 has been isolated and characterized by elemental analysis, NMR spectroscopy, and X-ray crystallography. 2 has been tested as a CO2 hydrogenation catalyst, however, it performed poorly under the conditions of catalysis used for 1. Complex 3a can be prepared by adding certain alcohols, such as MeOH, EtOH, or o-C6H5OH, to a solution ofmore » 1 in CDCl3. The chloride ion of 3a has been exchanged for the non-coordinating anions BPh4 or B(ArF )4 (B(ArF)4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate) to produce [(PMe3)4Ru(h2-OAc)]BPh4 (3b) and [(PMe3)4Ru(h2-OAc)]B(ArF)4 (3c). Both of these complexes have been isolated and characterized by elemental analysis, NMR spectroscopy, and in the case of 3b, X-ray crystallography. Complexes 3b and 3c perform just as well as 1 for CO2 hydrogenation to formic acid in the presence of an alcohol co-catalyst; however, 3b,c perform equally well without the added alcohol. High-pressure NMR has been used to investigate the mechanism of CO2 hydrogenation via 3a,b in the presence of base. Two of the intermediates involved have been identified as cis-(PMe3)4RuH2 (5) and cis-(PMe3)4Ru(H)O2CH (6), and the role of the base includes not only trapping of the formic acid product, but also initiation of the catalysis by aiding the conversion of 3b,c to 5.« less

A Study on BC Emission from Vehicles using Different Types of Fuel

NASA Astrophysics Data System (ADS)

Kim, K.; Son, J.; Kim, J.; Kim, S.; Park, G.; Sung, K.; Kim, I.; Chung, T.; Park, T.; Kang, S.; Ban, J.; Kim, J.; Hong, Y. D.; Woo, J. H.; Lee, T.

2017-12-01

Black carbon (BC) is an anthropogenic aerosol from fossil fuels, and biomass burning. It absorbs solar radiation, and heats the atmosphere leading 0.4W m-2 radiative forcing. BC is a particle that can cause serious effects on human body as well. Toxicological studies of black carbon suggests that BC may be an important carrier of toxic chemicals to human body. The recent researches show that one of the main precursor of BC is vehicle emission, but the inventory of BC emission rate from vehicle is inadequate in South Korea. This study tries to find differences of BC emission from different sizes of vehicles using different types of fuels. Fuels used in vehicles are gasoline, liquefied petroleum gas (LPG), and diesel. BC was directly measured from the tail pipe of vehicles using Aethalometer (AE33, Magee Scientific Corporation). This study was conducted in Transport Pollutant Research Center, National Institute of Environmental Research, South Korea. Measurement was progressed with the five different test modes of speeds. Speed modes includes 4.7, 17.3, 34.1, 65.4, and 97.3 km h-1. Emission rate of BC was high in the slowest speed mode, and showed decrease with increase of the speed of vehicles. Gasoline vehicles had the relatively higher emission rate of BC than the LPG vehicle, while the emission rate of BC for Diesel with DPF (Diesel Particle Filter) was observed to be the lowest.

Light and the City: Breast Cancer Risk Factors Differ Between Urban and Rural Women in Israel.

PubMed

Keshet-Sitton, Atalya; Or-Chen, Keren; Yitzhak, Sara; Tzabary, Ilana; Haim, Abraham

2017-06-01

Women are exposed to indoor and outdoor artificial light at night (ALAN) in urban and rural environments. Excessive exposure to hazardous ALAN containing short wavelength light may suppress pineal melatonin production and lead to an increased breast cancer (BC) risk. Our objective was to address the differences in BC risks related to light exposure in urban and rural communities. We examined indoor and outdoor light habits of BC patients and controls that had lived in urban and rural areas in a 5-year period, 10 to 15 years before the time of the study. Individual data, night time sleeping habits and individual exposure to ALAN habits were collected using a questionnaire. A total of 252 women (110 BC patients and 142 controls) participated in this study. The sample was divided to subgroups according to dwelling area and disease status. Age matching was completed between all subgroups. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for urban and rural women separately, using binary logistic regression. OR results of urban population (92 BC patients and 72 control) revealed that BC risk increases with daily use of cellphone (OR = 2.13, 95% CI = 1.01-4.49, P < .05) and residence near strong ALAN sources (OR = 1.51, 95% CI = 0.99-2.30, P < .06). Nevertheless, BC risk decreases if a woman was born in Israel (OR = 0.44, 95% CI = 0.21-0.93, P < .03), longer sleep duration (OR = 0.75, 95% CI = 0.53-1.05, P < .1), and reading with bed light illumination before retiring to sleep (OR = 0.77, 95% CI = 0.61-0.96, P < .02). Furthermore, in the rural population (18 BC patients and 66 control) BC risk increases with the number of years past since the last menstruation (OR = 1.12, 95% CI = 1.03-1.22, P < .01). However, BC risk decreases with longer sleep duration (OR = 0.53, 95% CI = 0.24-1.14, P < .1), reading with room light illumination before retiring to sleep (OR = 0.55, 95% CI = 0.29-1.06, P < .07), and sleeping with closed shutters during the night (OR = 0.66, 95% CI = 0.41-1.04, P < .08). These data support the idea that indoor and outdoor nighttime light exposures differ between urban and rural women. Therefore, we suggest that women can influence BC risk and incidence by applying protective personal lighting habits. Further studies with larger sample sizes are needed to strengthen the results.

Enhanced light absorption by mixed source black and brown carbon particles in UK winter

PubMed Central

Liu, Shang; Aiken, Allison C.; Gorkowski, Kyle; Dubey, Manvendra K.; Cappa, Christopher D.; Williams, Leah R.; Herndon, Scott C.; Massoli, Paola; Fortner, Edward C.; Chhabra, Puneet S.; Brooks, William A.; Onasch, Timothy B.; Jayne, John T.; Worsnop, Douglas R.; China, Swarup; Sharma, Noopur; Mazzoleni, Claudio; Xu, Lu; Ng, Nga L.; Liu, Dantong; Allan, James D.; Lee, James D.; Fleming, Zoë L.; Mohr, Claudia; Zotter, Peter; Szidat, Sönke; Prévôt, André S. H.

2015-01-01

Black carbon (BC) and light-absorbing organic carbon (brown carbon, BrC) play key roles in warming the atmosphere, but the magnitude of their effects remains highly uncertain. Theoretical modelling and laboratory experiments demonstrate that coatings on BC can enhance BC's light absorption, therefore many climate models simply assume enhanced BC absorption by a factor of ∼1.5. However, recent field observations show negligible absorption enhancement, implying models may overestimate BC's warming. Here we report direct evidence of substantial field-measured BC absorption enhancement, with the magnitude strongly depending on BC coating amount. Increases in BC coating result from a combination of changing sources and photochemical aging processes. When the influence of BrC is accounted for, observationally constrained model calculations of the BC absorption enhancement can be reconciled with the observations. We conclude that the influence of coatings on BC absorption should be treated as a source and regionally specific parameter in climate models. PMID:26419204

Breast cancer risk is increased in the years following false-positive breast cancer screening.

PubMed

Goossens, Mathijs C; De Brabander, Isabel; De Greve, Jacques; Vaes, Evelien; Van Ongeval, Chantal; Van Herck, Koen; Kellen, Eliane

2017-09-01

A small number of studies have investigated breast cancer (BC) risk among women with a history of false-positive recall (FPR) in BC screening, but none of them has used time-to-event analysis while at the same time quantifying the effect of false-negative diagnostic assessment (FNDA). FNDA occurs when screening detects BC, but this BC is missed on diagnostic assessment (DA). As a result of FNDA, screenings that detected cancer are incorrectly classified as FPR. Our study linked data recorded in the Flemish BC screening program (women aged 50-69 years) to data from the national cancer registry. We used Cox proportional hazards models on a retrospective cohort of 298 738 women to assess the association between FPR and subsequent BC, while adjusting for potential confounders. The mean follow-up was 6.9 years. Compared with women without recall, women with a history of FPR were at an increased risk of developing BC [hazard ratio=2.10 (95% confidence interval: 1.92-2.31)]. However, 22% of BC after FPR was due to FNDA. The hazard ratio dropped to 1.69 (95% confidence interval: 1.52-1.87) when FNDA was excluded. Women with FPR have a subsequently increased BC risk compared with women without recall. The risk is higher for women who have a FPR BI-RADS 4 or 5 compared with FPR BI-RADS 3. There is room for improvement of diagnostic assessment: 41% of the excess risk is explained by FNDA after baseline screening.

Biomarkers of folate and vitamin B12 and breast cancer risk: report from the EPIC cohort.

PubMed

Matejcic, M; de Batlle, J; Ricci, C; Biessy, C; Perrier, F; Huybrechts, I; Weiderpass, E; Boutron-Ruault, M C; Cadeau, C; His, M; Cox, D G; Boeing, H; Fortner, R T; Kaaks, R; Lagiou, P; Trichopoulou, A; Benetou, V; Tumino, R; Panico, S; Sieri, S; Palli, D; Ricceri, F; Bueno-de-Mesquita, H B As; Skeie, G; Amiano, P; Sánchez, M J; Chirlaque, M D; Barricarte, A; Quirós, J R; Buckland, G; van Gils, C H; Peeters, P H; Key, T J; Riboli, E; Gylling, B; Zeleniuch-Jacquotte, A; Gunter, M J; Romieu, I; Chajès, V

2017-03-15

Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (OR Q4-Q1  = 1.26; 95% CI 1.00-1.58; P trend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (OR Q4-Q1  = 1.29; 95% CI 1.02-1.62; P trend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation. © 2016 UICC.

Impacts of global, regional, and sectoral black carbon emission reductions on surface air quality and human mortality

NASA Astrophysics Data System (ADS)

Anenberg, S. C.; Talgo, K.; Arunachalam, S.; Dolwick, P.; Jang, C.; West, J. J.

2011-04-01

As a component of fine particulate matter (PM2.5), black carbon (BC) is associated with premature human mortality. BC also affects climate by absorbing solar radiation and reducing planetary albedo. Several studies have examined the climate impacts of BC emissions, but the associated health impacts have been studied less extensively. Here, we examine the surface PM2.5 and premature mortality impacts of halving anthropogenic BC emissions globally, from eight world regions, and from three major economic sectors. We use a global chemical transport model, MOZART-4, to simulate PM2.5 concentrations and a health impact function to calculate premature cardiopulmonary and lung cancer deaths. We estimate that halving global anthropogenic BC emissions reduces outdoor population-weighted average PM2.5 by 542 ng m-3 (1.8%) and avoids 157 000 (95% confidence interval, 120 000-194 000) annual premature deaths globally, with the vast majority occurring within the source region. While most of these avoided deaths can be achieved by halving East Asian emissions (54%), followed by South Asian emissions (31%), South Asian emissions have 50% greater mortality impacts per unit BC emitted than East Asian emissions. Globally, the contribution of residential, industrial, and transportation BC emissions to PM2.5-related mortality is 1.3, 1.2, and 0.6 times each sector's contribution to anthropogenic BC emissions, owing to the degree of co-location with population. Impacts of residential BC emissions are underestimated since indoor PM2.5 exposure is excluded. We estimate ~8 times more avoided deaths when BC and organic carbon (OC) emissions are halved together, suggesting that these results greatly underestimate the full air pollution-related mortality benefits of BC mitigation strategies which generally decrease both BC and OC. Confidence in our results would be strengthened by reducing uncertainties in emissions, model parameterization of aerosol processes, grid resolution, and PM2.5 concentration-mortality relationships globally.

User's manual for The TIM benefit-cost (TIM-BC) Tool (Version: 1.0.0)

DOT National Transportation Integrated Search

2015-07-04

This document serves as a users manual for the Traffic Incident Management Benefit-Cost Tool (TIM-BC) Version 1.0.0 - Safety Service Patrol Benefit-Cost (SSP-BC) Tool, which is used to assist State and local engineers and decisionmakers with evalu...

Molecular subtyping of bladder cancer using Kohonen self-organizing maps

PubMed Central

Borkowska, Edyta M; Kruk, Andrzej; Jedrzejczyk, Adam; Rozniecki, Marek; Jablonowski, Zbigniew; Traczyk, Magdalena; Constantinou, Maria; Banaszkiewicz, Monika; Pietrusinski, Michal; Sosnowski, Marek; Hamdy, Freddie C; Peter, Stefan; Catto, James WF; Kaluzewski, Bogdan

2014-01-01

Kohonen self-organizing maps (SOMs) are unsupervised Artificial Neural Networks (ANNs) that are good for low-density data visualization. They easily deal with complex and nonlinear relationships between variables. We evaluated molecular events that characterize high- and low-grade BC pathways in the tumors from 104 patients. We compared the ability of statistical clustering with a SOM to stratify tumors according to the risk of progression to more advanced disease. In univariable analysis, tumor stage (log rank P = 0.006) and grade (P < 0.001), HPV DNA (P < 0.004), Chromosome 9 loss (P = 0.04) and the A148T polymorphism (rs 3731249) in CDKN2A (P = 0.02) were associated with progression. Multivariable analysis of these parameters identified that tumor grade (Cox regression, P = 0.001, OR.2.9 (95% CI 1.6–5.2)) and the presence of HPV DNA (P = 0.017, OR 3.8 (95% CI 1.3–11.4)) were the only independent predictors of progression. Unsupervised hierarchical clustering grouped the tumors into discreet branches but did not stratify according to progression free survival (log rank P = 0.39). These genetic variables were presented to SOM input neurons. SOMs are suitable for complex data integration, allow easy visualization of outcomes, and may stratify BC progression more robustly than hierarchical clustering. PMID:25142434

Metallosupramolecular Architectures Formed with Ferrocene-Linked Bis-Bidentate Ligands: Synthesis, Structures, and Electrochemical Studies.

PubMed

Findlay, James A; McAdam, C John; Sutton, Joshua J; Preston, Dan; Gordon, Keith C; Crowley, James D

2018-04-02

The self-assembly of ligands of different geometries with metal ions gives rise to metallosupramolecular architectures of differing structural types. The rotational flexibility of ferrocene allows for conformational diversity, and, as such, self-assembly processes with 1,1'-disubstituted ferrocene ligands could lead to a variety of interesting architectures. Herein, we report a small family of three bis-bidentate 1,1'-disubstituted ferrocene ligands, functionalized with either 2,2'-bipyridine or 2-pyridyl-1,2,3-triazole chelating units. The self-assembly of these ligands with the (usually) four-coordinate, diamagnetic metal ions Cu(I), Ag(I), and Pd(II) was examined using a range of techniques including 1 H and DOSY NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, X-ray crystallography, and density functional theory calculations. Additionally, the electrochemical properties of these redox-active metallosupramolecular assemblies were examined using cyclic voltammetry and differential pulse voltammetry. The copper(I) complexes of the 1,1'-disubstituted ferrocene ligands were found to be coordination polymers, while the silver(I) and palladium(II) complexes formed discrete [1 + 1] or [2 + 2] metallomacrocyclic architectures.

Streptococcus mutans Protein Synthesis during Mixed-Species Biofilm Development by High-Throughput Quantitative Proteomics

PubMed Central

Klein, Marlise I.; Xiao, Jin; Lu, Bingwen; Delahunty, Claire M.; Yates, John R.; Koo, Hyun

2012-01-01

Biofilms formed on tooth surfaces are comprised of mixed microbiota enmeshed in an extracellular matrix. Oral biofilms are constantly exposed to environmental changes, which influence the microbial composition, matrix formation and expression of virulence. Streptococcus mutans and sucrose are key modulators associated with the evolution of virulent-cariogenic biofilms. In this study, we used a high-throughput quantitative proteomics approach to examine how S. mutans produces relevant proteins that facilitate its establishment and optimal survival during mixed-species biofilms development induced by sucrose. Biofilms of S. mutans, alone or mixed with Actinomyces naeslundii and Streptococcus oralis, were initially formed onto saliva-coated hydroxyapatite surface under carbohydrate-limiting condition. Sucrose (1%, w/v) was then introduced to cause environmental changes, and to induce biofilm accumulation. Multidimensional protein identification technology (MudPIT) approach detected up to 60% of proteins encoded by S. mutans within biofilms. Specific proteins associated with exopolysaccharide matrix assembly, metabolic and stress adaptation processes were highly abundant as the biofilm transit from earlier to later developmental stages following sucrose introduction. Our results indicate that S. mutans within a mixed-species biofilm community increases the expression of specific genes associated with glucan synthesis and remodeling (gtfBC, dexA) and glucan-binding (gbpB) during this transition (P<0.05). Furthermore, S. mutans up-regulates specific adaptation mechanisms to cope with acidic environments (F1F0-ATPase system, fatty acid biosynthesis, branched chain amino acids metabolism), and molecular chaperones (GroEL). Interestingly, the protein levels and gene expression are in general augmented when S. mutans form mixed-species biofilms (vs. single-species biofilms) demonstrating fundamental differences in the matrix assembly, survival and biofilm maintenance in the presence of other organisms. Our data provide insights about how S. mutans optimizes its metabolism and adapts/survives within the mixed-species community in response to a dynamically changing environment. This reflects the intricate physiological processes linked to expression of virulence by this bacterium within complex biofilms. PMID:23049864

Simulation of black carbon aerosol distribution over India: A sensitivity study to different convective schemes

NASA Astrophysics Data System (ADS)

Ghosh, Sudipta; Dey, Sagnik; Das, Sushant; Venkataraman, Chandra; Patil, Nitin U.

2017-04-01

Black carbon (BC) aerosols absorb solar radiation, thereby causing a warming at the top-of-the-atmosphere (TOA) in contrast to most of the other aerosol species that scatter radiation causing a cooling at TOA. BC is considered to be an important contributor of global warming, second only to CO2 with a net radiative forcing of 1.1 w/m2. They have important regional climate effects, because of their spatially non-uniform heating and cooling. So it is very important to understand the spatio-temporal distribution of BC over India. In this study, we have used a regional climate model RegCM4.5 to simulate BC distribution over India with a focus on the BC estimation. The importance of incorporation of regional emission inventory has been shown and the sensitivity of BC distribution to various convective schemes in the model has been explored. The model output has been validated with in-situ observations. It is quite evident that regional inventory is capturing larger columnar burden of BC and OC than the global inventory. The difference in BC burden is clear at many places with the largest difference (in the order from 2 x 10-11 kg m-2 sec-1 in global inventory to 4 x 10-11 kg m-2 sec-1 in regional inventory) being observed over the Indo-Gangetic Basin. This difference is mainly attributed to the local sources like kerosene lamp burning, residential cooking on solid biomass fuel and agricultural residue burning etc., that are not considered in the global inventory. The difference is also noticeable for OC. Thus BC burden has increased with incorporation of regional emission inventory in the model, suggesting the importance of regional inventory in improved simulation and estimation of aerosols in this region. BC distribution is also sensitive to choice of scheme with Emanuel scheme capturing a comparatively smaller BC burden during the monsoon than Tiedtke scheme. Further long-term simulation with customized model is required to examine impact of BC. Keywords: Black carbon, RegCM4, regional emission inventory, convective schemes.

Higher Atmosphere Heating due to black carbon Over the Northern Part of India

NASA Astrophysics Data System (ADS)

Tiwari, S.; Singh, S., , Dr

2017-12-01

Light-absorbing, atmospheric particles have gained greater attention in recent years because of their direct and indirect impacts on regional and global climate. Atmospheric black carbon (BC) aerosol (also called soot particle) is a leading climate warming agent, yet uncertainties in the global direct aerosol radiative forcing remain large. Based on a year of aerosol absorption measurements at seven wavelengths, BC concentrations were investigated in Dhanbad, the coal capital of India. Coal is routinely burned for cooking and residential heat as well as in small industries. The mean daily concentrations of ultraviolet-absorbing black carbon measured at 370 nm (UVBC) and black carbon measured at 880 nm (BC) were 9.8 ± 5.7 and 6.5 ± 3.8 μg m-3, respectively. The difference between UVBC and BC, Delta-C, is an indicator of biomass or residential coal burning and averaged 3.29 ± 4.61 μg m-3. An alternative approach uses the calculation of the Angstrom Exponent (AE) to estimate the amounts of biomass/coal and traffic BC. Biomass/coal burning contributed 87% and fossil fuel combustion contributed 13% to the annual average BC concentration. In the post-monsoon season, potential source contribution function analysis showed that air masses came from the central and northwestern Indo-Gangetic Plains resulting in mean UVBC values of 10.9 μg m-3 and BC of 7.2 μg m-3. The mean winter UVBC and BC concentrations were 15.0 and 10.1 μg m-3, respectively. These highest values were largely driven by local sources under conditions of poor dispersion. The direct radiative forcing (DRF) due to UVBC and BC at the surface (SFC) and the top of the atmosphere (TOA) were calculated. The mean atmospheric heating rates due to UVBC and BC were estimated to be 1.40°K day-1 and 1.18°K day-1, respectively. This high heating rate may affect the monsoon circulation in this region.

Tethered balloon-born and ground-based measurements of black carbon and particulate profiles within the lower troposphere during the foggy period in Delhi, India.

PubMed

Bisht, D S; Tiwari, S; Dumka, U C; Srivastava, A K; Safai, P D; Ghude, S D; Chate, D M; Rao, P S P; Ali, K; Prabhakaran, T; Panickar, A S; Soni, V K; Attri, S D; Tunved, P; Chakrabarty, R K; Hopke, P K

2016-12-15

The ground and vertical profiles of particulate matter (PM) were mapped as part of a pilot study using a Tethered balloon within the lower troposphere (1000m) during the foggy episodes in the winter season of 2015-16 in New Delhi, India. Measurements of black carbon (BC) aerosol and PM <2.5 and 10μm (PM 2.5 & PM 10 respectively) concentrations and their associated particulate optical properties along with meteorological parameters were made. The mean concentrations of PM 2.5 , PM 10 , BC 370 nm, and BC 880 nm were observed to be 146.8±42.1, 245.4±65.4, 30.3±12.2, and 24.1±10.3μgm -3 , respectively. The mean value of PM 2.5 was ~12 times higher than the annual US-EPA air quality standard. The fraction of BC in PM 2.5 that contributed to absorption in the shorter visible wavelengths (BC 370 nm ) was ~21%. Compared to clear days, the ground level mass concentrations of PM 2.5 and BC 370 nm particles were substantially increased (59% and 24%, respectively) during the foggy episode. The aerosol light extinction coefficient (σ ext ) value was much higher (mean: 610Mm -1 ) during the lower visibility (foggy) condition. Higher concentrations of PM 2.5 (89μgm -3 ) and longer visible wavelength absorbing BC 880 nm (25.7μgm -3 ) particles were observed up to 200m. The BC 880 nm and PM 2.5 aerosol concentrations near boundary layer (1km) were significantly higher (~1.9 and 12μgm -3 ), respectively. The BC (i.e BC tot ) aerosol direct radiative forcing (DRF) values were estimated at the top of the atmosphere (TOA), surface (SFC), and atmosphere (ATM) and its resultant forcing were - 75.5Wm -2 at SFC indicating the cooling effect at the surface. A positive value (20.9Wm -2 ) of BC aerosol DRF at TOA indicated the warming effect at the top of the atmosphere over the study region. The net DRF value due to BC aerosol was positive (96.4Wm -2 ) indicating a net warming effect in the atmosphere. The contribution of fossil and biomass fuels to the observed BC aerosol DRF values was ~78% and ~22%, respectively. The higher mean atmospheric heating rate (2.71Kday -1 ) by BC aerosol in the winter season would probably strengthen the temperature inversion leading to poor dispersion and affecting the formation of clouds. Serious detrimental impacts on regional climate due to the high concentrations of BC and PM (especially PM 2.5 ) aerosol are likely based on this study and suggest the need for immediate, stringent measures to improve the regional air quality in the northern India. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of Trichodysplasia Spinulosa-Associated Polyomavirus Capsid Protein as a New Carrier for Construction of Chimeric Virus-Like Particles Harboring Foreign Epitopes

PubMed Central

Gedvilaite, Alma; Kucinskaite-Kodze, Indre; Lasickiene, Rita; Timinskas, Albertas; Vaitiekaite, Ausra; Ziogiene, Danguole; Zvirbliene, Aurelija

2015-01-01

Recombinant virus-like particles (VLPs) represent a promising tool for protein engineering. Recently, trichodysplasia spinulosa-associated polyomavirus (TSPyV) viral protein 1 (VP1) was efficiently produced in yeast expression system and shown to self-assemble to VLPs. In the current study, TSPyV VP1 protein was exploited as a carrier for construction of chimeric VLPs harboring selected B and T cell-specific epitopes and evaluated in comparison to hamster polyomavirus VP1 protein. Chimeric VLPs with inserted either hepatitis B virus preS1 epitope DPAFR or a universal T cell-specific epitope AKFVAAWTLKAAA were produced in yeast Saccharomyces cerevisiae. Target epitopes were incorporated either at the HI or BC loop of the VP1 protein. The insertion sites were selected based on molecular models of TSPyV VP1 protein. The surface exposure of the insert positions was confirmed using a collection of monoclonal antibodies raised against the intact TSPyV VP1 protein. All generated chimeric proteins were capable to self-assemble to VLPs, which induced a strong immune response in mice. The chimeric VLPs also activated dendritic cells and T cells as demonstrated by analysis of cell surface markers and cytokine production profiles in spleen cell cultures. In conclusion, TSPyV VP1 protein represents a new potential carrier for construction of chimeric VLPs harboring target epitopes. PMID:26230706

Electrical Programming of Soft Matter: Using Temporally Varying Electrical Inputs To Spatially Control Self Assembly.

PubMed

Yan, Kun; Liu, Yi; Zhang, Jitao; Correa, Santiago O; Shang, Wu; Tsai, Cheng-Chieh; Bentley, William E; Shen, Jana; Scarcelli, Giuliano; Raub, Christopher B; Shi, Xiao-Wen; Payne, Gregory F

2018-02-12

The growing importance of hydrogels in translational medicine has stimulated the development of top-down fabrication methods, yet often these methods lack the capabilities to generate the complex matrix architectures observed in biology. Here we show that temporally varying electrical signals can cue a self-assembling polysaccharide to controllably form a hydrogel with complex internal patterns. Evidence from theory and experiment indicate that internal structure emerges through a subtle interplay between the electrical current that triggers self-assembly and the electrical potential (or electric field) that recruits and appears to orient the polysaccharide chains at the growing gel front. These studies demonstrate that short sequences (minutes) of low-power (∼1 V) electrical inputs can provide the program to guide self-assembly that yields hydrogels with stable, complex, and spatially varying structure and properties.

Observation of the decay Bc+/--->J/psipi+/- and measurement of the Bc+/- mass.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Genser, K; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyria, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-05-09

The Bc+/- meson is observed through the decay Bc+/--->J/psipi+/-, in data corresponding to an integrated luminosity of 2.4 fb(-1) recorded by the Collider Detector at Fermilab II detector at the Fermilab Tevatron. A signal of 108+/-15 candidates is observed, with a significance that exceeds 8sigma. The mass of the Bc+/- meson is measured to be 6275.6+/-2.9(stat)+/-2.5(syst) MeV/c2.

RICE ice core: Black Carbon reflects climate variability at Roosevelt Island, West Antarctica

NASA Astrophysics Data System (ADS)

Ellis, Aja; Edwards, Ross; Bertler, Nancy; Winton, Holly; Goodwin, Ian; Neff, Peter; Tuohy, Andrea; Proemse, Bernadette; Hogan, Chad; Feiteng, Wang

2015-04-01

The Roosevelt Island Climate Evolution (RICE) project successfully drilled a deep ice core from Roosevelt Island during the 2011/2012 and 2012/2013 seasons. Located in the Ross Ice Shelf in West Antarctica, the site is an ideal location for investigating climate variability and the past stability of the Ross Ice Shelf. Black carbon (BC) aerosols are emitted by both biomass burning and fossil fuels, and BC particles emitted in the southern hemisphere are transported in the atmosphere and preserved in Antarctic ice. The past record of BC is expected to be sensitive to climate variability, as it is modulated by both emissions and transport. To investigate BC variability over the past 200 years, we developed a BC record from two overlapping ice cores (~1850-2012) and a high-resolution snow pit spanning 2010-2012 (cal. yr). Consistent results are found between the snow pit profiles and ice core records. Distinct decadal trends are found with respect to BC particle size, and the record indicates a steady rise in BC particle size over the last 100 years. Differences in emission sources and conditions may be a possible explanation for changes in BC size. These records also show a significant increase in BC concentration over the past decade with concentrations rising over 1.5 ppb (1.5*10^-9 ng/g), suggesting a fundamental shift in BC deposition to the site.

Quantification of black carbon mixing state from traffic: Implications for aerosol optical properties

DOE PAGES

Willis, Megan D.; Healy, Robert M.; Riemer, Nicole; ...

2016-04-14

The climatic impacts of black carbon (BC) aerosol, an important absorber of solar radiation in the atmosphere, remain poorly constrained and are intimately related to its particle-scale physical and chemical properties. Using particle-resolved modelling informed by quantitative measurements from a soot-particle aerosol mass spectrometer, we confirm that the mixing state (the distribution of co-emitted aerosol amongst fresh BC-containing particles) at the time of emission significantly affects BC-aerosol optical properties even after a day of atmospheric processing. Both single particle and ensemble aerosol mass spectrometry observations indicate that BC near the point of emission co-exists with hydrocarbon-like organic aerosol (HOA) inmore » two distinct particle types: HOA-rich and BC-rich particles. The average mass fraction of black carbon in HOA-rich and BC-rich particle classes was < 0.1 and 0.8, respectively. Notably, approximately 90 % of BC mass resides in BC-rich particles. This new measurement capability provides quantitative insight into the physical and chemical nature of BC-containing particles and is used to drive a particle-resolved aerosol box model. Lastly, significant differences in calculated single scattering albedo (an increase of 0.1) arise from accurate treatment of initial particle mixing state as compared to the assumption of uniform aerosol composition at the point of BC injection into the atmosphere.« less

Size-resolved chemical composition, effective density, and optical properties of biomass burning particles

NASA Astrophysics Data System (ADS)

Zhai, Jinghao; Lu, Xiaohui; Li, Ling; Zhang, Qi; Zhang, Ci; Chen, Hong; Yang, Xin; Chen, Jianmin

2017-06-01

Biomass burning aerosol has an important impact on the global radiative budget. A better understanding of the correlations between the mixing states of biomass burning particles and their optical properties is the goal of a number of current studies. In this work, the effective density, chemical composition, and optical properties of rice straw burning particles in the size range of 50-400 nm were measured using a suite of online methods. We found that the major components of particles produced by burning rice straw included black carbon (BC), organic carbon (OC), and potassium salts, but the mixing states of particles were strongly size dependent. Particles of 50 nm had the smallest effective density (1.16 g cm-3) due to a relatively large proportion of aggregate BC. The average effective densities of 100-400 nm particles ranged from 1.35 to 1.51 g cm-3 with OC and inorganic salts as dominant components. Both density distribution and single-particle mass spectrometry showed more complex mixing states in larger particles. Upon heating, the separation of the effective density distribution modes confirmed the external mixing state of less-volatile BC or soot and potassium salts. The size-resolved optical properties of biomass burning particles were investigated at two wavelengths (λ = 450 and 530 nm). The single-scattering albedo (SSA) showed the lowest value for 50 nm particles (0.741 ± 0.007 and 0.889 ± 0.006) because of the larger proportion of BC content. Brown carbon played an important role for the SSA of 100-400 nm particles. The Ångström absorption exponent (AAE) values for all particles were above 1.6, indicating the significant presence of brown carbon in all sizes. Concurrent measurements in our work provide a basis for discussing the physicochemical properties of biomass burning aerosol and its effects on the global climate and atmospheric environment.

A Glutaredoxin·BolA Complex Serves as an Iron-Sulfur Cluster Chaperone for the Cytosolic Cluster Assembly Machinery*♦

PubMed Central

Frey, Avery G.; Palenchar, Daniel J.; Wildemann, Justin D.; Philpott, Caroline C.

2016-01-01

Cells contain hundreds of proteins that require iron cofactors for activity. Iron cofactors are synthesized in the cell, but the pathways involved in distributing heme, iron-sulfur clusters, and ferrous/ferric ions to apoproteins remain incompletely defined. In particular, cytosolic monothiol glutaredoxins and BolA-like proteins have been identified as [2Fe-2S]-coordinating complexes in vitro and iron-regulatory proteins in fungi, but it is not clear how these proteins function in mammalian systems or how this complex might affect Fe-S proteins or the cytosolic Fe-S assembly machinery. To explore these questions, we use quantitative immunoprecipitation and live cell proximity-dependent biotinylation to monitor interactions between Glrx3, BolA2, and components of the cytosolic iron-sulfur cluster assembly system. We characterize cytosolic Glrx3·BolA2 as a [2Fe-2S] chaperone complex in human cells. Unlike complexes formed by fungal orthologs, human Glrx3-BolA2 interaction required the coordination of Fe-S clusters, whereas Glrx3 homodimer formation did not. Cellular Glrx3·BolA2 complexes increased 6–8-fold in response to increasing iron, forming a rapidly expandable pool of Fe-S clusters. Fe-S coordination by Glrx3·BolA2 did not depend on Ciapin1 or Ciao1, proteins that bind Glrx3 and are involved in cytosolic Fe-S cluster assembly and distribution. Instead, Glrx3 and BolA2 bound and facilitated Fe-S incorporation into Ciapin1, a [2Fe-2S] protein functioning early in the cytosolic Fe-S assembly pathway. Thus, Glrx3·BolA is a [2Fe-2S] chaperone complex capable of transferring [2Fe-2S] clusters to apoproteins in human cells. PMID:27519415

Body Temperatures During Exercise in Deconditioned Dogs: Effect of NACL and Glucose Infusion

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.; Kruk, B.; Nazar, K.; Kaciuba-Usciko, H.

2000-01-01

Infusion of glucose (Glu) into normal exercising dogs attenuates the rise in rectal temperature (Delta-Tre) when compared with delta-Tre during FFA infusion or no infusion. Rates of rise and delta-=Tre levels are higher during exercise after confinement. Therefore, the purpose of this study was to determine if Glu infusion would attenuate the exercise-induced excess hyperthermia after deconditioning. Rectal and quadricep femoris muscle temperatures (Tmu) were measured in 7 male, mongrel dogs dogs (19.6 +/- SD 3.0 kg) during 90 minutes of treadmill exercise (3.1 +/-SD 0.2 W/kg) with infusion (30ml/min/kg) of 40% Glu or 0.9% NaCL before BC) and after confinement (AC) in cages (40 x 110 x 80 cm) for 8 wk. Mean (+/-SE body wt. were 19.6 +/- 1.1 kg BC and 19.5 +/- 1.1kg AC, exercise VO2 were not different (40.0 - 42.0 mi/min/kg-1). With NaCl AC, NaCl BC, GluAC, and GluBC: Delta-Tre were, 1.8, 1.4, 1.3 and 0.9C respectively; and Delta-Tmu were 2.3, 1.9, 1.6, and 1.4C. respectively (P<0.05 from GluBC). Compared with NaCl infusion, attenuated both Delta-Tre and Delta-Tmu BC and AC, respectively. Compared with GluBC, GluAC attenuated Delta-Tmu but not Delta-Tre. Thus. with similar heat production, the mechanism for attenuation at bad body temperature with Glu infusion must affect avenues of heat dissipation.

DsRNA-free transmissible hypovirulence associated with formation of intra-hyphal hyphae in Botrytis cinerea.

PubMed

Cao, Jian Bo; Zhou, Yu; Zhang, Lei; Zhang, Jing; Yang, Long; Qin, Li Hong; Jiang, Dao Hong; Li, Guo Qing; Huang, Hung-Chang

2011-07-01

A spontaneous mutant CanBc-3HV and its parental strain CanBc-3 of Botrytis cinerea were investigated in terms of pathogenicity, colony morphology, hypovirulence transmissibility, presence of double-stranded RNA (dsRNA), and formation of intra-hyphal hyphae (IH). Results showed that inoculation of CanBc-3HV on detached leaves of Brassica napus did not produce any visible necrotic lesions (20°C, 72h), whereas inoculation of CanBc-3 caused necrotic leaf lesions. Compared to CanBc-3, CanBc-3HV grew slowly, formed numerous mycelial sectors, sporulated sporadically and failed to produce sclerotia on potato dextrose agar (PDA) (20°C, 15d). Hypovirulence and the abnormal cultural characteristics of CanBc-3HV were transmissible from CanBc-3HV to CanBc-3 in pair cultures on PDA. However, the transmission was unsuccessful from CanBc-3HV to another virulent strain CanBc-2 of B. cinerea. These results suggest that transmission of the hypovirulence and the abnormal cultural characteristics of CanBc-3HV are strain-specific. No dsRNA was detected in mycelia of either CanBc-3HV or CanBc-3, implying that the hypovirulence of CanBc-3HV is caused by a transmissible element (TE) of non-RNA mycoviral origin. Formation of IH through self-infection was observed in CanBc-3HV, CanBc-3T1 (a hypovirulent derivative of CanBc-3 trans-infected by TE in CanBc-3HV), but was not observed in CanBc-3, suggesting that IH formation is associated with the hypovirulence of CanBc-3HV. To our knowledge, this is the first report of dsRNA-free transmissible hypovirulence associated with IH formation in B. cinerea. Copyright © 2011 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Atmospheric heating due to black carbon aerosol during the summer monsoon period over Ballia: A rural environment over Indo-Gangetic Plain

NASA Astrophysics Data System (ADS)

Tiwari, S.; Dumka, U. C.; Hopke, P. K.; Tunved, P.; Srivastava, A. K.; Bisht, D. S.; Chakrabarty, R. K.

2016-09-01

Black carbon (BC) aerosols are one of the most uncertain drivers of global climate change. The prevailing view is that BC mass concentrations are low in rural areas where industrialization and vehicular emissions are at a minimum. As part of a national research program called the "Ganga Basin Ground Based Experiment-2014 under the Cloud Aerosol Interaction and Precipitation Enhancement Experiment (CAIPEEX) Phase-III" of Ministry of Earth Sciences, Government of India, the continuous measurements of BC and particulate matter (PM) mass concentrations, were conducted in a rural environment in the highly-polluted Indo-Gangetic Plain region during 16th June to 15th August (monsoon period), 2014. The mean mass concentration of BC was 4.03 (± 0.85) μg m- 3 with a daily variability between 2.4 and 5.64 μg m- 3, however, the mean mass PM concentrations [near ultrafine (PM1.0), fine (PM2.5) and inhalable (PM10)] were 29.1(± 16.2), 34.7 (± 19.9) and 43.7 (± 28.3) μg m- 3, respectively. The contribution of BC in PM1.0 was approximately 13%, which is one of the highest being recorded. Diurnally, the BC mass concentrations were highest (mean: 5.89 μg m- 3) between 20:00 to 22:00 local time (LT) due to the burning of biofuels/biomass such as wood, dung, straw and crop residue mixed with dung by the local residents for cooking purposes. The atmospheric direct radiative forcing values due to the composite and BC aerosols were determined to be + 78.3, + 44.9, and + 45.0 W m- 2 and + 42.2, + 35.4 and + 34.3 W m- 2 during the months of June, July and August, respectively. The corresponding atmospheric heating rates (AHR) for composite and BC aerosols were 2.21, 1.26 and 1.26; and 1.19, 0.99 and 0.96 K day- 1 for the month of June, July and August, respectively, with a mean of 1.57 and 1.05 K day- 1 which was 33% lower AHR (BC) than for the composite particles during the study period. This high AHR underscores the importance of absorbing aerosols such as BC contributed by residential cooking using biofuels in India. Our study demonstrates the need for immediate, effective regulations and policies that mitigate the emission of BC particles from domestic cooking in rural areas of India.

The Q-cycle reviewed: How well does a monomeric mechanism of the bc(1) complex account for the function of a dimeric complex?

PubMed

Crofts, Antony R; Holland, J Todd; Victoria, Doreen; Kolling, Derrick R J; Dikanov, Sergei A; Gilbreth, Ryan; Lhee, Sangmoon; Kuras, Richard; Kuras, Mariana Guergova

2008-01-01

Recent progress in understanding the Q-cycle mechanism of the bc(1) complex is reviewed. The data strongly support a mechanism in which the Q(o)-site operates through a reaction in which the first electron transfer from ubiquinol to the oxidized iron-sulfur protein is the rate-determining step for the overall process. The reaction involves a proton-coupled electron transfer down a hydrogen bond between the ubiquinol and a histidine ligand of the [2Fe-2S] cluster, in which the unfavorable protonic configuration contributes a substantial part of the activation barrier. The reaction is endergonic, and the products are an unstable ubisemiquinone at the Q(o)-site, and the reduced iron-sulfur protein, the extrinsic mobile domain of which is now free to dissociate and move away from the site to deliver an electron to cyt c(1) and liberate the H(+). When oxidation of the semiquinone is prevented, it participates in bypass reactions, including superoxide generation if O(2) is available. When the b-heme chain is available as an acceptor, the semiquinone is oxidized in a process in which the proton is passed to the glutamate of the conserved -PEWY- sequence, and the semiquinone anion passes its electron to heme b(L) to form the product ubiquinone. The rate is rapid compared to the limiting reaction, and would require movement of the semiquinone closer to heme b(L) to enhance the rate constant. The acceptor reactions at the Q(i)-site are still controversial, but likely involve a "two-electron gate" in which a stable semiquinone stores an electron. Possible mechanisms to explain the cyt b(150) phenomenon are discussed, and the information from pulsed-EPR studies about the structure of the intermediate state is reviewed. The mechanism discussed is applicable to a monomeric bc(1) complex. We discuss evidence in the literature that has been interpreted as shown that the dimeric structure participates in a more complicated mechanism involving electron transfer across the dimer interface. We show from myxothiazol titrations and mutational analysis of Tyr-199, which is at the interface between monomers, that no such inter-monomer electron transfer is detected at the level of the b(L) hemes. We show from analysis of strains with mutations at Asn-221 that there are coulombic interactions between the b-hemes in a monomer. The data can also be interpreted as showing similar coulombic interaction across the dimer interface, and we discuss mechanistic implications.

Genetic Control of L-a and L-(Bc) Dsrna Copy Number in Killer Systems of SACCHAROMYCES CEREVISIAE

PubMed Central

Ball, Steven G.; Tirtiaux, Catherine; Wickner, Reed B.

1984-01-01

M dsRNA in yeast encodes a toxin precursor and immunity protein, whereas L-A dsRNA encodes the 81,000-dalton major protein of the intracellular particles in which both L-A and M are found. L-(BC) dsRNA(s) are found in particles with different coat proteins. We find that M dsRNA lowers the copy number of L-A, but not L-(BC). The SKI gene products lower the copy number of L-(BC), L-A, M1 and M2. This is the first known interaction of L-(BC) with any element of the killer systems. The MAK3, MAK10 and PET18 gene products are necessary for L-A maintenance and replication, but mutations in these genes do not affect L-(BC) copy number. Mutations in MAK1, MAK4, MAK7, MAK17 and MAK24 do not detectably affect copy number of L-(BC) or L-A. PMID:17246214

Akt phosphorylates Prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells

PubMed Central

Jiang, L; Dong, P; Zhang, Z; Li, C; Li, Y; Liao, Y; Li, X; Wu, Z; Guo, S; Mai, S; Xie, D; Liu, Z; Zhou, F

2015-01-01

Bladder cancer (BC) is very common and associated with significant morbidity and mortality, though the molecular underpinnings of its origination and progression remain poorly understood. In this study, we demonstrate that Prohibitin 1 (PHB) was overexpressed in human BC tissues and that PHB upregulation was associated with poor prognosis. We also found that PHB was necessary and sufficient for BC cell proliferation. Interestingly, the overexpressed PHB was primarily found within mitochondria, and we provide the first direct evidence that phosphorylation by Akt at Thr258 of PHB induces this mitochondrial localization. Inhibiton of Akt reverses these effects and inhibited the proliferation of BC cells. Finally, the phosphorylation of PHB was required for BC cell proliferation, further implicating the importance of the Akt in BC. Taken together, these findings identify the Akt/PHB signaling cascade as a novel mechanism of cancer cell proliferation and provide the scientific basis for the establishment of PHB as a new prognostic marker and treatment target for BC. PMID:25719244

Long non-coding RNA BRAF-regulated lncRNA 1 promotes lymph node invasion, metastasis and proliferation, and predicts poor prognosis in breast cancer.

PubMed

Jiang, Jing; Shi, Sheng-Hong; Li, Xu-Jun; Sun, Long; Ge, Qi-Dong; Li, Chao; Zhang, Wei

2018-06-01

Long non-coding RNAs (lncRNAs) are primary regulators of cancer development via their involvement in almost every aspect of cell biology. Recent studies have indicated that lncRNAs serve pivotal roles in breast cancer (BC) progression; however, to the best of our knowledge, the role of the lncRNA BRAF-regulated lncRNA 1 (BANCR) in BC has not yet been elucidated. The present study revealed that BANCR was overexpressed in BC cell lines and tissues, and could promote the clinical progression of disease, including increases in tumor size, lymph node metastasis and Tumor-Node-Metastasis stage. Furthermore, high BANCR expression was demonstrated to be associated with poor overall survival rates and early recurrence of BC in patients. Additionally, univariate and multivariate COX regression analyses identified high BANCR expression as an independent risk factor of poor prognosis of patients with BC. In addition, to verify the function of BANCR in BC cell lines, BANCR expression was silenced using short hairpin RNAs in MDA-MB-231 cells and overexpressed in MDA-MB-468 cells. An MTT assay and colony formation assay indicated that BANCR knockdown could suppress the proliferation of BC cells, whereas BANCR upregulation induced the proliferation of BC cells. Furthermore, BANCR silencing also reduced the migration and invasion of BC cells, as demonstrated via transwell migration and invasion assays. Consistently, the migration and invasion of BC cells increased upon BANCR ectopic overexpression in MDA-MB-468 cells. Mechanistically, matrix metallopeptidase 2/9 and epithelial-mesenchymal transition markers may be the potential targets of BANCR in regulating BC metastasis. In conclusion, BANCR overexpression could promote the clinical progression, metastasis and proliferation of BC and indicate poor prognosis of patients with BC. BANCR may therefore be a potential prognostic marker and therapeutic target of patients with BC.

The physicochemical stability and in vitro bioaccessibility of beta-carotene in oil-in- water sodium caseinate emulsions

USDA-ARS?s Scientific Manuscript database

Beta-carotene (BC), the most important dietary source of provitamin A, is necessary for optimum human health. BC is insoluble or only slightly soluble in most liquids but its bioavailability improves when ingested with fat. Therefore lipid emulsions are ideal matrices for BC delivery. BC (0.1%) in ...

Black carbon surface oxidation and organic composition of beech-wood soot aerosols

NASA Astrophysics Data System (ADS)

Corbin, J. C.; Lohmann, U.; Sierau, B.; Keller, A.; Burtscher, H.; Mensah, A. A.

2015-10-01

Soot particles are the most strongly light-absorbing particles commonly found in the atmosphere. They are major contributors to the radiative budget of the Earth and to the toxicity of atmospheric pollution. Atmospheric aging of soot may change its health- and climate-relevant properties by oxidizing the primary black carbon (BC) or organic particulate matter (OM) which, together with ash, comprise soot. This atmospheric aging, which entails the condensation of secondary particulate matter as well as the oxidation of the primary OM and BC emissions, is currently poorly understood. In this study, atmospheric aging of wood-stove soot aerosols was simulated in a continuous-flow reactor. The composition of fresh and aged soot particles was measured in real time by a dual-vaporizer aerosol-particle mass spectrometer (SP-AMS). The dual-vaporizer SP-AMS provided information on the OM and BC components of the soot as well as on refractory components internally mixed with BC. By switching the SP-AMS laser vaporizer off and using only the AMS thermal vaporizer (at 600 °C), information on the OM component only was obtained. In both modes, OM appeared to be generated largely by cellulose and/or hemicellulose pyrolysis and was only present in large amounts when new wood was added to the stove. In SP-AMS mode, BC signals otherwise dominated the mass spectrum. These signals consisted of ions related to refractory BC (rBC, C1-5+), oxygenated carbonaceous ions (CO1-2+), potassium (K+), and water (H2O+ and related fragments). The C4+ : C3+ ratio, but not the C1+ : C3+ ratio, was consistent with the BC-structure trends of Corbin et al. (2015c). The CO1-2+ signals likely originated from BC surface groups: upon aging, both CO+ and CO2+ increased relative to C1-3+ while CO2+ simultaneously increased relative to CO+. Factor analysis (positive matrix factorization) of SP-AMS and AMS data, using a modified error model to address peak-integration uncertainties, indicated that the surface composition of the BC was approximately constant across all stages of combustion for both fresh and aged samples. These results represent the first time-resolved measurements of in situ BC surface aging and suggest that the surface of beech-wood BC may be modelled as a single chemical species.

Structural and functional insight into TAF1-TAF7, a subcomplex of transcription factor II D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, Suparna; Lou, Xiaohua; Hwang, Peter

2014-07-01

Transcription factor II D (TFIID) is a multiprotein complex that nucleates formation of the basal transcription machinery. TATA binding protein-associated factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the regulation of eukaryotic transcription initiation and play key roles in preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a dissociable inhibitor of TAF1 histone acetyltransferase activity and that this event ensures appropriate assembly of the RNA polymerase II-mediated PIC before transcriptional initiation. Here, we report the 3D structure of a complex of yeast TAF1 with TAF7 at 2.9 Å resolution. The structuremore » displays novel architecture and is characterized by a large predominantly hydrophobic heterodimer interface and extensive cofolding of TAF subunits. There are no obvious similarities between TAF1 and known histone acetyltransferases. Instead, the surface of the TAF1–TAF7 complex contains two prominent conserved surface pockets, one of which binds selectively to an inhibitory trimethylated histone H3 mark on Lys27 in a manner that is also regulated by phosphorylation at the neighboring H3 serine. Our findings could point toward novel roles for the TAF1–TAF7 complex in regulation of PIC assembly via reading epigenetic histone marks.« less

Cycling to work in London and inhaled dose of black carbon.

PubMed

Nwokoro, Chinedu; Ewin, Clare; Harrison, Clare; Ibrahim, Mubin; Dundas, Isobel; Dickson, Iain; Mushtaq, Naseem; Grigg, Jonathan

2012-11-01

Modelling studies suggest that urban cycling is associated with an increased inhaled dose of fossil fuel-derived black carbon (BC). Using the amount of black material in airway macrophages as a marker of long-term inhaled BC, we sought to compare inhaled BC dose in London (UK) cyclists and non-cyclists. Airway macrophage carbon was assessed in 28 (58%) out of 48 healthy adults (14 cyclists and 14 non-cyclists) who attended for induced sputum. Short-term (24 h) exposure to BC was assessed on a representative working day in 27 out of 28 subjects. Serum interleukin (IL)-1β, IL-2, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor and tumour necrosis factor (TNF)-α were assessed in 26 out of the 28 subjects. Cyclists were found to have increased airway macrophage carbon when compared with non-cyclists (mean ± se 1.81 ± 0.21 versus 1.11 ± 0.07 μm(2); p<0.01). Short-term monitoring showed no difference in 24 h BC exposure between the two groups. However, cyclists were exposed to higher concentrations of BC during commuting (p<0.01). Airway macrophage carbon was associated with monitored commute BC (n=28; r=0.47, p<0.05). TNF-α was found to be increased in cyclists (p<0.05), but no other cytokines were increased. Commuting to work by bicycle in London is associated with increased long-term inhaled dose of BC. Whether cycling per se increases inhaled BC dose remains unclear.

Hmo1 directs pre-initiation complex assembly to an appropriate site on its target gene promoters by masking a nucleosome-free region

PubMed Central

Kasahara, Koji; Ohyama, Yoshifumi; Kokubo, Tetsuro

2011-01-01

Saccharomyces cerevisiae Hmo1 binds to the promoters of ∼70% of ribosomal protein genes (RPGs) at high occupancy, but is observed at lower occupancy on the remaining RPG promoters. In Δhmo1 cells, the transcription start site (TSS) of the Hmo1-enriched RPS5 promoter shifted upstream, while the TSS of the Hmo1-limited RPL10 promoter did not shift. Analyses of chimeric RPS5/RPL10 promoters revealed a region between the RPS5 upstream activating sequence (UAS) and core promoter, termed the intervening region (IVR), responsible for strong Hmo1 binding and an upstream TSS shift in Δhmo1 cells. Chromatin immunoprecipitation analyses showed that the RPS5-IVR resides within a nucleosome-free region and that pre-initiation complex (PIC) assembly occurs at a site between the IVR and a nucleosome overlapping the TSS (+1 nucleosome). The PIC assembly site was shifted upstream in Δhmo1 cells on this promoter, indicating that Hmo1 normally masks the RPS5-IVR to prevent PIC assembly at inappropriate site(s). This novel mechanism ensures accurate transcriptional initiation by delineating the 5′- and 3′-boundaries of the PIC assembly zone. PMID:21288884

The PHOTOSYNTHESIS AFFECTED MUTANT68–LIKE Protein Evolved from a PSII Assembly Factor to Mediate Assembly of the Chloroplast NAD(P)H Dehydrogenase Complex in Arabidopsis[W

PubMed Central

Armbruster, Ute; Rühle, Thilo; Kreller, Renate; Strotbek, Christoph; Zühlke, Jessica; Tadini, Luca; Blunder, Thomas; Hertle, Alexander P.; Qi, Yafei; Rengstl, Birgit; Nickelsen, Jörg; Frank, Wolfgang; Leister, Dario

2013-01-01

In vascular plants, the chloroplast NAD(P)H dehydrogenase complex (NDH-C) is assembled from five distinct subcomplexes, the membrane-spanning (subM) and the luminal (subL) subcomplexes, as well as subA, subB, and subE. The assembly process itself is poorly understood. Vascular plant genomes code for two related intrinsic thylakoid proteins, PHOTOSYNTHESIS-AFFECTED MUTANT68 (PAM68), a photosystem II assembly factor, and PHOTOSYNTHESIS-AFFECTED MUTANT68-LIKE (PAM68L). As we show here, inactivation of Arabidopsis thaliana PAM68L in the pam68l-1 mutant identifies PAM68L as an NDH-C assembly factor. The mutant lacks functional NDH holocomplexes and accumulates three distinct NDH-C assembly intermediates (subB, subM, and subA+L), which are also found in mutants defective in subB assembly (ndf5) or subM expression (CHLORORESPIRATORY REDUCTION4-3 mutant). NDH-C assembly in the cyanobacterium Synechocystis sp PCC 6803 and the moss Physcomitrella patens does not require PAM68 proteins, as demonstrated by the analysis of knockout lines for the single-copy PAM68 genes in these species. We conclude that PAM68L mediates the attachment of subB- and subM-containing intermediates to a complex that contains subA and subL. The evolutionary appearance of subL and PAM68L during the transition from mosses like P. patens to flowering plants suggests that the associated increase in the complexity of the NDH-C might have been facilitated by the recruitment of evolutionarily novel assembly factors like PAM68L. PMID:24096342

Enhancement of chromate reduction in soils by surface modified biochar.

PubMed

Mandal, Sanchita; Sarkar, Binoy; Bolan, Nanthi; Ok, Yong Sik; Naidu, Ravi

2017-01-15

Chromium (Cr) is one of the common metals present in the soils and may have an extremely deleterious environmental impact depending on its redox state. Among two common forms, trivalent Cr(III) is less toxic than hexavalent Cr(VI) in soils. Carbon (C) based materials including biochar could be used to alleviate Cr toxicity through converting Cr(VI) to Cr(III). Incubation experiments were conducted to examine Cr(VI) reduction in different soils (Soil 1: pH 7.5 and Soil 2: pH 5.5) with three manures from poultry (PM), cow (CM) and sheep (SM), three respective manure-derived biochars (PM biochar (PM-BC), CM biochar (CM-BC) and SM biochar (SM-BC)) and two modified biochars (modified PM-BC (PM-BC-M) and modified SM-BC (SM-BC-M)). Modified biochar was synthesized by incorporating chitosan and zerovalent iron (ZVI) during pyrolysis. Among biochars, highest Cr(VI) reduction was observed with PM-BC application (5%; w/w) (up to 88.12 mg kg -1 ; 45% reduction) in Soil 2 (pH 5.5). The modified biochars enhanced Cr(VI) reduction by 55% (SM-BC-M) compared to manure (29%, SM) and manure-derived biochars (40% reduction, SM-BC). Among the modified biochars, SM-BC-M showed a higher Cr(VI) reduction rate (55%) than PM-BC-M (48%) in Soil 2. Various oxygen-containing surface functional groups such as phenolic, carboxyl, carbonyl, etc. on biochar surface might act as a proton donor for Cr(VI) reduction and subsequent Cr(III) adsorption. This study underpins the immense potential of modified biochar in remediation of Cr(VI) contaminated soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Uptake of exogenous coenzyme Q and transport to mitochondria is required for bc1 complex stability in yeast coq mutants.

PubMed

Santos-Ocaña, Carlos; Do, Thai Q; Padilla, Sergio; Navas, Placido; Clarke, Catherine F

2002-03-29

Coenzyme Q (Q) is an essential component of the mitochondrial respiratory chain in eukaryotic cells but also is present in other cellular membranes where it acts as an antioxidant. Because Q synthesis machinery in Saccharomyces cerevisiae is located in the mitochondria, the intracellular distribution of Q indicates the existence of intracellular Q transport. In this study, the uptake of exogenous Q(6) by yeast and its transport from the plasma membrane to mitochondria was assessed in both wild-type and in Q-less coq7 mutants derived from four distinct laboratory yeast strains. Q(6) supplementation of medium containing ethanol, a non-fermentable carbon source, rescued growth in only two of the four coq7 mutant strains. Following culture in medium containing dextrose, the added Q(6) was detected in the plasma membrane of each of four coq7 mutants tested. This detection of Q(6) in the plasma membrane was corroborated by measuring ascorbate stabilization activity, as catalyzed by NADH-ascorbate free radical reductase, a transmembrane redox activity that provides a functional assay of plasma membrane Q(6). These assays indicate that each of the four coq7 mutant strains assimilate exogenous Q(6) into the plasma membrane. The two coq7 mutant strains rescued by Q(6) supplementation for growth on ethanol contained mitochondrial Q(6) levels similar to wild type. However, the content of Q(6) in mitochondria from the non-rescued strains was only 35 and 8%, respectively, of that present in the corresponding wild-type parental strains. In yeast strains rescued by exogenous Q(6), succinate-cytochrome c reductase activity was partially restored, whereas non-rescued strains contained very low levels of activity. There was a strong correlation between mitochondrial Q(6) content, succinate-cytochrome c reductase activity, and steady state levels of the cytochrome c(1) polypeptide. These studies show that transport of extracellular Q(6) to the mitochondria operates in yeast but is strain-dependent. When Q biosynthesis is disrupted in yeast strains with defects in the intracellular transport of exogenous Q, the bc(1) complex is unstable. These results indicate that delivery of exogenous Q(6) to mitochondria is required fore activity and stability of the bc(1) complex in yeast coq mutants.

Radiative absorption enhancement from coatings on black carbon aerosols.

PubMed

Cui, Xinjuan; Wang, Xinfeng; Yang, Lingxiao; Chen, Bing; Chen, Jianmin; Andersson, August; Gustafsson, Örjan

2016-05-01

The radiative absorption enhancement of ambient black carbon (BC), by light-refractive coatings of atmospheric aerosols, constitutes a large uncertainty in estimates of climate forcing. The direct measurements of radiative absorption enhancement require the experimentally-removing the coating materials in ambient BC-containing aerosols, which remains a challenge. Here, the absorption enhancement of the BC core by non-absorbing aerosol coatings was quantified using a two-step removal of both inorganic and organic matter coatings of ambient aerosols. The mass absorption cross-section (MAC) of decoated/pure atmospheric BC aerosols of 4.4±0.8m(2)g(-1) was enhanced to 9.6±1.8m(2)g(-1) at 678-nm wavelength for ambiently-coated BC aerosols at a rural Northern China site. The enhancement of MAC (EMAC) rises from 1.4±0.3 in fresh combustion emissions to ~3 for aged ambient China aerosols. The three-week high-intensity campaign observed an average EMAC of 2.25±0.55, and sulfates were primary drivers of the enhanced BC absorption. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Pseudoalteromonas sp. BC228 on digestive enzyme activity and immune response of juvenile sea cucumber ( Apostichopus japonicus)

NASA Astrophysics Data System (ADS)

Ma, Yuexin; Sun, Feixue; Zhang, Congyao; Bao, Pengyun; Cao, Shuqing; Zhang, Meiyan

2014-12-01

A marine bacterium, Pseudoalteromonas sp. BC228 was supplemented to feed in a feeding experiment aiming to determine its ability of enhancing the digestive enzyme activity and immune response of juvenile Apostichopus japonicus. Sea cucumber individuals were fed with the diets containing 0 (control), 105, 107 and 109 CFU g-1 diet of BC228 for 45 days. Results showed that intestinal trypsin and lipase activities were significantly enhanced by 107 and 109 CFU g-1 diet of BC228 in comparison with control ( P < 0.01). The phagocytic activity in the coelomocytes of sea cucumber fed the diet supplemented with 107 CFU g-1 diet of BC228 was significantly higher than that of those fed control diet ( P < 0.05). In addition, 105 and 107 CFU g-1 diet of BC228 significantly enhanced lysozyme and phenoloxidase activities in the coelomic fluid of sea cucumber, respectively, in comparison with other diets ( P < 0.01). Sea cucumbers, 10 each diet, were challenged with Vibrio splendidus NB13 after 45 days of feeding. It was found that the cumulative incidence and mortality of sea cucumber fed with BC228 containing diets were lower than those of animals fed control diet. Our findings evidenced that BC228 supplemented in diets improved the digestive enzyme activity of juvenile sea cucumber, stimulated its immune response and enhanced its resistance to the infection of V. splendidus.

Population-based home care services in breast cancer: utilization and costs

PubMed Central

Mittmann, N.; Isogai, P.K.; Saskin, R.; Liu, N.; Porter, J.M.; Cheung, M.C.; Leighl, N.B.; Hoch, J.S.; Trudeau, M.E.; Evans, W.K.; Dainty, K.N.; Earle, C.C.

2012-01-01

Objective To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc). Methods Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005–2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis. Results Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient–year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient–year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased. Interpretation Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population. PMID:23300362

Bacillus coagulans GBI-30, 6086 increases plant protein digestion in a dynamic, computer-controlled in vitro model of the small intestine (TIM-1).

PubMed

Keller, D; Van Dinter, R; Cash, H; Farmer, S; Venema, K

2017-05-30

The aim of this study was to assess the potential of the probiotic Bacillus coagulans GBI-30, 6086 [GanedenBC 30 ] (BC30) to aid in protein digestion of alimentary plant proteins. To test this, three plant proteins, from pea, soy and rice, were digested in a validated in vitro model of the stomach and small intestine (TIM-1) in the absence and in the presence of BC30. Samples were taken from the TIM-1 fractions that mimic uptake of amino acids by the host and analysed for α-amino nitrogen (AAN) and total nitrogen (TN). Both were increased by BC30 for all three plant proteins sources. The ratio of TN/AAN indicated that for pea protein digestion was increased by BC30, but the degree of polymerisation of the liberated small peptides and free amino acids was not changed. For soy and rice, however, BC30 showed a 2-fold reduction in the TN/AAN ratio, indicating that the liberated digestion products formed during digestion in the presence of BC30 were shorter peptides and more free amino acids, than those liberated in the absence of BC30. As BC30 increased protein digestion and uptake in the upper gastrointestinal (GI) tract, it consequently also reduced the amount of protein that would be delivered to the colon, which could there be fermented into toxic metabolites by the gut microbiota. Thus, the enhanced protein digestion by BC30 showed a dual benefit: enhanced amino acid bioavailability from plant proteins in the upper GI tract, and a healthier environment in the colon.

Impact of Grain Shape and Multiple Black Carbon Internal Mixing on Snow Albedo: Parameterization and Radiative Effect Analysis

NASA Astrophysics Data System (ADS)

He, Cenlin; Liou, Kuo-Nan; Takano, Yoshi; Yang, Ping; Qi, Ling; Chen, Fei

2018-01-01

We quantify the effects of grain shape and multiple black carbon (BC)-snow internal mixing on snow albedo by explicitly resolving shape and mixing structures. Nonspherical snow grains tend to have higher albedos than spheres with the same effective sizes, while the albedo difference due to shape effects increases with grain size, with up to 0.013 and 0.055 for effective radii of 1,000 μm at visible and near-infrared bands, respectively. BC-snow internal mixing reduces snow albedo at wavelengths < 1.5 μm, with negligible effects at longer wavelengths. Nonspherical snow grains show less BC-induced albedo reductions than spheres with the same effective sizes by up to 0.06 at ultraviolet and visible bands. Compared with external mixing, internal mixing enhances snow albedo reduction by a factor of 1.2-2.0 at visible wavelengths depending on BC concentration and snow shape. The opposite effects on albedo reductions due to snow grain nonsphericity and BC-snow internal mixing point toward a careful investigation of these two factors simultaneously in climate modeling. We further develop parameterizations for snow albedo and its reduction by accounting for grain shape and BC-snow internal/external mixing. Combining the parameterizations with BC-in-snow measurements in China, North America, and the Arctic, we estimate that nonspherical snow grains reduce BC-induced albedo radiative effects by up to 50% compared with spherical grains. Moreover, BC-snow internal mixing enhances the albedo effects by up to 30% (130%) for spherical (nonspherical) grains relative to external mixing. The overall uncertainty induced by snow shape and BC-snow mixing state is about 21-32%.

PHOTOSYNTHETIC PIGMENT AND GENETIC DIFFERENCES BETWEEN TWO SOUTHERN OCEAN MORPHOTYPES OF EMILIANIA HUXLEYI (HAPTOPHYTA)1.

PubMed

Cook, Suellen S; Whittock, Lucy; Wright, Simon W; Hallegraeff, Gustaaf M

2011-06-01

The widespread coccolithophorid Emiliania huxleyi (Lohmann) W. W. Hay et H. Mohler plays a pivotal role in the carbon pump and is known to exhibit significant morphological, genetic, and physiological diversity. In this study, we compared photosynthetic pigments and morphology of triplicate strains of Southern Ocean types A and B/C. The two morphotypes differed in width of coccolith distal shield elements (0.11-0.24 μm, type A; 0.06-0.12 μm, type B/C) and morphology of distal shield central area (grill of curved rods in type A; thin plain plate in type B/C) and showed differences in carotenoid composition. The mean 19'-hexanoyloxyfucoxanthin (Hex):chl a ratio in type B/C was >1, whereas the type A ratio was <1. The Hex:fucoxanthin (fuc) ratio for type B/C was 11 times greater than that for type A, and the proportion of fuc in type A was 6 times higher than that in type B/C. The fuc derivative 4-keto-19'-hexanoyloxyfucoxanthin (4-keto-hex) was present in type A but undetected in B/C. DNA sequencing of tufA distinguished morphotypes A, B/C (indistinguishable from B), and R, while little variation was observed within morphotypes. Thirty single nucleotide polymorphisms were identified in the 710 bp tufA sequence, of which 10 alleles were unique to B/C and B morphotypes, seven alleles were unique to type A, and six alleles were unique to type R. We propose that the morphologically, physiologically, and genetically distinct Southern Ocean type B/C sensu Young et al. (2003) be classified as E. huxleyi var. aurorae var. nov. S. S. Cook et Hallegr. © 2011 Phycological Society of America.

Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formation.

PubMed

Fogel, Adam I; Stagi, Massimiliano; Perez de Arce, Karen; Biederer, Thomas

2011-09-16

Synapses are specialized adhesion sites between neurons that are connected by protein complexes spanning the synaptic cleft. These trans-synaptic interactions can organize synapse formation, but their macromolecular properties and effects on synaptic morphology remain incompletely understood. Here, we demonstrate that the synaptic cell adhesion molecule SynCAM 1 self-assembles laterally via its extracellular, membrane-proximal immunoglobulin (Ig) domains 2 and 3. This cis oligomerization generates SynCAM oligomers with increased adhesive capacity and instructs the interactions of this molecule across the nascent and mature synaptic cleft. In immature neurons, cis assembly promotes the adhesive clustering of SynCAM 1 at new axo-dendritic contacts. Interfering with the lateral self-assembly of SynCAM 1 in differentiating neurons strongly impairs its synaptogenic activity. At later stages, the lateral oligomerization of SynCAM 1 restricts synaptic size, indicating that this adhesion molecule contributes to the structural organization of synapses. These results support that lateral interactions assemble SynCAM complexes within the synaptic cleft to promote synapse induction and modulate their structure. These findings provide novel insights into synapse development and the adhesive mechanisms of Ig superfamily members.

Ice residual properties in mixed-phase clouds at the high-alpine Jungfraujoch site.

PubMed

Kupiszewski, Piotr; Zanatta, Marco; Mertes, Stephan; Vochezer, Paul; Lloyd, Gary; Schneider, Johannes; Schenk, Ludwig; Schnaiter, Martin; Baltensperger, Urs; Weingartner, Ernest; Gysel, Martin

2016-10-27

Ice residual (IR) and total aerosol properties were measured in mixed-phase clouds (MPCs) at the high-alpine Jungfraujoch research station. Black carbon (BC) content and coating thickness of BC-containing particles were determined using single-particle soot photometers. The ice activated fraction (IAF), derived from a comparison of IR and total aerosol particle size distributions, showed an enrichment of large particles in the IR, with an increase in the IAF from values on the order of 10 -4 to 10 -3 for 100 nm (diameter) particles to 0.2 to 0.3 for 1 μm (diameter) particles. Nonetheless, due to the high number fraction of submicrometer particles with respect to total particle number, IR size distributions were still dominated by the submicrometer aerosol. A comparison of simultaneously measured number size distributions of BC-free and BC-containing IR and total aerosol particles showed depletion of BC by number in the IR, suggesting that BC does not play a significant role in ice nucleation in MPCs at the Jungfraujoch. The potential anthropogenic climate impact of BC via the glaciation effect in MPCs is therefore likely to be negligible at this site and in environments with similar meteorological conditions and a similar aerosol population. The IAF of the BC-containing particles also increased with total particle size, in a similar manner as for the BC-free particles, but on a level 1 order of magnitude lower. Furthermore, BC-containing IR were found to have a thicker coating than the BC-containing total aerosol, suggesting the importance of atmospheric aging for ice nucleation.

Subminimal Inhibitory Concentrations of the Disinfectant Benzalkonium Chloride Select for a Tolerant Subpopulation of Escherichia coli with Inheritable Characteristics

PubMed Central

Moen, Birgitte; Rudi, Knut; Bore, Erlend; Langsrud, Solveig

2012-01-01

Exposure of Escherichia coli to a subminimal inhibitory concentration (25% below MIC) of benzalkonium chloride (BC), an antimicrobial membrane-active agent commonly used in medical and food-processing environments, resulted in cell death and changes in cell morphology (filamentation). A small subpopulation (1–5% of the initial population) survived and regained similar morphology and growth rate as non-exposed cells. This subpopulation maintained tolerance to BC after serial transfers in medium without BC. To withstand BC during regrowth the cells up regulated a drug efflux associated gene (the acrB gene, member of the AcrAB-TolC efflux system) and changed expression of outer membrane porin genes (ompFW) and several genes involved in protecting the cell from the osmotic- and oxidative stress. Cells pre-exposed to osmotic- and oxidative stress (sodium chloride, salicylic acid and methyl viologen) showed higher tolerance to BC. A control and two selected isolates showing increased BC-tolerance after regrowth in BC was genome sequenced. No common point mutations were found in the BC- isolates but one point mutation in gene rpsA (Ribosomal protein S1) was observed in one of the isolates. The observed tolerance can therefore not solely be explained by the observed point mutation. The results indicate that there are several different mechanisms responsible for the regrowth of a tolerant subpopulation in BC, both BC-specific and general stress responses, and that sub-MIC of BC may select for phenotypic variants in a sensitive E. coli culture. PMID:22605968

Subminimal inhibitory concentrations of the disinfectant benzalkonium chloride select for a tolerant subpopulation of Escherichia coli with inheritable characteristics.

PubMed

Moen, Birgitte; Rudi, Knut; Bore, Erlend; Langsrud, Solveig

2012-01-01

Exposure of Escherichia coli to a subminimal inhibitory concentration (25% below MIC) of benzalkonium chloride (BC), an antimicrobial membrane-active agent commonly used in medical and food-processing environments, resulted in cell death and changes in cell morphology (filamentation). A small subpopulation (1-5% of the initial population) survived and regained similar morphology and growth rate as non-exposed cells. This subpopulation maintained tolerance to BC after serial transfers in medium without BC. To withstand BC during regrowth the cells up regulated a drug efflux associated gene (the acrB gene, member of the AcrAB-TolC efflux system) and changed expression of outer membrane porin genes (ompFW) and several genes involved in protecting the cell from the osmotic- and oxidative stress. Cells pre-exposed to osmotic- and oxidative stress (sodium chloride, salicylic acid and methyl viologen) showed higher tolerance to BC. A control and two selected isolates showing increased BC-tolerance after regrowth in BC was genome sequenced. No common point mutations were found in the BC- isolates but one point mutation in gene rpsA (Ribosomal protein S1) was observed in one of the isolates. The observed tolerance can therefore not solely be explained by the observed point mutation. The results indicate that there are several different mechanisms responsible for the regrowth of a tolerant subpopulation in BC, both BC-specific and general stress responses, and that sub-MIC of BC may select for phenotypic variants in a sensitive E. coli culture.

A 700 year sediment record of black carbon and polycyclic aromatic hydrocarbons near the EMEP air monitoring station in Aspvreten, Sweden

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marie Elmquist; Zdenek Zencak; Oerjan Gustafsson

2007-10-15

In view of poor constraints on historical combustion emissions, past environmental loadings of black carbon (BC) and polycyclic aromatic hydrocarbon (PAH) were reconstructed from dated lake sediment cores collected 70 km south of Stockholm, Sweden. Compared to several dramatic variations over the recent 150 years, the preindustrial loadings were steady within {+-}50% through the entire medieval with BC fluxes of 0.071 g m{sup -2} yr{sup -1} and PAH fluxes of 6 g m{sup -2} yr{sup -1}. In the wood-burning dominated century leading up to the industrial revolution around 1850, increasing BC fluxes were leading PAH fluxes. BC fluxes reached theirmore » millennial-scale maximum around 1920, whereas PAH fluxes increased exponentially to its record maximum around 1960, 50-fold above preindustrial values. For 1920-1950, BC fluxes consistently decreased as PAH fluxes kept increasing. Coal and coke represented >50% of the Swedish energy market in the 1930s. Combined with sharply decreasing (1,7-)/(1,7{+-}2,6-dimethylphenanthrene), indicative of diminishing wood combustion, and decreasing methylphenanthrenes/phenanthrene, indicative of higher-temperature combustion (coal instead of wood), the sediment archive suggests that the relative BC/PAH emission factors thus are lower for coal than for wood combustion. For the first time, both BC and PAH fluxes decreased after 1960. This trend break is a testament to the positive effects of decreasing reliance on petroleum fuels and a number of legislative actions aimed at curbing emissions and by 1990, the loading of BC was back at preindustrial levels, whereas that of PAH were the lowest since the 1910s. However, for the most recent period (1990-2004) the BC and PAH fluxes are no longer decreasing. 55 refs., 3 figs.« less

Impacts of global, regional, and sectoral black carbon emission reductions on surface air quality and human mortality

NASA Astrophysics Data System (ADS)

Anenberg, S. C.; Talgo, K.; Arunachalam, S.; Dolwick, P.; Jang, C.; West, J. J.

2011-07-01

As a component of fine particulate matter (PM2.5), black carbon (BC) is associated with premature human mortality. BC also affects climate by absorbing solar radiation and reducing planetary albedo. Several studies have examined the climate impacts of BC emissions, but the associated health impacts have been studied less extensively. Here, we examine the surface PM2.5 and premature mortality impacts of halving anthropogenic BC emissions globally and individually from eight world regions and three major economic sectors. We use a global chemical transport model, MOZART-4, to simulate PM2.5 concentrations and a health impact function to calculate premature cardiopulmonary and lung cancer deaths. We estimate that halving global anthropogenic BC emissions reduces outdoor population-weighted average PM2.5 by 542 ng m-3 (1.8 %) and avoids 157 000 (95 % confidence interval, 120 000-194 000) annual premature deaths globally, with the vast majority occurring within the source region. Most of these avoided deaths can be achieved by halving emissions in East Asia (China; 54 %), followed by South Asia (India; 31 %), however South Asian emissions have 50 % greater mortality impacts per unit BC emitted than East Asian emissions. Globally, halving residential, industrial, and transportation emissions contributes 47 %, 35 %, and 15 % to the avoided deaths from halving all anthropogenic BC emissions. These contributions are 1.2, 1.2, and 0.6 times each sector's portion of global BC emissions, owing to the degree of co-location with population globally. We find that reducing BC emissions increases regional SO4 concentrations by up to 28 % of the magnitude of the regional BC concentration reductions, due to reduced absorption of radiation that drives photochemistry. Impacts of residential BC emissions are likely underestimated since indoor PM2.5 exposure is excluded. We estimate ∼8 times more avoided deaths when BC and organic carbon (OC) emissions are halved together, suggesting that these results greatly underestimate the full air pollution-related mortality benefits of BC mitigation strategies which generally decrease both BC and OC. The choice of concentration-response factor and health effect thresholds affects estimated global avoided deaths by as much as 56 % but does not strongly affect the regional distribution. Confidence in our results would be strengthened by reducing uncertainties in emissions, model parameterization of aerosol processes, grid resolution, and PM2.5 concentration-mortality relationships globally.

Light Absorption of Black Carbon Aerosol and Its Radiative Forcing Effect in an Megacity Atmosphere in South China

NASA Astrophysics Data System (ADS)

Lan, Zijuan

2013-04-01

The effects of black carbon (BC) aerosol on climate warming have been the study focus in the recent decade, the regional effect of BC light absorption is more significant. The reduction of BC is now expected to have significant near-term climate change mitigation. Mass absorption efficient (MAE) was one of the important optical properties of BC aerosol for evaluating the BC on its radiative forcing effect, while BC mixing state is one main influencing factor for MAE. Models have estimated that BC radiative forcing can be increased by a factor of ~2 for internally versus externally mixed BC. On the other hand, some organic carbon had been found to significantly absorb light at UV or shorter wavelengths in the most recent studies, with strong spectral dependence. But large uncertainties still remain in determining the positive forcing effect of BC on global clime change due to the technical limitations. In this study, advanced instrumentation (a three-wavelength photoacoustic soot spectrometer (PASS-3) and a single particle soot photometer (SP2)) were used to measure black carbon aerosol and analyze its optical properties in a megacity in South China, Shenzhen, during the summer of 2011. It is in the southeast corner of the Pearl River Delta (PRD) region, neighboring Hong Kong to the south. During the campaign, the average BC mass concentration was 4.0±3.1 μg m-3, accounting for about 11% of PM2.5 mass concentration, which mainly came from fossil fuel combustion rather than biomass burning. The MAE of BC ranged from 5.0 to 8.5 m2 g-1, with an average value of 6.5±0.5 m2 g-1. The percentage of internally mixed BC was averagely 24.3±7.9% and positively correlated with the MAE. It is estimated that the internally mixed BC amplified MAE by about 7% during the campaign, suggesting that the BC absorption enhancement due to internal mixing in the real atmosphere is relatively low in comparison with the predictions by theoretical models, which stands in accordance with the new finding of a very recent Science magazine paper by Cappa.

Size distribution and mixing state of black carbon particles during a heavy air pollution episode in Shanghai

NASA Astrophysics Data System (ADS)

Gong, Xianda; Zhang, Ci; Chen, Hong; Nizkorodov, Sergey A.; Chen, Jianmin; Yang, Xin

2016-04-01

A Single Particle Aerosol Mass Spectrometer (SPAMS), a Single Particle Soot Photometer (SP2) and various meteorological instruments were employed to investigate the chemical and physical properties of black carbon (BC) aerosols during a regional air pollution episode in urban Shanghai over a 5-day period in December 2013. The refractory black carbon (rBC) mass concentrations measured by SP2 averaged 3.2 µg m-3, with the peak value of 12.1 µg m-3 at 04:26 LT on 7 December. The number of BC-containing particles captured by SPAMS in the size range 200-1200 nm agreed very well with that detected by SP2 (R2 = 0.87). A cluster analysis of the single particle mass spectra allowed for the separation of BC-containing particles into five major classes: (1) Pure BC; (2) BC attributed to biomass burning (BBBC); (3) K-rich BC-containing (KBC); (4) BC internally mixed with OC and ammonium sulfate (BCOC-SOx); (5) BC internally mixed with OC and ammonium nitrate (BCOC-NOx). The size distribution of internally mixed BC particles was bimodal. Detected by SP2, the condensation mode peaked around ˜ 230 nm and droplet mode peaked around ˜ 380 nm, with a clear valley in the size distribution around ˜ 320 nm. The condensation mode mainly consisted of traffic emissions, with particles featuring a small rBC core (˜ 60-80 nm) and a relatively thin absolute coating thickness (ACT, ˜ 50-130 nm). The droplet mode included highly aged traffic emission particles and biomass burning particles. The biomass burning particles had a larger rBC core (˜ 80-130 nm) and a thick ACT (˜ 110-300 nm). The highly aged traffic emissions had a smaller core (˜ 60-80 nm) and a very thick ACT (˜ 130-300 nm), which is larger than reported in any previous literature. A fast growth rate (˜ 20 nm h-1) of rBC with small core sizes was observed during the experiment. High concentrations pollutants like NO2 likely accelerated the aging process and resulted in a continuous size growth of rBC-containing particles from traffic emission.

[Molecular epidemiological study on HIV/AIDS under the follow-up program in Zhejiang province in 2009].

PubMed

Zhang, Jia-feng; Pan, Xiao-hong; Ding, Xiao-bei; Chen, Lin; Guo, Zhi-hong; Xu, Yun; Huang, Jing-jing

2013-01-01

To analyze the molecular epidemiological characteristics on HIV infectors/AIDS patients (HIV/AIDS) under a follow-up program in Zhejiang province in 2009. 303 cases were randomly sampled. Information on the cases was collected and followed by genomic DNA extraction. Gag gene fragments were amplified by nested PCR, followed by sequencing and bio-informatic analysis. The rate of success for sequence acquisition was 74.3% (225/303). Distributions of HIV subtypes were as follows: CRF01_AE (58.7%), CRF07_BC (13.8%), CRF08_BC (9.8%), B' (15.1%), C (1.8%), G (0.4%) and unassigned BC (unique recombinant form 0.4%). from the HIV BLAST analysis showed that the sources of strains with the highest homology involved in 10 provinces/municipalities (Liaoning, Guangxi, Yunnan, Henan, etc.) and five other countries (Thailand, Vietnam, India, South Africa and Libya). The CRF01_AE phylogenetic tree was divided into four clusters. The sequences of HIV/AIDS with homosexual transmission showed a gather in cluster 1, and mix with those infected through heterosexual contact. Circulating recombinant forms of HIV seemed to play a dominant role in Zhejiang province. Unique recombinant form and new subtype of HIV were found. People living with HIV under homosexual transmission and heterosexual transmission had a trend of interwoven with each other. Increase of both the diversity and complexity of HIV strains were also noticed in Zhejiang province.