The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels.

Science.gov (United States)

Salazar, Dominique A; Butler, Victoria J; Argouarch, Andrea R; Hsu, Tsung-Yuan; Mason, Amanda; Nakamura, Ayumi; McCurdy, Helen; Cox, David; Ng, Rachel; Pan, Gloria; Seeley, William W; Miller, Bruce L; Kao, Aimee W

2015-06-24

Mutations in the human progranulin gene resulting in protein haploinsufficiency cause frontotemporal lobar degeneration with TDP-43 inclusions. Although progress has been made in understanding the normal functions of progranulin and TDP-43, the molecular interactions between these proteins remain unclear. Progranulin is proteolytically processed into granulins, but the role of granulins in the pathogenesis of neurodegenerative disease is unknown. We used a Caenorhabditis elegans model of neuronal TDP-43 proteinopathy to specifically interrogate the contribution of granulins to the neurodegenerative process. Complete loss of the progranulin gene did not worsen TDP-43 toxicity, whereas progranulin heterozygosity did. Interestingly, expression of individual granulins alone had little effect on behavior. In contrast, when granulins were coexpressed with TDP-43, they exacerbated its toxicity in a variety of behaviors including motor coordination. These same granulins increased TDP-43 levels via a post-translational mechanism. We further found that in human neurodegenerative disease subjects, granulin fragments accumulated specifically in diseased regions of brain. To our knowledge, this is the first demonstration of a toxic role for granulin fragments in a neurodegenerative disease model. These studies suggest that presence of cleaved granulins, rather than or in addition to loss of full-length progranulin, may contribute to disease in TDP-43 proteinopathies. Copyright © 2015 the authors 0270-6474/15/359315-14$15.00/0.

Green Fluorescent Protein Changes the Conductance of Connexin 43 (Cx43) Hemichannels Reconstituted in Planar Lipid Bilayers*

Science.gov (United States)

Carnarius, Christian; Kreir, Mohamed; Krick, Marcel; Methfessel, Christoph; Moehrle, Volker; Valerius, Oliver; Brüggemann, Andrea; Steinem, Claudia; Fertig, Niels

2012-01-01

In mammalian tissues, connexin 43 (Cx43) is the most prominent member of the connexin family. In a single lipid bilayer, six connexin subunits assemble into a hemichannel (connexon). Direct communication of apposing cells is realized by two adjacent hemichannels, which can form gap junction channels. Here, we established an expression system in Pichia pastoris to recombinantly produce and purify Cx43 as well as Cx43 fused to green fluorescent protein (GFP). Proteins were isolated from crude cell membrane fractions via affinity chromatography. Cx43 and Cx43-GFP hemichannels were reconstituted in giant unilamellar vesicles as proven by fluorescence microscopy, and their electrophysiological behavior was analyzed on the single channel level by planar patch clamping. Cx43 and Cx43-GFP both showed an ohmic behavior and a voltage-dependent open probability. Cx43 hemichannels exhibited one major mean conductance of 224 ± 26 picosiemens (pS). In addition, a subconductance state at 124 ± 5 pS was identified. In contrast, the analysis of Cx43-GFP single channels revealed 10 distinct conductance states in the range of 15 to 250 pS, with a larger open probability at 0 mV as compared with Cx43, which suggests that intermolecular interactions between the GFP molecules alter the electrophysiology of the protein. PMID:22139870

26 CFR 43.0-1 - Introduction.

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2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 43.0-1 Section 43.0-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX ON TRANSPORTATION BY WATER § 43.0-1 Introduction. The regulations in this part 43 are designated...

16 CFR 4.3 - Time.

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2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Time. 4.3 Section 4.3 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE MISCELLANEOUS RULES § 4.3 Time. (a) Computation. Computation of any period of time prescribed or allowed by the rules in this chapter, by order of...

45 CFR 91.43 - Mediation.

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2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Mediation. 91.43 Section 91.43 Public Welfare... Enforcement Procedures § 91.43 Mediation. (a) HHS will promptly refer to a mediation agency designated by the... mediation process to the extent necessary to reach an agreement or make an informed judgment that an...

Tar DNA binding protein-43 (TDP-43 associates with stress granules: analysis of cultured cells and pathological brain tissue.

Directory of Open Access Journals (Sweden)

Liqun Liu-Yesucevitz

2010-10-01

Full Text Available Tar DNA Binding Protein-43 (TDP-43 is a principle component of inclusions in many cases of frontotemporal lobar degeneration (FTLD-U and amyotrophic lateral sclerosis (ALS. TDP-43 resides predominantly in the nucleus, but in affected areas of ALS and FTLD-U central nervous system, TDP-43 is aberrantly processed and forms cytoplasmic inclusions. The mechanisms governing TDP-43 inclusion formation are poorly understood. Increasing evidence indicates that TDP-43 regulates mRNA metabolism by interacting with mRNA binding proteins that are known to associate with RNA granules. Here we show that TDP-43 can be induced to form inclusions in cell culture and that most TDP-43 inclusions co-localize with SGs. SGs are cytoplasmic RNA granules that consist of mixed protein-RNA complexes. Under stressful conditions SGs are generated by the reversible aggregation of prion-like proteins, such as TIA-1, to regulate mRNA metabolism and protein translation. We also show that disease-linked mutations in TDP-43 increased TDP-43 inclusion formation in response to stressful stimuli. Biochemical studies demonstrated that the increased TDP-43 inclusion formation is associated with accumulation of TDP-43 detergent insoluble complexes. TDP-43 associates with SG by interacting with SG proteins, such as TIA-1, via direct protein-protein interactions, as well as RNA-dependent interactions. The signaling pathway that regulates SGs formation also modulates TDP-43 inclusion formation. We observed that inclusion formation mediated by WT or mutant TDP-43 can be suppressed by treatment with translational inhibitors that suppress or reverse SG formation. Finally, using Sudan black to quench endogenous autofluorescence, we also demonstrate that TDP-43 positive-inclusions in pathological CNS tissue co-localize with multiple protein markers of stress granules, including TIA-1 and eIF3. These data provide support for accumulating evidence that TDP-43 participates in the SG pathway.

Inflammation Induces TDP-43 Mislocalization and Aggregation.

Directory of Open Access Journals (Sweden)

Ana Sofia Correia

Full Text Available TAR DNA-binding protein 43 (TDP-43 is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Here we report that lipopolysaccharide (LPS-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.

16 CFR 1018.43 - Comprehensive review.

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2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Comprehensive review. 1018.43 Section 1018.43 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION GENERAL ADVISORY COMMITTEE MANAGEMENT Records, Annual Reports and Audits § 1018.43 Comprehensive review. A comprehensive review of all...

10 CFR 436.43 - Procurement planning.

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2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Procurement planning. 436.43 Section 436.43 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION FEDERAL ENERGY MANAGEMENT AND PLANNING PROGRAMS Agency Procurement of Energy Efficient Products § 436.43 Procurement planning. (a) Agencies should consider the...

32 CFR 2700.43 - Reproduction controls.

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2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Reproduction controls. 2700.43 Section 2700.43... SECURITY INFORMATION REGULATIONS Safeguarding § 2700.43 Reproduction controls. OMSN and SLNO shall maintain records to show the number and distribution of all OMSN originated classified documents. Reproduction of...

41 CFR 109-43.001 - Definition.

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2010-07-01

... PERSONAL PROPERTY § 109-43.001 Definition. DOE screening period means the period of time that reportable... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Definition. 109-43.001 Section 109-43.001 Public Contracts and Property Management Federal Property Management Regulations System...

28 CFR 550.43 - Drug counseling.

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2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Drug counseling. 550.43 Section 550.43... Drug Services (Urine Surveillance and Counseling for Sentenced Inmates in Contract CTCs) § 550.43 Drug counseling. (a) Drug counseling shall be provided to sentenced inmates in contract community treatment...

28 CFR 43.4 - Annual reports.

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2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Annual reports. 43.4 Section 43.4 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RECOVERY OF COST OF HOSPITAL AND MEDICAL CARE AND TREATMENT FURNISHED BY THE UNITED STATES § 43.4 Annual reports. The head of each Department or Agency...

46 CFR 167.43-1 - Application.

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2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 167.43-1 Section 167.43-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS PUBLIC NAUTICAL SCHOOL SHIPS Work Vests § 167.43-1 Application. (a) Provisions of this subpart shall apply to all vessels inspected and...

22 CFR 204.43 - Governing law.

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2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 204.43 Section 204.43 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT HOUSING GUARANTY STANDARD TERMS AND CONDITIONS Administration § 204.43 Governing law. This Guaranty shall be governed by and construed in accordance with the laws of...

32 CFR 701.43 - Fee declarations.

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2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Fee declarations. 701.43 Section 701.43 National... OFFICIAL RECORDS AVAILABILITY OF DEPARTMENT OF THE NAVY RECORDS AND PUBLICATION OF DEPARTMENT OF THE NAVY DOCUMENTS AFFECTING THE PUBLIC FOIA Fees § 701.43 Fee declarations. Requesters should submit a fee...

38 CFR 43.44 - Termination for convenience.

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2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Termination for convenience. 43.44 Section 43.44 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... convenience. Except as provided in § 43.43 awards may be terminated in whole or in part only as follows: (a...

12 CFR 561.43 - Savings association.

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2010-01-01

..., chartered under section 5 of the Act, or a building and loan, savings and loan, or homestead association, or... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Savings association. 561.43 Section 561.43... AFFECTING ALL SAVINGS ASSOCIATIONS § 561.43 Savings association. The term savings association means a...

29 CFR 785.43 - Medical attention.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Medical attention. 785.43 Section 785.43 Labor Regulations..., Medical Attention, Civic and Charitable Work, and Suggestion Systems § 785.43 Medical attention. Time spent by an employee in waiting for and receiving medical attention on the premises or at the direction...

22 CFR 221.43 - Governing law.

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2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 221.43 Section 221.43 Foreign... Administration § 221.43 Governing law. This Guarantee shall be governed by and construed in accordance with the laws of the United States of America governing contracts and commercial transactions of the United...

14 CFR 33.43 - Vibration test.

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2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Vibration test. 33.43 Section 33.43... STANDARDS: AIRCRAFT ENGINES Block Tests; Reciprocating Aircraft Engines § 33.43 Vibration test. (a) Each... configuration of the propeller type which is used for the endurance test, and using, for other engines, the same...

14 CFR 31.43 - Fitting factor.

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2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Fitting factor. 31.43 Section 31.43... STANDARDS: MANNED FREE BALLOONS Design Construction § 31.43 Fitting factor. (a) A fitting factor of at least... structure. This factor applies to all parts of the fitting, the means of attachment, and the bearing on the...

40 CFR 407.43 - [Reserved

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true [Reserved] 407.43 Section 407.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS CANNED AND PRESERVED FRUITS AND VEGETABLES PROCESSING POINT SOURCE CATEGORY Frozen Potato Products...

45 CFR 74.43 - Competition.

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2010-10-01

... to ensure objective contractor performance and eliminate unfair competitive advantage, contractors... 45 Public Welfare 1 2010-10-01 2010-10-01 false Competition. 74.43 Section 74.43 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR AWARDS...

45 CFR 2543.43 - Competition.

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2010-10-01

... to ensure objective contractor performance and eliminate unfair competitive advantage, contractors... 45 Public Welfare 4 2010-10-01 2010-10-01 false Competition. 2543.43 Section 2543.43 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE...

Identification of transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) as a novel factor for TNF-α expression upon lipopolysaccharide stimulation in human monocytes.

Science.gov (United States)

Murata, H; Hattori, T; Maeda, H; Takashiba, S; Takigawa, M; Kido, J; Nagata, T

2015-08-01

Tumor necrosis factor alpha (TNF-α) is a major cytokine implicated in various inflammatory diseases. The nature of the nuclear factors associated with human TNF-α gene regulation is not well elucidated. We previously identified a novel region located from -550 to -487 in human TNF-α promoter that did not contain the reported binding sites for nuclear factor kappa B (NF-κB) but showed lipopolysaccharide (LPS)-induced transcriptional activity. The purpose of this study is to identify novel factors that bind to the promoter region and regulate TNF-α expression. To identify DNA-binding proteins that bound to the target region of TNF-α promoter, a cDNA library from LPS-stimulated human monocytic cell line THP-1 was screened using a yeast one-hybrid system. Cellular localizations of the DNA-binding protein in the cells were examined by subcellular immunocytochemistry. Nuclear amounts of the protein in LPS-stimulated THP-1 cells were identified by western blot analysis. Expression of mRNA of the protein in the cells was quantified by real-time polymerase chain reaction. Electrophoretic mobility shift assays were performed to confirm the DNA-binding profile. Overexpression of the protein and knockdown of the gene were also performed to investigate the role for TNF-α expression. Several candidates were identified from the cDNA library and transactivation-responsive DNA-binding protein 43 (TARDBP43; TDP-43) was focused on. Western blot analysis revealed that nuclear TDP-43 protein was increased in the LPS-stimulated THP-1 cells. Expression of TDP-43 mRNA was already enhanced before TNF-α induction by LPS. Electrophoretic mobility shift assay analysis showed that nuclear extracts obtained by overexpressing FLAG-tagged TDP-43 bound to the -550 to -487 TNF-α promoter fragments. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-α expression. Knockdown of TDP-43 in THP-1 cells downregulated TNF-α expression. We identified TDP-43 as one of the novel

7 CFR 3016.43 - Enforcement.

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2010-01-01

... 7 Agriculture 15 2010-01-01 2010-01-01 false Enforcement. 3016.43 Section 3016.43 Agriculture Regulations of the Department of Agriculture (Continued) OFFICE OF THE CHIEF FINANCIAL OFFICER, DEPARTMENT OF AGRICULTURE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL...

7 CFR 958.43 - Accounting.

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2010-01-01

... 7 Agriculture 8 2010-01-01 2010-01-01 false Accounting. 958.43 Section 958.43 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... Accounting. (a) All funds received by the committee pursuant to the provisions of this part shall be used...

16 CFR 1.43 - Recommendations.

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2010-01-01

... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Recommendations. 1.43 Section 1.43 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE GENERAL... investigation. If, after investigation, it concludes that the law has been violated, it may make to such...

Molecular Neuropathology of TDP-43 Proteinopathies

Directory of Open Access Journals (Sweden)

Manuela Neumann

2009-01-01

Full Text Available The identification of TDP-43 as the major component of the pathologic inclusions in most forms of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U and amyotrophic lateral sclerosis (ALS resolved a long-standing enigma concerning the nature of the ubiquitinated disease protein under these conditions. Anti-TDP-43 immunohistochemistry and the recent development of novel tools, such as phosphorylation-specific TDP-43 antibodies, have increased our knowledge about the spectrum of pathological changes associated with FTLD-U and ALS and moreover, facilitated the neuropathological routine diagnosis of these conditions. This review summarizes the recent advances in our understanding on the molecular neuropathology and pathobiology of TDP-43 in FTLD and ALS.

USI A-43 resolution positions

International Nuclear Information System (INIS)

1983-04-01

NUREG-0869 is comprised of the following documents: Proposed Regulatory Guide 1.82, Revision 1, Sump for Emergency Core Cooling and Containment Spray Systems; The Value-Impact Statement for USI A-43, Containment Emergency Sump Performance; and Background and Summary of Minutes of Meetings of the Committee to Review Generic Requirements Regarding Unresolved Safety Issue A-43 Resolution. The report has been assembled to facilitate obtaining for comment feedback on the position developed for resolution of USI A-43. There are no licensing requirements contained in NUREG-0869, and it should be clearly noted that this for comment report will not be used as interim requirements

38 CFR 43.33 - Supplies.

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2010-07-01

...) Disposition. If there is a residual inventory of unused supplies exceeding $5,000 in total aggregate fair... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Supplies. 43.33 Section... Requirements Changes, Property, and Subawards § 43.33 Supplies. (a) Title. Title to supplies acquired under a...

43 CFR 426.2 - Definitions.

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2010-10-01

..., Kansas, Montana, Nebraska, Nevada, New Mexico, North Dakota, Oklahoma, Oregon, South Dakota, Texas, Utah..., Sections 203(b), 204, and 205 of the Reclamation Reform Act of 1982 (43 U.S.C. 390aa et seq.). Acreage... definition includes contracts made in accordance with the Distribution System Loans Act, as amended (43 U.S.C...

19 CFR 141.43 - Delegation to subagents.

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2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Delegation to subagents. 141.43 Section 141.43 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Powers of Attorney § 141.43 Delegation to subagents. (a) Resident...

7 CFR 43.101 - Meaning of words.

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2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Meaning of words. 43.101 Section 43.101 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... SAMPLING PLANS Definitions § 43.101 Meaning of words. Words used in this subpart in the singular form shall...

49 CFR 604.43 - Offer of proof.

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2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Offer of proof. 604.43 Section 604.43..., DEPARTMENT OF TRANSPORTATION CHARTER SERVICE Hearings. § 604.43 Offer of proof. A party whose evidence has... respond to the offer of proof, may offer the evidence on the record when filing an appeal. ...

14 CFR 77.43 - Nature of hearing.

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2010-01-01

... nature. As a factfinding procedure, each hearing is nonadversary and there are no formal pleadings or... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Nature of hearing. 77.43 Section 77.43... OBJECTS AFFECTING NAVIGABLE AIRSPACE Rules of Practice for Hearings Under Subpart D § 77.43 Nature of...

45 CFR 1801.43 - Allowance for books.

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2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Allowance for books. 1801.43 Section 1801.43... HARRY S. TRUMAN SCHOLARSHIP PROGRAM Payments to Finalists and Scholars § 1801.43 Allowance for books. The cost allowance for a Scholar's books is $1000 per year, or such higher amount published on the...

Oryza sativa Chloroplast Signal Recognition Particle 43 (OscpSRP43 Is Required for Chloroplast Development and Photosynthesis.

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Xiang-guang Lv

Full Text Available A rice chlorophyll-deficient mutant w67 was isolated from an ethyl methane sulfonate (EMS-induced IR64 (Oryza sativa L. ssp. indica mutant bank. The mutant exhibited a distinct yellow-green leaf phenotype in the whole plant growth duration with significantly reduced levels of chlorophyll and carotenoid, impaired chloroplast development and lowered capacity of photosynthesis compared with the wild-type IR64. Expression of a number of genes associated with chlorophyll metabolism, chloroplast biogenesis and photosynthesis was significantly altered in the mutant. Genetic analysis indicated that the yellow-green phenotype was controlled by a single recessive nuclear gene located on the short arm of chromosome 3. Using map-based strategy, the mutation was isolated and predicted to encode a chloroplast signal recognition particle 43 KD protein (cpSRP43 with 388 amino acid residuals. A single base substitution from A to T at position 160 resulted in a premature stop codon. OscpSRP43 was constitutively expressed in various organs with the highest level in the leaf. Functional complementation could rescue the mutant phenotype and subcellular localization showed that the cpSRP43:GFP fusion protein was targeted to the chloroplast. The data suggested that Oryza sativa cpSRP43 (OscpSRP43 was required for the normal development of chloroplasts and photosynthesis in rice.

Endolysosomal pathway activity protects cells from neurotoxic TDP-43

Directory of Open Access Journals (Sweden)

Christine Leibiger

2018-03-01

Full Text Available The accumulation of protein aggregates in neurons is a typical pathological hallmark of the motor neuron disease amyotrophic lateral sclerosis (ALS and of frontotemporal dementia (FTD. In many cases, these aggregates are composed of the 43 kDa TAR DNA-binding protein (TDP‑43. Using a yeast model for TDP‑43 proteinopathies, we observed that the vacuole (the yeast equivalent of lysosomes markedly contributed to the degradation of TDP‑43. This clearance occurred via TDP‑43-containing vesicles fusing with the vacuole through the concerted action of the endosomal-vacuolar (or endolysosomal pathway and autophagy. In line with its dominant role in the clearance of TDP‑43, endosomal-vacuolar pathway activity protected cells from the detrimental effects of TDP‑43. In contrast, enhanced autophagy contributed to TDP‑43 cytotoxicity, despite being involved in TDP‑43 degradation. TDP‑43’s interference with endosomal-vacuolar pathway activity may have two deleterious consequences. First, it interferes with its own degradation via this pathway, resulting in TDP‑43 accumulation. Second, it affects vacuolar proteolytic activity, which requires endosomal-vacuolar trafficking. We speculate that the latter contributes to aberrant autophagy. In sum, we propose that ameliorating endolysosomal pathway activity enhances cell survival in TDP‑43-associated diseases.

X-43A Flight Controls

Science.gov (United States)

Baumann, Ethan

2006-01-01

A viewgraph presentation detailing X-43A Flight controls at NASA Dryden Flight Research Center is shown. The topics include: 1) NASA Dryden, Overview and current and recent flight test programs; 2) Unmanned Aerial Vehicle Synthetic Aperture Radar (UAVSAR) Program, Program Overview and Platform Precision Autopilot; and 3) Hyper-X Program, Program Overview, X-43A Flight Controls and Flight Results.

46 CFR 113.43-5 - Power supply.

Science.gov (United States)

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Power supply. 113.43-5 Section 113.43-5 Shipping COAST... SYSTEMS AND EQUIPMENT Steering Failure Alarm Systems § 113.43-5 Power supply. Each steering failure alarm system must be supplied by a circuit that: (a) Is independent of other steering gear system and steering...

Effects of haloperidol on Kv4.3 potassium channels.

Science.gov (United States)

Lee, Hong Joon; Sung, Ki-Wug; Hahn, Sang June

2014-10-05

Haloperidol is commonly used in clinical practice to treat acute and chronic psychosis, but it also has been associated with adverse cardiovascular events. We investigated the effects of haloperidol on Kv4.3 currents stably expressed in CHO cells using a whole-cell patch-clamp technique. Haloperidol did not significantly inhibit the peak amplitude of Kv4.3, but accelerated the decay rate of inactivation of Kv4.3 in a concentration-dependent manner. Thus, the effects of haloperidol on Kv4.3 were estimated from the integral of the Kv4.3 currents during the depolarization pulse. The Kv4.3 was decreased by haloperidol in a concentration-dependent manner with an IC50 value of 3.6 μM. Haloperidol accelerated the decay rate of Kv4.3 inactivation and activation kinetics in a concentration-dependent manner, thereby decreasing the time-to-peak. Haloperidol shifted the voltage dependence of the steady-state activation and inactivation of Kv4.3 in a hyperpolarizing direction. Haloperidol also caused an acceleration of the closed-state inactivation of Kv4.3. Haloperidol produced a use-dependent block of Kv4.3, which was accompanied by a slowing of recovery from the inactivation of Kv4.3. These results suggest that haloperidol blocks Kv4.3 by both interacting with the open state of Kv4.3 channels during depolarization and accelerating the closed-state inactivation at subthreshold membrane potentials. Copyright © 2014 Elsevier B.V. All rights reserved.

The first orbital parameters and period variation of the short-period eclipsing binary AQ Boo

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Wang, Shuai; Zhang, Liyun; Pi, Qingfeng; Han, Xianming L.; Zhang, Xiliang; Lu, Hongpeng; Wang, Daimei; Li, TongAn

2016-10-01

We obtained the first VRI CCD light curves of the short-period contact eclipsing binary AQ Boo, which was observed on March 22 and April 19 in 2014 at Xinglong station of National Astronomical Observatories, and on January 20, 21 and February 28 in 2015 at Kunming station of Yunnan Observatories of Chinese Academy of Sciences, China. Using our six newly obtained minima and the minima that other authors obtained previously, we revised the ephemeris of AQ Boo. By fitting the O-C (observed minus calculated) values of the minima, the orbital period of AQ Boo shows a decreasing tendency P˙ = - 1.47(0.17) ×10-7 days/year. We interpret the phenomenon by mass transfer from the secondary (more massive) component to the primary (less massive) one. By using the updated Wilson & Devinney program, we also derived the photometric orbital parameters of AQ Boo for the first time. We conclude that AQ Boo is a near contact binary with a low contact factor of 14.43%, and will become an over-contact system as the mass transfer continues.

Magnesium Alloy WE43 and WE43-T5 - Mechanical and Thermal Properties

Science.gov (United States)

Xiang, Chongchen

Magnesium alloys are promising in aerospace, automotive and electronic industries due to low density, high specific strength and excellent machinability. A rare earth element alloy (WE43) is studied in as cast and heat treated conditions. Multiscale characterization is conducted to understand the nanomechanical response using a nanoindentor and microscale behavior using tensile tests. Further, compressive characterization is conducted across six orders of strain rate magnitudes from 10-3 to 3x103 s -1 under the range of liquid nitrogen (-196°C) to room temperature (25°C). Based on the results, a constitutive model is developed to estimate the plastic behavior of as-cast WE43 and WE43-T5 at different strain rates and under different temperatures. In addition, dynamic properties are studied using a dynamic mechanical analyzer at 1-100 Hz loading frequencies and the temperature range from 35°C to 500°C. Only Yttrium-rich cuboidal phase and zirconium-rich phase were present in WE43-T5 alloy and the eutectic phase was absent. Also, the grain size was reduced due to the hot rolling process. The difference in microstructure reflects into the mechanical properties. WE43-T5 specimens have improved mechanical properties over the as-cast alloy. Two transition temperatures are found at 210 and 250°C based on the storage and loss moduli results. The Mg24Y5 peak is found in the high temperature x-ray diffraction results along with a new Mg12Nd peak at those two temperature points. The corrosion behavior, studied by 7-day immersion in 3.5% NaCl solution, shows that the heat treated alloy has significantly lower corrosion rate than the as-cast alloy due to the absence of the eutectic mixture in the microstructure. With rapidly growing applications of magnesium alloys, particularly with rare earth elements, this study is expected to provide critical data and structure-property correlations that will help the scientific community.

14 CFR 99.43 - Contiguous U.S. ADIZ.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Contiguous U.S. ADIZ. 99.43 Section 99.43 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR TRAFFIC... Zones § 99.43 Contiguous U.S. ADIZ. The area bounded by a line from 43°15′N, 65°55′W; 44°21′N; 67°16′W...

7 CFR 43.105 - Operating characteristics (OC) curves.

Science.gov (United States)

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Operating characteristics (OC) curves. 43.105 Section 43.105 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE... CONTAINER REGULATIONS STANDARDS FOR SAMPLING PLANS Sampling Plans § 43.105 Operating characteristics (OC...

39 CFR 4.3 - Postmaster General.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Postmaster General. 4.3 Section 4.3 Postal Service....3 Postmaster General. The appointment and role of the Postmaster General are described at 39 U.S.C..., subject to 39 U.S.C. 1003(a) and 3686. ...

38 CFR 43.25 - Program income.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Program income. 43.25... Requirements Financial Administration § 43.25 Program income. (a) General. Grantees are encouraged to earn income to defray program costs. Program income includes income from fees for services performed, from the...

38 CFR 43.41 - Financial reporting.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Financial reporting. 43... Post-Award Requirements Reports, Records, Retention, and Enforcement § 43.41 Financial reporting. (a... may from time to time be authorized by OMB, for: (i) Submitting financial reports to Federal agencies...

43 CFR 43.220 - By when must I publish my drug-free workplace statement and establish my drug-free awareness...

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false By when must I publish my drug-free workplace statement and establish my drug-free awareness program? 43.220 Section 43.220 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients...

9 CFR 78.43 - Validated brucellosis-free States.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Validated brucellosis-free States. 78.43 Section 78.43 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... BRUCELLOSIS Designation of Brucellosis Areas § 78.43 Validated brucellosis-free States. Alabama, Alaska...

49 CFR 229.43 - Exhaust and battery gases.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Exhaust and battery gases. 229.43 Section 229.43... § 229.43 Exhaust and battery gases. (a) Products of combustion shall be released entirely outside the... conditions. (b) Battery containers shall be vented and batteries kept from gassing excessively. ...

Transposable elements in TDP-43-mediated neurodegenerative disorders.

Directory of Open Access Journals (Sweden)

Wanhe Li

Full Text Available Elevated expression of specific transposable elements (TEs has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD. Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.

Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12

Science.gov (United States)

Landouré, Guida; Zhu, Peng-Peng; Lourenço, Charles M.; Johnson, Janel O.; Toro, Camilo; Bricceno, Katherine V.; Rinaldi, Carlo; Meilleur, Katherine G.; Sangaré, Modibo; Diallo, Oumarou; Pierson, Tyler M.; Ishiura, Hiroyuki; Tsuji, Shoji; Hein, Nichole; Fink, John K.; Stoll, Marion; Nicholson, Garth; Gonzalez, Michael; Speziani, Fiorella; Dürr, Alexandra; Stevanin, Giovanni; Biesecker, Leslie G.; Accardi, John; Landis, Dennis M. D.; Gahl, William A.; Traynor, Bryan J.; Marques, Wilson; Züchner, Stephan; Blackstone, Craig; Fischbeck, Kenneth H.; Burnett, Barrington G.

2013-01-01

We report here the genetic basis for a form of progressive hereditary spastic paraplegia (SPG43) previously described in two Malian sisters. Exome sequencing revealed a homozygous missense variant (c.187G>C; p.Ala63Pro) in C19orf12, a gene recently implicated in neurodegeneration with brain iron accumulation (NBIA). The same mutation was subsequently also found in a Brazilian family with features of NBIA, and we identified another NBIA patient with a three-nucleotide deletion (c.197_199del; p.Gly66del). Haplotype analysis revealed that the p.Ala63Pro mutations have a common origin, but MRI scans showed no brain iron deposition in the Malian SPG43 subjects. Heterologous expression of these SPG43 and NBIA variants resulted in similar alterations in the subcellular distribution of C19orf12. The SPG43 and NBIA variants reported here as well as the most common C19orf12 missense mutation reported in NBIA patients are found within a highly-conserved, extended hydrophobic domain in C19orf12, underscoring the functional importance of this domain. PMID:23857908

Fluoxetin Upregulates Connexin 43 Expression in Astrocyte

Directory of Open Access Journals (Sweden)

Hossein Mostafavi

2014-02-01

Full Text Available Introduction: Recent studies have shown that astrocytes play major roles in normal and disease condition of the central nervous system including multiple sclerosis (MS. Molecular target therapy studies in MS have revealed that connexin-43 (Cx43 and Aquaporin-4 (AQP4 contents of astrocytes undergo expression alteration. Fluoxetine had some effects in MS patients unrelated to its known antidepressant effects. Some of fluoxetine effects were attributed to its capability of cAMP signaling pathway stimulation. This study aimed to investigate possible acute effects of fluoxetine on Cx43 and AQP4 expression in astrocyte.  Methods: Astrocytoma cells were treated for 24 hours with fluoxetine (10 and 20 &mug/ml with or without adenyl cyclase (AC and protein kinase A (PKA inhibition. Cx43 expression at both mRNA and protein levels and AQP4 expression at mRNA level were evaluated.  Results: Acquired results showed that fluoxetine with and without AC and PKA inhibition resulted in Cx43 up-regulation both in mRNA and protein levels, whereas AQP4 expression have not changed.  Discussion: In conclusion, data showed that fluoxetine alone and in the absence of serotonin acutely up-regulated Cx43 expression in astrocytes that can be assumed in molecular target therapy of MS patients. It seems that cAMP involvement in fluoxetine effects need more researches.

25 CFR 213.43 - Relinquishment of Government supervision.

Science.gov (United States)

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Relinquishment of Government supervision. 213.43 Section 213.43 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF RESTRICTED LANDS OF MEMBERS OF FIVE CIVILIZED TRIBES, OKLAHOMA, FOR MINING Removal of Restrictions § 213.43 Relinquishment of Government supervision....

42 CFR 4.3 - Purpose of the Library.

Science.gov (United States)

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Purpose of the Library. 4.3 Section 4.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.3 Purpose of the Library. The purpose of the Library is to assist the advancement of...

Activities of the summer operations of the 43rd Japanese Antarctic Research Expedition (JARE-43 in 2001-2002

Directory of Open Access Journals (Sweden)

Fumihiko Nishio

2013-03-01

Full Text Available The activities in the 2001-2002 austral summer of the 43rd Japanese Antarctic Research Expedition (JARE-43 are reported. JARE-43 consisted of 60 personnel including 20 summer and 40 wintering personnel. In addition, 7 observers joined the voyage of R/V Shirase. She left Harumi on Nov. 14 in 2001, and the 56 personel and 7 observers went on boad in Freemantle of Western Australia for Syowa Station, other 4 personel for another ship as mentioned below. R/V Shirase left the ground on Dec. 3 and arrived at the ice edge on Dec. 14, after carrying out marine observations on the cruise. She anchored at Syowa Station on Dec. 23, after the first flight on Dec. 18. All the cargo and fuel necessary for the wintering program of JARE-43 were unloaded and the missions for the summer party were forced to finish by the last flight on Feb. 12 in 2002. The helicopter, chartered by JARE-43, moved to Syowa Station from R/V Shirase on Dec. 23 and supported the observation programs until Feb. 3, including the inland areas of ice sheets. The observation on the Mizuho Ice Plateau for the seismic exploration programs was especially supported by air during the traverse. Constructions with engineering works and facilities update were conducted in the several areas in Syowa Station, and most of them were accomplished, some, however, left for the wintering party. In addition, 4 summer members carried out other marine observations using R/V Tangaroa chartered by JARE-43.

BD+43° 3654 - a blue straggler?

Science.gov (United States)

Gvaramadze, V. V.; Bomans, D. J.

2008-07-01

The astrometric data on the runaway star BD+43° 3654 are consistent with the origin of this O4If star in the center of the Cyg OB2 association, while BD+43° 3654 is younger than the association. To reconcile this discrepancy, we suggest that BD+43° 3654 is a blue straggler formed via a close encounter between two tight massive binaries in the core of Cyg OB2. A possible implication of this suggestion is that the very massive (and therefore apparently very young) stars in Cyg OB2 could be blue stragglers as well. We also suggest that the binary-binary encounter producing BD+43° 3654 might be responsible for ejection of two high-velocity stars (the stripped helium cores of massive stars) - the progenitors of the pulsars B2020+28 and B2021+51.

X-43A Vehicle During Ground Testing

Science.gov (United States)

1999-01-01

The X-43A Hypersonic Experimental Vehicle, or 'Hyper-X' is seen here undergoing ground testing at NASA's Dryden Flight Research Center, Edwards, California in December 1999. The X-43A was developed to research a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only

Differential expression of the Escherichia coli autoaggregation factor antigen 43

DEFF Research Database (Denmark)

Schembri, Mark; Hjerrild, Louise; Gjermansen, Morten

2003-01-01

Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia coli strains. Due to its excellent cell-to-cell aggregation characteristics, Ag43 expression confers clumping and fluffing of cells and promotes biofilm formation. Ag43 expression is repressed by the cellular redox...

Intracellular trafficking pathways of Cx43 gap junction channels.

Science.gov (United States)

Epifantseva, Irina; Shaw, Robin M

2018-01-01

Gap Junction (GJ) channels, including the most common Connexin 43 (Cx43), have fundamental roles in excitable tissues by facilitating rapid transmission of action potentials between adjacent cells. For instance, synchronization during each heartbeat is regulated by these ion channels at the cardiomyocyte cell-cell border. Cx43 protein has a short half-life, and rapid synthesis and timely delivery of those proteins to particular subdomains are crucial for the cellular organization of gap junctions and maintenance of intracellular coupling. Impairment in gap junction trafficking contributes to dangerous complications in diseased hearts such as the arrhythmias of sudden cardiac death. Of recent interest are the protein-protein interactions with the Cx43 carboxy-terminus. These interactions have significant impact on the full length Cx43 lifecycle and also contribute to trafficking of Cx43 as well as possibly other functions. We are learning that many of the known non-canonical roles of Cx43 can be attributed to the recently identified six endogenous Cx43 truncated isoforms which are produced by internal translation. In general, alternative translation is a new leading edge for proteome expansion and therapeutic drug development. This review highlights recent mechanisms identified in the trafficking of gap junction channels, involvement of other proteins contributing to the delivery of channels to the cell-cell border, and understanding of possible roles of the newly discovered alternatively translated isoforms in Cx43 biology. This article is part of a Special Issue entitled: Gap Junction Proteins edited by Jean Claude Herve. Copyright © 2017 Elsevier B.V. All rights reserved.

Aberrant Cx43 Expression and Mislocalization in Metastatic Human Melanomas.

Science.gov (United States)

Alaga, Katanya C; Crawford, Melissa; Dagnino, Lina; Laird, Dale W

2017-01-01

At present, it is unclear if melanocytes contain Cx43 gap junctions and whether Cx43 expression is regulated in melanoma onset and progression. To this end, we cultured pure populations of mouse melanocytes and found that they had no detectable Cx43 and exhibited an inability for dye transfer indicating they were devoid of functional gap junctions. Given the evidence that melanomas acquire the expression of other connexin isoforms during tumor progression, we assessed if Cx43 was also expressed and assembled into gap junctions at any stage of human melanoma onset and progression to distant metastases. Nearly all primary melanomas within the epidermis lacked Cx43. In contrast, nodal metastases expressed low levels of Cx43 which was markedly higher in distant metastases that had invaded vital organs. Importantly, in all stages of melanoma progression, Cx43 could be detected in intracellular compartments but was rarely assembled into gap junctions indicative of functional gap junction channels. Overall, these studies suggest that melanocytes do not form Cx43 homocellular gap junctions and even though Cx43 levels increase during melanoma progression, this connexin rarely assembles into gap junction structures.

43Ca NMR in solid state

Science.gov (United States)

Bellot, P.-V.; Trokiner, A.; Zhdanov, Yu.; Yakubovskii, A.

1998-02-01

In this paper we show that 43Ca is a suitable NMR probe to study the properties of high-Tc superconducting oxides. In the normal state, we report the temperature and doping dependencies of the spin susceptibility measured by 43Ca NMR. In the superconducting state and more exactly in the mixed state, by analysing 43Ca NMR linewidth, we have studied the magnetic induction distribution due to the presence of vortices and deduced λ, the penetration depth. Dans cet article, on montre que l'isotope 43 du calcium est une bonne sonde RMN pour l'étude des propriétés des oxydes supraconducteurs à haute température. Dans l'état normal, par la détermination du déplacement de la raie, en fonction de la température, on accède à la variation thermique de la susceptibilité de spin. Dans l'état supraconducteur et plus particulièrement dans l'état mixte, la largeur de raie RMN permet d'étudier la distribution d'induction magnétique due à la présence des vortex et de déterminer λ, la longueur de pénétration.

12 CFR 560.43 - Foreign assistance investments.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Foreign assistance investments. 560.43 Section... INVESTMENT Lending and Investment Powers for Federal Savings Associations § 560.43 Foreign assistance investments. Pursuant to HOLA section 5(c)(4)(C), a Federal savings association may make foreign assistance...

Glycosylation of the self-recognizing Escherichia coli Ag43 autotransporter protein

DEFF Research Database (Denmark)

Sherlock, O.; Dobrindt, U.; Jensen, J.B.

2006-01-01

a novel member to this exclusive group, namely, antigen 43 (Ag43), a self-recognizing autotransporter protein. By mass spectrometry Ag43 was demonstrated to be glycosylated by addition of heptose residues at several positions in the passenger domain. Glycosylation of Ag43 by the action of the Aah and Tib......C glycosyltransferases was observed in laboratory strains. Importantly, Ag43 was also found to be glycosylated in a wild-type strain, suggesting that Ag43-glycosylation may be a widespread phenomenon. Glycosylation of Ag43 does not seem to interfere with its self-associating properties. However, the glycosylated form...

40 CFR 279.43 - Used oil transportation.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Used oil transportation. 279.43... Facilities § 279.43 Used oil transportation. (a) Deliveries. A used oil transporter must deliver all used oil... comply with all applicable requirements under the U.S. Department of Transportation regulations in 49 CFR...

14 CFR 63.43 - Flight engineer courses.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight engineer courses. 63.43 Section 63...) AIRMEN CERTIFICATION: FLIGHT CREWMEMBERS OTHER THAN PILOTS Flight Engineers § 63.43 Flight engineer courses. An applicant for approval of a flight engineer course must submit a letter to the Administrator...

Antigen-43-mediated autoaggregation of Escherichia coli is blocked by fimbriation

DEFF Research Database (Denmark)

Hasman, Henrik; Chakraborty, Trinad; Klemm, Per

1999-01-01

that the expression of type 1 fimbriae and the expression of Ag43 are mutually exclusive. In the present report, we show, by use of well-defined mutants, that fimbriation abolishes Ag43-mediated autoaggregation but does not affect Ag43 expression. Autoaggregation is shown to require an intercellular Ag43-Ag43...

The SCFA receptor GPR43 and energy metabolism

Directory of Open Access Journals (Sweden)

Ikuo eKimura

2014-06-01

Full Text Available Free fatty acids (FFAs are essential nutrients and act as signaling molecules in various cellular processes via binding with FFA receptors. Of these receptors, GPR43 is activated by short chain fatty acids (SCFAs; e.g., acetate, propionate, and butyrate. During feeding, SCFAs are produced by microbial fermentation of dietary fiber in the gut, and these SCFAs become important energy sources for the host. The gut microbiota affects nutrient acquisition and energy regulation of the host and can influence the development of obesity, insulin resistance, and diabetes. Recently, GPR43 has been reported to regulate host energy homeostasis in the gastrointestinal tract and adipose tissues. Hence, GPR43 is also thought to be a potential drug target for metabolic disorders, such as obesity and diabetes. In this review, we summarize the identification, structure, and activities of GPR43, with a focus on host energy regulation, and present an essential overview of our current understanding of its physiological roles in host energy regulation that is mediated by gut microbiota. We also discuss the potential for GPR43 as a therapeutic target.

28 CFR 43.3 - Settlement and waiver of claims.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Settlement and waiver of claims. 43.3 Section 43.3 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RECOVERY OF COST OF HOSPITAL AND MEDICAL CARE AND TREATMENT FURNISHED BY THE UNITED STATES § 43.3 Settlement and waiver of claims. (a) The...

38 CFR 43.26 - Non-Federal audit.

Science.gov (United States)

2010-07-01

... awards in a fiscal year, shall: (1) Determine whether State or local subgrantees have met the audit... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Non-Federal audit. 43.26... Requirements Financial Administration § 43.26 Non-Federal audit. (a) Basic rule. Grantees and subgrantees are...

50 CFR 28.43 - Destruction of dogs and cats.

Science.gov (United States)

2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Destruction of dogs and cats. 28.43 Section 28.43 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR... VIOLATIONS OF PARTS 25, 26, AND 27 Impoundment Procedures § 28.43 Destruction of dogs and cats. Dogs and cats...

Connexin43 gene and its irradiation-induced expression

International Nuclear Information System (INIS)

Long Xianhui; Zhou Pingkun

2005-01-01

Gap junctions, composed of connexin protein subunits, provide the important channel for the intercellular communication. Connexin43, the most popular component of the connexin protein family, is widely expressed in multiple tissues and cell lines and plays an important role in cell proliferation, differention and tissue homeostasis. Recently it was reported that the expression of connexin43 gene is remarkedly up-regulated by low dose ionizing radiation, the available data suggest connexin43 gene to be a poten-tial sensitive bio-marker in radiation damage. (authors)

Thermodynamics of the oxidation-reduction reaction {2 glutathionered(aq) + NADPox(aq)=glutathioneox(aq) + NADPred(aq)}

International Nuclear Information System (INIS)

Tewari, Yadu B.; Goldberg, Robert N.

2003-01-01

Microcalorimetry, spectrophotometry, and high-performance liquid chromatography (h.p.l.c.) have been used to conduct a thermodynamic investigation of the glutathione reductase catalyzed reaction {2 glutathione red (aq) + NADP ox (aq)=glutathione ox (aq) + NADP red (aq)}. The reaction involves the breaking of a disulfide bond and is of particular importance because of the role glutathione red plays in the repair of enzymes. The measured values of the apparent equilibrium constant K ' for this reaction ranged from 0.5 to 69 and were measured over a range of temperature (288.15 K to 303.15 K), pH (6.58 to 8.68), and ionic strength I m (0.091 mol · kg -1 to 0.90 mol · kg -1 ). The results of the equilibrium and calorimetric measurements were analyzed in terms of a chemical equilibrium model that accounts for the multiplicity of ionic states of the reactants and products. These calculations led to values of thermodynamic quantities at T=298.15 K and I m =0 for a chemical reference reaction that involves specific ionic forms. Thus, for the reaction {2 glutathione red - (aq) + NADP ox 3- (aq)=glutathione ox 2- (aq) + NADP red 4- (aq) + H + (aq)}, the equilibrium constant K=(6.5±4.4)·10 -11 , the standard molar enthalpy of reaction Δ r H o m =(6.9±3.0) kJ · mol -1 , the standard molar Gibbs free energy change Δ r G o m =(58.1±1.7) kJ · mol -1 , and the standard molar entropy change Δ r S o m =-(172±12) J · K -1 · mol -1 . Under approximately physiological conditions (T=311.15 K, pH=7.0, and I m =0.25 mol · kg -1 the apparent equilibrium constant K ' ∼0.013. The results of the several studies of this reaction from the literature have also been examined and analyzed using the chemical equilibrium model. It was found that much of the literature is in agreement with the results of this study. Use of our results together with a value from the literature for the standard electromotive force E o for the NADP redox reaction leads to E o =0.166 V (T=298.15 K and I

76 FR 55740 - Proposed Collection; Comment Request for Notice 99-43

Science.gov (United States)

2011-09-08

... Notice 99-43 AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice and request for comments... Notice 99-43, Nonrecognition Exchanges under Section 897. DATES: Written comments should be received on... Number: Notice 99-43. Abstract: Notice 99-43 announces modification of the current rules under Temporary...

Connexin43 orthologues in vertebrates: phylogeny from fish to man

NARCIS (Netherlands)

van der Heyden, Marcel A. G.; van Eijk, Marleen; Wilders, Ronald; de Bakker, Jacques M. T.; Opthof, Tobias

2004-01-01

The gap junction protein connexin43 (Cx43) is widely expressed in all vertebrate species; however, in ventricular myocardium, Cx43 expression is restricted to mammalian species only, where it provides the molecular correlate for both electrical conduction and synchronization of the repolarization

Association of connexin43 with a receptor protein tyrosine phosphatase

NARCIS (Netherlands)

Giepmans, Ben N G; Feiken, Elles; Gebbink, Martijn F B G; Moolenaar, Wouter H

2003-01-01

Connexin-43(Cx43)-based gap junctional communication is transiently inhibited by certain G protein-coupled receptor agonists, including lysophosphatidic acid, endothelin and thrombin. Our previous studies have implicated the c-Src protein tyrosine kinase in mediating closure of Cx43 based gap

28 CFR 43.1 - Administrative determination and assertion of claims.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Administrative determination and assertion of claims. 43.1 Section 43.1 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RECOVERY OF COST OF HOSPITAL AND MEDICAL CARE AND TREATMENT FURNISHED BY THE UNITED STATES § 43.1 Administrative...

29 CFR 4281.43 - Notices of insolvency and annual updates.

Science.gov (United States)

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Notices of insolvency and annual updates. 4281.43 Section 4281.43 Labor Regulations Relating to Labor (Continued) PENSION BENEFIT GUARANTY CORPORATION INSOLVENCY... MASS WITHDRAWAL Benefit Suspensions § 4281.43 Notices of insolvency and annual updates. (a) Requirement...

Examination of tracer method using 43K produced with a cyclotron

International Nuclear Information System (INIS)

Yuida, Koichi; Kawarazaki, Yuji; Shibuya, Masao; Nozaki, Tadashi.

1980-01-01

The 43 K tracer produced with a cyclotron is contaminated with about the same amount of 42 K. During first 43 hours after the production, the rate of attenuation of its radioactivity was greater than the theoretical value of 43 K (half-life 22.4 hours) because of the rapid attenuation of radioactivity of the contaminating 42 K (half-life 12.4 hours). After that, however, the rate of attenuation in the radioactivity of 43 K tracer followed the attenuation curve of 22.4 hr half-life, i.e., the radioactivity of the contaminating 42 K was negligible. The potassium chloride fertilizer labelled with 43 K-tracer (or 42 K-tracer) was applied for 8 days (or 4.5 days in case of 42 K) to 2-month-old rice plants grown by hydroponics, and for 7 days to rice plants grown on soil (at ripening stage). The rice plants were then dried for 24 hours at 70 deg C, and the radioactivity was measured by a scintillation counter. 43 K was able to be traced for 13.3 days in the plants grown by hydroponics, and 42 K for 5.4 days, but 43 K was able to be traced only for 7.4 days in the plants grown on soil which absorb 43 K poorly. Since 43 K and 42 K are γ-ray emittors, and the energy is not low, microautoradiograms were not able to be made, but macroautoradiograms were made. The autoradiograms for 43 K and 42 K did not differ in resolution, and both were clear. The radioactivity of 43 K did not diminish so rapidly as 42 K, but was lost in one month. Such character of 43 K is beneficial both for tracer experiments and for the prevention of environmental pollution. (Kaihara, S.)

6 CFR 13.43 - Collection of civil penalties and assessments.

Science.gov (United States)

2010-01-01

... 6 Domestic Security 1 2010-01-01 2010-01-01 false Collection of civil penalties and assessments. 13.43 Section 13.43 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY PROGRAM FRAUD CIVIL REMEDIES § 13.43 Collection of civil penalties and assessments. Sections 3806 and 3808...

GPNMB ameliorates mutant TDP-43-induced motor neuron cell death.

Science.gov (United States)

Nagahara, Yuki; Shimazawa, Masamitsu; Ohuchi, Kazuki; Ito, Junko; Takahashi, Hitoshi; Tsuruma, Kazuhiro; Kakita, Akiyoshi; Hara, Hideaki

2017-08-01

Glycoprotein nonmetastatic melanoma protein B (GPNMB) aggregates are observed in the spinal cord of amyotrophic lateral sclerosis (ALS) patients, but the detailed localization is still unclear. Mutations of transactive response DNA binding protein 43kDa (TDP-43) are associated with neurodegenerative diseases including ALS. In this study, we evaluated the localization of GPNMB aggregates in the spinal cord of ALS patients and the effect of GPNMB against mutant TDP-43 induced motor neuron cell death. GPNMB aggregates were not localized in the glial fibrillary acidic protein (GFAP)-positive astrocyte and ionized calcium binding adaptor molecule-1 (Iba1)-positive microglia. GPNMB aggregates were localized in the microtubule-associated protein 2 (MAP-2)-positive neuron and neurofilament H non-phosphorylated (SMI-32)-positive neuron, and these were co-localized with TDP-43 aggregates in the spinal cord of ALS patients. Mock or TDP-43 (WT, M337V, and A315T) plasmids were transfected into mouse motor neuron cells (NSC34). The expression level of GPNMB was increased by transfection of mutant TDP-43 plasmids. Recombinant GPNMB ameliorated motor neuron cell death induced by transfection of mutant TDP-43 plasmids and serum-free stress. Furthermore, the expression of phosphorylated ERK1/2 and phosphorylated Akt were decreased by this stress, and these expressions were increased by recombinant GPNMB. These results indicate that GPNMB has protective effects against mutant TDP-43 stress via activating the ERK1/2 and Akt pathways, and GPNMB may be a therapeutic target for TDP-43 proteinopathy in familial and sporadic ALS. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

27 CFR 45.43 - Notice for smokeless tobacco.

Science.gov (United States)

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Notice for smokeless tobacco. 45.43 Section 45.43 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO REMOVAL OF TOBACCO PRODUCTS AND CIGARETTE PAPERS...

15 CFR 4.3 - Records under the FOIA.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Records under the FOIA. 4.3 Section 4.3 Commerce and Foreign Trade Office of the Secretary of Commerce DISCLOSURE OF GOVERNMENT... Government records, regardless of format, medium or physical characteristics, and include electronic records...

14 CFR 21.43 - Location of manufacturing facilities.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Location of manufacturing facilities. 21.43... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS Type Certificates § 21.43 Location of manufacturing facilities... location of the manufacturer's facilities places no undue burden on the FAA in administering applicable...

Cyclotron production of {sup 43}Sc for PET imaging

Energy Technology Data Exchange (ETDEWEB)

Walczak, Rafał [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Krajewski, Seweryn [Synektik S.A., Research and Development Center, Warsaw (Poland); Szkliniarz, Katarzyna [Department of Nuclear Physics, University of Silesia, Katowice (Poland); Sitarz, Mateusz [Heavy Ion Laboratory, University of Warsaw, Warsaw (Poland); Abbas, Kamel [Nuclear Security Unit, Joint Research Centre, Institute for Transuranium Elements, European Commission, Ispra (Italy); Choiński, Jarosław; Jakubowski, Andrzej; Jastrzębski, Jerzy [Heavy Ion Laboratory, University of Warsaw, Warsaw (Poland); Majkowska, Agnieszka [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland); Simonelli, Federica [Nuclear Decommissioning Unit, Joint Research Centre, Ispra Site Management Directorate, European Commission, Ispra (Italy); Stolarz, Anna; Trzcińska, Agnieszka [Heavy Ion Laboratory, University of Warsaw, Warsaw (Poland); Zipper, Wiktor [Department of Nuclear Physics, University of Silesia, Katowice (Poland); Bilewicz, Aleksander [Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw (Poland)

2015-12-04

Recently, significant interest in {sup 44}Sc as a tracer for positron emission tomography (PET) imaging has been observed. Unfortunately, the co-emission by {sup 44}Sc of high-energy γ rays (E{sub γ} = 1157, 1499 keV) causes a dangerous increase of the radiation dose to the patients and clinical staff. However, it is possible to produce another radionuclide of scandium—{sup 43}Sc—having properties similar to {sup 44}Sc but is characterized by much lower energy of the concurrent gamma emissions. This work presents the production route of {sup 43}Sc by α irradiation of natural calcium, its separation and purification processes, and the labeling of [DOTA,Tyr3] octreotate (DOTATATE) bioconjugate. Natural CaCO{sub 3} and enriched [{sup 40}Ca]CaCO{sub 3} were irradiated with alpha particles for 1 h in an energy range of 14.8–30 MeV at a beam current of 0.5 or 0.25 μA. In order to find the optimum method for the separation of {sup 43}Sc from irradiated calcium targets, three processes previously developed for {sup 44}Sc were tested. Radiolabeling experiments were performed with DOTATATE radiobioconjugate, and the stability of the obtained {sup 43}Sc-DOTATATE was tested in human serum. Studies of {sup nat}CaCO{sub 3} target irradiation by alpha particles show that the optimum alpha particle energies are in the range of 24–27 MeV, giving 102 MBq/μA/h of {sup 43}Sc radioactivity which creates the opportunity to produce several GBq of {sup 43}Sc. The separation experiments performed indicate that, as with {sup 44}Sc, due to the simplicity of the operations and because of the chemical purity of the {sup 43}Sc obtained, the best separation process is when UTEVA resin is used. The DOTATATE conjugate was labeled by the obtained {sup 43}Sc with a yield >98 % at elevated temperature. Tens of GBq activities of {sup 43}Sc of high radionuclidic purity can be obtainable for clinical applications by irradiation of natural calcium with an alpha beam.

Control of Vascular Smooth Muscle Cell Growth by Connexin 43

Directory of Open Access Journals (Sweden)

Chintamani eJoshi

2012-06-01

Full Text Available Connexin 43 (Cx43, the principal gap junction protein in vascular smooth muscle cells (VSMCs, regulates movement of ions and other signaling molecules through gap junction intercellular communication (GJIC and plays important roles in maintaining normal vessel function; however, many of the signaling mechanisms controlling Cx43 in VSMCs are not clearly described. The goal of this study was to investigate mechanisms of Cx43 regulation with respect to VSMC proliferation. Treatment of rat primary VSMCs with the cAMP analog 8Br-cAMP, the soluble guanylate cyclase (sGC stimulator BAY 41-2272 (BAY, or the Cx inducer diallyl disulfide (DADS significantly reduced proliferation after 72 h compared to vehicle controls. Bromodeoxyuridine uptake revealed reduction (p<.001 in DNA synthesis after 6 h and flow cytometry showed reduced (40% S phase cell numbers after 16 h in DADS-treated cells compared to controls. Cx43 expression significantly increased after 270 min treatment with 8Br-cAMP, 8Br-cGMP, BAY or DADS. Inhibition of PKA, PKG or PKC reversed 8Br-cAMP-stimulated increases in Cx43 expression, whereas only PKG or PKC inhibition reversed 8Br-cGMP- and BAY-stimulated increases in total Cx43. Interestingly, stimulation of Cx43 expression by DADS was not dependent on PKA, PKG or PKC. Using fluorescence recovery after photobleaching, only 8Br-cAMP or DADS increased GJIC with 8Br-cAMP mediated by PKC and DADS mediated by PKG. Further, DADS significantly increased phosphorylation at the MAPK-sensitive serine (Ser255 and Ser279, the cell cycle regulatory kinase-sensitive Ser262 and the PKC-sensitive Ser368 after 30 min while 8Br-cAMP significantly increased phosphorylation only at Ser279 compared to controls. This study demonstrates that 8Br-cAMP- and DADS-enhanced GJIC rather than Cx43 expression and/or phosphorylation plays an important role in regulation of VSMC proliferation and provides new insights into the growth-regulatory capacities of Cx43 in VSMCs.

20 CFR 219.43 - Evidence of child's dependency.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of child's dependency. 219.43... EVIDENCE REQUIRED FOR PAYMENT Evidence of Relationship § 219.43 Evidence of child's dependency. (a) When the dependency requirement must be met. Usually the dependency requirement must be met at one of the...

Treating ALS by Targeting Pathological TDP-43

Science.gov (United States)

2017-09-01

43) is the major aggregating disease protein in amyotrophic lateral sclerosis (ALS). Our previous work demonstrated pS409/410 TDP-43 mediates motor...or are likely to make an impact on the base of knowledge, theory , and research in the principal disciplinary field(s) of the project. Summarize using...provide the name only and indicate “no change.” Example: Name: Mary Smith Project Role : Graduate Student Researcher Identifier (e.g

Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression.

Science.gov (United States)

Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Fujii, Shiori; Miyauchi, Kazuki; Nakamura, Yoki; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2016-06-15

Peripheral nerve injury upregulates tumor necrosis factor (TNF) expression. In turn, connexin 43 (Cx43) expression in spinal astrocytes is downregulated by TNF. Therefore, restoration of spinal astrocyte Cx43 expression to normal level could lead to the reduction of nerve injury-induced pain. While the non-provitaminic carotenoid lycopene reverses thermal hyperalgesia in mice with painful diabetic neuropathy, the antinociceptive mechanism is not entirely clear. The current study evaluated whether the antinociceptive effect of lycopene is mediated through the modulation of Cx43 expression in spinal astrocytes. The effect of lycopene on Cx43 expression was examined in cultured rat spinal astrocytes. The effect of intrathecal lycopene on Cx43 expression and neuropathic pain were evaluated in mice with partial sciatic nerve ligation (PSNL). Treatment of cultured rat spinal astrocytes with lycopene reversed TNF-induced downregulation of Cx43 protein expression through a transcription-independent mechanism. By contrast, treatment of cultured spinal astrocytes with either pro-vitamin A carotenoid β-carotene or antioxidant N-acetyl cysteine had no effect on TNF-induced downregulation of Cx43 protein expression. In addition, repeated, but not single, intrathecal treatment with lycopene of mice with a partial sciatic nerve ligation significantly prevented not only the downregulation of Cx43 expression in spinal dorsal horn but mechanical hypersensitivity as well. The current findings suggest a significant spinal mechanism that mediates the analgesic effect of lycopene, through the restoration of normal spinal Cx43 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Connexin 43 expression in human and mouse testes with impaired spermatogenesis

Directory of Open Access Journals (Sweden)

M Kotula-Balak

2009-08-01

Full Text Available Connexin 43 (Cx43 belongs to a family of proteins that form gap junction channels. The aim of this study was to examine the expression of Cx43 in the testis of a patient with Klinefelter’s syndrome and of mice with the mosaic mutation and a partial deletion in the long arm of the Y chromosome. These genetic disorders are characterized by the presence of numerous degenerated seminiferous tubules and impaired spermatogenesis. In mouse testes, the expression and presence of Cx43 were detected by means of immunohistochemistry and Western blot analysis, respectively. In testes of Klinefelter’s patient only immunoexpression of Cx43 was detected. Regardless of the species Cx43 protein was ubiquitously distributed in testes of reproductively normal males, whereas in those with testicular disorders either a weak intensity of staining or no staining within the seminiferous tubules was observed. Moderate to strong or very strong staining was confined to the interstitial tissue. In an immunoblot analysis of testicular homogenates Cx43 appeared as one major band of approximately 43 kDa. Our study adds three more examples of pathological gonads in which the absence or apparent decrease of Cx43 expression within the seminiferous tubules was found. A positive correlation between severe spermatogenic impairment and loss of Cx43 immunoreactivity observed in this study supports previous data that gap junctions play a crucial role in spermatogenesis. Strong Cx43 expression detected mostly in the interstitial tissue of the Klinefelter’s patient may presumably be of importance in sustaining Leydig cell metabolic activity. However, the role of gap junction communication in the control of Leydig cell function seems to be more complex than originally thought.

24 CFR 26.43 - Subpoenas.

Science.gov (United States)

2010-04-01

... PROCEDURES Hearings Pursuant to the Administrative Procedure Act Discovery § 26.43 Subpoenas. (a) General... request for a subpoena in aid of discovery shall be filed in time to permit the conclusion of discovery 15...

U6 snRNA expression prevents toxicity in TDP-43-knockdown cells.

Directory of Open Access Journals (Sweden)

Masao Yahara

Full Text Available Depletion of amyotrophic lateral sclerosis (ALS-associated transactivation response (TAR RNA/DNA-binding protein 43 kDa (TDP-43 alters splicing efficiency of multiple transcripts and results in neuronal cell death. TDP-43 depletion can also disturb expression levels of small nuclear RNAs (snRNAs as spliceosomal components. Despite this knowledge, the relationship between cell death and alteration of snRNA expression during TDP-43 depletion remains unclear. Here, we knocked down TDP-43 in murine neuroblastoma Neuro2A cells and found a time lag between efficient TDP-43 depletion and appearance of cell death, suggesting that several mechanisms mediate between these two events. The amount of U6 snRNA was significantly decreased during TDP-43 depletion prior to increase of cell death, whereas that of U1, U2, and U4 snRNAs was not. Downregulation of U6 snRNA led to cell death, whereas transient exogenous expression of U6 snRNA counteracted the effect of TDP-43 knockdown on cell death, and slightly decreased the mis-splicing rate of Dnajc5 and Sortilin 1 transcripts, which are assisted by TDP-43. These results suggest that regulation of the U6 snRNA expression level by TDP-43 is a key factor in the increase in cell death upon TDP-43 loss-of-function.

14 CFR 65.43 - Rating privileges and exchange.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Rating privileges and exchange. 65.43... § 65.43 Rating privileges and exchange. (a) The holder of a senior rating on August 31, 1970, may at any time after that date exchange his rating for a facility rating at the same air traffic control...

47 CFR 43.61 - Reports of international telecommunications traffic.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Reports of international telecommunications traffic. 43.61 Section 43.61 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... Reports of international telecommunications traffic. (a) Each common carrier engaged in providing...

Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

International Nuclear Information System (INIS)

Talhouk, Rabih S.; Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania; El-Sabban, Marwan E.

2013-01-01

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

Energy Technology Data Exchange (ETDEWEB)

Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); El-Sabban, Marwan E., E-mail: me00@aub.edu.lb [Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon)

2013-12-10

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

40 CFR 81.43 - Metropolitan Toledo Interstate Air Quality Control Region.

Science.gov (United States)

2010-07-01

... Quality Control Region. 81.43 Section 81.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Air Quality Control Regions § 81.43 Metropolitan Toledo Interstate Air Quality Control Region. The Metropolitan Toledo Interstate Air Quality Control Region (Ohio-Michigan) consists of the territorial area...

Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin

NARCIS (Netherlands)

Giepmans, B N; Verlaan, I; Moolenaar, W H

2001-01-01

Gap junctions are composed of connexins that form transmembrane channels between adjacent cells. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated in the regulation of Cx43 channel gating. Interestingly, channel-independent processes regulated

Conceptual Design Plan SM-43 Replacement Project

Energy Technology Data Exchange (ETDEWEB)

University of California, Los Alamos National Laboratory, SCC Project Office

2000-11-01

The Los Alamos National Laboratory Conceptual Design Plan for the SM-43 Replacement Project outlines plans for replacing the SM-43 Administration Building. Topics include the reasons that replacement is considered a necessity; the roles of the various project sponsors; and descriptions of the proposed site and facilities. Also covered in this proposal is preliminary information on the project schedule, cost estimates, acquisition strategy, risk assessment, NEPA strategy, safety strategy, and safeguards and security. Spreadsheets provide further detail on space requirements, project schedules, and cost estimates.

Protein kinase C-dependent regulation of connexin43 gap junctions and hemichannels

DEFF Research Database (Denmark)

Alstrøm, Jette Skov; Stroemlund, Line Waring; Nielsen, Morten Schak

2015-01-01

Connexin43 (Cx43) generates intercellular gap junction channels involved in, among others, cardiac and brain function. Gap junctions are formed by the docking of two hemichannels from neighbouring cells. Undocked Cx43 hemichannels can upon different stimuli open towards the extracellular matrix...... and allow transport of molecules such as fluorescent dyes and ATP. A range of phosphorylated amino acids have been detected in the C-terminus of Cx43 and their physiological role has been intensively studied both in the gap junctional form of Cx43 and in its hemichannel configuration. We present the current...... knowledge of protein kinase C (PKC)-dependent regulation of Cx43 and discuss the divergent results....

40 CFR 710.43 - Definitions.

Science.gov (United States)

2010-07-01

... CHEMICAL INVENTORY REGULATIONS Inventory Update Reporting for 2006 and Beyond § 710.43 Definitions. In... person similarly situated might be expected to possess, control, or know. Master Inventory File means EPA's comprehensive list of chemical substances which constitute the Chemical Substances Inventory...

19 CFR 201.43 - Program.

Science.gov (United States)

2010-04-01

... UNITED STATES INTERNATIONAL TRADE COMMISSION GENERAL RULES OF GENERAL APPLICATION National Security Information § 201.43 Program. The Director of Administration is designated as the official of the Commission who is responsible for implementation and oversight of information security programs and procedures...

Gap junction protein connexin-43 interacts directly with microtubules

NARCIS (Netherlands)

Giepmans, B N; Verlaan, I; Hengeveld, T; Janssen, H; Calafat, J; Falk, M M; Moolenaar, W H

2001-01-01

Gap junctions are specialized cell-cell junctions that mediate intercellular communication. They are composed of connexin proteins, which form transmembrane channels for small molecules [1, 2]. The C-terminal tail of connexin-43 (Cx43), the most widely expressed connexin member, has been implicated

Identification and characterization of the pseudorabies virus UL43 protein

International Nuclear Information System (INIS)

Klupp, Barbara G.; Altenschmidt, Jan; Granzow, Harald; Fuchs, Walter; Mettenleiter, Thomas C.

2005-01-01

Among the least characterized herpesvirus membrane proteins are the homologs of UL43 of herpes simplex virus 1 (HSV-1). To identify and characterize the UL43 protein of pseudorabies virus (PrV), part of the open reading frame was expressed in Escherichia coli and used for immunization of a rabbit. The antiserum recognized in Western blots a 34-kDa protein in lysates of PrV infected cells and purified virions, demonstrating that the UL43 protein is a virion component. In indirect immunofluorescence analysis, the antiserum labeled vesicular structures in PrV infected cells which also contained glycoprotein B. To functionally analyze UL43, a deletion mutant was constructed lacking amino acids 23-332 of the 373aa protein. This mutant was only slightly impaired in replication as assayed by one-step growth kinetics, measurement of plaque sizes, and electron microscopy. Interestingly, the PrV UL43 protein was able to inhibit fusion induced by PrV glycoproteins in a transient expression-fusion assay to a similar extent as gM. Double mutant viruses lacking, in addition to UL43, the multiply membrane spanning glycoproteins K or M did not show a phenotype beyond that observed in the gK and gM single deletion mutants

X-43 Hypersonic Vehicle Technology Development

Science.gov (United States)

Voland, Randall T.; Huebner, Lawrence D.; McClinton, Charles R.

2005-01-01

NASA recently completed two major programs in Hypersonics: Hyper-X, with the record-breaking flights of the X-43A, and the Next Generation Launch Technology (NGLT) Program. The X-43A flights, the culmination of the Hyper-X Program, were the first-ever examples of a scramjet engine propelling a hypersonic vehicle and provided unique, convincing, detailed flight data required to validate the design tools needed for design and development of future operational hypersonic airbreathing vehicles. Concurrent with Hyper-X, NASA's NGLT Program focused on technologies needed for future revolutionary launch vehicles. The NGLT was "competed" by NASA in response to the President s redirection of the agency to space exploration, after making significant progress towards maturing technologies required to enable airbreathing hypersonic launch vehicles. NGLT quantified the benefits, identified technology needs, developed airframe and propulsion technology, chartered a broad University base, and developed detailed plans to mature and validate hypersonic airbreathing technology for space access. NASA is currently in the process of defining plans for a new Hypersonic Technology Program. Details of that plan are not currently available. This paper highlights results from the successful Mach 7 and 10 flights of the X-43A, and the current state of hypersonic technology.

28 CFR 43.2 - Obligations of persons receiving care and treatment.

Science.gov (United States)

2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Obligations of persons receiving care and treatment. 43.2 Section 43.2 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RECOVERY OF COST OF HOSPITAL AND MEDICAL CARE AND TREATMENT FURNISHED BY THE UNITED STATES § 43.2 Obligations of persons...

38 CFR 43.32 - Equipment.

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2010-07-01

... awarding agency. (d) Management requirements. Procedures for managing equipment (including replacement... return. (e) Disposition. When original or replacement equipment acquired under a grant or subgrant is no... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Equipment. 43.32 Section...

14 CFR 183.43 - Application.

Science.gov (United States)

2010-01-01

... REGULATIONS REPRESENTATIVES OF THE ADMINISTRATOR Organization Designation Authorization § 183.43 Application... structure, including a description of the proposed ODA Unit as it relates to the applicant's organizational structure; and (d) A proposed procedures manual as described in § 183.53 of this part. ...

34 CFR 686.43 - Obligation to repay the grant.

Science.gov (United States)

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Obligation to repay the grant. 686.43 Section 686.43 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION TEACHER EDUCATION ASSISTANCE FOR COLLEGE AND HIGHER EDUCATION (TEACH...

44 CFR 5.43 - Waiver or reduction of fees.

Science.gov (United States)

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Waiver or reduction of fees. 5.43 Section 5.43 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... requester's and/or intended user's identity and qualifications, expertise in the subject area and ability...

21 CFR 601.43 - Withdrawal procedures.

Science.gov (United States)

2010-04-01

... LICENSING Accelerated Approval of Biological Products for Serious or Life-Threatening Illnesses § 601.43... the required postmarketing study with due diligence; (3) Use after marketing demonstrates that...

Biochemical and kinetic characterisation of a novel xylooligosaccharide-upregulated GH43 β-d-xylosidase/α-l-arabinofuranosidase (BXA43) from the probiotic Bifidobacterium animalis subsp. lactis BB-12

DEFF Research Database (Denmark)

Viborg, Alexander Holm; Sørensen, Kim Ib; Gilad, Ofir

2013-01-01

The Bifidobacterium animalis subsp. lactis BB-12 gene BIF_00092, assigned to encode a β-d-xylosidase (BXA43) of glycoside hydrolase family 43 (GH43), was cloned with a C-terminal His-tag and expressed in Escherichia coli. BXA43 was purified to homogeneity from the cell lysate and found to be a dual......-specificity exo-hydrolase active on para-nitrophenyl-β-d-xylopyranoside (pNPX), para-nitrophenyl-α-L-arabinofuranoside (pNPA), β-(1 → 4)-xylopyranosyl oligomers (XOS) of degree of polymerisation (DP) 2–4, and birchwood xylan. A phylogenetic tree of the 92 characterised GH43 enzymes displayed five distinct groups...

Use of Lactobacillus helveticus BGRA43 for Manufacturing Fermented Milk Products

Directory of Open Access Journals (Sweden)

Jovanka Lukic

2013-01-01

Full Text Available Lactobacillus helveticus BGRA43 isolated from human intestines shows antimicrobial activity against foodborne pathogens and during fermentation in milk releases peptides with demonstrated anti-inflammatory properties. In this study, it was found that strain BGRA43 exhibits antimicrobial activity against human pathogens Yersinia enterocolitica, Shigella sonnei, S. flexneri and Streptococcus pneumoniae. Strain BGRA43 was able to survive in simulated gastric juice containing milk and retained cell number stability during the incubation in simulated intestinal conditions. In addition, LC/MS/MS analysis showed the ability of BGRA43 to hydrolyze β-lactoglobulin. Abundant growth of strain BGRA43 occurred in the presence of prebiotics inulin or concentrated oat bran β-glucan (Nutrim®, even when used as the sole carbon source. Similarly, strain BGRA43 grew satisfactorily in pure cow's or goat's milk as well as in the milk containing inulin or Nutrim®. Using the probiotic strain BGRA43 as a single starter strain, fermented milk products obtained from cow's or goat's milk with or without inulin or Nutrim® contained about 107 CFU/mL. The products were homogeneous and viscous and the best sensory scores were observed for fermented milk beverage made from reconstituted skimmed milk, whole cow's milk and whole goat's milk supplemented with 1 % inulin.

49 CFR 1242.43 - Administration (account XX-27-01).

Science.gov (United States)

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Administration (account XX-27-01). 1242.43 Section...-Equipment § 1242.43 Administration (account XX-27-01). Separate common expenses according to freight/passenger separation of the following accounts: Passenger and Other Revenue Equipment (XX-27-45) Work and...

30 CFR 36.43 - Determination of exhaust-gas composition.

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2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Determination of exhaust-gas composition. 36.43... TRANSPORTATION EQUIPMENT Test Requirements § 36.43 Determination of exhaust-gas composition. (a) Samples shall be..., hydrogen, methane, nitrogen, oxides of nitrogen, and aldehydes, or any other constituent prescribed by MSHA...

43 CFR 11.14 - Definitions.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Definitions. 11.14 Section 11.14 Public Lands: Interior Office of the Secretary of the Interior NATURAL RESOURCE DAMAGE ASSESSMENTS Introduction... assessment means the process of collecting, compiling, and analyzing information, statistics, or data through...

43 CFR 41.310 - Recruitment.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.310 Section 41.310 Public... in Admission and Recruitment Prohibited § 41.310 Recruitment. (a) Nondiscriminatory recruitment. A... recruitment and admission of students. A recipient may be required to undertake additional recruitment efforts...

43 CFR 41.540 - Advertising.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Advertising. 41.540 Section 41.540 Public... in Employment in Education Programs or Activities Prohibited § 41.540 Advertising. A recipient shall not in any advertising related to employment indicate preference, limitation, specification, or...

43 CFR 41.500 - Employment.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Employment. 41.500 Section 41.500 Public... in Employment in Education Programs or Activities Prohibited § 41.500 Employment. (a) General. (1) No... subjected to discrimination in employment, or recruitment, consideration, or selection therefor, whether...

41 CFR 109-43.307-52 - Nuclear-related or proliferation-sensitive personal property.

Science.gov (United States)

2010-07-01

... as practicable, any civilian utility or commercial value of the personal property. ... proliferation-sensitive personal property. 109-43.307-52 Section 109-43.307-52 Public Contracts and Property... MANAGEMENT REGULATIONS UTILIZATION AND DISPOSAL 43-UTILIZATION OF PERSONAL PROPERTY 43.3-Utilization of...

Heat-shock protein dysregulation is associated with functional and pathological TDP-43 aggregation

Science.gov (United States)

Chang, Hsiang-Yu; Hou, Shin-Chen; Way, Tzong-Der; Wong, Chi-Huey; Wang, I.-Fan

2013-11-01

Conformational disorders are involved in various neurodegenerative diseases. Reactive oxygen species (ROS) are the major contributors to neurodegenerative disease; however, ROS that affect the structural changes in misfolded disease proteins have yet to be well characterized. Here we demonstrate that the intrinsic propensity of TDP-43 to aggregate drives the assembly of TDP-43-positive stress granules and soluble toxic TDP-43 oligomers in response to a ROS insult via a disulfide crosslinking-independent mechanism. Notably, ROS-induced TDP-43 protein assembly correlates with the dynamics of certain TDP-43-associated chaperones. The heat-shock protein (HSP)-90 inhibitor 17-AAG prevents ROS-induced TDP-43 aggregation, alters the type of TDP-43 multimers and reduces the severity of pathological TDP-43 inclusions. In summary, our study suggests that a common mechanism could be involved in the pathogenesis of conformational diseases that result from HSP dysregulation.

TDP-43 causes differential pathology in neuronal versus glial cells in the mouse brain.

Science.gov (United States)

Yan, Sen; Wang, Chuan-En; Wei, Wenjie; Gaertig, Marta A; Lai, Liangxue; Li, Shihua; Li, Xiao-Jiang

2014-05-15

Mutations in TAR DNA-binding protein 43 (TDP-43) are associated with familial forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Although recent studies have revealed that mutant TDP-43 in neuronal and glial cells is toxic, how mutant TDP-43 causes primarily neuronal degeneration in an age-dependent manner remains unclear. Using adeno-associated virus (AAV) that expresses mutant TDP-43 (M337V) ubiquitously, we found that mutant TDP-43 accumulates preferentially in neuronal cells in the postnatal mouse brain. We then ubiquitously or selectively expressed mutant TDP-43 in neuronal and glial cells in the striatum of adult mouse brains via stereotaxic injection of AAV vectors and found that it also preferentially accumulates in neuronal cells. Expression of mutant TDP-43 in neurons in the striatum causes more severe degeneration, earlier death and more robust symptoms in mice than expression of mutant TDP-43 in glial cells; however, aging increases the expression of mutant TDP-43 in glial cells, and expression of mutant TDP-43 in older mice caused earlier onset of phenotypes and more severe neuropathology than that in younger mice. Although expression of mutant TDP-43 in glial cells via stereotaxic injection does not lead to robust neurological phenotypes, systemic inhibition of the proteasome activity via MG132 in postnatal mice could exacerbate glial TDP-43-mediated toxicity and cause mice to die earlier. Consistently, this inhibition increases the expression of mutant TDP-43 in glial cells in mouse brains. Thus, the differential accumulation of mutant TDP-43 in neuronal versus glial cells contributes to the preferential toxicity of mutant TDP-43 in neuronal cells and age-dependent pathology.

19 CFR 134.43 - Methods of marking specific articles.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Methods of marking specific articles. 134.43...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Method and Location of Marking Imported Articles § 134.43 Methods of marking specific articles. (a) Marking previously required by certain provisions of the...

9 CFR 124.43 - Administrative decision.

Science.gov (United States)

2010-01-01

... Diligence Hearing § 124.43 Administrative decision. Within 30 days after completion of the due diligence... publish the due diligence redetermination in the Federal Register, notify PTO of the redetermination, and...

Gap junction protein connexin43 exacerbates lung vascular permeability.

Directory of Open Access Journals (Sweden)

James J O'Donnell

Full Text Available Increased vascular permeability causes pulmonary edema that impairs arterial oxygenation and thus contributes to morbidity and mortality associated with Acute Respiratory Distress Syndrome and sepsis. Although components of intercellular adhesive and tight junctions are critical for maintaining the endothelial barrier, there has been limited study of the roles of gap junctions and their component proteins (connexins. Since connexins can modulate inflammatory signaling in other systems, we hypothesized that connexins may also regulate pulmonary endothelial permeability. The relationships between connexins and the permeability response to inflammatory stimuli were studied in cultured human pulmonary endothelial cells. Prolonged treatment with thrombin, lipopolysaccharide, or pathological cyclic stretch increased levels of mRNA and protein for the major connexin, connexin43 (Cx43. Thrombin and lipopolysaccharide both increased intercellular communication assayed by transfer of microinjected Lucifer yellow. Although thrombin decreased transendothelial resistance in these cells, the response was attenuated by pretreatment with the connexin inhibitor carbenoxolone. Additionally, the decreases of transendothelial resistance produced by either thrombin or lipopolysaccharide were attenuated by reducing Cx43 expression by siRNA knockdown. Both carbenoxolone and Cx43 knockdown also abrogated thrombin-induced phosphorylation of myosin light chain. Taken together, these data suggest that increased lung vascular permeability induced by inflammatory conditions may be amplified via increased expression of Cx43 and intercellular communication among pulmonary endothelial cells.

TDP-43 protein variants as biomarkers in amyotrophic lateral sclerosis.

Science.gov (United States)

Williams, Stephanie M; Khan, Galam; Harris, Brent T; Ravits, John; Sierks, Michael R

2017-01-25

TDP-43 aggregates accumulate in individuals affected by amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, representing potential diagnostic and therapeutic targets. Using an atomic force microscopy based biopanning protocol developed in our lab, we previously isolated 23 TDP-43 reactive antibody fragments with preference for human ALS brain tissue relative to frontotemporal dementia, a related neurodegeneration, and healthy samples from phage-displayed single chain antibody fragment (scFv) libraries. Here we further characterize the binding specificity of these different scFvs and identify which ones have promise for detecting ALS biomarkers in human brain tissue and plasma samples. We developed a sensitive capture ELISA for detection of different disease related TDP-43 variants using the scFvs identified from the ALS biopanning. We show that a wide variety of disease selective TDP-43 variants are present in ALS as the scFvs show different reactivity profiles amongst the ALS cases. When assaying individual human brain tissue cases, three scFvs (ALS-TDP6, ALS-TDP10 and ALS-TDP14) reacted with all the ALS cases and 12 others reacted with the majority of the ALS cases, and none of the scFvs reacted with any control samples. When assaying individual human plasma samples, 9 different scFvs reacted with all the sporadic ALS samples and again none of them reacted with any control samples. These 9 different scFvs had different patterns of reactivity with plasma samples obtained from chromosome 9 open reading frame 72 (c9orf72) cases indicating that these familial ALS genetic variants may display different TDP-43 pathology than sporadic ALS cases. These results indicated that a range of disease specific TDP-43 variants are generated in ALS patients with different variants being generated in sporadic and familial cases. We show that a small panel of scFvs recognizing different TDP-43 variants can generate a neuropathological and plasma biomarker

43 CFR 423.42 - Gambling.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Gambling. 423.42 Section 423.42 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR... Gambling. Commercial gambling in any form, or the operation of gambling devices, is prohibited on...

43 CFR 423.35 - Animals.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Animals. 423.35 Section 423.35 Public... Animals. (a) You must not bring pets or other animals into public buildings, public transportation vehicles, or sanitary facilities. This provision does not apply to properly trained animals assisting...

43 CFR 41.200 - Application.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application. 41.200 Section 41.200 Public Lands: Interior Office of the Secretary of the Interior NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Coverage § 41.200 Application...

43 CFR 17.201 - Application.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application. 17.201 Section 17.201 Public Lands: Interior Office of the Secretary of the Interior NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OF THE DEPARTMENT OF THE INTERIOR Nondiscrimination on the Basis of Handicap § 17.201 Application...

43 CFR 423.34 - Sanitation.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Sanitation. 423.34 Section 423.34 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR... Sanitation. (a) You must not bring or improperly dispose of refuse on Reclamation facilities, lands, and...

43 CFR 41.510 - Recruitment.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Recruitment. 41.510 Section 41.510 Public... in Employment in Education Programs or Activities Prohibited § 41.510 Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment...

43 CFR 4.1373 - Hearing.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Hearing. 4.1373 Section 4.1373 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Special Rules Applicable to Surface Coal Mining Hearings and Appeals Review of Osm Decisions Proposing to...

43 CFR 4.1383 - Hearing.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Hearing. 4.1383 Section 4.1383 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES Special Rules Applicable to Surface Coal Mining Hearings and Appeals Review of Office of Surface Mining...

43 CFR 4.1102 - Construction.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Construction. 4.1102 Section 4.1102 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES... Construction. These rules shall be construed to achieve the just, timely, and inexpensive determination of all...

Sequence and expression analyses of porcine ISG15 and ISG43 genes.

Science.gov (United States)

Huang, Jiangnan; Zhao, Shuhong; Zhu, Mengjin; Wu, Zhenfang; Yu, Mei

2009-08-01

The coding sequences of porcine interferon-stimulated gene 15 (ISG15) and the interferon-stimulated gene (ISG43) were cloned from swine spleen mRNA. The amino acid sequences deduced from porcine ISG15 and ISG43 genes coding sequence shared 24-75% and 29-83% similarity with ISG15s and ISG43s from other vertebrates, respectively. Structural analyses revealed that porcine ISG15 comprises two ubiquitin homologues motifs (UBQ) domain and a conserved C-terminal LRLRGG conjugating motif. Porcine ISG43 contains an ubiquitin-processing proteases-like domain. Phylogenetic analyses showed that porcine ISG15 and ISG43 were mostly related to rat ISG15 and cattle ISG43, respectively. Using quantitative real-time PCR assay, significant increased expression levels of porcine ISG15 and ISG43 genes were detected in porcine kidney endothelial cells (PK15) cells treated with poly I:C. We also observed the enhanced mRNA expression of three members of dsRNA pattern-recognition receptors (PRR), TLR3, DDX58 and IFIH1, which have been reported to act as critical receptors in inducing the mRNA expression of ISG15 and ISG43 genes. However, we did not detect any induced mRNA expression of IFNalpha and IFNbeta, suggesting that transcriptional activations of ISG15 and ISG43 were mediated through IFN-independent signaling pathway in the poly I:C treated PK15 cells. Association analyses in a Landrace pig population revealed that ISG15 c.347T>C (BstUI) polymorphism and the ISG43 c.953T>G (BccI) polymorphism were significantly associated with hematological parameters and immune-related traits.

19 CFR 147.43 - Entry under the Customs laws.

Science.gov (United States)

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Entry under the Customs laws. 147.43 Section 147.43 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF... the Customs laws. (a) Payment of duties and taxes. Any applicable duties and internal revenue taxes on...

Structure-function analysis of the self-recognizing Antigen 43 autotransporter protein from Escherichia coli

DEFF Research Database (Denmark)

Klemm, Per; Hjerrild, L.; Gjermansen, Morten

2004-01-01

Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia coli strains. Expression of Ag43 confers aggregation and fluffing of cells, promotes biofilm formation and is associated with enhanced resistance to antimicrobial agents. Ag43 is an autotransporter protein and consi......Antigen 43 (Ag43) is a self-recognizing surface adhesin found in most Escherichia coli strains. Expression of Ag43 confers aggregation and fluffing of cells, promotes biofilm formation and is associated with enhanced resistance to antimicrobial agents. Ag43 is an autotransporter protein......-clumping variants, we have pinpointed the region of the protein responsible for autoaggregation to be located within the N-terminal one-third of the passenger domain. Our data suggest that ionic interactions between charged residues residing in interacting pairs of Ag43(alpha) domains may be important for the self...

29 CFR 783.43 - Computation of seaman's minimum wage.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Computation of seaman's minimum wage. 783.43 Section 783.43...'s minimum wage. Section 6(b) requires, under paragraph (2) of the subsection, that an employee...'s minimum wage requirements by reason of the 1961 Amendments (see §§ 783.23 and 783.26). Although...

43 CFR 37.2 - Policy.

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2010-10-01

... will be determined through the agency resource management planning process with full public... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Policy. 37.2 Section 37.2 Public Lands: Interior Office of the Secretary of the Interior CAVE MANAGEMENT Cave Management-General § 37.2 Policy. It...

43 CFR 24.1 - Introduction.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Introduction. 24.1 Section 24.1 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE POLICY: STATE-FEDERAL RELATIONSHIPS § 24.1 Introduction. (a) In 1970, the Secretary of the Interior...

43 CFR 32.1 - Introduction.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Introduction. 32.1 Section 32.1 Public Lands: Interior Office of the Secretary of the Interior GRANTS TO STATES FOR ESTABLISHING YOUNG ADULT CONSERVATION CORPS (YACC) PROGRAM § 32.1 Introduction. (a) The Young Adult Conservation Corps (YACC) is...

43 CFR 17.502 - Application.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application. 17.502 Section 17.502 Public Lands: Interior Office of the Secretary of the Interior NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS... Programs or Activities Conducted by the Department of the Interior § 17.502 Application. This part applies...

43 CFR 27.2 - Application.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application. 27.2 Section 27.2 Public Lands: Interior Office of the Secretary of the Interior NONDISCRIMINATION IN ACTIVITIES CONDUCTED UNDER... II OF PUBLIC LAW 93-153 § 27.2 Application. This part applies to all activities, including...

43 CFR 41.405 - Housing.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Housing. 41.405 Section 41.405 Public... in Education Programs or Activities Prohibited § 41.405 Housing. (a) Generally. A recipient shall not... offer different services or benefits related to housing, except as provided in this section (including...

43 CFR 17.540 - Employment.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Employment. 17.540 Section 17.540 Public... Programs or Activities Conducted by the Department of the Interior § 17.540 Employment. No qualified handicapped person shall, on the basis of handicap, be subjected to discrimination in employment under any...

43 CFR 17.332 - Mediation.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Mediation. 17.332 Section 17.332 Public..., and Enforcement Procedures § 17.332 Mediation. (a) Referral of complaints for mediation. DOI will... participate in the mediation process to the extent necessary to reach an agreement or make an informed...

Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate

NARCIS (Netherlands)

van Zeijl, Leonie; Ponsioen, Bas; Giepmans, Ben N G; Ariaens, Aafke; Postma, Friso R; Várnai, Péter; Balla, Tamas; Divecha, Nullin; Jalink, Kees; Moolenaar, Wouter H

2007-01-01

Cell-cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell-cell communication is inhibited by depletion of phosphatidylinositol

Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

Directory of Open Access Journals (Sweden)

Katsuhisa Masaki

Full Text Available BACKGROUND: Multiple sclerosis (MS and neuromyelitis optica (NMO occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx pathology and disease aggressiveness in Asian patients with MS and NMO. METHODS/PRINCIPAL FINDINGS: Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD, six with MS, and 20 with other neurological diseases (OND. Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59, chronic active (n=58 and chronic inactive (n=23. Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090. Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296. Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. CONCLUSIONS

Overlapping but distinct TDP-43 and tau pathologic patterns in aged hippocampi.

Science.gov (United States)

Smith, Vanessa D; Bachstetter, Adam D; Ighodaro, Eseosa; Roberts, Kelly; Abner, Erin L; Fardo, David W; Nelson, Peter T

2018-03-01

Intracellular proteinaceous aggregates (inclusion bodies) are almost always detectable at autopsy in brains of elderly individuals. Inclusion bodies composed of TDP-43 and tau proteins often coexist in the same brain, and each of these pathologic biomarkers is associated independently with cognitive impairment. However, uncertainties remain about how the presence and neuroanatomical distribution of inclusion bodies correlate with underlying diseases including Alzheimer's disease (AD). To address this knowledge gap, we analyzed data from the University of Kentucky AD Center autopsy series (n = 247); none of the brains had frontotemporal lobar degeneration. A specific question for this study was whether neurofibrillary tangle (NFT) pathology outside of the Braak NFT staging scheme is characteristic of brains with TDP-43 pathology but lacking AD, that is those with cerebral age-related TDP-43 with sclerosis (CARTS). We also tested whether TDP-43 pathology is associated with comorbid AD pathology, and whether argyrophilic grains are relatively likely to be present in cases with, vs. without, TDP-43 pathology. Consistent with prior studies, hippocampal TDP-43 pathology was associated with advanced AD - Braak NFT stages V/VI. However, argyrophilic grain pathology was not more common in cases with TDP-43 pathology in this data set. In brains with CARTS (TDP-43[+]/AD[-] cases), there were more NFTs in dentate granule neurons than were seen in TDP-43[-]/AD[-] cases. These dentate granule cell NFTs could provide a proxy indicator of CARTS pathology in cases lacking substantial AD pathology. Immunofluorescent experiments in a subsample of cases found that, in both advanced AD and CARTS, approximately 1% of dentate granule neurons were PHF-1 immunopositive, whereas ∼25% of TDP-43 positive cells showed colocalized PHF-1 immunoreactivity. We conclude that NFTs in hippocampal dentate granule neurons are often present in CARTS, and TDP-43 pathology may be secondary to or

Chronic hypertension alters the expression of Cx43 in cardiovascular muscle cells

Directory of Open Access Journals (Sweden)

Haefliger J.-A.

2000-01-01

Full Text Available Connexin43 (Cx43, the predominant gap junction protein of muscle cells in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension on the expression of Cx43 in aorta and heart in three different models of experimental hypertension. Rats were made hypertensive either by clipping one renal artery (two kidney, one-clip renal (2K,1C model by administration of deoxycorticosterone and salt (DOCA-salt model or by inhibiting nitric oxide synthase with NG-nitro-L-arginine methyl ester (L-NAME model. After 4 weeks, rats of the three models showed a similar increase in intra-arterial mean blood pressure and in the thickness of the walls of both aorta and heart. Analysis of heart mRNA demonstrated no change in Cx43 expression in the three models compared to their respective controls. The same 2K,1C and DOCA-salt hypertensive animals expressed twice more Cx43 in aorta, and the 2K,1C rats showed an increase in arterial distensibility. In contrast, the aortae of L-NAME hypertensive rats were characterized by a 50% decrease in Cx43 and the carotid arteries did not show increased distensibility. Western blot analysis indicated that Cx43 was more phosphorylated in the aortae of 2K,1C rats than in those of L-NAME or control rats, indicating a differential regulation of aortic Cx43 in different models of hypertension. The data suggest that localized mechanical forces induced by hypertension affect Cx43 expression and that the cell-to-cell communication mediated by Cx43 channels may contribute to regulating the elasticity of the vascular wall.

TDP-43 in Familial and Sporadic Frontotemporal Lobar Degeneration with Ubiquitin Inclusions

NARCIS (Netherlands)

Cairns, Nigel J.; Neumann, Manuela; Bigio, Eileen H.; Holm, Ida E.; Troost, Dirk; Hatanpaa, Kimmo J.; Foong, Chan; White, Charles L.; Schneider, Julie A.; Kretzschmar, Hans A.; Carter, Deborah; Taylor-Reinwald, Lisa; Paulsmeyer, Katherine; Strider, Jeffrey; Gitcho, Michael; Goate, Alison M.; Morris, John C.; Mishrall, Manjari; Kwong, Linda K.; Stieber, Anna; Xu, Yan; Forman, Mark S.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Mackenzie, Ian R. A.

2007-01-01

TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called

43 CFR 24.7 - Exemptions.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Exemptions. 24.7 Section 24.7 Public Lands...-FEDERAL RELATIONSHIPS § 24.7 Exemptions. (a) Exempted from this policy are the following: (1) The control and regulation by the United States, in the area in which an international convention or treaty...

43 CFR 26.1 - Introduction.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Introduction. 26.1 Section 26.1 Public Lands: Interior Office of the Secretary of the Interior GRANTS TO STATES FOR ESTABLISHING YOUTH CONSERVATION CORPS PROGRAMS § 26.1 Introduction. (a) The Youth Conservation Corps (YCC) is a program of summer...

43 CFR 423.36 - Swimming.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Swimming. 423.36 Section 423.36 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR... Swimming. (a) You may swim, wade, snorkel, scuba dive, raft, or tube at your own risk in Reclamation waters...

43 CFR 3.5 - Application.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application. 3.5 Section 3.5 Public Lands: Interior Office of the Secretary of the Interior PRESERVATION OF AMERICAN ANTIQUITIES § 3.5 Application. Each application for a permit should be filed with the Secretary having jurisdiction, and must be...

43 CFR 3.10 - Reports.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Reports. 3.10 Section 3.10 Public Lands: Interior Office of the Secretary of the Interior PRESERVATION OF AMERICAN ANTIQUITIES § 3.10 Reports. At the close of each season's field work the permitee shall report in duplicate to the Smithsonian...

43 CFR 35.21 - Discovery.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery. 35.21 Section 35.21 Public... AND STATEMENTS § 35.21 Discovery. (a) The following types of discovery are authorized: (1) Requests...) Unless mutually agreed to by the parties, discovery is available only as ordered by the ALJ. The ALJ...

43 CFR 402.6 - Price.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Price. 402.6 Section 402.6 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR SALE OF LANDS IN FEDERAL RECLAMATION PROJECTS Public Lands § 402.6 Price. The price of land sold under this...

20 CFR 222.43 - How the one-half support determination is made.

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2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false How the one-half support determination is made. 222.43 Section 222.43 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT FAMILY RELATIONSHIPS Relationship as Parent, Grandchild, Brother or Sister § 222.43...

X-43A/Hyper-X Vehicle Arrives at NASA Dryden

Science.gov (United States)

1999-01-01

A close-up of the X-43A Hypersonic Experimental Vehicle, or 'Hyper-X,' in its protective shipping framework as it arrives at the Dryden Flight Research Center in October 1999. The X-43A was developed to research a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only

X-43A Hypersonic Experimental Vehicle - Artist Concept in Flight

Science.gov (United States)

1999-01-01

An artist's conception of the X-43A Hypersonic Experimental Vehicle, or 'Hyper-X' in flight. The X-43A was developed to flight test a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will

43 CFR 7.19 - Report.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Report. 7.19 Section 7.19 Public Lands... § 7.19 Report. (a) Each Federal land manager, when requested by the Secretary of the Interior, will... comprehensively report on activities carried out under provisions of the Act. (b) The Secretary of the Interior...

43 CFR 29.11 - Investment.

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2010-10-01

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43 CFR 402.10 - Patent.

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2010-10-01

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43 CFR 12.73 - Supplies.

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2010-10-01

... aggregate fair market value upon termination or completion of the award, and if the supplies are not needed... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Supplies. 12.73 Section 12.73 Public Lands... State and Local Governments Changes, Property, and Subawards § 12.73 Supplies. (a) Title. Title to...

43 CFR 3.16 - Seizure.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Seizure. 3.16 Section 3.16 Public Lands: Interior Office of the Secretary of the Interior PRESERVATION OF AMERICAN ANTIQUITIES § 3.16 Seizure. Any object of antiquity taken, or collection made, on lands owned or controlled by the United States, without...

Silencing the expression of connexin 43 decreases inflammation and joint destruction in experimental arthritis.

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Tsuchida, Shinji; Arai, Yuji; Kishida, Tsunao; Takahashi, Kenji A; Honjo, Kuniaki; Terauchi, Ryu; Inoue, Hiroaki; Oda, Ryo; Mazda, Osam; Kubo, Toshikazu

2013-04-01

The objective of the present study was to determine whether the expression of connexin 43 (Cx43) effected on inflammatory conditions in rat fibroblast-like synoviocytes (FLS) and on rat model of rheumatoid arthritis (RA). The expression of Cx43 in rat FLS stimulated with lipopolysaccharide (LPS) was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The effects of small-interfering RNA targeting Cx43 (siCx43) on pro-inflammatory cytokines and chemokine were assessed by real-time RT-PCR and enzyme-linked immunosorbent assay (ELISA). The therapeutic and side effects of siCx43 in a rat model of collagen-induced arthritis (CIA) were examined by in vivo electroporation method. LPS markedly enhanced Cx43 gene expression in rat FLS, with transfection of siCx43 suppressing the over-expression of pro-inflammatory cytokines and the chemokine. Treatment of CIA rats with siCx43 significantly ameliorated paw swelling, and significantly reduced histological arthritis scores and radiographic scores. In histological appearance of rat ankle joints, siCx43 treatment significantly decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive (osteoclast-like) cells. These findings indicated that siCx43 had anti-inflammatory effects in rat FLS and efficiently inhibited the development of CIA. Cx43 may play an important role in the pathophysiology of RA, and may be a potential target molecule for novel RA therapies. Copyright © 2012 Orthopaedic Research Society.

ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

International Nuclear Information System (INIS)

Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan; Jang, Deok-Jin; Lee, Jin-A

2013-01-01

Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival

ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

Energy Technology Data Exchange (ETDEWEB)

Han, Jeong-Ho; Yu, Tae-Hoon; Ryu, Hyun-Hee; Jun, Mi-Hee; Ban, Byung-Kwan [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of); Jang, Deok-Jin [Department of Applied Biology, College of Ecology and Environment, Kyungpook National University, 386, Gajang-dong, Sangju-si, Kyungbuk 742-711 (Korea, Republic of); Lee, Jin-A, E-mail: leeja@hnu.kr [Department of Biotechnology, College of Life Science and Nanotechnology, Hannam University, Dajeon 305-811 (Korea, Republic of)

2013-08-01

Tar-DNA binding protein of 43 kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons. Highlights: • The function of nuclear TDP-43 in neurite morphology in mature neurons. • Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. • Abnormal neurite morphology caused by missense mutants of TDP-43. • The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival.

45 CFR 400.43 - Requirements for documentation of refugee status.

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2010-10-01

... 45 Public Welfare 2 2010-10-01 2010-10-01 false Requirements for documentation of refugee status. 400.43 Section 400.43 Public Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE...

43 CFR 8.6 - Buildings.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Buildings. 8.6 Section 8.6 Public Lands: Interior Office of the Secretary of the Interior JOINT POLICIES OF THE DEPARTMENTS OF THE INTERIOR AND OF THE ARMY RELATIVE TO RESERVOIR PROJECT LANDS § 8.6 Buildings. Buildings for human occupancy as well as...

43 CFR 35.25 - Fees.

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2010-10-01

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43 CFR 424.1 - Regulations.

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2010-10-01

... provisions of Article 34 and 25 of repayment contract I1r-1534, dated September 20, 1948, between the United... supplemented, Articles 34, and 25 of the Repayment Contract I1r-1534 dated Sept. 20, 1948, between the United... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Regulations. 424.1 Section 424.1 Public...

14 CFR 43.12 - Maintenance records: Falsification, reproduction, or alteration.

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2010-01-01

..., reproduction, or alteration. 43.12 Section 43.12 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION... Maintenance records: Falsification, reproduction, or alteration. (a) No person may make or cause to be made..., kept, or used to show compliance with any requirement under this part; (2) Any reproduction, for...

Domain-Specific Partitioning of Uterine Artery Endothelial Connexin43 and Caveolin-1.

Science.gov (United States)

Ampey, Bryan C; Morschauser, Timothy J; Ramadoss, Jayanth; Magness, Ronald R

2016-10-01

Uterine vascular adaptations facilitate rises in uterine blood flow during pregnancy, which are associated with gap junction connexin (Cx) proteins and endothelial nitric oxide synthase. In uterine artery endothelial cells (UAECs), ATP activates endothelial nitric oxide synthase in a pregnancy (P)-specific manner that is dependent on Cx43 function. Caveolar subcellular domain partitioning plays key roles in ATP-induced endothelial nitric oxide synthase activation and nitric oxide production. Little is known regarding the partitioning of Cx proteins to caveolar domains or their dynamics with ATP treatment. We observed that Cx43-mediated gap junction function with ATP stimulation is associated with Cx43 repartitioning between the noncaveolar and caveolar domains. Compared with UAECs from nonpregnant (NP) ewes, levels of ATP, PGI2, cAMP, NOx, and cGMP were 2-fold higher (PLucifer yellow dye transfer, a response abrogated by Gap27, but not Gap 26, indicating involvement of Cx43, but not Cx37. Confocal microscopy revealed domain partitioning of Cx43 and caveolin-1. In pregnant UAECs, LC/MS/MS analysis revealed only Cx43 in the caveolar domain. In contrast, Cx37 was located only in the noncaveolar pool. Western analysis revealed that ATP increased Cx43 distribution (1.7-fold; P=0.013) to the caveolar domain, but had no effect on Cx37. These data demonstrate rapid ATP-stimulated repartitioning of Cx43 to the caveolae, where endothelial nitric oxide synthase resides and plays an important role in nitric oxide-mediated increasing uterine blood flow during pregnancy. © 2016 American Heart Association, Inc.

Histone deacetylase inhibition reduces cardiac Connexin43 expression and gap junction communication

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Qin eXu

2013-04-01

Full Text Available Histone deactylase (HDAC inhibitors are being investigated as novel therapies for cancer, inflammation, neurodegeneration, and heart failure. The effects of HDAC inhibitors on the functional expression of cardiac gap junctions (GJ are essentially unknown. The purpose of this study was to determine the effects of trichostatin A (TSA and vorinostat (VOR on functional GJ expression in ventricular cardiomyocytes. The effects of HDAC inhibition on connexin43 (Cx43 expression and functional GJ assembly were examined in primary cultured neonatal mouse ventricular myocytes. TSA and VOR reduced Cx43 mRNA, protein expression, and immunolocalized Cx43 GJ plaque area within ventricular myocyte monolayer cultures in a dose-dependent manner. Chromatin-immunoprecipitation experiments revealed altered protein interactions with the Cx43 promoter. VOR also altered the phosphorylation state of several key regulatory Cx43 phospho-serine sites. Patch clamp analysis revealed reduced electrical coupling between isolated ventricular myocyte pairs, altered transjunctional voltage-dependent inactivation kinetics, and steady state junctional conductance inactivation and recovery relationships. Single GJ channel conductance was reduced to 54 pS only by maximum inhibitory doses of TSA (>= 100 nM. These two hydroxamate pan-HDAC inhibitors exert multiple levels of regulation on ventricular GJ communication by altering Cx43 expression, GJ area, post-translational modifications (e.g. phosphorylation, acetylation, gating, and channel conductance. Although a 50% downregulation of Cx43 GJ communication alone may not be sufficient to slow ventricular conduction or induce arrhythmias, the development of class-selective HDAC inhibitors may help avoid the potential negative cardiovascular effects of pan-HDACI.

TC-PTP directly interacts with connexin43 to regulate gap junction intercellular communication

Science.gov (United States)

Li, Hanjun; Spagnol, Gaelle; Naslavsky, Naava; Caplan, Steve; Sorgen, Paul L.

2014-01-01

ABSTRACT Protein kinases have long been reported to regulate connexins; however, little is known about the involvement of phosphatases in the modulation of intercellular communication through gap junctions and the subsequent downstream effects on cellular processes. Here, we identify an interaction between the T-cell protein tyrosine phosphatase (TC-PTP, officially known as PTPN2) and the carboxyl terminus of connexin43 (Cx43, officially known as GJA1). Two cell lines, normal rat kidney (NRK) cells endogenously expressing Cx43 and an NRK-derived cell line expressing v-Src with temperature-sensitive activity, were used to demonstrate that EGF and v-Src stimulation, respectively, induced TC-PTP to colocalize with Cx43 at the plasma membrane. Cell biology experiments using phospho-specific antibodies and biophysical assays demonstrated that the interaction is direct and that TC-PTP dephosphorylates Cx43 residues Y247 and Y265, but does not affect v-Src. Transfection of TC-PTP also indirectly led to the dephosphorylation of Cx43 S368, by inactivating PKCα and PKCδ, with no effect on the phosphorylation of S279 and S282 (MAPK-dependent phosphorylation sites). Dephosphorylation maintained Cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-Src-mediated phosphorylation of Cx43. Understanding dephosphorylation, along with the well-documented roles of Cx43 phosphorylation, might eventually lead to methods to modulate the regulation of gap junction channels, with potential benefits for human health. PMID:24849651

TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion.

Science.gov (United States)

Xia, Qin; Wang, Hongfeng; Hao, Zongbing; Fu, Cheng; Hu, Qingsong; Gao, Feng; Ren, Haigang; Chen, Dong; Han, Junhai; Ying, Zheng; Wang, Guanghui

2016-01-18

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is characterized by selective loss of motor neurons in brain and spinal cord. TAR DNA-binding protein 43 (TDP-43) was identified as a major component of disease pathogenesis in ALS, frontotemporal lobar degeneration (FTLD), and other neurodegenerative disease. Despite the fact that TDP-43 is a multi-functional protein involved in RNA processing and a large number of TDP-43 RNA targets have been discovered, the initial toxic effect and the pathogenic mechanism underlying TDP-43-linked neurodegeneration remain elusive. In this study, we found that loss of TDP-43 strongly induced a nuclear translocation of TFEB, the master regulator of lysosomal biogenesis and autophagy, through targeting the mTORC1 key component raptor. This regulation in turn enhanced global gene expressions in the autophagy-lysosome pathway (ALP) and increased autophagosomal and lysosomal biogenesis. However, loss of TDP-43 also impaired the fusion of autophagosomes with lysosomes through dynactin 1 downregulation, leading to accumulation of immature autophagic vesicles and overwhelmed ALP function. Importantly, inhibition of mTORC1 signaling by rapamycin treatment aggravated the neurodegenerative phenotype in a TDP-43-depleted Drosophila model, whereas activation of mTORC1 signaling by PA treatment ameliorated the neurodegenerative phenotype. Taken together, our data indicate that impaired mTORC1 signaling and influenced ALP may contribute to TDP-43-mediated neurodegeneration. © 2015 The Authors.

Pharmacological reduction of ER stress protects against TDP-43 neuronal toxicity in vivo.

Science.gov (United States)

Vaccaro, Alexandra; Patten, Shunmoogum A; Aggad, Dina; Julien, Carl; Maios, Claudia; Kabashi, Edor; Drapeau, Pierre; Parker, J Alex

2013-07-01

C. elegans and D. rerio expressing mutant TAR DNA Binding Protein 43 (TDP-43) are powerful in vivo animal models for the genetics and pharmacology of amyotrophic lateral sclerosis (ALS). Using these small-animal models of ALS, we previously identified methylene blue (MB) as a potent suppressor of TDP-43 toxicity. Consequently here we investigated how MB might exert its neuroprotective properties and found that it acts through reduction of the endoplasmic reticulum (ER) stress response. We tested other compounds known to be active in the ER unfolded protein response in worms and zebrafish expressing mutant human TDP-43 (mTDP-43). We identified three compounds: salubrinal, guanabenz and a new structurally related compound phenazine, which also reduced paralysis, neurodegeneration and oxidative stress in our mTDP-43 models. Using C. elegans genetics, we showed that all four compounds act as potent suppressors of mTDP-43 toxicity through reduction of the ER stress response. Interestingly, these compounds operate through different branches of the ER unfolded protein pathway to achieve a common neuroprotective action. Our results indicate that protein-folding homeostasis in the ER is an important target for therapeutic development in ALS and other TDP-43-related neurodegenerative diseases. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

The Complex Subtype-Dependent Role of Connexin 43 (GJA1 in Breast Cancer

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Mélanie Busby

2018-02-01

Full Text Available Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43 in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression.

The Complex Subtype-Dependent Role of Connexin 43 (GJA1) in Breast Cancer

Science.gov (United States)

Busby, Mélanie; Hallett, Michael T.; Plante, Isabelle

2018-01-01

Gap junction transmembrane channels allow the transfer of small molecules between the cytoplasm of adjacent cells. They are formed by proteins named connexins (Cxs) that have long been considered as a tumor suppressor. This widespread view has been challenged by recent studies suggesting that the role of Connexin 43 (Cx43) in cancer is tissue- and stage-specific and can even promote tumor progression. High throughput profiling of invasive breast cancer has allowed for the construction of subtyping schemes that partition patients into at least four distinct intrinsic subtypes. This study characterizes Cx43 expression during cancer progression with each of the tumor subtypes using a compendium of publicly available gene expression data. In particular, we show that Cx43 expression depends greatly on intrinsic subtype. Tumor grade also co-varies with patient subtype, resulting in Cx43 co-expression with grade in a subtype-dependent manner. Better survival was associated with a high expression of Cx43 in unstratified and luminal tumors but with a low expression in Her2e subtype. A better understanding of Cx43 regulation in a subtype-dependent manner is needed to clarify the context in which Cx43 is associated with tumor suppression or cancer progression. PMID:29495625

43 CFR 27.12 - Judicial review.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Judicial review. 27.12 Section 27.12... UNDER TITLE II OF PUBLIC LAW 93-153 § 27.12 Judicial review. Action taken pursuant to this part is subject to judicial review. ...

8 CFR 1240.43 - Incompetent respondents.

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2010-01-01

... 1240.43 Aliens and Nationality EXECUTIVE OFFICE FOR IMMIGRATION REVIEW, DEPARTMENT OF JUSTICE IMMIGRATION REGULATIONS PROCEEDINGS TO DETERMINE REMOVABILITY OF ALIENS IN THE UNITED STATES Proceedings To Determine Deportability of Aliens in the United States: Hearing and Appeal (for Proceedings Commenced Prior...

43 CFR 4.1393 - Status of decision pending administrative review.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Status of decision pending administrative review. 4.1393 Section 4.1393 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT... Program; Federal Program for Indian Lands) § 4.1393 Status of decision pending administrative review. 43...

Effect of enhanced expression of connexin 43 on sunitinib-induced cytotoxicity in mesothelioma cells

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Miaki Uzu

2015-05-01

Full Text Available Connexin (Cx makes up a type of intercellular channel called gap junction (GJ. GJ plays a regulatory role in cellular physiology. The Cx expression level is often decreased in cancer cells compared to that in healthy ones, and the restoration of its expression has been shown to exert antiproliferative effects. This work aims to evaluate the effect of the restoration of connexin 43 (Cx43 (the most ubiquitous Cx subtype expression on sunitinib (SU-induced cytotoxicity in malignant mesothelioma (MM cells. Increased Cx43 expression in an MM cell line (H28 improved the ability of SU to inhibit receptor tyrosine kinase (RTK signaling. Moreover, higher Cx43 expression promoted SU-induced apoptosis. The cell viability test revealed that Cx43 enhanced the cytotoxic effect of SU in a GJ-independent manner. The effect of Cx43 on a proapoptotic factor, Bax, was then investigated. The interaction between Cx43 and Bax was confirmed by immunoprecipitation. Furthermore, higher Cx43 expression increased the production of a cleaved (active form of Bax during SU-induced apoptosis with no alteration in total Bax expression. These findings indicate that Cx43 most likely increases sensitivity to SU in H28 through direct interaction with Bax. In conclusion, we found that Cx43 overcame the chemoresistance of MM cells.

43 CFR 17.232 - Postsecondary education.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Postsecondary education. 17.232 Section 17... Postsecondary education. This section applies to postsecondary education and activities, including postsecondary vocational education programs or activities, that receive Federal financial assistance and to recipients that...

38 CFR 43.22 - Allowable costs.

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2010-07-01

... accounting standards that comply with cost principles acceptable to the Federal agency. ... Requirements Financial Administration § 43.22 Allowable costs. (a) Limitation on use of funds. Grant funds may... the grantee or subgrantee. (b) Applicable cost principles. For each kind of organization, there is a...

25 CFR 43.20 - Directory information.

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2010-04-01

... OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MAINTENANCE AND CONTROL OF STUDENT RECORDS IN BUREAU SCHOOLS § 43.20 Directory information. (a) Any educational institution making public directory..., address, telephone listing, date and place of birth, major field of study, participation in officially...

Novel mutations in TARDBP (TDP-43 in patients with familial amyotrophic lateral sclerosis.

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Nicola J Rutherford

2008-09-01

Full Text Available The TAR DNA-binding protein 43 (TDP-43 has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U, defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V were identified in the analysis of 92 familial ALS patients (3.3%, while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis.

Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

Science.gov (United States)

Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

2016-01-01

Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

Bibliography on Cold Regions Science and Technology. Volume 43. Part 2

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1989-12-01

North. Larionov, V.P.. ed. USA. Bates, R.E.. Cit3, (I988, pI07-II7, cog1 See talso): Logistica (1987, 91p, rus5 43-112 43-602 Military transportation ...Abbrsszzene, F. Achamal, E.M. de Current status and prospects for automatin of snow ava- Draining deicing pavings for bridge stabs (1989, p.14-19...engj 43.3732 Assilar, J.B., de Abdakarlmov, A.T. Development of sea ice in the Weddell Sea (1989, p.92-96, Elasticity solutions for semi-infinite ice

Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior.

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Feiguin, Fabian; Godena, Vinay K; Romano, Giulia; D'Ambrogio, Andrea; Klima, Raffaella; Baralle, Francisco E

2009-05-19

Pathological modifications in the highly conserved and ubiquitously expressed heterogeneous ribonucleoprotein TDP-43 were recently associated to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), a late-onset disorder that affects predominantly motoneurons [Neumann, M. et al. (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130-133, Sreedharan, J. et al. (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319, 1668-1672, Kabashi, E. et al. (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat. Genet. 40, 572-574]. However, the function of TDP-43 in vivo is unknown and a possible direct role in neurodegeneration remains speculative. Here, we report that flies lacking Drosophila TDP-43 appeared externally normal but presented deficient locomotive behaviors, reduced life span and anatomical defects at the neuromuscular junctions. These phenotypes were rescued by expression of the human protein in a restricted group of neurons including motoneurons. Our results demonstrate the role of this protein in vivo and suggest an alternative explanation to ALS pathogenesis that may be more due to the lack of TDP 43 function than to the toxicity of the aggregates.

The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

Energy Technology Data Exchange (ETDEWEB)

Chang, Chung-ke [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Wu, Tzong-Huah [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Institute of Biochemistry, Academia Sinica, Taipei 115, Taiwan (China); Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 300, Taiwan (China); Wu, Chu-Ya [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Graduate Institute of Engineering, National Taiwan University of Science and Technology, Taipei 106, Taiwan (China); Chiang, Ming-hui; Toh, Elsie Khai-Woon [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Hsu, Yin-Chih; Lin, Ku-Feng [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China); Liao, Yu-heng [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Huang, Tai-huang, E-mail: bmthh@gate.sinica.edu.tw [Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan (China); Department of Physics, National Taiwan Normal University, Taipei 106, Taiwan (China); Huang, Joseph Jen-Tse, E-mail: jthuang@chem.sinica.edu.tw [Institute of Chemistry, Academia Sinica, Taipei 115, Taiwan (China)

2012-08-24

Highlights: Black-Right-Pointing-Pointer The N-terminus of TDP-43 contains an independently folded structural domain (NTD). Black-Right-Pointing-Pointer The structural domains of TDP-43 are arranged in a beads-on-a-string fashion. Black-Right-Pointing-Pointer The NTD promotes TDP-43 oligomerization in a concentration-dependent manner. Black-Right-Pointing-Pointer The NTD may assist nucleic acid-binding activity of TDP-43. -- Abstract: TDP-43 is a DNA/RNA-binding protein associated with different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Here, the structural and physical properties of the N-terminus on TDP-43 have been carefully characterized through a combination of nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence anisotropy studies. We demonstrate for the first time the importance of the N-terminus in promoting TDP-43 oligomerization and enhancing its DNA-binding affinity. An unidentified structural domain in the N-terminus is also disclosed. Our findings provide insights into the N-terminal domain function of TDP-43.

Connexin 43 Communication Channels in Follicular Dendritic Cell Development and in Follicular Lymphomas

Directory of Open Access Journals (Sweden)

Hajnalka Rajnai

2015-01-01

Full Text Available Follicular dendritic cells (FDC show homo- and heterocellular metabolic coupling through connexin 43 (Cx43 gap junctions and support B cell selection and maturation in germinal centers. In follicular lymphomas B cells escape apoptosis while FDC develop abnormally. Here we tested Cx43 channels in reactive FDC development and follicular lymphomas. In culture, the treatment of FDC-B cell clusters (resembling to “ex vivo” germinal centers with Gap27 peptide, mimicking the 2nd extracellular loop of Cx43 protein, significantly impaired FDC-B cell cluster formation and cell survival. In untreated cultures of intact clusters, cell proliferation showed a moderate reduction. In tissues, Cx43 protein levels run parallel with the density of FDC both in reactive germinal centers and in malformed follicles of follicular lymphomas and showed strong upregulation in newly generated and/or degrading bi-/multinuclear FDC of rudimentary processes. However, the inverse correlation between Cx43 expression and B cell proliferation seen in reactive germinal centers was not detected in follicular lymphomas. Furthermore, Cx43 levels were not associated with either lymphoma grade or bone marrow involvement. Our results suggest that Cx43 channels are critical in FDC and “ex vivo” germinal center development and in the persistence of FDC in follicular lymphomas but do not affect tumor progression.

The role of the Cx43 C-terminus in GJ plaque formation and internalization

International Nuclear Information System (INIS)

Wayakanon, Praween; Bhattacharjee, Rajib; Nakahama, Ken-ichi; Morita, Ikuo

2012-01-01

Highlights: ► Cx43-GFP or -DsRed fusion proteins were expressed in HeLa cells. ► Roles of C-terminus were examined using various mutants. ► Gap junction plaque size was dependent on the length of C-terminus. ► C-terminus dependent gap junction plaque internalization was observed. -- Abstract: Connexin 43 (Cx43) is a major gap junction (GJ) protein found in many mammalian cell types. The C-terminal (CT) domain of Cx43 has unique characteristics in terms of amino acid (aa) sequence and its length differs from other connexins. This CT domain can be associated with protein partners to regulate GJ assembly and degradation, which results in the direct control of gap junction intercellular communication (GJIC). However, the essential roles of the CT regions involved in these mechanisms have not been fully elucidated. In this study, we aimed to investigate the specific regions of Cx43CT involved in GJ formation and internalization. Wild type Cx43 (382aa) and 10 CT truncated mutants were stably expressed in HeLa cells as GFP or DsRed tagged proteins. First, we found that the deletion of 235–382aa from Cx43 resulted in failure to make GJ and establish GJIC. Second, the Cx43 with 242–382aa CT deletion could form functional GJs and be internalized as annular gap junctions (AGJs). However, the plaques consisting of Cx43 with CT deletions (Δ242–382aa to Δ271–382aa) were longer than the plaques consisting of Cx43 with CT deletions (Δ302–382aa). Third, co-culture experiments of cells expressing wild type Cx43 (382) with cells expressing Cx43CT mutants revealed that the directions of GJ internalization were dependent on the length of the respective CT. Moreover, a specific region, 325–342aa residues of Cx43, played an important role in the direction of GJ internalization. These results showed the important roles of the Cx43 C-terminus in GJ expression and its turnover.

29 CFR 801.43 - Civil money penalties-payment and collection.

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2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false Civil money penalties-payment and collection. 801.43... OTHER LAWS APPLICATION OF THE EMPLOYEE POLYGRAPH PROTECTION ACT OF 1988 Enforcement § 801.43 Civil money... by certified check or by money order, made payable to the order of “Wage and Hour Division, Labor...

43 CFR 17.203 - Discrimination prohibited.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discrimination prohibited. 17.203 Section... Discrimination prohibited. (a) General. No qualified handicapped person shall, on the basis of handicap, be excluded from participation in, be denied the benefits of, or otherwise be subjected to discrimination...

43 CFR 24.5 - International agreements.

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2010-10-01

... WILDLIFE POLICY: STATE-FEDERAL RELATIONSHIPS § 24.5 International agreements. (a) International conventions... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false International agreements. 24.5 Section 24... shall be to recommend that the United States negotiate and accede to only those international agreements...

26 CFR 1.43-4 - Qualified enhanced oil recovery costs.

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2010-04-01

... 26 Internal Revenue 1 2010-04-01 2010-04-01 true Qualified enhanced oil recovery costs. 1.43-4... TAXES Credits Against Tax § 1.43-4 Qualified enhanced oil recovery costs. (a) Qualifying costs—(1) In... “qualified enhanced oil recovery costs” if the amounts are paid or incurred with respect to an asset which is...

Effect of zirconium purity on the glass-forming-ability and notch toughness of Cu{sub 43}Zr{sub 43}Al{sub 7}Be{sub 7}

Energy Technology Data Exchange (ETDEWEB)

Andersen, Laura M. [Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA (United States); Hofmann, Douglas C. [Materials Development and Manufacturing Technology Group, NASA Jet Propulsion Laboratory/California Institute of Technology, MS 18-105, 4800 Oak Grove Dr. Pasadena, CA 91109 (United States); Vecchio, Kenneth S., E-mail: kvecchio@ucsd.edu [Department of NanoEngineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA (United States)

2016-09-30

The effect of substituting standard grade zirconium lump (99.8% excluding up to 4% hafnium) for high purity zirconium crystal bar (99.5%) in a Cu{sub 43}Zr{sub 43}Al{sub 7}Be{sub 7} bulk metallic glass (BMG) is examined. The final hafnium content in the BMG specimens was found to range from 0 to 0.44 at%. Introducing low purity zirconium significantly decreased the glass-forming-ability and reduced the notch toughness of the BMG. In contrast, when adding high purity hafnium to Cu{sub 43}Zr{sub 43}Al{sub 7}Be{sub 7} made with high purity zirconium, no significant change in the glass-forming-ability or toughness was observed. This suggests that the introduction of low purity zirconium in BMGs creates a more complex response than a simple addition of hafnium. It is likely that other impurities in the material, such as oxygen, play a role in the complex crystallization kinetics and change in mechanical properties. The notch toughness was measured through four-point-bend tests, which showed a decrease in notch toughness from an average of ~53 MPa m{sup 1/2} for the high purity samples to an average of ~29 MPa m{sup 1/2} with full substitution of low purity zirconium. A similar decrease in glass-forming-ability and toughness is observed in commercially synthesized high purity Cu{sub 43}Zr{sub 43}Al{sub 7}Be{sub 7}. The large scale commercial process is expected to introduced some unintentional impurities, which decrease the properties of the BMG in the same way as the lower purity elements. Lastly, Weibull statistics are used to provide an analysis of variability in toughness for both ingots synthesized in a small laboratory arc-melter and those synthesized commercially.

Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice.

Science.gov (United States)

Szilvásy-Szabó, Anett; Varga, Edina; Beliczai, Zsuzsa; Lechan, Ronald M; Fekete, Csaba

2017-10-15

Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes. The Cx43-blocker, carbenoxolone, inhibited spreading of LY. The greatest density of Cx43-immunoreactive spots was observed in the cell membrane of α-tanycyte cell bodies. Cx43-immunoreactivity was also present in the membrane of β-tanycyte cell bodies, but in lower density. Processes of both types of tanycytes also contained Cx43-immunoreactivity. At the ultrastructural level, Cx43-immunoreactivity was present in the cell membrane of all types of tanycytes including their ventricular surface, but gap junctions were more frequent among α-tanycytes. Cx43-immunoreactivity was also observed in the cell membrane between contacting tanycyte endfeet processes, and between tanycyte endfeet process and axon varicosities in the external zone of the median eminence and capillaries in the arcuate nucleus and median eminence. These results suggest that gap junctions are present not only among tanycytes, but also between tanycytes and the axons of hypophysiotropic neurons. Cx43 hemichannels may also facilitate the transport between tanycytes and extracellular fluids, including the cerebrospinal fluid, extracellular space of the median eminence and bloodstream. Copyright © 2017 Elsevier B.V. All rights reserved.

43 CFR 7.32 - Supplemental definitions.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Supplemental definitions. 7.32 Section 7... RESOURCES Department of the Interior Supplemental Regulations § 7.32 Supplemental definitions. For purposes of this subpart, the following definitions will be used: (a) Site of religious or cultural importance...

37 CFR 251.43 - Written cases.

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2010-07-01

... and redirect) must be referenced. (d) In the case of a royalty fee distribution proceeding, each party... ROYALTY PANEL RULES AND PROCEDURES COPYRIGHT ARBITRATION ROYALTY PANEL RULES OF PROCEDURE Procedures of Copyright Arbitration Royalty Panels § 251.43 Written cases. (a) All parties who have filed a notice of...

43 CFR 418.15 - Operations monitoring.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Operations monitoring. 418.15 Section 418... THE INTERIOR OPERATING CRITERIA AND PROCEDURES FOR THE NEWLANDS RECLAMATION PROJECT, NEVADA Monitoring Diversions § 418.15 Operations monitoring. (a) The Bureau will work with the District to monitor Project...

43 CFR 4.436 - Reporter's fees.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Reporter's fees. 4.436 Section 4.436 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT HEARINGS AND APPEALS PROCEDURES... Fact § 4.436 Reporter's fees. Reporter's fees shall be borne by the Bureau. ...

43 CFR 427.1 - Water conservation.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Water conservation. 427.1 Section 427.1... INTERIOR WATER CONSERVATION RULES AND REGULATIONS § 427.1 Water conservation. (a) In general. The Secretary shall encourage the full consideration and incorporation of prudent and responsible water conservation...

43 CFR 34.4 - Discrimination prohibited.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discrimination prohibited. 34.4 Section 34... DURING CONSTRUCTION AND OPERATION OF THE ALASKA NATURAL GAS TRANSPORTATION SYSTEM § 34.4 Discrimination... part applies. (b) Specific actions in which discrimination is prohibited. No person shall directly or...

43 CFR 11.21 - Emergency restorations.

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2010-10-01

... Preassessment Phase § 11.21 Emergency restorations. (a) Reporting requirements and definition. (1) In the event of a natural resource emergency, the natural resource trustee shall contact the National Response... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Emergency restorations. 11.21 Section 11...

Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation

International Nuclear Information System (INIS)

Choudhary, Mayur; Naczki, Christine; Chen, Wenhong; Barlow, Keith D.; Case, L. Douglas; Metheny-Barlow, Linda J.

2015-01-01

Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support

Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes.

Science.gov (United States)

Ram, Rashmi; Wescott, Andrew P; Varandas, Katherine; Dirksen, Robert T; Blaxall, Burns C

2014-01-01

Mena, a member of the Ena/VASP family of actin regulatory proteins, modulates microfilaments and interacts with cytoskeletal proteins associated with heart failure. Mena is localized at the intercalated disc (ICD) of adult cardiac myocytes, colocalizing with numerous cytoskeletal proteins. Mena's role in the maintainence of mechanical myocardial stability at the cardiomyocyte ICD remains unknown. We hypothesized that Mena may modulate signals from the sarcolemma to the actin cytoskeleton at the ICD to regulate the expression and localization of connexin 43 (Cx43). The small GTPase Rac1 plays a pivotal role in the regulation of actin cytoskeletal reorganization and mediating morphological and transcriptional changes in cardiomyocytes. We found that Mena is associated with active Rac1 in cardiomyocytes and that RNAi knockdown of Mena increased Rac1 activity significantly. Furthermore, Mena knockdown increased Cx43 expression and altered Cx43 localization and trafficking at the ICD, concomitant with faster intercellular communication, as assessed by dye transfer between cardiomyocyte pairs. In mice overexpressing constitutively active Rac1, left ventricular Mena expression was increased significantly, concomitant with lateral redistribution of Cx43. These results suggest that Mena is a critical regulator of the ICD and is required for normal localization of Cx43 in part via regulation of Rac1.

X-43A: The First Flight of a Scramjet Powered Airplane

Science.gov (United States)

Corpening, Griff

2004-01-01

A viewgraph presentation describing the X-43A Scramjet engine is shown. The topics include: 1) Scramjets; 2) Overview of X-43A; 3) What Happened the 1st Time; 4) Return to Flight; and 5) What Happened the 2nd Time.

Analysis of Tank 38H (HTF-38-17-52, -53) and Tank 43H (HTF-43-17-54, -55) Samples for Support of the Enrichment Control and Corrosion Control Programs

Energy Technology Data Exchange (ETDEWEB)

Hay, M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Coleman, C. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Diprete, D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2017-08-09

SRNL analyzed samples from Tank 38H and Tank 43H to support ECP and CCP. The total uranium in the Tank 38H surface sample was 41.3 mg/L while the sub-surface sample was 43.5 mg/L. The Tank 43H samples contained total uranium concentrations of 28.5 mg/L in the surface sample and 28.1 mg/L in the sub-surface sample. The U-235 percentage ranged from 0.62% to 0.63% for the Tank 38H samples and Tank 43H samples. The total uranium and percent U-235 results in the table appear slightly lower than recent Tank 38H and Tank 43H uranium measurements. The plutonium results in the table show a large difference between the surface and sub-surface sample concentrations for Tank 38H. The Tank 43H plutonium results closely match the range of values measured on previous samples. The Cs-137 results for the Tank 38H surface and sub-surface samples show similar concentrations slightly higher than the concentrations measured in recent samples. The Cs-137 results for the two Tank 43H samples also show similar concentrations within the range of values measured on previous samples. The four samples show silicon concentrations somewhat lower than the previous samples with values ranging from 124 to 168 mg/L.

32 CFR 1630.43 - Class 4-D: Minister of religion.

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2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Class 4-D: Minister of religion. 1630.43 Section... CLASSIFICATION RULES § 1630.43 Class 4-D: Minister of religion. In accord with part 1645 of this chapter any registrant shall be placed in Class 4-D who is a: (a) Duly ordained minister of religion; or (b) Regular...

43 CFR 12.815 - Evaluating offers.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Evaluating offers. 12.815 Section 12.815 Public Lands: Interior Office of the Secretary of the Interior ADMINISTRATIVE AND AUDIT REQUIREMENTS AND... Act-Construction Materials § 12.815 Evaluating offers. (a) The restrictions of the Buy American Act do...

43 CFR 20.507 - Unlawful organizations.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Unlawful organizations. 20.507 Section 20... CONDUCT Other Employee Conduct Provisions § 20.507 Unlawful organizations. An employee may not advocate... organization that he or she knows advocates the violent overthrow of our constitutional form of government (5 U...

43 CFR 41.525 - Fringe benefits.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Fringe benefits. 41.525 Section 41.525... in Employment in Education Programs or Activities Prohibited § 41.525 Fringe benefits. (a) “Fringe benefits” defined. For purposes of these Title IX regulations, fringe benefits means: Any medical, hospital...

43 CFR 4.1130 - Discovery methods.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discovery methods. 4.1130 Section 4.1130... Special Rules Applicable to Surface Coal Mining Hearings and Appeals Discovery § 4.1130 Discovery methods. Parties may obtain discovery by one or more of the following methods— (a) Depositions upon oral...

Friction and wear behavior of TiC particle reinforced ZA43 matrix composites

Institute of Scientific and Technical Information of China (English)

谢贤清; 张荻; 刘金水; 吴人洁

2001-01-01

TiC/ZA43 composites were fabricated by XDTM and stirring-casting techniques. The tribology properties of the unreinforced ZA43 alloy and the composites were studied by using a block-on-ring apparatus. Experimental results show that the incorporation of TiC particles improves the microstructure of ZA43 matrix alloy. The coefficient of friction μ and the width of worn groove decrease with the increase of TiC volume fraction φ(TiC). The width of worn groove and μ of the composite during wear testing increase with increasing the applied load. Metallographic examinations reveal that unreinforced ZA43 alloy has deep ploughing grooves with obvious adhesion phenomenon, whereas TiC/ZA43 composites have smooth worn surface. Delamination formation is related to the fatigue cracks and the shear cracks on the surface.

28 CFR 513.43 - Inmate access to certain Bureau Program Statements.

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2010-07-01

... Statements. 513.43 Section 513.43 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE GENERAL... simple local access procedures described in this section to review certain Bureau Program Statements... 28 CFR), local access is available through the institution law library. (b) For a current Bureau...

Overexpression of the essential Sis1 chaperone reduces TDP-43 effects on toxicity and proteolysis

Science.gov (United States)

Park, Sei-Kyoung; Hong, Joo Y.; Arslan, Fatih; Tietsort, Alex; Tank, Elizabeth M. H.; Li, Xingli

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by selective loss of motor neurons with inclusions frequently containing the RNA/DNA binding protein TDP-43. Using a yeast model of ALS exhibiting TDP-43 dependent toxicity, we now show that TDP-43 overexpression dramatically alters cell shape and reduces ubiquitin dependent proteolysis of a reporter construct. Furthermore, we show that an excess of the Hsp40 chaperone, Sis1, reduced TDP-43’s effect on toxicity, cell shape and proteolysis. The strength of these effects was influenced by the presence of the endogenous yeast prion, [PIN+]. Although overexpression of Sis1 altered the TDP-43 aggregation pattern, we did not detect physical association of Sis1 with TDP-43, suggesting the possibility of indirect effects on TDP-43 aggregation. Furthermore, overexpression of the mammalian Sis1 homologue, DNAJB1, relieves TDP-43 mediated toxicity in primary rodent cortical neurons, suggesting that Sis1 and its homologues may have neuroprotective effects in ALS. PMID:28531192

28 CFR 570.43 - Inmates requiring a high degree of control and supervision.

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2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Inmates requiring a high degree of control and supervision. 570.43 Section 570.43 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE COMMUNITY PROGRAMS AND RELEASE COMMUNITY PROGRAMS Escorted Trips § 570.43 Inmates requiring a high degree of control and supervision. Only the...

The use of coronary vasodilators in myocardial imaging with 43K

International Nuclear Information System (INIS)

Markov, A.K.; Smith, R.O.; Oglethorpe, N.C.; Lehan, P.H.; Hellems, H.K.

1980-01-01

As an alternative procedure to the exercise stress test used in myocardial scanning, vasoactive drugs were employed to elicit deficits in blood flow to myocardial regions supplied by stenotic arteries. The data were collected from 35 dogs, some of which had partial stenosis on either major branch of the left coronary artery, and others which had Ameroid constrictor implants. The effects of lidoflazine, dipyridamole, and nitroglycerin on coronary hemodynamics and myocardial dispersion of 43 K in animals with partial stenosis were evaluated in ten acute experiments. In the pilot studies, four rapid serial rectilinear control scans from 43 K (750 μCi) were reported; dipyridamole, lidoflazine, or nitroglycerin were then administered intravenously. When the selected drug reached a peak vasodilatative effect, a second equal bolus of 43 K was given and four additional scans recorded. The control scans from dogs with partial stenosis or an Ameroid constrictor showed homogeneous distribution of the myocardial 43 K. When drugs were used, the region supplied by compromised circulation became apparent because of lower counts when compared to the normally perfused ones. Coronary vasodilators, as opposed to postexercise in myocardial imaging, have a lesser effect on cardiac dynamics, peripheral hemodynamics, and also double the 43 K uptake in normally perfused myocardium. (orig.) [de

Penile lesion from gunshot wound: a 43-case experience

Directory of Open Access Journals (Sweden)

Cavalcanti Andre G.

2006-01-01

Full Text Available OBJECTIVE: To demonstrate the main aspects of diagnosis, treatment and follow-up of 43 patients with gunshot wounds to the penis. MATERIALS AND METHODS: The location of the lesion, the presence of associated lesions, the performance of complementary exams, surgical treatment, postoperative complications and long term follow-up of 43 patients with penile lesions from gunshot wounds were retrospectively analyzed. RESULTS: Of 43 cases assessed, 41 were submitted to surgical exploration (95.3% and 2 were submitted to conservative treatment (4.7%. We found penile lesions involving the corpus cavernosum in 37 cases; the remaining 4 patients presented no lesions involving the corpus cavernosum, urethra or testicles but did in the superficial structures. Ten cases presented an association with testicular lesions and 14 cases association with anterior urethral lesions. CONCLUSION: Penile lesions from gunshot wounds should be treated with immediate surgical intervention. In exceptional situations featuring superficial lesions only conservative treatment may be applied.

Progranulin is neurotrophic in vivo and protects against a mutant TDP-43 induced axonopathy.

Directory of Open Access Journals (Sweden)

Angela S Laird

Full Text Available Mislocalization, aberrant processing and aggregation of TAR DNA-binding protein 43 (TDP-43 is found in the neurons affected by two related diseases, amyotrophic lateral sclerosis (ALS and frontotemporal lobe dementia (FTLD. These TDP-43 abnormalities are seen when TDP-43 is mutated, such as in familial ALS, but also in FTLD, caused by null mutations in the progranulin gene. They are also found in many patients with sporadic ALS and FTLD, conditions in which only wild type TDP-43 is present. The common pathological hallmarks and symptomatic cross over between the two diseases suggest that TDP-43 and progranulin may be mechanistically linked. In this study we aimed to address this link by establishing whether overexpression of mutant TDP-43 or knock-down of progranulin in zebrafish embryos results in motor neuron phenotypes and whether human progranulin is neuroprotective against such phenotypes. Mutant TDP-43 (A315T mutation induced a motor axonopathy characterized by short axonal outgrowth and aberrant branching, similar, but more severe, than that induced by mutant SOD1. Knockdown of the two zebrafish progranulin genes, grna and grnb, produced a substantial decrease in axonal length, with knockdown of grna alone producing a greater decrease in axonal length than grnb. Progranulin overexpression rescued the axonopathy induced by progranulin knockdown. Interestingly, progranulin also rescued the mutant TDP-43 induced axonopathy, whilst it failed to affect the mutant SOD1-induced phenotype. TDP-43 was found to be nuclear in all conditions described. The findings described here demonstrate that progranulin is neuroprotective in vivo and may have therapeutic potential for at least some forms of motor neuron degeneration.

43 CFR 418.29 - Project management.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Project management. 418.29 Section 418.29... INTERIOR OPERATING CRITERIA AND PROCEDURES FOR THE NEWLANDS RECLAMATION PROJECT, NEVADA Enforcement § 418.29 Project management. In addition to the provisions of § 418.28, if the District is found to be...

43 CFR 12.715 - Evaluating offers.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Evaluating offers. 12.715 Section 12.715... Act-Supplies § 12.715 Evaluating offers. (a) Unless the head of the grantee organization or a designee at a level no lower than the grantee's designated awarding official determines otherwise, the offered...

43 CFR 17.10 - Judicial review.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Judicial review. 17.10 Section 17.10... Origin § 17.10 Judicial review. Action taken pursuant to section 602 of the act is subject to judicial review as provided in section 603 of the act. [29 FR 16293, Dec. 4, 1964] ...

43 CFR 36.5 - Application review.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Application review. 36.5 Section 36.5... ACROSS, AND ACCESS INTO, CONSERVATION SYSTEM UNITS IN ALASKA § 36.5 Application review. (a) When there is... the purpose of coordinating appropriate Federal agency actions in the review and processing of the SF...

43 CFR 12.924 - Program income.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Program income. 12.924 Section 12.924... Requirements § 12.924 Program income. (a) Federal awarding agencies shall apply the standards set forth in this section in requiring recipient organizations to account for program income related to projects financed in...

43 CFR 12.65 - Program income.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Program income. 12.65 Section 12.65 Public... to State and Local Governments Post-Award Requirements § 12.65 Program income. (a) General. Grantees are encouraged to earn income to defray program costs. Program income includes income from fees for...

43 CFR 36.7 - Decision process.

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2010-10-01

... so notify the applicant in writing. (2) Each appropriate Federal agency in making its decision shall... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Decision process. 36.7 Section 36.7 Public Lands: Interior Office of the Secretary of the Interior TRANSPORTATION AND UTILITY SYSTEMS IN AND ACROSS...

43 CFR 20.201 - Ethics officials.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Ethics officials. 20.201 Section 20.201... Department Ethics Program § 20.201 Ethics officials. (a) Designated Agency Ethics Official refers to the official designated under 5 CFR 2638.201 to coordinate and manage the Department's ethics program. (b) The...

43 CFR 27.3 - Discrimination prohibited.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Discrimination prohibited. 27.3 Section 27... ISSUED UNDER TITLE II OF PUBLIC LAW 93-153 § 27.3 Discrimination prohibited. (a) General. No person shall... through contractual or other arrangements, subject an individual to discrimination on the grounds of race...

43 CFR 414.5 - Water quality.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Water quality. 414.5 Section 414.5 Public... APPORTIONMENT IN THE LOWER DIVISION STATES Water Quality and Environmental Compliance § 414.5 Water quality. (a) Water Quality is not guaranteed. The Secretary does not warrant the quality of water released or...

43 CFR 12.81 - Financial reporting.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Financial reporting. 12.81 Section 12.81... Agreements to State and Local Governments Reports, Records Retention, and Enforcement § 12.81 Financial reporting. (a) General. (1) Except as provided in paragraphs (a) (2) and (5) of this section, grantees will...

Axonal Transport of TDP-43 mRNA Granules Is Impaired by ALS-Causing Mutations

OpenAIRE

Alami, Nael H.; Smith, Rebecca B.; Carrasco, Monica A.; Williams, Luis A.; Winborn, Christina S.; Han, Steve S.W.; Kiskinis, Evangelos; Winborn, Brett; Freibaum, Brian D.; Kanagaraj, Anderson; Clare, Alison J.; Badders, Nisha M.; Bilican, Bilada; Chaum, Edward; Chandran, Siddharthan

2014-01-01

The RNA binding protein TDP-43 regulates RNA metabolism at multiple levels, including transcription, RNA splicing, and mRNA stability. TDP-43 is a major component of the cytoplasmic inclusions characteristic of amyotrophic lateral sclerosis and some types of frontotemporal lobar degeneration. The importance of TDP-43 in disease is underscored by the fact that dominant missense mutations are sufficient to cause disease, although the role of TDP-43 in pathogenesis is unknown. ...

Inhibition of connexin43 gap junction channels by the endocrine disruptor ioxynil

International Nuclear Information System (INIS)

Leithe, Edward; Kjenseth, Ane; Bruun, Jarle; Sirnes, Solveig; Rivedal, Edgar

2010-01-01

Gap junctions are intercellular plasma membrane domains containing channels that mediate transport of ions, metabolites and small signaling molecules between adjacent cells. Gap junctions play important roles in a variety of cellular processes, including regulation of cell growth and differentiation, maintenance of tissue homeostasis and embryogenesis. The constituents of gap junction channels are a family of trans-membrane proteins called connexins, of which the best-studied is connexin43. Connexin43 functions as a tumor suppressor protein in various tissue types and is frequently dysregulated in human cancers. The pesticide ioxynil has previously been shown to act as an endocrine disrupting chemical and has multiple effects on the thyroid axis. Furthermore, both ioxynil and its derivative ioxynil octanoate have been reported to induce tumors in animal bioassays. However, the molecular mechanisms underlying the possible tumorigenic effects of these compounds are unknown. In the present study we show that ioxynil and ioxynil octanoate are strong inhibitors of connexin43 gap junction channels. Both compounds induced rapid loss of connexin43 gap junctions at the plasma membrane and increased connexin43 degradation. Ioxynil octanoate, but not ioxynil, was found to be a strong activator of ERK1/2. The compounds also had different effects on the phosphorylation status of connexin43. Taken together, the data show that ioxynil and ioxynil octanoate are potent inhibitors of intercellular communication via gap junctions.

9 CFR 355.43 - Scope and applicability of rules of practice.

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2010-01-01

... AND VOLUNTARY INSPECTION AND CERTIFICATION CERTIFIED PRODUCTS FOR DOGS, CATS, AND OTHER CARNIVORA... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Scope and applicability of rules of practice. 355.43 Section 355.43 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT...

38 CFR 51.43 - Per diem and drugs and medicines-principles.

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2010-07-01

... medicines-principles. 51.43 Section 51.43 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... Per diem and drugs and medicines—principles. (a) As a condition for receiving payment of per diem... at the nursing home. Relevant cost principles are set forth in the Office of Management and Budget...

Genetic and functional analysis of the gene encoding GAP-43 in schizophrenia.

Science.gov (United States)

Shen, Yu-Chih; Tsai, Ho-Min; Cheng, Min-Chih; Hsu, Shih-Hsin; Chen, Shih-Fen; Chen, Chia-Hsiang

2012-02-01

In earlier reports, growth-associated protein 43 (GAP-43) has been shown to be critical for initial establishment or reorganization of synaptic connections, a process thought to be disrupted in schizophrenia. Additionally, abnormal GAP-43 expression in different brain regions has been linked to this disorder in postmortem brain studies. In this study, we investigated the involvement of the gene encoding GAP-43 in the susceptibility to schizophrenia. We searched for genetic variants in the promoter region and 3 exons (including both UTR ends) of the GAP-43 gene using direct sequencing in a sample of patients with schizophrenia (n=586) and non-psychotic controls (n=576), both being Han Chinese from Taiwan, and conducted an association and functional study. We identified 11 common polymorphisms in the GAP-43 gene. SNP and haplotype-based analyses displayed no associations with schizophrenia. Additionally, we identified 4 rare variants in 5 out of 586 patients, including 1 variant located at the promoter region (c.-258-4722G>T) and 1 synonymous (V110V) and 2 missense (G150R and P188L) variants located at exon 2. No rare variants were found in the control subjects. The results of the reporter gene assay demonstrated that the regulatory activity of construct containing c.-258-4722T was significantly lower as compared to the wild type construct (c.-258-4722G; panalysis also demonstrated the functional relevance of other rare variants. Our study lends support to the hypothesis of multiple rare mutations in schizophrenia, and it provides genetic clues that indicate the involvement of GAP-43 in this disorder. Copyright © 2011 Elsevier B.V. All rights reserved.

43 CFR 35.42 - Judicial review.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Judicial review. 35.42 Section 35.42... CLAIMS AND STATEMENTS § 35.42 Judicial review. Section 3805 of title 31, U.S. Code, authorizes judicial review by an appropriate U.S. District Court of a final decision of the Secretary imposing penalties or...

43 CFR 12.952 - Financial reporting.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Financial reporting. 12.952 Section 12.952... Requirements § 12.952 Financial reporting. (a) The following forms or such other forms as may be approved by OMB are authorized for obtaining financial information from recipients. (1) SF-269 or SF-269A...

Axonal transport of TDP-43 mRNA granules in neurons is impaired by ALS-causing mutations

Science.gov (United States)

Carrasco, Monica A.; Williams, Luis A.; Winborn, Christina S.; Han, Steve S. W.; Kiskinis, Evangelos; Winborn, Brett; Freibaum, Brian D.; Kanagaraj, Anderson; Clare, Alison J.; Badders, Nisha M.; Bilican, Bilada; Chaum, Edward; Chandran, Siddharthan; Shaw, Christopher E.; Eggan, Kevin C.; Maniatis, Tom; Taylor, J. Paul

2014-01-01

Summary The RNA binding protein TDP-43 regulates RNA metabolism at multiple levels, including transcription, RNA splicing, and mRNA stability. TDP-43 is a major component of the cytoplasmic inclusions characteristic of amyotrophic lateral sclerosis and some types of frontotemporal lobar degeneration. The importance of TDP-43 in disease is underscored by the fact that dominant missense mutations are sufficient to cause disease, although the role of TDP-43 in pathogenesis is unknown. Here we show that TDP-43 forms cytoplasmic mRNP granules that undergo bidirectional, microtubule-dependent transport in neurons in vitro and in vivo and facilitate delivery of target mRNA to distal neuronal compartments. TDP-43 mutations impair this mRNA transport function in vivo and in vitro, including in stem cell-derived motor neurons from ALS patients bearing any one of three different TDP-43 ALS-causing mutations. Thus, TDP43 mutations that cause ALS lead to partial loss of a novel cytoplasmic function of TDP-43. PMID:24507191

Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation.

Science.gov (United States)

Coyne, Alyssa N; Yamada, Shizuka B; Siddegowda, Bhavani Bagevalu; Estes, Patricia S; Zaepfel, Benjamin L; Johannesmeyer, Jeffrey S; Lockwood, Donovan B; Pham, Linh T; Hart, Michael P; Cassel, Joel A; Freibaum, Brian; Boehringer, Ashley V; Taylor, J Paul; Reitz, Allen B; Gitler, Aaron D; Zarnescu, Daniela C

2015-12-15

RNA dysregulation is a newly recognized disease mechanism in amyotrophic lateral sclerosis (ALS). Here we identify Drosophila fragile X mental retardation protein (dFMRP) as a robust genetic modifier of TDP-43-dependent toxicity in a Drosophila model of ALS. We find that dFMRP overexpression (dFMRP OE) mitigates TDP-43 dependent locomotor defects and reduced lifespan in Drosophila. TDP-43 and FMRP form a complex in flies and human cells. In motor neurons, TDP-43 expression increases the association of dFMRP with stress granules and colocalizes with polyA binding protein in a variant-dependent manner. Furthermore, dFMRP dosage modulates TDP-43 solubility and molecular mobility with overexpression of dFMRP resulting in a significant reduction of TDP-43 in the aggregate fraction. Polysome fractionation experiments indicate that dFMRP OE also relieves the translation inhibition of futsch mRNA, a TDP-43 target mRNA, which regulates neuromuscular synapse architecture. Restoration of futsch translation by dFMRP OE mitigates Futsch-dependent morphological phenotypes at the neuromuscular junction including synaptic size and presence of satellite boutons. Our data suggest a model whereby dFMRP is neuroprotective by remodeling TDP-43 containing RNA granules, reducing aggregation and restoring the translation of specific mRNAs in motor neurons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ultrastructure and regulation of lateralized connexin43 in the failing heart.

Science.gov (United States)

Hesketh, Geoffrey G; Shah, Manish H; Halperin, Victoria L; Cooke, Carol A; Akar, Fadi G; Yen, Timothy E; Kass, David A; Machamer, Carolyn E; Van Eyk, Jennifer E; Tomaselli, Gordon F

2010-04-02

Gap junctions mediate cell-to-cell electric coupling of cardiomyocytes. The primary gap junction protein in the working myocardium, connexin43 (Cx43), exhibits increased localization at the lateral membranes of cardiomyocytes in a variety of heart diseases, although the precise location and function of this population is unknown. To define the subcellular location of lateralized gap junctions at the light and electron microscopic level, and further characterize the biochemical regulation of gap junction turnover. By electron microscopy, we characterized gap junctions formed between cardiomyocyte lateral membranes in failing canine ventricular myocardium. These gap junctions were varied in structure and appeared to be extensively internalizing. Internalized gap junctions were incorporated into multilamellar membrane structures, with features characteristic of autophagosomes. Intracellular Cx43 extensively colocalized with the autophagosome marker GFP-LC3 when both proteins were exogenously expressed in HeLa cells, and endogenous Cx43 colocalized with GFP-LC3 in neonatal rat ventricular myocytes. Furthermore, a distinct phosphorylated form of Cx43, as well as the autophagosome-targeted form of LC3 (microtubule-associated protein light chain 3) targeted to lipid rafts in cardiac tissue, and both were increased in heart failure. Our data demonstrate a previously unrecognized pathway of gap junction internalization and degradation in the heart and identify a cellular pathway with potential therapeutic implications.

40 CFR 53.43 - Test procedures.

Science.gov (United States)

2010-07-01

... sampling zone (see § 53.42(d)). To meet the maximum blockage limit of § 53.42(a) or for convenience, part... PM10 § 53.43 Test procedures. (a) Sampling effectiveness—(1) Technical definition. The ratio (expressed... evenly spaced isokinetic samplers in the sampling zone (see § 53.42(d)) of the wind tunnel. Collect...

43 CFR 23.9 - Performance bond.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Performance bond. 23.9 Section 23.9 Public... LANDS § 23.9 Performance bond. (a)(1) Upon approval of an exploration plan or mining plan, the operator shall be required to file a suitable performance bond of not less than $2,000 with satisfactory surety...

The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

Directory of Open Access Journals (Sweden)

Chunman Li

2017-10-01

Full Text Available G-protein-coupled receptors (GPCRs constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

Analysis of tank 38H (HTF-38-17-18, -19) and tank 43H (HTF-43-17-20, -21) samples for support of the enrichment control and corrosion control programs

Energy Technology Data Exchange (ETDEWEB)

Hay, M. S. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Coleman, C. J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Diprete, D. P. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2017-03-01

SRNL analyzed samples from Tank 38H and Tank 43H to support ECP and CCP. The total uranium in the Tank 38H samples ranged from 53.7 mg/L for the surface sample to 57.0 mg/L in the sub-surface sample. The Tank 43H samples showed uranium concentrations of 46.2 mg/L for the surface sample and 45.7 mg/L in the sub-surface sample. The U-235 percentage was 0.63% in the Tank 38H samples and 0.62% in the Tank 43H samples. The total uranium and percent U-235 results appear consistent with recent Tank 38H and Tank 43H uranium measurements. The plutonium results for the Tank 38H surface sample are slightly higher than recent sample results, while the Tank 43H plutonium results are within the range of values measured on previous samples. The Cs-137 results for the Tank 38H surface and subsurface samples are slightly higher than the concentrations measured in recent samples. The Cs-137 results for the two Tank 43H samples are within the range of values measured on previous samples. The comparison of the sum of the cations in each sample versus the sum of the anions shows a difference of 23% for the Tank 38H surface sample and 18% for the Tank 43H surface sample. The four samples show silicon concentrations somewhat lower than the previous samples with values ranging from 80.2 to 105 mg/L.

Substitution studies of Mn and Fe in Ln{sub 6}W{sub 4}Al{sub 43} (Ln=Gd, Yb) and the structure of Yb{sub 6}Ti{sub 4}Al{sub 43}

Energy Technology Data Exchange (ETDEWEB)

Treadwell, LaRico J.; Watkins-Curry, Pilanda [Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803 (United States); Department of Chemistry, University of Texas at Dallas, Richardson, TX 75080 (United States); McAlpin, Jacob D. [Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803 (United States); Prestigiacomo, Joseph; Stadler, Shane [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70803 (United States); Chan, Julia Y., E-mail: Julia.Chan@utdallas.edu [Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803 (United States); Department of Chemistry, University of Texas at Dallas, Richardson, TX 75080 (United States)

2014-02-15

The synthesis and characterization of Mn- and Fe-substituted Ln{sub 6}W{sub 4}Al{sub 43} (Ln=Gd, Yb) and Yb{sub 6}Ti{sub 4}Al{sub 43} are reported. The compounds adopt the Ho{sub 6}Mo{sub 4}Al{sub 43} structure type with lattice parameters of a∼11 Å and c∼17.8 Å with structural site preferences for Mn and Fe. The magnetization of Yb{sub 6}W{sub 4}Al{sub 43} is sensitive to Mn and Fe doping, which is evident by an increase in the field dependent magnetization. Gd{sub 6}W{sub 4}Al{sub 43}, Gd{sub 6}W{sub 4}Al{sub 42.31(11)}Mn{sub 0.69(11)}, and Gd{sub 6}W{sub 4}Al{sub 41.69(12)}Fe{sub 1.30(12)} order antiferromagnetically in the ab- and c-directions at 15, 14, and 13 K, respectively, with positive Weiss constants, suggesting the presence of ferromagnetic exchange interactions. Anisotropic magnetization data of Gd{sub 6}W{sub 4}Al{sub 43−y}T{sub y} (T=Mn, Fe) analogs are discussed. - Graphical abstract: The magnetic susceptibility of Ln{sub 6}W{sub 4−x}Al{sub 43−y}T{sub x+y} (Ln = Gd, Yb; T= Mn, Fe). Display Omitted - Highlights: • Single crystals of Ln{sub 6}W{sub 4−x}Al{sub 43−y}T{sub x+y} were grown with Al-flux. • Anisotropic magnetic behavior were determined on single crystals. • Gd{sub 6}W{sub 4−x}Al{sub 43−y}T{sub x+y} (T=Mn, Fe) analogs order antiferromagnetically.

Mutant TDP-43 within motor neurons drives disease onset but not progression in amyotrophic lateral sclerosis.

Science.gov (United States)

Ditsworth, Dara; Maldonado, Marcus; McAlonis-Downes, Melissa; Sun, Shuying; Seelman, Amanda; Drenner, Kevin; Arnold, Eveline; Ling, Shuo-Chien; Pizzo, Donald; Ravits, John; Cleveland, Don W; Da Cruz, Sandrine

2017-06-01

Mutations in TDP-43 cause amyotrophic lateral sclerosis (ALS), a fatal paralytic disease characterized by degeneration and premature death of motor neurons. The contribution of mutant TDP-43-mediated damage within motor neurons was evaluated using mice expressing a conditional allele of an ALS-causing TDP-43 mutant (Q331K) whose broad expression throughout the central nervous system mimics endogenous TDP-43. TDP-43 Q331K mice develop age- and mutant-dependent motor deficits from degeneration and death of motor neurons. Cre-recombinase-mediated excision of the TDP-43 Q331K gene from motor neurons is shown to delay onset of motor symptoms and appearance of TDP-43-mediated aberrant nuclear morphology, and abrogate subsequent death of motor neurons. However, reduction of mutant TDP-43 selectively in motor neurons did not prevent age-dependent degeneration of axons and neuromuscular junction loss, nor did it attenuate astrogliosis or microgliosis. Thus, disease mechanism is non-cell autonomous with mutant TDP-43 expressed in motor neurons determining disease onset but progression defined by mutant acting within other cell types.

Cutaneous somatic and autonomic nerve TDP-43 deposition in amyotrophic lateral sclerosis.

Science.gov (United States)

Ren, Yuting; Liu, Wenxiu; Li, Yifan; Sun, Bo; Li, Yanran; Yang, Fei; Wang, Hongfen; Li, Mao; Cui, Fang; Huang, Xusheng

2018-05-26

To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner's corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P nerve fiber density (SGNFD) (P nerve fiber density (PNFD) (P nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.

Immunodiagnosis of paracoccidioidomycosis due to Paracoccidioides brasiliensis using a latex test: detection of specific antibody anti-gp43 and specific antigen gp43.

Directory of Open Access Journals (Sweden)

Priscila Oliveira Dos Santos

2015-02-01

Full Text Available Paracoccidioidomycosis (PCM is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations.A latex immunoassay using sensitized latex particles (SLPs with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43 was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF, and bronchoalveolar lavage (BAL from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0, specificity (93.94%, 95% CI 87.3-97.7, and positive (91.4% and negative (98.9% predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6, specificity (88.89%, 95% CI 81.0-94.3, and positive (85.1% and negative (97.8% predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924 and mAb17c-SLPs (k = 0.850, which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy.The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure

20 CFR 901.43 - Administrative Law Judge.

Science.gov (United States)

2010-04-01

....43 Employees' Benefits JOINT BOARD FOR THE ENROLLMENT OF ACTUARIES REGULATIONS GOVERNING THE... conduct proceedings upon complaints for the suspension or termination of enrolled actuaries. (b) Powers of... with any suspension or termination proceeding of an enrolled actuary, to do the following: (1...

Phenotype abnormality: 43 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available 43 http://metadb.riken.jp/db/SciNetS_ria224i/cria224u1ria224u549i abnormal for trait of behavioral quality... in organ named root during process named growth ... root ... abnormal ... growth ... behavioral quality

Improvement of Data Acquisition of the BRTR (PS-43) Seismic Array

Science.gov (United States)

Ozel, N. M.; Kocak, S.; Semin, K. U.; Necmioglu, O.; Destici, T. C.; Teoman, U.

2010-05-01

Bogazici University, Kandilli Observatory and Earthquake Research Institute(KOERI) is currently operating the BRTR( PS-43) seismic arrays located in the vicinity of Ankara and town Keskin, providing real-time data to IDC. PS-43 is composed of two sub-arrays, the medium-period array with a ~45km radius located in Ankara and the short-period array with ~3 km radius located in Keskin. In 2009, data availabilty of the BRTR is exceeded %98 that value is the requirment of IDC. Substantial contribution to obtain this availabiliy is implementing the improvements that mainly replacement of the grid type parabolic antennas with the heavy-duty dish antennas at necessary sites called the repeater sites RE-BRTR (CCF), RE-PS43 (Mt. Elmadag), CF-PS43 (Central Recording Building) and all MP sites. Even this renewed system is at the tentative stage, communication status of the seismic arrays are solid and continuous. BRTR is expecting another improvement, June 2010, about the power system at Mt. Elmadag and the MP site BR237. Completion of this improvement will be stabilize of our current mission.

Effects of androgen on immunohistochemical localization of androgen receptor and Connexin 43 in mouse ovary.

Science.gov (United States)

Yang, Mei; Li, Jianhua; An, Yulin; Zhang, Shuiwen

2015-10-01

Androgens have essential roles in the regulation of follicular development and female fertility. Androgen excess is the leading defect in polycystic ovary syndrome (PCOS) patients and involved in the ovarian dysfunction. The aim of this study was to elucidate the regarding regulatory role of androgen in the follicular development of female mouse. Immunohistochemical staining and Western blot analyses were performed to detect androgen receptor (AR) and Connexin 43 (Cx43) expression in ovaries from both control and testosterone-treated group mice. In this study, localizations of AR and Cx43 were dramatically altered in testosterone-treated mouse ovaries. In addition, AR expression was significantly increased, whereas Cx43 expression was markedly decreased after testosterone treatment. Alterations of AR and Cx43 expression by testosterone with concomitant reduction of MII oocytes. Overall, these results suggest the involvement of androgen in the regulation of AR and Cx43 localizations in mouse ovary. Alterations of AR and Cx43 expression by testosterone may affect normal folliculogenesis. Together these findings will enable us to begin understanding the important roles of AR and Cx43 actions in the regulation of follicular development, as well as providing insights into the role of AR and Cx43 actions in the androgen-associated reproductive diseases such as PCOS. Copyright © 2015 Elsevier Ltd. All rights reserved.

Identification of a functional interaction between Kv4.3 channels and c-Src tyrosine kinase.

Science.gov (United States)

Gomes, Pedro; Saito, Tomoaki; Del Corsso, Cris; Alioua, Abderrahmane; Eghbali, Mansoureh; Toro, Ligia; Stefani, Enrico

2008-10-01

Voltage-gated K(+) (Kv) channels are key determinants of cardiac and neuronal excitability. A substantial body of evidence has accumulated in support of a role for Src family tyrosine kinases in the regulation of Kv channels. In this study, we examined the possibility that c-Src tyrosine kinase participates in the modulation of the transient voltage-dependent K(+) channel Kv4.3. Supporting a mechanistic link between Kv4.3 and c-Src, confocal microscopy analysis of HEK293 cells stably transfected with Kv4.3 showed high degree of co-localization of the two proteins at the plasma membrane. Our results further demonstrate an association between Kv4.3 and c-Src by co-immunoprecipitation and GST pull-down assays, this interaction being mediated by the SH2 and SH3 domains of c-Src. Furthermore, we show that Kv4.3 is tyrosine phosphorylated under basal conditions. The functional relevance of the observed interaction between Kv4.3 and c-Src was established in patch-clamp experiments, where application of the Src inhibitor PP2 caused a decrease in Kv4.3 peak current amplitude, but not the inactive structural analogue PP3. Conversely, intracellular application of recombinant c-Src kinase or the protein tyrosine phosphatase inhibitor bpV(phen) increased Kv4.3 peak current amplitude. In conclusion, our findings provide evidence that c-Src-induced Kv4.3 channel activation involves their association in a macromolecular complex and suggest a role for c-Src-Kv4.3 pathway in regulating cardiac and neuronal excitability.

45 CFR 1309.43 - Use of grant funds to pay fees.

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2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Use of grant funds to pay fees. 1309.43 Section... Provisions § 1309.43 Use of grant funds to pay fees. Consistent with the cost principles referred to in 45 CFR part 74 and 45 CFR part 92, reasonable fees and costs associated with and necessary to the...

22 CFR 192.43 - Administration of benefits.

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2010-04-01

....43 Foreign Relations DEPARTMENT OF STATE HOSTAGE RELIEF VICTIMS OF TERRORISM COMPENSATION Educational... this part, shall apply in writing to the Director General of the Foreign Service, Department of State... those benefits. The Director General of the Foreign Service, on behalf of the Secretary of State, shall...

43 CFR 20.202 - Ethics program responsibilities.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Ethics program responsibilities. 20.202... AND CONDUCT Department Ethics Program § 20.202 Ethics program responsibilities. (a) The Designated Agency Ethics Official (or the alternate agency ethics official in his or her absence) shall coordinate...

47 CFR 43.21 - Transactions with affiliates.

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2010-10-01

... communications plant at the end of that year. This letter must be filed no later than April 1 of the following....21 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) REPORTS OF COMMUNICATION COMMON CARRIERS AND CERTAIN AFFILIATES § 43.21 Transactions with affiliates. (a...

14 CFR 399.43 - Treatment of leased aircraft.

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2010-01-01

... PROCEEDINGS) POLICY STATEMENTS STATEMENTS OF GENERAL POLICY Policies Relating to Rates and Tariffs § 399.43... purposes, it is the Board's policy to recognize actual rental expenses. In unusual circumstances where the...

Connexin43 hemichannels contributes to the disassembly of cell junctions through modulation of intracellular oxidative status

Directory of Open Access Journals (Sweden)

Yuan Chi

2016-10-01

Full Text Available Connexin (Cx hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupts the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of cell junctions. Here we tested this hypothesis. Exposure of renal tubular epithelial cells to Ca2+-free medium led to disassembly of tight and adherens junctions, as indicated by the reduced level of ZO-1 and cadherin, disorganization of F-actin, and severe drop in transepithelial electric resistance. These changes were preceded by an activation of Cx43 hemichannels, as revealed by extracellular efflux of ATP and intracellular influx of Lucifer Yellow. Inhibition of hemichannels with chemical inhibitors or Cx43 siRNA greatly attenuated the disassembly of cell junctions. Further analysis using fetal fibroblasts derived from Cx43 wide-type (Cx43+/+, heterozygous (Cx43+/- and knockout (Cx43-/- littermates showed that Cx43-positive cells (Cx43+/+ exhibited more dramatic changes in cell shape, F-actin, and cadherin in response to Ca2+ depletion, as compared to Cx43-null cells (Cx43-/-. Consistently, these cells had higher level of protein carbonyl modification and phosphorylation, and much stronger activation of P38 and JNK. Hemichannel opening led to extracellular loss of the major antioxidant glutathione (GSH. Supplement of cells with exogenous GSH or inhibition of oxidative sensitive kinases largely prevented the above-mentioned changes. Taken together, our study indicates that Cx43 hemichannels promote the disassembly of cell junctions through regulation of intracellular oxidative status.

Impact of loss-of-function mutations at the RNF43 locus on colorectal cancer development and progression.

Science.gov (United States)

Eto, Tsugio; Miyake, Keisuke; Nosho, Katsuhiko; Ohmuraya, Masaki; Imamura, Yu; Arima, Kota; Kanno, Shinichi; Fu, Lingfeng; Kiyozumi, Yuki; Izumi, Daisuke; Sugihara, Hidetaka; Hiyoshi, Yukiharu; Miyamoto, Yuji; Sawayama, Hiroshi; Iwatsuki, Masaaki; Baba, Yoshifumi; Yoshida, Naoya; Furukawa, Toru; Araki, Kimi; Baba, Hideo; Ishimoto, Takatsugu

2018-05-13

RNF43 mutations are frequently detected in colorectal cancer cells and lead to a loss of function of the ubiquitin E3 ligase. Here, we investigated the clinical significance of RNF43 mutations in a large Japanese cohort and the role of RNF43 at various stages of colorectal cancer development and progression. Mutation analysis of the RNF43 gene locus using pyrosequencing technology detected RNF43 hotspot mutations in 1 (0.88%) of 113 colorectal polyp cases and 30 (6.45%) of 465 colorectal cancer cases. Moreover, patients with colorectal cancer harboring mutated RNF43 experienced a higher recurrence rate than those harboring non-mutated RNF43. In addition, the growth of RNF43 wild-type colorectal cancer cell lines was significantly increased by RNF43 silencing. We generated Rnf43 knock-out mice in a C57BL/6N background using the CRISPR-Cas9 system. Although intestinal organoids from the Rnf43 knock-out mice did not show continuous growth compared with those from the wild-type mice in the absence of R-spondin, an azoxymethane (AOM)/dextran sodium sulfate (DSS) mouse model demonstrated that the tumors were markedly larger in the Rnf43 knock-out mice than in the wild-type mice. These findings provide evidence that Wnt signaling activation by RNF43 mutations during the tumorigenic stage enhances tumor growth and promotes a high recurrence rate in colorectal cancer patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

33 CFR 164.43 - Automatic Identification System Shipborne Equipment-Prince William Sound.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Automatic Identification System Shipborne Equipment-Prince William Sound. 164.43 Section 164.43 Navigation and Navigable Waters COAST GUARD... Automatic Identification System Shipborne Equipment—Prince William Sound. (a) Until December 31, 2004, each...

Phosphorylation of connexin43 on S279/282 may contribute to laminopathy-associated conduction defects

Energy Technology Data Exchange (ETDEWEB)

Chen, Steven C., E-mail: bug@uw.edu [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States); University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Kennedy, Brian K., E-mail: bkennedy@buckinstitute.org [University of Washington Department of Biochemistry, 1959 NE Pacific St., Seattle, WA 98195 (United States); Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945 (United States); Lampe, Paul D., E-mail: plampe@fhcrc.org [Fred Hutchinson Cancer Research Center (FHCRC), Public Health Sciences Division, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

2013-04-01

An understanding of the molecular mechanism behind the arrhythmic phenotype associated with laminopathies has yet to emerge. A-type lamins have been shown to interact and sequester activated phospho-ERK1/2(pERK1/2) at the nucleus. The gap junction protein connexin43 (Cx43) can be phosphorylated by pERK1/2 on S279/282 (pS279/282), inhibiting intercellular communication. We hypothesized that without A-type lamins, pS279/282 Cx43 will increase due to inappropriate phosphorylation by pERK1/2, resulting in decreased gap junction function. We observed a 1.6-fold increase in pS279/282 Cx43 levels in Lmna{sup −/−} mouse embryonic fibroblasts (MEFs) compared to Lmna{sup +/+}, and 1.8-fold more pERK1/2 co-precipitated from Lmna{sup −/−} MEFs with Cx43 antibodies. We found a 3-fold increase in the fraction of non-nuclear pERK1/2 and a concomitant 2-fold increase in the fraction of pS279/282 Cx43 in Lmna{sup −/−} MEFs by immunofluorescence. In an assay of gap junctional function, Lmna{sup −/−} MEFs transferred dye to 60% fewer partners compared to Lmna{sup +/+} controls. These results are mirrored in 5–6 week-old Lmna{sup −/−} mice compared to their Lmna{sup +/+} littermates as we detect increased pS279/282 Cx43 in gap junctions by immunofluorescence and 1.7-fold increased levels by immunoblot. We conclude that increased pS279/282 Cx43 in the Lmna{sup −/−} background results in decreased cell communication and may contribute to the arrhythmic pathology in vivo. - Highlights: ► Connexin43 phosphorylation plays a role in laminopathy-associated conduction defects. ► Loss of A-type lamin activity results in release of pERK1/2 from the nucleus. ► Increased cytoplasmic localization of pERK1/2 acts to phosphorylate S279/282 of Cx43. ► Phosphorylation of S279/282 on Cx43 decreases gap junction activity in cell culture. ► Mice lacking A-type lamins have increased phosphorylation on S279/282 of Cx43.

Assessment of TRMM 3B43 product for drought monitoring in Singapore

Science.gov (United States)

Tan, Mou Leong; Chua, Vivien P.; Tan, Kok Chooi; Brindha, K.

2017-10-01

Drought is one of the most hazardous natural disasters for human beings and the environment. Using only rain gauge is insufficient to monitor the drought pattern effectively as it impacts large areas. This situation is more critical on small island countries, with limited rain gauges for monitoring drought pattern over the ocean regions. This study aims to assess the capability of Tropical Rainfall Measuring Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) 3B43 product in monitoring drought in Singapore from 1998 to 2014. The Standardized Precipitation Index (SPI) at various time-scales is used for identifying drought patterns. Results show moderate to good correlations between TMPA- 3B43 and rain gauges in the SPI estimations. Besides that, TMPA-3B43 exhibits a similar temporal drought behavior as the rain gauges. These findings indicate the TMPA 3B43 product as a very useful tool to study drought pattern over Singapore.

PEMODELAN KONDUKTIVITAS ION DALAM STRUKTUR Li2Sc3(PO43 (Modeling Ionic Conductivity in Li2Sc3(PO43 Structure

Directory of Open Access Journals (Sweden)

Akram La Kilo

2011-11-01

Full Text Available ABSTRAK Fasa Li2Sc3(PO43 merupakan material konduktor superionik yang dapat diaplikasikan sebagai baterai yang dapat diisi ulang (rechargeable. Ion Li+ dalam struktur Li2Sc3(PO4 dapat mengalami migrasi dari posisi terisi ke posisi kosong. Penelitian ini telah memodelkan migrasi ion Li+ dalam struktur Li2Sc3(PO4 dengan menggunakan metode bond valence sum (BVS. Metode ini dapat memprediksi bilangan oksidasi suatu atom berdasarkan jarak dengan atom-atom tetangga. Source code berbasis BVS yang digunakan adalah JUMPITER yang mensimulasi efek gaya listrik eksternal yang bertindak pada ion litium sehingga nilai BVS litium dapat dipetakan terhadap jarak. Hasil simulasi menunjukkan bahwa konduksi ion Li+ dapat terjadi pada arah [010], [101], dan [120]. Namun, lintasan konduksi ion Li+ lebih mudah terjadi pada arah [120] atau bidang ab dengan nilai maksimum BVS adalah 0,982. ABSTRACT g-phase of Li2Sc3(PO43 is a lithium super ionic conductor which can be applied as a rechargeable lithium battery. Lithium ions of g-Li2Sc3(PO43 can migrate from occupied site to vacant site. In this research, simulation of Li+ ions migration in the structure of g-Li2Sc3(PO43 carried out using bond valence sum (BVS to predict the oxidation state of Li+ion based on the distance of the ion to neighboring atoms. BVS-based code used JUMPITER to simulate the effect of external electrical force acting on the lithium ions to produce the lithium BVS value which can be mapped to the distance. The simulation results shows that Li+ ion conduction can be occurred on [010], [101], and [120] directions. However, the Li ion conduction pathway occur more easily in the direction of [120] or ab plane with the BVS maximum value is 0.982.

43 CFR 24.3 - General jurisdictional principles.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false General jurisdictional principles. 24.3 Section 24.3 Public Lands: Interior Office of the Secretary of the Interior DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE POLICY: STATE-FEDERAL RELATIONSHIPS § 24.3 General jurisdictional principles. (a) In...

KV4.3 N-terminal deletion mutant Δ2–39

Science.gov (United States)

Hovind, Laura J; Skerritt, Matthew R

2011-01-01

Gating transitions in the KV4.3 N-terminal deletion mutant Δ2–39 were characterized in the absence and presence of KChIP2b. We particularly focused on gating characteristics of macroscopic (open state) versus closed state inactivation (CSI) and recovery. In the absence of KChIP2b Δ2–39 did not significantly alter the steady-state activation “a4” relationship or general CSI characteristics, but it did slow the kinetics of deactivation, macroscopic inactivation and macroscopic recovery. Recovery kinetics (for both WT KV4.3 and Δ2–39) were complicated and displayed sigmoidicity, a process which was enhanced by Δ2–39. Deletion of the proximal N-terminal domain therefore appeared to specifically slow mechanisms involved in regulating gating transitions occurring after the channel open state(s) had been reached. In the presence of KChIP2b Δ2–39 recovery kinetics (from both macroscopic and CSI) were accelerated, with an apparent reduction in initial sigmoidicity. Hyperpolarizing shifts in both “a4” and isochronal inactivation “i” were also produced. KChIP2b-mediated remodeling of KV4.3 gating transitions was therefore not obligatorily dependent upon an intact N-terminus. To account for these effects we propose that KChIP2 regulatory domains exist in KV4.3 α subunit regions outside of the proximal N-terminal. In addition to regulating macroscopic inactivation, we also propose that the KV4.3 N-terminus may act as a novel regulator of deactivation-recovery coupling. PMID:21057209

9 CFR 201.43 - Payment and accounting for livestock and live poultry.

Science.gov (United States)

2010-01-01

... and live poultry. 201.43 Section 201.43 Animals and Animal Products GRAIN INSPECTION, PACKERS AND... poultry. (a) Market agencies to make prompt accounting and transmittal of net proceeds. Each market agency... nature of the transaction. (b) Prompt payment for livestock and live poultry—terms and conditions. (1) No...

Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation.

Directory of Open Access Journals (Sweden)

Maria Vittoria Barone

Full Text Available BACKGROUND: Celiac Disease (CD is both a frequent disease (1:100 and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs

Core drilling of deep borehole OL-KR43 at Olkiluoto in Eurajoki 2006

Energy Technology Data Exchange (ETDEWEB)

Niinimaeki, R. [Suomen Malmi Oy, Espoo (Finland)

2006-12-15

Posiva Oy submitted an application to the Finnish Government in May 1999 for the Decision in Principle to choose Olkiluoto in the municipality of Eurajoki as the site of the final disposal facility for spent nuclear fuel. A positive decision was made at the end of 2000 by the Government. The Finnish Parliament ratified the decision in May 2001. The decision makes it possible for Posiva to focus the confirming bedrock investigations at Olkiluoto, where in the next few years an underground rock characterisation facility, ONKALO, will be constructed. As a part of the investigations Suomen Malmi Oy (Smoy) core drilled 1000.26 m and 45.01 m deep boreholes with a diameter of 75.7 mm at Olkiluoto in July - October 2006. The identification numbers of the boreholes are OL-KR43 and OL-KR43B, respectively. A set of monitoring measurements and samplings from the drilling and returning water was carried out during the drilling. Both the volume and the electric conductivity of the drilling water and the returning water were recorded. The drill rig was computer controlled and during drilling the computer recorded drilling parameters. The objective of all these measurements was to obtain more information about bedrock and groundwater properties. Sodium fluorescein was used as a label agent in the drilling water. The total volumes of the used drilling and flushing water were 1103 m{sup 3} and 16 m{sup 3} in boreholes OL-KR43 and OL-KR43B, respectively. Measured volumes of the returning water were 916m{sup 3} in borehole OL-KR43 and 13m{sup 3} in borehole OL-KR43B. The deviation of the boreholes was measured with the deviation measuring instruments EMS and Maxibor. Uniaxial compressive strength, Young's Modulus and Poisson's ratio were measured from the core samples. The average uniaxial compressive strength is about 131 MPa, the average Young's Modulus is 37 GPa and the average Poisson's ratio is 0.19. The main rock types are veined gneiss, diatexitic gneiss

c-Jun N-terminal kinase mediates AML1-ETO protein-induced connexin-43 expression

International Nuclear Information System (INIS)

Gao Fenghou; Wang Qiong; Wu Yingli; Li Xi; Zhao Kewen; Chen Guoqiang

2007-01-01

AML1-ETO fusion protein, a product of leukemia-related chromosomal translocation t(8;21), was reported to upregulate expression of connexin-43 (Cx43), a member of gap junction-constituted connexin family. However, its mechanism(s) remains unclear. By bioinformatic analysis, here we showed that there are two putative AML1-binding consensus sequences followed by two activated protein (AP)1 sites in the 5'-flanking region upstream to Cx43 gene. AML1-ETO could directly bind to these two AML1-binding sites in electrophoretic mobility shift assay, but luciferase reporter assay revealed that the AML1 binding sites were not indispensable for Cx43 induction by AML1-ETO protein. Conversely, AP1 sites exerted an important role in this event. In agreement, AML1-ETO overexpression in leukemic U937 cells activated c-Jun N-terminal kinase (JNK), while its specific inhibitor SP600125 effectively abrogated AML1-ETO-induced Cx43 expression, indicating that JNK signaling pathway contributes to AML1-ETO induced Cx43 expression. These results would shed new insights for understanding mechanisms of AML1-ETO-associated leukemogenesis

29 CFR 34.43 - Complaints and investigations.

Science.gov (United States)

2010-07-01

... Equal Pay Act of 1963, as amended (29 U.S.C. 206(d)), or the Age Discrimination in Employment Act of... Office of the Secretary of Labor IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY REQUIREMENTS OF THE JOB TRAINING PARTNERSHIP ACT OF 1982, AS AMENDED (JTPA) Compliance Procedures § 34.43...

43 CFR 3.17 - Preservation of collection.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Preservation of collection. 3.17 Section 3.17 Public Lands: Interior Office of the Secretary of the Interior PRESERVATION OF AMERICAN ANTIQUITIES § 3.17 Preservation of collection. Every collection made under the authority of the act and of...

50 CFR 23.43 - What are the requirements for a wildlife hybrid?

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2010-10-01

... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false What are the requirements for a wildlife hybrid? 23.43 Section 23.43 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF... IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) CONVENTION ON INTERNATIONAL TRADE IN ENDANGERED SPECIES OF WILD...

Jalgpall võttis 43 elu / Märt Hiietamm

Index Scriptorium Estoniae

Hiietamm, Märt

2001-01-01

Lõuna-Aafrika Vabariigi meistrivõistluste mängule Kaizer Chiefs - Orlando Pirates müüdi liiga palju pileteid. Suur inimhulk põhjustas 43 inimese surma ja umbes 250 vigastusi. Lisa: 10 suuremat katastroofi jalgpalli ajaloos

43 knowledge, attitude and practices of adolescent secondary

African Journals Online (AJOL)

Knowledge, Attitude and Practices of Adolescents to HIV/AIDS. 43 ... which 40% cited the media as source of information. Seventy ... through sex, mother to child, ... and parents, societal pressure, norms ... reported condom use as an effective.

Skeletal muscle expression of p43, a truncated thyroid hormone receptor α, affects lipid composition and metabolism.

Science.gov (United States)

Casas, François; Fouret, Gilles; Lecomte, Jérome; Cortade, Fabienne; Pessemesse, Laurence; Blanchet, Emilie; Wrutniak-Cabello, Chantal; Coudray, Charles; Feillet-Coudray, Christine

2018-02-01

Thyroid hormone is a major regulator of metabolism and mitochondrial function. Thyroid hormone also affects reactions in almost all pathways of lipids metabolism and as such is considered as the main hormonal regulator of lipid biogenesis. The aim of this study was to explore the possible involvement of p43, a 43 Kda truncated form of the nuclear thyroid hormone receptor TRα1 which stimulates mitochondrial activity. Therefore, using mouse models overexpressing p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the lipid composition in quadriceps muscle and in mitochondria. Here, we reported in the quadriceps muscle of p43-/- mice, a fall in triglycerides, an inhibition of monounsaturated fatty acids (MUFA) synthesis, an increase in elongase index and an decrease in desaturase index. However, in mitochondria from p43-/- mice, fatty acid profile was barely modified. In the quadriceps muscle of p43-Tg mice, MUFA content was decreased whereas the unsaturation index was increased. In addition, in quadriceps mitochondria of p43-Tg mice, we found an increase of linoleic acid level and unsaturation index. Last, we showed that cardiolipin content, a key phospholipid for mitochondrial function, remained unchanged both in quadriceps muscle and in its mitochondria whatever the mice genotype. In conclusion, this study shows that muscle lipid content and fatty acid profile are strongly affected in skeletal muscle by p43 levels. We also demonstrate that regulation of cardiolipin biosynthesis by the thyroid hormone does not imply p43.

Polyaspartic acid as a corrosion inhibitor for WE43 magnesium alloy

OpenAIRE

Lihui Yang; Yantao Li; Bei Qian; Baorong Hou

2015-01-01

The inhibition behavior of polyaspartic acid (PASP) as an environment-friendly corrosion inhibitor for WE43 magnesium alloy was investigated in 3.5 wt.% NaCl solution by means for EIS measurement, potentiodynamic polarization curve, and scanning electron microscopy. The results show that PASP can inhibit the corrosion of WE43 magnesium alloy. The maximum inhibition efficiency is achieved when PASP concentration is 400 ppm in this study.

Disruption of the Cx43/miR21 pathway leads to osteocyte apoptosis and increased osteoclastogenesis with aging.

Science.gov (United States)

Davis, Hannah M; Pacheco-Costa, Rafael; Atkinson, Emily G; Brun, Lucas R; Gortazar, Arancha R; Harris, Julia; Hiasa, Masahiro; Bolarinwa, Surajudeen A; Yoneda, Toshiyuki; Ivan, Mircea; Bruzzaniti, Angela; Bellido, Teresita; Plotkin, Lilian I

2017-06-01

Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency. Cx43-silenced MLO-Y4 osteocytic (Cx43 def ) cells undergo spontaneous cell death in culture through caspase-3 activation and exhibit increased levels of apoptosis-related genes, and only transfection of Cx43 constructs able to form gap junction channels reverses Cx43 def cell death. Cx43 def cells and bones from old mice exhibit reduced levels of the pro-survival microRNA miR21 and, consistently, increased levels of the miR21 target phosphatase and tensin homolog (PTEN) and reduced phosphorylated Akt, whereas PTEN inhibition reduces Cx43 def cell apoptosis. miR21 reduction is sufficient to induce apoptosis of Cx43-expressing cells and miR21 deletion in miR21 fl/fl bones increases apoptosis-related gene expression, whereas a miR21 mimic prevents Cx43 def cell apoptosis, demonstrating that miR21 lies downstream of Cx43. Cx43 def cells release more osteoclastogenic cytokines [receptor activator of NFκB ligand (RANKL)/high-mobility group box-1 (HMGB1)], and caspase-3 inhibition prevents RANKL/HMGB1 release and the increased osteoclastogenesis induced by conditioned media from Cx43 def cells, which is blocked by antagonizing HMGB1-RAGE interaction. These findings identify a novel Cx43/miR21/HMGB1/RANKL pathway involved in preventing osteocyte apoptosis that also controls osteoclast formation/recruitment and is impaired with aging. © 2017 The Authors. Aging Cell published by the Anatomical Society

43 CFR 12.84 - Termination for convenience.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Termination for convenience. 12.84 Section 12.84 Public Lands: Interior Office of the Secretary of the Interior ADMINISTRATIVE AND AUDIT... Termination for convenience. Except as provided in § 12.83 awards may be terminated in whole or in part only...

43 CFR 2.57 - Accounting for disclosures.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Accounting for disclosures. 2.57 Section 2... INFORMATION ACT Privacy Act § 2.57 Accounting for disclosures. (a) Maintenance of an accounting. (1) Where a... the person or agency to whom the disclosure was made. (3) Accountings prepared under this section...

43 CFR 35.41 - Stay pending appeal.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Stay pending appeal. 35.41 Section 35.41... CLAIMS AND STATEMENTS § 35.41 Stay pending appeal. (a) An initial decision is stayed automatically pending disposition of a motion for reconsideration or of an appeal to the Secretary. (b) No...

43 CFR 14.4 - Publication of petitions.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Publication of petitions. 14.4 Section 14.4 Public Lands: Interior Office of the Secretary of the Interior PETITIONS FOR RULEMAKING § 14.4 Publication of petitions. A petition for rulemaking may be published in the Federal Register if the official...

60Co γ-irradiation enhances expression of GAP-43 mRNA in rat brain

International Nuclear Information System (INIS)

Su Bingyin; Cai Wenqin; Zhang Chenggang

2001-01-01

Objective: To study the relationship between the expression of GAP-43 mRNA and nerve regeneration in rat brain after 60 Co γ-irradiation. Methods: Wistar rats were subjected to whole-body irradiation with 8 Gy 60 Co γ-rays. The expression of GAP-43 was detected by in situ hybridization histochemistry using Dig-cRNA probe. Results: It was found that the expression of GAP-43 mRNA increased in the cerebral cortex, caudate, putamen, globus pallidum, thalamus and hypothalamus one week after 8 Gy 60 Co γ-irradiation. The peak of GAP-43 mRNA expression was observed in the fourth week and then began to decrease but still remained at a higher than normal level. However, it decreased to a low level after 7 weeks. Conclusion: Enhanced expression of GAP-43 mRNA after 60 Co γ-irradiation in rat brain is associated with nerve regeneration and reconstruction of synapse

Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin proteasome system and macroautophagy.

Science.gov (United States)

Cascella, Roberta; Fani, Giulia; Capitini, Claudia; Rusmini, Paola; Poletti, Angelo; Cecchi, Cristina; Chiti, Fabrizio

2017-12-01

Amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions are neurodegenerative disorders that share the cytosolic deposition of TDP-43 (TAR DNA-binding protein 43) in the CNS. TDP-43 is well known as being actively degraded by both the proteasome and macroautophagy. The well-documented decrease in the efficiency of these clearance systems in aging and neurodegeneration, as well as the genetic evidence that many of the familial forms of TDP-43 proteinopathies involve genes that are associated with them, suggest that a failure of these protein degradation systems is a major factor that contributes to the onset of TDP-43-associated disorders. Here, we inserted preformed human TDP-43 aggregates in the cytosol of murine NSC34 and N2a cells in diffuse form and observed their degradation under conditions in which exogenous TDP-43 is not expressed and endogenous nuclear TDP-43 is not recruited, thereby allowing a time zero to be established in TDP-43 degradation and to observe its disposal kinetically and analytically. TDP-43 degradation was observed in the absence and presence of selective inhibitors and small interfering RNAs against the proteasome and autophagy. We found that cytosolic diffuse aggregates of TDP-43 can be distinguished in 3 different classes on the basis of their vulnerability to degradation, which contributed to the definition-with previous reports-of a total of 6 distinct classes of misfolded TDP-43 species that range from soluble monomer to undegradable macroaggregates. We also found that the proteasome and macroautophagy-degradable pools of TDP-43 are fully distinguishable, rather than in equilibrium between them on the time scale required for degradation, and that a significant crosstalk exists between the 2 degradation processes.-Cascella, R., Fani, G., Capitini, C., Rusmini, P., Poletti, A., Cecchi, C., Chiti, F. Quantitative assessment of the degradation of aggregated TDP-43 mediated by the ubiquitin

Complex role of connexin 43 in astrocytic tumors and possible promotion of glioma‑associated epileptic discharge (Review).

Science.gov (United States)

Dong, Hui; Zhou, Xing-Wang; Wang, Xiang; Yang, Yuan; Luo, Jie-Wen; Liu, Yan-Hui; Mao, Qing

2017-12-01

Connexin (Cx)43 is a multifunction protein which forms gap junction channels and hemi‑channels. It also contains abundant binding domains which possess the ability to interact with certain Cx43‑associated proteins and therefore serve a fundamental role in various physiological and pathological functions. However, the understanding of the association between cancer and Cx43 along with Cx43‑gap junctions (GJ) remains unclear. All available data illustrate that Cx43 and its associated GJ serve important functions in cancers. The expression levels of Cx43 demonstrate a downward trend and an increase in the levels of malignancy, particularly in astrocytomas. The GJ intercellular communication activity in glioma cells can be adjusted via Cx43 phosphorylation and through the combination of Cx43 and its associated protein. Available evidence reveals Cx43 as a tumor‑inhibiting factor that suppresses glioma growth and proliferation. However, its mechanism is also regarded as complicated and ambiguous. Furthermore, it is apparent that Cx43‑GJ and the carboxyl tail may contribute to glioma growth and proliferation too. However, this valuable role could be weakened by its effects on migration and invasiveness. The detailed mechanism remains unclear and full of controversies. Cx43 can enhance the motor ability and invasiveness of astrocytic glioma cells. It is also able to influence glioma cells to detach from the tumor core to the peritumoral neocortex. This peritumoral region has recently been regarded as the basic focus of glioma‑associated seizure. Thus, Cx43 may take part in the onset and development of glioma‑associated epileptic discharge. In addition, change and increase of Cx43 expression in GJs has been observed in seizure perilesional tissue, which is associated with brain tumors. Cx43 or GJ/hemi‑channels exert enduring effects in the promotion of glioma‑associated epileptic release through direct mass effects and change of the tumor microenvironment

Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.

Science.gov (United States)

Xu, Xin; Francis, Richard; Wei, Chih Jen; Linask, Kaari L; Lo, Cecilia W

2006-09-01

Connexin 43 knockout (Cx43alpha1KO) mice have conotruncal heart defects that are associated with a reduction in the abundance of cardiac neural crest cells (CNCs) targeted to the heart. In this study, we show CNCs can respond to changing fibronectin matrix density by adjusting their migratory behavior, with directionality increasing and speed decreasing with increasing fibronectin density. However, compared with wild-type CNCs, Cx43alpha1KO CNCs show reduced directionality and speed, while CNCs overexpressing Cx43alpha1 from the CMV43 transgenic mice show increased directionality and speed. Altered integrin signaling was indicated by changes in the distribution of vinculin containing focal contacts, and altered temporal response of Cx43alpha1KO and CMV43 CNCs to beta1 integrin function blocking antibody treatment. High resolution motion analysis showed Cx43alpha1KO CNCs have increased cell protrusive activity accompanied by the loss of polarized cell movement. They exhibited an unusual polygonal arrangement of actin stress fibers that indicated a profound change in cytoskeletal organization. Semaphorin 3A, a chemorepellent known to inhibit integrin activation, was found to inhibit CNC motility, but in the Cx43alpha1KO and CMV43 CNCs, cell processes failed to retract with semaphorin 3A treatment. Immunohistochemical and biochemical analyses suggested close interactions between Cx43alpha1, vinculin and other actin-binding proteins. However, dye coupling analysis showed no correlation between gap junction communication level and fibronectin plating density. Overall, these findings indicate Cx43alpha1 may have a novel function in mediating crosstalk with cell signaling pathways that regulate polarized cell movement essential for the directional migration of CNCs.

Gap junction intercellular communication mediated by connexin43 in astrocytes is essential for their resistance to oxidative stress.

Science.gov (United States)

Le, Hoa T; Sin, Wun Chey; Lozinsky, Shannon; Bechberger, John; Vega, José Luis; Guo, Xu Qiu; Sáez, Juan C; Naus, Christian C

2014-01-17

Oxidative stress induced by reactive oxygen species (ROS) is associated with various neurological disorders including aging, neurodegenerative diseases, as well as traumatic and ischemic insults. Astrocytes have an important role in the anti-oxidative defense in the brain. The gap junction protein connexin43 (Cx43) forms intercellular channels as well as hemichannels in astrocytes. In the present study, we investigated the contribution of Cx43 to astrocytic death induced by the ROS hydrogen peroxide (H2O2) and the mechanism by which Cx43 exerts its effects. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased ROS-induced astrocytic death, supporting a cell protective effect of functional Cx43 channels. H2O2 transiently increased hemichannel activity, but reduced gap junction intercellular communication (GJIC). GJIC in wild-type astrocytes recovered after 7 h, but was absent in Cx43 knock-out astrocytes. Blockage of Cx43 hemichannels incompletely inhibited H2O2-induced hemichannel activity, indicating the presence of other hemichannel proteins. Panx1, which is predicted to be a major hemichannel contributor in astrocytes, did not appear to have any cell protective effect from H2O2 insults. Our data suggest that GJIC is important for Cx43-mediated ROS resistance. In contrast to hypoxia/reoxygenation, H2O2 treatment decreased the ratio of the hypophosphorylated isoform to total Cx43 level. Cx43 has been reported to promote astrocytic death induced by hypoxia/reoxygenation. We therefore speculate the increase in Cx43 dephosphorylation may account for the facilitation of astrocytic death. Our findings suggest that the role of Cx43 in response to cellular stress is dependent on the activation of signaling pathways leading to alteration of Cx43 phosphorylation states.

Antigen 43-mediated autotransporter display, a versatile bacterial cell surface presentation system

DEFF Research Database (Denmark)

Kjærgaard, Kristian; Hasman, Henrik; Schembri, Mark

2002-01-01

bridges does not interfere with surface display, and Ag43 chimeras are correctly processed into alpha- and beta-modules, offering optional and easy release of the chimeric alpha-subunits. Furthermore, Ag43 can be displayed in many gram-negative bacteria. This feature is exploited for display of our...... chimeras in an attenuated Salmonella strain....

Thermodynamics and Efficiency of a CuCl(aq)/HCl(aq) Electrolyzer

International Nuclear Information System (INIS)

Hall, Derek M.; Akinfiev, Nikolay N.; LaRow, Eric G.; Schatz, Richard S.; Lvov, Serguei N.

2014-01-01

The high ionic strength and complex speciation of the anolyte solution within the CuCl(aq)/HCl(aq) electrolytic cell have impeded predictions of the energy requirements for the cell's electrolytic reaction at 25 °C and 1 bar. After collecting experimental open circuit potential (OCP) data and comparing the values obtained with predictions from prospective thermodynamic models, an approach to predict thermodynamic values and the overall efficiency was formulated. The compositions of the experimental measurements ranged from 2-2.5 mol of CuCl(aq) with 8-9 mol of HCl(aq) per kilogram of water in anolyte solution and 8-9 mol of HCl(aq) per kilogram of water in catholyte solution. From the OCP data, it was found that activity coefficient and speciation effects were critical in predicting the Gibbs energy, entropy and thermodynamic (intrinsic maximum) efficiency of the electrolytic cell. At equilibrium, all thermodynamic functions of the anolyte redox reactions were the same after activity coefficients and speciation effects were taken into account. The electrochemical reactions’ Gibbs energy and entropy were found to be 9700 J/mol and 2.18 J/(mol K) at 25 °C and 1 bar, which indicated that the reactions required a small amount of electrical and thermal energy to proceed. With thermodynamic values for the electrolytic reaction and experimental data from a CuCl(aq)/HCl(aq) electrolytic cell, the voltage, current, thermodynamic and overall efficiency were calculated. The overall efficiency ranged from 15 to 95% depending on the current density

43 CFR 15.13 - Report of accidents.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Report of accidents. 15.13 Section 15.13 Public Lands: Interior Office of the Secretary of the Interior KEY LARGO CORAL REEF PRESERVE § 15.13 Report of accidents. Accidents involving injury to life or property shall be reported as soon as possible...

43 CFR 4.1292 - Contents of petition.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Contents of petition. 4.1292 Section 4... PROCEDURES Special Rules Applicable to Surface Coal Mining Hearings and Appeals Petitions for Award of Costs and Expenses Under Section 525(e) of the Act § 4.1292 Contents of petition. (a) A petition filed under...

43 CFR 4.1305 - Amendment of petition.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Amendment of petition. 4.1305 Section 4... PROCEDURES Special Rules Applicable to Surface Coal Mining Hearings and Appeals Petitions for Review of... petition. (a) An individual filing a petition may amend it once as a matter of right before receipt by the...

43 CFR 4.452-7 - Reporter's fees.

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2010-10-01

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27 CFR 6.43 - Sale of equipment.

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2010-04-01

... OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Furnishing Things of Value § 6.43 Sale of equipment. A transaction in which equipment is sold to a retailer by an industry member, except as provided.... Further, the negotiation by an industry member of a special price to a retailer for equipment from an...

Polyaspartic acid as a corrosion inhibitor for WE43 magnesium alloy

Directory of Open Access Journals (Sweden)

Lihui Yang

2015-03-01

Full Text Available The inhibition behavior of polyaspartic acid (PASP as an environment-friendly corrosion inhibitor for WE43 magnesium alloy was investigated in 3.5 wt.% NaCl solution by means for EIS measurement, potentiodynamic polarization curve, and scanning electron microscopy. The results show that PASP can inhibit the corrosion of WE43 magnesium alloy. The maximum inhibition efficiency is achieved when PASP concentration is 400 ppm in this study.

Research Report: Intermittent hypobaric hypoxia and hyperbaric oxygen on GAP-43 in the rat carotid body.

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Peng, Zhengwu; Fan, Juan; Liu, Ling; Kuang, Fang; Xue, Fen; Wang, Bairen

2015-01-01

Adaptive changes in the carotid body (CB) including the expression of the growth-associated protein-43 (GAP-43) have been studied in response to low, but not high, oxygen exposure. Expression of GAP-43 in the CB of rats under different atmospheric pressures and oxygen partial pressure (PO2) conditions was investigated. Mature male Sprague-Dawley rats were exposed to intermittent hypobaric hypoxia (IHH, 0, 1, 2 and 3 weeks), intermittent hyperbaric oxygen (IHBO2, 0, 1, 5 and 10 days, sacrificed six hours or 24 hours after the last HBO2 exposure), and intermittent hyperbaric normoxia (IHN, same treatment pattern as IHBO2). GAP-43 was highly expressed (mainly in type I cells) in the CB of normal rats. IHH u-regulated GAP-43 expression in the CB with significant differences (immunohistochemical staining [IHC]: F(3,15)=40.64, P GAP-43 expression in the CB was inhibited by IHBO2 (controls vs. IHBO2 groups, IHC: F(6,30) = 15.85, P GAP-43 expression were found for IHN. These findings indicated that different PO2 conditions, but not air pressures, played an important role in the plasticity of the CB, and that GAP-43 might be a viable factor for the plasticity of the CB.

Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

Energy Technology Data Exchange (ETDEWEB)

Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States); Panda, Satya P., E-mail: panda@uthscsa.edu [The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229 (United States)

2011-08-05

Highlights: {yields} Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. {yields} First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. {yields} Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. {yields} Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. {yields} Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b{sub 5} and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)

International Nuclear Information System (INIS)

Polusani, Srikanth R.; Kar, Rekha; Riquelme, Manuel A.; Masters, Bettie Sue; Panda, Satya P.

2011-01-01

Highlights: → Humans with severe forms of cytochrome P450 oxidoreductase (CYPOR) mutations show bone defects as observed in Antley-Bixler Syndrome. → First report showing knockdown of CYPOR in osteoblasts decreased Connexin 43 (Cx43) protein levels. Cx43 is known to play an important role in bone modeling. → Knockdown of CYPOR decreased Gap Junctional Intercellular Communication and hemichannel activity. → Knockdown of CYPOR decreased Cx43 in mouse primary calvarial osteoblasts. → Decreased Cx43 expression was observed at the transcriptional level. -- Abstract: Cytochrome P450 oxidoreductase (CYPOR) is a microsomal electron-transferring enzyme containing both FAD and FMN as co-factors, which provides the reducing equivalents to various redox partners, such as cytochromes P450 (CYPs), heme oxygenase (HO), cytochrome b 5 and squalene monooxygenase. Human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like Syndrome (ABS). To elucidate the role of CYPOR in bone, we knocked-down CYPOR in multiple osteoblast cell lines using RNAi technology. In this study, knock-down of CYPOR decreased the expression of Connexin 43 (Cx43), known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreased Gap Junction Intercellular Communication (GJIC) and hemichannel activity. Promoter luciferase assays revealed that the decrease in expression of Cx43 in CYPOR knock-down cells was due to transcriptional repression. Primary osteoblasts isolated from bone specific Por knock-down mice calvariae confirmed the findings in the cell lines. Taken together, our study provides novel insights into the regulation of gap junction function by CYPOR and suggests that Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients.

Inhibition of connexin43 hemichannels impairs spatial short-term memory without affecting spatial working memory

Directory of Open Access Journals (Sweden)

Laura Walrave

2016-12-01

Full Text Available Astrocytes are active players in higher brain function as they can release gliotransmitters, which are essential for synaptic plasticity. Various mechanisms have been proposed for gliotransmission, including vesicular mechanisms as well as non-vesicular ones, for example by passive diffusion via connexin hemichannels (HCs. We here investigated whether interfering with connexin43 (Cx43 HCs influenced hippocampal spatial memory. We made use of the peptide Gap19 that blocks HCs but not gap junction channels and is specific for Cx43. To this end, we microinfused transactivator of transcription linked Gap19 (TAT-Gap19 into the brain ventricle of male NMRI mice and assessed spatial memory in a Y maze. We found that the in vivo blockade of Cx43 HCs did not affect the locomotor activity or spatial working memory in a spontaneous alternation Y maze task. Cx43 blockade did however significantly impair the spatial short-term memory in a delayed spontaneous alternation Y maze task. These results indicate that Cx43 HCs play a role in spatial short-term memory.

Amygdala TDP-43 Pathology in Frontotemporal Lobar Degeneration and Motor Neuron Disease.

Science.gov (United States)

Takeda, Takahiro; Seilhean, Danielle; Le Ber, Isabelle; Millecamps, Stéphanie; Sazdovitch, Véronique; Kitagawa, Kazuo; Uchihara, Toshiki; Duyckaerts, Charles

2017-09-01

TDP-43-positive inclusions are present in the amygdala in frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) including amyotrophic lateral sclerosis. Behavioral abnormalities, one of the chief symptoms of FTLD, could be, at least partly, related to amygdala pathology. We examined TDP-43 inclusions in the amygdala of patients with sporadic FTLD/MND (sFTLD/MND), FTLD/MND with mutation of the C9ORF72 (FTLD/MND-C9) and FTLD with mutation of the progranulin (FTLD-GRN). TDP-43 inclusions were common in each one of these subtypes, which can otherwise be distinguished on topographical and genetic grounds. Conventional and immunological stainings were performed and we quantified the numerical density of inclusions on a regional basis. TDP-43 inclusions in amygdala could be seen in 10 out of 26 sFTLD/MND cases, 5 out of 9 FTLD/MND-C9 cases, and all 4 FTLD-GRN cases. Their numerical density was lower in FTLD/MND-C9 than in sFTLD/MND and FTLD-GRN. TDP-43 inclusions were more numerous in the ventral region of the basolateral nucleus group in all subtypes. This contrast was apparent in sporadic and C9-mutated FTLD/MND, while it was less evident in FTLD-GRN. Such differences in subregional involvement of amygdala may be related to the region-specific neuronal connections that are differentially affected in FTLD/MND and FTLD-GRN. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Gap43 transcription modulation in the adult brain depends on sensory activity and synaptic cooperation.

Directory of Open Access Journals (Sweden)

Nicole Rosskothen-Kuhl

Full Text Available Brain development and learning is accompanied by morphological and molecular changes in neurons. The growth associated protein 43 (Gap43, indicator of neurite elongation and synapse formation, is highly expressed during early stages of development. Upon maturation of the brain, Gap43 is down-regulated by most neurons with the exception of subdivisions such as the CA3 region of hippocampus, the lateral superior olive (LSO and the central inferior colliculus (CIC. Little is known about the regulation of this mRNA in adult brains. We found that the expression of Gap43 mRNA in specific neurons can be modulated by changing sensory activity of the adult brain. Using the central auditory system of rats as a model, Gap43 protein and mRNA levels were determined in LSO and CIC of hearing-experienced rats unilaterally or bilaterally deafened or unilaterally stimulated by a cochlear implant (CI. Our data indicate that Gap43 is a marker useful beyond monitoring neuronal growth and synaptogenesis, reflecting also specific patterns of synaptic activities on specific neurons. Thus, unilateral loss of input to an adult auditory system directly causes asymmetrical expression of Gap43 mRNA between LSOs or CICs on both sides of the brainstem. This consequence can be prevented by simple-patterned stimulation of a dysfunctional ear by way of a CI. We suggest that as a function of input balance and activity pattern, Gap43 mRNA expression changes as cells associate converging afferent signals.

Analysis of the substrate recognition state of TDP-43 to single-stranded DNA using fluorescence correlation spectroscopy

Directory of Open Access Journals (Sweden)

Akira Kitamura

2018-07-01

Full Text Available Normal function and abnormal aggregation of transactivation response (TAR DNA/RNA-binding protein 43 kDa (TDP-43 are directly associated with the lethal genetic diseases: cystic fibrosis, amyotrophic lateral sclerosis (ALS, and frontotemporal lobar degeneration (FTLD. The binding of TDP-43 to single-stranded DNA (ssDNA or RNA is involved in transcriptional repression, regulation of RNA splicing, and RNA stabilization. Equilibrium dissociation constants (Kd of TDP-43 and ssDNA or RNA have been determined using various methods; however, methods that can measure Kd with high sensitivity in a short time using a small amount of TDP-43 in solution would be advantageous. Here, in order to determine the Kd of TDP-43 and fluorescence-labeled ssDNA as well as the binding stoichiometry, we use fluorescence correlation spectroscopy (FCS, which detects the slowed diffusion of molecular interactions in solution with single-molecule sensitivity, in addition to electrophoretic mobility shift assay (EMSA. Using tandem affinity chromatography of TDP-43 dually tagged with glutathione-S-transferase and poly-histidine tags, highly purified protein was obtained. FCS successfully detected specific interaction between purified TDP-43 and TG ssDNA repeats, with a Kd in the nanomolar range. The Kd of the TDP-43 mutant was not different from the wild type, although mutant oligomers, which did not bind ssDNA, were observed. Analysis of the fluorescence brightness per dimerized TDP-43/ssDNA complex was used to evaluate their binding stoichiometry. The results suggest that an assay combining FCS and EMSA can precisely analyze ssDNA recognition mechanisms, and that FCS may be applied for the rapid and quantitative determination of the interaction strength between TDP-43 and ssDNA or RNA. These methods will aid in the elucidation of the substrate recognition mechanism of ALS- and FTLD-associated variants of TDP-43.

43 CFR 4.117 - Service of papers.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Service of papers. 4.117 Section 4.117... Service of papers. A copy of all pleadings, briefs, motions, letters, or other papers filed with the Board, shall be served upon the other party at the time of filing. Service of papers may be made personally or...

43 CFR 4.840 - Offer of proof.

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2010-10-01

... the Interior-Effectuation of Title VI of the Civil Rights Act of 1964 Hearing § 4.840 Offer of proof. An offer of proof made in connection with an objection taken to any ruling of the administrative law... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Offer of proof. 4.840 Section 4.840 Public...

43 CFR 7.20 - Public awareness programs.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Public awareness programs. 7.20 Section 7.20 Public Lands: Interior Office of the Secretary of the Interior PROTECTION OF ARCHAEOLOGICAL RESOURCES Uniform Regulations § 7.20 Public awareness programs. (a) Each Federal land manager will establish a program to increase public awareness of the...

43 CFR 29.8 - Notification and advertisement.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Notification and advertisement. 29.8... LIABILITY FUND § 29.8 Notification and advertisement. (a) As soon as the person in charge of a vessel has... advertisement no later than 45 days from the date the Fund receives notice of the incident and shall continue...

HIGHER PREVALENCE OF TDP-43 PROTEINOPATHY IN COGNITIVELY NORMAL ASIANS: A CLINICOPATHOLOGICAL STUDY ON A MULTIETHNIC SAMPLE

Science.gov (United States)

Nascimento, Camila; Suemoto, Claudia K.; Rodriguez, Roberta D.; Di Lorenzo Alho, Ana Tereza; Leite, Renata P.; Farfel, Jose Marcelo; Pasqualucci, Carlos Alberto; Jacob-Filho, Wilson; Grinberg, Lea T.

2015-01-01

Transactive response DNA binding-protein 43 (TDP-43) proteinopathy is the major hallmark of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. It is also present in a subset of Alzheimer’s disease cases. Recently, few reports showed TDP-43 changes in cognitively normal elderly. In Caucasians, TDP-43 proteinopathy independently correlate with cognitive decline. However, it is challenging to establish direct links between cognitive and/or neuropsychiatric symptoms and protein inclusions in neurodegenerative diseases because individual cognitive reserves modify the threshold for clinical disease expression. Cognitive reserve is influenced by demographic, environmental and genetic factors. We investigated the relationships between demographic, clinical, and neuropathological variables and TDP-43 proteinopathy in a large multiethnic sample of cognitively normal elderly. TDP-43 proteinopathy were identified in 10.5%, independently associated with older age (p = 0.03) and Asian ethnicity (p = 0.002). Asians showed a higher prevalence of TDP-43 proteinopathy than Caucasians, even after adjustment for sex, age, Braak stage, and schooling (odds ratio = 3.50, confidence interval 1.41–8.69, p = 0.007). These findings suggested Asians older adults may be protected from the clinical manifestation of brain TDP-43 proteinopathy. Future studies are needed to identify possible race-related protective factors against clinical expression of TDP-43 proteinopathies. PMID:26260327

AQS Data Mart

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U.S. Environmental Protection Agency — The AQS Data Mart is a database that contains all of the information from the AQS system. It is a storehouse of air quality information that allows users to make...

40 CFR 424.43 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

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2010-07-01

... representing the degree of effluent reduction attainable by the application of the best available technology economically achievable. 424.43 Section 424.43 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Carbide Furnaces With Wet Air Pollution Control Devices Subcategory § 424.43 Effluent limitations...

Discharge Burnup Evaluation of Natural Uranium Loaded CANFLEX-43 Fuel Bundle

International Nuclear Information System (INIS)

Roh, Gyu Hong; Kim, Yong Hee; Kim, Won Young; Park, Joo Hwan

2009-11-01

Using WIMS-AECL code, which is 2-dimensional lattice core used in CANDU physics calculation, the discharge burnup of the natural uranium loaded CANFLEX-43 fuel bundle was evaluated by comparing the discharge burnup of standard 37 element fuel bundle. When the discharge burnup of the standard 37 element fuel is 7,200 MWd/MTU, that of the CANFLEX 43 fuel bundle was evaluated as 7,077 MWd/MTU, by applying the same lattice conditions for both fuel bundles

Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy

DEFF Research Database (Denmark)

Christensen, A H; Andersen, C B; Tybjærg-Hansen, A

2011-01-01

Christensen AH, Andersen CB, Tybjærg-Hansen A, Haunso S, Svendsen JH. Mutation analysis and evaluation of the cardiac localization of TMEM43 in arrhythmogenic right ventricular cardiomyopathy. A single report has associated mutations in TMEM43 (LUMA) with a distinctive form of arrhythmogenic right...... with anti-TMEM43, anti-plakoglobin, anti-plakophilin-2, anti-connexin-43, and anti-emerin antibodies was performed on myocardium from TMEM43-positive patients (n = 3) and healthy controls (n = 3). The genetic screening identified heterozygous variants in two families: one reported mutation (c.1073C> T......; in two related patients) and one novel variant (c.705+ 7G> A; in one patient) of unknown significance. All three patients fulfilled Task Force criteria and did not carry mutations in any other ARVC-related gene. Immunostaining with TMEM43 antibody showed intense staining of the sarcolemma. The signal...

24 CFR 902.43 - Management operations performance standards.

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2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Management operations performance... URBAN DEVELOPMENT PUBLIC HOUSING ASSESSMENT SYSTEM PHAS Indicator #3: Management Operations § 902.43 Management operations performance standards. (a) Management operations sub-indicators. The following sub...

48 CFR 43.203 - Change order accounting procedures.

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2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Change order accounting... CONTRACT MANAGEMENT CONTRACT MODIFICATIONS Change Orders 43.203 Change order accounting procedures. (a) Contractors' accounting systems are seldom designed to segregate the costs of performing changed work...

Proinflammatory cytokines downregulate connexin 43-gap junctions via the ubiquitin-proteasome system in rat spinal astrocytes.

Science.gov (United States)

Zhang, Fang Fang; Morioka, Norimitsu; Kitamura, Tomoya; Hisaoka-Nakashima, Kazue; Nakata, Yoshihiro

2015-09-04

Astrocytic gap junctions formed by connexin 43 (Cx43) are crucial for intercellular communication between spinal cord astrocytes. Various neurological disorders are associated with dysfunctional Cx43-gap junctions. However, the mechanism modulating Cx43-gap junctions in spinal astrocytes under pathological conditions is not entirely clear. A previous study showed that treatment of spinal astrocytes in culture with pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) decreased both Cx43 expression and gap junction intercellular communication (GJIC) via a c-jun N-terminal kinase (JNK)-dependent pathway. The current study further elaborates the intracellular mechanism that decreases Cx43 under an inflammatory condition. Cycloheximide chase analysis revealed that TNF-α (10 ng/ml) alone or in combination with IFN-γ (5 ng/ml) accelerated the degradation of Cx43 protein in cultured spinal astrocytes. The reduction of both Cx43 expression and GJIC induced by a mixture of TNF-α and IFN-γ were blocked by pretreatment with proteasome inhibitors MG132 (0.5 μM) and epoxomicin (25 nM), a mixture of TNF-α and IFN-γ significantly increased proteasome activity and Cx43 ubiquitination. In addition, TNF-α and IFN-γ-induced activation of ubiquitin-proteasome systems was prevented by SP600125, a JNK inhibitor. Together, these results indicate that a JNK-dependent ubiquitin-proteasome system is induced under an inflammatory condition that disrupts astrocytic gap junction expression and function, leading to astrocytic dysfunction and the maintenance of the neuroinflammatory state. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiotoxic Effects of Short-Term Doxorubicin Administration: Involvement of Connexin 43 in Calcium Impairment.

Science.gov (United States)

Pecoraro, Michela; Rodríguez-Sinovas, Antonio; Marzocco, Stefania; Ciccarelli, Michele; Iaccarino, Guido; Pinto, Aldo; Popolo, Ada

2017-10-11

The use of Doxorubicin (DOXO), a potent antineoplastic agent, is limited by the development of cardiotoxicity. DOXO-induced cardiotoxicity is multifactorial, although alterations in calcium homeostasis, seem to be involved. Since even the Connexin43 (Cx43) plays a pivotal role in these two phenomena, in this study we have analyzed the effects of DOXO on Cx43 expression and localization. Damage caused by anthracyclines on cardiomyocytes is immediate after each injection, in the present study we used a short-term model of DOXO-induced cardiomyopathy. C57BL/6j female mice were randomly divided in groups and injected with DOXO (2 or 10 mg/kg i.p.) for 1-3 or 7 days once every other day. Cardiac function was assessed by Echocardiography. Sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCAII) and phospholamban (PLB) expression were assessed by Western blot analysis, intracellular [Ca 2+ ] were detected spectrofluorometrically by means of Fura-2 pentakis (acetoxymethyl) ester (FURA-2AM), and Cx43 and pCx43 expression and localization was analyzed by Western blot and confirmed by immunofluorescence analysis. DOXO induces impairment in Ca 2+ homeostasis, already evident after a single administration, and affects Cx43 expression and localization. Our data suggest that DOXO-induced alterations in Ca 2+ homeostasis causes in the cells the induction of compensatory mechanisms until a certain threshold, above which cardiac injury is triggered.

16 CFR 301.43 - Use of deceptive trade or corporate names, trademarks or graphic representations prohibited.

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2010-01-01

..., trademarks or graphic representations prohibited. 301.43 Section 301.43 Commercial Practices FEDERAL TRADE... Regulations § 301.43 Use of deceptive trade or corporate names, trademarks or graphic representations prohibited. No person shall use in labeling, invoicing or advertising any fur or fur product a trade name...

43 CFR 46.110 - Incorporating consensus-based management.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Incorporating consensus-based management... § 46.110 Incorporating consensus-based management. (a) Consensus-based management incorporates direct... carry out those plans and activities. For the purposes of this Part, consensus-based management involves...

PKCθ is required for the activation of human T lymphocytes induced by CD43 engagement

International Nuclear Information System (INIS)

Rio, Roxana del; Rincon, Mercedes; Layseca-Espinosa, Esther; Fierro, Nora A.; Rosenstein, Yvonne; Pedraza-Alva, Gustavo

2004-01-01

The turnover of phosphoinositides leading to PKC activation constitutes one of the principal axes of intracellular signaling. In T lymphocytes, the enhanced and prolonged PKC activation resulting from the engagement of the TcR and co-receptor molecules ensures a productive T cell response. The CD43 co-receptor promotes activation and proliferation, by inducing IL-2 secretion and CD69 expression. CD43 engagement has been shown to promote phosphoinositide turnover and DAG production. Moreover, PKC activation was found to be required for the activation of the MAP kinase pathway in response to CD43 ligation. Here we show that CD43 engagement led to the membrane translocation and enzymatic activity of specific PKC isoenzymes: cPKC (α/β), nPKC (ε and θ), aPKC (ζ) and PKCμ. We also show that activation of PKCθ resulting from CD43 ligation induced CD69 expression through an ERK-dependent pathway leading to AP-1, NF-κB activation and an ERK independent pathway promoting NFAT activation. Together, these data suggest that PKCθ plays a critical role in the co-stimulatory functions of CD43 in human T cells

KCNE3 is an inhibitory subunit of the Kv4.3 potassium channel

DEFF Research Database (Denmark)

Lundby, Alicia; Olesen, Søren-Peter

2006-01-01

The mammalian Kv4.3 potassium channel is a fast activating and inactivating K+ channel widely distributed in mammalian tissues. Kv4.3 is the major component of various physiologically important currents ranging from A-type currents in the CNS to the transient outward potassium conductance in the ...

Glycosyltransferase family 43 is also found in early eukaryotes and has three subfamilies in Charophycean green algae.

Directory of Open Access Journals (Sweden)

Rahil Taujale

Full Text Available The glycosyltransferase family 43 (GT43 has been suggested to be involved in the synthesis of xylans in plant cell walls and proteoglycans in animals. Very recently GT43 family was also found in Charophycean green algae (CGA, the closest relatives of extant land plants. Here we present evidence that non-plant and non-animal early eukaryotes such as fungi, Haptophyceae, Choanoflagellida, Ichthyosporea and Haptophyceae also have GT43-like genes, which are phylogenetically close to animal GT43 genes. By mining RNA sequencing data (RNA-Seq of selected plants, we showed that CGA have evolved three major groups of GT43 genes, one orthologous to IRX14 (IRREGULAR XYLEM14, one orthologous to IRX9/IRX9L and the third one ancestral to all land plant GT43 genes. We confirmed that land plant GT43 has two major clades A and B, while in angiosperms, clade A further evolved into three subclades and the expression and motif pattern of A3 (containing IRX9 are fairly different from the other two clades likely due to rapid evolution. Our in-depth sequence analysis contributed to our overall understanding of the early evolution of GT43 family and could serve as an example for the study of other plant cell wall-related enzyme families.

On the development of markers for pathological TDP-43 in amyotrophic lateral sclerosis with and without dementia.

LENUS (Irish Health Repository)

Geser, F

2011-12-01

Pathological 43-kDa transactive response sequence DNA-binding protein (TDP-43) has been recognized as the major disease protein in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin positive, tau and α-synuclein negative inclusions (FTLD-U) and the transitional forms between these multisystem conditions. In order to develop TDP-43 into a successful ALS biomarker, the natural history of TDP-43 pathology needs to be characterized and the underlying pathophysiology established. Here we propose a spatial and temporal "two-axes" model of central nervous system vulnerability for TDP-43 linked degeneration and review recent studies on potential biomarkers related to pathological TDP-43 in the cerebrospinal fluid (CSF), blood, and skeletal muscle. The model includes the following two arms: Firstly, a "motor neuron disease" or "spinal cord\\/brainstem to motor cortex" axis (with degeneration possibly ascending from the lower motor neurons to the upper motor neurons); and secondly, a "dementia" or "corticoid\\/allocortex to neocortex" axis (with a probable spread of TDP-43 linked degeneration from the mediotemporal lobe to wider mesocortical and neocortical brain areas). At the cellular level, there is a gradual disappearance of normal TDP-43 in the nucleus in combination with the formation of pathological aggregates in the cell body and cellular processes, which can also be used to identify the stage of the disease process. Moreover, TDP-43 lesions in subpial\\/subependymal or perivascular localizations have been noted, and this might account for increased CSF and blood TDP-43 levels through mechanisms that remain to be elucidated.

Analysis of Tank 38H (HTF-38-16-80, 81) and Tank 43H (HTF-43-16-82, 83) Samples for Support of the Enrichment Control and Corrosion Control Programs

Energy Technology Data Exchange (ETDEWEB)

Hay, M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2016-10-24

SRNL analyzed samples from Tank 38H and Tank 43H to support ECP and CCP. The total uranium in the Tank 38H surface sample was 57.6 mg/L, while the sub-surface sample was 106 mg/L. The Tank 43H samples ranged from 50.0 to 51.9 mg/L total uranium. The U-235 percentage was consistent for all four samples at 0.62%. The total uranium and percent U-235 results appear consistent with recent Tank 38H and Tank 43H uranium measurements. The Tank 38H plutonium results show a large difference between the surface and sub-surface sample concentrations and somewhat higher concentrations than previous samples. The Pu-238 concentration is more than forty times higher in the Tank 38H sub-surface sample than the surface sample. The surface and sub-surface Tank 43H samples contain similar plutonium concentrations and are within the range of values measured on previous samples. The four samples analyzed show silicon concentrations somewhat higher than the previous sample with values ranging from 104 to 213 mg/L.

Connexin 43 Channels are Essential for Normal Bone Structure and Osteocyte Viability

Science.gov (United States)

Xu, Huiyun; Gu, Sumin; Riquelme, Manuel A.; Burra, Sirisha; Callaway, Danielle; Cheng, Hongyun; Guda, Teja; Schmitz, James; Fajardo, Roberto J.; Werner, Sherry L.; Zhao, Hong; Shang, Peng; Johnson, Mark L.; Bonewald, Lynda F.; Jiang, Jean X.

2014-01-01

Connexin (Cx) 43 serves important roles in bone function and development. Targeted deletion of Cx43 in osteoblasts or osteocytes leads to increased osteocyte apoptosis, osteoclast recruitment, and reduced biomechanical properties. Cx43 forms both gap junction channels and hemichannels, which mediate the communication between adjacent cells or between cell and extracellular environments, respectively. Two transgenic mouse models driven by a DMP1 promoter with the overexpression of dominant negative Cx43 mutants were generated to dissect the functional contribution of Cx43 gap junction channels and hemichannels in osteocytes. The R76W mutant blocks gap junction channel, but not hemichannel function, and the Δ130-136 mutant inhibits activity of both types of channels. Δ130-136 mice showed a significant increase in bone mineral density compared to WT and R76W mice. MicroCT analyses revealed a significant increase in total tissue and bone area in midshaft cortical bone of Δ130-136 mice. The bone marrow cavity was expanded, whereas the cortical thickness was increased and associated with increased bone formation along the periosteal area. However, there is no significant alteration in the structure of trabecular bone. Histologic sections of the midshaft showed increased apoptotic osteocytes in Δ130-136, but not in WT and R76W, mice which correlated with altered biomechanical and estimated bone material properties. Osteoclasts were increased along the endocortical surface in both transgenic mice with a greater effect in Δ130-136 mice which likely contributed to the increased marrow cavity. Interestingly, the overall expression of serum bone formation and resorption markers were higher in R76W mice. These findings suggest that osteocytic Cx43 channels play distinctive roles in the bone; hemichannels play a dominant role in regulating osteocyte survival, endocortical bone resorption and periosteal apposition, and gap junction communication is involved in the process of

45 CFR 1151.43 - Adoption of grievance procedures.

Science.gov (United States)

2010-10-01

... Enforcement § 1151.43 Adoption of grievance procedures. A recipient may adopt an internal grievance procedure... prohibited by this part. A responsible official should be designated to coordinate the recipient's efforts in connection with this section. Such procedures need not be established with respect to complaints from...

Sodium Aluminosilicate Formation in Tank 43H Simulants

International Nuclear Information System (INIS)

Wilmarth, W.R.; Walker, D.D.; Fink, S.D.

1997-11-01

This work studied the formation of a sodium aluminosilicate, Na 8 Al 6 Si 6 O 24 (NO 3 ) 2?4 H 2 O, at 40 degree 110 degree C in simulated waste solutions with varied amounts of silicon and aluminum. The data agree well with literature solubility data for sodalite, the analogous chloride salt. The following conclusions result from this work: (1) The study shows, by calculation and experiments, that evaporation of the September 1997 Tank 43H inventory will only form minor quantities of the aluminosilicate. (2) The data indicate that the rate of formation of the nitrate enclathrated sodalite solid at these temperatures falls within the residence time (<; 4 h) of liquid in the evaporator. (3) The silicon in entrained Frit 200 transferred to the evaporator with the Tank 43H salt solution will quantitatively convert to the sodium aluminosilicate. One kilogram of Frit 200 produces 2.1 kg of the sodium aluminosilicate

United Nations Charter, Chapter VII, Article 43: Now or Never.

Science.gov (United States)

Burkle, Frederick M

2018-04-25

For more than 75 years, the United Nations Charter has functioned without the benefit of Chapter VII, Article 43, which commits all United Nations member states "to make available to the Security Council, on its call, armed forces, assistance, facilities, including rights of passage necessary for the purpose of maintaining international peace and security." The consequences imposed by this 1945 decision have had a dramatic negative impact on the United Nation's functional capacity as a global body for peace and security. This article summarizes the struggle to implement Article 43 over the decades from the onset of the Cold War, through diplomatic attempts during the post-Cold War era, to current and often controversial attempts to provide some semblance of conflict containment through peace enforcement missions. The rapid growth of globalization and the capability of many nations to provide democratic protections to their populations are again threatened by superpower hegemony and the development of novel unconventional global threats. The survival of the United Nations requires many long overdue organizational structure and governance power reforms, including implementation of a robust United Nations Standing Task Force under Article 43. (Disaster Med Public Health Preparedness. 2018;page 1 of 8).

Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

Science.gov (United States)

Li, Nan; Mruk, Dolores D; Mok, Ka-Wai; Li, Michelle W M; Wong, Chris K C; Lee, Will M; Han, Daishu; Silvestrini, Bruno; Cheng, C Yan

2016-04-01

Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to

Impact of O-glycosylation on the molecular and cellular adhesion properties of the Escherichia coli autotransporter protein Ag43.

Science.gov (United States)

Reidl, Sebastian; Lehmann, Annika; Schiller, Roswitha; Salam Khan, A; Dobrindt, Ulrich

2009-08-01

Antigen 43 (Ag43) represents an entire family of closely related autotransporter proteins in Escherichia coli and has been described to confer aggregation and fluffing of cells, to promote biofilm formation, uptake and survival in macrophages as well as long-term persistence of uropathogenic E. coli in the murine urinary tract. Furthermore, it has been reported that glycosylation of the Ag43 passenger domain (alpha(43)) stabilizes its conformation and increases adhesion to Hep-2 cells. We characterized the role of Ag43 as an adhesin and the impact of O-glycosylation on the function of Ag43. To analyze whether structural variations in the alpha(43) domain correlate with different functional properties, we cloned 5 different agn43 alleles from different E. coli subtypes and tested them for autoaggregation, biofilm formation, adhesion to different eukaryotic cell lines as well as to purified components of the extracellular matrix. These experiments were performed with nonglycosylated and O-glycosylated Ag43 variants. We show for the first time that Ag43 mediates bacterial adhesion in a cell line-specific manner and that structural variations of the alpha(43) domain correlate with increased adhesive properties to proteins of the extracellular matrix such as collagen and laminin. Whereas O-glycosylation of many alpha(43) domains led to impaired autoaggregation and a significantly reduced adhesion to eukaryotic cell lines, their interaction with collagen was significantly increased. These data demonstrate that O-glycosylation is not a prerequisite for Ag43 function and that the different traits mediated by Ag43, i.e., biofilm formation, autoaggregation, adhesion to eukaryotic cells and extracellular matrix proteins, rely on distinct mechanisms.

Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

Directory of Open Access Journals (Sweden)

Rong-Hui Tu

2017-11-01

Full Text Available Background/Aims: Previous studies have shown that heat shock protein 90 (HSP90-mediated mitochondrial import of connexin 43 (Cx43 is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. Methods: Cellular models of hypoxic postconditioning (HPC from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS production was assessed with the peroxide-sensitive fluorescent probe 2′,7′-dichlorofluorescin in diacetate (DCFH-DA. The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA, ROS scavengers superoxide dismutase (SOD and catalase (CAT, and small interfering RNA (siRNA targeting Cx43 and HSP90 were also investigated. Results: HPC significantly reduced hypoxia/reoxygenation (H/R-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA or siRNA targeting

Different expressions of connexin 43 and 32 in the fibroblasts of human dental pulp.

Science.gov (United States)

Ibuki, N; Yamaoka, Y; Sawa, Y; Kawasaki, T; Yoshida, S

2002-06-01

The expression and localization of gap junctional proteins connexin (Cx) 26, 32, and 43 was examined in human dental pulp. Dental pulp tissues were obtained from human third molars immediately after extraction. Some pulp tissues were used for cell culture, and the rest for histological observations. Immunostaining for cultured dental pulp fibroblasts (DPFs) showed that Cx32 and 43 were expressed in human DPFs, and proteins corresponding to 27 (Cx32) and 43kDa (Cx43) were identified by Western blot analysis. Immunostaining for tissue sections showed that the expression of Cx32 and 43 was observed in the entire region of the pulp and further strong expression of Cx32 was established beneath the cell-rich zone. Considering the close relationship between Cx types and cell functions, the results indicate that DPFs beneath the cell-rich zone may have specific, Cx32-related functions. The cell rich zone is thought to contain progenitor odontoblasts that can be induced to differentiate into mature odontoblasts in response to wounding. Therefore, it may be hypothesized that DPFs just beneath the cell-rich zone produce proteins and induce odontoblast differentiation from the cells in the cell-rich zone.

A calorimetric and equilibrium investigation of the reaction {l_brace}methyl ferulate(aq) + H{sub 2}O(l) = methanol(aq) + ferulic acid(aq){r_brace}

Energy Technology Data Exchange (ETDEWEB)

Goldberg, Robert N., E-mail: robert.goldberg@nist.go [Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20876 (United States); Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250 (United States); Lang, Brian E., E-mail: brian.lang@nist.go [Biochemical Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20876 (United States); Selig, Michael J., E-mail: michael.selig@nrel.go [National Renewable Energy Laboratory, Biosciences Center, 1617 Cole Boulevard, Golden, CO 80401 (United States); Decker, Stephen R., E-mail: steve.decker@nrel.go [National Renewable Energy Laboratory, Biosciences Center, 1617 Cole Boulevard, Golden, CO 80401 (United States)

2011-03-15

Microcalorimetry and high-performance liquid chromatography (HPLC) have been used to conduct a thermodynamic investigation of the reaction: {l_brace}methyl ferulate(aq) + H{sub 2}O(l) = methanol(aq) + ferulic acid(aq){r_brace}, as catalyzed by feruloyl esterase. Values of the apparent equilibrium constant K' = (29.6 {+-} 0.7) (T = 298.15 K, citrate buffer at pH 4.98, ionic strength I = 0.39 mol {center_dot} kg{sup -1}) and of the calorimetrically determined enthalpy of reaction {Delta}{sub r}H(cal) = (4.0 {+-} 0.9) kJ {center_dot} mol{sup -1} (T = 298.15 K and citrate buffer at pH 4.81, I = 0.36 mol {center_dot} kg{sup -1}) were measured. A chemical equilibrium model, together with pKs and standard enthalpies of reaction {Delta}{sub r}H{sup 0} for the H{sup +}(aq) binding reactions of the reactants and products, was then used to calculate the values K = (1.89 {+-} 0.06) . 10{sup -4}, {Delta}{sub r}H{sup o} = (7.3 {+-} 1.7) kJ {center_dot} mol{sup -1}, {Delta}{sub r}G{sup o} = (21.25 {+-} 0.07) kJ {center_dot} mol{sup -1}, and {Delta}{sub r}S{sup o} = - (46.8 {+-} 5.7) J {center_dot} K{sup -1} {center_dot} mol{sup -1} for the chemical reference reaction {l_brace}methyl ferulate(aq) + H{sub 2}O(l) = methanol(aq) + ferulic acid{sup -}(aq) + H{sup +}(aq){r_brace}. These values of K and {Delta}{sub r}H{sup o} are similar in magnitude to the corresponding values reported for the reaction {l_brace}propyl gallate(aq) + H{sub 2}O(l) = 3,4,5-trihydroxybenzoic acid{sup -}(aq) + 1-propanol(aq) + H{sup +}(aq){r_brace}. The results obtained in this study can be used in a chemical equilibrium model to calculate how K' and other standard transformed properties such as the standard transformed enthalpy {Delta}{sub r}H'{sup o}, standard transformed Gibbs free energy {Delta}{sub r}G'{sup o}, and the change in binding of H{sup +}(aq), {Delta}{sub r}N(H{sup +}), vary with the independent variables T, pH, and I.

Estradiol Receptors Regulate Differential Connexin 43 Expression in F98 and C6 Glioma Cell Lines.

Directory of Open Access Journals (Sweden)

Zahra Moinfar

Full Text Available Glioma is the most common malignant primary brain tumour with male preponderance and poor prognosis. Glioma cells express variable amounts of connexin 43 (Cx43 and estrogen receptors (ERs. Both, Cx43 and ERs, play important roles in cell proliferation and migration. Therefore, we investigated the effects of 17-ß estradiol (E2 on Cx43 expression in two glioma cell lines with variable native expression of Cx43.F98 and C6 rat glioma cells were cultured for 24 h in the presence of 10 nM or 100 nM E2, and the E2-antagonist, Fulvestrant. An MTT assay was performed to evaluate cell viability. ERα, ERβ and Cx43 protein expressions were analysed by western blotting and Cx43 mRNA expression was analysed by real-time polymerase chain reaction. To quantify cell migration, an exclusive zone migration assay was used. Functional coupling of cells via gap junctions was examined using whole-cell patch-clamp technique.E2 reduced Cx43 expression in C6 cells, but increased Cx43 expression in F98 cultures. These effects were mediated via ERs. Moreover, E2 promoted C6 cell migration, but it did not affect F98 cell migration. The expression level of ERα was found to be high in C6, but low in F98 cells. ERβ was exclusively expressed in C6 cells. In addition, E2 treatment induced a significant decrease of ERβ in C6 cultures, while it decreased ERα expression in F98 glioma cells.These findings show that E2 differentially modulates Cx43 expression in F98 and C6 glioma cells, likely due to the differential expression of ERs in each of these cell lines. Our findings point to the molecular mechanisms that might contribute to the gender-specific differences in the malignancy of glioma and could have implications for therapeutic strategies against glioma.

Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

Science.gov (United States)

Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

2016-11-01

Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

Specific association of growth-associated protein 43 with calcium release units in skeletal muscles of lower vertebrates

Directory of Open Access Journals (Sweden)

G.A. Caprara

2014-10-01

Full Text Available Growth-associated protein 43 (GAP43, is a strictly conserved protein among vertebrates implicated in neuronal development and neurite branching. Since GAP43 structure contains a calmodulin-binding domain, this protein is able to bind calmodulin and gather it nearby membrane network, thus regulating cytosolic calcium and consequently calcium-dependent intracellular events. Even if for many years GAP43 has been considered a neuronal-specific protein, evidence from different laboratories described its presence in myoblasts, myotubes and adult skeletal muscle fibers. Data from our laboratory showed that GAP43 is localized between calcium release units (CRUs and mitochondria in mammalian skeletal muscle suggesting that, also in skeletal muscle, this protein can be a key player in calcium/calmodulin homeostasis. However, the previous studies could not clearly distinguish between a mitochondrion- or a triad-related positioning of GAP43. To solve this question, the expression and localization of GAP43 was studied in skeletal muscle of Xenopus and Zebrafish known to have triads located at the level of the Z-lines and mitochondria not closely associated with them. Western blotting and immunostaining experiments revealed the expression of GAP43 also in skeletal muscle of lower vertebrates (like amphibians and fishes, and that the protein is localized closely to the triad junction. Once more, these results and GAP43 structural features, support an involvement of the protein in the dynamic intracellular Ca2+ homeostasis, a common conserved role among the different species.

43 CFR 423.27 - Advertising and public solicitation.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Advertising and public solicitation. 423.27 Section 423.27 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION... of Conduct § 423.27 Advertising and public solicitation. You must not engage in advertising or...

25 CFR 36.43 - Standard XVI-Student activities.

Science.gov (United States)

2010-04-01

... § 36.43 Standard XVI—Student activities. All schools shall provide and maintain a well-balanced student..., and planned types of fund-raising activities. (c) School may participate in interscholastic sports and... sanctioned by the school. (g) All student activities involved only in fund raising are required to establish...

43 CFR 418.26 - Charges for water use.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Charges for water use. 418.26 Section 418... and Management § 418.26 Charges for water use. The District must maintain a financing and accounting... provides reasonable financial incentives for the economical and efficient use of water. ...

Synthesis, Structure, and Li-Ion Conductivity of LiLa(BH4)3X, X = Cl, Br, I

DEFF Research Database (Denmark)

Payandeh GharibDoust, SeyedHosein; Brighi, Matteo; Sadikin, Yolanda

2017-01-01

In this work, a new type of addition reaction between La(BH4)3 and LiX, X = Cl, Br, I, is used to synthesize LiLa(BH4)3Cl and two new compounds LiLa(BH4)3X, X = Br, I. This method increases the amounts of LiLa(BH4)3X and the sample purity. The highest Li-ion conductivity is observed for LiLa(BH4)...

77 FR 33735 - Notice of Issuance of Statement of Federal Financial Accounting Standard 43

Science.gov (United States)

2012-06-07

... FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Notice of Issuance of Statement of Federal Financial Accounting Standard 43 AGENCY: Federal Accounting Standards Advisory Board. ACTION: Notice. Board Action... Accounting Standards Advisory Board (FASAB) has issued Statement of Federal Financial Accounting Standard 43...

Differential diagnosis of amyotrophic lateral sclerosis from Guillain-Barré syndrome by quantitative determination of TDP-43 in cerebrospinal fluid.

Science.gov (United States)

Hosokawa, Masato; Arai, Tetsuaki; Yamashita, Makiko; Tsuji, Hiroshi; Nonaka, Takashi; Masuda-Suzukake, Masami; Tamaoka, Akira; Hasegawa, Masato; Akiyama, Haruhiko

2014-05-01

The aim of this study was to investigate whether an increased level of TAR DNA-binding protein 43 (TDP-43) in the cerebrospinal fluid (CSF) could be a biomarker for amyotrophic lateral sclerosis (ALS) and facilitate differential diagnosis of ALS from peripheral motor neuropathy. TDP-43 is the major constituent of neuronal and glial inclusions that neuropathologically characterize both ALS and tau-negative frontotemporal lobar degeneration. Recent discoveries of various missense mutations in the TDP-43 gene in familial ALS indicate a pivotal role of the aberrant accumulation of TDP-43 in neurodegeneration. Increased TDP-43 in the CSF could be a hallmark of ALS and other TDP-43 proteinopathy. Sandwich enzyme-linked immunosorbent assay (ELISA) was established to measure the concentration of TDP-43 in biological fluids. Culture supernatants of cells transfected with various TDP-43 constructs were used to confirm that the ELISA detected TDP-43. TDP-43 in the culture supernatant of TDP-43 transfected cells was detected by immunoprecipitation with subsequent immunoblotting and concentrations were successfully measured by sandwich ELISA. We then measured TDP-43 concentrations in the CSF of patients with ALS and Guillain-Barré syndrome (GBS). TDP-43 concentrations in CSF were significantly higher in ALS than in GBS (p = 0.016). The sensitivity of the diagnostic test was 71.4% and the specificity was 84.6%. Quantitative determination of TDP-43 concentrations in the CSF by sandwich ELISA is a potential laboratory test for differentiating ALS from peripheral motor neuropathies such as GBS.

TP43H60 tabletop projection TV; Table top projection terebi TP43H60

Energy Technology Data Exchange (ETDEWEB)

NONE

1999-03-01

The Company commercially produced a tabletop 43 type projection TV which completely changes an image of the existing projection TV. The main features are as follows: 1) By adopting the newly developed CRT, thin type screen and short-focus lens, TV was made compact, realizing high luminance and high contrast; 2) Color reproducibility is improved by adopting color filter lens and high accuracy blue elongation circuit; 3) The TV is loaded with the 9-point multi-convergence circuit which made color slippage adjustment of the whole screen possible; 4) It is equipped with a high quality screen use color difference inputting terminal. (translated by NEDO)

Artist Concept of X-43A/Hyper-X Hypersonic Experimental Research Vehicle in Flight

Science.gov (United States)

1998-01-01

An artist's conception of the X-43A Hypersonic Experimental Vehicle, or 'Hyper-X' in flight. The X-43A was developed to flight test a dual-mode ramjet/scramjet propulsion system at speeds from Mach 7 up to Mach 10 (7 to 10 times the speed of sound, which varies with temperature and altitude). Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will

Expanding Canadian renewable and conservation expenses class 43.1 to include solar

International Nuclear Information System (INIS)

2005-01-01

Class 43.1 is a tax measure that allows for accelerated write-offs of renewable energy products for business use. Technologies that are included in the class for accelerated write off include renewable energy sources such as wind, small hydro, geo-thermal, fuel cells, bio-gas, cogeneration systems, and district heating and solar. In 2005, the federal budget announced 2 changes to class 43.1 The write off rate has been increased from 30 per cent to 50 per cent. This change would reduce the effective cost of solar energy for business owners. The class has also been extended to include distribution assets for district energy assets and biogas equipment. However, no changes to the restrictions for solar were announced. The Canadian Solar Industries Association (CanSIA) argues that class 43.1 currently does not help the solar industries, nor do the proposed changes solve this situation. The restrictions placed on solar eliminate about 90 per cent of the industrial applications for solar that class 43.1 should support. Class 43.1 currently covers only 1 per cent of photovoltaic applications, 2 per cent of solar hot water applications, and 9 per cent of solar air heating applications. CanSIA claims that an increase in tax write-offs for photovoltaic systems, solar hot water, and solar air heating would help increase the solar market from 1,060 kW to a market size of 11,600 kW. CanSIA has made recommendations to the federal government to remove the size restrictions for PV systems and to remove the restrictions on applications for solar thermal systems. 2 tabs

Regulatory effect of connexin 43 on basal Ca2+ signaling in rat ventricular myocytes.

Directory of Open Access Journals (Sweden)

Chen Li

Full Text Available BACKGROUND: It has been found that gap junction-associated intracellular Ca(2+ [Ca(2+](i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca(2+ signaling, in particular the basal [Ca(2+](i activities, is unclear. METHODS AND RESULTS: Global and local Ca(2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY, respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43 with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca(2+ transients and local Ca(2+ sparks in monolayer NRVMs and Ca(2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP(3 butyryloxymethyl ester and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca(2+ signal and LY uptake by gap uncouplers, whereas blockade of IP(3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca(2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca(2+ signaling regulation in cardiomyocytes. CONCLUSIONS: These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca(2

43 CFR 18.300 - Professional and technical services.

Science.gov (United States)

2010-10-01

..., drafting or a legal document accompanying a bid or proposal by a lawyer is allowable. Similarly, technical... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Professional and technical services. 18... LOBBYING Activities by Other Than Own Employees § 18.300 Professional and technical services. (a) The...

43 CFR 4.1309 - Petition for discretionary review.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Petition for discretionary review. 4.1309... APPEALS PROCEDURES Special Rules Applicable to Surface Coal Mining Hearings and Appeals Petitions for Review of Proposed Individual Civil Penalty Assessments Under Section 518(f) of the Act § 4.1309 Petition...

43 CFR 4.100 - General rules and guidelines.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false General rules and guidelines. 4.100... rules and guidelines. (a) Effective date and applicability—(1) Effective date and general applicability..., in which event the period shall run to the end of the next business day. (e) General guidelines—(1...

43 CFR 423.25 - Vandalism, tampering, and theft.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Vandalism, tampering, and theft. 423.25 Section 423.25 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION... of Conduct § 423.25 Vandalism, tampering, and theft. (a) You must not tamper or attempt to tamper...

FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration

DEFF Research Database (Denmark)

Urwin, Hazel; Josephs, Keith A; Rohrer, Jonathan D

2010-01-01

Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92...

Mice lacking the p43 mitochondrial T3 receptor become glucose intolerant and insulin resistant during aging.

Directory of Open Access Journals (Sweden)

Christelle Bertrand

Full Text Available Thyroid hormones (TH play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3 receptor (p43 which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43-/- mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43-/- mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43-/- mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes.

Arabidopsis Raf-Like Mitogen-Activated Protein Kinase Kinase Kinase Gene Raf43 Is Required for Tolerance to Multiple Abiotic Stresses.

Directory of Open Access Journals (Sweden)

Nasar Virk

Full Text Available Mitogen-activated protein kinase (MAPK cascades are critical signaling modules that mediate the transduction of extracellular stimuli into intracellular response. A relatively large number of MAPKKKs have been identified in a variety of plant genomes but only a few of them have been studied for their biological function. In the present study, we identified an Arabidopsis Raf-like MAPKKK gene Raf43 and studied its function in biotic and abiotic stress response using a T-DNA insertion mutant raf43-1 and two Raf43-overexpressing lines Raf43-OE#1 and Raf43-OE#13. Expression of Raf43 was induced by multiple abiotic and biotic stresses including treatments with drought, mannitol and oxidative stress or defense signaling molecule salicylic acid and infection with necrotrophic fungal pathogen Botrytis cinerea. Seed germination and seedling root growth of raf43-1 were significantly inhibited on MS medium containing mannitol, NaCl, H2O2 or methyl viologen (MV while seed germination and seedling root growth of the Raf43-OE#1 and Raf43-OE#13 lines was similar to wild type Col-0 under the above stress conditions. Soil-grown raf43-1 plants exhibited reduced tolerance to MV, drought and salt stress. Abscisic acid inhibited significantly seed germination and seedling root growth of the raf43-1 line but had no effect on the two Raf43-overexpressing lines. Expression of stress-responsive RD17 and DREB2A genes was significantly down-regulated in raf43-1 plants. However, the raf43-1 and Raf43-overexpressing plants showed similar disease phenotype to the wild type plants after infection with B. cinerea or Pseudomonas syringae pv. tomato DC3000. Our results demonstrate that Raf43, encoding for a Raf-like MAPKKK, is required for tolerance to multiple abiotic stresses in Arabidopsis.

Comments on Resolution ANP 43/2007 and technical regulation of the system operational safety management - SGSO; Comentarios a Resolucao ANP 43/2007 e ao regulamento tecnico do sistema de gerenciamento da seguranca operacional - SGSO

Energy Technology Data Exchange (ETDEWEB)

Lima, Flavio Augusto Pimentel de [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil)

2012-07-01

Some of the provisions of ANP Board Resolution n. 43, in December, 6th, 2007 (R-ANP 43/2007) have to receive special attention by economic agents, in consideration of the excessive extent and fuzziness and also the absence of objective criteria to assess their fulfillment by the Concessionaire. This paper will comment the responsibility of the Concessionaire (as show in article 1st , 2nd paragraph, of R-ANP 43/2007); the ANP authority (as show in article 1st , 3rd paragraph, of R-ANP 43/2007); the delivery of Operational Security Documentation and the imposition of penalties for violations of the SGSO. In conclusion, this paper will indicated some aspects which, from a legal point of view, need to be improved to provide greater legal certainty for economic agents. (author)

TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila

Directory of Open Access Journals (Sweden)

Lies Vanden Broeck

2013-01-01

Full Text Available TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43 in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up- and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up- and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function.

43rd Aerospace Mechanisms Symposium

Science.gov (United States)

Boesiger, Edward A.

2016-01-01

The Aerospace Mechanisms Symposium (AMS) provides a unique forum for those active in the design, production and use of aerospace mechanisms. A major focus is the reporting of problems and solutions associated with the development and flight certification of new mechanisms. Sponsored and organized by the Mechanisms Education Association, responsibility for hosting the AMS is shared by the National Aeronautics and Space Administration and Lockheed Martin Space Systems Company (LMSSC). Now in its 43rd symposium, the AMS continues to be well attended, attracting participants from both the U.S. and abroad. The 43rd AMS was held in Santa Clara, California on May 4, 5 and 6, 2016. During these three days, 42 papers were presented. Topics included payload and positioning mechanisms, components such as hinges and motors, CubeSats, tribology, and mechanism testing. Hardware displays during the supplier exhibit gave attendees an opportunity to meet with developers of current and future mechanism components. The high quality of this symposium is a result of the work of many people, and their efforts are gratefully acknowledged. This extends to the voluntary members of the symposium organizing committee representing the eight NASA field centers, LMSSC, and the European Space Agency. Appreciation is also extended to the session chairs, the authors, and particularly the personnel at ARC responsible for the symposium arrangements and the publication of these proceedings. A sincere thank you also goes to the symposium executive committee who is responsible for the year-to-year management of the AMS, including paper processing and preparation of the program. The use of trade names of manufacturers in this publication does not constitute an official endorsement of such products or manufacturers, either expressed or implied, by the National Aeronautics and Space Administration.

43 CFR 20.401 - Interests in Federal lands.

Science.gov (United States)

2010-10-01

... Bureau of Land Management. (1) In accordance with 43 U.S.C. 11, employees of the Bureau of Land Management are prohibited from voluntarily acquiring a direct or indirect interest in Federal lands. (2... Survey are prohibited from having any personal or private interests in the lands or mineral wealth of the...

49 CFR 393.43 - Breakaway and emergency braking.

Science.gov (United States)

2010-10-01

... ACCESSORIES NECESSARY FOR SAFE OPERATION Brakes § 393.43 Breakaway and emergency braking. (a) Towing vehicle protection system. Every motor vehicle, if used to tow a trailer equipped with brakes, shall be equipped with... brake systems installed on towed vehicles shall be so designed, by the use of “no-bleed-back” relay...

43 CFR 17.251 - Drug and alcohol addicts.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Drug and alcohol addicts. 17.251 Section... Drug and alcohol addicts. A recipient that operates a general hospital or outpatient facility may not discriminate in admission or treatment against a drug or alcohol abuser or addict who is suffering from a...

43 CFR 29.6 - Financing, accounting, and audit.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Financing, accounting, and audit. 29.6 Section 29.6 Public Lands: Interior Office of the Secretary of the Interior TRANS-ALASKA PIPELINE LIABILITY FUND § 29.6 Financing, accounting, and audit. (a)(1) The Operator of the Pipeline shall notify...

43 CFR 41.520 - Job classification and structure.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Job classification and structure. 41.520 Section 41.520 Public Lands: Interior Office of the Secretary of the Interior NONDISCRIMINATION ON THE... classification and structure. A recipient shall not: (a) Classify a job as being for males or for females; (b...

43 CFR 19.7 - Private contributions and gifts.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Private contributions and gifts. 19.7... National Wilderness Preservation System § 19.7 Private contributions and gifts. (a) The Secretary is... contributions and gifts to be used to further the purposes of the act. The Secretary, under the authorization of...

43 CFR 23.7 - Approval of exploration plan.

Science.gov (United States)

2010-10-01

... measures to be taken to prevent or control fire, soil erosion, pollution of surface and ground water... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Approval of exploration plan. 23.7 Section 23.7 Public Lands: Interior Office of the Secretary of the Interior SURFACE EXPLORATION, MINING AND...

ORF43 of maize rayado fino virus is dispensable for systemic infection of maize and transmission by leafhoppers.

Science.gov (United States)

Edwards, Michael C; Weiland, John J; Todd, Jane; Stewart, Lucy R; Lu, Shunwen

2016-04-01

Maize rayado fino virus (MRFV) possesses an open reading frame (ORF43) predicted to encode a 43 kDa protein (p43) that has been postulated to be a viral movement protein. Using a clone of MRFV (pMRFV-US) from which infectious RNA can be produced, point mutations were introduced to either prevent initiation from three potential AUG initiation codons near the 5'-end of ORF43 or prematurely terminate translation of ORF43. Inoculation of maize seed via vascular puncture inoculation (VPI) resulted in plants exhibiting symptoms typical of MRFV infection for all mutants tested. Furthermore, corn leafhoppers (Dalbulus maidis) transmitted the virus mutants to healthy plants at a frequency similar to that for wild-type MRFV-US. Viral RNA recovered from plants infected with mutants both prior to and after leafhopper transmission retained mutations blocking ORF43 expression. The results indicate that ORF43 of MRFV is dispensable for both systemic infection of maize and transmission by leafhoppers.

Regulation of connexin26 and connexin43 expression in rat endometrium by ovarian steroid hormones.

Science.gov (United States)

Grümmer, R; Chwalisz, K; Mulholland, J; Traub, O; Winterhager, E

1994-12-01

A distinct spatial and temporal pattern of connexin26 and connexin43 (cx26 and cx43) expression was observed in the rat endometrium in response to embryo implantation; however, connexin expression was suppressed during the preimplantation period. Pseudopregnant rats did not show connexin mRNA, while artificial decidualization induced by a scratch led to a strong expression of cx26 and cx43 in the endometrium of these animals. In order to examine the regulatory effects of ovarian steroid hormones on connexin expression, ovariectomized rats were treated with progesterone (P) and/or estradiol-17 beta (E2). Untreated, ovariectomized animals expressed mRNA for cx43, but not for cx26. Endometrial expression of mRNA for both connexins was strongly enhanced by E2 treatment; immunolabeling revealed protein for cx26 in the uterine luminal epithelial cells and for cx43 in the uterine stromal cells. P treatment, either alone or in combination with E2, suppressed expression of connexin mRNA. P suppression in the presence of E2 was reversible when P was withdrawn. When administered on Days 0-2 of pregnancy, the antiprogestin onapristone inhibited the effect of P and gave rise to strong expression of both connexin transcripts. These results demonstrate that expression of cx26 and cx43 in the rat uterine endometrium is differentially regulated by E2 and P during early pregnancy.

An alternative mode of CD43 signal transduction activates pro-survival pathways of T lymphocytes.

Science.gov (United States)

Bravo-Adame, Maria Elena; Vera-Estrella, Rosario; Barkla, Bronwyn J; Martínez-Campos, Cecilia; Flores-Alcantar, Angel; Ocelotl-Oviedo, Jose Pablo; Pedraza-Alva, Gustavo; Rosenstein, Yvonne

2017-01-01

CD43 is one of the most abundant co-stimulatory molecules on a T-cell surface; it transduces activation signals through its cytoplasmic domain, contributing to modulation of the outcome of T-cell responses. The aim of this study was to uncover new signalling pathways regulated by this sialomucin. Analysis of changes in protein abundance allowed us to identify pyruvate kinase isozyme M2 (PKM2), an enzyme of the glycolytic pathway, as an element potentially participating in the signalling cascade resulting from the engagement of CD43 and the T-cell receptor (TCR). We found that the glycolytic activity of this enzyme was not significantly increased in response to TCR+CD43 co-stimulation, but that PKM2 was tyrosine phosphorylated, suggesting that it was performing moonlight functions. We report that phosphorylation of both Y 105 of PKM2 and of Y 705 of signal transducer and activator of transcription 3 was induced in response to TCR+CD43 co-stimulation, resulting in activation of the mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway. ERK5 and the cAMP response element binding protein (CREB) were activated, and c-Myc and nuclear factor-κB (p65) nuclear localization, as well as Bad phosphorylation, were augmented. Consistent with this, expression of human CD43 in a murine T-cell hybridoma favoured cell survival. Altogether, our data highlight novel signalling pathways for the CD43 molecule in T lymphocytes, and underscore a role for CD43 in promoting cell survival through non-glycolytic functions of metabolic enzymes. © 2016 John Wiley & Sons Ltd.

TDP-43 inclusion bodies formed in bacteria are structurally amorphous, non-amyloid and inherently toxic to neuroblastoma cells.

Directory of Open Access Journals (Sweden)

Claudia Capitini

Full Text Available Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Such inclusions have variably been described as amorphous aggregates or more structured deposits having an amyloid structure. Following the observations that bacterial inclusion bodies generally consist of amyloid aggregates, we have overexpressed full-length TDP-43 and C-terminal TDP-43 in E. coli, purified the resulting full-length and C-terminal TDP-43 containing inclusion bodies (FL and Ct TDP-43 IBs and subjected them to biophysical analyses to assess their structure/morphology. We show that both FL and Ct TDP-43 aggregates contained in the bacterial IBs do not bind amyloid dyes such as thioflavin T and Congo red, possess a disordered secondary structure, as inferred using circular dichroism and infrared spectroscopies, and are susceptible to proteinase K digestion, thus possessing none of the hallmarks for amyloid. Moreover, atomic force microscopy revealed an irregular structure for both types of TDP-43 IBs and confirmed the absence of amyloid-like species after proteinase K treatment. Cell biology experiments showed that FL TDP-43 IBs were able to impair the viability of cultured neuroblastoma cells when added to their extracellular medium and, more markedly, when transfected into their cytosol, where they are at least in part ubiquitinated and phosphorylated. These data reveal an inherently high propensity of TDP-43 to form amorphous aggregates, which possess, however, an inherently high ability to cause cell dysfunction. This indicates that a gain of toxic function caused by TDP-43 deposits is effective in TDP-43 pathologies, in addition to possible loss of function mechanisms originating from the cellular mistrafficking of the protein.

Defective cancellous bone structure and abnormal response to PTH in cortical bone of mice lacking Cx43 cytoplasmic C-terminus domain

Science.gov (United States)

Pacheco-Costa, Rafael; Davis, Hannah M.; Sorenson, Chad; Hon, Mary C.; Hassan, Iraj; Reginato, Rejane D.; Allen, Matthew R.; Bellido, Teresita; Plotkin, Lilian I.

2015-01-01

Connexin43 (Cx43) forms gap junction channels and hemichannels that allow the communication among osteocytes, osteoblasts, and osteoclasts. Cx43 carboxy-terminal (CT) domain regulates channel opening and intracellular signaling by acting as a scaffold for structural and signaling proteins. To determine the role of Cx43 CT domain in bone, mice in which one allele of full length Cx43 was replaced by a mutant lacking the CT domain (Cx43ΔCT/fl) were studied. Cx43ΔCT/fl mice exhibit lower cancellous bone volume but higher cortical thickness than Cx43fl/fl controls, indicating that the CT domain is involved in normal cancellous bone gain but opposes cortical bone acquisition. Further, Cx43ΔCT is able to exert the functions of full length osteocytic Cx43 on cortical bone geometry and mechanical properties, demonstrating that domains other than the CT are responsible for Cx43 function in cortical bone. In addition, parathyroid hormone (PTH) failed to increase endocortical bone formation or energy to failure, a mechanical property that indicates resistance to fracture, in cortical bone in Cx43ΔCT mice with or without osteocytic full length Cx43. On the other hand, bone mass and bone formation markers were increased by the hormone in all mouse models, regardless of whether full length or Cx43ΔCT were or not expressed. We conclude that Cx43 CT domain is involved in proper bone acquisition; and that Cx43 expression in osteocytes is dispensable for some but not all PTH anabolic actions. PMID:26409319

Synthesis, Structure, and Li-Ion Conductivity of LiLa(BH4)3X, X = Cl, Br, I

DEFF Research Database (Denmark)

GharibDoust, Seyed Hosein Payandeh; Brighi, Matteo; Sadikin, Yolanda

2017-01-01

In this work, a new type of addition reaction between La(BH4)3 and LiX, X = Cl, Br, I, is used to synthesize LiLa(BH4)3Cl and two new compounds LiLa(BH4)3X, X = Br, I. This method increases the amounts of LiLa(BH4)3X and the sample purity. The highest Li-ion conductivity is observed for LiLa(BH4...... with increasing lattice parameter, that is, increasing size of the halide ion in the structure. Thus, we conclude that the sizes of both windows are important for the lithium ion conduction in LiLa(BH4)3X compounds. The lithium ion conductivity is measured over one to three heating cycles and with different...

43 CFR 4.1101 - Jurisdiction of the Board.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Jurisdiction of the Board. 4.1101 Section... APPEALS PROCEDURES Special Rules Applicable to Surface Coal Mining Hearings and Appeals General Provisions § 4.1101 Jurisdiction of the Board. (a) The jurisdiction of the Board, as set forth in § 4.1(b)(3...

10 CFR 1045.43 - Systematic review for declassification.

Science.gov (United States)

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Systematic review for declassification. 1045.43 Section... Systematic review for declassification. (a) The Secretary shall ensure that RD documents, and the DoD shall... Classification (and with the DoD for FRD) to ensure the systematic review of RD and FRD documents. (c) Review of...

43 CFR 422.3 - Reclamation law enforcement policy.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Reclamation law enforcement policy. 422.3 Section 422.3 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR LAW ENFORCEMENT AUTHORITY AT BUREAU OF RECLAMATION PROJECTS § 422.3 Reclamation law enforcement policy. The law enforcement...

43 CFR 12.945 - Cost and price analysis.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Cost and price analysis. 12.945 Section 12... Requirements § 12.945 Cost and price analysis. Some form of cost or price analysis shall be made and documented in the procurement files in connection with every procurement action. Price analysis may be...

ASSESSMENT OF TECHNETIUM LEACHABILITY IN CEMENT STABILIZED BASIN 43 GROUNDWATER BRINE

International Nuclear Information System (INIS)

COOKE GA; DUNCAN JB; LOCKREM LL

2008-01-01

This report is an initial report on the laboratory effort executed under RPP-PLAN-33338, Test Plan for the Assessment of Technetium Leachability in Cement-Stabilized Basin 43 Groundwater Brine. This report delineates preliminary data obtained under subcontract 21065, release 30, from the RJ Lee Group, Inc., Center for Laboratory Sciences. The report is predicated on CLS RPT-816, Draft Report: Assessment of Technetium Leachability in Cement Stabilized Basin 43 Groundwater Brine. This document will be revised on receipt of the final RJ Lee Group, Inc., Center for Laboratory Sciences report, which will contain data subjected to quality control and quality assurance criteria

Young Stellar Objects in the Massive Star-forming Regions W51 and W43

Energy Technology Data Exchange (ETDEWEB)

Saral, G.; Audard, M. [Department of Astronomy, University of Geneva, Ch. d’Ecogia 16, 1290 Versoix (Switzerland); Hora, J. L.; Martínez-Galarza, J. R.; Smith, H. A. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Koenig, X. P. [Yale University, Department of Astronomy, 208101, New Haven, CT 06520-8101 (United States); Motte, F. [Institut de Plantologie et d’Astrophysique de Grenoble, Univ. Grenoble Alpes—CNRS-INSU, BP 53, F-38041 Grenoble Cedex 9 (France); Nguyen-Luong, Q. [National Astronomical Observatory of Japan, Chile Observatory, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan); Saygac, A. T. [Istanbul University, Faculty of Science, Astronomy and Space Sciences Department, Istanbul-Turkey (Turkey)

2017-04-20

We present the results of our investigation of the star-forming complexes W51 and W43, two of the brightest in the first Galactic quadrant. In order to determine the young stellar object (YSO) populations in W51 and W43 we used color–magnitude relations based on Spitzer mid-infrared and 2MASS/UKIDSS near-infrared data. We identified 302 Class I YSOs and 1178 Class II/transition disk candidates in W51, and 917 Class I YSOs and 5187 Class II/transition disk candidates in W43. We also identified tens of groups of YSOs in both regions using the Minimal Spanning Tree (MST) method. We found similar cluster densities in both regions, even though Spitzer was not able to probe the densest part of W43. By using the Class II/I ratios, we traced the relative ages within the regions and, based on the morphology of the clusters, we argue that several sites of star formation are independent of one another in terms of their ages and physical conditions. We used spectral energy distribution-fitting to identify the massive YSO (MYSO) candidates since they play a vital role in the star formation process, and then examined them to see if they are related to any massive star formation tracers such as UCH ii regions, masers, or dense fragments. We identified 17 MYSO candidates in W51, and 14 in W43, respectively, and found that groups of YSOs hosting MYSO candidates are positionally associated with H ii regions in W51, though we do not see any MYSO candidates associated with previously identified massive dense fragments in W43.

15 CFR 265.43 - Pets and other animals.

Science.gov (United States)

2010-01-01

... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Pets and other animals. 265.43 Section... animals. Except in connection with the conduct of official business on the site or with the approval of... person shall bring upon the site any cat, dog, or other animal, provided, however, that blind persons may...

43 CFR 41.455 - Textbooks and curricular material.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Textbooks and curricular material. 41.455 Section 41.455 Public Lands: Interior Office of the Secretary of the Interior NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs o...

Intracellular Cleavage of the Cx43 C-Terminal Domain by Matrix-Metalloproteases: A Novel Contributor to Inflammation?

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Marijke De Bock

2015-01-01

Full Text Available The coordination of tissue function is mediated by gap junctions (GJs that enable direct cell-cell transfer of metabolic and electric signals. GJs are formed by connexin (Cx proteins of which Cx43 is most widespread in the human body. Beyond its role in direct intercellular communication, Cx43 also forms nonjunctional hemichannels (HCs in the plasma membrane that mediate the release of paracrine signaling molecules in the extracellular environment. Both HC and GJ channel function are regulated by protein-protein interactions and posttranslational modifications that predominantly take place in the C-terminal domain of Cx43. Matrix metalloproteases (MMPs are a major group of zinc-dependent proteases, known to regulate not only extracellular matrix remodeling, but also processing of intracellular proteins. Together with Cx43 channels, both GJs and HCs, MMPs contribute to acute inflammation and a small number of studies reports on an MMP-Cx43 link. Here, we build further on these reports and present a novel hypothesis that describes proteolytic cleavage of the Cx43 C-terminal domain by MMPs and explores possibilities of how such cleavage events may affect Cx43 channel function. Finally, we set out how aberrant channel function resulting from cleavage can contribute to the acute inflammatory response during tissue injury.

Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio.

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Alexandra Vaccaro

Full Text Available The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates in a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS and related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans and zebrafish animal models expressing mutant human TDP-43 (A315T or G348C or FUS (S57Δ or R521H that reflect certain aspects of ALS including motor neuron degeneration, axonal deficits, and progressive paralysis. To explore the potential of our humanized transgenic C. elegans and zebrafish in identifying chemical suppressors of mutant TDP-43 and FUS neuronal toxicity, we tested three compounds with potential neuroprotective properties: lithium chloride, methylene blue and riluzole. We identified methylene blue as a potent suppressor of TDP-43 and FUS toxicity in both our models. Our results indicate that methylene blue can rescue toxic phenotypes associated with mutant TDP-43 and FUS including neuronal dysfunction and oxidative stress.

Methylene blue protects against TDP-43 and FUS neuronal toxicity in C. elegans and D. rerio.

Science.gov (United States)

Vaccaro, Alexandra; Patten, Shunmoogum A; Ciura, Sorana; Maios, Claudia; Therrien, Martine; Drapeau, Pierre; Kabashi, Edor; Parker, J Alex

2012-01-01

The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates in a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans and zebrafish animal models expressing mutant human TDP-43 (A315T or G348C) or FUS (S57Δ or R521H) that reflect certain aspects of ALS including motor neuron degeneration, axonal deficits, and progressive paralysis. To explore the potential of our humanized transgenic C. elegans and zebrafish in identifying chemical suppressors of mutant TDP-43 and FUS neuronal toxicity, we tested three compounds with potential neuroprotective properties: lithium chloride, methylene blue and riluzole. We identified methylene blue as a potent suppressor of TDP-43 and FUS toxicity in both our models. Our results indicate that methylene blue can rescue toxic phenotypes associated with mutant TDP-43 and FUS including neuronal dysfunction and oxidative stress.

Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

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Shuai Hou

2016-05-01

Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

16 CFR 1500.43a - Method of test for flashpoint of volatile flammable materials.

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2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Method of test for flashpoint of volatile flammable materials. 1500.43a Section 1500.43a Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION... shall intersect the plane of the underside of the cover. The cover is also provided with an orifice...

Evaluation of TG-43 recommended 2D-anisotropy function for elongated brachytherapy sources

International Nuclear Information System (INIS)

Awan, Shahid B.; Meigooni, Ali S.; Mokhberiosgouei, Ramin; Hussain, Manzoor

2006-01-01

The original and updated protocols recommended by Task Group 43 from the American Association of Physicists in Medicine (i.e., TG-43 and TG-43U1, respectively), have been introduced to unify brachytherapy source dosimetry around the world. Both of these protocols are based on experiences with sources less than 1.0 cm in length. TG-43U1 recommends that for 103 Pd sources, 2D anisotropy function F(r,θ), should be tabulated at a minimum for radial distances of 0.5, 1.0, 2.0, 3.0, and 5.0 cm. Anisotropy functions defined in these protocols are only valid when the point of calculation does not fall on the active length of the source. However, for elongated brachytherapy sources (active length >1 cm), some of the calculation points with r 103 Pd source at radial distances of 2.5, 3.0, and 4.0 cm were 2.95, 1.74, and 1.19, respectively, with differences up to about a factor of 3. Therefore, the validity of the linear interpolation technique for an elongated brachytherapy source with such a large variation in F(r,θ) needs to be investigated. In this project, application of the TG-43U1 formalism for dose calculation around an elongated RadioCoil trade mark sign 103 Pd brachytherapy source has been investigated. In addition, the linear interpolation techniques as described in TG-43U1 for seed type sources have been evaluated for a 5.0 cm long RadioCoil trade mark sign 103 Pd brachytherapy source. Application of a polynomial fit to F(r,θ) has also been investigated as an alternate approach to the linear interpolation technique. The results of these investigations indicate that the TG-43U1 formalism can be extended for elongated brachytherapy sources, if the two-dimensional (2D) anisotropy function is tabulated at a minimum for radial distances of 0.2, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0 cm, L/2, and L/2±0.2 cm. Moreover, with the addition of recommended radial distances for 2D anisotropy functions, the linear interpolation technique more closely replicates

Maple Syrup Decreases TDP-43 Proteotoxicity in a Caenorhabditis elegans Model of Amyotrophic Lateral Sclerosis (ALS).

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Aaron, Catherine; Beaudry, Gabrielle; Parker, J Alex; Therrien, Martine

2016-05-04

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing death of the motor neurons. Proteotoxicity caused by TDP-43 protein is an important aspect of ALS pathogenesis, with TDP-43 being the main constituent of the aggregates found in patients. We have previously tested the effect of different sugars on the proteotoxicity caused by the expression of mutant TDP-43 in Caenorhabditis elegans. Here we tested maple syrup, a natural compound containing many active molecules including sugars and phenols, for neuroprotective activity. Maple syrup decreased several age-dependent phenotypes caused by the expression of TDP-43(A315T) in C. elegans motor neurons and requires the FOXO transcription factor DAF-16 to be effective.

Connexin 43 Expression on Peripheral Blood Eosinophils: Role of Gap Junctions in Transendothelial Migration

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Harissios Vliagoftis

2014-01-01

Full Text Available Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

Evaluation of Connexin 43 Redistribution and Endocytosis in Astrocytes Subjected to Ischemia/Reperfusion or Oxygen-Glucose Deprivation and Reoxygenation

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Hongyan Xie

2017-01-01

Full Text Available Connexin 43 (Cx43 is the major component protein in astrocytic gap junction communication. Recent studies have shown the cellular processes of gap junction internalization and degradation, but many details remain unknown. This study investigated the distribution of Cx43 and its mechanism after ischemic insult. Astrocyte culture system and a model of ischemia/reperfusion (IR or oxygen-glucose deprivation and reoxygenation (OGDR were established. Cx43 distribution was observed by laser scanning confocal microscopy under different cultivation conditions. Western blot and RT-PCR assays were applied to quantify Cx43 and MAPRE1 (microtubule-associated protein RP/EB family member 1 expression at different time points. The total number of Cx43 was unchanged in the normal and IR/OGDR groups, but Cx43 particles in the cytoplasm of the IR/OGDR group were significantly greater than that of the normal group. Particles in the cytoplasm were significantly fewer after endocytosis was blocked by dynasore. There was no difference among the groups at each time point regarding protein or gene expression of MAPRE1. We concluded that internalization of Cx43 into the cytoplasm occurred during ischemia, which was partially mediated through endocytosis, not by the change of Cx43 quantity. Moreover, internalization was not related to microtubule transport.

43 CFR 12.60 - Standards for financial management systems.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Standards for financial management systems... AUDIT REQUIREMENTS AND COST PRINCIPLES FOR ASSISTANCE PROGRAMS Uniform Administrative Requirements for... Standards for financial management systems. (a) A State must expand and account for grant funds in...

Regulation of CD43-induced U937 homotypic aggregation

Czech Academy of Sciences Publication Activity Database

Cho, J. Y.; Chain, B.; M. Vives, J.; Hořejší, Václav; Katz, D. R.

2003-01-01

Roč. 290, č. 1 (2003), s. 155-167 ISSN 0014-4827 R&D Projects: GA MŠk LN00A026 Institutional research plan: CEZ:AV0Z5052915 Keywords : CD43 * cell adhesion Subject RIV: EC - Immunology Impact factor: 3.949, year: 2003

43 CFR 12.921 - Standards for financial management systems.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Standards for financial management systems... Organizations Post-Award Requirements § 12.921 Standards for financial management systems. (a) Federal awarding... information whenever practical. (b) Recipients' financial management systems shall provide for the following...

43 CFR 10.14 - Lineal descent and cultural affiliation.

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2010-10-01

... Hawaiian organization and the human remains, funerary objects, sacred objects, or objects of cultural... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Lineal descent and cultural affiliation... GRAVES PROTECTION AND REPATRIATION REGULATIONS General § 10.14 Lineal descent and cultural affiliation...

28 CFR 549.43 - Involuntary psychiatric treatment and medication.

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2010-07-01

... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Involuntary psychiatric treatment and... INSTITUTIONAL MANAGEMENT MEDICAL SERVICES Administrative Safeguards for Psychiatric Treatment and Medication § 549.43 Involuntary psychiatric treatment and medication. Title 18 U.S.C. 4241-4247 and federal court...

SEU43 fuel bundles in CANDU 600

International Nuclear Information System (INIS)

Catana, Alexandru; Prodea, Iosif; Danila, Nicolae; Prisecaru, Ilie; Dupleac, Daniel

2008-01-01

Cernavoda Unit 1 and Unit 2 are pressure tube 650 MWe nuclear stations moderated and cooled with heavy water, of Canada design, located in Romania. Fuelling is on-power and the plant is currently fuelled with natural uranium dioxide. Fuel is encapsulated in a 37 fuel rod assembly having a specific standard geometry (STD37). In order to reduce fuel cycle costs programs were initiated in Canada, South Korea and at SCN Pitesti, Romania for design and build of a new, improved geometry fuel bundle and some fuel compositions. Among fuel compositions, which are considered, is the slightly enriched uranium (SEU) fuel (0.96 w% U-235) with an associated burn-up increase from ∼7900 MWd/tU up to ∼15000 MWd/tU. Neutron analysis showed that the Canadian-Korean fuel bundle geometry with 43 rods called SEU (SEU43) can be used in already operated reactors. A new fuel bundle resulted. Extended, comprehensive analysis must be conducted in order to assess the TH behavior of SEU43 besides the neutron, mechanical (drag force, etc) analyses. In this paper, using the sub-channel approach, main thermal-hydraulic parameters were analyzed: pressure drop; fuel, sheath and coolant temperatures; coolant density; critical heat flux. Some significant differences versus standard fuel are outlined in the paper and some conclusions are drawn. While, by using this new fuel, there are many benefits to be attained like: fuel costs reduction, spent fuel waste minimization, increase in competitiveness of nuclear power generation against other sources of generation, etc., the safety margins must be, at least, conserved. The introduction of a new fuel bundle type, different in geometry and fuel composition, requires a detailed preparation, a testing program and a series of neutron and thermal-hydraulic analysis. The results reported by this paper is part of this effort. The feasibility to increase the enrichment from 0.71% U-235 (NU) to 0.96% U-235, with an estimated burn-up increase up to 14000 MWd

Evaluation of potassium-43 scintillation images during early myocardial ischemia in an animal model

International Nuclear Information System (INIS)

Haider, B.; Oldewurtel, H.A.; Moschos, C.B.; Regan, T.J.

1976-01-01

To assess the validity of myocardial imaging with potassium-43 ( 43 K) early after the onset of ischemia, the left anterior descending artery was occluded with a balloon tip catheter in 32 intact anesthetized dogs. /sup 99m/Technetium ventriculograms localized the left ventricle. 43 K was administered intravenously and serial images were obtained in four views using an Anger camera with a pinhole collimator. The heart was arrested after 60 minutes and removed for imaging and tissue counts to ascertain extracardiac and geometric factors. In normals (group 1) left ventricular images were relatively homogeneous, except for the thin walled apex, both in vivo and in the isolated heart. Equilibration with 43 K prior to ischemia (group 2) gave similar images to group 1, associated with a small reduction in tissue counts after one hour of ischemia. Group 3 was infused with 43 K after initiation of ischemia. Despite a reduction of 43 K counts in the ischemic area to less than one-fourth of the nonischemic site (P < 0.001), demonstration of a ''cold area'' in vivo was inconstant, occurring in only 34 percent of studies. Lead shielding did not improve accuracy. In the isolated heart the ability to detect the cold area was improved to 73 percent. However, when the left ventricle was incised and spread flat, so that low and high activity areas were contiguous rather than superimposed, a widespread area of ischemia was present without exception in the anterior wall. Use of a rectilinear scanner in seven animals failed to improve diagnostic yield; areas of reduced radioactivity were seen at the apex in normals by both techniques. Thus, while detection of low flow areas in the isolated heart is feasible by isotopic imaging early after the onset of ischemia, both extracardiac and geometric factors can contribute to qualitative and quantitative errors in vivo

Morphology-dependent electrocatalytic performance of Fe2(MoO43 for electro-oxidation of methanol in alkaline medium

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Daoming Zhang

2017-06-01

Full Text Available Electrochemically synthesized nanosphere, nanorod and nanotube Fe2(MoO43 at optimized temperature and current density are characterized with XRD, SEM, TEM, XPS. Crystal lattices of the three types Fe2(MoO43 detected by HRTEM are well matched with the simulation analysis results from Materials Studio 6.0 based on the inorganic crystal structure database (ICSD data and the modified XRD lattice parameters. The ratios of Fe/Mo on the surface resulted from XPS analysis are 1.47, 1.63 and 2.22 respectively for nanosphere, nanorod and nanotube. The mixture of Fe2(MoO43 with polytetrafluoroethylene dispersion are coated on glass carbon substrate as electrode for electrocatalytic performance test by cyclic voltammetries in 0.1 mol/L KOH and 1 mol/L methanol electrolyte. Methanol oxidation peak current density of the Nanotube- Fe2(MoO43/GCEs electrode is 3.27 mA/cm2 higher than 2.8 mA/cm2 of platinum foil electrode, which shows enhanced catalytic activity of Nanotube-Fe2(MoO43/GCEs. The cyclic stability in terms of peak current retention are 91%, 92% and 88% respectively for Nanosphere-Fe2(MoO43/GCE, Nanorod-Fe2(MoO43/GCE and Nanotube-Fe2(MoO43/GCE electrode after 220 cycles. It is concluded that nanosized Fe2(MoO43 could be promising alternative non-noble electro-catalysts for electro-oxidation of methanol in alkaline medium.

43 CFR 4.450-7 - Action by manager.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Action by manager. 4.450-7 Section 4.450-7... Fact § 4.450-7 Action by manager. (a) If an answer is not filed as required, the allegations of the complaint will be taken as admitted by the contestee and the manager will decide the case without a hearing...

43 CFR 46.310 - Contents of an environmental assessment.

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2010-10-01

... implementation without the need for further analysis. Adaptive management includes a monitoring component... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Contents of an environmental assessment... OF THE NATIONAL ENVIRONMENTAL POLICY ACT OF 1969 Environmental Assessments § 46.310 Contents of an...

Journal for Language Teaching - Vol 43, No 2 (2009)

African Journals Online (AJOL)

Monitoring the standard of a Grade 12 English First Additional Language Reading, Comprehension, Summary and Grammar Paper · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. W Coetzee, R Johl. http://dx.doi.org/10.4314/jlt.v43i2.56967 ...

Targeting connexin 43 in diabetic wound healing: Future perspectives

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Bajpai S

2009-01-01

Full Text Available The unknown mechanisms of impaired tissue repair in diabetes mellitus are making this disease a serious clinical problem for the physicians worldwide. The lacuna in the knowledge of the etiology of diabetic wounds necessitates more focused research in order to develop new targeting tools with higher efficacy for their effective management. Gap-junction proteins, connexins, have shown some promising results in the process of diabetic wound healing. Till now the role of connexins has been implicated in peripheral neuropathy, deafness, skin disorders, cataract, germ cell development and treatment of cancer. Recent findings have revealed that gap junctions play a key role in normal as well as diabetic wound healing. The purpose of this review is to provide the information related to etiology, epidemiology, clinical presentation of diabetic wounds and to analyze the role of connexin 43 (Cx43 in the diabetic wound healing process. The current control strategies and the future research challenges have also been discussed briefly in this review.

Cardiac cell therapy: overexpression of connexin43 in skeletal myoblasts and prevention of ventricular arrhythmias

NARCIS (Netherlands)

Fernandes, Sarah; van Rijen, Harold V. M.; Forest, Virginie; Evain, Stéphane; Leblond, Anne-Laure; Mérot, Jean; Charpentier, Flavien; de Bakker, Jacques M. T.; Lemarchand, Patricia

2009-01-01

Cell-based therapies have great potential for the treatment of cardiovascular diseases. Recently, using a transgenic mouse model Roell et al. reported that cardiac engraftment of connexin43 (Cx43)-overexpressing myoblasts in vivo prevents post-infarct arrhythmia, a common cause of death in patients

Deletion 1q43 encompassing only CHRM3 in a patient with autistic disorder.

Science.gov (United States)

Petersen, Andrea Klunder; Ahmad, Ausaf; Shafiq, Mustafa; Brown-Kipphut, Brigette; Fong, Chin-To; Anwar Iqbal, M

2013-02-01

Deletions on the distal portion of the long arm of chromosome 1 result in complex and highly variable clinical phenotypes which include intellectual disability, autism, seizures, microcephaly/craniofacial dysmorphology, corpus callosal agenesis/hypogenesis, cardiac and genital anomalies, hand and foot abnormalities and short stature. Genotype-phenotype correlation reported a minimum region of 2 Mb at 1q43-q44. We report on a 3 ½ year old male patient diagnosed with autistic disorder who has social withdrawal, eating problems, repetitive stereotypic behaviors including self-injurious head banging and hair pulling, and no seizures, anxiety, or mood swings. Array comparative genomic hybridization (aCGH) showed an interstitial deletion of 473 kb at 1q43 region (239,412,391-239,885,394; NCBI build37/hg19) harboring only CHRM3 (Acetylcholine Receptor, Muscarinic, 3; OMIM: 118494). Recently, another case with a de novo interstitial deletion of 911 kb at 1q43 encompassing three genes including CHRM3 was reported. The M3 muscarinic receptor influences a multitude of central and peripheral nervous system processes via its interaction with acetylcholine and may be an important modulator of behavior, learning and memory. We propose CHRM3 as a candidate gene responsible for our patient's specific phenotype as well as the overlapping phenotypic features of other patients with 1q43 or 1q43-q44 deletions. Copyright © 2013. Published by Elsevier Masson SAS.

The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis.

Science.gov (United States)

Chen, Han-Jou; Mitchell, Jacqueline C; Novoselov, Sergey; Miller, Jack; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline A; Cheetham, Michael E; Shaw, Christopher E

2016-05-01

Detergent-resistant, ubiquitinated and hyperphosphorylated Tar DNA binding protein 43 (TDP-43, encoded by TARDBP) neuronal cytoplasmic inclusions are the pathological hallmark in ∼95% of amyotrophic lateral sclerosis and ∼60% of frontotemporal lobar degeneration cases. We sought to explore the role for the heat shock response in the clearance of insoluble TDP-43 in a cellular model of disease and to validate our findings in transgenic mice and human amyotrophic lateral sclerosis tissues. The heat shock response is a stress-responsive protective mechanism regulated by the transcription factor heat shock factor 1 (HSF1), which increases the expression of chaperones that refold damaged misfolded proteins or facilitate their degradation. Here we show that manipulation of the heat shock response by expression of dominant active HSF1 results in a dramatic reduction of insoluble and hyperphosphorylated TDP-43 that enhances cell survival, whereas expression of dominant negative HSF1 leads to enhanced TDP-43 aggregation and hyperphosphorylation. To determine which chaperones were mediating TDP-43 clearance we over-expressed a range of heat shock proteins (HSPs) and identified DNAJB2a (encoded by DNAJB2, and also known as HSJ1a) as a potent anti-aggregation chaperone for TDP-43. DNAJB2a has a J domain, allowing it to interact with HSP70, and ubiquitin interacting motifs, which enable it to engage the degradation of its client proteins. Using functionally deleted DNAJB2a constructs we demonstrated that TDP-43 clearance was J domain-dependent and was not affected by ubiquitin interacting motif deletion or proteasome inhibition. This indicates that TDP-43 is maintained in a soluble state by DNAJB2a, leaving the total levels of TDP-43 unchanged. Additionally, we have demonstrated that the levels of HSF1 and heat shock proteins are significantly reduced in affected neuronal tissues from a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis and patients with

The relation of Cx43 and NMDA to visceral sensitization in rats with irritable bowel syndrome

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Jing-yu ZHANG

2016-01-01

Full Text Available Objective 　To study the relationship between connexin 43 (Cx43 and N-methyl-D-aspartate (NMDA receptors and visceral sensitization in the rats with irritable bowel syndrome (IBS. Methods 　Thirty rats were gavaged with Triehinella spiralis to reproduce the IBS model. These rats were randomly divided into IBS group, IBS+colon distension group, and IBS+STI-571+colon distension group, and other groups of normal rats were randomized into normal group and normal+colon distension group, with 10 rats in each group. Immunofluorescent double staining were used to observe the expressions of intestine Cx43 and sacral NMDA re ceptors of rats in all the groups. Results 　The Cx43 and sacral NMDA expressions in the normal group, normal+colon distension group and IBS group showed no significant changes (P>0.05, however, Cx43 and sacral NMDA expressions were significantly higher in IBS rats with colon distension as compared with those in normal group, normal+colon distension group, and IBS group (P<0.05, while they were significantly lower in the IBS+STI-571+colon distension group after STI-571 intervention (P<0.05. Conclusion 　Cx43 and sacral NMDA may be the most important factor of visceral sensitization in IBS rats. DOI: 10.11855/j.issn.0577-7402.2015.12.02

COMPARATIVE MODELLING AND LIGAND BINDING SITE PREDICTION OF A FAMILY 43 GLYCOSIDE HYDROLASE FROM Clostridium thermocellum

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Shadab Ahmed

2012-06-01

Full Text Available The phylogenetic analysis of Clostridium thermocellum family 43 glycoside hydrolase (CtGH43 showed close evolutionary relation with carbohydrate binding family 6 proteins from C. cellulolyticum, C. papyrosolvens, C. cellulyticum, and A. cellulyticum. Comparative modeling of CtGH43 was performed based on crystal structures with PDB IDs 3C7F, 1YIF, 1YRZ, 2EXH and 1WL7. The structure having lowest MODELLER objective function was selected. The three-dimensional structure revealed typical 5-fold beta–propeller architecture. Energy minimization and validation of predicted model with VERIFY 3D indicated acceptability of the proposed atomic structure. The Ramachandran plot analysis by RAMPAGE confirmed that family 43 glycoside hydrolase (CtGH43 contains little or negligible segments of helices. It also showed that out of 301 residues, 267 (89.3% were in most favoured region, 23 (7.7% were in allowed region and 9 (3.0% were in outlier region. IUPred analysis of CtGH43 showed no disordered region. Active site analysis showed presence of two Asp and one Glu, assumed to form a catalytic triad. This study gives us information about three-dimensional structure and reaffirms the fact that it has the similar core 5-fold beta–propeller architecture and so probably has the same inverting mechanism of action with the formation of above mentioned catalytic triad for catalysis of polysaccharides.

The gap junction protein connexin43 interacts with the second PDZ domain of the zona occludens-1 protein

NARCIS (Netherlands)

Giepmans, B N; Moolenaar, W H

1998-01-01

Gap junctions mediate cell-cell communication in almost all tissues and are composed of channel-forming integral membrane proteins, termed connexins [1-3]. Connexin43 (Cx43) is the most widely expressed and the most well-studied member of this family. Cx43-based cell-cell communication is regulated

Wild-type and A315T mutant TDP-43 exert differential neurotoxicity in a Drosophila model of ALS

Science.gov (United States)

Estes, Patricia S.; Boehringer, Ashley; Zwick, Rebecca; Tang, Jonathan E.; Grigsby, Brianna; Zarnescu, Daniela C.

2011-01-01

The RNA-binding protein TDP-43 has been linked to amyotrophic lateral sclerosis (ALS) both as a causative locus and as a marker of pathology. With several missense mutations being identified within TDP-43, efforts have been directed towards generating animal models of ALS in mouse, zebrafish, Drosophila and worms. Previous loss of function and overexpression studies have shown that alterations in TDP-43 dosage recapitulate hallmark features of ALS pathology, including neuronal loss and locomotor dysfunction. Here we report a direct in vivo comparison between wild-type and A315T mutant TDP-43 overexpression in Drosophila neurons. We found that when expressed at comparable levels, wild-type TDP-43 exerts more severe effects on neuromuscular junction architecture, viability and motor neuron loss compared with the A315T allele. A subset of these differences can be compensated by higher levels of A315T expression, indicating a direct correlation between dosage and neurotoxic phenotypes. Interestingly, larval locomotion is the sole parameter that is more affected by the A315T allele than wild-type TDP-43. RNA interference and genetic interaction experiments indicate that TDP-43 overexpression mimics a loss-of-function phenotype and suggest a dominant-negative effect. Furthermore, we show that neuronal apoptosis does not require the cytoplasmic localization of TDP-43 and that its neurotoxicity is modulated by the proteasome, the HSP70 chaperone and the apoptosis pathway. Taken together, our findings provide novel insights into the phenotypic consequences of the A315T TDP-43 missense mutation and suggest that studies of individual mutations are critical for elucidating the molecular mechanisms of ALS and related neurodegenerative disorders. PMID:21441568

TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

Science.gov (United States)

Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

2009-02-01

Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

High-Resolution RNA Maps Suggest Common Principles of Splicing and Polyadenylation Regulation by TDP-43

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Gregor Rot

2017-05-01

Full Text Available Many RNA-binding proteins (RBPs regulate both alternative exons and poly(A site selection. To understand their regulatory principles, we developed expressRNA, a web platform encompassing computational tools for integration of iCLIP and RNA motif analyses with RNA-seq and 3′ mRNA sequencing. This reveals at nucleotide resolution the “RNA maps” describing how the RNA binding positions of RBPs relate to their regulatory functions. We use this approach to examine how TDP-43, an RBP involved in several neurodegenerative diseases, binds around its regulated poly(A sites. Binding close to the poly(A site generally represses, whereas binding further downstream enhances use of the site, which is similar to TDP-43 binding around regulated exons. Our RNAmotifs2 software also identifies sequence motifs that cluster together with the binding motifs of TDP-43. We conclude that TDP-43 directly regulates diverse types of pre-mRNA processing according to common position-dependent principles.

Kuhjuvad maksuvõlad ulatuvad 4,3 miljardi kroonini / Hindrek Riikoja

Index Scriptorium Estoniae

Riikoja, Hindrek

2008-01-01

Eesti ettevõtted ja eraisikud on riigile kokku võlgu üle 4,3 miljardi krooni, millest peaks piisama suurema osa tuleval aastal ootava eelarve puudujäägi katmiseks. Lisa: 20 suuremat maksuvõlglast maksuameti andmetel

Zadolzhennosti po nalogam dostigajut 4,3 mlrd kron / Hindrek Riikoja

Index Scriptorium Estoniae

Riikoja, Hindrek

2008-01-01

Eesti ettevõtted ja eraisikud on riigile kokku võlgu üle 4,3 miljardi krooni, millest peaks piisama suurema osa tuleval aastal ootava eelarve puudujäägi katmiseks. Lisa: 20 suuremat maksuvõlglast maksuameti andmetel

43 CFR 17.250 - Health, welfare, and social services.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Health, welfare, and social services. 17... § 17.250 Health, welfare, and social services. This subpart applies to health, welfare, and other...) General. In providing health, welfare, or other social services or benefits, a recipient may not, on the...

43 CFR 423.38 - Operating vessels on Reclamation waters.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Operating vessels on Reclamation waters... WATERBODIES Rules of Conduct § 423.38 Operating vessels on Reclamation waters. (a) You must comply with... Reclamation waters, and with any restrictions established by an authorized official. (b) You must not operate...

43 CFR 426.8 - Nonresident aliens and foreign entities.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Nonresident aliens and foreign entities..., DEPARTMENT OF THE INTERIOR ACREAGE LIMITATION RULES AND REGULATIONS § 426.8 Nonresident aliens and foreign... reclamation law or these regulations, a nonresident alien or foreign entity that directly holds land in a...

43 CFR 12.935 - Supplies and other expendable property.

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2010-10-01

... of unused supplies exceeding $5,000 in total aggregate value upon termination or completion of the... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Supplies and other expendable property. 12... Organizations Post-Award Requirements § 12.935 Supplies and other expendable property. (a) Title to supplies and...

Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis

Directory of Open Access Journals (Sweden)

Patricia S. Estes

2013-05-01

Amyotrophic lateral sclerosis (ALS is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. We show that TDP-43-driven neurodegeneration phenotypes are dose- and age-dependent. In motor neurons, TDP-43 appears restricted to nuclei, which are significantly misshapen due to mutant but not wild-type protein expression. In glia and in the developing neuroepithelium, TDP-43 associates with cytoplasmic puncta. TDP-43-containing RNA granules are motile in cultured motor neurons, although wild-type and mutant variants exhibit different kinetic properties. At the neuromuscular junction, the expression of TDP-43 in motor neurons versus glia leads to seemingly opposite synaptic phenotypes that, surprisingly, translate into comparable locomotor defects. Finally, we explore sleep as a behavioral readout of TDP-43 expression and find evidence of sleep fragmentation consistent with hyperexcitability, a suggested mechanism in ALS. These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies.

Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis.

Science.gov (United States)

Estes, Patricia S; Daniel, Scott G; McCallum, Abigail P; Boehringer, Ashley V; Sukhina, Alona S; Zwick, Rebecca A; Zarnescu, Daniela C

2013-05-01

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. We show that TDP-43-driven neurodegeneration phenotypes are dose- and age-dependent. In motor neurons, TDP-43 appears restricted to nuclei, which are significantly misshapen due to mutant but not wild-type protein expression. In glia and in the developing neuroepithelium, TDP-43 associates with cytoplasmic puncta. TDP-43-containing RNA granules are motile in cultured motor neurons, although wild-type and mutant variants exhibit different kinetic properties. At the neuromuscular junction, the expression of TDP-43 in motor neurons versus glia leads to seemingly opposite synaptic phenotypes that, surprisingly, translate into comparable locomotor defects. Finally, we explore sleep as a behavioral readout of TDP-43 expression and find evidence of sleep fragmentation consistent with hyperexcitability, a suggested mechanism in ALS. These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies.

29 CFR 1602.43 - Commission's remedy for school systems' or districts' failure to file report.

Science.gov (United States)

2010-07-01

...' failure to file report. Any school system or district failing or refusing to file report EEO-5 when... 29 Labor 4 2010-07-01 2010-07-01 false Commission's remedy for school systems' or districts' failure to file report. 1602.43 Section 1602.43 Labor Regulations Relating to Labor (Continued) EQUAL...

Frontotemporal dementia with trans-activation response DNA-binding protein 43 presenting with catatonic syndrome.

Science.gov (United States)

Watanabe, Ryohei; Kawakami, Ito; Onaya, Mitsumoto; Higashi, Shinji; Arai, Nobutaka; Akiyama, Haruhiko; Hasegawa, Masato; Arai, Tetsuaki

2017-11-07

Catatonia is a clinical syndrome characterized by symptoms such as immobility, mutism, stupor, stereotypy, echophenomena, catalepsy, automatic obedience, posturing, negativism, gegenhalten and ambitendency. This syndrome occurs mostly in mood disorder and schizophrenic patients, and is related to neuronal dysfunction involving the frontal lobe. Some cases of frontotemporal dementia (FTD) with catatonia have been reported, but these cases were not examined by autopsy. Here, we report on a FTD case which showed catatonia after the first episode of brief psychotic disorder. At the age of 58, the patient had a sudden onset of disorganized behavior and meaningless speech. Psychotropic drugs were effective for catatonic symptoms. However, after remission apathy, hyperorality, socially inappropriate behavior, hoarding, and an instinctive grasp reaction appeared and persisted. Brain MRI showed significant atrophy of the bilateral fronto-temporal lobes. A neuropathological examination revealed extensive trans-activation response DNA-binding protein 43 (TDP-43) positive neurocytoplasmic inclusions and dystrophic neurites in the brain, including the cerebral cortex, basal ganglia, and brainstem. Pathological diagnosis was frontotemporal lobar degeneration (FTLD) with TDP-43 (FTLD-TDP) type C, which was also confirmed by the band pattern of C-terminal fragments of TDP-43 on western blotting of sarkosyl-insoluble fractions extracted from the frozen brain. Dysfunction of the thalamus, globus pallidus, supplementary motor area, amygdala and cingulate cortex have been said to be related to the catatonic syndrome. In this case, these areas were affected, showing abnormal TDP-43-positive structures. Further studies are expected to confirm further clinical - pathological correlations to FTLD. © 2017 Japanese Society of Neuropathology.

43 CFR 12.950 - Purpose of reports and records.

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2010-10-01

... Requirements § 12.950 Purpose of reports and records. Sections 12.951 through 12.953 set forth the procedures for monitoring and reporting on the recipient's financial and program performance and the necessary... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Purpose of reports and records. 12.950...

43 CFR 12.830 - Buy American Act-Construction materials.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Buy American Act-Construction materials... Assistance Programs Buy American Act-Construction Materials § 12.830 Buy American Act—Construction materials...—Construction Materials (a) The Buy American Act (41 U.S.C. 10) provides that the Government give preference to...

Transgenic expression of B-50/GAP-43 in mature olfactory neurons triggers downregulation of native B-50/GAP-43 expression in immature olfactory neurons

NARCIS (Netherlands)

Holtmaat, Anthony J D G; Huizinga, C T; Margolis, F L; Gispen, Willem Hendrik; Verhaagen, J

1999-01-01

The adult mammalian olfactory neuroepithelium is an unusual neural tissue, since it maintains its capacity to form new neurons throughout life. Newly formed neurons differentiate in the basal layers of the olfactory neuroepithelium and express B-50/GAP-43, a protein implicated in neurite outgrowth.

TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

International Nuclear Information System (INIS)

Arai, Tetsuaki; Hasegawa, Masato; Akiyama, Haruhiko; Ikeda, Kenji; Nonaka, Takashi; Mori, Hiroshi; Mann, David; Tsuchiya, Kuniaki; Yoshida, Mari; Hashizume, Yoshio; Oda, Tatsuro

2006-01-01

Ubiquitin-positive tau-negative neuronal cytoplasmic inclusions and dystrophic neurites are common pathological features in frontotemporal lobar degeneration (FTLD) with or without symptoms of motor neuron disease and in amyotrophic lateral sclerosis (ALS). Using biochemical and immunohistochemical analyses, we have identified a TAR DNA-binding protein of 43 kDa (TDP-43), a nuclear factor that functions in regulating transcription and alternative splicing, as a component of these structures in FTLD. Furthermore, skein-like inclusions, neuronal intranuclear inclusions, and glial inclusions in the spinal cord of ALS patients are also positive for TDP-43. Dephosphorylation treatment of the sarkosyl insoluble fraction has shown that abnormal phosphorylation takes place in accumulated TDP-43. The common occurrence of intracellular accumulations of TDP-43 supports the hypothesis that these disorders represent a clinicopathological entity of a single disease, and suggests that they can be newly classified as a proteinopathy of TDP-43

Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala.

Science.gov (United States)

Stehberg, Jimmy; Moraga-Amaro, Rodrigo; Salazar, Christian; Becerra, Alvaro; Echeverría, Cesar; Orellana, Juan A; Bultynck, Geert; Ponsaerts, Raf; Leybaert, Luc; Simon, Felipe; Sáez, Juan C; Retamal, Mauricio A

2012-09-01

Recent in vitro evidence indicates that astrocytes can modulate synaptic plasticity by releasing neuroactive substances (gliotransmitters). However, whether gliotransmitter release from astrocytes is necessary for higher brain function in vivo, particularly for memory, as well as the contribution of connexin (Cx) hemichannels to gliotransmitter release, remain elusive. Here, we microinfused into the rat basolateral amygdala (BLA) TAT-Cx43L2, a peptide that selectively inhibits Cx43-hemichannel opening while maintaining synaptic transmission or interastrocyte gap junctional communication. In vivo blockade of Cx43 hemichannels during memory consolidation induced amnesia for auditory fear conditioning, as assessed 24 h after training, without affecting short-term memory, locomotion, or shock reactivity. The amnesic effect was transitory, specific for memory consolidation, and was confirmed after microinfusion of Gap27, another Cx43-hemichannel blocker. Learning capacity was recovered after coinfusion of TAT-Cx43L2 and a mixture of putative gliotransmitters (glutamate, glutamine, lactate, d-serine, glycine, and ATP). We propose that gliotransmitter release from astrocytes through Cx43 hemichannels is necessary for fear memory consolidation at the BLA. Thus, the present study is the first to demonstrate a physiological role for astroglial Cx43 hemichannels in brain function, making these channels a novel pharmacological target for the treatment of psychiatric disorders, including post-traumatic stress disorder.

43 CFR 2.47 - Records subject to Privacy Act.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Records subject to Privacy Act. 2.47 Section 2.47 Public Lands: Interior Office of the Secretary of the Interior RECORDS AND TESTIMONY; FREEDOM OF INFORMATION ACT Privacy Act § 2.47 Records subject to Privacy Act. The Privacy Act applies to all...

43 CFR 17.220 - Preschool, elementary, and secondary education.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Preschool, elementary, and secondary education. 17.220 Section 17.220 Public Lands: Interior Office of the Secretary of the Interior NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OF THE DEPARTMENT OF THE INTERIOR Nondiscrimination on the Basis of Handicap § 17.220 Preschool, elementary,...

RNF43 is mutated less frequently in Lynch Syndrome compared with sporadic microsatellite unstable colorectal cancers.

Science.gov (United States)

Fennell, Lochlan J; Clendenning, Mark; McKeone, Diane M; Jamieson, Saara H; Balachandran, Samanthy; Borowsky, Jennifer; Liu, John; Kawamata, Futoshi; Bond, Catherine E; Rosty, Christophe; Burge, Matthew E; Buchanan, Daniel D; Leggett, Barbara A; Whitehall, Vicki L J

2018-01-01

The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome. The entire coding region of RNF43 was Sanger sequenced in 24 colorectal cancers from 23 patients who either (i) carried a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH6, MSH2, PMS2), or (ii) showed immunohistochemical loss of expression of one or more of the DNA mismatch repair proteins, was BRAF wild type at V600E, were under 60 years of age at diagnosis, and demonstrated no promoter region methylation for MLH1 in tumor DNA. A validation cohort of 44 colorectal cancers from mismatch repair germline mutation carriers from the Australasian Colorectal Cancer Family Registry (ACCFR) were sequenced for the most common truncating mutation hotspots (X117 and X659). RNF43 mutations were found in 9 of 24 (37.5%) Lynch syndrome colorectal cancers. The majority of mutations were frameshift deletions in the G659 G7 repeat tract (29%); 2 cancers (2/24, 8%) from the one patient harbored frameshift mutations at codon R117 (C6 repeat tract) within exon 3. In the ACCFR validation cohort, RNF43 hotspot mutations were identified in 19/44 (43.2%) of samples, which was not significantly different to the initial series. The proportion of mutant RNF43 in Lynch syndrome related colorectal cancers is significantly lower than the previously reported mutation rate found in sporadic MSI colorectal cancers. These findings identify further genetic differences between sporadic and hereditary colorectal cancers. This may be because Lynch Syndrome cancers

Facial Onset Sensory and Motor Neuronopathy: Further Evidence for a TDP-43 Proteinopathy

Directory of Open Access Journals (Sweden)

Besa Ziso

2015-04-01

Full Text Available Three patients with the clinical and investigation features of facial onset sensory and motor neuronopathy (FOSMN syndrome are presented, one of whom came to a post-mortem examination. This showed TDP-43-positive inclusions in the bulbar and spinal motor neurones as well as in the trigeminal nerve nuclei, consistent with a neurodegenerative pathogenesis. These data support the idea that at least some FOSMN cases fall within the spectrum of the TDP-43 proteinopathies, and represent a focal form of this pathology.

43 CFR 45.3 - How are time periods computed?

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false How are time periods computed? 45.3... IN FERC HYDROPOWER LICENSES General Provisions § 45.3 How are time periods computed? (a) General... run is not included. (2) The last day of the period is included. (i) If that day is a Saturday, Sunday...

43 CFR 2.19 - When will bureaus waive fees?

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false When will bureaus waive fees? 2.19 Section... OF INFORMATION ACT Requests for Records under the FOIA § 2.19 When will bureaus waive fees? (a) Fees... section and appendix D to this part. The burden is on you to justify entitlement to a fee waiver. Requests...

43 CFR Appendix A to Part 10 - Sample Summary

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Sample Summary A Appendix A to Part 10... REPATRIATION REGULATIONS Pt. 10, App. A Appendix A to Part 10—Sample Summary The following is a generic sample and should be used as a guideline for preparation of summaries tailoring the information to the...

Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43 revealed by MD simulations.

Directory of Open Access Journals (Sweden)

Fei Xiao

Full Text Available The gap junction protein connexin43 (Cx43 binds to the second PDZ domain of Zonula occludens-1 (ZO-1 through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9 and Ser (-10 of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9 significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation.

19 CFR 210.43 - Petitions for review of initial determinations on matters other than temporary relief.

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2010-04-01

... matters other than temporary relief. 210.43 Section 210.43 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT..., the Federal Trade Commission, the U.S. Customs Service, and such other departments and agencies as the...

Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

Science.gov (United States)

Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

2016-07-01

Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

Prolonged labour associated with lower expression of syndecan 3 and connexin 43 in human uterine tissue

Directory of Open Access Journals (Sweden)

Malmström Anders

2006-05-01

Full Text Available Abstract Background Prolonged labour is associated with greater morbidity and mortality for mother and child. Connexin 43 is a major myometrial gap junction protein found in human myometrium. Syndecan 3 seems to prevail in the human uterus among heparan sulphate proteoglycans, showing the most significant increase during labour. The aims of the present study were to investigate syndecan 3 and connexin 43 mRNA expressions and protein distributions in human uterine tissue during normal and prolonged labour. Methods Uterine isthmic biopsies were collected from non-pregnant (n = 7, term pregnant women not in labour (n = 14, in normal labour (n = 7 and in prolonged labour (n = 7. mRNA levels of syndecan 3 and connexin 43 were determined by real time RT-PCR. The localization and expression were demonstrated by immunohistochemistry and confocal microscopy. Results In women with prolonged labour, the mRNA expressions of syndecan 3 and Connexin 43 were considerably lower than the expression level at normal labour (p Conclusion The high expression of syndecan 3 and connexin 43 and their co-localization to the smooth muscle bundles during normal labour, together with the significant reduction in prolonged labour, may indicate a role for these proteins in the co-ordination of myometrial contractility.

X-43A Undergoing Controlled Radio Frequency Testing in the Benefield Anechoic Facility at Edwards Ai

Science.gov (United States)

2000-01-01

The X-43A Hypersonic Experimental (Hyper-X) Vehicle hangs suspended in the cavernous Benefield Aenechoic Facility at Edwards Air Force Base during radio frequency tests in January 2000. Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will be able to carry heavier payloads. Another unique aspect of the X-43A vehicle is the airframe integration

γ-Secretase Modulators and Presenilin 1 Mutants Act Differently on Presenilin/γ-Secretase Function to Cleave Aβ42 and Aβ43

Directory of Open Access Journals (Sweden)

Masayasu Okochi

2013-01-01

Full Text Available Deciphering the mechanism by which the relative Aβ42(43 to total Aβ ratio is regulated is central to understanding Alzheimer disease (AD etiology; however, the mechanisms underlying changes in the Aβ42(43 ratio caused by familial mutations and γ-secretase modulators (GSMs are unclear. Here, we show in vitro and in living cells that presenilin (PS/γ-secretase cleaves Aβ42 into Aβ38, and Aβ43 into Aβ40 or Aβ38. Approximately 40% of Aβ38 is derived from Aβ43. Aβ42(43 cleavage is involved in the regulation of the Aβ42(43 ratio in living cells. GSMs increase the cleavage of PS/γ-secretase-bound Aβ42 (increase kcat and slow its dissociation from the enzyme (decrease kb, whereas PS1 mutants and inverse GSMs show the opposite effects. Therefore, we suggest a concept to describe the Aβ42(43 production process and propose how GSMs act, and we suggest that a loss of PS/γ-secretase function to cleave Aβ42(43 may initiate AD and might represent a therapeutic target.

Journal of Mining and Geology - Vol 43, No 1 (2007)

African Journals Online (AJOL)

Hydrogeochemical and bacteriological investigation of groundwater in Agbor area, southern Nigeria · EMAIL FULL TEXT EMAIL FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. SB Olobaniyi, JE Ogala, NB Nfor, 79-89. http://dx.doi.org/10.4314/jmg.v43i1.18867 ...

43 CFR 4.1365 - Status of decision pending administrative review.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Status of decision pending administrative... Status of decision pending administrative review. The filing of a request for review shall not stay the effectiveness of the OSMRE decision pending completion of administrative review. ...

A cancer-associated RING finger protein, RNF43, is a ubiquitin ligase that interacts with a nuclear protein, HAP95

International Nuclear Information System (INIS)

Sugiura, Takeyuki; Yamaguchi, Aya; Miyamoto, Kentaro

2008-01-01

RNF43 is a recently discovered RING finger protein that is implicated in colon cancer pathogenesis. This protein possesses growth-promoting activity but its mechanism remains unknown. In this study, to gain insight into the biological action of RNF43 we characterized it biochemically and intracellularly. A combination of indirect immunofluorescence analysis and biochemical fractionation experiments suggests that RNF43 resides in the endoplasmic reticulum (ER) as well as in the nuclear envelope. Sucrose density gradient fractionation demonstrates that RNF43 co-exists with emerin, a representative inner nuclear membrane protein in the nuclear subcompartment. The cell-free system with pure components reveals that recombinant RNF43 fused with maltose-binding protein has autoubiquitylation activity. By the yeast two-hybrid screening we identified HAP95, a chromatin-associated protein interfacing the nuclear envelope, as an RNF43-interacting protein and substantiated this interaction in intact cells by the co-immunoprecipitation experiments. HAP95 is ubiquitylated and subjected to a proteasome-dependent degradation pathway, however, the experiments in which 293 cells expressing both RNF43 and HAP95 were treated with a proteasome inhibitor, MG132, show that HAP95 is unlikely to serve as a substrate of RNF43 ubiquitin ligase. These results infer that RNF43 is a resident protein of the ER and, at least partially, the nuclear membrane, with ubiquitin ligase activity and may be involved in cell growth control potentially through the interaction with HAP95

Expression of growth-associated protein B-50/GAP43 in dorsal root ganglia and sciatic nerve during regenerative sprouting

NARCIS (Netherlands)

Gispen, W.H.; Zee, C.E.E.M. van der; Nielander, H.B.; Vos, J.P.; Lopes da Silva, S.; Verhaagen, J.; Oestreicher, J.; Schrama, L.H.

1989-01-01

Recently it has been shown that B-50 is identical to the neuron- specific, growth-associated protein GAP43. The present study reports on the fate of B-50/GAP43 mRNA and B-50/GAP43 protein, determined by radioimmunoassay, in a rat model of peripheral nerve regeneration (sciatic nerve crush) over a

Vacuolating encephalitis in mice infected by human coronavirus OC43

International Nuclear Information System (INIS)

Jacomy, Helene; Talbot, Pierre J.

2003-01-01

Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development of an experimental animal model. Virus inoculation of 21-day postnatal C57BL/6 and BALB/c mice led to a generalized infection of the whole CNS, demonstrating HCoV-OC43 neuroinvasiveness and neurovirulence. This acute infection targeted neurons, which underwent vacuolation and degeneration while infected regions presented strong microglial reactivity and inflammatory reactions. Damage to the CNS was not immunologically mediated and microglial reactivity was instead a consequence of direct virus-mediated neuronal injury. Although this acute encephalitis appears generally similar to that induced by murine coronaviruses, an important difference rests in the prominent spongiform-like degeneration that could trigger neuropathology in surviving animals

The Cx43-like connexin protein Cx40.8 is differentially localized during fin ontogeny and fin regeneration.

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Sarah V Gerhart

Full Text Available Connexins (Cx are the subunits of gap junctions, membraneous protein channels that permit the exchange of small molecules between adjacent cells. Cx43 is required for cell proliferation in the zebrafish caudal fin. Previously, we found that a Cx43-like connexin, cx40.8, is co-expressed with cx43 in the population of proliferating cells during fin regeneration. Here we demonstrate that Cx40.8 exhibits novel differential subcellular localization in vivo, depending on the growth status of the fin. During fin ontogeny, Cx40.8 is found at the plasma membrane, but Cx40.8 is retained in the Golgi apparatus during regeneration. We next identified a 30 amino acid domain of Cx40.8 responsible for its dynamic localization. One possible explanation for the differential localization is that Cx40.8 contributes to the regulation of Cx43 in vivo, perhaps modifying channel activity during ontogenetic growth. However, we find that the voltage-gating properties of Cx40.8 are similar to Cx43. Together our findings reveal that Cx40.8 exhibits differential subcellular localization in vivo, dependent on a discrete domain in its carboxy terminus. We suggest that the dynamic localization of Cx40.8 differentially influences Cx43-dependent cell proliferation during ontogeny and regeneration.

Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

Energy Technology Data Exchange (ETDEWEB)

Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Aschner, Michael [Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461 (United States); Luo, Wen-Jing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jing-Yuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health and the Ministry-of-Education' s Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

2016-04-15

As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

Cellular uptake of lead in the blood-cerebrospinal fluid barrier: Novel roles of Connexin 43 hemichannel and its down-regulations via Erk phosphorylation

International Nuclear Information System (INIS)

Song, Han; Zheng, Gang; Liu, Yang; Shen, Xue-Feng; Zhao, Zai-Hua; Aschner, Michael; Luo, Wen-Jing; Chen, Jing-Yuan

2016-01-01

As the structural basis of blood-cerebrospinal fluid barrier (BCB), epithelial cells in the choroid plexus (CP) are targets for lead (Pb). Pb is known to accumulate in the CP; however, the mechanism of Pb uptake in the choroidal epithelial cells remains unknown. Recently, hemichannels of Connexin 43 (Cx43), the most ubiquitously expressed gap junction proteins in the CP, were found to be important pathways for many substances. This study was designed to investigate the roles of Cx43 in Pb uptake in the epithelial cells. Autometallography was used to outline Pb's subcellular location, and the characteristics of Pb transport into CP cells, including concentration- and time-dependence were analyzed by atomic absorption spectroscopy. Knockdown/overexpression of Cx43 with transient siRNA/plasmids transfections before Pb exposure diminished/increased the Pb accumulation. In the Z310 cell-based doxycycline-inducible Cx43 expression cell line (iZCx43), doxycycline induced a significant increase (3-fold) in Pb uptake, corresponding to the increased Cx43 levels. Activation of Cx43 hemichannels by reduced serum conditions caused an increase of Pb concentrations. Cx43-induced Pb uptake was attenuated after blockage of Cx43 hemichannels with its inhibitor, carbenoxolone. Additionally, down-regulation of Cx43 protein levels by Pb exposure paralleled cellular Pb concentrations in the time study. Concomitantly, expressions of phosphor-Src and phosphor-Erk were both significantly increased by Pb. However, inactivation of Erk, not Src pathway, reversed Pb-induced downregulation of Cx43. Taken together, these data establish that Pb can accumulate in the BCB and validate the role of Cx43 hemichannel in Pb uptake and its regulations through Erk phosphorylation. - Highlights: • Pb is sequestrated in choroid plexus both in vivo and in vitro. • Cx43 knockdown/overexpression prevents/increases Pb accumulations. • Cx43 hemichannels are required for Pb uptake. • Pb-induced Erk

Revisiting the Phase Curves of WASP-43b: Confronting Re-analyzed Spitzer Data with Cloudy Atmospheres

DEFF Research Database (Denmark)

Mendonça, João M.; Malik, Matej; Demory, Brice-Olivier

2018-01-01

red noise due to intra-pixel sensitivity, which leads to greater fluxes emanating from the nightside of WASP-43b, thus reducing the tension between theory and data. On the theoretical front, we construct cloud-free and cloudy atmospheres of WASP-43b using our Global Circulation Model (GCM), THOR...

22 CFR 96.43 - Case tracking, data management, and reporting.

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2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Case tracking, data management, and reporting... Accreditation and Approval Responding to Complaints and Records and Reports Management § 96.43 Case tracking, data management, and reporting. (a) When acting as the primary provider, the agency or person maintains...

Revisiting the Phase Curves of WASP-43b: Confronting Re-analyzed Spitzer Data with Cloudy Atmospheres

Science.gov (United States)

Mendonça, João M.; Malik, Matej; Demory, Brice-Olivier; Heng, Kevin

2018-04-01

Recently acquired Hubble and Spitzer phase curves of the short-period hot Jupiter WASP-43b make it an ideal target for confronting theory with data. On the observational front, we re-analyze the 3.6 and 4.5 μm Spitzer phase curves and demonstrate that our improved analysis better removes residual red noise due to intra-pixel sensitivity, which leads to greater fluxes emanating from the nightside of WASP-43b, thus reducing the tension between theory and data. On the theoretical front, we construct cloud-free and cloudy atmospheres of WASP-43b using our Global Circulation Model (GCM), THOR, which solves the non-hydrostatic Euler equations (compared to GCMs that typically solve the hydrostatic primitive equations). The cloud-free atmosphere produces a reasonable fit to the dayside emission spectrum. The multi-phase emission spectra constrain the cloud deck to be confined to the nightside and have a finite cloud-top pressure. The multi-wavelength phase curves are naturally consistent with our cloudy atmospheres, except for the 4.5 μm phase curve, which requires the presence of enhanced carbon dioxide in the atmosphere of WASP-43b. Multi-phase emission spectra at higher spectral resolution, as may be obtained using the James Webb Space Telescope, and a reflected-light phase curve at visible wavelengths would further constrain the properties of clouds in WASP-43b.

Design, synthesis and molecular docking study of thienopyrimidin-4(3H-thiones as antifungal agents

Directory of Open Access Journals (Sweden)

Sanjay B. Bari

2017-01-01

Full Text Available In an attempt to find a new class of antimicrobial agents, a series of thienopyrimidin-4(3H-thiones 4(H1–H36 were synthesized and evaluated for in vitro antifungal activity against Candida albicans (NCIM 3471, Aspergillus niger (NCIM 545, and Penicillium chrysogenum (NCIM 709. The title compounds were synthesized by thionation of thienopyrimidin-4(3H-ones 3(H1–H36 using Lawesson’s reagent. All the compounds were characterized using elemental analytical (C, H, and N and spectral (FT-IR, 1H NMR, 13C NMR and MS data. Among the tested compounds, 5-(4-chlorophenyl-2-(pyridin-3-ylthieno[2,3-d]pyrimidine-4(3H-thione 4(H11, 2-sulfanyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4(3H-thione 4(H18, and 2-(butylsulfanyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidine-4(3H-thione 4(H32 were identified as potentially excellent antifungal agents. They exhibited potent antifungal activity against C. albicans (MIC; 4 μg/mL, A. niger (MIC; 2 μg/mL, and P. chrysogenum (MIC; 2 μg/mL comparable with that of ketoconazole. The binding mode of compounds by SP docking studies shows that it fits well into the active site cavity of DHFR. Lipinski’s rule and in silico ADME pharmacokinetic parameters are within the acceptable range defined for human use thereby indicating their potential as drug-like molecules.

Spitzer observations of the thermal emission from WASP-43b

Energy Technology Data Exchange (ETDEWEB)

Blecic, Jasmina; Harrington, Joseph; Stevenson, Kevin B.; Hardy, Ryan A.; Cubillos, Patricio E.; Hardin, Matthew; Bowman, Oliver; Nymeyer, Sarah [Planetary Sciences Group, Department of Physics, University of Central Florida, Orlando, FL 32816-2385 (United States); Madhusudhan, Nikku [Department of Physics and Department of Astronomy, Yale University, New Haven, CT 06511 (United States); Anderson, David R.; Hellier, Coel; Smith, Alexis M. S. [Astrophysics Group, Keele University, Keele, Staffordshire ST5 5BG (United Kingdom); Cameron, Andrew Collier, E-mail: jasmina@physics.ucf.edu [SUPA, School of Physics and Astronomy, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9SS (United Kingdom)

2014-02-01

WASP-43b is one of the closest-orbiting hot Jupiters, with a semimajor axis of a = 0.01526 ± 0.00018 AU and a period of only 0.81 days. However, it orbits one of the coolest stars with a hot Jupiter (T {sub *} = 4520 ± 120 K), giving the planet a modest equilibrium temperature of T {sub eq} = 1440 ± 40 K, assuming zero Bond albedo and uniform planetary energy redistribution. The eclipse depths and brightness temperatures from our jointly fit model are 0.347% ± 0.013% and 1670 ± 23 K at 3.6 μm and 0.382% ± 0.015% and 1514 ± 25 K at 4.5 μm. The eclipse timings improved the estimate of the orbital period, P, by a factor of three (P = 0.81347436 ± 1.4 × 10{sup –7} days) and put an upper limit on the eccentricity (e=0.010{sub −0.007}{sup +0.010}). We use our Spitzer eclipse depths along with four previously reported ground-based photometric observations in the near-infrared to constrain the atmospheric properties of WASP-43b. The data rule out a strong thermal inversion in the dayside atmosphere of WASP-43b. Model atmospheres with no thermal inversions and fiducial oxygen-rich compositions are able to explain all the available data. However, a wide range of metallicities and C/O ratios can explain the data. The data suggest low day-night energy redistribution in the planet, consistent with previous studies, with a nominal upper limit of about 35% for the fraction of energy incident on the dayside that is redistributed to the nightside.

43 CFR 45.4 - What deadlines apply to pending applications?

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What deadlines apply to pending applications? 45.4 Section 45.4 Public Lands: Interior Office of the Secretary of the Interior CONDITIONS AND PRESCRIPTIONS IN FERC HYDROPOWER LICENSES General Provisions § 45.4 What deadlines apply to pending applications...

Genomic Analysis of 15 Human Coronaviruses OC43 (HCoV-OC43s Circulating in France from 2001 to 2013 Reveals a High Intra-Specific Diversity with New Recombinant Genotypes

Directory of Open Access Journals (Sweden)

Nathalie Kin

2015-05-01

Full Text Available Human coronavirus OC43 (HCoV-OC43 is one of five currently circulating human coronaviruses responsible for respiratory infections. Like all coronaviruses, it is characterized by its genome’s high plasticity. The objectives of the current study were to detect genetically distinct genotypes and eventually recombinant genotypes in samples collected in Lower Normandy between 2001 and 2013. To this end, we sequenced complete nsp12, S, and N genes of 15 molecular isolates of HCoV-OC43 from clinical samples and compared them to available data from the USA, Belgium, and Hong-Kong. A new cluster E was invariably detected from nsp12, S, and N data while the analysis of nsp12 and N genes revealed the existence of new F and G clusters respectively. The association of these different clusters of genes in our specimens led to the description of thirteen genetically distinct genotypes, among which eight recombinant viruses were discovered. Identification of these recombinant viruses, together with temporal analysis and tMRCA estimation, provides important information for understanding the dynamics of the evolution of these epidemic coronaviruses.

43 CFR 2.15 - Will I be charged fees?

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Will I be charged fees? 2.15 Section 2.15... INFORMATION ACT Requests for Records under the FOIA § 2.15 Will I be charged fees? Bureaus will charge fees consistent with the provisions in §§ 2.16 and 2.17. The fee schedule in appendix C to this part applies to...

Assessment of MODIS BRDF/Albedo Model Parameters (MCD43A1 Collection 6) for directional reflectance retrieval

Science.gov (United States)

Che, X.; Feng, M.; Sexton, J. O.; Channan, S.; Yang, Y.; Song, J.

2017-12-01

Reflection of solar radiation from Earth's surface is the basis for retrieving many higher-level terrestrial attributes such as vegetation indices and albedo. However, reflectance varies with the illumination and viewing geometry of observation (Bi-directional Reflectance Distribution Function (BRDF)) even with constant surface properties, and correcting for these artifacts increases precision of comparisons of images and time series acquired from satellites with different illumination and observation geometries. The operational MODIS processing inverts MODIS BRDF/Albedo Model Parameters (MCD43A1) to retrieve directional reflectance at any solar and view angles, and recently the MCD43A1 (Collection 6) was updated and distributed. We quantified the ability of MCD43A1 Collection 6 for retrieving directional reflectance compared to Collection 5 and tested whether changes in the land surface change over a 16-day composite period affect time series of directional reflectance. Correcting the Terra MODIS daily Surface Reflectance (MOD09GA) to the illumination and view geometries of coincidental Aqua MODIS daily Surface Reflectance (MYD09GA), MCD43A4 Collection 6 and Landsat-5 TM imagery show that the BRDF-corrected results using MCD43A1 Collection 6 hold a higher consistency with higher R2 (0.63 0.955), the slopes close to unity (0.718 0.955) and the lower RMSD (0.422 3.142) and MAE (0.282 1.735) reduced by about 10% than Collection 5. A simple parameter calibration to evaluate the variability of the roughness (R) and the volumetric (V) BRDF parameters for MCD43A1 Collection 6 shows that the assumption of stable land surface characteristic over 16-days composite period, used for BRDF parameters inversion, is plausible in spite of small improvement of directional reflectance and BRDF parameters time series. The larger fluctuations for the MCD43A1 Collection 6 do not have a discernable impact on the reflectance time series. All of these results shows that MCD43A1 Collection

27 CFR 28.43 - Evidence of exportation and lading for use on vessels and aircraft: beer.

Science.gov (United States)

2010-04-01

... and lading for use on vessels and aircraft: beer. 28.43 Section 28.43 Alcohol, Tobacco Products and... lading for use on vessels and aircraft: beer. (a) Exportation. The exportation of beer to a foreign... certificate issued by an official of the country or possession where the beer has actually landed; or (6) Any...

Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source

International Nuclear Information System (INIS)

White, Shane A.; Landry, Guillaume; Reniers, Brigitte; Fonseca, Gabriel Paiva; Holt, Randy; Rusch, Thomas; Beaulieu, Luc; Verhaegen, Frank

2014-01-01

Purpose: The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy ( w,m ) and dose to medium (D m,m ), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. Results: All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D 90 to PTV was reduced by between ∼4% and ∼40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%–15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. Conclusions: TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources

43 CFR 422.5 - Responsibilities of the Law Enforcement Administrator.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Responsibilities of the Law Enforcement Administrator. 422.5 Section 422.5 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR LAW ENFORCEMENT AUTHORITY AT BUREAU OF RECLAMATION PROJECTS Responsibilities § 422.5 Responsibilities of...

43 CFR 41.440 - Health and insurance benefits and services.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Health and insurance benefits and services... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 41.440 Health and insurance... insurance benefit, service, policy, or plan to any of its students, a recipient shall not discriminate on...

43 CFR 418.2 - How Project water may be used.

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2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false How Project water may be used. 418.2..., DEPARTMENT OF THE INTERIOR OPERATING CRITERIA AND PROCEDURES FOR THE NEWLANDS RECLAMATION PROJECT, NEVADA General Provisions § 418.2 How Project water may be used. Project water may be delivered only to serve...

Enteric Glia Mediate Neuron Death in Colitis Through Purinergic Pathways That Require Connexin-43 and Nitric OxideSummary

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Isola A.M. Brown

2016-01-01

Full Text Available Background & Aims: The concept of enteric glia as regulators of intestinal homeostasis is slowly gaining acceptance as a central concept in neurogastroenterology. Yet how glia contribute to intestinal disease is still poorly understood. Purines generated during inflammation drive enteric neuron death by activating neuronal P2X7 purine receptors (P2X7R; triggering adenosine triphosphate (ATP release via neuronal pannexin-1 channels that subsequently recruits intracellular calcium ([Ca2+]i in surrounding enteric glia. We tested the hypothesis that the activation of enteric glia contributes to neuron death during inflammation. Methods: We studied neuroinflammation in vivo using the 2,4-dinitrobenzene sulfonic acid model of colitis and in situ using whole-mount preparations of human and mouse intestine. Transgenic mice with a targeted deletion of glial connexin-43 (Cx43 [GFAP::CreERT2+/−/Cx43f/f] were used to specifically disrupt glial signaling pathways. Mice deficient in inducible nitric oxide (NO synthase (iNOS−/− were used to study NO production. Protein expression and oxidative stress were measured using immunohistochemistry and in situ Ca2+ and NO imaging were used to monitor glial [Ca2+]i and [NO]i. Results: Purinergic activation of enteric glia drove [Ca2+]i responses and enteric neuron death through a Cx43-dependent mechanism. Neurotoxic Cx43 activity, driven by NO production from glial iNOS, was required for neuron death. Glial Cx43 opening liberated ATP and Cx43-dependent ATP release was potentiated by NO. Conclusions: Our results show that the activation of glial cells in the context of neuroinflammation kills enteric neurons. Mediators of inflammation that include ATP and NO activate neurotoxic pathways that converge on glial Cx43 hemichannels. The glial response to inflammatory mediators might contribute to the development of motility disorders. Keywords: Enteric Nervous System, Hemichannels

Induction of Biofilm Formation in the Betaproteobacterium Burkholderia unamae CK43B Exposed to Exogenous Indole and Gallic Acid

Science.gov (United States)

Kim, Dongyeop; Sitepu, Irnayuli R.

2013-01-01

Burkholderia unamae CK43B, a member of the Betaproteobacteria that was isolated from the rhizosphere of a Shorea balangeran sapling in a tropical peat swamp forest, produces neither indole nor extracellular polymeric substances associated with biofilm formation. When cultured in a modified Winogradsky's medium supplemented with up to 1.7 mM indole, B. unamae CK43B maintains its planktonic state by cell swelling and effectively degrades exogenous indole. However, in medium supplemented with 1.7 mM exogenous indole and 1.0 mM gallic acid, B. unamae CK43B produced extracellular polymeric substances and formed a biofilm. The concentration indicated above of gallic acid alone had no effect on either the growth or the differentiation of B. unamae CK43B cells above a certain concentration threshold, whereas it inhibited indole degradation by B. unamae CK43B to 3-hydroxyindoxyl. In addition, coculture of B. unamae CK43B with indole-producing Escherichia coli in nutrient-rich Luria-Bertani medium supplemented with 1.0 mM gallic acid led to the formation of mixed cell aggregates. The viability and active growth of B. unamae CK43B cells in a coculture system with Escherichia coli were evidenced by fluorescence in situ hybridization. Our data thus suggest that indole facilitates intergenus communication between indole-producing gammaproteobacteria and some indole-degrading bacteria, particularly in gallic acid-rich environments. PMID:23747701

S3b amino acid substitutions and ancillary subunits alter the affinity of Heteropoda venatoria toxin 2 for Kv4.3.

Science.gov (United States)

DeSimone, Christopher V; Lu, YiChun; Bondarenko, Vladimir E; Morales, Michael J

2009-07-01

Heteropoda venatoria toxin 2 (HpTx2) is an inhibitor cystine knot (ICK)-gating modifier toxin that selectively inhibits Kv4 channels. To characterize the molecular determinants of interaction, we performed alanine scanning of the Kv4.3 S3b region. HpTx2-Kv4.3 interaction had an apparent K(d) value of 2.3 microM. Two alanine mutants in Kv4.3 increased K(d) values to 6.4 microM for V276A and 25 microM for L275A. Simultaneous mutation of both amino acids to alanine nearly eliminated toxin interaction. Unlike Hanatoxin and other well characterized ICK toxins, HpTx2 binding does not require a charged amino acid for interaction. To determine whether the identity of the S3b binding site amino acids altered HpTx2 specificity, we constructed Kv4.3 [LV275IF]. This mutation decreased the K(d) value to 0.54 microM, suggesting that the hydrophobic character of the putative binding site is the most important property for interaction with HpTx2. One mutant, N280A, caused stronger interaction of HpTx2 with Kv4.3; the K(d) value for Kv4.3 [N280A] was 0.26 microM. To understand Kv4.3-based transient outward currents in native tissues, we tested the affinity of HpTx2 for Kv4.3 coexpressed with KChIP2b. The toxin's K(d) value for Kv4.3 + KChIP2b was 0.95 microM. KChIP2b stabilizes the closed state of Kv4.3, suggesting that the increased toxin affinity is due to increased stabilization of the closed state. These data show that HpTx2 binding to Kv4.3 has aspects in common with other ICK gating modifier toxins but that the interventions that increase toxin affinity suggest flexibility toward channel binding that belies its unusual specificity for Kv4 channels.

Overexpression of Cx43 in cells of the myocardial scar: Correction of post-infarct arrhythmias through heterotypic cell-cell coupling.

Science.gov (United States)

Roell, Wilhelm; Klein, Alexandra M; Breitbach, Martin; Becker, Torsten S; Parikh, Ashish; Lee, Jane; Zimmermann, Katrin; Reining, Shaun; Gabris, Beth; Ottersbach, Annika; Doran, Robert; Engelbrecht, Britta; Schiffer, Miriam; Kimura, Kenichi; Freitag, Patricia; Carls, Esther; Geisen, Caroline; Duerr, Georg D; Sasse, Philipp; Welz, Armin; Pfeifer, Alexander; Salama, Guy; Kotlikoff, Michael; Fleischmann, Bernd K

2018-05-08

Ventricular tachycardia (VT) is the most common and potentially lethal complication following myocardial infarction (MI). Biological correction of the conduction inhomogeneity that underlies re-entry could be a major advance in infarction therapy. As minimal increases in conduction of infarcted tissue markedly influence VT susceptibility, we reasoned that enhanced propagation of the electrical signal between non-excitable cells within a resolving infarct might comprise a simple means to decrease post-infarction arrhythmia risk. We therefore tested lentivirus-mediated delivery of the gap-junction protein Connexin 43 (Cx43) into acute myocardial lesions. Cx43 was expressed in (myo)fibroblasts and CD45 + cells within the scar and provided prominent and long lasting arrhythmia protection in vivo. Optical mapping of Cx43 injected hearts revealed enhanced conduction velocity within the scar, indicating Cx43-mediated electrical coupling between myocytes and (myo)fibroblasts. Thus, Cx43 gene therapy, by direct in vivo transduction of non-cardiomyocytes, comprises a simple and clinically applicable biological therapy that markedly reduces post-infarction VT.

The preparation and graphene surface coating NaTi_2(PO_4)_3 as cathode material for lithium ion batteries

International Nuclear Information System (INIS)

Li, Na; Wang, Yanping; Rao, Richuan; Dong, Xiongzi; Zhang, Xianwen; Zhu, Sane

2017-01-01

Graphical abstract: The NaTi_2(PO_4)_3/graphene composite is used directly as cathode electrode material for lithium-ion battery by using metal lithium as an anode electrode. Meanwhile, the electrochemical properties of the composite in this system is firstly studied in detail. The NaTi_2(PO_4)_3/graphene composite exhibits the better rate and cyclic performance than NaTi_2(PO_4)_3, which is ascribed to its stable 3-D framework and the enhanced electronic conduction resulting from the graphene sheets surface modification. - Highlights: • The graphene coated NaTi_2(PO_4)_3 was prepared by a simple sol-gel method followed by calcination. • The electrochemical properties of the NaTi_2(PO_4)_3/graphene composite was firstly studied in detail when used as cathode electrode material for lithium-ion batteries. • The electrochemical reaction mechanism of NaTi_2(PO_4)_3/graphene composite was investigated by ex situ XRD. - Abstract: The graphene coated NaTi_2(PO_4)_3 has been fabricated via a simple sol-gel process followed by calcination. The NaTi_2(PO_4)_3/graphene (NTP/G) composite is used directly as cathode electrode material for lithium-ion battery and the electrochemical properties of the composite in this system is firstly studied in detail. In the charge-discharge process, two Li"+ can occupy octahedral M (2) site and be reversibly intercalated into the 3D framework of NTP through the ion conduction channel where almost all of Na"+ are immobilized to sustain the framework. At 5C rate, the capacity retention of the NTP/G composite after 800 cycles is still up to 82.7%. The superior electrochemical properties of NTP/G is ascribed to its stable 3-D framework and the enhanced electronic conduction resulting from the graphene sheets surface modification.

Revisiting the Energy Budget of WASP-43b: Enhanced Day–Night Heat Transport

Energy Technology Data Exchange (ETDEWEB)

Keating, Dylan; Cowan, Nicolas B. [Department of Physics, McGill University, 3600 rue University, Montréal, QC H3A 2T8 (Canada)

2017-11-01

The large day–night temperature contrast of WASP-43b has so far eluded explanation. We revisit the energy budget of this planet by considering the impact of reflected light on dayside measurements and the physicality of implied nightside temperatures. Previous analyses of the infrared eclipses of WASP-43b have assumed reflected light from the planet is negligible and can be ignored. We develop a phenomenological eclipse model including reflected light, thermal emission, and water absorption, and we use it to fit published Hubble and Spitzer eclipse data. We infer a near-infrared geometric albedo of 24% ± 1% and a cooler dayside temperature of 1483 ± 10 K. Additionally, we perform light curve inversion on the three published orbital phase curves of WASP-43b and find that each suggests unphysical, negative flux on the nightside. By requiring non-negative brightnesses at all longitudes, we correct the unphysical parts of the maps and obtain a much hotter nightside effective temperature of 1076 ± 11 K. The cooler dayside and hotter nightside suggest a heat recirculation efficiency of 51% for WASP-43b, essentially the same as for HD 209458b, another hot Jupiter with nearly the same temperature. Our analysis therefore reaffirms the trend that planets with lower irradiation temperatures have more efficient day–night heat transport. Moreover, we note that (1) reflected light may be significant for many near-IR eclipse measurements of hot Jupiters, and (2) phase curves should be fit with physically possible longitudinal brightness profiles—it is insufficient to only require that the disk-integrated light curve be non-negative.

43 CFR 422.7 - Authorization to perform law enforcement duties.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Authorization to perform law enforcement duties. 422.7 Section 422.7 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR LAW ENFORCEMENT AUTHORITY AT BUREAU OF RECLAMATION PROJECTS Program Requirements § 422.7 Authorization to perfor...

Evaluation of IMERG and TRMM 3B43 Monthly Precipitation Products over Mainland China