Functions of Adaptor Protein (AP)-3 and AP-1 in Tyrosinase Sorting from Endosomes to MelanosomesD⃞

PubMed Central

Theos, Alexander C.; Tenza, Danièle; Martina, José A.; Hurbain, Ilse; Peden, Andrew A.; Sviderskaya, Elena V.; Stewart, Abigail; Robinson, Margaret S.; Bennett, Dorothy C.; Cutler, Daniel F.; Bonifacino, Juan S.; Marks, Michael S.; Raposo, Graça

2005-01-01

Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies. PMID:16162817

Artificial pancreas (AP) clinical trial participants' acceptance of future AP technology.

PubMed

Bevier, Wendy C; Fuller, Serena M; Fuller, Ryan P; Rubin, Richard R; Dassau, Eyal; Doyle, Francis J; Jovanovič, Lois; Zisser, Howard C

2014-09-01

Artificial pancreas (AP) systems are currently an active field of diabetes research. This pilot study examined the attitudes of AP clinical trial participants toward future acceptance of the technology, having gained firsthand experience. After possible influencers of AP technology adoption were considered, a 34-question questionnaire was developed. The survey assessed current treatment satisfaction, dimensions of clinical trial participant motivation, and variables of the technology acceptance model (TAM). Forty-seven subjects were contacted to complete the survey. The reliability of the survey scales was tested using Cronbach's α. The relationship of the factors to the likelihood of AP technology adoption was explored using regression analysis. Thirty-six subjects (76.6%) completed the survey. Of the respondents, 86.1% were either highly likely or likely to adopt the technology once available. Reliability analysis of the survey dimensions revealed good internal consistency, with scores of >0.7 for current treatment satisfaction, convenience (motivation), personal health benefit (motivation), perceived ease of use (TAM), and perceived usefulness (TAM). Linear modeling showed that future acceptance of the AP was significantly associated with TAM and the motivation variables of convenience plus the individual item benefit to others (R(2)=0.26, P=0.05). When insulin pump and continuous glucose monitor use were added, the model significance improved (R(2)=0.37, P=0.02). This pilot study demonstrated that individuals with direct AP technology experience expressed high likelihood of future acceptance. Results support the factors of personal benefit, convenience, perceived usefulness, and perceived ease of use as reliable scales that suggest system adoption in this highly motivated patient population.

Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes

PubMed Central

Sitaram, Anand; Dennis, Megan K.; Chaudhuri, Rittik; De Jesus-Rojas, Wilfredo; Tenza, Danièle; Setty, Subba Rao Gangi; Wood, Christopher S.; Sviderskaya, Elena V.; Bennett, Dorothy C.; Raposo, Graça; Bonifacino, Juan S.; Marks, Michael S.

2012-01-01

Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine–based sorting signal in the pigment cell–specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1– and AP-3–favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs. PMID:22718909

Physico-chemical profiles of the wobble ↔ Watson-Crick G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) tautomerisations: a QM/QTAIM comprehensive survey.

PubMed

Brovarets', Ol'ha O; Voiteshenko, Ivan S; Hovorun, Dmytro M

2017-12-20

This study is intended to clarify in detail the tautomeric transformations of the wobble (w) G*·2AP(w) and A·2AP(w) nucleobase mispairs involving 2-aminopurine (2AP) into the Watson-Crick (WC) G·2AP(WC) and A*·2AP(WC) base mispairs (asterisks denote mutagenic tautomers of the DNA bases), respectively, by quantum-mechanical methods and Bader's Quantum Theory of Atoms in Molecules. Our previously reported methodology has been used, which allows the evolution of the physico-chemical parameters to be tracked along the entire internal reaction coordinate (IRC), not exclusively in the stationary states of these reactions. These biologically important G*·2AP(w) ↔ G·2AP(WC) and A·2AP(w) ↔ A*·2AP(WC) w ↔ WC tautomerisations, which are involved in mutagenic tautomerically-conformational pathways, determine the origin of the transitions and transversions induced by 2AP. In addition, it is established that they proceed through planar, highly stable, zwitterionic transition states and they exhibit similar physico-chemical profiles and stages of sequential intrapair proton transfer, followed by spatial rearrangement of the nucleobases relative to each other within the base pairs. These w ↔ WC tautomerisations occur non-dissociatively and are accompanied by a significant alteration in geometry (from wobble to Watson-Crick and vice versa) and redistribution of the specific intermolecular interactions, which can be divided into 10 patterns including AHB H-bonds and loosened A-H-B covalent bridges along the IRC of tautomerisation. Based on the redistribution of the geometrical and electron-topological parameters of the intrapair hydrogen bonds, exactly 9 key points have been allocated to characterize the evolution of these reactions.

Metallized solid rocket propellants based on AN/AP and PSAN/AP for access to space

NASA Astrophysics Data System (ADS)

Levi, S.; Signoriello, D.; Gabardi, A.; Molinari, M.; Galfetti, L.; Deluca, L. T.; Cianfanelli, S.; Klyakin, G. F.

2009-09-01

Solid rocket propellants based on dual mixes of inorganic crystalline oxidizers (ammonium nitrate (AN) and ammonium perchlorate (AP)) with binder and a mixture of micrometric-nanometric aluminum were investigated. Ammonium nitrate is a low-cost oxidizer, producing environment friendly combustion products but with lower specific impulse compared to AP. The better performance obtained with AP and the low quantity of toxic emissions obtained by using AN have suggested an interesting compromise based on a dual mixture of the two oxidizers. To improve the thermal response of raw AN, different types of phase stabilized AN (PSAN) and AN/AP co-crystals were investigated.

AP reclamation and reuse in RSRM propellant

NASA Technical Reports Server (NTRS)

Miks, Kathryn F.; Harris, Stacey A.

1995-01-01

A solid propellant ingredient reclamation pilot plant has been evaluated at the Strategic Operations of Thiokol Corporation, located in Brigham City, Utah. The plant produces AP wet cake (95 percent AP, 5 percent water) for recycling at AP vendors. AP has been obtained from two standard propellant binder systems (PBAN and HTPB). Analytical work conducted at Thiokol indicates that the vendor-recrystallized AP meets Space Shuttle propellant specification requirements. Thiokol has processed 1-, 5-, and 600-gallon propellant mixes with the recrystallized AP. Processing, cast, cure, ballistic, mechanical, and safety properties have been evaluated. Phillips Laboratory static-test-fired 70-pound and 800-pound BATES motors. The data indicate that propellant processed with reclaimed AP has nominal properties.

Molecular and biochemical characterisation of two aspartic proteinases TcAP1 and TcAP2 from Theobroma cacao seeds.

PubMed

Laloi, Maryse; McCarthy, James; Morandi, Olivia; Gysler, Christof; Bucheli, Peter

2002-09-01

Aspartic proteinase (EC 3.4.23) activity plays a pivotal role in the degradation of Theobroma cacao L. seed proteins during the fermentation step of cacao bean processing. Therefore, this enzyme is believed to be critical for the formation of the peptide and amino acid cocoa flavor precursors that occurs during fermentation. Using cDNA cloning and northern blot analysis, we show here that there are at least two distinct aspartic proteinase genes ( TcAP1 and TcAP2) expressed during cacao seed development. Both genes are expressed early during seed development and their mRNA levels decrease towards the end of seed maturation. TcAP2 is expressed at a much higher level than TcAP1, although the expression of TcAP1 increases slightly during germination. The proteins encoded by TcAP1 and TcAP2 are relatively different from each other (73% identity). This, and the fact that the two corresponding genes have different expression patterns, suggests that the TcAP1 and TcAP2 proteins may have different functions in the maturing seeds and during germination. Because the TcAP2 gene is expressed at a much higher level during seed development than TcAP1, it is likely that the TcAP2 protein is primarily responsible for the majority of the industrially important protein hydrolysis that occurs during cacao bean fermentation. Finally, TcAP2 has been functionally expressed in the yeast Yarrowia lipolytica. The secreted recombinant protein is able to hydrolyse bovine haemoglobin at acidic pH and is sensitive to pepstatin A, confirming that TcAP2 encodes an aspartic proteinase, and strongly suggests that this gene encodes the well-characterized aspartic proteinase of mature cacao seeds.

VGLUT2 Trafficking Is Differentially Regulated by Adaptor Proteins AP-1 and AP-3

PubMed Central

Li, Haiyan; Santos, Magda S.; Park, Chihyung K.; Dobry, Yuriy; Voglmaier, Susan M.

2017-01-01

Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity. Increasing evidence suggests individual synaptic vesicle proteins use specific sorting signals to engage specialized biochemical mechanisms to regulate their recycling. We observed that VGLUT2 recycles differently in response to high frequency stimulation than VGLUT1. Here we further explore the trafficking of VGLUT2 using a pHluorin-based reporter, VGLUT2-pH. VGLUT2-pH exhibits slower rates of both exocytosis and endocytosis than VGLUT1-pH. VGLUT2-pH recycling is slower than VGLUT1-pH in both hippocampal neurons, which endogenously express mostly VGLUT1, and thalamic neurons, which endogenously express mostly VGLUT2, indicating that protein identity, not synaptic vesicle membrane or neuronal cell type, controls sorting. We characterize sorting signals in the C-terminal dileucine-like motif, which plays a crucial role in VGLUT2 trafficking. Disruption of this motif abolishes synaptic targeting of VGLUT2 and essentially eliminates endocytosis of the transporter. Mutational and biochemical analysis demonstrates that clathrin adaptor proteins (APs) interact with VGLUT2 at the dileucine-like motif. VGLUT2 interacts with AP-2, a well-studied adaptor protein for clathrin mediated endocytosis. In addition, VGLUT2 also interacts with the alternate adaptors, AP-1 and AP-3. VGLUT2 relies on distinct recycling mechanisms from VGLUT1. Abrogation of these differences by pharmacological and molecular inhibition reveals that

VGLUT2 Trafficking Is Differentially Regulated by Adaptor Proteins AP-1 and AP-3.

PubMed

Li, Haiyan; Santos, Magda S; Park, Chihyung K; Dobry, Yuriy; Voglmaier, Susan M

2017-01-01

Release of the major excitatory neurotransmitter glutamate by synaptic vesicle exocytosis depends on glutamate loading into synaptic vesicles by vesicular glutamate transporters (VGLUTs). The two principal isoforms, VGLUT1 and 2, exhibit a complementary pattern of expression in adult brain that broadly distinguishes cortical (VGLUT1) and subcortical (VGLUT2) systems, and correlates with distinct physiological properties in synapses expressing these isoforms. Differential trafficking of VGLUT1 and 2 has been suggested to underlie their functional diversity. Increasing evidence suggests individual synaptic vesicle proteins use specific sorting signals to engage specialized biochemical mechanisms to regulate their recycling. We observed that VGLUT2 recycles differently in response to high frequency stimulation than VGLUT1. Here we further explore the trafficking of VGLUT2 using a pHluorin-based reporter, VGLUT2-pH. VGLUT2-pH exhibits slower rates of both exocytosis and endocytosis than VGLUT1-pH. VGLUT2-pH recycling is slower than VGLUT1-pH in both hippocampal neurons, which endogenously express mostly VGLUT1, and thalamic neurons, which endogenously express mostly VGLUT2, indicating that protein identity, not synaptic vesicle membrane or neuronal cell type, controls sorting. We characterize sorting signals in the C-terminal dileucine-like motif, which plays a crucial role in VGLUT2 trafficking. Disruption of this motif abolishes synaptic targeting of VGLUT2 and essentially eliminates endocytosis of the transporter. Mutational and biochemical analysis demonstrates that clathrin adaptor proteins (APs) interact with VGLUT2 at the dileucine-like motif. VGLUT2 interacts with AP-2, a well-studied adaptor protein for clathrin mediated endocytosis. In addition, VGLUT2 also interacts with the alternate adaptors, AP-1 and AP-3. VGLUT2 relies on distinct recycling mechanisms from VGLUT1. Abrogation of these differences by pharmacological and molecular inhibition reveals that

Greenhouse evaluation of Bacillus subtilis AP-01 and Trichoderma harzianum AP-001 in controlling tobacco diseases.

PubMed

Maketon, Monchan; Apisitsantikul, Jirasak; Siriraweekul, Chatchai

2008-04-01

Two biological control agents, Bacillus subtilis AP-01 (Larminar(™)) and Trichoderma harzianum AP-001 (Trisan(™)) alone or/in combination were investigated in controlling three tobacco diseases, including bacterial wilt (Ralstonia solanacearum), damping-off (Pythium aphanidermatum), and frogeye leaf spot (Cercospora nicotiana). Tests were performed in greenhouse by soil sterilization prior to inoculation of the pathogens. Bacterial-wilt and damping off pathogens were drenched first and followed with the biological control agents and for comparison purposes, two chemical fungicides. But for frogeye leaf spot, which is an airborne fungus, a spraying procedure for every treatment including a chemical fungicide was applied instead of drenching. Results showed that neither B. subtilis AP-01 nor T harzianum AP-001 alone could control the bacterial wilt, but when combined, their controlling capabilities were as effective as a chemical treatment. These results were also similar for damping-off disease when used in combination. In addition, the combined B. subtilis AP-01 and T. harzianum AP-001 resulted in a good frogeye leaf spot control, which was not significantly different from the chemical treatment.

Project W-211, initial tank retrieval systems, description of operations for 241-AP-102 and 241-AP-104

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

RIECK, C.A.

1999-02-25

The primary purpose of the Initial Tank Retrieval Systems (ITRS) is to provide systems for retrieval of radioactive wastes stored in underground double-shell tanks (DSTS) for transfer to alternate storage, evaporation, pretreatment or treatment, while concurrently reducing risks associated with safety watch list and other DSTs. This Description of Operations (DOO) defines the control philosophy for the waste retrieval system for tanks 241-AP-102 (AP-102) and 241-AP-104 (AP-104). This DOO will provide a basis for the detailed design of the Retrieval Control System (RCS) for AP-102 and AP-104 and establishes test criteria for the RCS. The test criteria will be usedmore » during qualification testing and acceptance testing to verify operability.« less

An AP Calculus Classroom Amusement Park

ERIC Educational Resources Information Center

Ferguson, Sarah

2016-01-01

Throughout the school year, AP Calculus teachers strive to teach course content comprehensively and swiftly in an effort to finish all required material before the AP Calculus exam. As early May approaches and the AP Calculus test looms, students and teachers nervously complete lessons, assignments, and assessments to ensure student preparation.…

Alejarse como proceso social: niños y ancianos «abandonados» en Ayacucho1

PubMed Central

Leinaweaver, Jessaca

2013-01-01

En investigaciones previas sobre el acogimiento familiar y la adopción en Ayacucho, se ha podido descubrir cómo los ayacuchanos adquieren y producen relaciones sociales. Mientras negocian creativamente los discursos y espacios construidos simultáneamente por instituciones, comunidades, y estructuras sociales, van adquiriendo nuevas formas de relacionarse. Este artículo discute el proceso opuesto: el deshacerse de relaciones de parentesco, y el proceso social del abandono o alejamiento. Cuando se aleja a una persona de su familia o su comunidad, los que se quedan en ella llegan a entenderse como ciertos tipos de personas. En los estudios de caso discutidos aquí, recopilados a través de una detallada y cuidadosa observación participante y de entrevistas etnográficas grabadas entre 2001 y 2007, se puede ver cómo, después de un alejamiento social, los individuos que alejan se reinterpretan como sujetos que se encuentran superándose o volviéndose modernos, o bien sacrificándose. PMID:25177044

Advanced APS impacts on vehicle payloads

NASA Technical Reports Server (NTRS)

Schneider, Steven J.; Reed, Brian D.

1989-01-01

Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethylhydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination of scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

Advanced APS Impacts on Vehicle Payloads

NASA Technical Reports Server (NTRS)

Schneider, Steven J.; Reed, Brian D.

1989-01-01

Advanced auxiliary propulsion system (APS) technology has the potential to both, increase the payload capability of earth-to-orbit (ETO) vehicles by reducing APS propellant mass, and simplify ground operations and logistics by reducing the number of fluids on the vehicle and eliminating toxic, corrosive propellants. The impact of integrated cryogenic APS on vehicle payloads is addressed. In this system, launch propulsion system residuals are scavenged from integral launch propulsion tanks for use in the APS. Sufficient propellant is preloaded into the APS to return to earth with margin and noncomplete scavenging assumed. No propellant conditioning is required by the APS, but ambient heat soak is accommodated. High temperature rocket materials enable the use of the unconditioned hydrogen/oxygen in the APS and are estimated to give APS rockets specific impulse of up to about 444 sec. The payload benefits are quantified and compared with an uprated monomethyl hydrazine/nitrogen tetroxide system in a conservative fashion, by assuming a 25.5 percent weight growth for the hydrogen/oxygen system and a 0 percent weight growth for the uprated system. The combination and scavenging and high performance gives payload impacts which are highly mission specific. A payload benefit of 861 kg (1898 lbm) was estimated for a Space Station Freedom rendezvous mission and 2099 kg (4626 lbm) for a sortie mission, with payload impacts varying with the amount of launch propulsion residual propellants. Missions without liquid propellant scavenging were estimated to have payload penalties, however, operational benefits were still possible.

77 FR 24480 - Application for New Awards; Advanced Placement (AP) Test Fee Program-Reopening the AP Test Fee...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

... DEPARTMENT OF EDUCATION Application for New Awards; Advanced Placement (AP) Test Fee Program--Reopening the AP Test Fee Fiscal Year 2012 Competition AGENCY: Office of Elementary and Secondary Education (OESE), Department of Education. ACTION: Notice reopening the AP Test Fee fiscal year 2012 competition...

Structural characterization of the N-terminal mineral modification domains from the molluscan crystal-modulating biomineralization proteins, AP7 and AP24.

PubMed

Wustman, Brandon A; Morse, Daniel E; Evans, John Spencer

2004-08-05

The AP7 and AP24 proteins represent a class of mineral-interaction polypeptides that are found in the aragonite-containing nacre layer of mollusk shell (H. rufescens). These proteins have been shown to preferentially interfere with calcium carbonate mineral growth in vitro. It is believed that both proteins play an important role in aragonite polymorph selection in the mollusk shell. Previously, we demonstrated the 1-30 amino acid (AA) N-terminal sequences of AP7 and AP24 represent mineral interaction/modification domains in both proteins, as evidenced by their ability to frustrate calcium carbonate crystal growth at step edge regions. In this present report, using free N-terminal, C(alpha)-amide "capped" synthetic polypeptides representing the 1-30 AA regions of AP7 (AP7-1 polypeptide) and AP24 (AP24-1 polypeptide) and NMR spectroscopy, we confirm that both N-terminal sequences possess putative Ca (II) interaction polyanionic sequence regions (2 x -DD- in AP7-1, -DDDED- in AP24-1) that are random coil-like in structure. However, with regard to the remaining sequences regions, each polypeptide features unique structural differences. AP7-1 possesses an extended beta-strand or polyproline type II-like structure within the A11-M10, S12-V13, and S28-I27 sequence regions, with the remaining sequence regions adopting a random-coil-like structure, a trait common to other polyelectrolyte mineral-associated polypeptide sequences. Conversely, AP24-1 possesses random coil-like structure within A1-S9 and Q14-N16 sequence regions, and evidence for turn-like, bend, or loop conformation within the G10-N13, Q17-N24, and M29-F30 sequence regions, similar to the structures identified within the putative elastomeric proteins Lustrin A and sea urchin spicule matrix proteins. The similarities and differences in AP7 and AP24 N-terminal domain structure are discussed with regard to joint AP7-AP24 protein modification of calcium carbonate growth. Copyright 2004 Wiley Periodicals, Inc.

Observational studies of roAp stars

NASA Astrophysics Data System (ADS)

Sachkov, M.

2014-11-01

Rapidly oscillating Ap (roAp) stars are high-overtone, low-degree p-mode pulsators that are also chemically peculiar magnetic A stars. Until recently the classical asteroseismic analysis i.e. frequency analysis, of these stars was based on ground and space photometric observations. Significant progress was achieved through access to uninterrupted, ultra-high-precision data from MOST, COROT and Kepler satellites. Over the last ten years the study of roAp stars has been altered drastically from an observational point of view through studies of time-resolved, high-resolution spectra. Their unusual pulsational characteristics, caused by an interplay between the short vertical lengths of the pulsation waves and strong stratification of chemical elements, allow us to examine the upper roAp atmosphere in more detail than is possible for any star except the Sun. In this paper I review the results of recent studies of the pulsations of roAp stars.

Distribución del continuo ultravioleta e infrarrojo en estrellas Be

NASA Astrophysics Data System (ADS)

Cruzado, A.; Ringuelet, A.; di Rocco, H.

Estamos interesados en interpretar los excesos de flujo infrarrojo y/o ultravioleta observados en estrellas Be con respecto al de estrellas B normales, así como su posible correlación. Una envoltura rodeando la estrella distingue una estrella Be de una B normal; para explicar las observaciones es necesario entonces tener en cuenta todos los posibles procesos físicos que en ella tienen lugar. Adoptando un modelo atmosférico específico, hemos estudiado el proceso de recombinación dielectrónica de metales como MgII y FeII, teniendo en cuenta la posible influencia de la opacidad del medio en el flujo emitido.

Comparative Ballistic Performance of 20mm AP M95 and 20mm AP M75 Projectiles against Rolled Homogeneous Steel Armor

DTIC Science & Technology

1960-05-01

Dominic A. Piccione, " Comparative Ballistic Performanceof 20mm AP M95 and 20mm AP M75 Projectiles againstRolled Homogeneous Steel Armor (U)’\\ WAL-TR-160.1/1... COMPARATIVE BALLISTIC PERFORMANCE OF 20MM AP M95 AND 20MM AP M75 PROJECTILES AGAINST ROLLED HOMOGENEOUS STEEL ARMOR (U) TECHNICAL REPORT NO. WAL TR I60.l/I(c...o > -< Abt9sortf bl O *_, o o -o WATERTOWN ARSENAL LABORATORIES co COMPARATIVE BALLISTIC PERFORMANCE OF 20MM AP M95 AND 20MM AP M75

APS Education and Diversity Efforts

NASA Astrophysics Data System (ADS)

Prestridge, Katherine; Hodapp, Theodore

2015-11-01

American Physical Society (APS) has a wide range of education and diversity programs and activities, including programs that improve physics education, increase diversity, provide outreach to the public, and impact public policy. We present the latest programs spearheaded by the Committee on the Status of Women in Physics (CSWP), with highlights from other diversity and education efforts. The CSWP is working to increase the fraction of women in physics, understand and implement solutions for gender-specific issues, enhance professional development opportunities for women in physics, and remedy issues that impact gender inequality in physics. The Conferences for Undergraduate Women in Physics, Professional Skills Development Workshops, and our new Professional Skills program for students and postdocs are all working towards meeting these goals. The CSWP also has site visit and conversation visit programs, where department chairs request that the APS assess the climate for women in their departments or facilitate climate discussions. APS also has two significant programs to increase participation by underrepresented minorities (URM). The newest program, the APS National Mentoring Community, is working to provide mentoring to URM undergraduates, and the APS Bridge Program is an established effort that is dramatically increasing the number of URM PhDs in physics.

Ap4A induces apoptosis in human cultured cells.

PubMed

Vartanian, A; Alexandrov, I; Prudowski, I; McLennan, A; Kisselev, L

1999-07-30

Diadenosine oligophosphates (Ap(n)A) have been proposed as intracellular and extracellular signaling molecules in animal cells. The ratio of diadenosine 5',5'''-P1,P3-triphosphate to diadenosine 5',5'''-P1,P4-tetraphosphate (Ap3A/Ap4A) is sensitive to the cellular status and alters when cultured cells undergo differentiation or are treated with interferons. In cells undergoing apoptosis induced by DNA topoisomerase II inhibitor VP16, the concentration of Ap3A decreases significantly while that of Ap4A increases. Here, we have examined the effects of exogenously added Ap3A and Ap4A on apoptosis and morphological differentiation. Penetration of Ap(n)A into cells was achieved by cold shock. Ap4A at 10 microM induced programmed cell death in human HL60, U937 and Jurkat cells and mouse VMRO cells and this effect appeared to require Ap4A breakdown as hydrolysis-resistant analogues of Ap4A were inactive. On its own, Ap3A induced neither apoptosis nor cell differentiation but did display strong synergism with the protein kinase C activators 12-deoxyphorbol-13-O-phenylacetate and 12-deoxyphorbol-13-O-phenylacetate-20-acetate in inducing differentiation of HL60 cells. We propose that Ap4A and Ap3A are physiological antagonists in determination of the cellular status: Ap4A induces apoptosis whereas Ap3A is a co-inductor of differentiation. In both cases, the mechanism of signal transduction remains unknown.

APS Science 2007.

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

Not Available

2008-05-30

This report provides research highlights from the Advanced Photon Source (APS). Although these highlights represent less than 10% of the published work from the APS in 2007, they give a flavor of the diversity and impact of user research at the facility. In the strategic planning the aim is to foster the growth of existing user communities and foresee new areas of research. This coming year finds the APS engaged in putting together, along with the users, a blueprint for the next five years, and making the case for a set of prioritized investments in beamlines, the accelerator, and infrastructure,more » each of which will be transformational in terms of scientific impact. As this is written plans are being formulated for an important user workshop on October 20-21, 2008, to prioritize strategic plans. The fruit from past investments can be seen in this report. Examples include the creation of a dedicated beamline for x-ray photon correlation spectroscopy at Sector 8, the evolution of dedicated high-energy x-ray scattering beamlines at sectors 1 and 11, a dedicated imaging beamline at Sector 32, and new beamlines for inelastic scattering and powder diffraction. A single-pulse facility has been built in collaboration with Sector 14 (BioCARS) and Phil Anfinrud at the National Institutes of Health, which will offer exceptionally high flux for single-pulse diffraction. The nanoprobe at Sector 26, built and operated jointly by the Argonne Center for Nanoscale Materials and the X-ray Operations and Research (XOR) section of the APS X-ray Science Division, has come on line to define the state of the art in nanoscience.« less

High concentrations of intracellular Ap4A and/or Ap5A in developing Myxococcus xanthus cells inhibit sporulation.

PubMed

Kimura, Yoshio; Tanaka, Chihiro; Sasaki, Katsuho; Sasaki, Masashi

2017-01-01

Diadenosine polyphosphates (ApnA) are thought to act as signalling molecules regulating stress responses and biofilm formation in prokaryotes. However, ApnA function in Myxococcus xanthus remains unknown. Here, we investigated the role of ApnA in M. xanthus, using the wild-type and ApnA hydrolase (apaH) mutant strains exposed to various stress conditions. In both wild-type and apaH mutant cells cultured on starvation medium (CF agar), the levels of intracellular diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) increased several fold during the first 16 h of development and decreased gradually thereafter. The levels of Ap4A and Ap5A in the apaH mutant were about 5- and 11-fold higher than those in the wild-type strain at 16 h, respectively. ApnA hydrolase activity of the wild-type strain increased 1.5-fold during the first 8 h of development, and it then gradually decreased. The apaH mutant formed spores 1-2 days after the wild-type strain did, and the yield of viable spores was 5.5 % of that in the wild-type strain 5 days after inoculation onto CF agar. These results suggest the possibility that high intracellular levels of Ap4A and/or Ap5A may inhibit M. xanthus sporulation at the early stage of development and that the bacteria reduce intracellular Ap4A and Ap5A accumulation through ApnA hydrolase activity.

Comparison of Spectral and Scintillation Properties of LuAP:Ce and LuAP:Ce,Sc Single Crystals

NASA Astrophysics Data System (ADS)

Petrosyan, Ashot G.; Derdzyan, Marina; Ovanesyan, Karine; Shirinyan, Grigori; Lecoq, Paul; Auffray, Etiennette; Kronberger, Matthias; Frisch, Benjamin; Pedrini, Christian; Dujardin, Christophe

2009-10-01

Scintillation properties of LuAP:Ce and LuAP:Ce,Sc crystal series were studied under excitation by gamma-rays from a 137Cs source. Both series demonstrated comparable optical quality in terms of underlying absorption at 260 nm, slope of the optical edge and transmission in the range of emission. The light yield of LuAP:Ce crystals measured in 0.2 cm times 0.2 cm times 0.8 cm pixels increases linearly with the Ce concentration reaching at 0.58 at. % 6448 plusmn 322 ph/MeV and 9911 plusmn 496 ph/MeV in the long and in the short directions respectively (the light yield ratio is 65%) and shows no sign of light saturation. The energy resolution is found to depend, among other factors, on the uniformity of Ce concentration within the pixels and is improved to 7.1 plusmn 0.4% (I = 0.2 cm), 9.5 plusmn 0.5% (I = 0.8 cm). Intentional co-doping with Sc + ions was tested and resulted in increase of the Ce distribution coefficient to about 0.3. This enabled to increase the concentration of Ce in LuAP:Ce,Sc crystals up to 0.7 at. %, while conserving high optical quality. In contrast to LuAP:Ce, the light yield in LuAP:Ce,Sc crystals does not increase with Ce concentration, the photo peak being gradually suppressed. The involved mechanisms are discussed basing on measurements of the unit cell volumes, Ce concentration uniformity, x-ray rocking spectra, absorption spectra of pure and variously doped LuAP crystals, and emission spectra under different excitations.

ParamAP: Standardized Parameterization of Sinoatrial Node Myocyte Action Potentials.

PubMed

Rickert, Christian; Proenza, Catherine

2017-08-22

Sinoatrial node myocytes act as cardiac pacemaker cells by generating spontaneous action potentials (APs). Much information is encoded in sinoatrial AP waveforms, but both the analysis and the comparison of AP parameters between studies is hindered by the lack of standardized parameter definitions and the absence of automated analysis tools. Here we introduce ParamAP, a standalone cross-platform computational tool that uses a template-free detection algorithm to automatically identify and parameterize APs from text input files. ParamAP employs a graphic user interface with automatic and user-customizable input modes, and it outputs data files in text and PDF formats. ParamAP returns a total of 16 AP waveform parameters including time intervals such as the AP duration, membrane potentials such as the maximum diastolic potential, and rates of change of the membrane potential such as the diastolic depolarization rate. ParamAP provides a robust AP detection algorithm in combination with a standardized AP parameter analysis over a wide range of AP waveforms and firing rates, owing in part to the use of an iterative algorithm for the determination of the threshold potential and the diastolic depolarization rate that is independent of the maximum upstroke velocity, a parameter that can vary significantly among sinoatrial APs. Because ParamAP is implemented in Python 3, it is also highly customizable and extensible. In conclusion, ParamAP is a powerful computational tool that facilitates quantitative analysis and enables comparison of sinoatrial APs by standardizing parameter definitions and providing an automated work flow. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Preparing Students for the AP Psychology Exam

ERIC Educational Resources Information Center

Whitlock, Kristin

2013-01-01

The Advanced Placement Psychology exam is one of the fastest growing exams offered by the College Board. The average percent of change in the number of students taking this exam over the past five years is 12.4%. With 238,962 students taking the exam in 2013, the AP Psychology exam is the sixth largest exam, surpassing AP Biology and AP World…

Power Saving Control for Battery-Powered Portable WLAN APs

NASA Astrophysics Data System (ADS)

Ogawa, Masakatsu; Hiraguri, Takefumi

This paper proposes a power saving control function for battery-powered portable wireless LAN (WLAN) access points (APs) to extend the battery life. The IEEE802.11 standard does not support power saving control for APs. To enable a sleep state for an AP, the AP forces the stations (STAs) to refrain from transmitting frames using the network allocation vector (NAV) while the AP is sleeping. Thus the sleep state for the AP can be employed without causing frame loss at the STAs. Numerical analysis and computer simulation reveal that the newly proposed control technique conserves power compared to the conventional control.

Chromosome localization of human genes for clathrin adaptor polypeptides AP2{beta} and AP50 and the clathrin-binding protein, VCP

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

Druck, T.; Gu, Y.; Prabhala, G.

1995-11-01

Clathrin-coated vesicles, involved in endocytosis and Golgi processing, have a surface lattice containing clathrin triskelia and stoichiometric amounts of additional components termed {open_quotes}assembly proteins,{close_quotes} or APs. The AP form at the plasma membrane, AP2, is composed of two large subunits of 100-115 kDa, denoted AP2{alpha} and AP2{beta}, a medium chain of 50 kDa, designated AP50, and a small chain. We have determined human chromosomal locations of genes for a large AP2{beta} (CLAPB1) and a medium (CLAPM1) AP subunit and of a novel clathrin-binding protein, VCP, that binds clathrin simultaneously with A1`s. Chromosomal in situ hybridization of a human genomic clonemore » demonstrated that the CLAPM1 gene mapped to chromosome region 3q28. The gene for the CLAPB1 large subunit was mapped to 17q11.2-q12 by PCR amplification of an AP2{beta} fragment from a panel of rodent-human hybrid DNAs. To map the human VCP sequence, a human-specific probe was made by RT-PCR of human mRNA using oligonucleotide primers from conserved regions of the porcine sequence. The amplified human fragment served as probe on Southern blots of hybrid DNAs to determine that the human VCP locus maps to chromosome region 9pter-q34. 13 refs., 2 figs.« less

AP Powerhouse Creates High Expectations for Dallas Students: Spreading the AP Challenge to Students and Teachers.

ERIC Educational Resources Information Center

Nelson, Colleen McCain

2001-01-01

Describes how veteran teacher Joan Vinson has made Advanced Placement (AP) a "cool thing to do" for minority students. With the help of private funding and a Texas-size enthusiasm, she is also convincing more teachers to take on the AP challenge, with a focus on quality over quantity. (EV)

AP-1 subunits: quarrel and harmony among siblings.

PubMed

Hess, Jochen; Angel, Peter; Schorpp-Kistner, Marina

2004-12-01

The AP-1 transcription factor is mainly composed of Jun, Fos and ATF protein dimers. It mediates gene regulation in response to a plethora of physiological and pathological stimuli, including cytokines, growth factors, stress signals, bacterial and viral infections, as well as oncogenic stimuli. Studies in genetically modified mice and cells have highlighted a crucial role for AP-1 in a variety of cellular events involved in normal development or neoplastic transformation causing cancer. However, emerging evidence indicates that the contribution of AP-1 to determination of cell fates critically depends on the relative abundance of AP-1 subunits, the composition of AP-1 dimers, the quality of stimulus, the cell type and the cellular environment. Therefore, AP-1-mediated regulation of processes such as proliferation, differentiation, apoptosis and transformation should be considered within the context of a complex dynamic network of signalling pathways and other nuclear factors that respond simultaneously.

Proactive AP Selection Method Considering the Radio Interference Environment

NASA Astrophysics Data System (ADS)

Taenaka, Yuzo; Kashihara, Shigeru; Tsukamoto, Kazuya; Yamaguchi, Suguru; Oie, Yuji

In the near future, wireless local area networks (WLANs) will overlap to provide continuous coverage over a wide area. In such ubiquitous WLANs, a mobile node (MN) moving freely between multiple access points (APs) requires not only permanent access to the Internet but also continuous communication quality during handover. In order to satisfy these requirements, an MN needs to (1) select an AP with better performance and (2) execute a handover seamlessly. To satisfy requirement (2), we proposed a seamless handover method in a previous study. Moreover, in order to achieve (1), the Received Signal Strength Indicator (RSSI) is usually employed to measure wireless link quality in a WLAN system. However, in a real environment, especially if APs are densely situated, it is difficult to always select an AP with better performance based on only the RSSI. This is because the RSSI alone cannot detect the degradation of communication quality due to radio interference. Moreover, it is important that AP selection is completed only on an MN, because we can assume that, in ubiquitous WLANs, various organizations or operators will manage APs. Hence, we cannot modify the APs for AP selection. To overcome these difficulties, in the present paper, we propose and implement a proactive AP selection method considering wireless link condition based on the number of frame retransmissions in addition to the RSSI. In the evaluation, we show that the proposed AP selection method can appropriately select an AP with good wireless link quality, i.e., high RSSI and low radio interference.

Peculiar Traits of Coarse AP

DTIC Science & Technology

2014-01-01

propellant. Since coarse AP in particles larger than about 150 microns are used in great majority for AP oxidized solid propellants, the nature of...Microscopic amounts of liquid containing water were contained in the reactive centers. The maximum size for reactive centers was reasoned to be...bond in the original chlorate ion. Oxygen atom swapping between chlorate and perchlorate ions would provide chlorate migration without use of forces

AP Human Geography and Success on the AP Test

ERIC Educational Resources Information Center

Roncone, John; Newhalfen, Nate

2013-01-01

Classroom projects that explore culture and globalization enhance the curriculum and help students see how geography directly connects to their lives. These authors contend that a project-based approach can supplement the teaching of an AP Human Geography course, and visualize this course as an essential tool for students to truly understand how…

Crystal structures of Salmonella typhimurium propionate kinase and its complex with Ap4A: evidence for a novel Ap4A synthetic activity.

PubMed

Simanshu, Dhirendra K; Savithri, H S; Murthy, M R N

2008-03-01

Propionate kinase catalyses the last step in the anaerobic breakdown of L-threonine to propionate in which propionyl phosphate and ADP are converted to propionate and ATP. Here we report the structures of propionate kinase (TdcD) in the native form as well as in complex with diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) by X-ray crystallography. Structure of TdcD obtained after cocrystallization with ATP showed Ap4A bound to the active site pocket suggesting the presence of Ap4A synthetic activity in TdcD. Binding of Ap4A to the enzyme was confirmed by the structure determination of a TdcD-Ap4A complex obtained after cocrystallization of TdcD with commercially available Ap4A. Mass spectroscopic studies provided further evidence for the formation of Ap4A by propionate kinase in the presence of ATP. In the TdcD-Ap4A complex structure, Ap4A is present in an extended conformation with one adenosine moiety present in the nucleotide binding site and other in the proposed propionate binding site. These observations tend to support direct in-line transfer of phosphoryl group during the kinase reaction. 2007 Wiley-Liss, Inc.

AP Courses Get Audited for Quality

ERIC Educational Resources Information Center

Ashford, Ellie

2007-01-01

As the college admissions process has gotten much more competitive, the number of high school students taking Advanced Placement (AP) courses has soared. At the same time, policymakers and education leaders seek to get more minorities and students not on the college track to sign up for AP and other rigorous classes. But as high schools have…

Analogs of diadenosine tetraphosphate (Ap4A).

PubMed

Guranowski, Andrzej

2003-01-01

This review summarizes our knowledge of analogs and derivatives of diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), the most extensively studied member of the dinucleoside 5',5"'-P1,Pn-polyphosphate (NpnN) family. After a short discussion of enzymes that may be responsible for the accumulation and degradation of Np4)N's in the cell, this review focuses on chemically and/or enzymatically produced analogs and their practical applications. Particular attention is paid to compounds that have aided the study of enzymes involved in the metabolism of Ap4A (Np4N'). Certain Ap4A analogs were alternative substrates of Ap4A-degrading enzymes and/or acted as enzyme inhibitors, some other helped to establish enzyme mechanisms, increased the sensitivity of certain enzyme assays or produced stable enzyme:ligand complexes for structural analysis.

ONLINE MINIMIZATION OF VERTICAL BEAM SIZES AT APS

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

Sun, Yipeng

In this paper, online minimization of vertical beam sizes along the APS (Advanced Photon Source) storage ring is presented. A genetic algorithm (GA) was developed and employed for the online optimization in the APS storage ring. A total of 59 families of skew quadrupole magnets were employed as knobs to adjust the coupling and the vertical dispersion in the APS storage ring. Starting from initially zero current skew quadrupoles, small vertical beam sizes along the APS storage ring were achieved in a short optimization time of one hour. The optimization results from this method are briefly compared with the onemore » from LOCO (Linear Optics from Closed Orbits) response matrix correction.« less

Seguridad del paciente en Radioterapia Intraoperatoria: Impacto de los elementos controlados por el Radiofisico

NASA Astrophysics Data System (ADS)

Tarjuelo, Juan Lopez

Introduccion: En la administracion de la radioterapia intervienen profesionales y equipos de tratamiento, por lo que existe el riesgo de error y se precisa que dicho equipamiento funcione conforme a lo esperado. A los radiofisicos les corresponde participar en las actividades de garantia o aseguramiento de la calidad, incluyendo el control de calidad de los equipos, y en la evaluacion de los riesgos asociados. La radioterapia intraoperatoria (RIO) es una tecnica radioterapica de intensificacion de dosis, altamente selectiva, dirigida a volumenes anatomicos restringidos durante el tratamiento quirurgico oncologico, basada en la administracion de una dosis absorbida alta por medio de un haz de electrones tras el examen visual directo del lecho tumoral. Como incorporar los ultimos avances en el refuerzo de la seguridad en radioterapia es una tarea ambiciosa y compleja, resulta mas concreta y de inmediata aplicacion su introduccion en la RIO. El objetivo es analizar los elementos que reducen los riesgos y aumentan la seguridad en la RIO y su dosimetria, y valorar la funcion del radiofisico en esta labor. Material y metodos: Se emplearon el planificador Radiance de GMV y el acelerador lineal de los tratamientos de RIO Elekta Precise, controlado con el verificador diario de haces Daily QA Check 1090 y medido con las camaras de ionizacion PPC 40, FC65-G y FC65-P de PTW-Freiburg, a su vez verificadas con fuentes radiactivas adecuadas de estroncio-90 modelos CDP y CDC de IBA Dosimetry. Se realizo un analisis de modos de fallo y efectos (failure mode and effect analysis, FMEA) con el fin de identificar los elementos que forman la RIO y aplicar las herramientas necesarias para la minimizacion de los riesgos y la mejora de la seguridad en la tecnica. Se estudiaron las verificaciones diarias de dicho acelerador Precise con el control estadistico de procesos (statistical process control, SPC) y se simularon intervenciones para devolverlo al estado llamado en control. El SPC

apGA: An adaptive parallel genetic algorithm

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

Liepins, G.E.; Baluja, S.

1991-01-01

We develop apGA, a parallel variant of the standard generational GA, that combines aggressive search with perpetual novelty, yet is able to preserve enough genetic structure to optimally solve variably scaled, non-uniform block deceptive and hierarchical deceptive problems. apGA combines elitism, adaptive mutation, adaptive exponential scaling, and temporal memory. We present empirical results for six classes of problems, including the DeJong test suite. Although we have not investigated hybrids, we note that apGA could be incorporated into other recent GA variants such as GENITOR, CHC, and the recombination stage of mGA. 12 refs., 2 figs., 2 tabs.

APS deposition facility upgrades and future plans

NASA Astrophysics Data System (ADS)

Conley, Ray; Shi, Bing; Erdmann, Mark; Izzo, Scott; Assoufid, Lahsen; Goetze, Kurt; Mooney, Tim; Lauer, Kenneth

2014-09-01

The Advanced Photon Source (APS) has recently invested resources to upgrade or replace aging deposition systems with modern equipment. Of the three existing deposition systems, one will receive an upgrade, while two are being replaced. A design which adds a three-substrate planetary for the APS rotary deposition system is almost complete. The replacement for the APS large deposition system, dubbed the "Modular Deposition System", has been conceptually designed and is in the procurement process. Eight cathodes will sputter horizontally on mirrors up to 1.5 meters in length. This new instrument is designed to interface with ion-milling instruments and various metrology equipment for ion-beam figuring. A third linear machine, called the APS Profile Coating System, has two cathodes and is designed to accept substrates up to 200mm in length. While this machine is primarily intended for fabrication of figured KB mirrors using the profile-coating technique, it has also been used to produce multilayer monochromators for beamline use.

75 FR 75666 - Advanced Placement (AP) Test Fee Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

... DEPARTMENT OF EDUCATION [CFDA No. 84.330B] Advanced Placement (AP) Test Fee Program AGENCY: Office... AP Test Fee fiscal year (FY) 2011 competition. SUMMARY: On September 1, 2010, we published in the Federal Register (75 FR 53681) a notice inviting applications for the AP Test Fee FY 2011 competition...

X Linkage of AP3A, a Homolog of the Y-Linked MADS-Box Gene AP3Y in Silene latifolia and S. dioica

PubMed Central

Penny, Rebecca H.; Montgomery, Benjamin R.; Delph, Lynda F.

2011-01-01

Background The duplication of autosomal genes onto the Y chromosome may be an important element in the evolution of sexual dimorphism.A previous cytological study reported on a putative example of such a duplication event in a dioecious tribe of Silene (Caryophyllaceae): it was inferred that the Y-linked MADS-box gene AP3Y originated from a duplication of the reportedly autosomal orthologAP3A. However, a recent study, also using cytological methods, indicated that AP3A is X-linked in Silenelatifolia. Methodology/Principal Findings In this study, we hybridized S. latifolia and S. dioicato investigate whether the pattern of X linkage is consistent among distinct populations, occurs in both species, and is robust to genetic methods. We found inheritance patterns indicative of X linkage of AP3A in widely distributed populations of both species. Conclusions/Significance X linkage ofAP3A and Y linkage of AP3Yin both species indicates that the genes' ancestral progenitor resided on the autosomes that gave rise to the sex chromosomesand that neither gene has moved between chromosomes since species divergence.Consequently, our results do not support the contention that inter-chromosomal gene transfer occurred in the evolution of SlAP3Y from SlAP3A. PMID:21533056

Diadenosine polyphosphates (Ap3A and Ap4A) behave as alarmones triggering the synthesis of enzymes of the phenylpropanoid pathway in Arabidopsis thaliana.

PubMed

Pietrowska-Borek, Małgorzata; Nuc, Katarzyna; Zielezińska, Małgorzata; Guranowski, Andrzej

2011-12-01

It is known that cells under stress accumulate various dinucleoside polyphosphates, compounds suggested to function as alarmones. In plants, the phenylpropanoid pathways yield metabolites protecting these organisms against various types of stress. Observations reported in this communication link these two phenomena and provide an example of a metabolic "addressee" for an "alarm" signaled by diadenosine triphosphate (Ap3A) or diadenosine tetraphosphate (Ap4A). In response to added Ap3A or Ap4A, seedlings of Arabidopsis thaliana incubated in full nutrition medium increased both the expression of the genes for and the specific activity of phenylalanine ammonia-lyase and 4-coumarate:coenzyme A ligase, enzymes that control the beginning of the phenylpropanoid pathway. Neither adenine mononucleotides (AMP, ADP or ATP) nor adenosine evoked such effects. Reactions catalyzed in vitro by these enzymes were not affected by Ap3A or Ap4A.

Multipurpose active pixel sensor (APS)-based microtracker

NASA Astrophysics Data System (ADS)

Eisenman, Allan R.; Liebe, Carl C.; Zhu, David Q.

1998-12-01

A new, photon-sensitive, imaging array, the active pixel sensor (APS) has emerged as a competitor to the CCD imager for use in star and target trackers. The Jet Propulsion Laboratory (JPL) has undertaken a program to develop a new generation, highly integrated, APS-based, multipurpose tracker: the Programmable Intelligent Microtracker (PIM). The supporting hardware used in the PIM has been carefully selected to enhance the inherent advantages of the APS. Adequate computation power is included to perform star identification, star tracking, attitude determination, space docking, feature tracking, descent imaging for landing control, and target tracking capabilities. Its first version uses a JPL developed 256 X 256-pixel APS and an advanced 32-bit RISC microcontroller. By taking advantage of the unique features of the APS/microcontroller combination, the microtracker will achieve about an order-of-magnitude reduction in mass and power consumption compared to present state-of-the-art star trackers. It will also add the advantage of programmability to enable it to perform a variety of star, other celestial body, and target tracking tasks. The PIM is already proving the usefulness of its design concept for space applications. It is demonstrating the effectiveness of taking such an integrated approach in building a new generation of high performance, general purpose, tracking instruments to be applied to a large variety of future space missions.

Automated Plasma Spray (APS) process feasibility study

NASA Technical Reports Server (NTRS)

Fetheroff, C. W.; Derkacs, T.; Matay, I. M.

1981-01-01

An automated plasma spray (APS) process was developed to apply two layer (NiCrAlY and ZrO2-12Y2O3) thermal barrier coatings to aircraft and stationary gas turbine engine blade airfoils. The APS process hardware consists of four subsystems: a mechanical positioning subsystem incorporating two interlaced six degree of freedom assemblies (one for coating deposition and one for coating thickness monitoring); a noncoherent optical metrology subsystem (for in process gaging of the coating thickness buildup at specified points on the specimen); a microprocessor based adaptive system controller (to achieve the desired overall thickness profile on the specimen); and commerical plasma spray equipment. Over fifty JT9D first stage aircraft turbine blade specimens, ten W501B utility turbine blade specimens and dozens of cylindrical specimens were coated with the APS process in preliminary checkout and evaluation studies. The best of the preliminary turbine blade specimens achieved an overall coating thickness uniformity of 53 micrometers (2.1 mils), much better than is achievable manually. Comparative evaluations of coating thickness uniformity for manually sprayed and APS coated specimens were performed. One of the preliminary turbine blade evaluation specimens was subjected to a torch test and metallographic evaluation. Some cylindrical specimens coated with the APS process survived up to 2000 cycles in subsequent burner rig testing.

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-30

efforts—the Expedited, Non-Developmental Item (NDI) APS effort and the Modular Active Protection System (MAPS) effort. The Marines describe their...17 Modular Active Protection System (MAPS) Effort .......................................................... 18 The Marine Corps APS...Merkava Mark 4 tank was designed around the Trophy APS. 32 The Army’s Modular Active Protection System (MAPS) effort, described below, is intended to

Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly

PubMed Central

Hardies, Katia; May, Patrick; Djémié, Tania; Tarta-Arsene, Oana; Deconinck, Tine; Craiu, Dana; Helbig, Ingo; Suls, Arvid; Balling, Rudy; Weckhuysen, Sarah; De Jonghe, Peter; Hirst, Jennifer; Afawi, Zaid; Barisic, Nina; Baulac, Stéphanie; Caglayan, Hande; Depienne, Christel; De Kovel, Carolien G.F.; Dimova, Petia; Guerrero-López, Rosa; Guerrini, Renzo; Hjalgrim, Helle; Hoffman-Zacharska, Dorota; Jahn, Johanna; Klein, Karl Martin; Koeleman, Bobby P.C.; Leguern, Eric; Lehesjoki, Anna-Elina; Lemke, Johannes; Lerche, Holger; Marini, Carla; Muhle, Hiltrud; Rosenow, Felix; Serratosa, Jose M.; Møller, Rikke S.; Stephani, Ulrich; Striano, Pasquale; Talvik, Tiina; Von Spiczak, Sarah; Weber, Yvonne; Zara, Federico

2015-01-01

We report two siblings with infantile onset seizures, severe developmental delay and spastic paraplegia, in whom whole-genome sequencing revealed compound heterozygous mutations in the AP4S1 gene, encoding the σ subunit of the adaptor protein complex 4 (AP-4). The effect of the predicted loss-of-function variants (p.Gln46Profs*9 and p.Arg97*) was further investigated in a patient's fibroblast cell line. We show that the premature stop mutations in AP4S1 result in a reduction of all AP-4 subunits and loss of AP-4 complex assembly. Recruitment of the AP-4 accessory protein tepsin, to the membrane was also abolished. In retrospect, the clinical phenotype in the family is consistent with previous reports of the AP-4 deficiency syndrome. Our study reports the second family with mutations in AP4S1 and describes the first two patients with loss of AP4S1 and seizures. We further discuss seizure phenotypes in reported patients, highlighting that seizures are part of the clinical manifestation of the AP-4 deficiency syndrome. We also hypothesize that endosomal trafficking is a common theme between heritable spastic paraplegia and some inherited epilepsies. PMID:25552650

Sorting of Pmel17 to melanosomes through the plasma membrane by AP1 and AP2: evidence for the polarized nature of melanocytes

PubMed Central

Valencia, Julio C.; Watabe, Hidenori; Chi, An; Rouzaud, Francois; Chen, Kevin G.; Vieira, Wilfred D.; Takahashi, Kaoruko; Yamaguchi, Yuji; Berens, Werner; Nagashima, Kunio; Shabanowitz, Jeffrey; Hunt, Donald F.; Appella, Ettore; Hearing, Vincent J.

2015-01-01

Summary Adaptor proteins (AP) play important roles in the sorting of proteins from the trans-Golgi network, but how they function in the sorting of various melanosome-specific proteins such as Pmel17, an essential structural component of melanosomes, in melanocytes is unknown. We characterized the processing and trafficking of Pmel17 via adaptor protein complexes within melanocytic cells. Proteomics analysis detected Pmel17, AP1 and AP2, but not AP3 or AP4 in early melanosomes. Real-time PCR, immunolabeling and tissue in-situ hybridization confirmed the coexpression of AP1 isoforms μ1A and μ1B (expressed only in polarized cells) in melanocytes and keratinocytes, but expression of μ1B is missing in some melanoma cell lines. Transfection with AP1 isoforms (μ1A or μ1B) showed two distinct distribution patterns that involved Pmel17, and only μ1B was able to restore the sorting of Pmel17 to the plasma membrane in cells lacking μ1B expression. Finally, we established that expression of μ1B is regulated physiologically in melanocytes by UV radiation or DKK1. These results show that Pmel17 is sorted to melanosomes by various intracellular routes, directly or indirectly through the plasma membrane, and the presence of basolateral elements in melanocytes suggests their polarized nature. PMID:16492709

Neuronal Activity and the Expression of Clathrin Assembly Protein AP180

PubMed Central

Wu, Fangbai; Mattson, Mark P.; Yao, Pamela J.

2010-01-01

The clathrin assembly protein AP180 is known to promote the assembly of clathrin-coated vesicles in the neuron. However, it is unknown whether the expression of AP180 is influenced by neuronal activity. In this study, we report that chronic depolarization results in a reduction of AP180 from hippocampal neurons, while acute depolarization causes a dispersed synaptic distribution of AP180. Activity-induced effects are observed only for AP180, but not for the structurally-related clathrin assembly proteins CALM, epsin1, or HIP1. These findings suggest that AP180 levels and synaptic distribution are highly sensitive to neuronal activity. PMID:20937255

Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models

NASA Astrophysics Data System (ADS)

Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

2015-04-01

The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

Low Earth orbit assessment of proton anisotropy using AP8 and AP9 trapped proton models.

PubMed

Badavi, Francis F; Walker, Steven A; Santos Koos, Lindsey M

2015-04-01

The completion of the International Space Station (ISS) in 2011 has provided the space research community with an ideal evaluation and testing facility for future long duration human activities in space. Ionized and secondary neutral particles radiation measurements inside ISS form the ideal tool for validation of radiation environmental models, nuclear reaction cross sections and transport codes. Studies using thermo-luminescent detectors (TLD), tissue equivalent proportional counter (TPEC), and computer aided design (CAD) models of early ISS configurations confirmed that, as input, computational dosimetry at low Earth orbit (LEO) requires an environmental model with directional (anisotropic) capability to properly describe the exposure of trapped protons within ISS. At LEO, ISS encounters exposure from trapped electrons, protons and geomagnetically attenuated galactic cosmic rays (GCR). For short duration studies at LEO, one can ignore trapped electrons and ever present GCR exposure contributions during quiet times. However, within the trapped proton field, a challenge arises from properly estimating the amount of proton exposure acquired. There exist a number of models to define the intensity of trapped particles. Among the established trapped models are the historic AE8/AP8, dating back to the 1980s and the recently released AE9/AP9/SPM. Since at LEO electrons have minimal exposure contribution to ISS, this work ignores the AE8 and AE9 components of the models and couples a measurement derived anisotropic trapped proton formalism to omnidirectional output from the AP8 and AP9 models, allowing the assessment of the differences between the two proton models. The assessment is done at a target point within the ISS-11A configuration (circa 2003) crew quarter (CQ) of Russian Zvezda service module (SM), during its ascending and descending nodes passes through the south Atlantic anomaly (SAA). The anisotropic formalism incorporates the contributions of proton narrow

AccuNet/AP (Associated Press) Multimedia Archive

ERIC Educational Resources Information Center

Young, Terrence E., Jr.

2004-01-01

The AccuNet/AP Multimedia Archive is an electronic library containing the AP's current photos and a selection of pictures from their enormous print and negative library, as well as text and graphic material. It is composed of two photo databases as well as graphics, text, and audio databases. The features of this database are briefly described in…

LaAP2L1, a heterosis-associated AP2/EREBP transcription factor of Larix, increases organ size and final biomass by affecting cell proliferation in Arabidopsis.

PubMed

Li, Ai; Zhou, Yanan; Jin, Chuan; Song, Wenqin; Chen, Chengbin; Wang, Chunguo

2013-11-01

In Larix and in some crops, heterosis is prevalent and has been widely used in breeding to produce excellent varieties. However, the molecular basis of heterosis in Larix remains ambiguous. LaAP2L1, a member of the AP2/EREBP transcription factor family, has been suggested to be involved in heterosis in Larix hybrids. Here, the function and regulation of LaAP2L1 were further explored. Overexpression of LaAP2L1 led to markedly enlarged organs and heterosis-like traits in Arabidopsis. Fresh weight of leaves was almost twice as great as in vector controls. Likewise, seed yield of 35S::LaAP2L1 individual plants was >200% greater than that of control plants. The enlarged organs and heterosis-like traits displayed by 35S::LaAP2L1 plants were mainly due to enhanced cell proliferation and prolonged growth duration. At the molecular level, LaAP2L1 upregulated the expression of ANT, EBP1, and CycD3;1 and inhibited the expression of ARGOS in 35S::LaAP2L1 plants, suggesting an important molecular role of LaAP2L1 in regulating plant organ development. These findings provide new insights into the formation of heterosis in woody plants and suggest that LaAP2L1 has potential applications in breeding high-yielding crops and energy plants. In addition, 50 AP2/EREBP transcription factors, including LaAP2L1, in Larix were identified by transcriptome sequencing, and phylogenetic analysis was conducted. This provided information that will be important in further revealing the functions of these transcription factors.

The APS in Public Affairs

NASA Astrophysics Data System (ADS)

Lustig, Harry

2000-04-01

Although the American Physical Society was created for the interchange of scientific ideas, the call to the founding meeting included the observation that the organization "could not fail to have an important influence in all matters affecting the interest of physicists". However for most of its history APS did not behave like "just another interest group in American society". Instead, at the beginning, it limited itself to such successful initiatives as the creation of the Bureau of Standards and such unsuccessful ones as adoption of the metric system. After World War II, speaking out on behalf of the freedom of science and scientists, such as Astin, Condon, and Oppenheimer, became important. In the 1970's, pushed by members, the Society became more "political", sponsoring sessions and studies on defense issues, taking a stand for the Equal Rights Amendment and creating the Panel on Public Affairs and the Forum on Physics and Society. Only in the last fifteen years has the APS unabashedly lobbied for the economic interests of physics and physicists. Adopting this new, if unavoidable role may have unintended consequences for the willingness and effectiveness of APS in speaking out on other public issues.

Influence of diadenosine tetraphosphate (Ap4A) on lipid metabolism.

PubMed

Rüsing, D; Verspohl, E J

2004-01-01

Diadenosine polyphosphates (Ap(x)A) are physiologically released and may be partly involved in the pathogenesis of diabetes mellitus. Ap(4)A (diadenosine tetraphosphate) leads to an increase in blood glucose while it decreases insulin levels in plasma. A possible link between Ap(x)A and diabetes mellitus-associated diseases such as insulin resistance and hyperlipidemia (plasma free fatty acids, cholesterol and its biosynthesis, triacylglycerols) has not been investigated yet. Parameters such as free fatty acid and cholesterol content in blood were determined enzymically. The biosynthesis of cholesterol and triacylglycerols was determined in HepG2 cells using the radioactive precursor [(14)C]-acetate and by using gas chromatography. Plasma free fatty acids were significantly decreased 5 and 10 min after an Ap(4)A bolus (0.75 mg kg(-1) b.w.) given to rats. Plasma cholesterol was reduced 5 and 60 min after Ap(4)A administration. LPDS (lipoprotein-deficient serum)-stimulated cholesterol biosynthesis in HepG2 cells was significantly reduced after 1 h incubation with Ap(4)A. Triacylglycerol (TAG) biosynthesis in HepG2 cells was not significantly influenced by Ap(4)A; there was just a tendency for a concentration-dependent decrease in TAG levels. In conclusion Ap(4)A as a diabetogenetic compound is not likely to be responsible for the development of insulin resistance or of hyperlipidemia. Parameters such as free fatty acids, cholesterol and triacylglycerols are not elevated by Ap(4)A, but are even decreased. Ap(4)A seems to be involved in the development of diabetes mellitus by increasing blood glucose and decreasing plasma insulin as shown earlier, but not in diabetes mellitus-associated diseases such as insulin resistance or hyperlipidemia.

Final report for tank 241-AP-108, grab samples 8AP-96-1, 8AP-96-2 and 8AP-96-FB

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

Esch, R.A.

1996-04-19

This document is the final report deliverable for the tank 241-AP-108 grab samples. The samples were subsampled and analyzed in accordance with the TSAP. Included in this report are the results for the Waste Compatibility analyses, with the exception of DSC and thermogravimetric analysis (TGA) results which were presented in the 45 Day report (Part 2 of this document). The raw data for all analyses, with the exception of DSC and TGA, are also included in this report.

Predictive Validity Study of the APS Writing and Reading Tests [and] Validating Placement Rules for the APS Writing Test.

ERIC Educational Resources Information Center

College of the Canyons, Valencia, CA. Office of Institutional Development.

California's College of the Canyons has used the College Board Assessment and Placement Services (APS) test to assess students' abilities in basic and college English since spring 1993. These two reports summarize data from a May 1994 study of the predictive validity of the APS writing and reading tests and a June 1994 effort to validate the cut…

AP Physics 1 & 2; Some Things Old and Some Things New

NASA Astrophysics Data System (ADS)

Morse, Robert

2015-04-01

In fall September 2014, AP Physics 1 and AP Physics 2 replaced the AP Physics B curriculum, with the first exams in the new courses coming up in May 2015. In this talk I will give an overview of the history and rationale for the changes, describe the process of developing the new Curriculum Framework, discuss changes in emphasis compared to AP Physics B, including the emphasis on laboratory work. Finally, I will give examples of the difference in the style of the questions to be used in the new AP exams.

A CoAP-Based Network Access Authentication Service for Low-Power Wide Area Networks: LO-CoAP-EAP.

PubMed

Garcia-Carrillo, Dan; Marin-Lopez, Rafael; Kandasamy, Arunprabhu; Pelov, Alexander

2017-11-17

The Internet-of-Things (IoT) landscape is expanding with new radio technologies. In addition to the Low-Rate Wireless Personal Area Network (LR-WPAN), the recent set of technologies conforming the so-called Low-Power Wide Area Networks (LP-WAN) offers long-range communications, allowing one to send small pieces of information at a reduced energy cost, which promotes the creation of new IoT applications and services. However, LP-WAN technologies pose new challenges since they have strong limitations in the available bandwidth. In general, a first step prior to a smart object being able to gain access to the network is the process of network access authentication. It involves authentication, authorization and key management operations. This process is of vital importance for operators to control network resources. However, proposals for managing network access authentication in LP-WAN are tailored to the specifics of each technology, which could introduce interoperability problems in the future. In this sense, little effort has been put so far into providing a wireless-independent solution for network access authentication in the area of LP-WAN. To fill this gap, we propose a service named Low-Overhead CoAP-EAP (LO-CoAP-EAP), which is based on previous work designed for LR-WPAN. LO-CoAP-EAP integrates the use of Authentication, Authorization and Accounting (AAA) infrastructures and the Extensible Authentication Protocol (EAP) protocol. For this integration, we use the Constrained Application Protocol (CoAP) to design a network authentication service independent of the type of LP-WAN technology. LO-CoAP-EAP represents a trade-off between flexibility, wireless technology independence, scalability and performance in LP-WAN.

A CoAP-Based Network Access Authentication Service for Low-Power Wide Area Networks: LO-CoAP-EAP

PubMed Central

Garcia-Carrillo, Dan; Marin-Lopez, Rafael; Kandasamy, Arunprabhu; Pelov, Alexander

2017-01-01

The Internet-of-Things (IoT) landscape is expanding with new radio technologies. In addition to the Low-Rate Wireless Personal Area Network (LR-WPAN), the recent set of technologies conforming the so-called Low-Power Wide Area Networks (LP-WAN) offers long-range communications, allowing one to send small pieces of information at a reduced energy cost, which promotes the creation of new IoT applications and services. However, LP-WAN technologies pose new challenges since they have strong limitations in the available bandwidth. In general, a first step prior to a smart object being able to gain access to the network is the process of network access authentication. It involves authentication, authorization and key management operations. This process is of vital importance for operators to control network resources. However, proposals for managing network access authentication in LP-WAN are tailored to the specifics of each technology, which could introduce interoperability problems in the future. In this sense, little effort has been put so far into providing a wireless-independent solution for network access authentication in the area of LP-WAN. To fill this gap, we propose a service named Low-Overhead CoAP-EAP (LO-CoAP-EAP), which is based on previous work designed for LR-WPAN. LO-CoAP-EAP integrates the use of Authentication, Authorization and Accounting (AAA) infrastructures and the Extensible Authentication Protocol (EAP) protocol. For this integration, we use the Constrained Application Protocol (CoAP) to design a network authentication service independent of the type of LP-WAN technology. LO-CoAP-EAP represents a trade-off between flexibility, wireless technology independence, scalability and performance in LP-WAN. PMID:29149040

NECAPs are negative regulators of the AP2 clathrin adaptor complex

PubMed Central

Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J

2018-01-01

Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1, the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. PMID:29345618

The History of the APS Shock Compression of Condensed Matter Topical Group

NASA Astrophysics Data System (ADS)

Forbes, Jerry W.

2001-06-01

To provide broader scientific recognition and to advance the science of shock-compressed condensed matter, a group of APS members worked within the Society to make this technical field an active part of APS. Individual papers were given at APS meetings starting in the 1950’s and then later whole sessions were organized starting at the 1967 Pasadena meeting. Topical conferences began in 1979 in Pullman, WA where George Duvall and Dennis Hayes were co-chairs. Most all early topical conferences were sanctioned by the APS while those held after 1985 were official APS meetings. In 1984, after consulting with a number of people in the shock wave field, Robert Graham circulated a petition to form an APS topical group. He obtained signatures from a balanced cross-section of the community. William Havens, the executive secretary of APS, informed Robert Graham by letter on November 28, 1984 that the APS Council had officially accepted the formation of this topical group at its October 28, 1984 meeting. The first election occurred July 23, 1985 where Robert Graham was elected chairman, William Nellis vice-chairman, and Jerry Forbes secretary/treasurer. The topical group remains viable today by holding a topical conference in odd numbered years and shock wave sessions at APS general meetings in even numbered years A major benefit of being an official unit of APS is the allotment of APS fellows every year. The APS shock compression award established in 1987, has also provided broad recognition of many major scientific accomplishments in this field.

Estudio fenomenologico del conocimiento curricular y conocimiento de contenido en maestros de matematica a nivel secundario

NASA Astrophysics Data System (ADS)

Cardona Tomassini, Ivan Javier

ecuacion de la recta, las rectas verticales y horizontales y la solucion de ecuaciones cuadraticas. Lo cual permite concluir que los participantes demuestran mejor dominio del conocimiento procesal que del conocimiento conceptual. Estos es un reflejo del efecto de una instruccion enfocada en desarrollar los procesos algoritmicos ya que la explicacion con sentido de los procesos pasa a un segundo plano.

AP2 hemicomplexes contribute independently to synaptic vesicle endocytosis

PubMed Central

Gu, Mingyu; Liu, Qiang; Watanabe, Shigeki; Sun, Lin; Hollopeter, Gunther; Grant, Barth D; Jorgensen, Erik M

2013-01-01

The clathrin adaptor complex AP2 is thought to be an obligate heterotetramer. We identify null mutations in the α subunit of AP2 in the nematode Caenorhabditis elegans. α-adaptin mutants are viable and the remaining μ2/β hemicomplex retains some function. Conversely, in μ2 mutants, the alpha/sigma2 hemicomplex is localized and is partially functional. α-μ2 double mutants disrupt both halves of the complex and are lethal. The lethality can be rescued by expression of AP2 components in the skin, which allowed us to evaluate the requirement for AP2 subunits at synapses. Mutations in either α or μ2 subunits alone reduce the number of synaptic vesicles by about 30%; however, simultaneous loss of both α and μ2 subunits leads to a 70% reduction in synaptic vesicles and the presence of large vacuoles. These data suggest that AP2 may function as two partially independent hemicomplexes. DOI: http://dx.doi.org/10.7554/eLife.00190.001 PMID:23482940

Teaching Materials and Strategies for the AP Music Theory Exam

ERIC Educational Resources Information Center

Lively, Michael T.

2017-01-01

Each year, many students take the Advanced Placement (AP) Music Theory Exam, and the majority of these students enroll in specialized AP music theory classes as part of the preparation process. For the teachers of these AP music theory classes, a number of challenges are presented by the difficulty and complexity of the exam subject material as…

NECAPs are negative regulators of the AP2 clathrin adaptor complex.

PubMed

Beacham, Gwendolyn M; Partlow, Edward A; Lange, Jeffrey J; Hollopeter, Gunther

2018-01-18

Eukaryotic cells internalize transmembrane receptors via clathrin-mediated endocytosis, but it remains unclear how the machinery underpinning this process is regulated. We recently discovered that membrane-associated muniscin proteins such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor complex to an open, active conformation that is then phosphorylated (Hollopeter et al., 2014). Here we report that loss of ncap-1 , the sole C. elegans gene encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open, phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the closed, inactive conformation of AP2. Consistent with this model, NECAPs preferentially bind open and phosphorylated forms of AP2 in vitro and localize with constitutively open AP2 mutants in vivo. NECAPs do not associate with phosphorylation-defective AP2 mutants, implying that phosphorylation precedes NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate AP2. © 2018, Beacham et al.

Is the Shine off the A.P. Apple?

ERIC Educational Resources Information Center

Hurwitz, Nina; Hurwitz, Sol

2003-01-01

Describes challenges facing College Board's efforts to expand Advanced Placement (A.P.) courses to provide equal access to previously underserved low-performing urban and rural school students while maintaining the program's high academic standards. Includes list of strategies school boards can use to achieve greater access to A.P. courses while…

AP233: An Information Model for Systems Engineering

NASA Technical Reports Server (NTRS)

Siebes, Georg

2009-01-01

In today's world, information is abundant. We have no problems generating it. But we are challenged to find, organize, and exchange information. center dot A standardized model of information can help. Such a model nearly completed its development for Systems Engineering. It is referred to as AP233 (AP = Application Protocol).

The Role of AP and the Composition Program.

ERIC Educational Resources Information Center

Mahala, Daniel; Vivion, Michael

1993-01-01

Suggests that most programs have not based their acceptance of advanced placement credit on reasoned endorsement of the views of language, literature, and rhetoric that AP exams present. Criticizes the views implicit in the AP program and shows how they conflict with the goals of one particular college composition program. (RS)

Prevention of Breast Cell Transformation by Blockade of the AP-1 Transcription Factor

DTIC Science & Technology

2000-10-01

Distribution Unlimited 13. ABSTRACT (Maximum 200 Words) In this study, we are investigating the role of AP- M in controlling breast cell growth and...serum and these growth factors depend on AP-1 to transduce proliferative signal. AP- M blockade induced by the expression of TAM67 inhibits breast...demonstrated that TAM67 inhibits basal AP-1 activity and AP- M activity stimulated by several different growth factors. We have also discovered that AP-1

AP@home: a novel European approach to bring the artificial pancreas home.

PubMed

Heinemann, Lutz; Benesch, Carsten; DeVries, J Hans

2011-11-01

The development of an artificial pancreas (AP) made huge strides from 2006 to 2008 and a large number of activities are going on in this area of research. Until now, most AP systems under development were tested only under highly controlled conditions. The aim of our project, funded by the European Union, is to develop an AP system to such a level that it can be studied under daily life conditions at the home of patients with diabetes (hence AP@home). Based on a subcutaneous-subcutaneous closed-loop strategy (i.e., glucose sensing and insulin infusion in the subcutaneous tissue), two different approaches will be taken to achieve this aim: a two-port AP system and a single-port AP system. The two-port AP system will use off-the-shelf-components for the glucose sensor and insulin pump in combination with closed-loop algorithms generated in Europe. As to the single-port AP system, two different innovative single-port systems will be developed; in this case, continuous glucose monitoring and insulin infusion will take place via a single catheter. The first clinical trials with the two-port AP system under controlled clinical conditions have started and good progress has been made in the development of the single-port AP systems. We believe that our consortium of 12 European partners, which builds on existing achievements and close cooperation between academic centers and industry, can contribute substantially to the development of an AP system that can be used by patients in daily life. © 2011 Diabetes Technology Society.

Glossary for the implementation of Health in All Policies (HiAP).

PubMed

Freiler, Alix; Muntaner, Carles; Shankardass, Ketan; Mah, Catherine L; Molnar, Agnes; Renahy, Emilie; O'Campo, Patricia

2013-12-01

Health in All Policies (HiAP) is becoming increasingly popular as a governmental strategy to improve population health by coordinating action across health and non-health sectors. A variety of intersectoral initiatives may be used in HiAP that frame health determinants as the bridge between policies and health outcomes. The purpose of this glossary is to present concepts and terms useful in understanding the implementation of HiAP as a cross-sectoral policy. The concepts presented here were applied and elaborated over the course of case studies of HiAP in multiple jurisdictions, which used key informant interviews and the systematic review of literature to study the implementation of specific HiAP initiatives.

The APS SASE FEL : modeling and code comparison.

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

Biedron, S. G.

A self-amplified spontaneous emission (SASE) free-electron laser (FEL) is under construction at the Advanced Photon Source (APS). Five FEL simulation codes were used in the design phase: GENESIS, GINGER, MEDUSA, RON, and TDA3D. Initial comparisons between each of these independent formulations show good agreement for the parameters of the APS SASE FEL.

EPA’s AP-42 development methodology: Converting or rerating current AP-42 datasets

USDA-ARS?s Scientific Manuscript database

In August 2013, the U.S. Environmental Protection Agency’s (EPA) published their new methodology for updating the Compilation of Air Pollution Emission Factors (AP-42). The “Recommended Procedures for Development of Emissions Factors and Use of the WebFIRE Database” instructs that the ratings of the...

Investigación del USGS sobre el ecosistema de arrecifes de coral en el Atlántico

USGS Publications Warehouse

Kuffner, Ilsa B.; Yates, Kimberly K.; Zawada, David G.; Richey, Julie N.; Kellogg, Christina A.; Toth, Lauren T.; Torres-Garcia, Legna M.

2015-10-23

Los arrecifes de coral son estructuras sólidas, biomineralizadas que protegen comunidades costeras actuando como barreras protectoras de peligros tales como los huracanes y los tsunamis. Estos proveen arena a las playas a través de procesos naturales de erosión, fomentan la industria del turismo, las actividades recreacionales y proveen hábitats pesqueros esenciales. La conti-nua degradación mundial de ecosistemas de arrecifes de coral está bien documentada. Existe la necesidad de enfoque y organización de la ciencia para entender los procesos complejos físicos y biológicos e interacciones que están afectando el estado de los arrecifes coralinos y su capacidad para responder a un entorno cambiante.

AP1000{sup R} licensing and deployment in the United States

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

Jordan, R. P.; Russ, P. A.; Filiak, P. P.

2012-07-01

In recent years, both domestic and foreign utilities have turned to the standardized Westinghouse AP1000 plant design in satisfying their near - and long-term - sustainable energy needs. As direct support to these actions, licensing the AP1000 design has played a significant role by providing one of the fundamental bases in clearing regulatory hurdles leading to the start of new plant construction. Within the U.S. alone, Westinghouse AP1000 licensing activities have reached unprecedented milestones with the approvals of both AP1000 Design Certification and Southern Company's combined construction permit and operating license (COL) application directly supporting the construction of two newmore » nuclear plants in Georgia. Further COL application approvals are immediately pending for an additional two AP1000 plants in South Carolina. And, across the U.S. nuclear industry spectrum, there are 10 other COL applications under regulatory review representing some 16 new plants at 10 sites. In total, these actions represent the first wave of new plant licensing under the regulatory approval process since 1978. Fundamental to the Nuclear Regulatory Commission's AP1000 Design Certification is the formal recognition of the AP1000 passive safety design through regulatory acceptance rulemaking. Through recognition and deployment of the AP1000 Design Certification, the utility licensee / operator of this reactor design are now offered an opportunity to use a simplified 'one-step' combined license process, thereby managing substantial back-end construction schedule risk from regulatory and intervention delays. Application of this regulatory philosophy represents both acceptance and encouragement of standardized reactor designs like the AP1000. With the recent AP1000 Design Certification and utility COL acceptances, the fundamental licensing processes of this philosophy have successfully proven the attainment of significant milestones with the next stage licensing actions

A seven-year northern sky survey of Ap stars for rapid variability

NASA Technical Reports Server (NTRS)

Nelson, Matthew J.; Kreidl, Tobias J.

1993-01-01

A high-speed photometric survey of 120 Ap stars in the northern sky, has been conducted, between 1985 and 1991, in order to search for rapid variability. Stars of spectral types, namely from B8 to F4, have been selected for the survey. The selected pulsational variable stars occupy the hotter regions of the instability strip of the Hertzsprung-Russel diagram. Noted is the absence of pulsations in the hotter B8-A3 Ap stars; this does not, however, preclude the existence of pulsations, since HD 218495 was recently discovered to be a rapidly oscillating Ap (roAp) star. The primary result of this study is that various combinations of photometric indices, while pointing towards roAp stars having the characteristic signatures of cool, SrCrEu stars, still fail to isolate the roAp phenomenon from similar nonpulsating Ap stars. Color-magnitude and color-color diagrams are presented in order to complete this survey.

SEPTUM MAGNET DESIGN FOR THE APS-U

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

Abliz, M.; Jaski, M.; Xiao, A.

2017-06-25

The Advanced Photon Source is in the process of upgrading its storage ring from a double-bend to a multi-bend lattice as part of the APS Upgrade Project (APS-U). A swap-out injection scheme is planned for the APS-U to keep a constant beam current and to enable a small dynamic aperture. A septum magnet with a minimum thickness of 2 mm and an injection field of 1.06 T has been designed, delivering the required total deflecting angle is 89 mrad with a ring energy of 6 GeV. The stored beam chamber has an 8 mm x 6 mm super-ellipsoidal aperture. Themore » magnet is straight; however, it is tilted in yaw, roll, and pitch from the stored beam chamber to meet the on axis swap out injection requirements for the APS-U lattice. In order to minimize the leakage field inside the stored beam chamber, four different techniques were utilized in the design. As a result, the horizontal deflecting angle of the stored beam was held to only 5 µrad, and the integrated skew quadrupole inside the stored beam chamber was held to 0.09 T. The detailed techniques that were applied to the design, field multipoles, and resulting trajectories of the injected and stored beams are reported.« less

Radioactive air emissions notice of construction for installation and operation of a waste retrieval system and tanks 241-AP-102 and 241-AP-104 project

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

DEXTER, M.L.

1999-11-15

This document serves as a notice of construction (NOC) pursuant to the requirements of Washington Administrative Code (WAC) 246 247-060, and as a request for approval to modify pursuant to 40 Code of Federal Regulations (CFR) 61 07 for the installation and operation of one waste retrieval system in the 24 1 AP-102 Tank and one waste retrieval system in the 241 AP 104 Tank Pursuant to 40 CFR 61 09 (a)( 1) this application is also intended to provide anticipated initial start up notification Its is requested that EPA approval of this application will also constitute EPA acceptance ofmore » the initial start up notification Project W 211 Initial Tank Retrieval Systems (ITRS) is scoped to install a waste retrieval system in the following double-shell tanks 241-AP 102-AP 104 AN 102, AN 103, AN-104, AN 105, AY 102 AZ 102 and SY-102 between now and the year 2011. Because of the extended installation schedules and unknowns about specific activities/designs at each tank, it was decided to submit NOCs as that information became available This NOC covers the installation and operation of a waste retrieval system in tanks 241 AP-102 and 241 AP 104 Generally this includes removal of existing equipment installation of new equipment and construction of new ancillary equipment and buildings Tanks 241 AP 102 and 241 AP 104 will provide waste feed for immobilization into a low activity waste (LAW) product (i.e. glass logs) The total effective dose equivalent (TEDE) to the offsite maximally exposed individual (MEI) from the construction activities is 0 045 millirem per year The unabated TEDE to the offsite ME1 from operation of the mixer pumps is 0 042 millirem per year.« less

AP-2α and AP-2β cooperatively orchestrate homeobox gene expression during branchial arch patterning.

PubMed

Van Otterloo, Eric; Li, Hong; Jones, Kenneth L; Williams, Trevor

2018-01-25

The evolution of a hinged moveable jaw with variable morphology is considered a major factor behind the successful expansion of the vertebrates. DLX homeobox transcription factors are crucial for establishing the positional code that patterns the mandible, maxilla and intervening hinge domain, but how the genes encoding these proteins are regulated remains unclear. Herein, we demonstrate that the concerted action of the AP-2α and AP-2β transcription factors within the mouse neural crest is essential for jaw patterning. In the absence of these two proteins, the hinge domain is lost and there are alterations in the size and patterning of the jaws correlating with dysregulation of homeobox gene expression, with reduced levels of Emx, Msx and Dlx paralogs accompanied by an expansion of Six1 expression. Moreover, detailed analysis of morphological features and gene expression changes indicate significant overlap with various compound Dlx gene mutants. Together, these findings reveal that the AP-2 genes have a major function in mammalian neural crest development, influencing patterning of the craniofacial skeleton via the DLX code, an effect that has implications for vertebrate facial evolution, as well as for human craniofacial disorders. © 2018. Published by The Company of Biologists Ltd.

Advancing beyond AP Courses

ERIC Educational Resources Information Center

Hammond, Bruce G.

2009-01-01

A quiet revolution is picking up steam in the nation's private secondary schools, with broad implications for college admissions and for teaching and learning on both sides of the transition from high school to college. About 50 of the nation's leading college-preparatory schools have opted out of the College Board's Advanced Placement (AP)…

An improved model for the combustion of AP composite propellants

NASA Technical Reports Server (NTRS)

Cohen, N. S.; Strand, L. D.

1981-01-01

This paper presents several improvements to the BDP model of steady-state burning of AP composite solid propellants. The Price-Boggs-Derr model of AP monopropellant burning is incorporated to represent the AP. A separate energy equation is written for the binder to permit a different surface temperature from the AP; this includes an analysis of the sharing of primary diffusion flame energy, and correction of a BDP model inconsistency in treating the binder regression rate. A method for assembling component contributions to calculate the burning rates of multimodal propellants is also presented. Results are shown in the form of representative burning rate curves, comparisons with data, and calculated internal details of interest. Ideas for future work are discussed in an Appendix.

NOS1 mediates AP1 nuclear translocation and inflammatory response.

PubMed

Srivastava, Mansi; Baig, Mirza S

2018-06-01

A hallmark of the AP1 functioning is its nuclear translocation, which induces proinflammatory cytokine expression and hence the inflammatory response. After endotoxin shock AP1 transcription factor, which comprises Jun, ATF2, and Fos family of proteins, translocates into the nucleus and induces proinflammatory cytokine expression. In the current study, we found, NOS1 inhibition prevents nuclear translocation of the AP1 transcription factor subunits. Pharmacological inhibition of NOS1 impedes translocation of subunits into the nucleus, suppressing the transcription of inflammatory genes causing a diminished inflammatory response. In conclusion, the study shows the novel mechanism of NOS1- mediated AP1 nuclear translocation, which needs to be further explored. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Incorporating Ninth-Grade PSAT/NMSQT® Scores into AP Potential™ Predictions for AP® European History and AP World History. Statistical Report 2014-1

ERIC Educational Resources Information Center

Zhang, Xiuyuan; Patel, Priyank; Ewing, Maureen

2015-01-01

Historically, AP Potential™ correlations and expectancy tables have been based on 10th-and 11th-grade PSAT/NMSQT® examinees and 11th-and 12th-grade AP® examinees for all subjects (Zhang, Patel, & Ewing,2014; Ewing, Camara, & Millsap, 2006; Camara & Millsap, 1998). However, a large number of students take AP European History and AP…

Isolation and characterization of diadenosine tetraphosphate (Ap4A) hydrolase from Schizosaccharomyces pombe.

PubMed

Robinson, A K; de la Peña, C E; Barnes, L D

1993-02-13

An enzyme that catalyzes the asymmetric hydrolysis of Ap4A has been partially purified from the fission yeast, Schizosaccharomyces pombe. The crude supernatant fraction from log-phase cells was fractionated by (NH4)2SO4 precipitation followed by chromatography on DEAE-cellulose, Red A dye-ligand and QAE-Sepharose resins. Two peaks of Ap4A hydrolase activity, designated major and minor, were separated on the Red A dye-ligand resin. Both the major and minor Ap4A hydrolase have an apparent molecular mass of 49 kDa based on gel filtration chromatography. On a SDS polyacrylamide gel, a protein of 22 kDa exhibited Ap4A hydrolase activity. Both forms of the enzyme have a Km value in the range of 22 to 36 microM for Ap4A. Both forms of the enzyme asymmetrically hydrolyze Ap4A to AMP and ATP as determined by HPLC. Ap4A is the optimal substrate among several nucleotides and dinucleoside polyphosphates tested at 10 microM. A divalent metal cation is required for activity. Concentrations of Pi below 30 mM stimulate Ap4A hydrolase while higher concentrations inhibit the activity. Pi is not a substrate for this Ap4A-degradative enzyme. Fluoride, from 50 microM to 20 mM, has no significant effect on Ap4A hydrolase activity.

AP: A Critical Examination of the Advanced Placement Program

ERIC Educational Resources Information Center

Sadler, Philip M.; Sonnert, Gerhard; Tai, Robert; Klopfenstein, Kirstin

2016-01-01

The Advanced Placement (AP) program was created to enhance the experience of gifted students as they transition from high school to college. "AP: A Critical Examination of the Advanced Placement Program," edited by Philip M. Sadler, Gerhard Sonnert, Robert Tai, and Kirstin Klopfenstein (2010, Harvard Education Press), questions the…

AP Studio Art as an Enabling Constraint for Secondary Art Education

ERIC Educational Resources Information Center

Graham, Mark A.

2009-01-01

Advanced Placement (AP) Studio Art is an influential force in secondary art education as is evident in the 31,800 portfolios submitted for review in 2008. From the perspectives of a high school educator and AP Reader, this author has observed how the constraints of the AP program can be used to generate support for high school art programs and…

MULTI-OBJECTIVE ONLINE OPTIMIZATION OF BEAM LIFETIME AT APS

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

Sun, Yipeng

In this paper, online optimization of beam lifetime at the APS (Advanced Photon Source) storage ring is presented. A general genetic algorithm (GA) is developed and employed for some online optimizations in the APS storage ring. Sextupole magnets in 40 sectors of the APS storage ring are employed as variables for the online nonlinear beam dynamics optimization. The algorithm employs several optimization objectives and is designed to run with topup mode or beam current decay mode. Up to 50\\% improvement of beam lifetime is demonstrated, without affecting the transverse beam sizes and other relevant parameters. In some cases, the top-upmore » injection efficiency is also improved.« less

Shuttle APS propellant thermal conditioner study

NASA Technical Reports Server (NTRS)

Pearson, W. E.

1971-01-01

A study program was performed to allow selection of thermal conditioner assemblies for superheating O2 and H2 at supercritical pressures. The application was the auxiliary propulsion system (APS) for the space shuttle vehicle. The O2/H2 APS propellant feed system included propellant conditioners, of which the thermal conditioner assemblies were a part. Cryogens, pumped to pressures above critical, were directed to the thermal conditioner assembly included: (1) a gas generator assembly with ignition system and bipropellant valves, which burned superheated O2 and H2 at rich conditions; (2) a heat exchanger assembly for thermal conditioning of the cryogenic propellant; and (3) a dump nozzle for heat exchanger exhaust.

HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2

PubMed Central

Lubben, Nienke B.; Sahlender, Daniela A.; Motley, Alison M.; Lehner, Paul J.; Benaroch, Philippe

2007-01-01

Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin acidic cluster sorting protein (PACS) 1, adaptor protein (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, in which Nef uses AP-1 to direct MHC-I to endosomes and lysosomes. Here, we show that knocking down either AP-1 or clathrin with small interfering RNA inhibits the down-regulation of HLA-A2 (an MHC-I isotype) by Nef in HeLa cells. However, knocking down PACS-1 has no effect, not only on Nef-induced down-regulation of HLA-A2 but also on the localization of other proteins containing acidic cluster motifs. Surprisingly, knocking down AP-2 actually enhances Nef activity. Immuno-electron microscopy labeling of Nef-expressing cells indicates that HLA-A2 is rerouted not to the TGN, but to endosomes. In AP-2–depleted cells, more of the HLA-A2 localizes to the inner vesicles of multivesicular bodies. We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment. PMID:17581864

The History of the APS Topical Group on Shock Compression of Condensed Matter

NASA Astrophysics Data System (ADS)

Forbes, Jerry W.

2002-07-01

In order to provide broader scientific recognition and to advance the science of shock compressed condensed matter, a group of American Physical Society (APS) members worked within the Society to make this field an active part of the APS. Individual papers were presented at APS meetings starting in the 1940's and shock wave sessions were organized starting with the 1967 Pasadena meeting. Shock wave topical conferences began in 1979 in Pullman, WA. Signatures were obtained on a petition in 1984 from a balanced cross-section of the shock wave community to form an APS Topical Group (TG). The APS Council officially accepted the formation of the Shock Compression of Condensed Matter (SCCM) TG at its October 1984 meeting. This action firmly aligned the shock wave field with a major physical science organization. Most early topical conferences were sanctioned by the APS while those held after 1992 were official APS meetings. The topical group organizes a shock wave topical conference in odd numbered years while participating in shock wave/high pressure sessions at APS general meetings in even numbered years.

Diadenosine tetraphosphate (Ap4A) - an E. coli alarmone or a damage metabolite?

PubMed

Despotović, Dragana; Brandis, Alexander; Savidor, Alon; Levin, Yishai; Fumagalli, Laura; Tawfik, Dan S

2017-07-01

Under stress, metabolism is changing: specific up- or down-regulation of proteins and metabolites occurs as well as side effects. Distinguishing specific stress-signaling metabolites (alarmones) from side products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate (Ap4A) - a side product of aminoacyl-tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in Escherichia coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown. We defined a set of criteria for distinguishing alarmones from damage metabolites to systematically classify Ap4A. In a nutshell, no indications for a signaling cascade that is triggered by Ap4A were found; rather, we found that Ap4A is efficiently removed in a constitutive, nonregulated manner. Several fold perturbations in Ap4A concentrations have no effect, yet accumulation at very high levels is toxic due to disturbance of zinc homeostasis, and also because Ap4A's structural overlap with ATP can result in spurious binding and inactivation of ATP-binding proteins. Overall, Ap4A met all criteria for a damage metabolite. While we do not exclude any role in signaling, our results indicate that the damage metabolite option should be considered as the null hypothesis when examining Ap4A and other metabolites whose levels change upon stress. © 2017 Federation of European Biochemical Societies.

Raising Rigor, Getting Results: Lessons Learned from AP Expansion

ERIC Educational Resources Information Center

Wakelyn, David

2009-01-01

Advanced Placement (AP), which enables high school students to take introductory college-level courses, is the nation's oldest example of a rigorous, common curriculum. Students who score well on AP exams are more likely to persist in college and earn a degree. The Advanced Placement Expansion project of the National Governors Association Center…

Data-Based Decision Making: The Road to AP Equity

ERIC Educational Resources Information Center

Edwards, Kelcey; Duggan, Odette

2012-01-01

Presented at the Advanced Placement Annual Conference (APAC) in Lake Buena Vista, FL in July 2012. This presentation reviews concepts central to achieving equitable AP access and success for all willing and academically prepared students. We analyze trends in participation and performance by race/ethnicity from the AP Report to the Nation and…

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

PubMed Central

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-01-01

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis. Images PMID:1408831

The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

PubMed

Diccianni, M B; Imagawa, M; Muramatsu, M

1992-10-11

Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A.

PubMed

Baker, Matthew D; Holloway, Daniel E; Swaminathan, G Jawahar; Acharya, K Ravi

2006-01-17

Eosinophil-derived neurotoxin (EDN) is a catalytically proficient member of the pancreatic ribonuclease superfamily secreted along with other eosinophil granule proteins during innate host defense responses and various eosinophil-related inflammatory and allergic diseases. The ribonucleolytic activity of EDN is central to its antiviral and neurotoxic activities and possibly to other facets of its biological activity. To probe the importance of this enzymatic activity further, specific inhibitors will be of great aid. Derivatives of 5'-ADP are among the most potent inhibitors currently known. Here, we use X-ray crystallography to investigate the binding of four natural nucleotides containing this moiety. 5'-ATP binds in two alternative orientations, one occupying the B2 subsite in a conventional manner and one being a retro orientation with no ordered adenosine moiety. Diadenosine triphosphate (Ap3A) and diadenosine tetraphosphate (Ap4A) bind with one adenine positioned at the B2 subsite, the polyphosphate chain extending across the P1 subsite in an ill-defined conformation, and a disordered second adenosine moiety. Diadenosine pentaphosphate (Ap5A), the most avid inhibitor of this series, binds in a completely ordered fashion with one adenine positioned conventionally at the B2 subsite, the polyphosphate chain occupying the P1 and putative P(-1) subsites, and the other adenine bound in a retro-like manner at the edge of the B1 subsite. The binding mode of each of these inhibitors has features seen in previously determined structures of adenosine diphosphates. We examine the structure-affinity relationships of these inhibitors and discuss the implications for the design of improved inhibitors.

Modeling Instruction in AP Physics C: Mechanics and Electricity and Magnetism

NASA Astrophysics Data System (ADS)

Belcher, Nathan Tillman

This action research study used data from multiple assessments in Mechanics and Electricity and Magnetism to determine the viability of Modeling Instruction as a pedagogy for students in AP Physics C: Mechanics and Electricity and Magnetism. Modeling Instruction is a guided-inquiry approach to teaching science in which students progress through the Modeling Cycle to develop a fully-constructed model for a scientific concept. AP Physics C: Mechanics and Electricity and Magnetism are calculus-based physics courses, approximately equivalent to first-year calculus-based physics courses at the collegiate level. Using a one-group pretest-posttest design, students were assessed in Mechanics using the Force Concept Inventory, Mechanics Baseline Test, and 2015 AP Physics C: Mechanics Practice Exam. With the same design, students were assessed in Electricity and Magnetism on the Brief Electricity and Magnetism Assessment, Electricity and Magnetism Conceptual Assessment, and 2015 AP Physics C: Electricity and Magnetism Practice Exam. In a one-shot case study design, student scores were collected from the 2017 AP Physics C: Mechanics and Electricity and Magnetism Exams. Students performed moderately well on the assessments in Mechanics and Electricity and Magnetism, demonstrating that Modeling Instruction is a viable pedagogy in AP Physics C: Electricity and Magnetism.

The Role of the Clathrin Adaptor AP-1: Polarized Sorting and Beyond

PubMed Central

Nakatsu, Fubito; Hase, Koji; Ohno, Hiroshi

2014-01-01

The selective transport of proteins or lipids by vesicular transport is a fundamental process supporting cellular physiology. The budding process involves cargo sorting and vesicle formation at the donor membrane and constitutes an important process in vesicular transport. This process is particularly important for the polarized sorting in epithelial cells, in which the cargo molecules need to be selectively sorted and transported to two distinct destinations, the apical or basolateral plasma membrane. Adaptor protein (AP)-1, a member of the AP complex family, which includes the ubiquitously expressed AP-1A and the epithelium-specific AP-1B, regulates polarized sorting at the trans-Golgi network and/or at the recycling endosomes. A growing body of evidence, especially from studies using model organisms and animals, demonstrates that the AP-1-mediated polarized sorting supports the development and physiology of multi-cellular units as functional organs and tissues (e.g., cell fate determination, inflammation and gut immune homeostasis). Furthermore, a possible involvement of AP-1B in the pathogenesis of human diseases, such as Crohn’s disease and cancer, is now becoming evident. These data highlight the significant contribution of AP-1 complexes to the physiology of multicellular organisms, as master regulators of polarized sorting in epithelial cells. PMID:25387275

Molecular Basis for Enhancement of the Meiotic DMCI Recombinase by RAD51AP1

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

Dray, Eloise; Dunlop, Myun Hwa; Kauppi, Liisa

Homologous recombination is needed for meiotic chromosome segregation, genome maintenance, and tumor suppression. RAD51AP1 (RAD51 Associated Protein 1) has been shown to interact with and enhance the recombinase activity of RAD51. Accordingly, genetic ablation of RAD51AP1 leads to enhanced sensitivity to and also chromosome aberrations upon DNA damage, demonstrating a role for RAD51AP1 in mitotic homologous recombination. Here we show physical association of RAD51AP1 with the meiosis-specific recombinase DMC1 and a stimulatory effect of RAD51AP1 on the DMC1-mediated D-loop reaction. Mechanistic studies have revealed that RAD51AP1 enhances the ability of the DMC1 presynaptic filament to capture the duplex DNA partnermore » and to assemble the synaptic complex, in which the recombining DNA strands are homologously aligned. We also provide evidence that functional co-operation is dependent on complex formation between DMC1 and RAD51AP1, and that distinct epitopes in RAD51AP1 mediate interactions with RAD51 and DMC1. Finally, we show that RAD51AP1 is expressed in mouse testes, and that RAD51AP1 foci co-localize with a subset of DMC1 foci in spermatocytes. These results suggest that RAD51AP1 also serves an important role in meiotic homologous recombination.« less

Implementation and Initial Validation of the APS English Test [and] The APS English-Writing Test at Golden West College: Evidence for Predictive Validity.

ERIC Educational Resources Information Center

Isonio, Steven

In May 1991, Golden West College (California) conducted a validation study of the English portion of the Assessment and Placement Services for Community Colleges (APS), followed by a predictive validity study in July 1991. The initial study was designed to aid in the implementation of the new test at GWC by comparing data on APS use at other…

BLOC-2, AP-3, and AP-1 Proteins Function in Concert with Rab38 and Rab32 Proteins to Mediate Protein Trafficking to Lysosome-related Organelles*

PubMed Central

Bultema, Jarred J.; Ambrosio, Andrea L.; Burek, Carolyn L.; Di Pietro, Santiago M.

2012-01-01

Lysosome-related organelles (LROs) are synthesized in specialized cell types where they largely coexist with conventional lysosomes. Most of the known cellular transport machinery involved in biogenesis are ubiquitously expressed and shared between lysosomes and LROs. Examples of common components are the adaptor protein complex-3 (AP-3) and biogenesis of lysosome-related organelle complex (BLOC)-2. These protein complexes control sorting and transport of newly synthesized integral membrane proteins from early endosomes to both lysosomes and LROs such as the melanosome. However, it is unknown what factors cooperate with the ubiquitous transport machinery to mediate transport to LROs in specialized cells. Focusing on the melanosome, we show that the ubiquitous machinery interacts with cell type-specific Rab proteins, Rab38 and Rab32, to facilitate transport to the maturing organelle. BLOC-2, AP-3, and AP-1 coimmunoprecipitated with Rab38 and Rab32 from MNT-1 melanocytic cell extracts. BLOC-2, AP-3, AP-1, and clathrin partially colocalized with Rab38 and Rab32 by confocal immunofluorescence microscopy in MNT-1 cells. Rab38- and Rab32-deficient MNT-1 cells displayed abnormal trafficking and steady state levels of known cargoes of the BLOC-2, AP-3, and AP-1 pathways, the melanin-synthesizing enzymes tyrosinase and tyrosinase-related protein-1. These observations support the idea that Rab38 and Rab32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs. Additionally, analysis of tyrosinase-related protein-2 and total melanin production indicates that Rab32 has unique functions that cannot be carried out by Rab38 in melanosome biogenesis. PMID:22511774

BLOC-2, AP-3, and AP-1 proteins function in concert with Rab38 and Rab32 proteins to mediate protein trafficking to lysosome-related organelles.

PubMed

Bultema, Jarred J; Ambrosio, Andrea L; Burek, Carolyn L; Di Pietro, Santiago M

2012-06-01

Lysosome-related organelles (LROs) are synthesized in specialized cell types where they largely coexist with conventional lysosomes. Most of the known cellular transport machinery involved in biogenesis are ubiquitously expressed and shared between lysosomes and LROs. Examples of common components are the adaptor protein complex-3 (AP-3) and biogenesis of lysosome-related organelle complex (BLOC)-2. These protein complexes control sorting and transport of newly synthesized integral membrane proteins from early endosomes to both lysosomes and LROs such as the melanosome. However, it is unknown what factors cooperate with the ubiquitous transport machinery to mediate transport to LROs in specialized cells. Focusing on the melanosome, we show that the ubiquitous machinery interacts with cell type-specific Rab proteins, Rab38 and Rab32, to facilitate transport to the maturing organelle. BLOC-2, AP-3, and AP-1 coimmunoprecipitated with Rab38 and Rab32 from MNT-1 melanocytic cell extracts. BLOC-2, AP-3, AP-1, and clathrin partially colocalized with Rab38 and Rab32 by confocal immunofluorescence microscopy in MNT-1 cells. Rab38- and Rab32-deficient MNT-1 cells displayed abnormal trafficking and steady state levels of known cargoes of the BLOC-2, AP-3, and AP-1 pathways, the melanin-synthesizing enzymes tyrosinase and tyrosinase-related protein-1. These observations support the idea that Rab38 and Rab32 are the specific factors that direct the ubiquitous machinery to mediate transport from early endosomes to maturing LROs. Additionally, analysis of tyrosinase-related protein-2 and total melanin production indicates that Rab32 has unique functions that cannot be carried out by Rab38 in melanosome biogenesis.

AP-102/104 Retrieval control system qualification test procedure

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

RIECK, C.A.

1999-05-18

This Qualification Test Procedure documents the results of the qualification testing that was performed on the Project W-211, ''Initial Tank Retrieval Systems,'' retrieval control system (RCS) for tanks 241-AP-102 and 241-AP-104. The results confirm that the RCS has been programmed correctly and that the two related hardware enclosures have been assembled in accordance with the design documents.

Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.

PubMed

Eriksson, Daniel; Dalin, Frida; Eriksson, Gabriel Nordling; Landegren, Nils; Bianchi, Matteo; Hallgren, Åsa; Dahlqvist, Per; Wahlberg, Jeanette; Ekwall, Olov; Winqvist, Ola; Catrina, Sergiu-Bogdan; Rönnelid, Johan; Hulting, Anna-Lena; Lindblad-Toh, Kerstin; Alimohammadi, Mohammad; Husebye, Eystein S; Knappskog, Per Morten; Rosengren Pielberg, Gerli; Bensing, Sophie; Kämpe, Olle

2018-01-01

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1. To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease. We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE. In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure. We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications. Copyright © 2017 Endocrine Society

Building Reading, Writing and Analysis in the AP U.S. History Classroom

ERIC Educational Resources Information Center

Heller, Stephen; Stacy, Jason

2013-01-01

The building of historical thinking skills has historically been a lonely endeavor for AP U.S. history teachers. Many often generate their own pedagogy, perhaps modified from an AP workshop or generally gleaned from released exam essay questions. However, as currently scheduled, in 2014, the AP U.S. history exam will undergo a redesign that will…

A New Photometric Study of Ap and Am Stars in the Infrared

NASA Astrophysics Data System (ADS)

Chen, P. S.; Liu, J. Y.; Shan, H. G.

2017-05-01

In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer (WISE), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1-3 μm region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free-free emissions. It is also shown that in the 3-12 μm region, the majority of Ap stars and Am stars have very similar behavior, I.e., in the W1-W2 (3.4-4.6 μm) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W2-W3 (4.6-12 μm) region they have no or little infrared excess. In addition, in the 12-22 μm region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free-free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.

Uso Del Condón en Adolescentes Nahuas, un Modelo Explicativo.

PubMed

Tirado, María de Los Ángeles Meneses; Benavides-Torres, Raquel A; Navarro, Sergio Meneses; de la Colina, Juan Antonio Doncel; Rodríguez, Dora Julia Onofre; Hernández, Francisco Javier Baéz

2018-03-01

En México, la población indígena supera los siete millones de habitantes, en Puebla el grupo más representativo es el Náhuatl. Sin embargo, las condiciones de vida, salud, educación y transporte son precarias para esta población. En los adolescentes, las responsabilidades como el matrimonio, la familia y los compromisos ante la comunidad, favorecen conductas de riesgo sexual que dificultan su desarrollo económico, social y reproductivo. El objetivo fue proponer un modelo explicativo del uso del condón en adolescentes nahuas. Método. Bajo el marco de la teoría social cognitiva, el concepto de valores culturales de Leininger y el proceso de la sustracción teórica, se desarrolló este artículo. Se muestran las relaciones del modelo con las proposiciones y los factores que influyen en el uso del condón para este grupo específico. Finalmente, el modelo explica las variables de interés, los niveles de abstracción y las relaciones entre sí en el contexto náhuatl. El siguiente paso será implementar los indicadores empíricos para conocer el grado de influencia de los factores personales y ambientales hacia el uso del condón en adolescentes nahuas. Resultados que aportarán información para el desarrollo del conocimiento en enfermería y la reducción de riesgo sexual de esta población.

Glaucoma patients present increased levels of diadenosine tetraphosphate, Ap(4)A, in the aqueous humour.

PubMed

Castany, Marta; Jordi, Isabel; Catala, Jaume; Gual, Arcadi; Morales, Miguel; Gasull, Xavier; Pintor, Jesus

2011-03-01

Previous studies have shown the presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in the aqueous humour (AH) of different species. When topically applied to the rabbit cornea, Ap(4)A decreased IOP while Ap(5)A increased it. Here we study the presence of dinucleoside polyphosphates in the AH from human patients with or without glaucoma. AH was obtained at the time of cataract surgery from patients with (n=16) or without (n=10) primary open-angle glaucoma. AH (0.1-0.2 ml) was collected at the beginning of surgery through a corneal paracentesis and immediately cooled in liquid nitrogen, kept frozen and protected from light. AH aliquots were analyzed by HPLC for the presence of Ap(4)A and Ap(5)A. Both, Ap(4)A and Ap(5)A were detected in the AH of both experimental groups. No significant differences were found for Ap(5)A. In contrast, Ap(4)A levels were increased by ∼15-fold in the AH from glaucomatous eyes ranging from 19.5±9.2 nM in normal individuals to 286.03±30.9 nM in glaucomatous patients. In conclusion, both Ap(4)A and Ap(5)A were detected for the first time in human AH. Interestingly, glaucomatous eyes presented elevated concentrations of Ap(4)A compared to controls. The role of Ap(4)A needs to be elucidated but it may help to protect the autonomic innervation in the ciliary body/trabecular meshwork. Also, because of its higher levels in glaucoma patients it may be considered as a possible glaucoma biomarker. Copyright © 2010 Elsevier Ltd. All rights reserved.

X-ray optics simulation and beamline design for the APS upgrade

NASA Astrophysics Data System (ADS)

Shi, Xianbo; Reininger, Ruben; Harder, Ross; Haeffner, Dean

2017-08-01

The upgrade of the Advanced Photon Source (APS) to a Multi-Bend Achromat (MBA) will increase the brightness of the APS by between two and three orders of magnitude. The APS upgrade (APS-U) project includes a list of feature beamlines that will take full advantage of the new machine. Many of the existing beamlines will be also upgraded to profit from this significant machine enhancement. Optics simulations are essential in the design and optimization of these new and existing beamlines. In this contribution, the simulation tools used and developed at APS, ranging from analytical to numerical methods, are summarized. Three general optical layouts are compared in terms of their coherence control and focusing capabilities. The concept of zoom optics, where two sets of focusing elements (e.g., CRLs and KB mirrors) are used to provide variable beam sizes at a fixed focal plane, is optimized analytically. The effects of figure errors on the vertical spot size and on the local coherence along the vertical direction of the optimized design are investigated.

Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations.

PubMed

Vahlensieck, U; Bokník, P; Gombosová, I; Huke, S; Knapp, J; Linck, B; Lüss, H; Müller, F U; Neumann, J; Deng, M C; Scheld, H H; Jankowski, H; Schlüter, H; Zidek, W; Zimmermann, N; Schmitz, W

1999-02-01

Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.

Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination

PubMed Central

Mortensen, Franziska; Schneider, Daniel; Barbic, Tanja; Sladewska-Marquardt, Anna; Kühnle, Simone; Marx, Andreas; Scheffner, Martin

2015-01-01

Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein. PMID:26216987

Aerosol-delivered programmed cell death 4 enhanced apoptosis, controlled cell cycle and suppressed AP-1 activity in the lungs of AP-1 luciferase reporter mice.

PubMed

Hwang, S-K; Jin, H; Kwon, J T; Chang, S-H; Kim, T H; Cho, C-S; Lee, K H; Young, M R; Colburn, N H; Beck, G R; Yang, H-S; Cho, M-H

2007-09-01

The long-term survival of lung cancer patients treated with conventional therapies remains poor and therefore the need for novel approaches remains high. This has led to the re-emergence of aerosol delivery as a therapeutic intervention. In this study, glucosylated polyethylenimine (GPEI) was used as carrier to investigate programmed cell death 4 (PDCD4) and PDCD4 mutant (D418A), an eIF4A-binding mutant, on PDCD4-related signaling and activator protein-1 (AP-1) activity in the lungs of AP-1 luciferase reporter mice. After confirming the efficiency of GPEI as a carrier in lungs, the effects of aerosol-delivered PDCD4 were investigated in AP-1 luciferase reporter mice. Aerosol delivery of GPEI/PDCD4 through a nose-only inhalation facilitated the apoptosis of lungs whereas aerosol PDCD4 mutant did not. Also, such aerosol delivery regulated proteins relevant to cell-cycle control and suppressed AP-1 activity. Results obtained by western blot analysis, immunohistochemistry, luciferase assay and deoxynucleotidyl-transferase-mediated nick end labeling study suggest that combined actions such as facilitating apoptosis, controlling cell cycle and suppression of AP-1 activity by PDCD4 may provide useful tool for designing lung tumor prevention and treatment by which PDCD4 functions as a transformation suppressor in the future.

APS-U LATTICE DESIGN FOR OFF-AXIS ACCUMULATION

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

Sun, Yipeng; Borland, M.; Lindberg, R.

2017-06-25

A 67-pm hybrid-seven-bend achromat (H7BA) lattice is being proposed for a future Advanced Photon Source (APS) multi-bend-achromat (MBA) upgrade project. This lattice design pushes for smaller emittance and requires use of a swap-out (on-axis) injection scheme due to limited dynamic acceptance. Alternate lattice design work has also been performed for the APS upgrade to achieve better beam dynamics performance than the nominal APS MBA lattice, in order to allow off-axis accumulation. Two such alternate H7BA lattice designs, which target a still-low emittance of 90 pm, are discussed in detail in this paper. Although the single-particle-dynamics performance is good, simulations ofmore » collective effects indicate that surprising difficulty would be expected accumulating high single-bunch charge in this lattice. The brightness of the 90-pm lattice is also a factor of two lower than the 67-pm H7BA lattice.« less

A paradoxical increase of a metabolite upon increased expression of its catabolic enzyme: the case of diadenosine tetraphosphate (Ap4A) and Ap4A phosphorylase I in Saccharomyces cerevisiae.

PubMed Central

Avila, D M; Robinson, A K; Kaushal, V; Barnes, L D

1991-01-01

The APA1 gene in Saccharomyces cerevisiae encodes Ap4A phosphorylase I, the catabolic enzyme for diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A). APA1 has been inserted into a multicopy plasmid and into a centromeric plasmid with a GAL1 promoter. Enhanced expression of APA1 via the plasmids resulted in 10- and 90-fold increases in Ap4A phosphorylase activity, respectively, as assayed in vitro. However, the intracellular concentration of Ap4A exhibited increases of 2- and 15-fold, respectively, from the two different plasmids. Intracellular Ap4A increased 3- to 20-fold during growth on galactose of a transformant with APA1 under the control of the GAL1 promoter. Intracellular adenosine 5'-P1-tetraphospho-P4-5"'-guanosine (Ap4G) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G) also increased in the transformant under these conditions. The chromosomal locus of APA1 has been disrupted in a haploid strain. The Ap4A phosphorylase activity decreased by 80% and the intracellular Ap4A concentration increased by a factor of five in the null mutant. These results with the null mutant agree with previous results reported by Plateau et al. (P. Plateau, M. Fromant, J.-M. Schmitter, J.-M. Buhler, and S. Blancquet, J. Bacteriol. 171:6437-6445, 1989). The paradoxical increase in Ap4A upon enhanced expression of APA1 indicates that the metabolic consequences of altered gene expression may be more complex than indicated solely by assay of enzymatic activity of the gene product. PMID:1660456

A paradoxical increase of a metabolite upon increased expression of its catabolic enzyme: the case of diadenosine tetraphosphate (Ap4A) and Ap4A phosphorylase I in Saccharomyces cerevisiae.

PubMed

Avila, D M; Robinson, A K; Kaushal, V; Barnes, L D

1991-12-01

The APA1 gene in Saccharomyces cerevisiae encodes Ap4A phosphorylase I, the catabolic enzyme for diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A). APA1 has been inserted into a multicopy plasmid and into a centromeric plasmid with a GAL1 promoter. Enhanced expression of APA1 via the plasmids resulted in 10- and 90-fold increases in Ap4A phosphorylase activity, respectively, as assayed in vitro. However, the intracellular concentration of Ap4A exhibited increases of 2- and 15-fold, respectively, from the two different plasmids. Intracellular Ap4A increased 3- to 20-fold during growth on galactose of a transformant with APA1 under the control of the GAL1 promoter. Intracellular adenosine 5'-P1-tetraphospho-P4-5"'-guanosine (Ap4G) and diguanosine 5',5"'-P1,P4-tetraphosphate (Gp4G) also increased in the transformant under these conditions. The chromosomal locus of APA1 has been disrupted in a haploid strain. The Ap4A phosphorylase activity decreased by 80% and the intracellular Ap4A concentration increased by a factor of five in the null mutant. These results with the null mutant agree with previous results reported by Plateau et al. (P. Plateau, M. Fromant, J.-M. Schmitter, J.-M. Buhler, and S. Blancquet, J. Bacteriol. 171:6437-6445, 1989). The paradoxical increase in Ap4A upon enhanced expression of APA1 indicates that the metabolic consequences of altered gene expression may be more complex than indicated solely by assay of enzymatic activity of the gene product.

Clinical application of diadenosine tetraphosphate (Ap4A:F-1500) for controlled hypotension.

PubMed

Kikuta, Y; Ohiwa, E; Okada, K; Watanabe, A; Haruki, S

1999-01-01

In our animal study, it was revealed that diadenosine tetraphosphate (Ap4A:F-1500) has a dose-dependent hypotension effect of up to 60% decrease in mean arterial pressure compared to control value. Furthermore, in healthy male volunteers, the safety of Ap4A up to 4 mg.min-1 was confirmed. In patients who require surgical procedures under general anesthesia together with controlled hypotension, hypotension was induced by Ap4A in order to examine its hypotensive effect and modulating action on the blood pressure. Ten patients who required controlled hypotension and who were scheduled for elective surgery under general anesthesia were studied. Anesthesia was maintained with isoflurane (n = 7) or sevoflurane (n = 3) in oxygen-nitrous oxide. Controlled hypotension was induced by Ap4A administered at a rate of 10-20 micrograms.kg-1.min-1. The dose was adjusted at a maximum rate of 80 micrograms.kg-1.min-1 until the target blood pressure was achieved. Arterial blood pressure and heart rate were monitored. Arterial samples were drawn at 4 separate time points to measure the concentration of Ap4A in the plasma. The time required for attaining the target blood pressure after initiation of Ap4A infusion was about 16 min, and the time lapse between withdrawal of infusion to recovery of blood pressure was about 18 min. No reflex tachycardia was observed during infusion of Ap4A and no rebound hypertension was evident after withdrawal. The plasma Ap4A concentration increased in response to the acceleration rate of Ap4A administration with a tendency of augmented hypotensive effect. As it produces an excellent hypotensive effect together with a modulating action on blood pressure, Ap4A was assessed as useful in producing controlled hypotension.

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-30

safe enough for operational use, the benefits of MAPS relative to non-developmental efforts, MAPS’ impacts on NDI APS performance and costs, the Army’s...APSs Effective and Safe Enough for Operational Use? .............................. 24 What are the Benefits of MAPS Relative to Non-Developmental...corrosion—which will also factor into their eventual APS plans. Potential issues for Congress include whether current NDI APSs are effective and

Health in All Policies (HiAP) governance: lessons from network governance.

PubMed

Khayatzadeh-Mahani, Akram; Ruckert, Arne; Labonté, Ronald; Kenis, Patrick; Akbari-Javar, Mohammad Reza

2018-05-25

The Health in All Policies (HiAP) approach requires formal and sustained governance structures and mechanisms to ensure that the policies of various non-health sectors maximize positive and minimize negative impacts on population health. In this paper, we demonstrate the usefulness of a network perspective in understanding and contributing to the effectiveness of HiAP. We undertook an exploratory, qualitative case study of a HiAP structure in Iran, the Kerman province Council of Health and Food Security (CHFS) with diverse members from health and non-health sectors. We analyzed relevant policy texts and interviewed 32 policy actors involved in the CHFS. Data were analyzed using within-case analysis and constant comparative methodology. Our findings suggest that CHFS governance from a network perspective drew in practice on elements of two competing network governance modes: the network administrative organization (NAO) and the lead organization mode. Our results also show that a shift from a hierarchical and market-based mode of interaction to a network logic within CHFS has not yet taken place. In addition, CHFS suffers from large membership and an inability to address complex 'wicked problems', as well as low trust, legitimacy and goal consensus among its members. Drawing on other HiAP studies and commentaries, insights from organization network theory, and in-depth findings from our case study, we conclude that a NAO may be the most effective mode of governance for tackling complex social problems in HiAP structures. Since similar studies are limited, and our single case study may not be transferable across all contexts, we suggest that further research be undertaken to explore HiAP structures from a network perspective in different institutional and cultural settings. With increasing emphasis given to HiAP approaches in national and international health policy discourse, it is important that comparative knowledge about the effectiveness of HiAP governance

Pentoxifylline Treatment in Acute Pancreatitis (AP)

ClinicalTrials.gov

2018-02-21

Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

A New Photometric Study of Ap and Am Stars in the Infrared

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

Chen, P. S.; Liu, J. Y.; Shan, H. G., E-mail: chenps@ynao.ac.cn

In this paper, 426 well known confirmed Ap and Am stars are photometrically studied in the infrared. The 2MASS, Wide-field Infrared Survey Explorer ( WISE ), and IRAS data are employed to make analyses. The results in this paper have shown that in the 1–3 μ m region over 90% Ap and Am stars have no or little infrared excesses, and infrared radiations in the near-infrared from these stars are probably dominated by the free–free emissions. It is also shown that in the 3–12 μ m region, the majority of Ap stars and Am stars have very similar behavior, i.e.,more » in the W 1– W 2 (3.4–4.6 μ m) region, over half of Ap and Am stars have clear infrared excesses, which are possibly due to the binarity, the multiplicity, and/or the debris disk, but in the W 2– W 3 (4.6–12 μ m) region they have no or little infrared excess. In addition, in the 12–22 μ m region, some of Ap stars and Am stars show the infrared excesses and infrared radiations for these Ap and Am stars are probably due to the free–free emissions. In addition, it is seen that the probability of being the binarity, the multiplicity and/or the debris disk for Am stars is much higher than that for Ap stars. Furthermore, it can be seen that, in general, no relations can be found between infrared colors and spectral types either for Ap stars or for Am stars.« less

AE8/AP8 Implementations in AE9/AP9, IRBEM, and SPENVIS

DTIC Science & Technology

2014-02-18

period applies to orbit generation only; AE8/AP8 utilizes geomagnetic field models from other epochs as specified in the table below.) SHIELDOSE2 model...finite and semi- infinite slab data tables for Bremsstrahlung have been reversed [Heynderickx, private communication, May 2013]. This correction is...Cain, J. C., S. J. Hendricks, R. A. Langel, and W. V. Hudson (1967), A proposed model for the international geomagnetic reference field, 1965, J

Functional Analysis of AP-2 α and μ2 Subunits

PubMed Central

Motley, Alison M.; Berg, Nicola; Taylor, Marcus J.; Sahlender, Daniela A.; Hirst, Jennifer; Owen, David J.

2006-01-01

The AP-2 adaptor complex plays a key role in cargo recognition and clathrin-coated vesicle formation at the plasma membrane. To investigate the functions of individual binding sites and domains of the AP-2 complex in vivo, we have stably transfected HeLa cells with wild-type and mutant small interfering RNA–resistant α and μ2 subunits and then used siRNA knockdowns to deplete the endogenous proteins. Mutating the PtdIns(4,5)P2 binding site of α, the phosphorylation site of μ2, or the YXXΦ binding site of μ2 impairs AP-2 function, as assayed by transferrin uptake. In contrast, removing the C-terminal appendage domain of α, or mutating the PtdIns(4,5)P2 binding site of μ2, has no apparent effect. However, adding a C-terminal GFP tag to α renders it completely nonfunctional. These findings demonstrate that there is some functional redundancy in the binding sites of the various AP-2 subunits, because no single mutation totally abolishes function. They also help to explain why GFP-tagged AP-2 never appears to leave the plasma membrane in some live cell imaging studies. Finally, they establish a new model system that can be used both for additional structure-function analyses, and as a way of testing tagged constructs for function in vivo. PMID:17035630

Army and Marine Corps Active Protection System (APS) Efforts

DTIC Science & Technology

2016-08-23

with hard or soft kill capabilities to a variety of threats, including rocket -propelled grenades (RPGs) and anti-tank guided missiles (ATGMs). APS...of threats, including rocket -propelled grenades (RPGs) and anti-tank guided missiles (ATGMs). APS technologies are not new, and a number of nations...training. 1 RPGs are basically single man-portable, shoulder-fired, unguided rockets . RPGs have been widely proliferated but can be mitigated to a

ION EFFECTS IN THE APS PARTICLE ACCUMULATOR RING

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

Calvey, J.; Harkay, K.; Yao, CY.

2017-06-25

Trapped ions in the APS Particle Accumulator Ring (PAR) lead to a positive coherent tune shift in both planes, which increases along the PAR cycle as more ions accumulate. This effect has been studied using an ion simulation code developed at SLAC. After modifying the code to include a realistic vacuum profile, multiple ionization, and the effect of shaking the beam to measure the tune, the simulation agrees well with our measurements. This code has also been used to evaluate the possibility of ion instabilities at the high bunch charge needed for the APS-Upgrade.

Coaching in the AP Classroom

ERIC Educational Resources Information Center

Fornaciari, Jim

2013-01-01

Many parallels exist between quality coaches and quality classroom teachers--especially AP teachers, who often feel the pressure to produce positive test results. Having developed a series of techniques and strategies for building a team-oriented winning culture on the field, Jim Fornaciari writes about how he adapted those methods to work in the…

Molecular dynamics simulations of AP/HMX composite with a modified force field.

PubMed

Zhu, Wei; Wang, Xijun; Xiao, Jijun; Zhu, Weihua; Sun, Huai; Xiao, Heming

2009-08-15

An all-atom force field for ammonium perchlorate (AP) is developed with the framework of pcff force field. The structural parameters of AP obtained with the modified force field are in good agreement with experimental values. Molecular dynamics (MD) simulations have been performed to investigate AP/HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane) composite at different temperatures. The binding energies, thermal expansion coefficient, and the trigger bond lengths of HMX in the AP/HMX composite have been obtained. The binding energies of the system increase slightly with temperature increasing, peak at 245K, and then gradually decrease. The volume thermal expansion coefficient of the AP/HMX composite has been derived from the volume variation with temperature. As the temperature rises, the maximal lengths of the trigger bond N-NO(2) of HMX increase gradually. The simulated results indicate that the maximal length of trigger bond can be used as a criterion for judging the sensitivity of energetic composite.

Ten Things to Consider When Teaching AP U.S. History

ERIC Educational Resources Information Center

Libresco, Andrea S.

2013-01-01

This article describes 10 recommendations for creativity, higher-order thinking, and meaningful learning activities that can be used to guide teachers in constructing an engaging AP course: (1) Be on the committee that decides how students will be selected for AP; (2) Maximize time and connections through blocks of time with an English colleague;…

APS Goes to ComicCon and Other Tales: Reaching out for Physics

NASA Astrophysics Data System (ADS)

Kirby, Kate

2012-10-01

Broadly interpreting the core mission of APS ``to advance and diffuse the knowledge of physics", APS carries out programmatic activities in Education, Outreach, International Affairs, Public Affairs, and Advocacy, which benefit the physics community as well as society at large. These programs are highly valued by APS members who know about them, but the challenge has been to find ways to effectively communicate to our members about all the good things we are doing. APS programs have also achieved significant recognition in the external community for their outstanding quality and success. I will describe several examples of how we ``reach out" to promote physics and physics education in a variety of venues.

AP Geography, Environmental Science Thrive

ERIC Educational Resources Information Center

Robelen, Erik W.

2012-01-01

Geography may not be particularly known as a hot topic among today's students--even some advocates suggest it suffers from an image problem--but by at least one measure, the subject is starting to come into its own. Across more than 30 topics covered in the Advanced Placement (AP) program, participation in geography is rising faster than any…

Synthesis and binding properties of new selective ligands for the nucleobase opposite the AP site.

PubMed

Abe, Yukiko; Nakagawa, Osamu; Yamaguchi, Rie; Sasaki, Shigeki

2012-06-01

DNA is continuously damaged by endogenous and exogenous factors such as oxidative stress or DNA alkylating agents. These damaged nucleobases are removed by DNA N-glycosylase and form apurinic/apyrimidinic sites (AP sites) as intermediates in the base excision repair (BER) pathway. AP sites are also representative DNA damages formed by spontaneous hydrolysis. The AP sites block DNA polymerase and a mismatch nucleobase is inserted opposite the AP sites by polymerization to cause acute toxicities and mutations. Thus, AP site specific compounds have attracted much attention for therapeutic and diagnostic purposes. In this study, we have developed nucleobase-polyamine conjugates as the AP site binding ligand by expecting that the nucleobase part would play a role in the specific recognition of the nucleobase opposite the AP site by the Watson-Crick base pair formation and that the polyamine part should contribute to the access of the ligand to the AP site by a non-specific interaction to the DNA phosphate backbone. The nucleobase conjugated with 3,3'-diaminodipropylamine (A-ligand, G-ligand, C-ligand, T-ligand and U-ligand) showed a specific stabilization of the duplex containing the AP site depending on the complementary combination with the nucleobase opposite the AP site; that is A-ligand to T, G-ligand to C, C-ligand to G, T- and U-ligand to A. The thermodynamic binding parameters clearly indicated that the specific stabilization is due to specific binding of the ligands to the complementary AP site. These results have suggested that the complementary base pairs of the Watson-Crick type are formed at the AP site. Copyright © 2012 Elsevier Ltd. All rights reserved.

The adipocyte fatty acid–binding protein aP2 is required in allergic airway inflammation

PubMed Central

Shum, Bennett O.V.; Mackay, Charles R.; Gorgun, Cem Z.; Frost, Melinda J.; Kumar, Rakesh K.; Hotamisligil, Gökhan S.; Rolph, Michael S.

2006-01-01

The adipocyte fatty acid–binding protein aP2 regulates systemic glucose and lipid metabolism. We report that aP2, in addition to being abundantly expressed by adipocytes, is also expressed by human airway epithelial cells and shows a striking upregulation following stimulation of epithelial cells with the Th2 cytokines IL-4 and IL-13. Regulation of aP2 mRNA expression by Th2 cytokines was highly dependent on STAT6, a transcription factor with a major regulatory role in allergic inflammation. We examined aP2-deficient mice in a model of allergic airway inflammation and found that infiltration of leukocytes, especially eosinophils, into the airways was highly dependent on aP2 function. T cell priming was unaffected by aP2 deficiency, suggesting that aP2 was acting locally within the lung, and analysis of bone marrow chimeras implicated non-hematopoietic cells, most likely bronchial epithelial cells, as the site of action of aP2 in allergic airway inflammation. Thus, aP2 regulates allergic airway inflammation and may provide a link between fatty acid metabolism and asthma. PMID:16841093

SARS coronavirus protein 7a interacts with human Ap4A-hydrolase.

PubMed

Vasilenko, Natalia; Moshynskyy, Igor; Zakhartchouk, Alexander

2010-02-09

The SARS coronavirus (SARS-CoV) open reading frame 7a (ORF 7a) encodes a 122 amino acid accessory protein. It has no significant sequence homology with any other known proteins. The 7a protein is present in the virus particle and has been shown to interact with several host proteins; thereby implicating it as being involved in several pathogenic processes including apoptosis, inhibition of cellular protein synthesis, and activation of p38 mitogen activated protein kinase. In this study we present data demonstrating that the SARS-CoV 7a protein interacts with human Ap4A-hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17). Ap4A-hydrolase is responsible for metabolizing the "allarmone" nucleotide Ap4A and therefore likely involved in regulation of cell proliferation, DNA replication, RNA processing, apoptosis and DNA repair. The interaction between 7a and Ap4A-hydrolase was identified using yeast two-hybrid screening. The interaction was confirmed by co-immunoprecipitation from cultured human cells transiently expressing V5-His tagged 7a and HA tagged Ap4A-hydrolase. Human tissue culture cells transiently expressing 7a and Ap4A-hydrolase tagged with EGFP and Ds-Red2 respectively show these proteins co-localize in the cytoplasm.

The 8th Annual AP[R] Report to the Nation

ERIC Educational Resources Information Center

College Board, 2012

2012-01-01

In classrooms around the country, AP (Advanced Placement) teachers are preparing students for tomorrow by teaching them how to think and learn today. AP students learn to construct solid arguments, test theories, and see many sides of an issue--the kind of thinking that solves tough problems both in and outside the classroom, in college and…

Expansion and stress responses of the AP2/EREBP superfamily in cotton.

PubMed

Liu, Chunxiao; Zhang, Tianzhen

2017-01-31

The allotetraploid cotton originated from one hybridization event between an extant progenitor of Gosssypium herbaceum (A 1 ) or G. arboreum (A 2 ) and another progenitor, G. raimondii Ulbrich (D 5 ) 1-1.5 million years ago (Mya). The APETALA2/ethylene-responsive element binding protein (AP2/EREBP) transcription factors constitute one of the largest and most conserved gene families in plants. They are characterized by their AP2 domain, which comprises 60-70 amino acids, and are classified into four main subfamilies: the APETALA2 (AP2), Related to ABI3/VP1 (RAV), Dehydration-Responsive Element Binding protein (DREB) and Ethylene-Responsive Factor (ERF) subfamilies. The AP2/EREBP genes play crucial roles in plant growth, development and biotic and abiotic stress responses. Hence, understanding the molecular characteristics of cotton stress tolerance and gene family expansion would undoubtedly facilitate cotton resistance breeding and evolution research. A total of 269 AP2/EREBP genes were identified in the G. raimondii (D5) cotton genome. The protein domain architecture and intron/exon structure are simple and relatively conserved within each subfamily. They are distributed throughout all chromosomes but are clustered on various chromosomes due to genomic tandem duplication. We identified 73 tandem duplicated genes and 221 segmental duplicated gene pairs which contributed to the expansion of AP2/EREBP superfamily. Of them, tandem duplication was the most important force of the expansion of the B3 group. Transcriptome analysis showed that 504 AP2/EREBP genes were expressed in at least one tested G. hirsutum TM-1 tissues. In G. hirsutum, 151 non-repeated genes of the DREB and ERF subfamily genes were responsive to different stresses: 132 genes were induced by cold, 63 genes by drought and 94 genes by heat. qRT-PCR confirmed that 13 GhDREB and 15 GhERF genes were induced by cold and/or drought. No transcripts detected for 53 of the 111 tandem duplicated genes in TM-1

Amphioxus and lamprey AP-2 genes: implications for neural crest evolution and migration patterns

NASA Technical Reports Server (NTRS)

Meulemans, Daniel; Bronner-Fraser, Marianne

2002-01-01

The neural crest is a uniquely vertebrate cell type present in the most basal vertebrates, but not in cephalochordates. We have studied differences in regulation of the neural crest marker AP-2 across two evolutionary transitions: invertebrate to vertebrate, and agnathan to gnathostome. Isolation and comparison of amphioxus, lamprey and axolotl AP-2 reveals its extensive expansion in the vertebrate dorsal neural tube and pharyngeal arches, implying co-option of AP-2 genes by neural crest cells early in vertebrate evolution. Expression in non-neural ectoderm is a conserved feature in amphioxus and vertebrates, suggesting an ancient role for AP-2 genes in this tissue. There is also common expression in subsets of ventrolateral neurons in the anterior neural tube, consistent with a primitive role in brain development. Comparison of AP-2 expression in axolotl and lamprey suggests an elaboration of cranial neural crest patterning in gnathostomes. However, migration of AP-2-expressing neural crest cells medial to the pharyngeal arch mesoderm appears to be a primitive feature retained in all vertebrates. Because AP-2 has essential roles in cranial neural crest differentiation and proliferation, the co-option of AP-2 by neural crest cells in the vertebrate lineage was a potentially crucial event in vertebrate evolution.

CLEARING MAGNET DESIGN FOR APS-U

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

Abliz, M.; Grimmer, J.; Jaski, Y.

2017-06-25

The Advanced Photon Source is in the process of developing an upgrade (APS-U) of the storage ring. The upgrade will be converting the current double bend achromat (DBA) lattice to a multi-bend achromat (MBA) lattice. In addition, the storage ring will be operated at 6 GeV and 200 mA with regular swap-out injection to keep the stored beam current constant [1]. The swap-out injection will take place with beamline shutters open. For radiation safety to ensure that no electrons can exit the storage ring, a passive method of protecting the beamline and containing the electrons inside the storage ring ismore » proposed. A clearing magnet will be located in all beamline front ends inside the storage ring tunnel. This article will discuss the features and design of the clearing magnet scheme for APS-U.« less

Magnetic Doppler imaging of Ap stars

NASA Astrophysics Data System (ADS)

Silvester, J.; Wade, G. A.; Kochukhov, O.; Landstreet, J. D.; Bagnulo, S.

2008-04-01

Historically, the magnetic field geometries of the chemically peculiar Ap stars were modelled in the context of a simple dipole field. However, with the acquisition of increasingly sophisticated diagnostic data, it has become clear that the large-scale field topologies exhibit important departures from this simple model. Recently, new high-resolution circular and linear polarisation spectroscopy has even hinted at the presence of strong, small-scale field structures, which were completely unexpected based on earlier modelling. This project investigates the detailed structure of these strong fossil magnetic fields, in particular the large-scale field geometry, as well as small scale magnetic structures, by mapping the magnetic and chemical surface structure of a selected sample of Ap stars. These maps will be used to investigate the relationship between the local field vector and local surface chemistry, looking for the influence the field may have on the various chemical transport mechanisms (i.e., diffusion, convection and mass loss). This will lead to better constraints on the origin and evolution, as well as refining the magnetic field model for Ap stars. Mapping will be performed using high resolution and signal-to-noise ratio time-series of spectra in both circular and linear polarisation obtained using the new-generation ESPaDOnS (CFHT, Mauna Kea, Hawaii) and NARVAL spectropolarimeters (Pic du Midi Observatory). With these data we will perform tomographic inversion of Doppler-broadened Stokes IQUV Zeeman profiles of a large variety of spectral lines using the INVERS10 magnetic Doppler imaging code, simultaneously recovering the detailed surface maps of the vector magnetic field and chemical abundances.

Sesión clínica de los NIH de tumores del estroma gastrointestinal (TEGI) infantiles y de tipo natural | Center for Cancer Research

Cancer.gov

Fecha de la sesión: Del 20 al 22 de junio de 2018 Esta solicitud es el primero de un proceso de varios pasos para considerar su participación en nuestra próxima sesión clínica de TEGI infantiles y de tipo natural. Por favor, lea las tres páginas y responda completamente todas las preguntas:

Los plaguicidas y la contaminacion del medio ambiente Venezolano

USGS Publications Warehouse

Stickel, L.F.; Stickel, W.H.

1972-01-01

RESUMEN DE RECOMENDACIONES Recomendaciones para el Programa de Investigacion: 1. Establecer un sistema de muestreo biologico para detectar los niveles tendencias de los productos quimicos toxicos en un peque?o numero de si tios representativos. 2. Mantener continua vigilancia de la contaminacion ambiental, mediante la seleccion acertadamente dirigida de las zonas afectadas y de las fuentes de contaminacion. 3. Realizar estudios acerca de las poblaciones de animales silvestres, y del exito de los procesos reproductivos de las especies o grupos clayes de animales que se consideran mas gravemente afectados. 4. Preparar recomendaciones para una accion gubernamental de proteccion al hombre, a la fauna silvestre y al medio ambiente. Recomendaciones para la Accion Administrativa: 1. Establecer limites a la tolerancia de los residuos de plaguicidas en los alimentos. Constituye una medida clave para disminuir la contaminacion ambiental. 2. Establecer normas de calidad del agua para las corrientes, represas, la gos y otros cuerpos. Es la segunda medida clave para reducir la contaminacion del ambiente 3. Exigir un tratamiento adecuado de los efluentes industriales, especialmente antes de que se construyan las nuevas plantas. 4. Exigir a los agricultores que en el uso de plaguicidas sigan los consejos tecnicos autorizados y negar a los vendedores el derecho a recomendar productos por su cuenta. 5. Tomar medidas para recoger y eliminar los recipientes y sobrantes de los plaguicidas.

[Cloning, subcellular localization, and heterologous expression of ApNAC1 gene from Andrographis paniculata].

PubMed

Wang, Jian; Qi, Meng-Die; Guo, Juan; Shen, Ye; Lin, Hui-Xin; Huang, Lu-Qi

2017-03-01

Andrographis paniculata is widely used as medicinal herb in China for a long time and andrographolide is its main medicinal constituent. To investigate the underlying andrographolide biosynthesis mechanisms, RNA-seq for A. paniculata leaves with MeJA treatment was performed. In A. paniculata transcriptomic data, the expression pattern of one member of NAC transcription factor family (ApNAC1) matched with andrographolide accumulation. The coding sequence of ApNAC1 was cloned by RT-PCR, and GenBank accession number was KY196416. The analysis of bioinformatics showed that the gene encodes a peptide of 323 amino acids, with a predicted relative molecular weight of 35.9 kDa and isoelectric point of 6.14. To confirm the subcellular localization, ApNAC1-GFP was transiently expressed in A. paniculata protoplast. The results indicated that ApNAC1 is a nucleus-localized protein. The analysis of real-time quantitative PCR revealed that ApNAC1 gene predominantly expresses in leaves. Compared with control sample, its expression abundance sharply increased with methyl jasmonate treatment. Based on its expression pattern, ApNAC1 gene might involve in andrographolide biosynthesis. ApNAC1 was heterologously expressed in Escherichia coli and recombinant protein was purified by Ni-NTA agarose. Further study will help us to understand the function of ApNAC1 in andrographolide biosynthesis. Copyright© by the Chinese Pharmaceutical Association.

IKKα contributes to UVB-induced VEGF expression by regulating AP-1 transactivation

PubMed Central

Dong, Wen; Li, Yi; Gao, Ming; Hu, Meiru; Li, Xiaoguang; Mai, Sanyue; Guo, Ning; Yuan, Shengtao; Song, Lun

2012-01-01

Exposure to ultraviolet B (UVB) irradiation from sunlight induces the upregulation of VEGF, a potent angiogenic factor that is critical for mediating angiogenesis-associated photodamage. However, the molecular mechanisms related to UVB-induced VEGF expression have not been fully defined. Here, we demonstrate that one of the catalytic subunits of the IκB kinase complex (IKK), IKKα, plays a critical role in mediating UVB-induced VEGF expression in mouse embryonic fibroblasts (MEFs), which requires IKKα kinase activity but is independent of IKKβ, IKKγ and the transactivation of NF-κB. We further show that the transcriptional factor AP-1 functions as the downstream target of IKKα that is responsible for VEGF induction under UVB exposure. Both the accumulation of AP-1 component, c-Fos and the transactivation of AP-1 by UVB require the activated IKKα located within the nucleus. Moreover, nuclear IKKα can associate with c-Fos and recruit to the vegf promoter regions containing AP-1-responsive element and then trigger phosphorylation of the promoter-bound histone H3. Thus, our results have revealed a novel independent role for IKKα in controlling VEGF expression during the cellular UVB response by regulating the induction of the AP-1 component and phosphorylating histone H3 to facilitate AP-1 transactivation. Targeting IKKα shows promise for the prevention of UVB-induced angiogenesis and the associated photodamage. PMID:22169952

Magnetic Measurements of Storage Ring Magnets for the APS Upgrade Project

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

Doose, C.; Dejus, R.; Jaski, M.

2017-06-01

Extensive prototyping of storage ring magnets is ongoing at the Advanced Photon Source (APS) in support of the APS Multi-Bend Achromat (MBA) upgrade project (APS-U) [1]. As part of the R&D activities four quadrupole magnets with slightly different geometries and pole tip materials, and one sextupole magnet with vanadium permendur (VP) pole tips were designed, built and tested. Magnets were measured individually using a rotating coil and a Hall probe for detailed mapping of the magnetic field. Magnets were then assembled and aligned relative to each other on a steel support plate and concrete plinth using precision machined surfaces tomore » gain experience with the alignment method chosen for the APS-U storage ring magnets. The required alignment of magnets on a common support structure is 30 μm rms. Measurements of magnetic field quality, strength and magnet alignment after subjecting the magnets and assemblies to different tests are presented.« less

P alpha-chiral phosphorothioate analogues of bis(5'-adenosyl)tetraphosphate (Ap4A); their enzymatic synthesis and degradation.

PubMed Central

Lazewska, D; Guranowski, A

1990-01-01

Synthesis of Sp and Rp diastereomers of Ap4A alpha S has been characterized in two enzymatic systems, the lysyl-tRNA synthetase from Escherichia coli and the Ap4A alpha, beta-phosphorylase from Saccharomyces cerevisiae. The synthetase was able to use both (Sp)ATP alpha S and (Rp)ATP alpha S as acceptors of adenylate thus yielding corresponding monothioanalogues of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S. No dithiophosphate analogue was formed. Relative synthetase velocities of the formation of Ap4A,(Sp) Ap4A alpha S and (Rp)Ap4A alpha S were 1:0.38:0.15, and the computed Km values for (Sp)ATP alpha S and (Rp)ATP alpha S were 0.48 and 1.34 mM, respectively. The yeast Ap4A phosphorylase synthesized (Sp)Ap4A alpha S and (Rp)Ap4A alpha S using adenosine 5'-phosphosulfate (APS) as source of adenylate. The adenylate was accepted by corresponding thioanalogues of ATP. In that system, relative velocities of Ap4A, (Sp)Ap4A alpha S and (Rp)Ap4A alpha S formation were 1:0.15:0.60. The two isomeric phosphorothioate analogues of Ap4A were tested as substrates for the following specific Ap4A-degrading enzymes: (asymmetrical) Ap4A hydrolase (EC 3.6.1.17) from yellow lupin (Lupinus luteus) seeds hydrolyzed each of the analogues to AMP and the corresponding isomer of ATP alpha S; (symmetrical) Ap4A hydrolase (EC 3.6.1.41) from E. coli produced ADP and the corresponding diastereomer of ADP alpha S; and Ap4A phosphorylase (EC 2.7.7.53) from S. cerevisiae cleaved the Rp isomer only at the unmodified end yielding ADP and (Rp)ATP alpha S whereas the Sp isomer was degraded non-specifically yielding a mixture of ADP, (Sp)ADP alpha S, ATP and (Sp)ATP alpha S. For all the Ap4A-degrading enzymes, the Rp isomer of Ap4A alpha S appeared to be a better substrate than its Sp counterpart; stereoselectivity of the three enzymes for the Ap4A alpha S diastereomers is 51, 6 and 2.5, respectively. Basic kinetic parameters of the degradation reactions are presented and structural requirements of

Understanding and Using the New Guided-Inquiry AP Chemistry Laboratory Manual

ERIC Educational Resources Information Center

Cacciatore, Kristen L.

2014-01-01

To support teaching and learning in the advanced placement (AP) chemistry laboratory, the College Board published a laboratory manual, "AP Chemistry Guided-Inquiry Experiments: Applying the Science Practices," in 2013 as part of the redesigned course. This article provides a discussion of the rationale for the existence of the manual as…

Panel Discussion : Report of the APS Ad-Hoc Committee on LGBT Issues

NASA Astrophysics Data System (ADS)

Atherton, Tim; Barthelemy, Ramon; Garmon, Savannah; Reeves, Kyle; APS Ad-Hoc Committee on LGBT Issues Team

Following the presentation of the findings and recommendations of the APS Ad-Hoc Committee on LGBT Issues (C-LGBT) by Committee Chair Michael Falk, a panel discussion will be held featuring several members of the committee. The discussion will focus on how APS can best ensure the recommendations of the committee are carried out in a timely fashion and other ideas on future APS efforts toward LGBT inclusion in physics. Discussion topics will also include the research and other input that shaped the committee's findings and recommendations.

Cardioprotective effect of diadenosine tetraphosphate (AP4A) cardioplegia in isolated rat hearts.

PubMed

Ahmet, I; Sawa, Y; Nishimura, M; Matsuda, H

2000-01-01

Preischemic administration of diadenosine tetraphosphate (AP4A) has been shown to be cardioprotective. We evaluated the protective effect of AP4A when used as a cardioplegic adjuvant and tested contributions of the ATP-sensitive potassium channel (K ATP channel), adenosine receptor (AR), and purine 2y receptor (P2yR) to the effect of AP4A. Isolated buffer-perfused rat hearts were subjected to 23 min of ischemia (37 degrees C) followed by 20 min of reperfusion. Cardioplegia solution (St. Thomas Hospital solution) was infused during the first 3 min of ischemia. AP4A (10 microM) or AP4A with glibenclamide (K ATP channel blocker, 100 microM), 8-SPT (AR antagonist, 300 microM) or reactive blue (P2yR antagonist, 13 nM) were added to the cardioplegia solution. Compared with the cardioplegia solution alone, administration of AP4A with the solution significantly increased the recovery of rate-pressure production (75% +/- 11% vs 58% +/- 10%; P < 0.05) and dp/dt at the end of reperfusion, and reduced the leakage of creatine kinase (3.2 +/- 3.7 vs 13.2 +/- 10.1 IU/g; P < 0.05) during reperfusion. This effect was reversed by coadministration of glibenclamide or reactive blue but not 8-SPT. The addition of AP4A into the cardioplegia solution led to an added cardioprotective effect, either by opening the K ATP channel or by activating P2yR.

Using a Classroom Response System to Improve Multiple-Choice Performance in AP[R] Physics

ERIC Educational Resources Information Center

Bertrand, Peggy

2009-01-01

Participation in rigorous high school courses such as Advanced Placement (AP[R]) Physics increases the likelihood of college success, especially for students who are traditionally underserved. Tackling difficult multiple-choice exams should be part of any AP program because well-constructed multiple-choice questions, such as those on AP exams and…

Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval

PubMed Central

Hirst, Jennifer; Itzhak, Daniel N.; Antrobus, Robin; Borner, Georg H. H.

2018-01-01

The AP-5 adaptor protein complex is presumed to function in membrane traffic, but so far nothing is known about its pathway or its cargo. We have used CRISPR-Cas9 to knock out the AP-5 ζ subunit gene, AP5Z1, in HeLa cells, and then analysed the phenotype by subcellular fractionation profiling and quantitative mass spectrometry. The retromer complex had an altered steady-state distribution in the knockout cells, and several Golgi proteins, including GOLIM4 and GOLM1, were depleted from vesicle-enriched fractions. Immunolocalisation showed that loss of AP-5 led to impaired retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR), GOLIM4, and GOLM1 from endosomes back to the Golgi region. Knocking down the retromer complex exacerbated this phenotype. Both the CIMPR and sortilin interacted with the AP-5–associated protein SPG15 in pull-down assays, and we propose that sortilin may act as a link between Golgi proteins and the AP-5/SPG11/SPG15 complex. Together, our findings suggest that AP-5 functions in a novel sorting step out of late endosomes, acting as a backup pathway for retromer. This provides a mechanistic explanation for why mutations in AP-5/SPG11/SPG15 cause cells to accumulate aberrant endolysosomes, and highlights the role of endosome/lysosome dysfunction in the pathology of hereditary spastic paraplegia and other neurodegenerative disorders. PMID:29381698

Human Papillomavirus Type 16 E6 Induces Self-Ubiquitination of the E6AP Ubiquitin-Protein Ligase

PubMed Central

Kao, Wynn H.; Beaudenon, Sylvie L.; Talis, Andrea L.; Huibregtse, Jon M.; Howley, Peter M.

2000-01-01

The E6 protein of the high-risk human papillomaviruses (HPVs) and the cellular ubiquitin-protein ligase E6AP form a complex which causes the ubiquitination and degradation of p53. We show here that HPV16 E6 promotes the ubiquitination and degradation of E6AP itself. The half-life of E6AP is shorter in HPV-positive cervical cancer cells than in HPV-negative cervical cancer cells, and E6AP is stabilized in HPV-positive cancer cells when expression of the viral oncoproteins is repressed. Expression of HPV16 E6 in cells results in a threefold decrease in the half-life of transfected E6AP. E6-mediated degradation of E6AP requires (i) the binding of E6 to E6AP, (ii) the catalytic activity of E6AP, and (iii) activity of the 26S proteasome, suggesting that E6-E6AP interaction results in E6AP self-ubiquitination and degradation. In addition, both in vitro and in vivo experiments indicate that E6AP self-ubiquitination results primarily from an intramolecular transfer of ubiquitin from the active-site cysteine to one or more lysine residues; however, intermolecular transfer can also occur in the context of an E6-mediated E6AP multimer. Finally, we demonstrate that an E6 mutant that is able to immortalize human mammary epithelial cells but is unable to degrade p53 retains its ability to bind and degrade E6AP, raising the possibility that E6-mediated degradation of E6AP contributes to its ability to transform mammalian cells. PMID:10864652

Comparison of a CCD and an APS for soft X-ray diffraction

NASA Astrophysics Data System (ADS)

Stewart, Graeme; Bates, R.; Blue, A.; Clark, A.; Dhesi, S. S.; Maneuski, D.; Marchal, J.; Steadman, P.; Tartoni, N.; Turchetta, R.

2011-12-01

We compare a new CMOS Active Pixel Sensor (APS) to a Princeton Instruments PIXIS-XO: 2048B Charge Coupled Device (CCD) with soft X-rays tested in a synchrotron beam line at the Diamond Light Source (DLS). Despite CCDs being established in the field of scientific imaging, APS are an innovative technology that offers advantages over CCDs. These include faster readout, higher operational temperature, in-pixel electronics for advanced image processing and reduced manufacturing cost. The APS employed was the Vanilla sensor designed by the MI3 collaboration and funded by an RCUK Basic technology grant. This sensor has 520 x 520 square pixels, of size 25 μm on each side. The sensor can operate at a full frame readout of up to 20 Hz. The sensor had been back-thinned, to the epitaxial layer. This was the first time that a back-thinned APS had been demonstrated at a beam line at DLS. In the synchrotron experiment soft X-rays with an energy of approximately 708 eV were used to produce a diffraction pattern from a permalloy sample. The pattern was imaged at a range of integration times with both sensors. The CCD had to be operated at a temperature of -55°C whereas the Vanilla was operated over a temperature range from 20°C to -10°C. We show that the APS detector can operate with frame rates up to two hundred times faster than the CCD, without excessive degradation of image quality. The signal to noise of the APS is shown to be the same as that of the CCD at identical integration times and the response is shown to be linear, with no charge blooming effects. The experiment has allowed a direct comparison of back thinned APS and CCDs in a real soft x-ray synchrotron experiment.

Molecular Basis for Association of PIPKIγ-p90 with Clathrin Adaptor AP-2*

PubMed Central

Kahlfeldt, Nina; Vahedi-Faridi, Ardeschir; Koo, Seong Joo; Schäfer, Johannes G.; Krainer, Georg; Keller, Sandro; Saenger, Wolfram; Krauss, Michael; Haucke, Volker

2010-01-01

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an essential determinant in clathrin-mediated endocytosis (CME). In mammals three type I phosphatidylinositol-4-phosphate 5-kinase (PIPK) enzymes are expressed, with the Iγ-p90 isoform being highly expressed in the brain where it regulates synaptic vesicle (SV) exo-/endocytosis at nerve terminals. How precisely PI(4,5)P2 metabolism is controlled spatially and temporally is still uncertain, but recent data indicate that direct interactions between type I PIPK and components of the endocytic machinery, in particular the AP-2 adaptor complex, are involved. Here we demonstrated that PIPKIγ-p90 associates with both the μ and β2 subunits of AP-2 via multiple sites. Crystallographic data show that a peptide derived from the splice insert of the human PIPKIγ-p90 tail binds to a cognate recognition site on the sandwich subdomain of the β2 appendage. Partly overlapping aromatic and hydrophobic residues within the same peptide also can engage the C-terminal sorting signal binding domain of AP-2μ, thereby potentially competing with the sorting of conventional YXXØ motif-containing cargo. Biochemical and structure-based mutagenesis analysis revealed that association of the tail domain of PIPKIγ-p90 with AP-2 involves both of these sites. Accordingly the ability of overexpressed PIPKIγ tail to impair endocytosis of SVs in primary neurons largely depends on its association with AP-2β and AP-2μ. Our data also suggest that interactions between AP-2 and the tail domain of PIPKIγ-p90 may serve to regulate complex formation and enzymatic activity. We postulate a model according to which multiple interactions between PIPKIγ-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P2 synthesis during clathrin-mediated SV endocytosis. PMID:19903820

Structural modeling and molecular simulation analysis of HvAP2/EREBP from barley.

PubMed

Pandey, Bharati; Sharma, Pradeep; Tyagi, Chetna; Goyal, Sukriti; Grover, Abhinav; Sharma, Indu

2016-06-01

AP2/ERF transcription factors play a critical role in plant development and stress adaptation. This study reports the three-dimensional ab initio-based model of AP2/EREBP protein of barley and its interaction with DNA. Full-length coding sequence of HvAP2/EREBP gene isolated from two Indian barley cultivars, RD 2503 and RD 31, was used to model the protein. Of five protein models obtained, the one with lowest C-score was chosen for further analysis. The N- and C-terminal regions of HvAP2 protein were found to be highly disordered. The dynamic properties of AP2/EREBP and its interaction with DNA were investigated by molecular dynamics simulation. Analysis of trajectories from simulation yielded the equilibrated conformation between 2-10ns for protein and 7-15ns for protein-DNA complex. We established relationship between DNA having GCC box and DNA-binding domain of HvAP2/EREBP was established by modeling 11-base-pair-long nucleotide sequence and HvAP2/EREBP protein using ab initio method. Analysis of protein-DNA interaction showed that a β-sheet motif constituting amino acid residues THR105, ARG100, ARG93, and ARG83 seems to play important role in stabilizing the complex as they form strong hydrogen bond interactions with the DNA motif. Taken together, this study provides first-hand comprehensive information detailing structural conformation and interactions of HvAP2/EREBP proteins in barley. The study intensifies the role of computational approaches for preliminary examination of unknown proteins in the absence of experimental information. It also provides molecular insight into protein-DNA binding for understanding and enhancing abiotic stress resistance for improving the water use efficiency in crop plants.

CMOS-APS Detectors for Solar Physics: Lessons Learned during the SWAP Preflight Calibration

NASA Astrophysics Data System (ADS)

de Groof, A.; Berghmans, D.; Nicula, B.; Halain, J.-P.; Defise, J.-M.; Thibert, T.; Schühle, U.

2008-05-01

CMOS-APS imaging detectors open new opportunities for remote sensing in solar physics beyond what classical CCDs can provide, offering far less power consumption, simpler electronics, better radiation hardness, and the possibility of avoiding a mechanical shutter. The SWAP telescope onboard the PROBA2 technology demonstration satellite of the European Space Agency will be the first actual implementation of a CMOS-APS detector for solar physics in orbit. One of the goals of the SWAP project is precisely to acquire experience with the CMOS-APS technology in a real-live space science context. Such a precursor mission is essential in the preparation of missions such as Solar Orbiter where the extra CMOS-APS functionalities will be hard requirements. The current paper concentrates on specific CMOS-APS issues that were identified during the SWAP preflight calibration measurements. We will discuss the different readout possibilities that the CMOS-APS detector of SWAP provides and their associated pros and cons. In particular we describe the “image lag” effect, which results in a contamination of each image with a remnant of the previous image. We have characterised this effect for the specific SWAP implementation and we conclude with a strategy on how to successfully circumvent the problem and actually take benefit of it for solar monitoring.

Ecto-diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A)-hydrolase is expressed as an ectoenzyme in a variety of mammalian and human cells and adds new aspects to the turnover of Ap4A.

PubMed

von Drygalski, A; Ogilvie, A

2000-01-01

Ap4A and other dinucleotides participate in the regulation of hemostasis and blood pressure control. With the exception of two previously reported surface anchored ectoAp4A-hydrolases on bovine aortic endothelial and chromaffine cells, all Ap4A-hydrolases reported are intracellular or freely soluble. We demonstrated that ectoAp4A-hydrolases are present on a broad variety of cell types of different species: rat mesangial, bovine corneal epithelial, human Hep-G2 and peridontal cells. Ectoenzyme properties were evaluated on rat mesangium cells. Chromatography of purified plasma membranes on Sephacel 300 resulted in enrichment of ectoAp4A-hydrolase and in separation from ectoATPase. In contrast to ATPase, Ap4A-hydrolase was stable at room temperature. EctoAp4A-hydrolase also recognized ATP as substrate, and therefore is not highly specific. The molecular weight was 180 kD. Unlike ectoAMPase ectoAp4A-hydrolase was not attached via a glycosyl-phosphatidylinositol (GPI)-moiety. Concentrations of PI-PLC 10-100-fold higher than effective for ectoAMPase cleavage (10-100 mU/ml) plus extensively extended incubation times up to eight hours did not result in cleavage of ectoAp4A-hydrolase. The enzyme ectoAp4A-hydrolase might presage a direction for pharmaceutical manipulation in the control of blood pressure and hemostasis.

Neurobiología del autismo y TDAH mediante técnicas de neuroimagen: divergencias y convergencias

PubMed Central

Proal, Erika; Olvera, Jorge González; Blancas, Aurea S.; Chalita, Pablo J.; Castellanos, F. Xavier

2013-01-01

En el área clínica algunos síntomas del trastorno por déficit de atención e hiperactividad (TDAH), se presentan en los pacientes con trastorno del espectro autista (TEA). Se ha demostrado que existen alteraciones en circuitos cerebrales que impactan en fallas cognitivas y de comportamiento específicas de cada uno de estos trastornos. Sin embargo, han sido poco estudiados los correlatos cerebrales que hay detrás tanto de las similitudes como de las diferencias sintomatológicas. En la presente revisión se analizaron los estudios meta-analíticos existentes estructurales y funcionales en TDAH y TEA. Por un lado, se observaron convergencias en circuitos como el dorsal atencional, de funciones ejecutivas, visual, somatomotor y circuito de activación por defecto. Estas similitudes posiblemente explican las manifestaciones comórbidas entre los trastornos como la falla en la integración de información, motricidad fina y procesos atencionales específicos. Por otro lado, específicamente en el TDAH se observan déficits en el circuito de recompensa y ventral atencional, sistemas involucrados en la medición de efectos de reforzamiento y monitoreo atencional. En TEA los circuitos más afectados fueron los implicados en procesos de cognición social y lenguaje. En conclusión, existen correlatos neuronales en TEA que explican las manifestaciones clínicas tanto convergentes como divergentes presentes en TDAH. PMID:23897144

AP1000{sup R} severe accident features and post-Fukushima considerations

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

Scobel, J. H.; Schulz, T. L.; Williams, M. G.

2012-07-01

The AP1000{sup R} passive nuclear power plant is uniquely equipped to withstand an extended station blackout scenario such as the events following the earthquake and tsunami at Fukushima without compromising core and containment integrity. The AP1000 plant shuts down the reactor, cools the core, containment and spent fuel pool for more than 3 days using passive systems that do not require AC or DC power or operator actions. Following this passive coping period, minimal operator actions are needed to extend the operation of the passive features to 7 days using installed equipment. To provide defense-in-depth for design extension conditions, themore » AP1000 plant has engineered features that mitigate the effects of core damage. Engineered features retain damaged core debris within the reactor vessel as a key feature. Other aspects of the design protect containment integrity during severe accidents, including unique features of the AP1000 design relative to passive containment cooling with water and air, and hydrogen management. (authors)« less

AfAP2-1, An Age-Dependent Gene of Aechmea fasciata, Responds to Exogenous Ethylene Treatment

PubMed Central

Lei, Ming; Li, Zhi-Ying; Wang, Jia-Bin; Fu, Yun-Liu; Ao, Meng-Fei; Xu, Li

2016-01-01

The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads remains unknown. Here, we identified an APETALA2 (AP2)-like gene, AfAP2-1, in Aechmea fasciata. AfAP2-1 contains two AP2 domains and is a nuclear-localized protein. It functions as a transcriptional activator, and the activation domain is located in the C-terminal region. The expression level of AfAP2-1 is higher in juvenile plants than in adult plants, and the AfAP2-1 transcript level was rapidly and transiently reduced in plants treated with exogenous ethylene. Overexpression of AfAP2-1 in Arabidopsis thaliana results in an extremely delayed flowering phenotype. These results suggested that AfAP2-1 responds to ethylene and is a putative age-dependent flowering regulator in A. fasciata. PMID:26927090

Aviation Safety Program: Weather Accident Prevention (WxAP) Development of WxAP System Architecture And Concepts of Operation

NASA Technical Reports Server (NTRS)

Grantier, David

2003-01-01

This paper presents viewgraphs on the development of the Weather Accident Prevention (WxAP) System architecture and Concept of Operation (CONOPS) activities. The topics include: 1) Background Information on System Architecture/CONOPS Activity; 2) Activity Work in Progress; and 3) Anticipated By-Products.

AP-1 Oligodeoxynucleotides Reduce Aortic Elastolysis in a Murine Model of Marfan Syndrome.

PubMed

Arif, Rawa; Zaradzki, Marcin; Remes, Anca; Seppelt, Philipp; Kunze, Reiner; Schröder, Hannes; Schwill, Simon; Ensminger, Stephan M; Robinson, Peter N; Karck, Matthias; Müller, Oliver J; Hecker, Markus; Wagner, Andreas H; Kallenbach, Klaus

2017-12-15

Marfan syndrome is characterized by high expression of matrix metalloproteinases (MMPs) in aortic smooth muscle cells (AoSMCs) associated with medial elastolysis and aortic root aneurysm. We aimed to reduce aortic elastolysis through decrease of MMP expression with decoy oligodeoxynucleotides (dODNs) neutralizing the transcription factor activating factor-1 (AP-1). AP-1 abundance in nuclear extracts as well as MMP-2 and MMP-9 expression were significantly increased in isolated mAoSMC of mgR/mgR Marfan mice compared to wild-type cells. Exposure to AP-1 neutralizing dODNs resulted in a significant reduction of basal and interleukin-1β-stimulated MMP expression and activity in mAoSMCs. Moreover, increased migration and formation of superoxide radical anions was substantially decreased in mAoSMCs by AP-1 dODN treatment. Aortic grafts from donor Marfan mice were treated with AP-1- dODN ex vivo and implanted as infrarenal aortic interposition grafts in mgR/mgR mice. Pretreatment of aortic grafts with AP-1 dODN led to reduced elastolysis, macrophage infiltration, and MMP activity. Permeability of the endothelial monolayer was increased for dODN in mgR/mgR aortae with observed loss of tight junction proteins ZO-1 and occludin, enabling dODN to reach the tunica media. Targeting AP-1 activity offers a new potential strategy to treat the vascular phenotype associated with Marfan syndrome. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Structural Determinants of DNA Binding by a P. falciparum ApiAP2 Transcriptional Regulator

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

Lindner, Scott E.; De Silva, Erandi K.; Keck, James L.

2010-11-05

Putative transcription factors have only recently been identified in the Plasmodium spp., with the major family of regulators comprising the Apicomplexan Apetala2 (AP2) proteins. To better understand the DNA-binding mechanisms of these transcriptional regulators, we characterized the structure and in vitro function of an AP2 DNA-binding domain from a prototypical Apicomplexan AP2 protein, PF14{_}0633 from Plasmodium falciparum. The X-ray crystal structure of the PF14{_}0633 AP2 domain bound to DNA reveals a {beta}-sheet fold that binds the DNA major groove through base-specific and backbone contacts; a prominent {alpha}-helix supports the {beta}-sheet structure. Substitution of predicted DNA-binding residues with alanine weakened ormore » eliminated DNA binding in solution. In contrast to plant AP2 domains, the PF14{_}0633 AP2 domain dimerizes upon binding to DNA through a domain-swapping mechanism in which the {alpha}-helices of the AP2 domains pack against the {beta}-sheets of the dimer mates. DNA-induced dimerization of PF14{_}0633 may be important for tethering two distal DNA loci together in the nucleus and/or for inducing functional rearrangements of its domains to facilitate transcriptional regulation. Consistent with a multisite binding mode, at least two copies of the consensus sequence recognized by PF14{_}0633 are present upstream of a previously identified group of sporozoite-stage genes. Taken together, these findings illustrate how Plasmodium has adapted the AP2 DNA-binding domain for genome-wide transcriptional regulation.« less

Back to the Future: Merit or Equity in AP Social Studies?

ERIC Educational Resources Information Center

Stevens, Robert

2013-01-01

In an effort to address severe budget deficits at both the state and local levels, schools and educational programs are being asked to trim budgets. The Advanced Placement Program is one program that will certainly be scrutinized. This article presents a general overview of AP social studies, a brief history of the AP social studies program, and…

Airborne Precision Spacing (APS) Dependent Parallel Arrivals (DPA)

NASA Technical Reports Server (NTRS)

Smith, Colin L.

2012-01-01

The Airborne Precision Spacing (APS) team at the NASA Langley Research Center (LaRC) has been developing a concept of operations to extend the current APS concept to support dependent approaches to parallel or converging runways along with the required pilot and controller procedures and pilot interfaces. A staggered operations capability for the Airborne Spacing for Terminal Arrival Routes (ASTAR) tool was developed and designated as ASTAR10. ASTAR10 has reached a sufficient level of maturity to be validated and tested through a fast-time simulation. The purpose of the experiment was to identify and resolve any remaining issues in the ASTAR10 algorithm, as well as put the concept of operations through a practical test.

COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

PubMed

Gao, Shujun; Fang, Lekun; Phan, Liem Minh; Qdaisat, Aiham; Yeung, Sai-Ching J; Lee, Mong-Hong

2015-09-29

Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.

Degraded λ-carrageenan activates NF-κB and AP-1 pathways in macrophages and enhances LPS-induced TNF-α secretion through AP-1.

PubMed

Chen, Haimin; Wang, Feng; Mao, Haihua; Yan, Xiaojun

2014-07-01

Carrageenan (CGN), a high molecular weight sulfated polysaccharide, is a traditional ingredient used in food industry. Its degraded forms have been identified as potential carcinogens, although the mechanism remains unclear. The effects of degraded λ-carrageenan (λ-dCGN) on murine RAW264.7 cells and human THP-1-derived macrophage cells were investigated by studying its actions on tumor necrosis factor alpha (TNF-α) secretion, Toll-like receptor 4 (TLR4) expression, and activation of nuclear factor-κb (NF-κB) and activation protein-1 (AP-1) pathways. We found that λ-dCGN was much stronger than native λ-CGN in the activation of macrophages to secrete TNF-α. Treatment of RAW264.7 cells with λ-dCGN resulted in the upregulation of TLR4, CD14 and MD-2 expressions, but it did not increase the binding of lipopolysacchride (LPS) with macrophages. Meanwhile, λ-dCGN treatment activated NF-κB via B-cell lymphoma/leukemia 10 (Bcl10) and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) phosphorylation. In addition, λ-dCGN induced extracellular signal-regulated kinases/1/2/mitogen-activated protein kinases (ERK1/2/MAPK) and AP-1 activation. Interestingly, pretreatment of RAW264.7 cells with λ-dCGN markedly enhanced LPS-stimulated TNF-α secretion. This pretreatment resulted in the enhanced phosphorylation of ERK1/2 and c-Jun N-terminal kinase (JNK) and intensified activation of AP-1. λ-dCGN induced an inflammatory reaction via both NF-κB and AP-1, and enhanced the inflammatory effect of LPS through AP-1 activation. The study demonstrated the role of λ-dCGN to induce the inflammatory reaction and to aggravate the effect of LPS on macrophages, suggesting that λ-dCGN produced during food processing and gastric digestion may be a safety concern. Copyright © 2014 Elsevier B.V. All rights reserved.

A method of semi-quantifying β-AP in brain PET-CT 11C-PiB images.

PubMed

Jiang, Jiehui; Lin, Xiaoman; Wen, Junlin; Huang, Zhemin; Yan, Zhuangzhi

2014-01-01

Alzheimer's disease (AD) is a common health problem for elderly populations. Positron emission tomography-computed tomography (PET-CT)11C-PiB for beta-P (amyloid-β peptide, β-AP) imaging is an advanced method to diagnose AD in early stage. However, in practice radiologists lack a standardized value to semi-quantify β-AP. This paper proposes such a standardized value: SVβ-AP. This standardized value measures the mean ratio between the dimension of β-AP areas in PET and CT images. A computer aided diagnosis approach is also proposed to achieve SVβ-AP. A simulation experiment was carried out to pre-test the technical feasibility of the CAD approach and SVβ-AP. The experiment results showed that it is technically feasible.

241-AP Tank Farm Construction Extent of Condition Review for Tank Integrity

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

Barnes, Travis J.; Gunter, Jason R.; Reeploeg, Gretchen E.

2014-04-04

This report provides the results of an extent of condition construction history review for the 241-AP tank farm. The construction history of the 241-AP tank farm has been reviewed to identify issues similar to those experienced during tank AY-102 construction. Those issues and others impacting integrity are discussed based on information found in available construction records, using tank AY-102 as the comparison benchmark. In the 241-AP tank farm, the sixth double-shell tank farm constructed, tank bottom flatness, refractory material quality, post-weld stress relieving, and primary tank bottom weld rejection were improved.

WCPSS Advanced Placement (AP) Test Results, 2009-10. E&R Report No. 10.29

ERIC Educational Resources Information Center

McMillen, Brad

2010-01-01

Analysis of WCPSS' 2009-10 AP reports from the College Board reveal that the number and proportion of WCPSS students taking AP courses and exams continues to grow. Between 1996-97 and 2009-10, the number of students enrolled in WCPSS grew by approximately 63% and the number taking AP exams increased by 238% with a corresponding increase in exams…

78 FR 21817 - Amendment of Restricted Area R-6601; Fort A.P. Hill, VA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

...; Airspace Docket No. 12-AEA-7] RIN 2120-AA66 Amendment of Restricted Area R-6601; Fort A.P. Hill, VA AGENCY... limits and time of designation of restricted area R-6601, Fort A.P. Hill, VA. The U.S. Army requested... limits and increase the time of designation of restricted area R-6601, Fort A.P. Hill, VA, (77 FR 35308...

HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

PubMed

Shen, Qing-Tao; Ren, Xuefeng; Zhang, Rui; Lee, Il-Hyung; Hurley, James H

2015-10-23

The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat. Copyright © 2015, American Association for the Advancement of Science.

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

PubMed Central

Hirst, Jennifer; Madeo, Marianna; Smets, Katrien; Edgar, James R.; Schols, Ludger; Li, Jun; Yarrow, Anna; Deconinck, Tine; Baets, Jonathan; Van Aken, Elisabeth; De Bleecker, Jan; Datiles, Manuel B.; Roda, Ricardo H.; Liepert, Joachim; Züchner, Stephan; Mariotti, Caterina; De Jonghe, Peter; Blackstone, Craig

2016-01-01

Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders. PMID:27606357

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis

PubMed Central

Worth, Danielle; Huang, Sherri

2018-01-01

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host. PMID:29718996

Transcriptional repression by ApiAP2 factors is central to chronic toxoplasmosis.

PubMed

Radke, Joshua B; Worth, Danielle; Hong, David; Huang, Sherri; Sullivan, William J; Wilson, Emma H; White, Michael W

2018-05-01

Tachyzoite to bradyzoite development in Toxoplasma is marked by major changes in gene expression resulting in a parasite that expresses a new repertoire of surface antigens hidden inside a modified parasitophorous vacuole called the tissue cyst. The factors that control this important life cycle transition are not well understood. Here we describe an important transcriptional repressor mechanism controlling bradyzoite differentiation that operates in the tachyzoite stage. The ApiAP2 factor, AP2IV-4, is a nuclear factor dynamically expressed in late S phase through mitosis/cytokinesis of the tachyzoite cell cycle. Remarkably, deletion of the AP2IV-4 locus resulted in the expression of a subset of bradyzoite-specific proteins in replicating tachyzoites that included tissue cyst wall components BPK1, MCP4, CST1 and the surface antigen SRS9. In the murine animal model, the mis-timing of bradyzoite antigens in tachyzoites lacking AP2IV-4 caused a potent inflammatory monocyte immune response that effectively eliminated this parasite and prevented tissue cyst formation in mouse brain tissue. Altogether, these results indicate that suppression of bradyzoite antigens by AP2IV-4 during acute infection is required for Toxoplasma to successfully establish a chronic infection in the immune-competent host.

Foundations for College and Beyond: Looking Back on AP Art History

ERIC Educational Resources Information Center

Schoenbohm, Laurel

2013-01-01

It was years after this author's AP Art History course in high school, and two years after college. She and some friends decided to fill a day during the Thanksgiving visits appreciating fine art. Prior to that AP course her senior year of high school, touring an art museum had seemed like the equivalent of going to the dentist. But after…

ATP6AP2 over-expression causes morphological alterations in the hippocampus and in hippocampus-related behaviour.

PubMed

Bracke, A; Schäfer, S; von Bohlen Und Halbach, V; Klempin, F; Bente, K; Bracke, K; Staar, D; van den Brandt, J; Harzsch, S; Bader, M; Wenzel, U O; Peters, J; von Bohlen Und Halbach, O

2018-02-23

The (pro)renin receptor [(P)RR], also known as ATP6AP2 [ATPase 6 accessory protein 2], is highly expressed in the brain. ATP6AP2 plays a role in early brain development, adult hippocampal neurogenesis and in cognitive functions. Lack of ATP6AP2 has deleterious effects, and mutations of ATP6AP2 in humans are associated with, e.g. X-linked intellectual disability. However, little is known about the effects of over-expression of ATP6AP2 in the adult brain. We hypothesized that mice over-expressing ATP6AP2 in the brain might exhibit altered neuroanatomical features and behavioural responses. To this end, we investigated heterozygous transgenic female mice and confirmed increased levels of ATP6AP2 in the brain. Our data show that over-expression of ATP6AP2 does not affect adult hippocampal neurogenesis, exercise-induced cell proliferation, or dendritic spine densities in the hippocampus. Only a reduced ventricular volume on the gross morphological level was found. However, ATP6AP2 over-expressing mice displayed altered exploratory behaviour with respect to the hole-board and novel object recognition tests. Moreover, primary adult hippocampal neural stem cells over-expressing ATP6AP2 exhibit a faster cell cycle progression and increased cell proliferation. Together, in contrast to the known deleterious effects of ATP6AP2 depletion, a moderate over-expression results in moderate behavioural changes and affects cell proliferation rate in vitro.

Ultraviolet photometry from the orbiting astronomical observatory. 8: The blue Ap stars

NASA Technical Reports Server (NTRS)

Leckrone, D. S.

1973-01-01

The filter photometers in the Wisconsin Experiment Package on OAO-2 were used to obtain data for a carefully selected set of 24 blue Ap stars and 31 comparison standard B and A dwarfs and giants for a program of relative photometry. Observations were made in seven bandpasses over the effective wavelength range 1430A-4250A. The Ap stars observed include members of the Si, Hg-Mn and Sr-Cr-Eu peculiarity classes. Most of them are too blue in B-V for their published MK spectral classes. The blue Ap stars are markedly deficient in emitted ultraviolet flux and are underluminous as compared to normal stars with the same UBV colors. The Hg-Mn stars appear less flux deficient in the ultraviolet for their UBV colors than do Si or Sr-cr-Eu stars. Most of the Ap stars observed possess ultraviolet flux distributions, or ultraviolet color temperatures, consistent with their published MK spectral classes to well within the classification uncertainties.

A second-generation superconducting undulator cryostat for the APS

NASA Astrophysics Data System (ADS)

Fuerst, J.; Hasse, Q.; Ivanyushenkov, Y.; Kasa, M.; Shiroyanagi, Y.

2017-12-01

A second-generation cryocooler-based cryostat has been designed and built to support a new helically wound superconducting undulator (SCU) magnet for the Advanced Photon Source (APS) at Argonne National Laboratory (ANL). The design represents an evolution of existing SCU cryostats currently in operation in the APS storage ring. Value engineering and lessons learned have resulted in a smaller, cheaper, and simpler cryostat design compatible with existing planar magnets as well as the new helically wound device. We describe heat load and quench response results, design and operational details, and the “build-to-spec” procurement strategy.

Structuring the AP Art History Course

ERIC Educational Resources Information Center

Herscher, Walter R.

2013-01-01

While AP (Advanced Placement) Art History may be taught within the art department in many schools, social studies teachers are equally capable of teaching the course well. They have the historical background to discuss the reasons for changes in art styles. A teacher's preparation is similar to teaching a course stressing political history,…

The Promise of AP World History

ERIC Educational Resources Information Center

Saldaña, Cristóbal T.

2013-01-01

AP World History is the ideal history course. It introduces students to 10,000 years of world history, and demands critical reading, critical writing, and critical thinking skills on the part of both the teacher and the students. It requires students to build their expertise in reading their textbook, and places demands on the teacher to assign…

Baseline water quality of Long Meadow Lake, Ponds AP-9 and AP-10, and Black Dog Creek, Hennepin and Dakota counties, Minnesota

USGS Publications Warehouse

Payne, G.A.

1977-01-01

Long Meadow Lake, Black Dog Creek, and Ponds AP-9 and AP-10 which lie in an area designated for a trunk highway bridge crossing the Minnesota River, were sampled for baseline water quality prior to construction of the bridge. Data collected show that dissolved solids fluctuate seasonally. Dissolved oxygen:/ranged from less than 1 milligram per liter under an ice cover to 13-9 milligrams per liter in the September sample at site 4 in Long Meadow Lake. The phytoplankton analyses showed pulses in algae populations, blue-green algae being the dominant type in at least one sample from each of the water courses.

Ectopic expression of Jatropha curcas APETALA1 (JcAP1) caused early flowering in Arabidopsis, but not in Jatropha

PubMed Central

Tang, Mingyong; Tao, Yan-Bin

2016-01-01

Jatropha curcas is a promising feedstock for biofuel production because Jatropha oil is highly suitable for the production of biodiesel and bio-jet fuels. However, Jatropha exhibits a low seed yield as a result of unreliable and poor flowering. APETALA1 (AP1) is a floral meristem and organ identity gene in higher plants. The flower meristem identity genes of Jatropha have not yet been identified or characterized. To better understand the genetic control of flowering in Jatropha, an AP1 homolog (JcAP1) was isolated from Jatropha. An amino acid sequence analysis of JcAP1 revealed a high similarity to the AP1 proteins of other perennial plants. JcAP1 was expressed in inflorescence buds, flower buds, sepals and petals. The highest expression level was observed during the early developmental stage of the flower buds. The overexpression of JcAP1 using the cauliflower mosaic virus (CaMV) 35S promoter resulted in extremely early flowering and abnormal flowers in transgenic Arabidopsis plants. Several flowering genes downstream of AP1 were up-regulated in the JcAP1-overexpressing transgenic plant lines. Furthermore, JcAP1 overexpression rescued the phenotype caused by the Arabidopsis AP1 loss-of-function mutant ap1-11. Therefore, JcAP1 is an ortholog of AtAP1, which plays a similar role in the regulation of flowering in Arabidopsis. However, the overexpression of JcAP1 in Jatropha using the same promoter resulted in little variation in the flowering time and floral organs, indicating that JcAP1 may be insufficient to regulate flowering by itself in Jatropha. This study helps to elucidate the function of JcAP1 and contributes to the understanding of the molecular mechanisms of flower development in Jatropha. PMID:27168978

Physical interaction between the strawberry allergen Fra a 1 and an associated partner FaAP: Interaction of Fra a 1 proteins and FaAP.

PubMed

Franz-Oberdorf, Katrin; Langer, Andreas; Strasser, Ralf; Isono, Erika; Ranftl, Quirin L; Wunschel, Christian; Schwab, Wilfried

2017-10-01

The strawberry fruit allergens Fra a 1.01E, Fra a 1.02 and Fra a 1.03 belong to the group of pathogenesis-related 10 (PR-10) proteins and are homologs of the major birch pollen Bet v 1 and apple allergen Mal d 1. Bet v 1 related proteins are the most extensively studied allergens but their physiological function in planta remains elusive. Since Mal d 1-Associated Protein has been previously identified as interaction partner of Mal d 1 we studied the binding of the orthologous Fra a 1-Associated Protein (FaAP) to Fra a 1.01E/1.02/1.03. As the C-terminal sequence of FaAP showed strong auto-activation activity in yeast 2-hybrid analysis a novel time resolved DNA-switching system was successfully applied. Fra a 1.01E, Fra a 1.02, and Fra a 1.03 bind to FaAP with K D of 4.5 ± 1.1, 15 ± 3, and 11 ± 2 nM, respectively. Fra a 1.01E forms a dimer, whereas Fra a 1.02 and Fra a 1.03 bind as monomer. The results imply that PR-10 proteins might be integrated into a protein-interaction network and FaAP binding appears to be essential for the physiological function of the Fra a 1 proteins. © 2017 Wiley Periodicals, Inc.

Building a world-class A/P function: how UPMC went paperless.

PubMed

DeLuca, Michael; Smith, Corey

2010-03-01

UPMC engaged people, processes, and technology to move its A/P function from a highly manual, paper-based operation to a completely automated process. UPMC's CFO hired a chief supply chain officer to develop a strategic plan, and UPMC named a value analysis team to gain clinician buy-in. UPMC automated A/P by enabling receipt of electronic invoices. UPMC streamlined its processes for invoices.

P1,P4-diadenosine tetraphosphate (Ap4A) inhibits proximal tubular reabsorption of sodium in rats.

PubMed

Stiepanow-Trzeciak, Anna; Jankowski, Maciej; Angielski, Stefan; Szczepanska-Konkel, Miroslawa

2007-01-01

P1,P4-diadenosine tetraphosphate (Ap4A) is a vasoactive dinucleotide possessing natriuretic activity. It is unclear, however, which part of the nephron is the target site of action for Ap4A. We evaluated the tubular sites of Ap4A action using the lithium clearance technique. Ap4A at a priming dose of 2 micromol/kg with subsequent infusion at 20 nmol/kg/min increased fractional water and sodium excretion 2.5- and 5.6-fold, respectively. Moreover, Ap4A increased lithium clearance 1.9-fold and fractional lithium excretion 2.8-fold. Fractional water and sodium excretion from distal nephron segments was not significantly affected by Ap4A. These results suggest that Ap4A induces natriuresis mainly through inhibition of proximal tubular reabsorption of sodium. Copyright 2007 S. Karger AG, Basel.

Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1

PubMed Central

Malina, Jaroslav; Scott, Peter; Brabec, Viktor

2015-01-01

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo–helical ‘flexicate’ complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3]4+ incorporating the common NN–NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo–helical complexes for cancer chemotherapy. PMID:25940617

Analytical Model of Large Data Transactions in CoAP Networks

PubMed Central

Ludovici, Alessandro; Di Marco, Piergiuseppe; Calveras, Anna; Johansson, Karl H.

2014-01-01

We propose a novel analytical model to study fragmentation methods in wireless sensor networks adopting the Constrained Application Protocol (CoAP) and the IEEE 802.15.4 standard for medium access control (MAC). The blockwise transfer technique proposed in CoAP and the 6LoWPAN fragmentation are included in the analysis. The two techniques are compared in terms of reliability and delay, depending on the traffic, the number of nodes and the parameters of the IEEE 802.15.4 MAC. The results are validated trough Monte Carlo simulations. To the best of our knowledge this is the first study that evaluates and compares analytically the performance of CoAP blockwise transfer and 6LoWPAN fragmentation. A major contribution is the possibility to understand the behavior of both techniques with different network conditions. Our results show that 6LoWPAN fragmentation is preferable for delay-constrained applications. For highly congested networks, the blockwise transfer slightly outperforms 6LoWPAN fragmentation in terms of reliability. PMID:25153143

Genome-wide investigation and expression analysis of AP2-ERF gene family in salt tolerant common bean

PubMed Central

Kavas, Musa; Kizildogan, Aslihan; Gökdemir, Gökhan; Baloglu, Mehmet Cengiz

2015-01-01

Apetala2-ethylene-responsive element binding factor (AP2-ERF) superfamily with common AP2-DNA binding domain have developmentally and physiologically important roles in plants. Since common bean genome project has been completed recently, it is possible to identify all of the AP2-ERF genes in the common bean genome. In this study, a comprehensive genome-wide in silico analysis identified 180 AP2-ERF superfamily genes in common bean (Phaseolus vulgaris). Based on the amino acid alignment and phylogenetic analyses, superfamily members were classified into four subfamilies: DREB (54), ERF (95), AP2 (27) and RAV (3), as well as one soloist. The physical and chemical characteristics of amino acids, interaction between AP2-ERF proteins, cis elements of promoter region of AP2-ERF genes and phylogenetic trees were predicted and analyzed. Additionally, expression levels of AP2-ERF genes were evaluated by in silico and qRT-PCR analyses. In silico micro-RNA target transcript analyses identified nearly all PvAP2-ERF genes as targets of by 44 different plant species' miRNAs were identified in this study. The most abundant target genes were PvAP2/ERF-20-25-62-78-113-173. miR156, miR172 and miR838 were the most important miRNAs found in targeting and BLAST analyses. Interactome analysis revealed that the transcription factor PvAP2-ERF78, an ortholog of Arabidopsis At2G28550, was potentially interacted with at least 15 proteins, indicating that it was very important in transcriptional regulation. Here we present the first study to identify and characterize the AP2-ERF transcription factors in common bean using whole-genome analysis, and the findings may serve as a references for future functional research on the transcription factors in common bean. PMID:27152109

Diagnostic utility of aP2/FABP4 expression in soft tissue tumours.

PubMed

Kashima, T G; Turley, H; Dongre, A; Pezzella, F; Athanasou, N A

2013-04-01

Adipocyte P2 (aP2), also known as fatty acid-binding protein 4 (FABP4), is a fatty acid-binding protein found in the cytoplasm of cells of adipocyte differentiation. In this study, we examined a large number of soft tissue tumours with a commercial polyclonal anti-aP2/FABP4 antibody and a newly developed mouse monoclonal antibody raised against this protein to determine the diagnostic utility of aP2/FABP4 as a marker of tumours of adipose differentiation. A mouse monoclonal antibody, clone 175d, was raised against a mixture of synthetic peptides corresponding to the amino acid sequence of residues 10-28 and 121-132 of the human aP2/FABP4 protein. Antigen expression with polyclonal and monoclonal antibodies was immunohistochemically determined in paraffin sections of normal adipose tissue and a wide range of benign and malignant primary soft tissue tumours (n = 200). aP2/FABP4 was expressed around the cytoplasmic lipid vacuole in white and brown fat cells in benign lipomas and hibernomas. Immature fat cells and lipoblasts in spindle cell/pleomorphic lipoma, atypical lipomatous tumour/well-differentiated liposarcoma, myxoid/round cell liposarcoma and pleomorphic liposarcoma also reacted strongly for aP2/FABP4. No specific staining was seen in non-adipose benign and malignant mesenchymal and non-mesenchymal tumours. aP2/FABP4 is expressed by mature and immature fat cells and is a marker of tumours of adipose differentiation. Immunophenotypic aP2/FABP4 expression is useful in identifying lipoblasts, and immunohistochemistry with polyclonal/monoclonal anti-aP2/FABP4 antibodies should be useful in distinguishing liposarcoma from other malignancies, particularly round cell, myxoid and pleomorphic soft tissue sarcomas.

AP4M1 is abnormally expressed in oxygen-glucose deprived hippocampal neurons.

PubMed

Zhang, J; Cheng, X Y; Sheng, G Y

2014-03-20

AP4M1 mutations have been suggested to be associated with autosomal recessive cerebral palsy syndrome. But the pathogenic mechanism remains uncertain. The purpose of this study is to investigate whether and how AP4M1 expression is changed in injured neurons. Primary cultured hippocampal neurons were prepared for this experiment. They were subjected to oxygen-glucose deprivation (OGD) leading to apoptosis, mimicking brain ischemia. Neuron-specific enolase (NSE) was labeled immunofluorescently to confirm that the purity of neuron was higher than 90%. Real-time PCR and western blotting were performed to measure the gene expression. AP4M1 was labeled with MAP2 or Tau-1 to observe the distribution. We found that the AP4M1 protein levels immediately after the procedure were similar between the OGD group and the sham group. However, down-regulation was observed 12h after the reperfusion, and became more notable at 24h. The real-time PCR showed similar results, except that the down-regulation of mRNA was able to be detected immediately after the OGD. Immunofluorescent labeling revealed AP4M1 distributed in the dendrites of normal neurons, but it redistributed to the axons after the OGD procedure. In conclusion, AP4M1 is not only down-regulated at both the mRNA and protein levels, but also redistributed from dendrites to axons in oxygen-glucose deprived hippocampal neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chlamydia trachomatis CT771 (nudH) is an asymmetric Ap4A hydrolase.

PubMed

Barta, Michael L; Lovell, Scott; Sinclair, Amy N; Battaile, Kevin P; Hefty, P Scott

2014-01-14

Asymmetric diadenosine 5',5‴-P(1),P(4)-tetraphosphate (Ap4A) hydrolases are members of the Nudix superfamily that asymmetrically cleave the metabolite Ap4A into ATP and AMP while facilitating homeostasis. The obligate intracellular mammalian pathogen Chlamydia trachomatis possesses a single Nudix family protein, CT771. As pathogens that rely on a host for replication and dissemination typically have one or zero Nudix family proteins, this suggests that CT771 could be critical for chlamydial biology and pathogenesis. We identified orthologues to CT771 within environmental Chlamydiales that share active site residues suggesting a common function. Crystal structures of both apo- and ligand-bound CT771 were determined to 2.6 Å and 1.9 Å resolution, respectively. The structure of CT771 shows a αβα-sandwich motif with many conserved elements lining the putative Nudix active site. Numerous aspects of the ligand-bound CT771 structure mirror those observed in the ligand-bound structure of the Ap4A hydrolase from Caenorhabditis elegans. These structures represent only the second Ap4A hydrolase enzyme member determined from eubacteria and suggest that mammalian and bacterial Ap4A hydrolases might be more similar than previously thought. The aforementioned structural similarities, in tandem with molecular docking, guided the enzymatic characterization of CT771. Together, these studies provide the molecular details for substrate binding and specificity, supporting the analysis that CT771 is an Ap4A hydrolase (nudH).

BDNF mRNA abundance regulated by antidromic action potentials and AP-LTD in hippocampus.

PubMed

Bukalo, Olena; Lee, Philip R; Fields, R Douglas

2016-12-02

Action-potential-induced LTD (AP-LTD) is a form of synaptic plasticity that reduces synaptic strength in CA1 hippocampal neurons firing antidromically during sharp-wave ripples. This firing occurs during slow-wave sleep and quiet moments of wakefulness, which are periods of offline replay of neural sequences learned during encoding sensory information. Here we report that rapid and persistent down-regulation of different mRNA transcripts of the BDNF gene accompanies AP-LTD, and that AP-LTD is abolished in mice with the BDNF gene knocked out in CA1 hippocampal neurons. These findings increase understanding of the mechanism of AP-LTD and the cellular mechanisms of memory consolidation. Published by Elsevier Ireland Ltd.

AP1S3 Mutations Are Associated with Pustular Psoriasis and Impaired Toll-like Receptor 3 Trafficking

PubMed Central

Setta-Kaffetzi, Niovi; Simpson, Michael A.; Navarini, Alexander A.; Patel, Varsha M.; Lu, Hui-Chun; Allen, Michael H.; Duckworth, Michael; Bachelez, Hervé; Burden, A. David; Choon, Siew-Eng; Griffiths, Christopher E.M.; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M.B.; Prins, Christa; Smahi, Asma; Trembath, Richard C.; Fraternali, Franca; Smith, Catherine H.; Barker, Jonathan N.; Capon, Francesca

2014-01-01

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. PMID:24791904

The Adaptor Protein CD2AP Is a Coordinator of Neurotrophin Signaling-Mediated Axon Arbor Plasticity

PubMed Central

Harrison, Benjamin J.; Venkat, Gayathri; Lamb, James L.; Hutson, Tom H.; Drury, Cassa; Rau, Kristofer K.; Bunge, Mary Barlett; Mendell, Lorne M.; Gage, Fred H.; Johnson, Richard D.; Hill, Caitlin E.; Rouchka, Eric C.; Moon, Lawrence D.F.

2016-01-01

Growth of intact axons of noninjured neurons, often termed collateral sprouting, contributes to both adaptive and pathological plasticity in the adult nervous system, but the intracellular factors controlling this growth are largely unknown. An automated functional assay of genes regulated in sensory neurons from the rat in vivo spared dermatome model of collateral sprouting identified the adaptor protein CD2-associated protein (CD2AP; human CMS) as a positive regulator of axon growth. In non-neuronal cells, CD2AP, like other adaptor proteins, functions to selectively control the spatial/temporal assembly of multiprotein complexes that transmit intracellular signals. Although CD2AP polymorphisms are associated with increased risk of late-onset Alzheimer's disease, its role in axon growth is unknown. Assessments of neurite arbor structure in vitro revealed CD2AP overexpression, and siRNA-mediated knockdown, modulated (1) neurite length, (2) neurite complexity, and (3) growth cone filopodia number, in accordance with CD2AP expression levels. We show, for the first time, that CD2AP forms a novel multiprotein complex with the NGF receptor TrkA and the PI3K regulatory subunit p85, with the degree of TrkA:p85 association positively regulated by CD2AP levels. CD2AP also regulates NGF signaling through AKT, but not ERK, and regulates long-range signaling though TrkA+/RAB5+ signaling endosomes. CD2AP mRNA and protein levels were increased in neurons during collateral sprouting but decreased following injury, suggesting that, although typically considered together, these two adult axonal growth processes are fundamentally different. These data position CD2AP as a major intracellular signaling molecule coordinating NGF signaling to regulate collateral sprouting and structural plasticity of intact adult axons. SIGNIFICANCE STATEMENT Growth of noninjured axons in the adult nervous system contributes to adaptive and maladaptive plasticity, and dysfunction of this process may

Comparative hemodynamic effects of hypotension induced by diadenosine tetraphosphate (AP4A) and ATP in dogs.

PubMed

Takeda, Shohei; Inada, Yutaka; Fukui, Noriyuki; Tomaru, Teruaki

1997-03-01

ATP and diadenosine tetraphosphate (AP 4 A) have been shown to produce vasodilation mediated by P 1 - and P 2 -purinoceptor, respectively. The differing mechanisms involved in this vasodilating activity may induce different systemic hemodynamic changes. We compared the hemodynamic effects of AP 4 A-induced hypotension with those induced by ATP. Fourteen mongrel dogs were anesthetized with 0.87% halothane in oxygen (1 MAC). After the baseline period, mean arterial pressure was reduced to 60 mmHg for 60 min by the infusion of AP 4 A or ATP. The ATP- and AP 4 A-induced hypotension resulted in a maximum reduction in systemic vascular resistance of 43% and 46%, respectively (P<0.01), associated with a significant increase in stroke volume index. With ATP, a 20% of maximum increase (P<0.05) in cardiac index (CI) was observed during the induced hypotension. In contrast, AP 4 A-induced hypotension did not result in any changes in CI throughout the observation period. The varying results concerning CI during the ATP- and AP 4 A-induced hypotension were probably due to differences in ventricular filling pressure, since AP 4 A-induced hypotension was associated with decreases (P<0.01) in both right atrial and pulmonary capillary wedge pressures, whereas neither of these variables significantly changed with ATP. The hypotension induced by either ATP or AP 4 A was associated with a significant decrease in heart rate (HR). However, both the magnitude and duration of decreases in HR due to ATP-induced hypotension were more pronounced than those seen with AP 4 A. In conclusion, while both drugs were equally capable of inducing hypotension, our results suggest that AP 4 A was more suitable for induced hypotension because of its potent vasodilatory action with venodilation and less negative chronotropic action.

Aps and Tep Chemical Characterization: Link Between The Dom and Pom Pools

NASA Astrophysics Data System (ADS)

Gogou, A.; Repeta, D. J.

The ocean inventory of dissolved organic carbon (DOC) is approximately 750 GT, comprising one of the Earth's largest carbon reservoirs on Earth. Despite its potential significance, the mechanisms that lead to DOM production and to spatial and temporal variations of DOM concentration in the world ocean are poorly understood. Chemical characterization studies show that up to 50% of HMW DOM is a structurally well-defined class of acylated polysaccharides (APS), which exhibits novel molecular-level characteris tics. Although APS synthesis occurs in the euphotic zone, a large fraction of the marine inventory of APS (appr. 10-30 GT C), resides in the deep ocean, and is approximately equal in mass to the total marine inventory of particulate organic carbon. While radiocarbon dating of deep sea DOC yields very old apparent ages (4000-6000 ybp), radiocarbon measurements made by our group on individual APS sugars shows that APS in the deep ocean has a radiocarbon value of +56 per mil, equivalent to surface water POC and DIC. This is the first clear evidence for the presence of "young" DOC in the deep ocean. One mechanism that could be important for the rapid removal of APS from surface seawater is physical removal by macroaggregates. To investigate the significance of this mechanism, we studied the chemical composition of surface-active POM (TEP) produced naturally on surface waters and in laboratory experiments, after bubbling of HMW DOM isolated from algal cultures. 1H-NMR spectral properties and molecular-level distribution of neutral sugars in natural and artificially produced TEP closely resembled those observed for cultured and oceanic HMW DOM, while they are significantly different from those of suspended particulate matter in the ocean (Gogou and Repeta, 2000). The results of these experiments provide evidence that POM with similar chemical characteristics to HMW DOM can be produced from algal-derived DOM in the surface ocean.

AP American History and the History Major: Keeping Body and Soul Together.

ERIC Educational Resources Information Center

Holbo, Paul S.

For college-level American History, in the high school advanced placement (AP) program and on university campuses, these are the best of times and the worst of times. For the American History AP program, the early 1970's were difficult times, with the examinations under attack as elitist and irrelevant to contemporary problems. The program…

Health in All Policies (HiAP) framework for country action.

PubMed

2014-06-01

This document serves as a 'starter's kit' for applying Health in All Policies (HiAP) in decision-making and implementation at national and subnational levels. It can be easily adapted for use in different country contexts and at the regional and global levels. WHAT IS HIAP?: HiAP is an approach to public policies across sectors that systematically takes into account the health implications of decisions, seeks synergies and avoids harmful health impacts in order to improve population health and health equity. As a concept, it reflects the principles of: legitimacy, accountability, transparency and access to information, participation, sustainability and collaboration across sectors and levels of government. Health and health equity are values in their own right and are also important prerequisites for achieving many other societal goals. Many of the determinants of health and health inequities in populations have social, environmental and economic origins that extend beyond the direct influence of the health sector and health policies. Thus, public policies in all sectors and at different levels of governance can have a significant impact on population health and health equity. The Framework sets out six key components that should be addressed in order to put the HiAP approach into action: (1) establish the need and priorities for HiAP, (2) frame planned action, (3) identify supportive structures and processes, (4) facilitate assessment and engagement, (5) ensure monitoring, evaluation and reporting, (6) build capacity. These components are not fixed in order or priority. Rather, individual countries will adopt and adjust the components in ways that are most relevant for their specific governance, economic and social contexts. Although governments as a whole bear the ultimate responsibility for the health of their citizens, health authorities at all levels are key actors in promoting HiAP. They should therefore actively seek opportunities to collaborate with and

Synthesis and properties of ApA analogues with shortened phosphonate internucleotide linkage.

PubMed

Králíková, Sárka; Buděšínský, Miloš; Barvík, Ivan; Masojídková, Milena; Točík, Zdeněk; Rosenberg, Ivan

2011-01-01

A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2 '-d(ApA) analogues with the α-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 ″ internucleotide linkage, isopolar but non-isosteric with the phosphodiester one, were synthesized and their hybridization properties with polyU studied. Due to the chirality on the 5 '-carbon atom of the modified internucleotide linkage bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the α-hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues with 3 '(2 ')-O-P-CH(2)-C4 ″ linkage lacking the 5 '-hydroxyl were synthesized. Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the modified sugar-phosphate backbone, along with the hybridization measurements, revealed remarkable differences in the stability of complexes with polyU, depending on the 5 '-carbon atom configuration. Potential usefulness of the α-hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

Crystal structure of wild-type and mutant human Ap4A hydrolase.

PubMed

Ge, Honghua; Chen, Xiaofang; Yang, Weili; Niu, Liwen; Teng, Maikun

2013-03-01

Ap4A hydrolase (asymmetrical diadenosine tetraphosphate hydrolase, EC 3.6.1.17), an enzyme involved in a number of biological processes, is characterized as cleaving the polyphosphate chain at the fourth phosphate from the bound adenosine moiety. This paper presents the crystal structure of wild-type and E58A mutant human Ap4A hydrolase. Similar to the canonical Nudix fold, human Ap4A hydrolase shows the common αβα-sandwich architecture. Interestingly, two sulfate ions and one diphosphate coordinated with some conserved residues were observed in the active cleft, which affords a better understanding of a possible mode of substrate binding. Copyright © 2013 Elsevier Inc. All rights reserved.

Shape-selective recognition of DNA abasic sites by metallohelices: inhibition of human AP endonuclease 1.

PubMed

Malina, Jaroslav; Scott, Peter; Brabec, Viktor

2015-06-23

Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo-helical complexes for cancer chemotherapy. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Component Database for the APS Upgrade

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

Veseli, S.; Arnold, N. D.; Jarosz, D. P.

The Advanced Photon Source Upgrade (APS-U) project will replace the existing APS storage ring with a multi-bend achromat (MBA) lattice to provide extreme transverse coherence and extreme brightness x-rays to its users. As the time to replace the existing storage ring accelerator is of critical concern, an aggressive one-year removal/installation/testing period is being planned. To aid in the management of the thousands of components to be installed in such a short time, the Component Database (CDB) application is being developed with the purpose to identify, document, track, locate, and organize components in a central database. Three major domains are beingmore » addressed: Component definitions (which together make up an exhaustive "Component Catalog"), Designs (groupings of components to create subsystems), and Component Instances (“Inventory”). Relationships between the major domains offer additional "system knowledge" to be captured that will be leveraged with future tools and applications. It is imperative to provide sub-system engineers with a functional application early in the machine design cycle. Topics discussed in this paper include the initial design and deployment of CDB, as well as future development plans.« less

Engaging Cuban Physicists Through the APS/CPS Partnership

NASA Astrophysics Data System (ADS)

Lerch, Irving A.; Lerch, Irving A.

In his reflections on Cuban physics, Marcelo Alonso urges APS to take steps to promote interactions between Cuban and US physicists. As an introduction to Marcello's essay, this note will summarize past and current activities.

AP1S3 mutations are associated with pustular psoriasis and impaired Toll-like receptor 3 trafficking.

PubMed

Setta-Kaffetzi, Niovi; Simpson, Michael A; Navarini, Alexander A; Patel, Varsha M; Lu, Hui-Chun; Allen, Michael H; Duckworth, Michael; Bachelez, Hervé; Burden, A David; Choon, Siew-Eng; Griffiths, Christopher E M; Kirby, Brian; Kolios, Antonios; Seyger, Marieke M B; Prins, Christa; Smahi, Asma; Trembath, Richard C; Fraternali, Franca; Smith, Catherine H; Barker, Jonathan N; Capon, Francesca

2014-05-01

Adaptor protein complex 1 (AP-1) is an evolutionary conserved heterotetramer that promotes vesicular trafficking between the trans-Golgi network and the endosomes. The knockout of most murine AP-1 complex subunits is embryonically lethal, so the identification of human disease-associated alleles has the unique potential to deliver insights into gene function. Here, we report two founder mutations (c.11T>G [p.Phe4Cys] and c.97C>T [p.Arg33Trp]) in AP1S3, the gene encoding AP-1 complex subunit σ1C, in 15 unrelated individuals with a severe autoinflammatory skin disorder known as pustular psoriasis. Because the variants are predicted to destabilize the 3D structure of the AP-1 complex, we generated AP1S3-knockdown cell lines to investigate the consequences of AP-1 deficiency in skin keratinocytes. We found that AP1S3 silencing disrupted the endosomal translocation of the innate pattern-recognition receptor TLR-3 (Toll-like receptor 3) and resulted in a marked inhibition of downstream signaling. These findings identify pustular psoriasis as an autoinflammatory phenotype caused by defects in vesicular trafficking and demonstrate a requirement of AP-1 for Toll-like receptor homeostasis. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genomic and transcriptomic analysis of the AP2/ERF superfamily in Vitis vinifera

PubMed Central

2010-01-01

Background The AP2/ERF protein family contains transcription factors that play a crucial role in plant growth and development and in response to biotic and abiotic stress conditions in plants. Grapevine (Vitis vinifera) is the only woody crop whose genome has been fully sequenced. So far, no detailed expression profile of AP2/ERF-like genes is available for grapevine. Results An exhaustive search for AP2/ERF genes was carried out on the Vitis vinifera genome and their expression profile was analyzed by Real-Time quantitative PCR (qRT-PCR) in different vegetative and reproductive tissues and under two different ripening stages. One hundred and forty nine sequences, containing at least one ERF domain, were identified. Specific clusters within the AP2 and ERF families showed conserved expression patterns reminiscent of other species and grapevine specific trends related to berry ripening. Moreover, putative targets of group IX ERFs were identified by co-expression and protein similarity comparisons. Conclusions The grapevine genome contains an amount of AP2/ERF genes comparable to that of other dicot species analyzed so far. We observed an increase in the size of specific groups within the ERF family, probably due to recent duplication events. Expression analyses in different aerial tissues display common features previously described in other plant systems and introduce possible new roles for members of some ERF groups during fruit ripening. The presented analysis of AP2/ERF genes in grapevine provides the bases for studying the molecular regulation of berry development and the ripening process. PMID:21171999

[Atp6ap2/ (Pro) renin Receptor is Required for Laminar Formation during Retinal Development in Mice].

PubMed

Kanda, Atsuhiro

2015-11-01

(Pro) renin receptor [(P) RR], a key molecule for tissue renin-angiotensin system, was originally identified as Atp6ap2, an accessory subunit for vacuolar H(+)-ATPase that is a multi-subunit proton pump involved in fundamental cellular physiology. In this study, to elucidate the physiological functions of Atp6ap2/ (P) RR during retinal development in mammals, we used Cre-LoxP system to generate photoreceptor-specific conditional knock-out (CKO) mice, and revealed a critical role of Atp6ap2/(P) RR in photoreceptor development. Deletion of photoreceptor Atp6ap2/ (P) RR did not affect retinal cell differentiation, but led to laminar disorganization in the photoreceptor layer with dysfunction of photoreceptors. Cell adhesion and polarity molecules, all of which were co-localized with Atp6ap2 at the apical edge of the developing retina, were dispersed together with mislocalization of retinal progenitors apart from the apical surface in Atp6ap2 conditional knockout mice. Among these molecules, co-immunoprecipitation using retinal homogenates and Atp6ap2/(P) RR-transfected cells showed that Atp6ap2/(P) RR interacted with partitioning defective 3 homolog (Par3) protein, known to play a pivotal role in planar cell polarity in the Par-atypical protein kinase C system. Atp6ap2 interacted with Par3 protein that plays a pivotal role in planar cell polarity. Our data provide a novel function of Atp6ap2 required as a cell polarity determinant for retinal laminar formation.

Cultural Diversity in AP Art History

ERIC Educational Resources Information Center

Bolte, Frances R.

2006-01-01

Teaching AP Art History is like running on a treadmill that is moving faster than a teacher can run. Many teachers are out of breath before the end of the term and wonder how in the world they can cover every chapter. Because time is short and art from pre-history through to the present, including the non-European traditions, must be covered, this…

An Insider's History of Some of the Significant Changes In the APS from the 1960s to Today

NASA Astrophysics Data System (ADS)

Schwartz, Brian

2014-03-01

It has been over 50 years since I first joined the American Physical Society. A lot has changed. The APS in the 60s did not have a single Forum and all divisions were related to sub-field of physics research plus the History of Physics Division. The APS governance and meeting's structure did not provide for issues relate to physics and society, undergraduate and graduate education, minorities, women, industrial physics, international physics, communication of science, and many more subjects quite typical of APS in 2014. From the start, I was a very active member of APS and one of the original petitioners for the Division on Physics and Society. Ultimately this led to the APS Forum structure, the Panel on Public Affairs and many APS formal committees. Two of the major impetuses for change in the late 60s were the need to debate the role of science in the unpopular war in Vietnam and the overproduction and poor employment prospects for new Ph.D.s. I, and colleagues, (with little original encouragement from the APS leadership), arranged for the discussion on many new topics at the meeting and proposed changes within the governance of the Society. In the late 1980s I joined the APS and was involved in many changes over the next 20 years. ultimately as Associate Executive Officer and Director of the APS Centennial in 1999. As indicated earlier, I've been with the APS for over 50 years and will present its history as a participant-insider. Topic covered include my surprise election to the APS governance in 1972, the establishment of the Forum on Physics and Society (and the restrictions imposed on its governance), my role as the father (or mother) of the women's movement at APS, the complexities and politics of the move of APS headquarters from New York to College Park, the establishment of the tabloid APS News and many more subjects. Currently I am producing staged-readings of science-based plays at the March and April 2014 APS meetings for the Forum on History of

78 FR 19691 - Applications for New Awards; Advanced Placement (AP) Test Fee Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-02

... DEPARTMENT OF EDUCATION Applications for New Awards; Advanced Placement (AP) Test Fee Program... Information Advanced Placement Test Fee Program. Notice inviting applications for new awards for fiscal year... Program: The AP Test Fee program awards grants to eligible State educational agencies (SEAs) to enable...

77 FR 8848 - Application for New Awards; Advanced Placement (AP) Test Fee Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

... DEPARTMENT OF EDUCATION Application for New Awards; Advanced Placement (AP) Test Fee Program... Information: Advanced Placement Test Fee Program. Notice inviting applications for new awards for fiscal year... Description Purpose of Program: The AP Test Fee program awards grants to eligible State educational agencies...

5',5'''-P1, P4 diadenosine tetraphosphate (Ap4A): a putative initiator of DNA replication.

PubMed

Baril, E F; Coughlin, S A; Zamecnik, P C

1985-01-01

The proposal that Ap4A acts as an inducer of DNA replication is based primarily on two pieces of evidence (7). The intracellular levels of Ap4A increase ten- to 1000-fold as cells progress into S phase and the introduction of Ap4A into nonproliferating cells stimulated DNA synthesis. There is also some additional suggestive evidence such as the binding of Ap4A to a protein that is associated with multiprotein forms of the replicative DNA polymerase alpha and the ability of this enzyme to use Ap4A as a primer for DNA synthesis in vitro with single-stranded DNA templates. These observations have stimulated interest in the cellular metabolism of Ap4A. This is well since there is a great need for additional experimentation in order to clearly establish Ap4A as an inducer of DNA replication. Microinjection experiments of Ap4A into quiescent cells are needed in order to ascertain if Ap4A will stimulate DNA replication and possibly cell division in intact cells. Studies of the effects of nonhydrolyzable analogs of Ap4A on DNA replication in intact quiescent cells could also prove valuable. Although Ap4A can function as a primer for in vitro DNA synthesis by DNA polymerase alpha this may not be relevant in regard to its in vivo role in DNA replication. Ap4A in vivo could interact with key protein(s) in DNA replication and in this way act as an effector molecule in the initiation of DNA replication. In this regard the interaction of Ap4A with a protein associated with a multiprotein form of DNA polymerase alpha isolated from S-phase cells is of interest. More experiments are required to determine if there is a specific target protein(s) for Ap4A in vivo and what its role in DNA replication is. The cofractionation of tryptophanyl-tRNA synthetase with the replicative DNA polymerase alpha from animal and plant cells is of interest. The DNA polymerase alpha from synchronized animal cells also interacted with Ap4A. Although the plant cell alpha-like DNA polymerase did not

Preparation and characterization of superfine ammonium perchlorate (AP) crystals through ceramic membrane anti-solvent crystallization

NASA Astrophysics Data System (ADS)

Ma, Zhenye; Li, Cheng; Wu, Rujun; Chen, Rizhi; Gu, Zhenggui

2009-10-01

In this paper, a novel ceramic membrane anti-solvent crystallization (CMASC) method was proposed for the safe and rapid preparation ammonium perchlorate (AP) crystals, in which the acetone and ethyl acetate were chosen as solvent and anti-solvent, respectively. Comparing with the conventional liquid anti-solvent crystallization (LASC), CMASC which successfully introduces ceramic membrane with regular pore structure to the LASC as feeding medium, is favorable to control the rate of feeding rate and, therefore, to obtain size and morphology controllable AP. Several kinds of micro-sized AP particles with different morphology were obtained including polyhedral-like, quadrate-like to rod-like. The effect of processing parameters on the crystal size and shape of AP crystals such as volume ratio of anti-solvent to solvent, feeding pressure and crystallization temperature were investigated. It is found that higher volume ratio of anti-solvent to solvent, higher feeding pressure and higher temperature result in smaller particle size. Scaning electron microscopy (SEM) and X-ray diffraction (XRD) were used to characterize the resulting AP crystals. The nucleation and growth kinetic of the resulting AP crystals were also discussed.

Overexpression of two PsnAP1 genes from Populus simonii × P. nigra causes early flowering in transgenic tobacco and Arabidopsis.

PubMed

Zheng, Tangchun; Li, Shuang; Zang, Lina; Dai, Lijuan; Yang, Chuanping; Qu, Guan-Zheng

2014-01-01

In Arabidopsis, AP1 is a floral meristem identity gene and plays an important role in floral organ development. In this study, PsnAP1-1 and PsnAP1-2 were isolated from the male reproductive buds of poplar (Populus simonii × P. nigra), which are the orthologs of AP1 in Arabidopsis, by sequence analysis. Northern blot and qRT-PCR analysis showed that PsnAP1-1 and PsnAP1-2 exhibited high expression level in early inflorescence development of poplar. Subcellular localization showed the PsnAP1-1 and PsnAP1-2 proteins are localized in the nucleus. Overexpression of PsnAP1-1 and PsnAP1-2 in tobacco under the control of a CaMV 35S promoter significantly enhanced early flowering. These transgenic plants also showed much earlier stem initiation and higher rates of photosynthesis than did wild-type tobacco. qRT-PCR analysis further indicated that overexpression of PsnAP1-1 and PsnAP1-2 resulted in up-regulation of genes related to flowering, such as NtMADS4, NtMADS5 and NtMADS11. Overexpression of PsnAP1-1 and PsnAP1-2 in Arabidopsis also induced early flowering, but did not complement the ap1-10 floral morphology to any noticeable extent. This study indicates that PsnAP1-1 and PsnAP1-2 play a role in floral transition of poplar.

Overexpression of Two PsnAP1 Genes from Populus simonii × P. nigra Causes Early Flowering in Transgenic Tobacco and Arabidopsis

PubMed Central

Zheng, Tangchun; Li, Shuang; Zang, Lina; Dai, Lijuan; Yang, Chuanping; Qu, Guan-Zheng

2014-01-01

In Arabidopsis, AP1 is a floral meristem identity gene and plays an important role in floral organ development. In this study, PsnAP1-1 and PsnAP1-2 were isolated from the male reproductive buds of poplar (Populus simonii × P. nigra), which are the orthologs of AP1 in Arabidopsis, by sequence analysis. Northern blot and qRT-PCR analysis showed that PsnAP1-1 and PsnAP1-2 exhibited high expression level in early inflorescence development of poplar. Subcellular localization showed the PsnAP1-1 and PsnAP1-2 proteins are localized in the nucleus. Overexpression of PsnAP1-1 and PsnAP1-2 in tobacco under the control of a CaMV 35S promoter significantly enhanced early flowering. These transgenic plants also showed much earlier stem initiation and higher rates of photosynthesis than did wild-type tobacco. qRT-PCR analysis further indicated that overexpression of PsnAP1-1 and PsnAP1-2 resulted in up-regulation of genes related to flowering, such as NtMADS4, NtMADS5 and NtMADS11. Overexpression of PsnAP1-1 and PsnAP1-2 in Arabidopsis also induced early flowering, but did not complement the ap1-10 floral morphology to any noticeable extent. This study indicates that PsnAP1-1 and PsnAP1-2 play a role in floral transition of poplar. PMID:25360739

College Board Readies Plans for AP Audits

ERIC Educational Resources Information Center

Klein, Alyson

2006-01-01

This article describes the educators mixed reviews regarding the audit system planned by the College Board to scrutinize high school Advanced Placement courses. Teachers of AP courses are required to submit materials to the College Board proving that their course syllabuses meet the program's curricular requirements. It is the most extensive…

Automated Plasma Spray (APS) process feasibility study: Plasma spray process development and evaluation

NASA Technical Reports Server (NTRS)

Fetheroff, C. W.; Derkacs, T.; Matay, I. M.

1979-01-01

An automated plasma spray (APS) process was developed to apply two layer (NiCrAlY and ZrO2-12Y2O3) thermal-barrier coatings to aircraft gas turbine engine blade airfoils. The APS process hardware consists of four subsystems: a mechanical blade positioner incorporating two interlaced six-degree-of-freedom assemblies; a noncoherent optical metrology subsystem; a microprocessor-based adaptive system controller; and commercial plasma spray equipment. Over fifty JT9D first stage turbine blades specimens were coated with the APS process in preliminary checkout and evaluation studies. The best of the preliminary specimens achieved an overall coating thickness uniformity of + or - 53 micrometers, much better than is achievable manually. Factors limiting this performance were identified and process modifications were initiated accordingly. Comparative evaluations of coating thickness uniformity for manually sprayed and APS coated specimens were initiated. One of the preliminary evaluation specimens was subjected to a torch test and metallographic evaluation.

PREFACE: Asia-Pacific Interdisciplinary Research Conference 2011 (AP-IRC 2011)

NASA Astrophysics Data System (ADS)

Sandhu, Adarsh; Okada, Hiroshi; Maekawa, Toru; Okano, Ken

2012-03-01

AP-IRC Logo Scientists, engineers, entrepreneurs and policymakers gather at the first truly interdisciplinary conference held in Asia-Pacific http://www.apirc.jp/ The inaugural Asia-Pacific Interdisciplinary Research Conference 2011 (AP-IRC 2011) was held at Toyohashi University of Technology (Toyohashi Tech) on 17-18 November 2011. The conference is a forum for enhancing mutual understanding between scientists, engineers, policymakers and experts from a wide spectrum of pure and applied sciences, to resolve the daunting global issues facing mankind. The conference attracted approximately 300 participants including delegates from France, Germany, India, Indonesia, Korea, Malaysia, Russia, Sweden, United Kingdom, USA and Vietnam. AP-IRC 2011 was chaired by Dr Yoshiyuki Sakaki, President of Toyohashi Tech, who opened the proceedings by stressing the importance of an interdisciplinary approach to research, to resolve global scientific and technical issues. Recalling his own experience as the leader of Japan's efforts in the Human Genome Project, Sakaki also encouraged participants to make an effort to try to understand the sometimes difficult concepts and terminology of other areas of research. The presentations at AP-IRC 2011 were divided into three focus sessions: innovative mechano-magneto-electronic systems, life sciences, and green science and technology. A total of 174 papers were presented over the two-day conference including eight by invited speakers. Highlights of AP-IRC 2011 included a first-hand account of the damage caused by the massive earthquake in March 2011 to experimental facilities at Tohoku University by Masayoshi Esashi; the fascinating world of bees and the inborn numerical competence of humans and animals by Hans J Gross; research on robots and cognition-enabled technical systems at Technische Universität München by Sandra Hirche; the history of events leading to the invention of the world's strongest NdFeB permanent magnet by Masato Sagawa

An Ap-Structure with Finslerian Flavor II:. Torsion, Curvature and Other Objects

NASA Astrophysics Data System (ADS)

Wanas, M. I.; Kamal, Mona M.

An absolute parallelism (AP-) space having Finslerian properties is called FAP-space. This FAP-structure is wider than both conventional AP and Finsler structures. In the present work, more geometric objects as curvature and torsion tensors are derived in the context of this structure. Also second order tensors, usually needed for physical applications, are derived and studied. Furthermore, the anti-curvature and the W-tensor are defined for the FAP-structure. Relations between Riemannian, AP, Finsler and FAP structures are given. These relations facilitate comparison between results of applications carried out in the framework of these structures. We hope that the use of the FAP-structure, in applications may throw some light on some of the problems facing geometric field theories.

Automated Procurement System (APS): Project management plan (DS-03), version 1.2

NASA Technical Reports Server (NTRS)

Murphy, Diane R.

1994-01-01

The National Aeronautics and Space Administration (NASA) Marshall Space Flight Center (MSFC) is implementing an Automated Procurement System (APS) to streamline its business activities that are used to procure goods and services. This Project Management Plan (PMP) is the governing document throughout the implementation process and is identified as the APS Project Management Plan (DS-03). At this point in time, the project plan includes the schedules and tasks necessary to proceed through implementation. Since the basis of APS is an existing COTS system, the implementation process is revised from the standard SDLC. The purpose of the PMP is to provide the framework for the implementation process. It discusses the roles and responsibilities of the NASA project staff, the functions to be performed by the APS Development Contractor (PAI), and the support required of the NASA computer support contractor (CSC). To be successful, these three organizations must work together as a team, working towards the goals established in this Project Plan. The Project Plan includes a description of the proposed system, describes the work to be done, establishes a schedule of deliverables, and discusses the major standards and procedures to be followed.

Prediction of three-dimensional femoral offset from AP pelvis radiographs in primary hip osteoarthritis.

PubMed

Merle, C; Waldstein, W; Pegg, E C; Streit, M R; Gotterbarm, T; Aldinger, P R; Murray, D W; Gill, H S

2013-08-01

In pre-operative planning for total hip arthroplasty (THA), femoral offset (FO) is frequently underestimated on AP pelvis radiographs as a result of inaccurate patient positioning, imprecise magnification, and radiographic beam divergence. The aim of the present study was to evaluate the accuracy and reliability of predicting three-dimensional (3-D) FO from standardised AP pelvis radiographs. In a retrospective cohort study, pre-operative AP pelvis radiographs, AP hip radiographs and CT scans of a consecutive series of 345 patients (345 hips, 146 males, 199 females, mean age 60 (range: 40-79) years, mean body-mass-index 27 (range: 19-57)kg/m(2)) with primary end-stage hip OA were reviewed. Patients were positioned according to a standardised protocol and all images were calibrated. Using validated custom programmes, FO was measured on corresponding radiographs and CT scans. Measurement reliability was evaluated using intra-class-correlation-coefficients. To predict 3-D FO from AP pelvis measurements and to assess the accuracy compared to CT, the entire cohort was randomly split into subgroups A and B. Gender specific regression equations were derived from group A (245 patients) and the accuracy of prediction was evaluated in group B (100 patients) using Bland-Altman plots. In the entire cohort, mean FO was 39.2mm (95%CI: 38.5-40.0mm) on AP pelvis radiographs, 44.1mm (95%CI: 43.4-44.9mm) on AP hip radiographs and 44.6mm (95%CI: 44.0-45.2mm) on CT scans. In group B, we observed no significant difference between gender specific predicted FO (males: 48.0mm, 95%CI: 47.1-48.8mm; females: 42.0mm, 95%CI: 41.1-42.8mm) and FO as measured on CT (males: 47.7mm, 95%CI: 46.1-49.4mm, p=0.689; females: 41.6mm, 95%CI: 40.3-43.0mm, p=0.607). The present study suggests that FO can be accurately and reliably predicted from AP pelvis radiographs in patients with primary end-stage hip osteoarthritis. Our findings support the surgeon in pre-operative templating on AP-pelvis radiographs

75 FR 20774 - Establishment of Class E Airspace; Fort A.P. Hill, VA

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-21

...-0739; Airspace Docket No. 09-AEA-14] Establishment of Class E Airspace; Fort A.P. Hill, VA AGENCY... December 7, 2009 that establishes Class E airspace at Fort A.P. Hill, VA. DATES: Effective Date: 0901 UTC... Service Center, Federal Aviation Administration, P.O. Box 20636, Atlanta, Georgia 30320; telephone (404...

A glossary of terms for understanding political aspects in the implementation of Health in All Policies (HiAP).

PubMed

Oneka, Goldameir; Vahid Shahidi, Faraz; Muntaner, Carles; Bayoumi, Ahmed M; Mahabir, Deb Finn; Freiler, Alix; O'Campo, Patricia; Shankardass, Ketan

2017-08-01

Health in All Policies (HiAP) is a strategy that seeks to integrate health considerations into the development, implementation and evaluation of policies across various non-health sectors of the government. Over the past 15 years, there has been an increase in the uptake of HiAP by local, regional and national governments. Despite the growing popularity of this approach, most existing literature on HiAP implementation remains descriptive rather than explanatory in its orientation. Moreover, prior research has focused on the more technical aspects of the implementation process. Thus, studies that aim to 'build capacity to promote, implement and evaluate HiAP' abound. Conversely, there is little emphasis on the political aspects of HiAP implementation. Neglecting the role of politics in shaping the use of HiAP is problematic, since health and the strategies by which it is promoted are partially political.This glossary addresses the politics gap in the existing literature by drawing on theoretical concepts from political, policy, and public health sciences to articulate a framework for studying how political mechanisms influence HiAP implementation. To this end, the glossary forms part of an on-going multiple explanatory case study of HiAP implementation, HARMONICS (HiAP Analysis using Realist Methods on International Case Studies, harmonics-hiap.ca), and is meant to expand on a previously published glossary addressing the topic of HiAP implementation more broadly. Collectively, these glossaries offer a conceptual toolkit for understanding how politics explains implementation outcomes of HiAP. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection

PubMed Central

Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L.; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

2015-01-01

African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity. PMID:25915900

CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection.

PubMed

Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

2015-01-01

African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.

AP-Cloud: Adaptive particle-in-cloud method for optimal solutions to Vlasov–Poisson equation

DOE PAGES

Wang, Xingyu; Samulyak, Roman; Jiao, Xiangmin; ...

2016-04-19

We propose a new adaptive Particle-in-Cloud (AP-Cloud) method for obtaining optimal numerical solutions to the Vlasov–Poisson equation. Unlike the traditional particle-in-cell (PIC) method, which is commonly used for solving this problem, the AP-Cloud adaptively selects computational nodes or particles to deliver higher accuracy and efficiency when the particle distribution is highly non-uniform. Unlike other adaptive techniques for PIC, our method balances the errors in PDE discretization and Monte Carlo integration, and discretizes the differential operators using a generalized finite difference (GFD) method based on a weighted least square formulation. As a result, AP-Cloud is independent of the geometric shapes ofmore » computational domains and is free of artificial parameters. Efficient and robust implementation is achieved through an octree data structure with 2:1 balance. We analyze the accuracy and convergence order of AP-Cloud theoretically, and verify the method using an electrostatic problem of a particle beam with halo. Here, simulation results show that the AP-Cloud method is substantially more accurate and faster than the traditional PIC, and it is free of artificial forces that are typical for some adaptive PIC techniques.« less

AP-Cloud: Adaptive Particle-in-Cloud method for optimal solutions to Vlasov–Poisson equation

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

Wang, Xingyu; Samulyak, Roman, E-mail: roman.samulyak@stonybrook.edu; Computational Science Initiative, Brookhaven National Laboratory, Upton, NY 11973

We propose a new adaptive Particle-in-Cloud (AP-Cloud) method for obtaining optimal numerical solutions to the Vlasov–Poisson equation. Unlike the traditional particle-in-cell (PIC) method, which is commonly used for solving this problem, the AP-Cloud adaptively selects computational nodes or particles to deliver higher accuracy and efficiency when the particle distribution is highly non-uniform. Unlike other adaptive techniques for PIC, our method balances the errors in PDE discretization and Monte Carlo integration, and discretizes the differential operators using a generalized finite difference (GFD) method based on a weighted least square formulation. As a result, AP-Cloud is independent of the geometric shapes ofmore » computational domains and is free of artificial parameters. Efficient and robust implementation is achieved through an octree data structure with 2:1 balance. We analyze the accuracy and convergence order of AP-Cloud theoretically, and verify the method using an electrostatic problem of a particle beam with halo. Simulation results show that the AP-Cloud method is substantially more accurate and faster than the traditional PIC, and it is free of artificial forces that are typical for some adaptive PIC techniques.« less

AP-Cloud: Adaptive particle-in-cloud method for optimal solutions to Vlasov–Poisson equation

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

Wang, Xingyu; Samulyak, Roman; Jiao, Xiangmin

We propose a new adaptive Particle-in-Cloud (AP-Cloud) method for obtaining optimal numerical solutions to the Vlasov–Poisson equation. Unlike the traditional particle-in-cell (PIC) method, which is commonly used for solving this problem, the AP-Cloud adaptively selects computational nodes or particles to deliver higher accuracy and efficiency when the particle distribution is highly non-uniform. Unlike other adaptive techniques for PIC, our method balances the errors in PDE discretization and Monte Carlo integration, and discretizes the differential operators using a generalized finite difference (GFD) method based on a weighted least square formulation. As a result, AP-Cloud is independent of the geometric shapes ofmore » computational domains and is free of artificial parameters. Efficient and robust implementation is achieved through an octree data structure with 2:1 balance. We analyze the accuracy and convergence order of AP-Cloud theoretically, and verify the method using an electrostatic problem of a particle beam with halo. Here, simulation results show that the AP-Cloud method is substantially more accurate and faster than the traditional PIC, and it is free of artificial forces that are typical for some adaptive PIC techniques.« less

Gapminder: An AP Human Geography Lab Assignment

ERIC Educational Resources Information Center

Keller, Kenneth H.

2012-01-01

This lesson is designed as a lab assignment for Advanced Placement (AP) Human Geography students wherein they use the popular Gapminder web site to compare levels of development in countries from different world regions. For this lesson, it is important for the teacher to practice with Gapminder before giving the assignment to students. (Contains…

The Demographic Wave: Rethinking Hispanic AP Trends

ERIC Educational Resources Information Center

Edwards, Kelcey; Sawtell, Ellen

2013-01-01

Presented at the Advanced Placement Annual Conference (APAC) in Las Vegas, NV in July 2013. This presentation reviews new research examining the AP® experience of Hispanic graduates over the past decade. Topics include an in-depth look at the AP Spanish Language and Culture gateway hypothesis and trends in family characteristics such as parent…

The AP Descriptive Chemistry Question: Student Errors

ERIC Educational Resources Information Center

Crippen, Kent; Brooks, David W.

2005-01-01

For over a decade, the authors have been involved in a design theory experiment providing software for high school students preparing for the descriptive question on the Advanced Placement (AP) chemistry examination. Since 1997, the software has been available as a Web site offering repeatable practice. This study describes a 4-year project during…

Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.

PubMed

Zeng, Qi-bing; Xu, Yu-yan; Yu, Xian; Yang, Jun; Hong, Feng; Zhang, Ai-hua

2014-01-01

Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity. Copyright © 2013. Published by Elsevier B.V.

Adipocyte fatty acid-binding protein, aP2, alters late atherosclerotic lesion formation in severe hypercholesterolemia.

PubMed

Boord, Jeffrey B; Maeda, Kazuhisa; Makowski, Liza; Babaev, Vladimir R; Fazio, Sergio; Linton, MacRae F; Hotamisligil, Gökhan S

2002-10-01

The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Mice deficient in aP2 and apolipoprotein E (aP2(-/-)apoE(-/-) mice) and apolipoprotein E-deficient control mice (apoE(-/-) mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE(-/-) control mice, male and female aP2(-/-)apoE(-/-) mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis.

Modulation of KvAP Unitary Conductance and Gating by 1-Alkanols and Other Surface Active Agents

PubMed Central

Finol-Urdaneta, Rocio K.; McArthur, Jeffrey R.; Juranka, Peter F.; French, Robert J.; Morris, Catherine E.

2010-01-01

Abstract The actions of alcohols and anesthetics on ion channels are poorly understood. Controversy continues about whether bilayer restructuring is relevant to the modulatory effects of these surface active agents (SAAs). Some voltage-gated K channels (Kv), but not KvAP, have putative low affinity alcohol-binding sites, and because KvAP structures have been determined in bilayers, KvAP could offer insights into the contribution of bilayer mechanics to SAA actions. We monitored KvAP unitary conductance and macroscopic activation and inactivation kinetics in PE:PG/decane bilayers with and without exposure to classic SAAs (short-chain 1-alkanols, cholesterol, and selected anesthetics: halothane, isoflurane, chloroform). At levels that did not measurably alter membrane specific capacitance, alkanols caused functional changes in KvAP behavior including lowered unitary conductance, modified kinetics, and shifted voltage dependence for activation. A simple explanation is that the site of SAA action on KvAP is its entire lateral interface with the PE:PG/decane bilayer, with SAA-induced changes in surface tension and bilayer packing order combining to modulate the shape and stability of various conformations. The KvAP structural adjustment to diverse bilayer pressure profiles has implications for understanding desirable and undesirable actions of SAA-like drugs and, broadly, predicts that channel gating, conductance and pharmacology may differ when membrane packing order differs, as in raft versus nonraft domains. PMID:20197029

Functional Identification and Characterization of the Brassica Napus Transcription Factor Gene BnAP2, the Ortholog of Arabidopsis Thaliana APETALA2

PubMed Central

Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered. PMID:22479468

Functional identification and characterization of the Brassica napus transcription factor gene BnAP2, the ortholog of Arabidopsis thaliana APETALA2.

PubMed

Yan, Xiaohong; Zhang, Lei; Chen, Bo; Xiong, Zhiyong; Chen, Chunli; Wang, Lijun; Yu, Jingyin; Lu, Changming; Wei, Wenhui

2012-01-01

BnAP2, an APETALA2 (AP2)-like gene, has been isolated from Brassica napus cultivar Zhongshuang 9. The cDNA of BnAP2, with 1, 299 bp in length, encoded a transcription factor comprising of 432 amino acid residues. Results from complementary experiment indicated that BnAP2 was completely capable of restoring the phenotype of Arabidopsis ap2-11 mutant. Together with the sequence and expression data, the complementation data suggested that BnAP2 encodes the ortholog of AtAP2. To address the transcriptional activation of BnAP2, we performed transactivation assays in yeast. Fusion protein of BnAP2 with GAL4 DNA binding domain strongly activated transcription in yeast, and the transactivating activity of BnAP2 was localized to the N-terminal 100 amino acids. To further study the function of BnAP2 involved in the phenotype of B. napus, we used a transgenic approach that involved targeted RNA interference (RNAi) repression induced by ihp-RNA. Floral various phenotype defectives and reduced female fertility were observed in B. napus BnAP2-RNAi lines. Loss of the function of BnAP2 gene also resulted in delayed sepal abscission and senescence with the ethylene-independent pathway. In the strong BnAP2-RNAi lines, seeds showed defects in shape, structure and development and larger size. Strong BnAP2-RNAi and wild-type seeds initially did not display a significant difference in morphology at 10 DAF, but the development of BnAP2-RNAi seeds was slower than that of wild type at 20 DAF, and further at 30 DAF, wild-type seeds were essentially at their final size, whereas BnAP2-RNAi seeds stopped growing and developing and gradually withered.

Chemical synthesis of 5'-pyrophosphate and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. CD study of the effect of 5'-phosphate groups on the conformation of 3'-5' GpG.

PubMed Central

Tomasz, J; Simoncsits, A; Kajtár, M; Krug, R M; Shatkin, A J

1978-01-01

A simple, two-step method is described for the synthesis of the 5'-pyro- and triphosphate derivatives of 3'-5' ApA, ApG, GpA and GpG. The readily accessible 2'(3')-5' ApA, ApG, GpA and GpG were converted in one step to the corresponding 5'-phosphoramidate derivatives which were then transformed to the 5'-pyro- and triphosphates. CD spectra of 3'-5' pn GpG (n = 0,1,2 or 3) derivatives, measured at pH 1, indicated stabilization of the (syn) G+p (anti)G conformation by the 5'-phosphate groups. PMID:211490

Loss of AP-5 results in accumulation of aberrant endolysosomes: defining a new type of lysosomal storage disease

PubMed Central

Hirst, Jennifer; Edgar, James R.; Esteves, Typhaine; Darios, Frédéric; Madeo, Marianna; Chang, Jaerak; Roda, Ricardo H.; Dürr, Alexandra; Anheim, Mathieu; Gellera, Cinzia; Li, Jun; Züchner, Stephan; Mariotti, Caterina; Stevanin, Giovanni; Blackstone, Craig; Kruer, Michael C.; Robinson, Margaret S.

2015-01-01

Adaptor proteins (AP 1–5) are heterotetrameric complexes that facilitate specialized cargo sorting in vesicular-mediated trafficking. Mutations in AP5Z1, encoding a subunit of the AP-5 complex, have been reported to cause hereditary spastic paraplegia (HSP), although their impact at the cellular level has not been assessed. Here we characterize three independent fibroblast lines derived from skin biopsies of patients harbouring nonsense mutations in AP5Z1 and presenting with spastic paraplegia accompanied by neuropathy, parkinsonism and/or cognitive impairment. In all three patient-derived lines, we show that there is complete loss of AP-5 ζ protein and a reduction in the associated AP-5 µ5 protein. Using ultrastructural analysis, we show that these patient-derived lines consistently exhibit abundant multilamellar structures that are positive for markers of endolysosomes and are filled with aberrant storage material organized as exaggerated multilamellar whorls, striated belts and ‘fingerprint bodies’. This phenotype can be replicated in a HeLa cell culture model by siRNA knockdown of AP-5 ζ. The cellular phenotype bears striking resemblance to features described in a number of lysosomal storage diseases (LSDs). Collectively, these findings reveal an emerging picture of the role of AP-5 in endosomal and lysosomal homeostasis, illuminates a potential pathomechanism that is relevant to the role of AP-5 in neurons and expands the understanding of recessive HSPs. Moreover, the resulting accumulation of storage material in endolysosomes leads us to propose that AP-5 deficiency represents a new type of LSDs. PMID:26085577

A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.

PubMed

Modrzynska, Katarzyna; Pfander, Claudia; Chappell, Lia; Yu, Lu; Suarez, Catherine; Dundas, Kirsten; Gomes, Ana Rita; Goulding, David; Rayner, Julian C; Choudhary, Jyoti; Billker, Oliver

2017-01-11

A family of apicomplexa-specific proteins containing AP2 DNA-binding domains (ApiAP2s) was identified in malaria parasites. This family includes sequence-specific transcription factors that are key regulators of development. However, functions for the majority of ApiAP2 genes remain unknown. Here, a systematic knockout screen in Plasmodium berghei identified ten ApiAP2 genes that were essential for mosquito transmission: four were critical for the formation of infectious ookinetes, and three were required for sporogony. We describe non-essential functions for AP2-O and AP2-SP proteins in blood stages, and identify AP2-G2 as a repressor active in both asexual and sexual stages. Comparative transcriptomics across mutants and developmental stages revealed clusters of co-regulated genes with shared cis promoter elements, whose expression can be controlled positively or negatively by different ApiAP2 factors. We propose that stage-specific interactions between ApiAP2 proteins on partly overlapping sets of target genes generate the complex transcriptional network that controls the Plasmodium life cycle. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The Freshman Nine: Helping High School Freshmen Be Successful in AP Human Geography

ERIC Educational Resources Information Center

Garner, Jennifer

2012-01-01

Teaching AP Human Geography to freshmen seems like a daunting task and while there are many arguments both for and against offering the course to freshmen, for many teachers it is reality. In this article, the author offers nine tips to help high school freshmen be successful in the course and on the AP exam.

Size response of an SMPS-APS system to commercial multi-walled carbon nanotubes

NASA Astrophysics Data System (ADS)

Lee, Seung-Bok; Lee, Jun-Hyun; Bae, Gwi-Nam

2010-02-01

Carbon nanotubes (CNTs) are representative-engineered nanomaterials with unique properties. The safe production of CNTs urgently requires reliable tools to assess inhalation exposure. In this study, on-line aerosol instruments were employed to detect the release of multi-walled CNTs (MWCNTs) in workplace environments. The size responses of aerosol instruments consisting of both a scanning mobility particle sizer (SMPS) and an aerodynamic particle sizer (APS) were examined using five types of commercial MWCNTs. A MWCNT solution and powder were aerosolized using atomizing and shaking methods, respectively. Regardless of the phase and purity, the aerosolized MWCNTs showed consistent size distributions with both SMPS and APS. The SMPS and APS measurements revealed a dominant broad peak at approximately 200-400 nm and a distinct narrow peak at approximately 2 μm, respectively. Comparing with field application of the two aerosol instruments, the APS response could be a fingerprint of the MWCNTs in a real workplace environment. A modification of the atomizing method is recommended for the long-term inhalation toxicity studies.

Environmental and Sustainable Technology Evaluation: Mold-Resistant Armacell Insulation--Armacell LLC, AP Armaflex Black

EPA Science Inventory

The ESTE test program measured the mold resistance of Armacell AP Armaflex Black insulation. Tests for emissions of VOCs and formaldehyde were also performed. AP Armaflex Roll Insulation is a black flexible closed-cell, fiber-free elastomeric thermal insulation. The expanded clos...

Hypermethylation of AP-2Alpha as a Prognostic Marker for DCIS

DTIC Science & Technology

2008-05-01

Unfortunately, among the methylation status of the AP2, CYCLIN D, ECAD , GSTP, and SSOCS genes, either as individual genes, or in combinations, no...0.61 to 4.10) 1.00 (referent) 0.35 ECAD M UM 0 100 3 97 GSTP M UM 40 60 24 76 2.02 (0.72 to 5.64) 1.00...Missing data: 1.4% for AP2, CYCLIN D, ECAD , GSTP; 4.2% for SSOCS; 2.8% for nuclear grade. §M=methylated; UM=unmethylated; +Two-sided

APS-Workshop on Characterization of MMIC (Monolithic Microwave Integrated Circuit) Devices for Array Antenna

NASA Technical Reports Server (NTRS)

Smetana, Jerry (Editor); Mittra, Raj (Editor); Laprade, Nick; Edward, Bryan; Zaghloul, Amir

1987-01-01

The IEEE AP-S ADCOM is attempting to expand its educational, tutorial and information exchange activities as a further benefit to all members. To this end, ADCOM will be forming specialized workshops on topics of interest to its members. The first such workshop on Characterization and Packaging of MMIC Devices for Array Antennas was conceived. The workshop took place on June 13, 1986 as part of the 1986 International Symposium sponsored by IEEE AP-S and URSI in Philadelphia, PA, June 9-13, 1986. The workshop was formed to foster the interchange of ideas among MMIC device users and to provide a forum to collect and focus information among engineers experienced and interested in the topic. After brief presentations by the panelists and comments from attendees on several subtopics, the group was divided into working committees. Each committee evaluated and made recommendations on one of the subtopics.

Experimental Evaluation of Unicast and Multicast CoAP Group Communication

PubMed Central

Ishaq, Isam; Hoebeke, Jeroen; Moerman, Ingrid; Demeester, Piet

2016-01-01

The Internet of Things (IoT) is expanding rapidly to new domains in which embedded devices play a key role and gradually outnumber traditionally-connected devices. These devices are often constrained in their resources and are thus unable to run standard Internet protocols. The Constrained Application Protocol (CoAP) is a new alternative standard protocol that implements the same principals as the Hypertext Transfer Protocol (HTTP), but is tailored towards constrained devices. In many IoT application domains, devices need to be addressed in groups in addition to being addressable individually. Two main approaches are currently being proposed in the IoT community for CoAP-based group communication. The main difference between the two approaches lies in the underlying communication type: multicast versus unicast. In this article, we experimentally evaluate those two approaches using two wireless sensor testbeds and under different test conditions. We highlight the pros and cons of each of them and propose combining these approaches in a hybrid solution to better suit certain use case requirements. Additionally, we provide a solution for multicast-based group membership management using CoAP. PMID:27455262

Comparative transcriptome profiling of upland (VS16) and lowland (AP13) ecotypes of switchgrass.

PubMed

Ayyappan, Vasudevan; Saha, Malay C; Thimmapuram, Jyothi; Sripathi, Venkateswara R; Bhide, Ketaki P; Fiedler, Elizabeth; Hayford, Rita K; Kalavacharla, Venu Kal

2017-01-01

Transcriptomes of two switchgrass genotypes representing the upland and lowland ecotypes will be key tools in switchgrass genome annotation and biotic and abiotic stress functional genomics. Switchgrass (Panicum virgatum L.) is an important bioenergy feedstock for cellulosic ethanol production. We report genome-wide transcriptome profiling of two contrasting tetraploid switchgrass genotypes, VS16 and AP13, representing the upland and lowland ecotypes, respectively. A total of 268 million Illumina short reads (50 nt) were generated, of which, 133 million were obtained in AP13 and the rest 135 million in VS16. More than 90% of these reads were mapped to the switchgrass reference genome (V1.1). We identified 6619 and 5369 differentially expressed genes in VS16 and AP13, respectively. Gene ontology and KEGG pathway analysis identified key genes that regulate important pathways including C4 photosynthesis, photorespiration and phenylpropanoid metabolism. A series of genes (33) involved in photosynthetic pathway were up-regulated in AP13 but only two genes showed higher expression in VS16. We identified three dicarboxylate transporter homologs that were highly expressed in AP13. Additionally, genes that mediate drought, heat, and salinity tolerance were also identified. Vesicular transport proteins, syntaxin and signal recognition particles were seen to be up-regulated in VS16. Analyses of selected genes involved in biosynthesis of secondary metabolites, plant-pathogen interaction, membrane transporters, heat, drought and salinity stress responses confirmed significant variation in the relative expression reflected in RNA-Seq data between VS16 and AP13 genotypes. The phenylpropanoid pathway genes identified here are potential targets for biofuel conversion.

Nuclear Reactor Safety--The APS Submits its Report

ERIC Educational Resources Information Center

Physics Today, 1975

1975-01-01

Presents the summary section of the American Physical Society (APS) report on the safety features of the light-water reactor, reviews the design, construction, and operation of a reactor and outlines the primary engineered safety features. Summarizes the major recommendations of the study group. (GS)

Geminivirus-encoded TrAP suppressor inhibits the histone methyltransferase SUVH4/KYP to counter host defense

PubMed Central

Castillo-González, Claudia; Liu, Xiuying; Huang, Changjun; Zhao, Changjiang; Ma, Zeyang; Hu, Tao; Sun, Feng; Zhou, Yijun; Zhou, Xueping; Wang, Xiu-Jie; Zhang, Xiuren

2015-01-01

Transcriptional gene silencing (TGS) can serve as an innate immunity against invading DNA viruses throughout Eukaryotes. Geminivirus code for TrAP protein to suppress the TGS pathway. Here, we identified an Arabidopsis H3K9me2 histone methyltransferase, Su(var)3-9 homolog 4/Kryptonite (SUVH4/KYP), as a bona fide cellular target of TrAP. TrAP interacts with the catalytic domain of KYP and inhibits its activity in vitro. TrAP elicits developmental anomalies phenocopying several TGS mutants, reduces the repressive H3K9me2 mark and CHH DNA methylation, and reactivates numerous endogenous KYP-repressed loci in vivo. Moreover, KYP binds to the viral chromatin and controls its methylation to combat virus infection. Notably, kyp mutants support systemic infection of TrAP-deficient Geminivirus. We conclude that TrAP attenuates the TGS of the viral chromatin by inhibiting KYP activity to evade host surveillance. These findings provide new insight on the molecular arms race between host antiviral defense and virus counter defense at an epigenetic level. DOI: http://dx.doi.org/10.7554/eLife.06671.001 PMID:26344546

FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2.

PubMed

Steen, Kaylee A; Xu, Hongliang; Bernlohr, David A

2017-01-15

Obesity-linked metabolic disease is mechanistically associated with the accumulation of proinflammatory macrophages in adipose tissue, leading to increased reactive oxygen species (ROS) production and chronic low-grade inflammation. Previous work has demonstrated that deletion of the adipocyte fatty acid-binding protein (FABP4/aP2) uncouples obesity from inflammation via upregulation of the uncoupling protein 2 (UCP2). Here, we demonstrate that ablation of FABP4/aP2 regulates systemic redox capacity and reduces cellular protein sulfhydryl oxidation and, in particular, oxidation of mitochondrial protein cysteine residues. Coincident with the loss of FABP4/aP2 is the upregulation of the antioxidants superoxide dismutase (SOD2), catalase, methionine sulfoxide reductase A, and the 20S proteasome subunits PSMB5 and αβ. Reduced mitochondrial protein oxidation in FABP4/aP2 -/- macrophages attenuates the mitochondrial unfolded-protein response (mtUPR) as measured by expression of heat shock protein 60, Clp protease, and Lon peptidase 1. Consistent with a diminished mtUPR, FABP4/aP2 -/- macrophages exhibit reduced expression of cleaved caspase-1 and NLRP3. Secretion of interleukin 1β (IL-1β), in response to inflammasome activation, is ablated in FABP4/aP2 -/- macrophages, as well as in FABP4/aP2 inhibitor-treated cells, but partially rescued in FABP4/aP2-null macrophages when UCP2 is silenced. Collectively, these data offer a novel pathway whereby FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2 expression. Copyright © 2017 American Society for Microbiology.

Translocation pathway of protein substrates in ClpAP protease

PubMed Central

Ishikawa, Takashi; Beuron, Fabienne; Kessel, Martin; Wickner, Sue; Maurizi, Michael R.; Steven, Alasdair C.

2001-01-01

Intracellular protein degradation, which must be tightly controlled to protect normal proteins, is carried out by ATP-dependent proteases. These multicomponent enzymes have chaperone-like ATPases that recognize and unfold protein substrates and deliver them to the proteinase components for digestion. In ClpAP, hexameric rings of the ClpA ATPase stack axially on either face of the ClpP proteinase, which consists of two apposed heptameric rings. We have used cryoelectron microscopy to characterize interactions of ClpAP with the model substrate, bacteriophage P1 protein, RepA. In complexes stabilized by ATPγS, which bind but do not process substrate, RepA dimers are seen at near-axial sites on the distal surface of ClpA. On ATP addition, RepA is translocated through ≈150 Å into the digestion chamber inside ClpP. Little change is observed in ClpAP, implying that translocation proceeds without major reorganization of the ClpA hexamer. When translocation is observed in complexes containing a ClpP mutant whose digestion chamber is already occupied by unprocessed propeptides, a small increase in density is observed within ClpP, and RepA-associated density is also seen at other axial sites. These sites appear to represent intermediate points on the translocation pathway, at which segments of unfolded RepA subunits transiently accumulate en route to the digestion chamber. PMID:11287666

Effects of aluminum and iron nanoparticle additives on composite AP/HTPB solid propellant regression rate

NASA Astrophysics Data System (ADS)

Styborski, Jeremy A.

This project was started in the interest of supplementing existing data on additives to composite solid propellants. The study on the addition of iron and aluminum nanoparticles to composite AP/HTPB propellants was conducted at the Combustion and Energy Systems Laboratory at RPI in the new strand-burner experiment setup. For this study, a large literature review was conducted on history of solid propellant combustion modeling and the empirical results of tests on binders, plasticizers, AP particle size, and additives. The study focused on the addition of nano-scale aluminum and iron in small concentrations to AP/HTPB solid propellants with an average AP particle size of 200 microns. Replacing 1% of the propellant's AP with 40-60 nm aluminum particles produced no change in combustive behavior. The addition of 1% 60-80 nm iron particles produced a significant increase in burn rate, although the increase was lesser at higher pressures. These results are summarized in Table 2. The increase in the burn rate at all pressures due to the addition of iron nanoparticles warranted further study on the effect of concentration of iron. Tests conducted at 10 atm showed that the mean regression rate varied with iron concentration, peaking at 1% and 3%. Regardless of the iron concentration, the regression rate was higher than the baseline AP/HTPB propellants. These results are summarized in Table 3.

Decreased gene expression of CD2AP in Chinese patients with sporadic Alzheimer's disease.

PubMed

Tao, Qing-Qing; Liu, Zhi-Jun; Sun, Yi-Min; Li, Hong-Lei; Yang, Ping; Liu, De-Shan; Jiang, Bin; Li, Xiao-Yan; Xu, Jian-Feng; Wu, Zhi-Ying

2017-08-01

Many sporadic Alzheimer's disease (SAD) risk genes have been identified in the last decades, but most of them have not been consistently accepted. Here, we sought to identify SAD-associated genes and their potential mechanisms involved in SAD pathogenesis. A 2-stage design was employed. In stage 1, 95 variants in 75 genes that were previously reported as SAD-risk genes in Caucasian populations were evaluated in 1857 subjects (422 SAD patients and 1435 controls). In stage 2, a subset of promising variants found in stage 1 were further evaluated in an independent cohort of 1001 subjects (254 SAD and 747 controls). Variants in CD2AP were significantly associated with SAD risk in our subjects. Furthermore, CD2AP gene expression in peripheral blood lymphocytes (PBL) from 209 SAD patients and 213 controls was determined. CD2AP gene expression in PBL was significantly decreased in patients with SAD as compared with controls. Our study suggests that CD2AP is an SAD-risk gene in Chinese Han population and CD2AP gene expression is decreased in the PBL of patients with SAD, indicating its possible systemic involvement in SAD. Copyright © 2017 Elsevier Inc. All rights reserved.

Gene Duplication and Transference of Function in the paleoAP3 Lineage of Floral Organ Identity Genes

PubMed Central

Galimba, Kelsey D.; Martínez-Gómez, Jesús; Di Stilio, Verónica S.

2018-01-01

The floral organ identity gene APETALA3 (AP3) is a MADS-box transcription factor involved in stamen and petal identity that belongs to the B-class of the ABC model of flower development. Thalictrum (Ranunculaceae), an emerging model in the non-core eudicots, has AP3 homologs derived from both ancient and recent gene duplications. Prior work has shown that petals have been lost repeatedly and independently in Ranunculaceae in correlation with the loss of a specific AP3 paralog, and Thalictrum represents one of these instances. The main goal of this study was to conduct a functional analysis of the three AP3 orthologs present in Thalictrum thalictroides, representing the paleoAP3 gene lineage, to determine the degree of redundancy versus divergence after gene duplication. Because Thalictrum lacks petals, and has lost the petal-specific AP3, we also asked whether heterotopic expression of the remaining AP3 genes contributes to the partial transference of petal function to the first whorl found in insect-pollinated species. To address these questions, we undertook functional characterization by virus-induced gene silencing (VIGS), protein–protein interaction and binding site analyses. Our results illustrate partial redundancy among Thalictrum AP3s, with deep conservation of B-class function in stamen identity and a novel role in ectopic petaloidy of sepals. Certain aspects of petal function of the lost AP3 locus have apparently been transferred to the other paralogs. A novel result is that the protein products interact not only with each other, but also as homodimers. Evidence presented here also suggests that expression of the different ThtAP3 paralogs is tightly integrated, with an apparent disruption of B function homeostasis upon silencing of one of the paralogs that codes for a truncated protein. To explain this result, we propose two testable alternative scenarios: that the truncated protein is a dominant negative mutant or that there is a compensational

Adipocyte Fatty Acid–Binding Protein, aP2, Alters Late Atherosclerotic Lesion Formation in Severe Hypercholesterolemia

PubMed Central

Boord, Jeffrey B.; Maeda, Kazuhisa; Makowski, Liza; Babaev, Vladimir R.; Fazio, Sergio; Linton, MacRae F.; Hotamisligil, Gökhan S.

2014-01-01

Objective The adipocyte fatty acid-binding protein, aP2, has important effects on insulin resistance, lipid metabolism, and atherosclerosis. Its expression in macrophages enhances early foam cell formation and atherosclerosis in vivo. This study was designed to determine whether aP2 deficiency has a similar effect in the setting of advanced atherosclerosis and severe hypercholesterolemia. Methods and Results Mice deficient in aP2 and apolipoprotein E (aP2−/−apoE−/− mice) and apolipoprotein E-deficient control mice (apoE−/− mice) were fed a Western diet for 14 weeks. No significant differences in fasting serum levels of cholesterol, triglycerides, or free fatty acids were found between groups for each sex. Compared with apoE−/− control mice, male and female aP2−/−apoE−/− mice had significant reductions in mean atherosclerotic lesion size in the proximal aorta, en face aorta, and innominate/right carotid artery. Feeding the Western diet in the apoE-deficient background did not cause a significant reduction in insulin sensitivity in vivo, as determined by steady-state serum glucose levels and insulin tolerance testing. Conclusions These data demonstrate an important role for aP2 expression in the advanced stages of atherosclerotic lesion formation. Thus, aP2 provides an important physiological link between different features of the metabolic syndrome and is a potential target for therapy of atherosclerosis. PMID:12377750

Time Trials--An AP Physics Challenge Lab

ERIC Educational Resources Information Center

Jones, David

2009-01-01

I have come to the conclusion that for high school physics classroom and laboratory experiences, simpler is better! In this paper I describe a very simple and effective lab experience that my AP students have thoroughly enjoyed year after year. I call this lab exercise "Time Trials." The experiment is simple in design and it is a lot of fun for…

AP-IO: asynchronous pipeline I/O for hiding periodic output cost in CFD simulation.

PubMed

Xiaoguang, Ren; Xinhai, Xu

2014-01-01

Computational fluid dynamics (CFD) simulation often needs to periodically output intermediate results to files in the form of snapshots for visualization or restart, which seriously impacts the performance. In this paper, we present asynchronous pipeline I/O (AP-IO) optimization scheme for the periodically snapshot output on the basis of asynchronous I/O and CFD application characteristics. In AP-IO, dedicated background I/O processes or threads are in charge of handling the file write in pipeline mode, therefore the write overhead can be hidden with more calculation than classic asynchronous I/O. We design the framework of AP-IO and implement it in OpenFOAM, providing CFD users with a user-friendly interface. Experimental results on the Tianhe-2 supercomputer demonstrate that AP-IO can achieve a good optimization effect for the periodical snapshot output in CFD application, and the effect is especially better for massively parallel CFD simulations, which can reduce the total execution time up to about 40%.

AP-IO: Asynchronous Pipeline I/O for Hiding Periodic Output Cost in CFD Simulation

PubMed Central

Xiaoguang, Ren; Xinhai, Xu

2014-01-01

Computational fluid dynamics (CFD) simulation often needs to periodically output intermediate results to files in the form of snapshots for visualization or restart, which seriously impacts the performance. In this paper, we present asynchronous pipeline I/O (AP-IO) optimization scheme for the periodically snapshot output on the basis of asynchronous I/O and CFD application characteristics. In AP-IO, dedicated background I/O processes or threads are in charge of handling the file write in pipeline mode, therefore the write overhead can be hidden with more calculation than classic asynchronous I/O. We design the framework of AP-IO and implement it in OpenFOAM, providing CFD users with a user-friendly interface. Experimental results on the Tianhe-2 supercomputer demonstrate that AP-IO can achieve a good optimization effect for the periodical snapshot output in CFD application, and the effect is especially better for massively parallel CFD simulations, which can reduce the total execution time up to about 40%. PMID:24955390

A Proxy Design to Leverage the Interconnection of CoAP Wireless Sensor Networks with Web Applications

PubMed Central

Ludovici, Alessandro; Calveras, Anna

2015-01-01

In this paper, we present the design of a Constrained Application Protocol (CoAP) proxy able to interconnect Web applications based on Hypertext Transfer Protocol (HTTP) and WebSocket with CoAP based Wireless Sensor Networks. Sensor networks are commonly used to monitor and control physical objects or environments. Smart Cities represent applications of such a nature. Wireless Sensor Networks gather data from their surroundings and send them to a remote application. This data flow may be short or long lived. The traditional HTTP long-polling used by Web applications may not be adequate in long-term communications. To overcome this problem, we include the WebSocket protocol in the design of the CoAP proxy. We evaluate the performance of the CoAP proxy in terms of latency and memory consumption. The tests consider long and short-lived communications. In both cases, we evaluate the performance obtained by the CoAP proxy according to the use of WebSocket and HTTP long-polling. PMID:25585107

Overexpression of BpAP1 induces early flowering and produces dwarfism in Betula platyphylla × Betula pendula.

PubMed

Huang, Haijiao; Wang, Shan; Jiang, Jing; Liu, Guifeng; Li, Huiyu; Chen, Su; Xu, Huanwen

2014-08-01

The involvement of APETALA1 (AP1) in the flowering transition has been the focus of much research. Here, we produced Betula platyphylla × Betula pendula (birch) lines that overexpressed BpAP1 using Agrobacterium-mediated transformation; we obtained five independent 35S::BpAP1 transgenic lines. Polymerase chain reaction (PCR), Southern, northern and western analyses were used to identify the transformants. As determined by quantitative real-time PCR (qRT-PCR), BpAP1 expression in roots, shoots, leaves and terminal buds of 35S::BpAP1 transgenic lines was significantly higher than that in the wild type (WT, P < 0.01). The average height of 2-year-old 35S::BpAP1 plants was significantly lower (41.17%) than that of non-transgenic plants. In the 35S::BpAP1 lines, inflorescences emerged successively beginning 2 months after transplanting. In addition, the length-diameter ratio of fully developed male and female inflorescences were both significantly less than those of the WT (P < 0.05), i.e. the morphological characteristic was stubby. The male inflorescences emerged early, with empty, draped anthers, and pollen was rarely produced, whereas the female floret structure was not different from WT. The pistils developed normally and could accept pollen, leading to the production of hybrid progeny (F1 ). F1 plants completed flowering within only 1 year after sowing. We demonstrate that BpAP1 can be inherited through sexual reproduction. Overexpression of BpAP1 caused early flowering and dwarfism; these lines had an obviously shortened juvenile phase. These results greatly increase our understanding of the mechanisms underlying the flowering transition and enhance genetic studies of birch traits, and they open up new possibilities for the breeding of birch and other woody plants. © 2013 Scandinavian Plant Physiology Society.

Moto del Sole intorno al baricentro del sistema solare

NASA Astrophysics Data System (ADS)

Piovan, Luciano; Milani, Franco

2006-06-01

The paper discusses the Sun's motion around the barycentre of the Solar System determined by the ever-changing dispositon of the planets over approximately 2000 years. Files of high-quality data taken from international sites were used in common personal computers. The Sun shows a repetitive behaviour, where an apocycle (ApC, decennial period in which the Sun moves very far from the barycentre) is followed by a pericycle (PeC, decennial period in which the Sun moves very near the barycentre) and by another ApC, etc. Periodicities exist in the short period (supercycles, SpC, lasting about 40 years and made of two sequences ApC-PeC, each lasting 20 years), in the mean period (phases comprising a sequence of 4 to 5 SpC, then lasting approximately 160 or 200 years respectively, mean value 180 years), and in the long period (hypercycles, IpC, consisting of two phases, lasting approximately 360 or 400 years). During one phase, the successive ApCs start opposed to each other in ecliptical coordinates and end nearly superimposed; during the following phase the ApCs start superimposed one over the other and end opposed to each other in ecliptical coordinates. The phase length, whose mean value is about 180 years, is very near the modulation of the maxima of the sunspot cycle (178.7 years). The periodicities found are modulated mainly by the alignment of Jupiter, or by both Jupiter and Saturn, with the Sun and the barycentre of the Solar System.

Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

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

Wiese, Claudia; Dray, Eloise; Groesser, Torsten

2007-04-11

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1more » functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.« less

Accurate age determinations of several nearby open clusters containing magnetic Ap stars

NASA Astrophysics Data System (ADS)

Silaj, J.; Landstreet, J. D.

2014-06-01

Context. To study the time evolution of magnetic fields, chemical abundance peculiarities, and other characteristics of magnetic Ap and Bp stars during their main sequence lives, a sample of these stars in open clusters has been obtained, as such stars can be assumed to have the same ages as the clusters to which they belong. However, in exploring age determinations in the literature, we find a large dispersion among different age determinations, even for bright, nearby clusters. Aims: Our aim is to obtain ages that are as accurate as possible for the seven nearby open clusters α Per, Coma Ber, IC 2602, NGC 2232, NGC 2451A, NGC 2516, and NGC 6475, each of which contains at least one magnetic Ap or Bp star. Simultaneously, we test the current calibrations of Te and luminosity for the Ap/Bp star members, and identify clearly blue stragglers in the clusters studied. Methods: We explore the possibility that isochrone fitting in the theoretical Hertzsprung-Russell diagram (i.e. log (L/L⊙) vs. log Te), rather than in the conventional colour-magnitude diagram, can provide more precise and accurate cluster ages, with well-defined uncertainties. Results: Well-defined ages are found for all the clusters studied. For the nearby clusters studied, the derived ages are not very sensitive to the small uncertainties in distance, reddening, membership, metallicity, or choice of isochrones. Our age determinations are all within the range of previously determined values, but the associated uncertainties are considerably smaller than the spread in recent age determinations from the literature. Furthermore, examination of proper motions and HR diagrams confirms that the Ap stars identified in these clusters are members, and that the presently accepted temperature scale and bolometric corrections for Ap stars are approximately correct. We show that in these theoretical HR diagrams blue stragglers are particularly easy to identify. Conclusions: Constructing the theoretical HR diagram

A Novel GLP1 Receptor Interacting Protein ATP6ap2 Regulates Insulin Secretion in Pancreatic Beta Cells*

PubMed Central

Dai, Feihan F.; Bhattacharjee, Alpana; Liu, Ying; Batchuluun, Battsetseg; Zhang, Ming; Wang, Xinye Serena; Huang, Xinyi; Luu, Lemieux; Zhu, Dan; Gaisano, Herbert; Wheeler, Michael B.

2015-01-01

GLP1 activates its receptor, GLP1R, to enhance insulin secretion. The activation and transduction of GLP1R requires complex interactions with a host of accessory proteins, most of which remain largely unknown. In this study, we used membrane-based split ubiquitin yeast two-hybrid assays to identify novel GLP1R interactors in both mouse and human islets. Among these, ATP6ap2 (ATPase H+-transporting lysosomal accessory protein 2) was identified in both mouse and human islet screens. ATP6ap2 was shown to be abundant in islets including both alpha and beta cells. When GLP1R and ATP6ap2 were co-expressed in beta cells, GLP1R was shown to directly interact with ATP6ap2, as assessed by co-immunoprecipitation. In INS-1 cells, overexpression of ATP6ap2 did not affect insulin secretion; however, siRNA knockdown decreased both glucose-stimulated and GLP1-induced insulin secretion. Decreases in GLP1-induced insulin secretion were accompanied by attenuated GLP1 stimulated cAMP accumulation. Because ATP6ap2 is a subunit required for V-ATPase assembly of insulin granules, it has been reported to be involved in granule acidification. In accordance with this, we observed impaired insulin granule acidification upon ATP6ap2 knockdown but paradoxically increased proinsulin secretion. Importantly, as a GLP1R interactor, ATP6ap2 was required for GLP1-induced Ca2+ influx, in part explaining decreased insulin secretion in ATP6ap2 knockdown cells. Taken together, our findings identify a group of proteins that interact with the GLP1R. We further show that one interactor, ATP6ap2, plays a novel dual role in beta cells, modulating both GLP1R signaling and insulin processing to affect insulin secretion. PMID:26272612

76 FR 82079 - AP1000 Design Certification Amendment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

... reference Revision 15 of the design control document (DCD) (ADAMS Accession No. ML053460400), which... to DAC in the areas of piping design (Chapter 3), instrumentation and control (I&C) systems (Chapter... Systems Manual, as described in the AP1000 Design Control Document, Revision 17, meets the criteria of...

Structure and substrate-binding mechanism of human Ap4A hydrolase.

PubMed

Swarbrick, James D; Buyya, Smrithi; Gunawardana, Dilantha; Gayler, Kenwyn R; McLennan, Alexander G; Gooley, Paul R

2005-03-04

Asymmetric diadenosine 5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) hydrolases play a major role in maintaining homeostasis by cleaving the metabolite diadenosine tetraphosphate (Ap(4)A) back into ATP and AMP. The NMR solution structures of the 17-kDa human asymmetric Ap(4)A hydrolase have been solved in both the presence and absence of the product ATP. The adenine moiety of the nucleotide predominantly binds in a ring stacking arrangement equivalent to that observed in the x-ray structure of the homologue from Caenorhabditis elegans. The binding site is, however, markedly divergent to that observed in the plant/pathogenic bacteria class of enzymes, opening avenues for the exploration of specific therapeutics. Binding of ATP induces substantial conformational and dynamic changes that were not observed in the C. elegans structure. In contrast to the C. elegans homologue, important side chains that play a major role in substrate binding do not have to reorient to accommodate the ligand. This may have important implications in the mechanism of substrate recognition in this class of enzymes.

30 Years of APS Congressional Fellows: Looking Back and Looking Forward

NASA Astrophysics Data System (ADS)

2003-04-01

In 1973 AAAS launched a Congressional Fellows Program, and APS was one of three founding participants. Since then, APS has funded one or two Fellows annually to work with a Congressional Committee or on the personal staff of a Member of Congress. These fellows individually and collectively have had and continue to have a large impact in Washington. Six Fellows from different periods of the 30-year program, including a current Member of Congress, will present their views and assessments of the Fellowship program. They will address how it affected them, what it has done for the country and how APS should plan for the future. There will be ample time for questions and discussion. Panelists: Ben Cooper, Association of Oil Pipe Lines (Fellow, 1973-74) Rush Holt, Member, House of Representatives (Fellow, 1982-83) Jane Alexander, Office of Naval Research (Fellow, 1986-87) Duncan Moore, University of Rochester (Fellow, 1993-94) Peter Rooney, House Committee on Science (Fellow, 1997-98) Sherri Stephan, Senate Committee on Government Affairs (Fellow, 2000-01)

Effect of diadenosine tetraphosphate (AP4A) on coronary arterial microvessels in the beating canine heart.

PubMed

Sugimura, A; Kanatsuka, H; Tanikawa, T; Ong, B H; Shirato, K

2000-11-01

Diadenosine tetraphosphate (AP4A) can be released from activated platelets and the present study examined its effect on coronary arterial microvessels. The role of purinoceptors in the coronary microcirculation in vivo was also investigated. In open chest dogs, coronary arterioles were observed using a microscope with a floating objective. In Protocol 1, AP4A (1, 10, 100 and 1,000 micromol/L) was superfused onto the heart surface before and during the superfusion of 10 micromol/L of 8-phenyltheophylline (8-PT), a P1 purinoceptor blocker. In Protocol 2, AP4A (0.1, 1, 10, and 100 nmol x kg(-1) x min(-1)) was infused into the left anterior descending coronary artery before and during the superfusion of 10 micromol/L of 8-PT. In addition to 8-PT, 30 micromol/L of pyridoxalphosphate-6-azophenyl 2',4'-disulphonic acid (PPADS), a P2X purinoceptor blocker in Protocol 3, or 300 micromol/L of N(omega)-nitro-L-arginine (LNNA) in Protocol 4, was continuously superfused, and 4 doses of AP4A were cumulatively superfused as in Protocol 1. In Protocol 5, 10 micromol/L of alpha,beta-methylene ATP, an agonist of P2X purinoceptors, was superfused for 60 min. Superfused AP4A dilated arterioles in a dose-dependent manner. The magnitude of dilatation was greater in smaller arterioles (small vessel < or = 150 microm: 24.5+/-2.2% vs large vessel > 150 microm: 10.6+/-1.5% at a dose of 1,000 micromol/L, p<0.001). On the other hand, intraluminally applied AP4A also dilated arterioles, but no size dependency was shown. In the presence of 8-PT, vasodilatory responses to superfused and intraluminally applied AP4A were attenuated and the lower doses of AP4A constricted arterioles. This vasoconstrictor effect was not affected by PPADS. The vasodilatory effect of the higher doses of AP4A was almost abolished in the presence of LNNA. Alpha,beta-methylene ATP had no effect on coronary microvascular diameters. AP4A has bidirectional effects on coronary arterial microvessels: vasodilatory effects

Genome-Wide Investigation and Expression Profiling of AP2/ERF Transcription Factor Superfamily in Foxtail Millet (Setaria italica L.)

PubMed Central

Lata, Charu; Mishra, Awdhesh Kumar; Muthamilarasan, Mehanathan; Bonthala, Venkata Suresh; Khan, Yusuf; Prasad, Manoj

2014-01-01

The APETALA2/ethylene-responsive element binding factor (AP2/ERF) family is one of the largest transcription factor (TF) families in plants that includes four major sub-families, namely AP2, DREB (dehydration responsive element binding), ERF (ethylene responsive factors) and RAV (Related to ABI3/VP). AP2/ERFs are known to play significant roles in various plant processes including growth and development and biotic and abiotic stress responses. Considering this, a comprehensive genome-wide study was conducted in foxtail millet (Setaria italica L.). A total of 171 AP2/ERF genes were identified by systematic sequence analysis and were physically mapped onto nine chromosomes. Phylogenetic analysis grouped AP2/ERF genes into six classes (I to VI). Duplication analysis revealed that 12 (∼7%) SiAP2/ERF genes were tandem repeated and 22 (∼13%) were segmentally duplicated. Comparative physical mapping between foxtail millet AP2/ERF genes and its orthologs of sorghum (18 genes), maize (14 genes), rice (9 genes) and Brachypodium (6 genes) showed the evolutionary insights of AP2/ERF gene family and also the decrease in orthology with increase in phylogenetic distance. The evolutionary significance in terms of gene-duplication and divergence was analyzed by estimating synonymous and non-synonymous substitution rates. Expression profiling of candidate AP2/ERF genes against drought, salt and phytohormones revealed insights into their precise and/or overlapping expression patterns which could be responsible for their functional divergence in foxtail millet. The study showed that the genes SiAP2/ERF-069, SiAP2/ERF-103 and SiAP2/ERF-120 may be considered as potential candidate genes for further functional validation as well for utilization in crop improvement programs for stress resistance since these genes were up-regulated under drought and salinity stresses in ABA dependent manner. Altogether the present study provides new insights into evolution, divergence and systematic

Genome-wide investigation and expression profiling of AP2/ERF transcription factor superfamily in foxtail millet (Setaria italica L.).

PubMed

Lata, Charu; Mishra, Awdhesh Kumar; Muthamilarasan, Mehanathan; Bonthala, Venkata Suresh; Khan, Yusuf; Prasad, Manoj

2014-01-01

The APETALA2/ethylene-responsive element binding factor (AP2/ERF) family is one of the largest transcription factor (TF) families in plants that includes four major sub-families, namely AP2, DREB (dehydration responsive element binding), ERF (ethylene responsive factors) and RAV (Related to ABI3/VP). AP2/ERFs are known to play significant roles in various plant processes including growth and development and biotic and abiotic stress responses. Considering this, a comprehensive genome-wide study was conducted in foxtail millet (Setaria italica L.). A total of 171 AP2/ERF genes were identified by systematic sequence analysis and were physically mapped onto nine chromosomes. Phylogenetic analysis grouped AP2/ERF genes into six classes (I to VI). Duplication analysis revealed that 12 (∼7%) SiAP2/ERF genes were tandem repeated and 22 (∼13%) were segmentally duplicated. Comparative physical mapping between foxtail millet AP2/ERF genes and its orthologs of sorghum (18 genes), maize (14 genes), rice (9 genes) and Brachypodium (6 genes) showed the evolutionary insights of AP2/ERF gene family and also the decrease in orthology with increase in phylogenetic distance. The evolutionary significance in terms of gene-duplication and divergence was analyzed by estimating synonymous and non-synonymous substitution rates. Expression profiling of candidate AP2/ERF genes against drought, salt and phytohormones revealed insights into their precise and/or overlapping expression patterns which could be responsible for their functional divergence in foxtail millet. The study showed that the genes SiAP2/ERF-069, SiAP2/ERF-103 and SiAP2/ERF-120 may be considered as potential candidate genes for further functional validation as well for utilization in crop improvement programs for stress resistance since these genes were up-regulated under drought and salinity stresses in ABA dependent manner. Altogether the present study provides new insights into evolution, divergence and systematic

Novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies.

PubMed

Wright, Michael; Miller, Andrew D

2006-02-15

Tandem synthetic-biosynthetic procedures were used to prepare two novel fluorescent labelled affinity probes for diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A)-binding studies. These compounds (dial-mant-Ap4A and azido-mant-Ap4A) are shown to clearly distinguish known Ap4A-binding proteins from Escherichia coli (LysU and GroEL) and a variety of other control proteins. Successful labelling of chaperonin GroEL appears to be allosteric with respect to the well-characterized adenosine 5'-triphosphate (ATP)-binding site, suggesting that GroEL possesses a distinct Ap4A-binding site.

A Comparison of Van Allen Belt Radiation Environment Modeling Programs: AE8/AP8 Legacy, AE9/AP9, and SPENVIS

NASA Technical Reports Server (NTRS)

Reed, Evan; Pellish, Jonathan

2016-01-01

In the space surrounding Earth there exists an active radiation environment consisting mostly of electrons and protons that have been trapped by Earths magnetic field. This radiation, also known as the Van Allen Belts, has the potential to damage man-made satellites in orbit; thus, proper precautions must be taken to shield NASA assets from this phenomenon. Data on the Van Allen Belts has been collected continuously by a multitude of space-based instruments since the beginning of space exploration. Subsequently, using theory to fill in the gaps in the collected data, computer models have been developed that take in the orbital information of a hypothetical mission and output the expected particle fluence and flux for that orbit. However, as new versions of the modeling system are released, users are left wondering how the new version differs from the old. Therefore, we performed a comparison of three different editions of the modeling system: AE8/AP8 (legacy), which is included in the model 9 graphical user interface as an option for ones calculations, AE9/AP9, and the Space Environment Information System (SPENVIS), which is an online-based form of AE8/AP8 developed by NASA and the European Space Agency that changed the code to allow the program to extrapolate data to predict fluence and flux at higher energies. Although this evaluation is still ongoing, it is predicted that the model 8 (legacy) and SPENVIS version will have identical outputs with the exception of the extended energy levels from SPENVIS, while model 9 will provide different fluences than model 8 based on additional magnetic field descriptions and on-orbit data.

Development of cotton gin PM2.5 emission factors for EPA’S AP-42

USDA-ARS?s Scientific Manuscript database

The Compilation of Air Pollution Emission Factors (AP-42) emission factors are assigned ratings, from A (Excellent) to E (Poor), based on the quality of data used to develop them. AP-42 currently contains no PM2.5 cotton gin emission factors. In an effort to develop science-based data for regulating...

AP1000{sup R} nuclear power plant safety overview for spent fuel cooling

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

Gorgemans, J.; Mulhollem, L.; Glavin, J.

2012-07-01

The AP1000{sup R} plant is an 1100-MWe class pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance, safety and costs. The AP1000 design uses passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems such as AC power, component cooling water, service water or HVAC. Furthermore, these passive features 'fail safe' during a non-LOCA event such that DC power and instrumentation are not required. The AP1000 also has simple, active, defense-in-depth systems to support normal plant operations. These active systems provide the first levelmore » of defense against more probable events and they provide investment protection, reduce the demands on the passive features and support the probabilistic risk assessment. The AP1000 passive safety approach allows the plant to achieve and maintain safe shutdown in case of an accident for 72 hours without operator action, meeting the expectations provided in the U.S. Utility Requirement Document and the European Utility Requirements for passive plants. Limited operator actions are required to maintain safe conditions in the spent fuel pool via passive means. In line with the AP1000 approach to safety described above, the AP1000 plant design features multiple, diverse lines of defense to ensure spent fuel cooling can be maintained for design-basis events and beyond design-basis accidents. During normal and abnormal conditions, defense-in-depth and other systems provide highly reliable spent fuel pool cooling. They rely on off-site AC power or the on-site standby diesel generators. For unlikely design basis events with an extended loss of AC power (i.e., station blackout) or loss of heat sink or both, spent fuel cooling can still be provided indefinitely: - Passive systems, requiring minimal or no operator actions, are sufficient for at least 72 hours under all

Zinc as a second messenger of mitogenic induction. Effects on diadenosine tetraphosphate (Ap4A) and DNA synthesis.

PubMed

Grummt, F; Weinmann-Dorsch, C; Schneider-Schaulies, J; Lux, A

1986-03-01

DNA synthesis and adenosine(5')tetraphosphate(5')adenosine (Ap4A) levels decrease in cells treated with EDTA. The inhibitory effect of EDTA can be reversed with micromolar amounts of ZnCl2. ZnCl2 in micromolar concentrations also inhibits Ap4A hydrolase and stimulates amino acid-dependent Ap4A synthesis, suggesting that Zn2+ is modulating intracellular Ap4A pools. Serum addition to G1-arrested cells enhances uptake of Zn, whereas serum depletion leads to a fivefold decrease of the rates of zinc uptake. These results are discussed by regarding Zn2+ as a putative 'second messenger' of mitogenic induction and Ap4A as a possible 'third messenger' and trigger of DNA synthesis.

Analysis of the AP-42, supplement 5 emission model.

DOT National Transportation Integrated Search

1976-01-01

This report examines the performance of the source strength model presented in the U.S. Environmental Protection Agency publication AP-42, Supplement 5 relative to field data gathered during the AIRPOL project and relative to the previous source stre...

Neuropsychological correlates of transcription factor AP-2Beta, and its interaction with COMT and MAOA in healthy females.

PubMed

Schabram, Ina; Eggermann, Thomas; Siegel, Steven J; Gründer, Gerhard; Zerres, Klaus; Vernaleken, Ingo

2013-01-01

The transcription factor AP-2β has been shown to impact clinical and neuropsychological properties. Apparently, it regulates the transcription of genes that code for molecules which are part of the catecholaminergic transmission system. This investigation focuses on possible effects of the transcription factor AP-2β intron 2 polymorphism on cognitive performance parameters. This hypothesis-driven investigation examined the effects and interactions of the transcription factor AP-2β intron 2 polymorphism, the Val158Met catechol-O-methyltransferase (COMT) polymorphism, and the variable number of tandem repeat polymorphism of monoamine oxidase A (MAOA) on cognitive performance parameters within a group of 200 healthy women (age: mean ± SD, 23.93 ± 3.33 years). The AP-2β polymorphism significantly influenced cognitive performance (in particular, the Trail Making Test part B), whereas the MAOA and COMT polymorphisms did not. However, there was an interaction effect of the AP-2β × MAOA × COMT genotypes on the decision bias β of the degraded-stimulus version of the continuous performance task. Only the Val158Met COMT polymorphism showed an influence on personality questionnaires (openness and self-transcendence; NEO Five-Factor Inventory, Temperament and Character Inventory). The transcription factor AP-2β intron 2 polymorphism had more influence on cognition than the MAOA and COMT polymorphisms. Possibly, the AP-2β genotype might influence cognition through pathways other than those that regulate MAOA and COMT transcription. Interactions of transcription factor AP-2β, COMT, and MAOA polymorphisms suggest higher leverage effects of transcription factor AP-2β in subjects with high dopamine availability. Copyright © 2013 S. Karger AG, Basel.

The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair.

PubMed

Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

2016-10-01

USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1.

The USP1-UAF1 complex interacts with RAD51AP1 to promote homologous recombination repair

PubMed Central

Cukras, Scott; Lee, Euiho; Palumbo, Emily; Benavidez, Pamela; Moldovan, George-Lucian; Kee, Younghoon

2016-01-01

ABSTRACT USP1 deubiquitinating enzyme and its stoichiometric binding partner UAF1 play an essential role in promoting DNA homologous recombination (HR) repair in response to various types of DNA damaging agents. Deubiquitination of FANCD2 may be attributed to the key role of USP1-UAF1 complex in regulating HR repair, however whether USP1-UAF1 promotes HR repair independently of FANCD2 deubiquitination is not known. Here we show evidence that the USP1-UAF1 complex has a FANCD2-independent function in promoting HR repair. Proteomic search of UAF1-interacting proteins revealed that UAF1 associates with RAD51AP1, a RAD51-interacting protein implicated in HR repair. We show that UAF1 mediates the interaction between USP1 and RAD51AP1, and that depletion of USP1 or UAF1 led to a decreased stability of RAD51AP1. Protein interaction mapping analysis identified some key residues within RAD51AP1 required for interacting with the USP1-UAF1 complex. Cells expressing the UAF1 interaction-deficient mutant of RAD51AP1 show increased chromosomal aberrations in response to Mitomycin C treatment. Moreover, similar to the RAD51AP1 depleted cells, the cells expressing UAF1-interaction deficient RAD51AP1 display persistent RAD51 foci following DNA damage exposure, indicating that these factors regulate a later step during the HR repair. These data altogether suggest that the USP1-UAF1 complex promotes HR repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1. PMID:27463890

BLOC-1 Interacts with BLOC-2 and the AP-3 Complex to Facilitate Protein Trafficking on Endosomes

PubMed Central

Di Pietro, Santiago M.; Falcón-Pérez, Juan M.; Tenza, Danièle; Setty, Subba R.G.; Marks, Michael S.; Raposo, Graça

2006-01-01

The adaptor protein (AP)-3 complex is a component of the cellular machinery that controls protein sorting from endosomes to lysosomes and specialized related organelles such as melanosomes. Mutations in an AP-3 subunit underlie a form of Hermansky-Pudlak syndrome (HPS), a disorder characterized by abnormalities in lysosome-related organelles. HPS in humans can also be caused by mutations in genes encoding subunits of three complexes of unclear function, named biogenesis of lysosome-related organelles complex (BLOC)-1, -2, and -3. Here, we report that BLOC-1 interacts physically and functionally with AP-3 to facilitate the trafficking of a known AP-3 cargo, CD63, and of tyrosinase-related protein 1 (Tyrp1), a melanosomal membrane protein previously thought to traffic only independently of AP-3. BLOC-1 also interacts with BLOC-2 to facilitate Tyrp1 trafficking by a mechanism apparently independent of AP-3 function. Both BLOC-1 and -2 localize mainly to early endosome-associated tubules as determined by immunoelectron microscopy. These findings support the idea that BLOC-1 and -2 represent hitherto unknown components of the endosomal protein trafficking machinery. PMID:16837549

The E3 ubiquitin ligase Trim7 mediates c-Jun/AP-1 activation by Ras signalling

PubMed Central

Chakraborty, Atanu; Diefenbacher, Markus E.; Mylona, Anastasia; Kassel, Olivier; Behrens, Axel

2015-01-01

The c-Jun/AP-1 transcription factor controls key cellular behaviours, including proliferation and apoptosis, in response to JNK and Ras/MAPK signalling. While the JNK pathway has been well characterised, the mechanism of activation by Ras was elusive. Here we identify the uncharacterised ubiquitin ligase Trim7 as a critical component of AP-1 activation via Ras. We found that MSK1 directly phosphorylates Trim7 in response to direct activation by the Ras–Raf–MEK–ERK pathway, and this modification stimulates Trim7 E3 ubiquitin ligase activity. Trim7 mediates Lys63-linked ubiquitination of the AP-1 coactivator RACO-1, leading to RACO-1 protein stabilisation. Consequently, Trim7 depletion reduces RACO-1 levels and AP-1-dependent gene expression. Moreover, transgenic overexpression of Trim7 increases lung tumour burden in a Ras-driven cancer model, and knockdown of Trim7 in established xenografts reduces tumour growth. Thus, phosphorylation-ubiquitination crosstalk between MSK1, Trim7 and RACO-1 completes the long sought-after mechanism linking growth factor signalling and AP-1 activation. PMID:25851810

The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

PubMed Central

Garces de los Fayos Alonso, Ines; Lagger, Sabine; Merkel, Olaf; Kenner, Lukas

2018-01-01

The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma. PMID:29597249

Molecular cloning of Rab5 (ApRab5) in Aiptasia pulchella and its retention in phagosomes harboring live zooxanthellae.

PubMed

Chen, Ming-Chyuan; Cheng, Ying-Min; Hong, Min-Chang; Fang, Lee-Shing

2004-11-19

The intracellular association of symbiotic dinoflagellates (zooxanthellae) with marine cnidarians is the very foundation of the highly productive and diversified coral reef ecosystems. To reveal its underlying molecular mechanisms, we previously cloned ApRab7, a Rab7 homologue of the sea anemone Aiptasia pulchella, and demonstrated its selective exclusion from phagosomes containing live zooxanthellae, but not from those containing either dead or photosynthesis-impaired algae. In this study, Rab5 was characterized, due to its key role in endocytosis and phagocytosis acting upstream of Rab7. The Aiptasia Rab5 homologue (ApRab5) is 79.5% identical to human Rab5C and contains all Rab-specific signature motifs. Subcellular fractionation study showed that ApRab5 is mainly cytosolic. EGFP reporter and phagocytosis studies indicated that membrane-associated ApRab5 is present in early endocytic and phagocytic compartments, and is able to promote their fusion. Significantly, immunofluorescence study showed that the majority of phagosomes containing either resident or newly internalized live zooxanthellae were labeled with ApRab5, while those containing either heat-killed or photosynthesis-impaired algae were mostly negative for ApRab5 staining whereas the opposite was observed for ApRab7. We propose that active phagosomal retention of ApRab5 is part of the mechanisms employed by live zooxanthellae to: (1) persist inside their host cells and (2) exclude ApRab7 from their phagosomes, thereby, establishing and/or maintaining an endosymbiotic relationship with their cnidarian hosts.

Cold-fusion television show angers APS

NASA Astrophysics Data System (ADS)

Cartwright, Jon

2009-06-01

Cold fusion has been controversial since its inception on 23 March 1989, when chemists Martin Fleischmann and Stanley Pons at the University of Utah in the US announced that they had achieved a sustained nuclear-fusion reaction at room temperature. Two decades on, a US television documentary about the field has stirred up fresh debate after it linked the American Physical Society (APS) to an evaluation of some cold-fusion results by Robert Duncan, a physicist and vice chancellor of the University of Missouri.

AP-8 trapped proton environment for solar maximum and solar minimum. [Computer accessible models

NASA Technical Reports Server (NTRS)

Sawyer, D. M.; Vette, J. I.

1976-01-01

Data sets from Ov-3 and Azur indicate a need for improvement in models of the stably trapped proton flux with energies between 0.1 and 400 MeV. Two computer accessible models are described: AP8MAX and AP8MIN. The models are presented in the form of nomographs, B-L plots, R-lambda plots, and equatorial radial profiles. Nomographs of the orbit-integrated fluxes are also discussed. The models are compared with each other, with the data, and with previous AP models. Requirements for future improvements include more complete data coverage and periodic comparisons with new data sets as they become available. The machine-sensible format in which the models are available are described.

Proteomic identification of E6AP as a molecular target of tamoxifen in MCF7 cells.

PubMed

Lochab, Savita; Pal, Pooja; Kanaujiya, Jitendra K; Tripathi, Shashi B; Kapoor, Isha; Bhatt, Madan L B; Sanyal, Sabyasachi; Behre, Gerhard; Trivedi, Arun K

2012-05-01

Tamoxifen (Tam) is most widely used selective estrogen receptor modulator (SERM) for treatment of hormone-responsive breast cancer. Despite being regularly used in clinical therapy for breast cancer since 1971, the mechanism of Tam action remains largely unclear. In order to gain insights into Tam-mediated antibreast cancer actions, we applied 2DE and MS based proteomics approach to identify target proteins of Tam. We identified E6-associated protein, i.e. E6AP (UBE3A) among others to be regulated by Tam that otherwise is upregulated in breast tumors. We confirmed our 2DE finding by immunoblotting and further show that Tam leads to inhibition of E6AP expression presumably by promoting its autoubiquitination, which is coupled with nuclear export and subsequent proteasome-mediated degradation. Furthermore, we show that Tam- and siE6AP-mediated inhibition of E6AP leads to enhanced G0-G1 growth arrest and apoptosis, which is also evident from significant upregulation of cytochrome-c, Bax, p21, and PARP cleavage. Taken together, our data suggest that, Tam-targeted E6AP inhibition is in fact required for Tam-mediated antibreast cancer actions. Thus, E6AP may be a therapeutic target in breast cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protein phosphatase AP2C1 negatively regulates basal resistance and defense responses to Pseudomonas syringae.

PubMed

Shubchynskyy, Volodymyr; Boniecka, Justyna; Schweighofer, Alois; Simulis, Justinas; Kvederaviciute, Kotryna; Stumpe, Michael; Mauch, Felix; Balazadeh, Salma; Mueller-Roeber, Bernd; Boutrot, Freddy; Zipfel, Cyril; Meskiene, Irute

2017-02-01

Mitogen-activated protein kinases (MAPKs) mediate plant immune responses to pathogenic bacteria. However, less is known about the cell autonomous negative regulatory mechanism controlling basal plant immunity. We report the biological role of Arabidopsis thaliana MAPK phosphatase AP2C1 as a negative regulator of plant basal resistance and defense responses to Pseudomonas syringae. AP2C2, a closely related MAPK phosphatase, also negatively controls plant resistance. Loss of AP2C1 leads to enhanced pathogen-induced MAPK activities, increased callose deposition in response to pathogen-associated molecular patterns or to P. syringae pv. tomato (Pto) DC3000, and enhanced resistance to bacterial infection with Pto. We also reveal the impact of AP2C1 on the global transcriptional reprogramming of transcription factors during Pto infection. Importantly, ap2c1 plants show salicylic acid-independent transcriptional reprogramming of several defense genes and enhanced ethylene production in response to Pto. This study pinpoints the specificity of MAPK regulation by the different MAPK phosphatases AP2C1 and MKP1, which control the same MAPK substrates, nevertheless leading to different downstream events. We suggest that precise and specific control of defined MAPKs by MAPK phosphatases during plant challenge with pathogenic bacteria can strongly influence plant resistance. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

AP1 binding site is another target of FGF2 regulation of bone sialoprotein gene transcription.

PubMed

Takai, Hideki; Araki, Shouta; Mezawa, Masaru; Kim, Dong-Soon; Li, Xinyue; Yang, Li; Li, Zhengyang; Wang, Zhitao; Nakayama, Youhei; Ogata, Yorimasa

2008-02-29

Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. We previously reported that fibroblast growth factor 2 (FGF2) regulates BSP gene transcription via FGF2 response element (FRE) in the proximal promoter of rat BSP gene. We here report that activator protein 1 (AP1) binding site overlapping with glucocorticoid response element (GRE) AP1/GRE in the rat BSP gene promoter is another target of FGF2. Using the osteoblastic cell line ROS17/2.8, we determined that BSP mRNA levels increased by 10 ng/ml FGF2 at 6 and 12 h. Runx2 protein levels increased by FGF2 (10 ng/ml) at 3 h. Treatment of ROS17/2.8 cells with FGF2 (10 ng/ml, 12 h) increased luciferase activities of constructs including -116 to +60 and -938 to +60 of the rat BSP gene promoter. Effects of FGF2 abrogated in constructs included 2 bp mutations in the FRE and AP1/GRE elements. Luciferase activities induced by FGF2 were blocked by tyrosine kinase inhibitor herbimycin A, src-tyrosine kinase inhibitor PP1 and MAP kinase kinase inhibitor U0126. Gel shift analyses showed that FGF2 increased binding of FRE and AP1/GRE elements. Notably, the AP1/GRE-protein complexes were supershifted by Smad1 and c-Fos antibodies, c-Jun and Dlx5 antibodies disrupted the complexes formation, on the other hand AP1/GRE-protein complexes did not change by Runx2 antibody. These studies demonstrate that FGF2 stimulates BSP gene transcription by targeting the FRE and AP1/GRE elements in the rat BSP gene promoter.

An Updated AP2 Beamline TURTLE Model

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

Gormley, M.; O'Day, S.

1991-08-23

This note describes a TURTLE model of the AP2 beamline. This model was created by D. Johnson and improved by J. Hangst. The authors of this note have made additional improvements which reflect recent element and magnet setting changes. The magnet characteristics measurements and survey data compiled to update the model will be presented. A printout of the actual TURTLE deck may be found in appendix A.

APS: 125 Years of Progress of Physiology as a Scientific Discipline and a Profession

ERIC Educational Resources Information Center

Carroll, Robert G.; Frank, Martin; Ra'anan, Alice; Matyas, Marsha L.

2013-01-01

The Experimental Biology 2012 meeting in San Diego, CA, included events to celebrate the 125th anniversary of the founding of the American Physiological Society (APS) and reflect on the recent accomplishments of the society. Most of the APS activities in the past quarter century were guided by a series of strategic plans. Membership in the APS…

Tank 241-AP-103 08/1999 Compatibility Grab Samples and Analytical Results for the Final Report

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

BELL, K.E.

1999-12-09

This document is the format IV, final report for the tank 241-AP-103 (AP-103) grab samples taken in August 1999 to address waste compatibility concerns. Chemical, radiochemical, and physical analyses on the tank AP-103 samples were performed as directed in ''Compatibility Grub Sampling and Analysis Plan for Fiscal Year 1999'' (Sasaki 1999a). Any deviations from the instructions provided in the tank sampling and analysis plan (TSAP) were discussed in this narrative. No notification limits were exceeded.

Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli

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

Burnouf, D.; Fuchs, R.P.P.; Gauthier, C.

1990-08-01

The mutation spectrum induced by the widely used antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP(d(ApG)) adducts, although they account for only 25% of the lesions formed are {approx}5 times more mutagenic than the major GG adduct. The authors report the construction of vectors bearing a single cisDDP(d(ApG)) lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5{prime} base of the adduct.more » Single A {yields} T transversions are mainly observed (80%), whereas A {yields} G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5{prime} to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP(d(ApG)) adducts are not blocking lesions. The high mutation specificity of cisDDP-(d(ApG))-induced mutagenesis is discussed in relation to structural data.« less

Lightweight CoAP-Based Bootstrapping Service for the Internet of Things.

PubMed

Garcia-Carrillo, Dan; Marin-Lopez, Rafael

2016-03-11

The Internet of Things (IoT) is becoming increasingly important in several fields of industrial applications and personal applications, such as medical e-health, smart cities, etc. The research into protocols and security aspects related to this area is continuously advancing in making these networks more reliable and secure, taking into account these aspects by design. Bootstrapping is a procedure by which a user obtains key material and configuration information, among other parameters, to operate as an authenticated party in a security domain. Until now solutions have focused on re-using security protocols that were not developed for IoT constraints. For this reason, in this work we propose a design and implementation of a lightweight bootstrapping service for IoT networks that leverages one of the application protocols used in IoT : Constrained Application Protocol (CoAP). Additionally, in order to provide flexibility, scalability, support for large scale deployment, accountability and identity federation, our design uses technologies such as the Extensible Authentication Protocol (EAP) and Authentication Authorization and Accounting (AAA). We have named this service CoAP-EAP. First, we review the state of the art in the field of bootstrapping and specifically for IoT. Second, we detail the bootstrapping service: the architecture with entities and interfaces and the flow operation. Third, we obtain performance measurements of CoAP-EAP (bootstrapping time, memory footprint, message processing time, message length and energy consumption) and compare them with PANATIKI. The most significant and constrained representative of the bootstrapping solutions related with CoAP-EAP. As we will show, our solution provides significant improvements, mainly due to an important reduction of the message length.

Lightweight CoAP-Based Bootstrapping Service for the Internet of Things

PubMed Central

Garcia-Carrillo, Dan; Marin-Lopez, Rafael

2016-01-01

The Internet of Things (IoT) is becoming increasingly important in several fields of industrial applications and personal applications, such as medical e-health, smart cities, etc. The research into protocols and security aspects related to this area is continuously advancing in making these networks more reliable and secure, taking into account these aspects by design. Bootstrapping is a procedure by which a user obtains key material and configuration information, among other parameters, to operate as an authenticated party in a security domain. Until now solutions have focused on re-using security protocols that were not developed for IoT constraints. For this reason, in this work we propose a design and implementation of a lightweight bootstrapping service for IoT networks that leverages one of the application protocols used in IoT : Constrained Application Protocol (CoAP). Additionally, in order to provide flexibility, scalability, support for large scale deployment, accountability and identity federation, our design uses technologies such as the Extensible Authentication Protocol (EAP) and Authentication Authorization and Accounting (AAA). We have named this service CoAP-EAP. First, we review the state of the art in the field of bootstrapping and specifically for IoT. Second, we detail the bootstrapping service: the architecture with entities and interfaces and the flow operation. Third, we obtain performance measurements of CoAP-EAP (bootstrapping time, memory footprint, message processing time, message length and energy consumption) and compare them with PANATIKI. The most significant and constrained representative of the bootstrapping solutions related with CoAP-EAP. As we will show, our solution provides significant improvements, mainly due to an important reduction of the message length. PMID:26978362

Coming Soon: CADRE (Career Advancement and Development Resources and Education) website for all APS members

USDA-ARS?s Scientific Manuscript database

The Council of the American Phytopathological Society (APS) approved an initiative in February 2013 to create a web resource called CADRE (Career Advancement and Development Resources and Education). CADRE is to provide APS members an archive of articles, videos, and webinars about a variety of prof...

Flexible Unicast-Based Group Communication for CoAP-Enabled Devices †

PubMed Central

Ishaq, Isam; Hoebeke, Jeroen; Van den Abeele, Floris; Rossey, Jen; Moerman, Ingrid; Demeester, Piet

2014-01-01

Smart embedded objects will become an important part of what is called the Internet of Things. Applications often require concurrent interactions with several of these objects and their resources. Existing solutions have several limitations in terms of reliability, flexibility and manageability of such groups of objects. To overcome these limitations we propose an intermediately level of intelligence to easily manipulate a group of resources across multiple smart objects, building upon the Constrained Application Protocol (CoAP). We describe the design of our solution to create and manipulate a group of CoAP resources using a single client request. Furthermore we introduce the concept of profiles for the created groups. The use of profiles allows the client to specify in more detail how the group should behave. We have implemented our solution and demonstrate that it covers the complete group life-cycle, i.e., creation, validation, flexible usage and deletion. Finally, we quantitatively analyze the performance of our solution and compare it against multicast-based CoAP group communication. The results show that our solution improves reliability and flexibility with a trade-off in increased communication overhead. PMID:24901978

Isolation and characterization of the Jatropha curcas APETALA1 (JcAP1) promoter conferring preferential expression in inflorescence buds.

PubMed

Tao, Yan-Bin; He, Liang-Liang; Niu, Longjian; Xu, Zeng-Fu

2016-08-01

The 1.5 kb JcAP1 promoter from the biofuel plant Jatropha curcas is predominantly active in the inflorescence buds of transgenic plants, in which the -1313/-1057 region is essential for maintaining the activity. Arabidopsis thaliana APETALA1 (AP1) is a MADS-domain transcription factor gene that functions primarily in flower development. We isolated a homolog of AP1 from Jatropha curcas (designated JcAP1), which was shown to exhibit flower-specific expression in Jatropha. JcAP1 is first expressed in inflorescence buds and continues to be primarily expressed in the sepals. We isolated a 1.5 kb JcAP1 promoter and evaluated its activity in transgenic Arabidopsis and Jatropha using the β-glucuronidase (GUS) reporter gene. In transgenic Arabidopsis and Jatropha, the inflorescence buds exhibited notable GUS activity, whereas the sepals did not. Against expectations, the JcAP1 promoter was active in the anthers of Arabidopsis and Jatropha and was highly expressed in Jatropha seeds. An analysis of promoter deletions in transgenic Arabidopsis revealed that deletion of the -1313/-1057 region resulted in loss of JcAP1 promoter activity in the inflorescence buds and increased activity in the anthers. These results suggested that some regulatory sequences in the -1313/-1057 region are essential for maintaining promoter activity in inflorescence buds and can partly suppress activity in the anthers. Based on these findings, we hypothesized that other elements located upstream of the 1.5 kb JcAP1 promoter may be required for flower-specific activation. The JcAP1 promoter characterized in this study can be used to drive transgene expression in both the inflorescence buds and seeds of Jatropha.

Using ProHits to store, annotate and analyze affinity purification - mass spectrometry (AP-MS) data

PubMed Central

Liu, Guomin; Zhang, Jianping; Choi, Hyungwon; Lambert, Jean-Philippe; Srikumar, Tharan; Larsen, Brett; Nesvizhskii, Alexey I.; Raught, Brian; Tyers, Mike; Gingras, Anne-Claude

2012-01-01

Affinity purification coupled with mass spectrometry (AP-MS) is a robust technique used to identify protein-protein interactions. With recent improvements in sample preparation, and dramatic advances in MS instrumentation speed and sensitivity, this technique is becoming more widely used throughout the scientific community. To meet the needs of research groups both large and small, we have developed software solutions for tracking, scoring and analyzing AP-MS data. Here, we provide details for the installation and utilization of ProHits, a Laboratory Information Management System designed specifically for AP-MS interaction proteomics. This protocol explains: (i) how to install the complete ProHits system, including modules for the management of mass spectrometry files and the analysis of interaction data, and (ii) alternative options for the use of pre-existing search results in simpler versions of ProHits, including a virtual machine implementation of our ProHits Lite software. We also describe how to use the main features of the software to analyze AP-MS data. PMID:22948730

Large amplitude change in spot-induced rotational modulation of the Kepler Ap star KIC 2569073

NASA Astrophysics Data System (ADS)

Drury, Jason A.; Murphy, Simon J.; Derekas, Aliz; Sódor, Ádám; Stello, Dennis; Kuehn, Charles A.; Bedding, Timothy R.; Bognár, Zsófia; Szigeti, László; Szakáts, Róbert; Sárneczky, Krisztián; Molnár, László

2017-11-01

An investigation of the 200 × 200 pixel `superstamp' images of the centres of the open clusters NGC 6791 and NGC 6819 allows for the identification and study of many variable stars that were not included in the Kepler target list. KIC 2569073 (V = 14.22), is a particularly interesting variable Ap star that we discovered in the NGC 6791 superstamp. With a rotational period of 14.67 d and 0.034 mag variability, it has one of the largest peak-to-peak variations of any known Ap star. Colour photometry reveals an antiphase correlation between the B band, and the V, R and I bands. This Ap star is a rotational variable, also known as an α2 CVn star, and is one of only a handful of Ap stars observed by Kepler. While no change in spot period or amplitude is observed within the 4 yr Kepler time series, the amplitude shows a large increase compared to ground-based photometry obtained two decades ago.

Construction of a dictionary of laboratory tests mapped to LOINC at AP-HP.

PubMed

Cormont, Sylvie; Buemi, Antoine; Horeau, Thierry; Zweigenbaum, Pierre; Lepage, Eric

2008-11-06

We report on the ongoing process implemented at Assistance Publique-Hôpitaux de Paris (AP-HP), the largest hospital system in Europe, to build a common reference for laboratory tests in French with LOINC mappings. At the time of writing, it contained 24,000 tests, covering all fields of biology, in use in 19 AP-HP hospitals, 30% of which had a mapping to LOINC with a peak of over 60% in biochemistry.

APS undulator and wiggler sources: Monte-Carlo simulation

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

Xu, S.L.; Lai, B.; Viccaro, P.J.

1992-02-01

Standard insertion devices will be provided to each sector by the Advanced Photon Source. It is important to define the radiation characteristics of these general purpose devices. In this document,results of Monte-Carlo simulation are presented. These results, based on the SHADOW program, include the APS Undulator A (UA), Wiggler A (WA), and Wiggler B (WB).

HIT collaborative base project at APS of Argonne

NASA Astrophysics Data System (ADS)

Liu, H.; Wang, L.

2012-12-01

Harbin Institute of Technology (HIT) launched collaborative base project at Argonne National Laboratory in 2010, and progress will be presented in this paper. The staff and students from HIT involved in advanced technological developments, which included tomography. high energy PDF, diffraction and scattering, and inelastic scattering techniques in APS to study structures changes under high pressure conditions.

Inhibition of benzopyrene diol epoxide-induced apoptosis by cadmium (II) is AP-1-independent: role of extracelluler signal related kinase

PubMed Central

Mukherjee, Jagat J.; Gupta, Suresh K.; Kumar, Subodh

2010-01-01

Cadmium, a major metal constituent of tobacco smoke, elicits synergistic enhancement of cell transformation when combined with benzo[a]pyrene (BP) or other PAHs. The mechanism underlying this synergism is not clearly understood. We observed that (+/−)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), an ultimate carcinogen of BP, induces apoptosis in promotion sensitive mouse epidermal JB6 Cl41 cells at non-cytotoxic concentrations. BPDE also activates AP-1 several folds in AP-1 reporter JB6 cells. Cadmium at non-cytotoxic concentrations inhibits both AP-1 activation and apoptosis in response to BPDE. Since AP-1 is known to be involved in stress-induced apoptosis we investigated whether inhibition of AP-1 by cadmium has any role in the inhibition of BPDE-induced apoptosis. MAP kinases (particularly ERKs, p38 and JNKs) are known to have important role in DNA damage-induced AP-1 activation. We observed that ERK and JNK, but not p38 MAP kinase, are involved in BPDE-induced AP-1 activation. Effect of cadmium on MAP kinases and the effect of inhibition of above three MAP kinases on BPDE-induced AP-1 activation and apoptosis indicate that AP-1 is probably not involved in BPDE-induced apoptosis. Cadmium up-regulates BPDE-activated ERKs and ERK inhibition by U0126 relieves cadmium-mediated inhibition of BPDE-induced apoptosis. We suggest that cadmium inhibits BPDE-induced apoptosis not involving AP-1 but probably through a different mechanism by up-regulating ERK which is known to promote cell survival. PMID:18093576

AP214, an analogue of α-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality

PubMed Central

Doi, Kent; Hu, Xuzhen; Yuen, Peter S.T.; Leelahavanichkul, Asada; Yasuda, Hideo; Kim, Soo Mi; Schnermann, Jürgen; Jonassen, Thomas E.N.; Frøkiær, Jørgen; Nielsen, Søren; Star, Robert A.

2008-01-01

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. α-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new α-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 hr after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-α and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-κB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis. PMID:18354376

Ap4A is not an efficient Zn(II) binding agent. A concerted potentiometric, calorimetric and NMR study.

PubMed

Wszelaka-Rylik, Małgorzata; Witkiewicz-Kucharczyk, Aleksandra; Wójcik, Jacek; Bal, Wojciech

2007-05-01

Diadenosine 5',5''-P(1)P(4) tetraphosphate (Ap(4)A) has been considered as an intracellular partner for Zn(II). We applied potentiometry, ITC and NMR to study protonation equilibria of Ap(4)A and Zn(II) complexation by this dinucleotide. The values of binding constants obtained by these three techniques under various experimental conditions coherently demonstrated that Ap(4)A binds Zn(II) weakly, with an apparent binding constant of ca. 10(4) at neutral pH. Such a low stability of Zn(II) complexes with Ap(4)A excludes a possibility for interactions between these two agents in vivo.

The augmented anticancer potential of AP9-cd loaded solid lipid nanoparticles in human leukemia Molt-4 cells and experimental tumor.

PubMed

Bhushan, Shashi; Kakkar, Vandita; Pal, Harish Chandra; Mondhe, D M; Kaur, Indu Pal

2016-01-25

AP9-cd, a novel lignan composition from Cedrus deodara has significant anticancer potential, and to further enhance its activity, it was lucratively encumbered into solid lipid nanoparticles (SLNs). These nanoparticles were formulated by micro-emulsion technique with 70% drug trap competence. AP9-cd-SLNs were regular, solid, globular particles in the range of 100-200 nm, which were confirmed by electron microscopic studies. Moreover, AP9-cd-SLNs were found to be stable for up to six months in terms of color, particle size, zeta potential, drug content and entrapment. AP9-cd-SLNs have 30-50% higher cytotoxic and apoptotic potential than the AP9-cd alone. The augmented anticancer potential of AP9-cd-SLNs was observed in cytotoxic IC50 value, apoptosis signaling cascade and in Ehrlich ascites tumor (EAT) model. AP9-cd-SLNs induce apoptosis in Molt-4 cells via both intrinsic and extrinsic pathway. Moreover, the dummy nanoparticles (SLNs without AP9-cd) did not have any cytotoxic effect in cancer as well as in normal cells. Consequently, SLNs of AP9-cd significantly augment the apoptotic and antitumor potential of AP9-cd. The present study provides a podium for ornamental the remedial latent via novel delivery systems like solid lipid nanoparticles. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Brain synaptosomes display a diadenosine tetraphosphate (Ap4A)-mediated Ca2+ influx distinct from ATP-mediated influx.

PubMed

Pivorun, E B; Nordone, A

1996-06-01

Studies undertaken to compare the effects of Ap4A and ATP on altering intrasynaptosomal Ca2+ levels from deermouse brain reveal that both ligands induce a rapid influx of extracellular Ca2+. The Ca2+ profile elicited by 167 microM Ap4A is "spike-like" (half-time for decline to baseline, 19.1 +/- 1.2 sec), in contrast to the gradual decline observed with ATP (104.0 +/- 7.4 sec). DIDS (4-4'-diisothiocyano-2,2'-disulfonic acid stilbene) and suramin preincubation alter only the ATP-induced Ca2+ profile. Cross-desensitization studies indicate that prior application of ATP does not significantly affect the Ca2+ influx elicited by Ap4A, and that prior application of Ap4A does not affect the Ca2+ influx elicited by ATP. These results demonstrate that extracellular Ap4A and ATP elicit distinct intrasynaptosomal Ca2+ influx profiles, and suggest that these two nucleotides may be interacting with distinct purinoceptor subclasses or purinoceptor-effector complexes. Subjecting the synaptosomes simultaneously to depolarization and Ap4A, or to depolarization and ATP, induces an additive effect on Ca2+ influx. Preincubation with verapamil negates the effects of depolarization without modifying the ligand-elicited Ca2+ fluxes. These results indicate the presence of Ap4A and ATP ligand-gated channels that may function as modulators of neuronal activity.

Matrix proteins of Nipah and Hendra viruses interact with beta subunits of AP-3 complexes.

PubMed

Sun, Weina; McCrory, Thomas S; Khaw, Wei Young; Petzing, Stephanie; Myers, Terrell; Schmitt, Anthony P

2014-11-01

Paramyxoviruses and other negative-strand RNA viruses encode matrix proteins that coordinate the virus assembly process. The matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. Using a co-affinity purification strategy, we have identified the beta subunit of the AP-3 adapter protein complex, AP3B1, as a binding partner for the M proteins of the zoonotic paramyxoviruses Nipah virus and Hendra virus. Binding function was localized to the serine-rich and acidic Hinge domain of AP3B1, and a 29-amino-acid Hinge-derived polypeptide was sufficient for M protein binding in coimmunoprecipitation assays. Virus-like particle (VLP) production assays were used to assess the relationship between AP3B1 binding and M protein function. We found that for both Nipah virus and Hendra virus, M protein expression in the absence of any other viral proteins led to the efficient production of VLPs in transfected cells, and this VLP production was potently inhibited upon overexpression of short M-binding polypeptides derived from the Hinge region of AP3B1. Both human and bat (Pteropus alecto) AP3B1-derived polypeptides were highly effective at inhibiting the production of VLPs. VLP production was also impaired through small interfering RNA (siRNA)-mediated depletion of AP3B1 from cells. These findings suggest that AP-3-directed trafficking processes are important for henipavirus particle production and identify a new host protein-virus protein binding interface that could become a useful target in future efforts to develop small molecule inhibitors to combat paramyxoviral infections. Henipaviruses cause deadly infections in humans, with a mortality rate of about 40%. Hendra virus outbreaks in Australia, all involving horses and some involving transmission to humans, have been a continuing problem. Nipah virus caused a large outbreak in Malaysia in 1998, killing 109 people

Matrix Proteins of Nipah and Hendra Viruses Interact with Beta Subunits of AP-3 Complexes

PubMed Central

Sun, Weina; McCrory, Thomas S.; Khaw, Wei Young; Petzing, Stephanie; Myers, Terrell

2014-01-01

ABSTRACT Paramyxoviruses and other negative-strand RNA viruses encode matrix proteins that coordinate the virus assembly process. The matrix proteins link the viral glycoproteins and the viral ribonucleoproteins at virus assembly sites and often recruit host machinery that facilitates the budding process. Using a co-affinity purification strategy, we have identified the beta subunit of the AP-3 adapter protein complex, AP3B1, as a binding partner for the M proteins of the zoonotic paramyxoviruses Nipah virus and Hendra virus. Binding function was localized to the serine-rich and acidic Hinge domain of AP3B1, and a 29-amino-acid Hinge-derived polypeptide was sufficient for M protein binding in coimmunoprecipitation assays. Virus-like particle (VLP) production assays were used to assess the relationship between AP3B1 binding and M protein function. We found that for both Nipah virus and Hendra virus, M protein expression in the absence of any other viral proteins led to the efficient production of VLPs in transfected cells, and this VLP production was potently inhibited upon overexpression of short M-binding polypeptides derived from the Hinge region of AP3B1. Both human and bat (Pteropus alecto) AP3B1-derived polypeptides were highly effective at inhibiting the production of VLPs. VLP production was also impaired through small interfering RNA (siRNA)-mediated depletion of AP3B1 from cells. These findings suggest that AP-3-directed trafficking processes are important for henipavirus particle production and identify a new host protein-virus protein binding interface that could become a useful target in future efforts to develop small molecule inhibitors to combat paramyxoviral infections. IMPORTANCE Henipaviruses cause deadly infections in humans, with a mortality rate of about 40%. Hendra virus outbreaks in Australia, all involving horses and some involving transmission to humans, have been a continuing problem. Nipah virus caused a large outbreak in Malaysia in 1998

PSAT Component Scores as a Predictor of Success on AP Exam Performance for Diverse Students

ERIC Educational Resources Information Center

Richardson, Cristianne C.; Gonzalez, Alejandro; Leal, Lonnie; Castillo, Mary Z.; Carman, Carol A.

2016-01-01

While studies have shown the positive effect of the Advanced Placement (AP) program on college readiness, there are still barriers preventing minority and low socioeconomic status (SES) students who possess high academic potential from participating in the opportunity that AP courses offer. One tool that could help identify students for…

Periodic variation in the geomagnetic activity - A study based on the Ap index

NASA Technical Reports Server (NTRS)

De Gonzalez, Alicia L. C.; Gonzalez, Walter D.; Dutra, Severino L. G.; Tsurutani, Bruce T.

1993-01-01

The monthly and daily samples of the Ap index for the interval from 1932 through 1982 were studied using the power spectrum technique. Results obtained for Bartel's period (about 27 days), the semiannual period, the dual-peak solar cycle distribution of geomagnetic storms, and certain other medium-scale periodicities are examined in detail. In addition, results on the cumulative occurrence number of storms per decade as a function of the Ap and Dst indices for the storm are presented.

Obstetrical APS: is there a place for hydroxychloroquine to improve the pregnancy outcome?

PubMed

Mekinian, Arsene; Costedoat-Chalumeau, Nathalie; Masseau, Agathe; Tincani, Angela; De Caroli, Sara; Alijotas-Reig, Jaume; Ruffatti, Amelia; Ambrozic, Ales; Botta, Angela; Le Guern, Véronique; Fritsch-Stork, Ruth; Nicaise-Roland, Pascale; Carbonne, Bruno; Carbillon, Lionel; Fain, Olivier

2015-01-01

The use of the conventional APS treatment (the combination of low-dose aspirin and LMWH) dramatically improved the obstetrical prognosis in primary obstetrical APS (OAPS). The persistence of adverse pregnancy outcome raises the need to find other drugs to improve obstetrical outcome. Hydroxychloroquine is widely used in patients with various autoimmune diseases, particularly SLE. Antimalarials have many anti-inflammatory, anti-aggregant and immune-regulatory properties: they inhibit phospholipase activity, stabilize lysosomal membranes, block the production of several pro-inflammatory cytokines and, in addition, impair complement-dependent antigen-antibody reactions. There is ample evidence of protective effects of hydroxychloroquine in OAPS similar to the situation in SLE arising from in vitro studies of pathophysiological working mechanism of hydroxychloroquine. However, the clinical data on the use of hydroxychloroquine in primary APS are lacking and prospective studies are necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis.

PubMed

Campagne, Cécile; Ripoll, Léa; Gilles-Marsens, Floriane; Raposo, Graça; Delevoye, Cédric

2018-02-14

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease.

AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis

PubMed Central

Campagne, Cécile; Ripoll, Léa; Gilles-Marsens, Floriane; Raposo, Graça

2018-01-01

Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease. PMID:29443872

The most interesting roAp target for MONS: HR1217 ?

NASA Astrophysics Data System (ADS)

Knudsen, M. R.

2000-04-01

The roAp star HR1217 is presented as a good and possibly the best roAp target for MONS and the progress of the 1998 3-site STACC Campaign is briefly summarized incl. the first detection of EW oscillation in Hα and Hβ in this star, alongside evidence of EW varying with the phase of rotation. HR1217 has 6 known oscillation frequencies of which the four strongest appear to be rotationally split with photometric amplitudes ~< 1 mmag. The problem with groundbased observations is the 3-day-alias beating with neighbouring peaks which limits our chances for a solid mode id. With 30 days (2.4ṡ Prot) on MONS CAM we should have the needed observational data for doing asteroseismology on a magnetic star at last!

Assimilation and implications of AE-9/AP-9 in the design process of JPL missions

NASA Astrophysics Data System (ADS)

de Soria-Santacruz Pich, M.; Jun, I.

2015-12-01

The NASA AE-8/AP-8 has been the standard geospace environment specification for decades. This model describes the energetic particle environment around the Earth and is currently the default model used in the design of space missions at the Jet Propulsion Laboratory (JPL). Moreover, the model plays a critical role in the determination of the shielding and survivability of the satellites orbiting our planet. A recent update supported by the Air Force Research Laboratory (AFRL) and the National Reconnaissance Office (NRO), the AE-9/AP-9 model, was released in September 2012 and included many improvements like increased spatial resolution and the specification of the uncertainty due to instrument errors or space weather variability. A current effort at JPL is in place with the objective of making a decision within the Laboratory on the transition from AE-8/AP-8 to the new AE-9/AP-9. In this study we present the results of this effort, which involves the comparison between both versions of the model for different satellite orbits, the comparison between AE-9/AP-9 and in-situ satellite data from the Van Allen Probes and the OSTM/Jason 2 satellite, and the implications of adopting the new model for spacecraft design in terms of survivability, shielding, single event effects, and spacecraft charging.

Systematic CRISPR-Cas9-Mediated Modifications of Plasmodium yoelii ApiAP2 Genes Reveal Functional Insights into Parasite Development

PubMed Central

Zhang, Cui; Li, Zhenkui; Cui, Huiting; Jiang, Yuanyuan; Yang, Zhenke; Wang, Xu; Gao, Han; Liu, Cong; Zhang, Shujia

2017-01-01

ABSTRACT Malaria parasites have a complex life cycle with multiple developmental stages in mosquito and vertebrate hosts, and different developmental stages express unique sets of genes. Unexpectedly, many transcription factors (TFs) commonly found in eukaryotic organisms are absent in malaria parasites; instead, a family of genes encoding proteins similar to the plant Apetala2 (ApiAP2) transcription factors is expanded in the parasites. Several malaria ApiAP2 genes have been shown to play a critical role in parasite development; however, the functions of the majority of the ApiAP2 genes remain to be elucidated. In particular, no study on the Plasmodium yoelii ApiAP2 (PyApiAP2) gene family has been reported so far. This study systematically investigated the functional roles of PyApiAP2 genes in parasite development. Twenty-four of the 26 PyApiAP2 genes were selected for disruption, and 12 were successfully knocked out using the clustered regularly interspaced short palindromic repeat–CRISPR-associated protein 9 (CRISPR-Cas9) method. The effects of gene knockout (KO) on parasite development in mouse and mosquito stages were evaluated. Ten of 12 successfully disrupted genes, including two genes that have not been functionally characterized in any Plasmodium species previously, were shown to be critical for P. yoelii development of sexual and mosquito stages. Additionally, seven of the genes were labeled for protein expression analysis, revealing important information supporting their functions. This study represents the first systematic functional characterization of the P. yoelii ApiAP2 gene family and discovers important insights on the roles of the ApiAP2 genes in parasite development. PMID:29233900

DisAp-dependent striated fiber elongation is required to organize ciliary arrays

PubMed Central

Galati, Domenico F.; Bonney, Stephanie; Kronenberg, Zev; Clarissa, Christina; Yandell, Mark; Elde, Nels C.; Jerka-Dziadosz, Maria; Giddings, Thomas H.; Frankel, Joseph

2014-01-01

Cilia-organizing basal bodies (BBs) are microtubule scaffolds that are visibly asymmetrical because they have attached auxiliary structures, such as striated fibers. In multiciliated cells, BB orientation aligns to ensure coherent ciliary beating, but the mechanisms that maintain BB orientation are unclear. For the first time in Tetrahymena thermophila, we use comparative whole-genome sequencing to identify the mutation in the BB disorientation mutant disA-1. disA-1 abolishes the localization of the novel protein DisAp to T. thermophila striated fibers (kinetodesmal fibers; KFs), which is consistent with DisAp’s similarity to the striated fiber protein SF-assemblin. We demonstrate that DisAp is required for KFs to elongate and to resist BB disorientation in response to ciliary forces. Newly formed BBs move along KFs as they approach their cortical attachment sites. However, because they contain short KFs that are rotated, BBs in disA-1 cells display aberrant spacing and disorientation. Therefore, DisAp is a novel KF component that is essential for force-dependent KF elongation and BB orientation in multiciliary arrays. PMID:25533842

P4-ATPase Requirement for AP-1/Clathrin Function in Protein Transport from the trans-Golgi Network and Early Endosomes

PubMed Central

Liu, Ke; Surendhran, Kavitha; Nothwehr, Steven F.

2008-01-01

Drs2p is a resident type 4 P-type ATPase (P4-ATPase) and potential phospholipid translocase of the trans-Golgi network (TGN) where it has been implicated in clathrin function. However, precise protein transport pathways requiring Drs2p and how it contributes to clathrin-coated vesicle budding remain unclear. Here we show a functional codependence between Drs2p and the AP-1 clathrin adaptor in protein sorting at the TGN and early endosomes of Saccharomyces cerevisiae. Genetic criteria indicate that Drs2p and AP-1 operate in the same pathway and that AP-1 requires Drs2p for function. In addition, we show that loss of AP-1 markedly increases Drs2p trafficking to the plasma membrane, but does not perturb retrieval of Drs2p from the early endosome back to the TGN. Thus AP-1 is required at the TGN to sort Drs2p out of the exocytic pathway, presumably for delivery to the early endosome. Moreover, a conditional allele that inactivates Drs2p phospholipid translocase (flippase) activity disrupts its own transport in this AP-1 pathway. Drs2p physically interacts with AP-1; however, AP-1 and clathrin are both recruited normally to the TGN in drs2Δ cells. These results imply that Drs2p acts independently of coat recruitment to facilitate AP-1/clathrin-coated vesicle budding from the TGN. PMID:18508916

Genome-wide identification and phylogenetic analysis of the AP2/ERF gene superfamily in sweet orange (Citrus sinensis).

PubMed

Ito, T M; Polido, P B; Rampim, M C; Kaschuk, G; Souza, S G H

2014-09-26

Sweet orange (Citrus sinensis) plays an important role in the economy of more than 140 countries, but it is grown in areas with intermittent stressful soil and climatic conditions. The stress tolerance could be addressed by manipulating the ethylene response factor (ERF) transcription factors because they orchestrate plant responses to environmental stress. We performed an in silico study on the ERFs in the expressed sequence tag database of C. sinensis to identify potential genes that regulate plant responses to stress. We identified 108 putative genes encoding protein sequences of the AP2/ERF superfamily distributed within 10 groups of amino acid sequences. Ninety-one genes were assembled from the ERF family containing only one AP2/ERF domain, 13 genes were assembled from the AP2 family containing two AP2/ERF domains, and four other genes were assembled from the RAV family containing one AP2/ERF domain and a B3 domain. Some conserved domains of the ERF family genes were disrupted into a few segments by introns. This irregular distribution of genes in the AP2/ERF superfamily in different plant species could be a result of genomic losses or duplication events in a common ancestor. The in silico gene expression revealed that 67% of AP2/ERF genes are expressed in tissues with usual plant development, and 14% were expressed in stressed tissues. Because the AP2/ERF superfamily is expressed in an orchestrated way, it is possible that the manipulation of only one gene may result in changes in the whole plant function, which could result in more tolerant crops.

Autonomous star sensor ASTRO APS: flight experience on Alphasat

NASA Astrophysics Data System (ADS)

Schmidt, U.; Fiksel, T.; Kwiatkowski, A.; Steinbach, I.; Pradarutti, B.; Michel, K.; Benzi, E.

2015-06-01

Jena-Optronik GmbH, located in Jena/Germany, has profound experience in designing and manufacturing star trackers since the early 80s. Today the company has a worldwide leading position in supplying geo-stationary and Earth observation satellites with robust and reliable star tracker systems. In the first decade of the new century Jena-Optronik received a development contract (17317/2003/F/WE) from the European Space Agency to establish the technologically challenging elements for which advanced star tracker technologies as CMOS Active Pixel Sensors were being introduced or were considered strategic. This activity was performed in the frame of the Alphabus large platform pre-development lead by ESA and the industrial Joint Project Team consisting of Astrium (now Airbus Defence and Space), Thales Alenia Space and CNES (Centre national d'études spatiales). The new autonomous star tracker, ASTRO APS (Active Pixel Sensor), extends the Jena-Optronik A stro-series CCD-based star tracker products taken the full benefit of the CMOS APS technology. ASTRO APS is a fully autonomous compact star tracker carrying either the space-qualified radiation hard STAR1000 or the HAS2 APS detectors. The star tracker is one of four Technology Demonstration Payloads (TDP6) carried by Alphasat as hosted payload in the frame of a successful Private Public Partnership between ESA and Inmarsat who owns and operates the satellite as part of its geo-stationary communication satellites fleet. TDP6 supports also directly TDP1, a Laser Communication Terminal, for fine pointing tasks. Alphasat was flawlessly brought in orbit at the end of July 2013 by a European Ariane 5 launcher. Only a few hours after launch the star tracker received its switch ON command and acquired nominally within 6 s the inertial 3-axes attitude. In the following days of the early in-orbit operations of Alphasat the TDP6 unit tracked reliably all the spacecraft maneuvers including the 0.1 and 0.2°/s spin stabilization for

Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration

PubMed Central

Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A.W.; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M.; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J.; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G.; Humeau, Yann; Schenck, Annette; Herault, Yann

2015-01-01

ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2Camk2aCre/0 mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2Camk2aCre/0 mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2Camk2aCre/0 mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2Camk2aCre/0 mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. PMID:26376863

Conditional depletion of intellectual disability and Parkinsonism candidate gene ATP6AP2 in fly and mouse induces cognitive impairment and neurodegeneration.

PubMed

Dubos, Aline; Castells-Nobau, Anna; Meziane, Hamid; Oortveld, Merel A W; Houbaert, Xander; Iacono, Giovanni; Martin, Christelle; Mittelhaeuser, Christophe; Lalanne, Valérie; Kramer, Jamie M; Bhukel, Anuradha; Quentin, Christine; Slabbert, Jan; Verstreken, Patrik; Sigrist, Stefan J; Messaddeq, Nadia; Birling, Marie-Christine; Selloum, Mohammed; Stunnenberg, Henk G; Humeau, Yann; Schenck, Annette; Herault, Yann

2015-12-01

ATP6AP2, an essential accessory component of the vacuolar H+ ATPase (V-ATPase), has been associated with intellectual disability (ID) and Parkinsonism. ATP6AP2 has been implicated in several signalling pathways; however, little is known regarding its role in the nervous system. To decipher its function in behaviour and cognition, we generated and characterized conditional knockdowns of ATP6AP2 in the nervous system of Drosophila and mouse models. In Drosophila, ATP6AP2 knockdown induced defective phototaxis and vacuolated photoreceptor neurons and pigment cells when depleted in eyes and altered short- and long-term memory when depleted in the mushroom body. In mouse, conditional Atp6ap2 deletion in glutamatergic neurons (Atp6ap2(Camk2aCre/0) mice) caused increased spontaneous locomotor activity and altered fear memory. Both Drosophila ATP6AP2 knockdown and Atp6ap2(Camk2aCre/0) mice presented with presynaptic transmission defects, and with an abnormal number and morphology of synapses. In addition, Atp6ap2(Camk2aCre/0) mice showed autophagy defects that led to axonal and neuronal degeneration in the cortex and hippocampus. Surprisingly, axon myelination was affected in our mutant mice, and axonal transport alterations were observed in Drosophila. In accordance with the identified phenotypes across species, genome-wide transcriptome profiling of Atp6ap2(Camk2aCre/0) mouse hippocampi revealed dysregulation of genes involved in myelination, action potential, membrane-bound vesicles and motor behaviour. In summary, ATP6AP2 disruption in mouse and fly leads to cognitive impairment and neurodegeneration, mimicking aspects of the neuropathology associated with ATP6AP2 mutations in humans. Our results identify ATP6AP2 as an essential gene for the nervous system. © The Author 2015. Published by Oxford University Press.

The non-competitive acetylcholinesterase inhibitor APS12-2 is a potent antagonist of skeletal muscle nicotinic acetylcholine receptors

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

Grandič, Marjana; Aráoz, Romulo; Molgó, Jordi

APS12-2, a non-competitive acetylcholinesterase inhibitor, is one of the synthetic analogs of polymeric alkylpyridinium salts (poly-APS) isolated from the marine sponge Reniera sarai. In the present work the effects of APS12-2 were studied on isolated mouse phrenic nerve–hemidiaphragm muscle preparations, using twitch tension measurements and electrophysiological recordings. APS12-2 in a concentration-dependent manner blocked nerve-evoked isometric muscle contraction (IC{sub 50} = 0.74 μM), without affecting directly-elicited twitch tension up to 2.72 μM. The compound (0.007–3.40 μM) decreased the amplitude of miniature endplate potentials until a complete block by concentrations higher than 0.68 μM, without affecting their frequency. Full size endplate potentials,more » recorded after blocking voltage-gated muscle sodium channels, were inhibited by APS12-2 in a concentration-dependent manner (IC{sub 50} = 0.36 μM) without significant change in the resting membrane potential of the muscle fibers up to 3.40 μM. The compound also blocked acetylcholine-evoked inward currents in Xenopus oocytes in which Torpedo (α1{sub 2}β1γδ) muscle-type nicotinic acetylcholine receptors (nAChRs) have been incorporated (IC{sub 50} = 0.0005 μM), indicating a higher affinity of the compound for Torpedo (α1{sub 2}β1γδ) than for the mouse (α1{sub 2}β1γε) nAChR. Our data show for the first time that APS12-2 blocks neuromuscular transmission by a non-depolarizing mechanism through an action on postsynaptic nAChRs of the skeletal neuromuscular junction. -- Highlights: ► APS12-2 produces concentration-dependent inhibition of nerve-evoked muscle contraction in vitro. ► APS12-2 blocks MEPPs and EPPs at the neuromuscular junction. APS12-2 blocks ACh-activated current in Xenopus oocytes incorporated with Torpedo nAChRs.« less

The Development of Multiple-Choice Items Consistent with the AP Chemistry Curriculum Framework to More Accurately Assess Deeper Understanding

ERIC Educational Resources Information Center

Domyancich, John M.

2014-01-01

Multiple-choice questions are an important part of large-scale summative assessments, such as the advanced placement (AP) chemistry exam. However, past AP chemistry exam items often lacked the ability to test conceptual understanding and higher-order cognitive skills. The redesigned AP chemistry exam shows a distinctive shift in item types toward…

Naturally occurring phenolic acids modulate TPA-induced activation of EGFR, AP-1, and STATs in mouse epidermis.

PubMed

Cichocki, Michał; Dałek, Miłosz; Szamałek, Mateusz; Baer-Dubowska, Wanda

2014-01-01

Epidermal growth factor receptor (EGFR) plays an important role in epithelial carcinogenesis and appears to be involved in STATs activation. In this study we investigated the possible interference of naturally occurring phenolic acids with EGFR, activator protein-1 (AP-1), and signal transducers and activators of transcription (STATs) pathways activated by topical application of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Balb/c mice epidermis. Pretreatment with tannic or chlorogenic acid resulted in a significant decrease in the phosphorylation of EGFR Y-1068 and Y-1173 tyrosine residues, which was accompanied by reduced activation of AP-1. Tannic acid decreased also the c-Jun AP-1 subunit level and binding to TPA response element (TRE) (3- and 2-fold in comparison with TPA-treated group respectively). Simultaneous reduction of JNK activity might be responsible for reduced activation of AP-1. In contrast to these more complex phenolics, protocatechuic acid increased the activity of JNK and was also the most efficient inhibitor of STATs activation. These results indicate that naturally occurring phenolic acids, by decreasing EGFR, AP-1, and STATs activation, may modulate other elements both upstream and downstream in these pathways and thus inhibit the tumor development. Although more complex phenolics affect mainly the EGFR/AP-1 pathway, STATs seem to be the most important targets for simple compounds, such as protocatechuic acid.

L-Cysteine and L-AP4 microinjections in the rat caudal ventrolateral medulla decrease arterial blood pressure.

PubMed

Takemoto, Yumi

2014-12-01

The thiol amino acid L-cysteine increases arterial blood pressure (ABP) when injected into the cerebrospinal fluid space in conscious rats, indicating a pressor response to centrally acting L-cysteine. A prior synaptic membrane binding assay suggests that L-cysteine has a strong affinity for the L-2-amino-4-phosphonobutyric acid (L-AP4) binding site. The central action of L-cysteine may be vial-AP4 sensitive receptors. The present study investigated cardiovascular responses to L-cysteine and L-ap4 microinjected into the autonomic area of the caudal ventrolateral medulla (CVLM) where inhibitory neurons regulate ABP via pre-sympathetic vasomotor neurons. Both the injection of L-cysteine and L-AP4 in the CVLM sites identified with L-glutamate produced the same depressor and bradycardic responses in urethane-anesthetized rats. Neither a prior antagonist microinjection of MK801 for the N-methyl-D-aspartate (NMDA) receptor nor CNQX for the non-NMDA receptor attenuated the responses to L-cysteine, but the combination of the two receptor blocking with an additional prior injection abolished the response. In contrast, either receptor blockade alone abolished the response to L-AP4, indicating distinct mechanisms between responses to L-cysteine and L-AP4 in the CVLM. The results indicate that the CVLM is a central active site for L-cysteine's cardiovascular response. Central L-cysteine's action could be independent of the L-AP4 sensitive receptors. Cardiovascular regulation may involve endogenous L-cysteine in the CVLM. Further multidisciplinary examinations are required to elaborate on L-cysteine's functional roles in the CVLM. Copyright © 2014 Elsevier B.V. All rights reserved.

A polymorphic region in the human transcription factor AP-2beta gene is associated with specific personality traits.

PubMed

Damberg, M; Garpenstrand, H; Alfredsson, J; Ekblom, J; Forslund, K; Rylander, G; Oreland, L

2000-03-01

Transcription factor AP-2beta is implicated in playing an important role during embryonic development of different parts of the brain, eg, midbrain, hindbrain, spinal cord, dorsal and cranial root ganglia.1,2 The gene encoding AP-2beta contains a polymorphic region which includes a tetranucleotide repeat of [CAAA] four or five times, located in intron 2 between nucleotides 12593 and 12612.3 Since the midbrain contains structures important for variables such as mood and personality, we have investigated if the AP-2beta genotype is associated with personality traits estimated by the Karolinska Scales of Personality (KSP). Identification of transcription factor genes as candidate genes in psychiatric disorders is a novel approach to further elucidate the genetic factors that, together with environmental factors, are involved in the expression of specific psychiatric phenotypes. The AP-2beta genotype and KSP scores were determined for 137 Caucasian volunteers (73 females and 64 males). The personality traits muscular tension, guilt, somatic anxiety, psychastenia and indirect aggression were significantly associated with the specific AP-2beta genotype, albeit with significant difference between genders. Based on this result the human AP-2beta gene seems to be an important candidate gene for personality disorders. Moreover, the present results suggest that the structure of the intron 2 region of the AP-2beta gene is one factor that contributes to development of the constitutional component of specific personality traits.

APS8, a Polymeric Alkylpyridinium Salt Blocks α7 nAChR and Induces Apoptosis in Non-Small Cell Lung Carcinoma

PubMed Central

Zovko, Ana; Viktorsson, Kristina; Lewensohn, Rolf; Kološa, Katja; Filipič, Metka; Xing, Hong; Kem, William R.; Paleari, Laura; Turk, Tom

2013-01-01

Naturally occurring 3-alkylpyridinium polymers (poly-APS) from the marine sponge Reniera sarai, consisting of monomers containing polar pyridinium and nonpolar alkyl chain moieties, have been demonstrated to exert a wide range of biological activities, including a selective cytotoxicity against non-small cell lung cancer (NSCLC) cells. APS8, an analog of poly-APS with defined alkyl chain length and molecular size, non-competitively inhibits α7 nicotinic acetylcholine receptors (nAChRs) at nanomolar concentrations that are too low to be acetylcholinesterase (AChE) inhibitory or generally cytotoxic. In the present study we show that APS8 inhibits NSCLC tumor cell growth and activates apoptotic pathways. APS8 was not toxic for normal lung fibroblasts. Furthermore, in NSCLC cells, APS8 reduced the adverse anti-apoptotic, proliferative effects of nicotine. Our results suggest that APS8 or similar compounds might be considered as lead compounds to develop antitumor therapeutic agents for at least certain types of lung cancer. PMID:23880932

Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.

PubMed

Li, Li-Li; Melero-Fernandez de Mera, Raquel M; Chen, Jia; Ba, Wei; Kasri, Nael Nadif; Zhang, Mingjie; Courtney, Michael J

2015-05-13

The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity. Copyright © 2015 the authors 0270-6474/15/357349-16$15.00/0.

Gender, Academics and Interscholastic Sports Participation at the School Level: A Gender-specific Analysis of the Relationship between Interscholastic Sports Participation and AP Enrollment

PubMed Central

Veliz, Philip; Shakib, Sohaila

2014-01-01

While literature demonstrates that interscholastic sports participation is associated with positive academic outcomes, this relationship is rarely analyzed at a macro-level (the school-level). To date, there is no research examining whether increases in schools’ female and male interscholastic sports participation rates is associated with increases in female and male AP enrollment rates. Using a national sample of 4,644 public high schools during the 2009-2010 school year, we test several gender-specific hypotheses linked with the association between schools’ sport participation rates and advanced placement enrollment rates (AP math, AP science, AP foreign language, and overall AP enrollment). The findings reveal that schools’ female and male sports participation rates have a positive association with schools’ female and male AP math, AP science, AP foreign language, and overall AP enrollment rates. Moreover, the findings suggest that females benefit more than males in regard to the positive relationship between interscholastic sports and AP enrollment. PMID:24910475

Effects of environmental estrogenic chemicals on AP1 mediated transcription with estrogen receptors alpha and beta.

PubMed

Fujimoto, Nariaki; Honda, Hiroaki; Kitamura, Shigeyuki

2004-01-01

There has been much discussion concerning endocrine disrupting chemicals suspected of exerting adverse effects in both wildlife and humans. Since the majority of these compounds are estrogenic, a large number of in vitro tests for estrogenic characteristics have been developed for screening purpose. One reliable and widely used method is the reporter gene assay employing estrogen receptors (ERs) and a reporter gene with a cis-acting estrogen responsive element (ERE). Other elements such as AP1 also mediate estrogenic signals and the manner of response could be quite different from that of ERE. Since this has yet to be explored, the ER mediated AP1 activity in response to a series of environmental estrogens was investigated in comparison with ERE findings. All the compounds exhibited estrogenic properties with ERE-luc and their AP1 responses were quite similar. These was one exception, however, p,p'-DDT (1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane) did not exert any AP1-luc activity, while it appeared to be estrogenic at 10(-7) to 10(-5)M with the ERE action. None of the compounds demonstrated ER beta:AP1 activity. These data suggest that significant differences can occur in responses through the two estrogen pathways depending on environmental chemicals.

5-Substituents in the uridine moiety and their effect on the conformation of ApU-type dinucleoside phosphates.

PubMed

Hillen, W; Gassen, G

1978-03-29

The ApU analogues ApT, Apcl5U, Apbr5U, Apa5U and Apno5(2)U were synthesized with the aid of ribonuclease U2 starting from 2',3'-cyclic Ap and the respective uridine derivatives. For these compounds the ultraviolet data, the difference spectra, the hypochromism and the temperature dependence of the CD spectra are reported. The dimerisation shifts of the pyrimidine protons which were obtained from the 100 MHz PMR spectra confirm the optical results. The influence of the substituents in the 5 position of the uracil ring on base-base interaction and the conformation of the dinucleoside phosphates is discussed with respect to the van der Waals radii and the electronic effects of these groups. As calculated from the hypochromism the dinucleoside phosphates can be arranged according to decreasing base-base interaction: Apno5(2)U greater than Apbr5U approximately ApT greater than Apcl5U greater than ApU greater than Apa5U.

Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins.

PubMed

Mishra, S K; Agostinelli, N R; Brett, T J; Mizukami, I; Ross, T S; Traub, L M

2001-12-07

Clathrin-mediated endocytosis is a major pathway for the internalization of macromolecules into the cytoplasm of eukaryotic cells. The principle coat components, clathrin and the AP-2 adaptor complex, assemble a polyhedral lattice at plasma membrane bud sites with the aid of several endocytic accessory proteins. Here, we show that huntingtin-interacting protein 1 (HIP1), a binding partner of huntingtin, copurifies with brain clathrin-coated vesicles and associates directly with both AP-2 and clathrin. The discrete interaction sequences within HIP1 that facilitate binding are analogous to motifs present in other accessory proteins, including AP180, amphiphysin, and epsin. Bound to a phosphoinositide-containing membrane surface via an epsin N-terminal homology (ENTH) domain, HIP1 associates with AP-2 to provide coincident clathrin-binding sites that together efficiently recruit clathrin to the bilayer. Our data implicate HIP1 in endocytosis, and the similar modular architecture and function of HIP1, epsin, and AP180 suggest a common role in lipid-regulated clathrin lattice biogenesis.

AP39, a mitochondria‐targeting hydrogen sulfide (H2S) donor, protects against myocardial reperfusion injury independently of salvage kinase signalling

PubMed Central

Karwi, Qutuba G; Bornbaum, Julia; Boengler, Kerstin; Torregrossa, Roberta; Whiteman, Matthew; Wood, Mark E; Schulz, Rainer

2017-01-01

Background and Purpose H2S protects myocardium against ischaemia/reperfusion injury. This protection may involve the cytosolic reperfusion injury salvage kinase (RISK) pathway, but direct effects on mitochondrial function are possible. Here, we investigated the potential cardioprotective effect of a mitochondria‐specific H2S donor, AP39, at reperfusion against ischaemia/reperfusion injury. Experimental Approach Anaesthetized rats underwent myocardial ischaemia (30 min)/reperfusion (120 min) with randomization to receive interventions before reperfusion: vehicle, AP39 (0.01, 0.1, 1 μmol·kg−1), or control compounds AP219 and ADT‐OH (1 μmol·kg−1). LY294002, L‐NAME or ODQ were used to investigate the involvement of the RISK pathway. Myocardial samples harvested 5 min after reperfusion were analysed for RISK protein phosphorylation and isolated cardiac mitochondria were used to examine the direct mitochondrial effects of AP39. Key Results AP39, dose‐dependently, reduced infarct size. Inhibition of either PI3K/Akt, eNOS or sGC did not affect this effect of AP39. Western blot analysis confirmed that AP39 did not induce phosphorylation of Akt, eNOS, GSK‐3β or ERK1/2. In isolated subsarcolemmal and interfibrillar mitochondria, AP39 significantly attenuated mitochondrial ROS generation without affecting respiratory complexes I or II. Furthermore, AP39 inhibited mitochondrial permeability transition pore (PTP) opening and co‐incubation of mitochondria with AP39 and cyclosporine A induced an additive inhibitory effect on the PTP. Conclusion and Implications AP39 protects against reperfusion injury independently of the cytosolic RISK pathway. This cardioprotective effect could be mediated by inhibiting PTP via a cyclophilin D‐independent mechanism. Thus, selective delivery of H2S to mitochondria may be therapeutically applicable for employing the cardioprotective utility of H2S. PMID:27930802

One-step affinity tag purification of full-length recombinant human AP-1 complexes from bacterial inclusion bodies using a polycistronic expression system

PubMed Central

Wang, Wei-Ming; Lee, A-Young; Chiang, Cheng-Ming

2008-01-01

The AP-1 transcription factor is a dimeric protein complex formed primarily between Jun (c-Jun, JunB, JunD) and Fos (c-Fos, FosB, Fra-1, Fra-2) family members. These distinct AP-1 complexes are expressed in many cell types and modulate target gene expression implicated in cell proliferation, differentiation, and stress responses. Although the importance of AP-1 has long been recognized, the biochemical characterization of AP-1 remains limited in part due to the difficulty in purifying full-length, reconstituted dimers with active DNA-binding and transcriptional activity. Using a combination of bacterial coexpression and epitope-tagging methods, we successfully purified all 12 heterodimers (3 Jun × 4 Fos) of full-length human AP-1 complexes as well as c-Jun/c-Jun, JunD/JunD, and c-Jun/JunD dimers from bacterial inclusion bodies using one-step nickel-NTA affinity tag purification following denaturation and renaturation of coexpressed AP-1 subunits. Coexpression of two constitutive components in a dimeric AP-1 complex helps stabilize the proteins when compared with individual protein expression in bacteria. Purified dimeric AP-1 complexes are functional in sequence-specific DNA binding, as illustrated by electrophoretic mobility shift assays and DNase I footprinting, and are also active in transcription with in vitro-reconstituted human papillomavirus (HPV) chromatin containing AP-1-binding sites in the native configuration of HPV nucleosomes. The availability of these recombinant full-length human AP-1 complexes has greatly facilitated mechanistic studies of AP-1-regulated gene transcription in many biological systems. PMID:18329890

Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the Eye.

PubMed

Crooke, Almudena; Guzman-Aranguez, Ana; Carracedo, Gonzalo; de Lara, Maria J Perez; Pintor, Jesus

Diadenosine tetraphosphate abbreviated Ap 4 A is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of Ap 4 A are mostly carried out by P2Y 2 receptors, but the participation of P2X2 and P2Y 6 in processes such as the regulation of intraocular pressure (IOP), together with the P2Y 2 , is pivotal. Beyond the physiological role, this dinucleotide can present on the ocular surface keeping a right production of tear secretion or regulating IOP. It is important to note that exogenous application of Ap 4 A to cells or animal models can significantly modify pathophysiological conditions and thus is an attractive therapeutic molecule. The ocular location where Ap 4 A actions have not been fully elucidated is in the retina. Although some analogues show interesting actions on pathological situations such as retinal detachment, little is known about the real effect of this dinucleotide, this being one of the challenges that require pursuing in the near future.

Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2

PubMed Central

Pechstein, Arndt; Bacetic, Jelena; Vahedi-Faridi, Ardeschir; Gromova, Kira; Sundborger, Anna; Tomlin, Nikolay; Krainer, Georg; Vorontsova, Olga; Schäfer, Johannes G.; Owe, Simen G.; Cousin, Michael A.; Saenger, Wolfram; Shupliakov, Oleg; Haucke, Volker

2010-01-01

Clathrin-mediated synaptic vesicle (SV) recycling involves the spatiotemporally controlled assembly of clathrin coat components at phosphatidylinositiol (4, 5)-bisphosphate [PI(4,5)P2]-enriched membrane sites within the periactive zone. Such spatiotemporal control is needed to coordinate SV cargo sorting with clathrin/AP2 recruitment and to restrain membrane fission and synaptojanin-mediated uncoating until membrane deformation and clathrin coat assembly are completed. The molecular events underlying these control mechanisms are unknown. Here we show that the endocytic SH3 domain-containing accessory protein intersectin 1 scaffolds the endocytic process by directly associating with the clathrin adaptor AP2. Acute perturbation of the intersectin 1-AP2 interaction in lamprey synapses in situ inhibits the onset of SV recycling. Structurally, complex formation can be attributed to the direct association of hydrophobic peptides within the intersectin 1 SH3A-B linker region with the “side sites” of the AP2 α- and β-appendage domains. AP2 appendage association of the SH3A-B linker region inhibits binding of the inositol phosphatase synaptojanin 1 to intersectin 1. These data identify the intersectin-AP2 complex as an important regulator of clathrin-mediated SV recycling in synapses. PMID:20160082

Analysis of magnetic activity of the rapidly rotating stars He 373 and AP 225

NASA Astrophysics Data System (ADS)

Kolbin, A. I.; Tsymbal, V. V.

2017-06-01

Spectroscopic and photometric data for the two rapidly rotating members of the α Persei cluster He 373 and AP 225 are analyzed. Improved estimates have been obtained for the projected equatorial rotation velocities: v sin i = 164 km/s for He 323 and v sin i = 129 km/s for AP 225. Multi-band photometric mapping is used to map the spot distributions on the surfaces of the two stars. The fractional spotted areas S and mean temperature difference Δ T between the unspotted photosphere and the spots are estimated ( S = 7% and Δ T = 1000 K for He 373; S = 9% and Δ T = 800 K for AP 225). The H α line profiles of both stars have variable emission components whose widths are used to deduce the presence of extended regions of emission reaching the corotation radius.

Concepciones Alternativas de "Fotosintesis" en estudiantes Universitarios del curso basico de Biologia y posibles correcciones con el Modelo Educativo MODEF

NASA Astrophysics Data System (ADS)

De Jesus Roman, Sandra

Concepciones Alternativas de Fotosíntesis en estudiantes Universitariosdel curso básico de Biología y posibles correcciones con el Modelo Educativo MODEF El modelo educativo para la enseñanza de Fotosíntesis (MODEF) se implantó para trabajar el problema de las concepciones alternativas (CA) en un curso de Biología General. Se evaluaron los resultados en cuanto al logro del aprendizaje significativo. La pregunta central de la investigación fue: ¿Cómo aporta el modelo educativo en la didáctica y comprensión del tema de fotosíntesis? Se efectuó una investigación acción con una fase cuantitativa y una cualitativa. Para la fase cuantitativa se elaboró una prueba para determinar las concepciones alternativas, se validó y se sometió a los estudiantes que participaron en el estudio antes y después de ofrecer la unidad de metabolismo celular. Los participantes eran estudiantes de primer año de la Universidad de Puerto Rico en Bayamón (UPRB). Se llevó a cabo un análisis de consistencia interna de la prueba mediante el método Alfa de Cronbach. Se analizaron las contestaciones a cada pregunta mediante la prueba de Ji cuadrado de contingencia, se efectuó la prueba de t y el coeficiente r de Pearson. La fase cualitativa incluyó la observación participativa de la investigadora- profesora, las reflexiones de los estudiantes y la información de las entrevistas semi-estructuradas que se realizaron a tres estudiantes del curso. El análisis se llevó a cabo mediante el Modelo de Wolcott. Se trabajaron diez CA de las cuales siete fueron corregidas mediante el Modelo MODEF. Las actividades más importantes para el proceso de aprendizaje incluyeron el trabajo de investigación o búsqueda de información para hacer una presentación digital, la elaboración de tablas, los mapas de conceptos, el uso de visuales o videos y las analogías para explicar conceptos o procesos. En conclusión: se recomienda el uso del Modelo MODEF para la discusión del tema de

Mechanism of action of novel lung edema therapeutic AP301 by activation of the epithelial sodium channel.

PubMed

Shabbir, Waheed; Scherbaum-Hazemi, Parastoo; Tzotzos, Susan; Fischer, Bernhard; Fischer, Hendrik; Pietschmann, Helmut; Lucas, Rudolf; Lemmens-Gruber, Rosa

2013-12-01

AP301 [Cyclo(CGQRETPEGAEAKPWYC)], a cyclic peptide comprising the human tumor necrosis factor lectin-like domain (TIP domain) sequence, is currently being developed as a treatment for lung edema and has been shown to reduce extravascular lung water and improve lung function in mouse, rat, and pig models. The current paradigm for liquid homeostasis in the adult mammalian lung is that passive apical uptake of sodium via the amiloride-sensitive epithelial Na⁺ channel (ENaC) and nonselective cyclic-nucleotide-gated cation channels creates the major driving force for reabsorption of water through the alveolar epithelium in addition to other ion channels such as potassium and chloride channels. AP301 can increase amiloride-sensitive current in A549 cells as well as in freshly isolated type II alveolar epithelial cells from different species. ENaC is expressed endogenously in all of these cell types. Consequently, this study was undertaken to determine whether ENaC is the specific target of AP301. The effect of AP301 in A549 cells as well as in human embryonic kidney cells and Chinese hamster ovary cells heterologously expressing human ENaC subunits (α, β, γ, and δ) was measured in patch clamp experiments. The congener TIP peptide AP318 [Cyclo(4-aminobutanoic acid-GQRETPEGAEAKPWYD)] activated ENaC by increasing single-channel open probability. AP301 increased current in proteolytically activated (cleaved) but not near-silent (uncleaved) ENaC in a reversible manner. αβγ- or δβγ-ENaC coexpression was required for maximal activity. No increase in current was observed after deglycosylation of extracellular domains of ENaC. Thus, our data suggest that the specific interaction of AP301 with both endogenously and heterologously expressed ENaC requires precedent binding to glycosylated extracellular loop(s).

[Association of Schizophrenia and its Clinical Implications with the NOS1AP Gene in the Colombian Population].

PubMed

Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya

2012-06-01

The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail

PubMed Central

Roeth, Jeremiah F.; Williams, Maya; Kasper, Matthew R.; Filzen, Tracey M.; Collins, Kathleen L.

2004-01-01

To avoid immune recognition by cytotoxic T lymphocytes (CTLs), human immunodeficiency virus (HIV)-1 Nef disrupts the transport of major histocompatibility complex class I molecules (MHC-I) to the cell surface in HIV-infected T cells. However, the mechanism by which Nef does this is unknown. We report that Nef disrupts MHC-I trafficking by rerouting newly synthesized MHC-I from the trans-Golgi network (TGN) to lysosomal compartments for degradation. The ability of Nef to target MHC-I from the TGN to lysosomes is dependent on expression of the μ1 subunit of adaptor protein (AP) AP-1A, a cellular protein complex implicated in TGN to endolysosomal pathways. We demonstrate that in HIV-infected primary T cells, Nef promotes a physical interaction between endogenous AP-1 and MHC-I. Moreover, we present data that this interaction uses a novel AP-1 binding site that requires amino acids in the MHC-I cytoplasmic tail. In sum, our evidence suggests that binding of AP-1 to the Nef–MHC-I complex is an important step required for inhibition of antigen presentation by HIV. PMID:15569716

Prevention & treatment of obstetrical complications in APS: Is hydroxychloroquine the Holy Grail we are looking for?

PubMed

Meroni, Pier Luigi

2016-12-01

Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory. Copyright © 2016. Published by Elsevier Ltd.

An Analysis of the Relationship between School-Level AP® Professional Development Activity and Subsequent Student AP Performance. Research Report No. 2012-8

ERIC Educational Resources Information Center

Laitusis, Vytas

2012-01-01

The overarching purpose behind this evaluation was to gauge the impact of AP professional development (PD) on AP student outcomes in a state with a significant rate of PD implementation. The evaluation attempted to predict the level of student AP performance by the number of AP professional development events attended by teachers in that school in…

Comportamiento del Helio en estrellas químicamente peculiares

NASA Astrophysics Data System (ADS)

Malaroda, S. M.; López García, Z.; Leone, F.; Catalano, F.

Las estrellas químicamente peculiares (CP) se caracterizan por tener deficiencias y sobreabundancias de algunos elementos químicos de hasta 106 veces la abundancia solar. Además presentan variaciones en las líneas espectrales. Se piensa que ello se debe a que los campos magnéticos presentes en este tipo de estrellas son principalmente dipolares, con un eje de simetría diferente del eje de rotación. La distribución de los elementos sobreabundantes y deficientes no es homogénea sobre la superficie estelar y las variaciones observadas serían una consecuencia directa de la rotación estelar. Entre los elementos con abundancia anómala se encuentra el Helio, cuyas líneas tienen intensidades que no son consistentes con una abundancia normal, que no puede ser determinada del modo usual, o sea, considerando una atmósfera con composición solar. Con el fin de determinar la abundancia de este elemento, se inició un estudio de estrellas anómalas de Helio, Hew y He strong. Además se determinarán las abundancias de otros elementos anómalos como ser el Si, Cr, Mg, Mn y Fe. Las mismas se determinan del modo tradicional, o sea: a) medida de los anchos equivalentes de las líneas de los distintos elementos analizados; b) adopción de la temperatura efectiva, gravedad y abundancia del Helio; c) cálculo del modelo de atmósfera d) comparación con las observaciones y reinicio de un proceso iterativo hasta lograr un acuerdo entre todos los parámetros analizados. Las observaciones se llevaron a cabo en el Complejo Astronómico El Leoncito. Se observaron setenta y ocho estrellas anómalas de Helio. En este momento se está procediendo a calcular las abundancias correspondientes a los distintos elementos químicos. Para ello se hace uso de los modelos de Kurucz, ATLAS9. Los cálculos NLTE de las líneas de Helio se llevan a cabo con el programa MULTI y se compararán con los realizados con el programa WIDTH9 de Kurucz (LTE), con el objeto de resaltar la importancia de

Free and ATP-bound structures of Ap4A hydrolase from Aquifex aeolicus V5.

PubMed

Jeyakanthan, Jeyaraman; Kanaujia, Shankar Prasad; Nishida, Yuya; Nakagawa, Noriko; Praveen, Surendran; Shinkai, Akeo; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Sekar, Kanagaraj

2010-02-01

Asymmetric diadenosine tetraphosphate (Ap(4)A) hydrolases degrade the metabolite Ap(4)A back into ATP and AMP. The three-dimensional crystal structure of Ap(4)A hydrolase (16 kDa) from Aquifex aeolicus has been determined in free and ATP-bound forms at 1.8 and 1.95 A resolution, respectively. The overall three-dimensional crystal structure of the enzyme shows an alphabetaalpha-sandwich architecture with a characteristic loop adjacent to the catalytic site of the protein molecule. The ATP molecule is bound in the primary active site and the adenine moiety of the nucleotide binds in a ring-stacking arrangement equivalent to that observed in the X-ray structure of Ap(4)A hydrolase from Caenorhabditis elegans. Binding of ATP in the active site induces local conformational changes which may have important implications in the mechanism of substrate recognition in this class of enzymes. Furthermore, two invariant water molecules have been identified and their possible structural and/or functional roles are discussed. In addition, modelling of the substrate molecule at the primary active site of the enzyme suggests a possible path for entry and/or exit of the substrate and/or product molecule.

The New APS Topical Group on the Physics of Climate: History, Objectives and Panel Discussion

NASA Astrophysics Data System (ADS)

Brasseur, James; Behringer, Robert

2013-03-01

The GPC Chair will introduce the new APS Topical Group on the Physics of Climate (GPC), describe its history and objectives, and introduce the current GPC leadership before opening the floor to a panel discussion. The GPC resulted from two petitions that emerged from the controversy that followed the APS Statement on Climate Change (see APS website). The two proposals were merged and an organization committee formed by the APS leadership. After a long organizational period in 2011, the GPC bylaws were finalized with the following key objective: The objective of the GPC shall be to promote the advancement and diffusion of knowledge concerning the physics, measurement, and modeling of climate processes, within the domain of natural science and outside the domains of societal impact and policy, legislation and broader societal issues. The objective includes the integration of scientific knowledge and analysis methods across disciplines to address the dynamical complexities and uncertainties of climate physics. The GPC Invited and Focus Sessions at this March meeting are the inaugural GPC events. The Program Committee Chair will moderate a panel between the attending GPC leadership and audience to solicit suggestions for potential future GPC events that advance the GPC objectives.

AP, Dual Enrollment, and the Survival of Honors Education

ERIC Educational Resources Information Center

Guzy, Annmarie

2016-01-01

A new admissions crisis has begun to emerge in the honors community. In an increasing number of states, legislatures are mandating uniform minimum AP and dual enrollment credits that public colleges and universities must accept, and consequently the honors students that have been admitted based in part on their willingness to take on challenging…

Luteolin, a flavonoid, inhibits AP-1 activation by basophils.

PubMed

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio

2006-02-03

Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

Luteolin, a flavonoid, inhibits AP-1 activation by basophils

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

Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke

Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812more » cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.« less

Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex.

PubMed

Alqarni, Saad S M; Murthy, Andal; Zhang, Wei; Przewloka, Marcin R; Silva, Ana P G; Watson, Aleksandra A; Lejon, Sara; Pei, Xue Y; Smits, Arne H; Kloet, Susan L; Wang, Hongxin; Shepherd, Nicholas E; Stokes, Philippa H; Blobel, Gerd A; Vermeulen, Michiel; Glover, David M; Mackay, Joel P; Laue, Ernest D

2014-08-08

The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

FSGS3/CD2AP is a barbed-end capping protein that stabilizes actin and strengthens adherens junctions

PubMed Central

Brieher, William M.

2013-01-01

By combining in vitro reconstitution biochemistry with a cross-linking approach, we have identified focal segmental glomerulosclerosis 3/CD2-associated protein (FSGS3/CD2AP) as a novel actin barbed-end capping protein responsible for actin stability at the adherens junction. FSGS3/CD2AP colocalizes with E-cadherin and α-actinin-4 at the apical junction in polarized Madin-Darby canine kidney (MDCK) cells. Knockdown of FSGS3/CD2AP compromised actin stability and decreased actin accumulation at the adherens junction. Using a novel apparatus to apply mechanical stress to cell–cell junctions, we showed that knockdown of FSGS3/CD2AP compromised adhesive strength, resulting in tearing between cells and disruption of barrier function. Our results reveal a novel function of FSGS3/CD2AP and a previously unrecognized role of barbed-end capping in junctional actin dynamics. Our study underscores the complexity of actin regulation at cell–cell contacts that involves actin activators, inhibitors, and stabilizers to control adhesive strength, epithelial behavior, and permeability barrier integrity. PMID:24322428

The temperate Burkholderia phage AP3 of the Peduovirinae shows efficient antimicrobial activity against B. cenocepacia of the IIIA lineage.

PubMed

Roszniowski, Bartosz; Latka, Agnieszka; Maciejewska, Barbara; Vandenheuvel, Dieter; Olszak, Tomasz; Briers, Yves; Holt, Giles S; Valvano, Miguel A; Lavigne, Rob; Smith, Darren L; Drulis-Kawa, Zuzanna

2017-02-01

Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.

AP-1/σ1B-adaptin mediates endosomal synaptic vesicle recycling, learning and memory

PubMed Central

Glyvuk, Nataliya; Tsytsyura, Yaroslav; Geumann, Constanze; D'Hooge, Rudi; Hüve, Jana; Kratzke, Manuel; Baltes, Jennifer; Böning, Daniel; Klingauf, Jürgen; Schu, Peter

2010-01-01

Synaptic vesicle recycling involves AP-2/clathrin-mediated endocytosis, but it is not known whether the endosomal pathway is also required. Mice deficient in the tissue-specific AP-1–σ1B complex have impaired synaptic vesicle recycling in hippocampal synapses. The ubiquitously expressed AP-1–σ1A complex mediates protein sorting between the trans-Golgi network and early endosomes. Vertebrates express three σ1 subunit isoforms: A, B and C. The expressions of σ1A and σ1B are highest in the brain. Synaptic vesicle reformation in cultured neurons from σ1B-deficient mice is reduced upon stimulation, and large endosomal intermediates accumulate. The σ1B-deficient mice have reduced motor coordination and severely impaired long-term spatial memory. These data reveal a molecular mechanism for a severe human X-chromosome-linked mental retardation. PMID:20203623

Genome-wide analysis of the AP2/ERF family in Musa species reveals divergence and neofunctionalisation during evolution

PubMed Central

Lakhwani, Deepika; Pandey, Ashutosh; Dhar, Yogeshwar Vikram; Bag, Sumit Kumar; Trivedi, Prabodh Kumar; Asif, Mehar Hasan

2016-01-01

AP2/ERF domain containing transcription factor super family is one of the important regulators in the plant kingdom. The involvement of AP2/ERF family members has been elucidated in various processes associated with plant growth, development as well as in response to hormones, biotic and abiotic stresses. In this study, we carried out genome-wide analysis to identify members of AP2/ERF family in Musa acuminata (A genome) and Musa balbisiana (B genome) and changes leading to neofunctionalisation of genes. Analysis identified 265 and 318 AP2/ERF encoding genes in M. acuminata and M. balbisiana respectively which were further classified into ERF, DREB, AP2, RAV and Soloist groups. Comparative analysis indicated that AP2/ERF family has undergone duplication, loss and divergence during evolution and speciation of the Musa A and B genomes. We identified nine genes which are up-regulated during fruit ripening and might be components of the regulatory machinery operating during ethylene-dependent ripening in banana. Tissue-specific expression analysis of the genes suggests that different regulatory mechanisms might be involved in peel and pulp ripening process through recruiting specific ERFs in these tissues. Analysis also suggests that MaRAV-6 and MaERF026 have structurally diverged from their M. balbisiana counterparts and have attained new functions during ripening. PMID:26733055

Genome-wide analysis of the AP2/ERF family in Musa species reveals divergence and neofunctionalisation during evolution.

PubMed

Lakhwani, Deepika; Pandey, Ashutosh; Dhar, Yogeshwar Vikram; Bag, Sumit Kumar; Trivedi, Prabodh Kumar; Asif, Mehar Hasan

2016-01-06

AP2/ERF domain containing transcription factor super family is one of the important regulators in the plant kingdom. The involvement of AP2/ERF family members has been elucidated in various processes associated with plant growth, development as well as in response to hormones, biotic and abiotic stresses. In this study, we carried out genome-wide analysis to identify members of AP2/ERF family in Musa acuminata (A genome) and Musa balbisiana (B genome) and changes leading to neofunctionalisation of genes. Analysis identified 265 and 318 AP2/ERF encoding genes in M. acuminata and M. balbisiana respectively which were further classified into ERF, DREB, AP2, RAV and Soloist groups. Comparative analysis indicated that AP2/ERF family has undergone duplication, loss and divergence during evolution and speciation of the Musa A and B genomes. We identified nine genes which are up-regulated during fruit ripening and might be components of the regulatory machinery operating during ethylene-dependent ripening in banana. Tissue-specific expression analysis of the genes suggests that different regulatory mechanisms might be involved in peel and pulp ripening process through recruiting specific ERFs in these tissues. Analysis also suggests that MaRAV-6 and MaERF026 have structurally diverged from their M. balbisiana counterparts and have attained new functions during ripening.

DETAIL VIEW OF WINCH USED TO RAISE AND LOWER AP ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAIL VIEW OF WINCH USED TO RAISE AND LOWER AP 93W, ROOF LEVEL, PLATFORM D-SOUTH, HB-3, FACING WEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

Automated Procurement System (APS) revised project management plan (DS-03)

NASA Technical Reports Server (NTRS)

Murphy, Diane R.

1995-01-01

The Project Plan is the governing document for the implementation of the Automated Procurement System (APS). It includes a description of the proposed system, describes the work to be done, establishes a schedule of deliverables, and discusses the major standards and procedures to be followed.

AP1000{sup R} design robustness against extreme external events - Seismic, flooding, and aircraft crash

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

Pfister, A.; Goossen, C.; Coogler, K.

2012-07-01

Both the International Atomic Energy Agency (IAEA) and the U.S. Nuclear Regulatory Commission (NRC) require existing and new nuclear power plants to conduct plant assessments to demonstrate the unit's ability to withstand external hazards. The events that occurred at the Fukushima-Dai-ichi nuclear power station demonstrated the importance of designing a nuclear power plant with the ability to protect the plant against extreme external hazards. The innovative design of the AP1000{sup R} nuclear power plant provides unparalleled protection against catastrophic external events which can lead to extensive infrastructure damage and place the plant in an extended abnormal situation. The AP1000 plantmore » is an 1100-MWe pressurized water reactor with passive safety features and extensive plant simplifications that enhance construction, operation, maintenance and safety. The plant's compact safety related footprint and protection provided by its robust nuclear island structures prevent significant damage to systems, structures, and components required to safely shutdown the plant and maintain core and spent fuel pool cooling and containment integrity following extreme external events. The AP1000 nuclear power plant has been extensively analyzed and reviewed to demonstrate that it's nuclear island design and plant layout provide protection against both design basis and extreme beyond design basis external hazards such as extreme seismic events, external flooding that exceeds the maximum probable flood limit, and malicious aircraft impact. The AP1000 nuclear power plant uses fail safe passive features to mitigate design basis accidents. The passive safety systems are designed to function without safety-grade support systems (such as AC power, component cooling water, service water, compressed air or HVAC). The plant has been designed to protect systems, structures, and components critical to placing the reactor in a safe shutdown condition within the steel containment

Altered distribution of ATG9A and accumulation of axonal aggregates in neurons from a mouse model of AP-4 deficiency syndrome

PubMed Central

De Pace, Raffaella; Damme, Markus; Mattera, Rafael; Jarnik, Michal; Hoffmann, Victoria; Morris, H. Douglas; Han, Tae-Un; Mancini, Grazia M. S.; Buonanno, Andrés

2018-01-01

The hereditary spastic paraplegias (HSP) are a clinically and genetically heterogeneous group of disorders characterized by progressive lower limb spasticity. Mutations in subunits of the heterotetrameric (ε-β4-μ4-σ4) adaptor protein 4 (AP-4) complex cause an autosomal recessive form of complicated HSP referred to as “AP-4 deficiency syndrome”. In addition to lower limb spasticity, this syndrome features intellectual disability, microcephaly, seizures, thin corpus callosum and upper limb spasticity. The pathogenetic mechanism, however, remains poorly understood. Here we report the characterization of a knockout (KO) mouse for the AP4E1 gene encoding the ε subunit of AP-4. We find that AP-4 ε KO mice exhibit a range of neurological phenotypes, including hindlimb clasping, decreased motor coordination and weak grip strength. In addition, AP-4 ε KO mice display a thin corpus callosum and axonal swellings in various areas of the brain and spinal cord. Immunohistochemical analyses show that the transmembrane autophagy-related protein 9A (ATG9A) is more concentrated in the trans-Golgi network (TGN) and depleted from the peripheral cytoplasm both in skin fibroblasts from patients with mutations in the μ4 subunit of AP-4 and in various neuronal types in AP-4 ε KO mice. ATG9A mislocalization is associated with increased tendency to accumulate mutant huntingtin (HTT) aggregates in the axons of AP-4 ε KO neurons. These findings indicate that the AP-4 ε KO mouse is a suitable animal model for AP-4 deficiency syndrome, and that defective mobilization of ATG9A from the TGN and impaired autophagic degradation of protein aggregates might contribute to neuroaxonal dystrophy in this disorder. PMID:29698489

AP: A Critical Examination of the Advanced Placement Program

ERIC Educational Resources Information Center

Sadler, Philip M., Ed.; Sonnert, Gerhard, Ed.; Tai, Robert H., Ed.; Klopfenstein, Kristin, Ed.

2010-01-01

With an annual yearly growth rate of 9.3 percent over the last two decades, Advanced Placement courses have become a juggernaut in American high school education. AP courses are routinely perceived as an indicator of educational rigor, and many schools push to enroll low-income or minority students in these courses in the hope of preparing them…

Ap4A and ADP-beta-S binding to P2 purinoceptors present on rat brain synaptic terminals.

PubMed Central

Pintor, J.; Díaz-Rey, M. A.; Miras-Portugal, M. T.

1993-01-01

1. Diadenosine tetraphosphate (Ap4A) a dinucleotide stored and released from rat brain synaptic terminals presents two types of affinity binding sites in synaptosomes. When [3H]-Ap4A was used for binding studies a Kd value of 0.10 +/- 0.014 nM and a Bmax value of 16.6 +/- 1.2 fmol mg-1 protein were obtained for the high affinity binding site from the Scatchard analysis. The second binding site, obtained by displacement studies, showed a Ki value of 0.57 +/- 0.09 microM. 2. Displacement of [3H]-Ap4A by non-labelled Ap4A and P2-purinoceptor ligands showed a displacement order of Ap4A > adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) > 5'-adenylyl-imidodiphosphate (AMP-PNP) > alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP) in both sites revealed by the Ki values of 0.017 nM, 0.030 nM, 0.058 nM and 0.147 nM respectively for the high affinity binding site and values of 0.57 microM, 0.87 microM, 2.20 microM and 4.28 microM respectively for the second binding site. 3. Studies of the P2-purinoceptors present in synaptosomes were also performed with [35S]-ADP-beta-S. This radioligand showed two binding sites the first with Kd and Bmax values of 0.11 +/- 0.022 nM and 3.9 +/- 2.1 fmol mg-1 of protein respectively for the high affinity binding site obtained from the Scatchard plot. The second binding site showed a Ki of 0.018 +/- 0.0035 microM obtained from displacement curves. 4. Competition studies with diadenosine polyphosphates of [35S]-ADP-beta-S binding showed a displacement order of Ap4A > Ap5A > Ap6A in the high affinity binding site and Ki values of 0.023 nM, 0.081 nM and 5.72 nM respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8485620

Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering

PubMed Central

Raza, M. Hashim; Mattera, Rafael; Morell, Robert; Sainz, Eduardo; Rahn, Rachel; Gutierrez, Joanne; Paris, Emily; Root, Jessica; Solomon, Beth; Brewer, Carmen; Basra, M. Asim Raza; Khan, Shaheen; Riazuddin, Sheikh; Braun, Allen; Bonifacino, Juan S.; Drayna, Dennis

2015-01-01

Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of-function mutations in this gene. AP4E1 encodes the ε subunit of the heterotetrameric (ε-β4-μ4-σ4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the μ4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6-phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering. PMID:26544806

The Impact of AP® Achievement Institute I on Students' AP Performance. Research Report No. 2012-7

ERIC Educational Resources Information Center

Bausmith, Jennifer Merriman; Laitusis, Vytas

2012-01-01

The AP Achievement Institute I (APAI I) is a four-day professional development program offered to teachers and administrators by EXCELerator™, a district reform program operated by the College Board. The APAI I program is designed to help teachers develop effective AP instructional strategies for a diverse student body and to help district,…

A proposed STAR microvertex detector using Active Pixel Sensors with some relevant studies on APS performance

NASA Astrophysics Data System (ADS)

Kleinfelder, S.; Li, S.; Bieser, F.; Gareus, R.; Greiner, L.; King, J.; Levesque, J.; Matis, H. S.; Oldenburg, M.; Ritter, H. G.; Retiere, F.; Rose, A.; Schweda, K.; Shabetai, A.; Sichtermann, E.; Thomas, J. H.; Wieman, H. H.; Bichsel, H.

2006-09-01

A vertex detector that can measure particles with charm or bottom quarks would dramatically expand the physics capability of the STAR detector at RHIC. To accomplish this, we are proposing to build the Heavy Flavor Tracker (HFT) using 2×2 cm Active Pixels Sensors (APS). Ten of these APS chips will be arranged on a ladder (0.28% of a radiation length) at radii of 1.5 and at 5.0 cm. We have examined several properties of APS chips, so that we can characterize the performance of this detector. Using 1.5 GeV/ c electrons, we have measured the charge collected and compared it to the expected charge. To achieve high efficiency, we have considered two different cluster finding algorithms and found that the choice of algorithm is dependent on noise level. We have demonstrated that a Scanning Electron Microscope can probe properties of an APS chip. In particular, we studied several position resolution algorithms. Finally, we studied the properties of pixel pitches from 5 to 30 μm.

Displacement damage effects on CMOS APS image sensors induced by neutron irradiation from a nuclear reactor

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Huang, Shaoyan; Liu, Minbo

The experiments of displacement damage effects on CMOS APS image sensors induced by neutron irradiation from a nuclear reactor are presented. The CMOS APS image sensors are manufactured in the standard 0.35 μm CMOS technology. The flux of neutron beams was about 1.33 × 10{sup 8} n/cm{sup 2}s. The three samples were exposed by 1 MeV neutron equivalent-fluence of 1 × 10{sup 11}, 5 × 10{sup 11}, and 1 × 10{sup 12} n/cm{sup 2}, respectively. The mean dark signal (K{sub D}), dark signal spike, dark signal non-uniformity (DSNU), noise (V{sub N}), saturation output signal voltage (V{sub S}), and dynamic rangemore » (DR) versus neutron fluence are investigated. The degradation mechanisms of CMOS APS image sensors are analyzed. The mean dark signal increase due to neutron displacement damage appears to be proportional to displacement damage dose. The dark images from CMOS APS image sensors irradiated by neutrons are presented to investigate the generation of dark signal spike.« less

The Relationship of AP® Teacher Practices and Student AP Exam Performance. Research Report No. 2007-5. ETS RR-05-10

ERIC Educational Resources Information Center

Paek, Pamela L.; Braun, Henry; Trapani, Catherine; Ponte, Eva; Powers, Don

2008-01-01

This report analyzes the relationship of Advanced Placement Program® (AP®) teacher practices and student performance on AP Biology and AP U.S. History Exams. Using a national survey of AP teachers, the study developed four models for each subject with public school teachers only and both public and nonpublic school teachers, using two standards of…

Determination of L-AP4-bound human mGlu8 receptor amino terminal domain structure and the molecular basis for L-AP4’s group III mGlu receptor functional potency and selectivity

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

Schkeryantz, Jeffery M.; Chen, Qi; Ho, Joseph D.

Here, L-2-Amino-4-phosphonobutyric acid (L-AP4) is a known potent and selective agonist for the Group III mGlu receptors. However, it does not show any selectivity among the individual group III mGlu subtypes. In order to understand the molecular basis for this group selectivity, we solved the first human mGlu8 amino terminal domain (ATD) crystal structures in complex with L-glu and L-AP4. In comparison with other published L-glu-bound mGlu ATD structures, we have observed L-glu binds in a significantly different manner in mGlu1. Furthermore, these new structures provided evidence that both the electronic and steric nature of the distal phosphate of L-AP4more » contribute to its exquisite Group III functional agonist potency and selectivity.« less

Ca(2+)-stores mobilization by diadenosine tetraphosphate, Ap4A, through a putative P2Y purinoceptor in adrenal chromaffin cells.

PubMed Central

Castro, E.; Pintor, J.; Miras-Portugal, M. T.

1992-01-01

1. Diadenosine tetraphosphate (Ap4A) evoked a concentration-dependent increase in cytosolic [Ca2+] in resting chromaffin cells. The EC50 value for this action was 28.2 +/- 6.6 microM. This effect was also produced by diadenosine pentaphosphate (Ap5A) with an EC50 of 50 +/- 7 microM. 2. In contrast with this effect, pretreatment with Ap4A or Ap5A induced a 30% reduction in Ca2+ entry following 10 microM dimethylphenylpiperazinium. 3. The elevation in cytosolic [Ca2+] induced by Ap4A was persistent in approximately 100 nM external [Ca2+] and was sensitive to depletion of internal Ca2+ stores by a bradykinin prepulse or whole cell depletion in Ca2+. 4. The effect of Ap4A was mimicked and desensitized by the agonist adenosine 5'-O-(2-thiodiphosphate), and blocked by the P2Y-receptor antagonist, cibachrome blue. The P2X-receptor agonist alpha,beta-methylene adenosine 5'-triphosphate was inactive both by itself or in combination with Ap4A. This is compatible with a P2Y-purinoceptor-mediated action. PMID:1393282

Ca(2+)-stores mobilization by diadenosine tetraphosphate, Ap4A, through a putative P2Y purinoceptor in adrenal chromaffin cells.

PubMed

Castro, E; Pintor, J; Miras-Portugal, M T

1992-08-01

1. Diadenosine tetraphosphate (Ap4A) evoked a concentration-dependent increase in cytosolic [Ca2+] in resting chromaffin cells. The EC50 value for this action was 28.2 +/- 6.6 microM. This effect was also produced by diadenosine pentaphosphate (Ap5A) with an EC50 of 50 +/- 7 microM. 2. In contrast with this effect, pretreatment with Ap4A or Ap5A induced a 30% reduction in Ca2+ entry following 10 microM dimethylphenylpiperazinium. 3. The elevation in cytosolic [Ca2+] induced by Ap4A was persistent in approximately 100 nM external [Ca2+] and was sensitive to depletion of internal Ca2+ stores by a bradykinin prepulse or whole cell depletion in Ca2+. 4. The effect of Ap4A was mimicked and desensitized by the agonist adenosine 5'-O-(2-thiodiphosphate), and blocked by the P2Y-receptor antagonist, cibachrome blue. The P2X-receptor agonist alpha,beta-methylene adenosine 5'-triphosphate was inactive both by itself or in combination with Ap4A. This is compatible with a P2Y-purinoceptor-mediated action.

High diadenosine tetraphosphate (Ap4A) level in germ cells and embryos of sea urchin and Xenopus and its effect on DNA synthesis.

PubMed

Weinmann-Dorsch, C; Grummt, F

1985-09-01

Ap4A levels in sperms, eggs and different developmental stages of sea urchin (Psammechinus miliaris) and (Xenopus laevis) were determined by a method based on ATP measurement with luciferin/luciferase after splitting diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A) into ATP and AMP. Appreciable storage pools of Ap4A were found in unfertilized eggs of Psammechinus and Xenopus as well as in sea urchin sperms. The actual Ap4A concentration of 28 microM in sperm represents the highest Ap4A level so far observed in eukaryotic cells. Upon fertilization an instant onset of de novo synthesis of Ap4A was demonstrated. Ap4A levels during early embryogenesis of P. miliaris and X. laevis (2.5-4 microM) are higher than those in exponentially growing mammalian culture cells and mammalian fetuses. Microinjection of Ap4A into unfertilized eggs of Psammechinus miliaris caused a 3-7 fold increase of DNA synthesis in comparison with mock-injected eggs.

Heparin (GAG-hed) inhibits LCR activity of human papillomavirus type 18 by decreasing AP1 binding.

PubMed

Villanueva, Rita; Morales-Peza, Néstor; Castelán-Sánchez, Irma; García-Villa, Enrique; Tapia, Rocio; Cid-Arregui, Angel; García-Carrancá, Alejandro; López-Bayghen, Esther; Gariglio, Patricio

2006-08-31

High risk HPVs are causative agents of anogenital cancers. Viral E6 and E7 genes are continuously expressed and are largely responsible for the oncogenic activity of these viruses. Transcription of the E6 and E7 genes is controlled by the viral Long Control Region (LCR), plus several cellular transcription factors including AP1 and the viral protein E2. Within the LCR, the binding and activity of the transcription factor AP1 represents a key regulatory event in maintaining E6/E7 gene expression and uncontrolled cell proliferation. Glycosaminoglycans (GAGs), such as heparin, can inhibit tumour growth; they have also shown antiviral effects and inhibition of AP1 transcriptional activity. The purpose of this study was to test the heparinoid GAG-hed, as a possible antiviral and antitumoral agent in an HPV18 positive HeLa cell line. Using in vivo and in vitro approaches we tested GAG-hed effects on HeLa tumour cell growth, cell proliferation and on the expression of HPV18 E6/E7 oncogenes. GAG-hed effects on AP1 binding to HPV18-LCR-DNA were tested by EMSA. We were able to record the antitumoral effect of GAG-hed in vivo by using as a model tumours induced by injection of HeLa cells into athymic female mice. The antiviral effect of GAG-hed resulted in the inhibition of LCR activity and, consequently, the inhibition of E6 and E7 transcription. A specific diminishing of cell proliferation rates was observed in HeLa but not in HPV-free colorectal adenocarcinoma cells. Treated HeLa cells did not undergo apoptosis but the percentage of cells in G2/M phase of the cell cycle was increased. We also detected that GAG-hed prevents the binding of the transcription factor AP1 to the LCR. Direct interaction of GAG-hed with the components of the AP1 complex and subsequent interference with its ability to correctly bind specific sites within the viral LCR may contribute to the inhibition of E6/E7 transcription and cell proliferation. Our data suggest that GAG-hed could have antitumoral

Integrating Particulate Representations into AP Chemistry and Introductory Chemistry Courses

ERIC Educational Resources Information Center

Prilliman, Stephen G.

2014-01-01

The College Board's recently revised curriculum for advanced placement (AP) chemistry places a strong emphasis on conceptual understanding, including representations of particle phenomena. This change in emphasis is informed by years of research showing that students could perform algorithmic calculations but not explain those calculations…

Characterization of ApB73, a virulence factor important for colonization of Zea mays by the smut Ustilago maydis

PubMed Central

Stirnberg, Alexandra

2016-01-01

Summary The biotrophic fungus Ustilago maydis, the causal agent of corn smut disease, uses numerous small secreted effector proteins to suppress plant defence responses and reshape the host metabolism. However, the role of specific effectors remains poorly understood. Here, we describe the identification of ApB73 (Apathogenic in B73), an as yet uncharacterized protein essential for the successful colonization of maize by U. maydis. We show that apB73 is transcriptionally induced during the biotrophic stages of the fungal life cycle. The deletion of the apB73 gene results in cultivar‐specific loss of gall formation in the host. The ApB73 protein is conserved among closely related smut fungi. However, using virulence assays, we show that only the orthologue of the maize‐infecting head smut Sporisorium reilianum can complement the mutant phenotype of U. maydis. Although microscopy shows that ApB73 is secreted into the biotrophic interface, it seems to remain associated with fungal cell wall components or the fungal plasma membrane. Taken together, the results show that ApB73 is a conserved and important virulence factor of U. maydis that localizes to the interface between the pathogen and its host Zea mays. PMID:27279632

bZIP transcription factor CgAP1 is essential for oxidative stress tolerance and full virulence of the poplar anthracnose fungus Colletotrichum gloeosporioides.

PubMed

Sun, Yingjiao; Wang, Yonglin; Tian, Chengming

2016-10-01

Yeast AP1 transcription factor is a regulator of oxidative stress response. Here, we report the identification and characterization of CgAP1, an ortholog of YAP1 in poplar anthracnose fungus Colletotrichum gloeosporioides. The expression of CgAP1 was highly induced by reactive oxygen species. CgAP1 deletion mutants displayed enhanced sensitivity to oxidative stress compared with the wild-type strain, and their poplar leaf virulence was obviously reduced. However, the mutants exhibited no obvious defects in aerial hyphal growth, conidia production, and appressoria formation. CgAP1::eGFP fusion protein localized to the nucleus after TBH (tert-Butyl hydroperoxide) treatment, suggesting that CgAP1 functions as a redox sensor in C. gloeosporioides. In addition, CgAP1 prevented the accumulation of ROS during early stages of biotrophic growth. CgAP1 also acted as a positive regulator of several ROS-related genes (i.e., Glr1, Hyr1, and Cyt1) involved in the antioxidative response. These results highlight the key regulatory role of CgAP1 transcription factor in oxidative stress response and provide insights into the function of ROS detoxification in virulence of C. gloeosporioides. Copyright © 2016 Elsevier Inc. All rights reserved.

Atmospheric Pressure-Thermal Desorption (AP-TD)/Electrospray Ionization-Mass Spectrometry for the Rapid Analysis of Bacillus Spores

USDA-ARS?s Scientific Manuscript database

A technique is described where an atmospheric pressure-thermal desorption (AP-TD) device and electrospray ionization (ESI)-mass spectrometry are coupled and used for the rapid analysis of Bacillus spores in complex matrices. The resulting AP-TD/ESI-MS technique combines the generation of volatile co...

Structure of the two-domain hexameric APS kinase from Thiobacillus denitrificans: structural basis for the absence of ATP sulfurylase activity

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

Gay, Sean C.; Segel, Irwin H.; Fisher, Andrew J., E-mail: fisher@chem.ucdavis.edu

2009-10-01

APS kinase from Thiobacillus denitrificans contains an inactive N-terminal ATP sulfurylase domain. The structure presented unveils the first hexameric assembly for an APS kinase, and reveals that structural changes in the N-terminal domain disrupt the ATP sulfurylase active site thus prohibiting activity. The Tbd-0210 gene of the chemolithotrophic bacterium Thiobacillus denitrificans is annotated to encode a 60.5 kDa bifunctional enzyme with ATP sulfurylase and APS kinase activity. This putative bifunctional enzyme was cloned, expressed and structurally characterized. The 2.95 Å resolution X-ray crystal structure reported here revealed a hexameric assembly with D{sub 3} symmetry. Each subunit contains a large N-terminalmore » sulfurylase-like domain and a C-terminal APS kinase domain reminiscent of the two-domain fungal ATP sulfurylases of Penicillium chrysogenum and Saccharomyces cerevisiae, which also exhibit a hexameric assembly. However, the T. denitrificans enzyme exhibits numerous structural and sequence differences in the N-terminal domain that render it inactive with respect to ATP sulfurylase activity. Surprisingly, the C-terminal domain does indeed display APS kinase activity, indicating that this gene product is a true APS kinase. Therefore, these results provide the first structural insights into a unique hexameric APS kinase that contains a nonfunctional ATP sulfurylase-like domain of unknown function.« less

AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis

PubMed Central

Delevoye, Cédric; Hurbain, Ilse; Tenza, Danièle; Sibarita, Jean-Baptiste; Uzan-Gafsou, Stéphanie; Ohno, Hiroshi; Geerts, Willie J.C.; Verkleij, Arie J.; Salamero, Jean; Marks, Michael S.

2009-01-01

Specialized cell types exploit endosomal trafficking to deliver protein cargoes to cell type–specific lysosome-related organelles (LROs), but how endosomes are specified for this function is not known. In this study, we show that the clathrin adaptor AP-1 and the kinesin motor KIF13A together create peripheral recycling endosomal subdomains in melanocytes required for cargo delivery to maturing melanosomes. In cells depleted of AP-1 or KIF13A, a subpopulation of recycling endosomes redistributes to pericentriolar clusters, resulting in sequestration of melanosomal enzymes like Tyrp1 in vacuolar endosomes and consequent inhibition of melanin synthesis and melanosome maturation. Immunocytochemistry, live cell imaging, and electron tomography reveal AP-1– and KIF13A-dependent dynamic close appositions and continuities between peripheral endosomal tubules and melanosomes. Our results reveal that LRO protein sorting is coupled to cell type–specific positioning of endosomes that facilitate endosome–LRO contacts and are required for organelle maturation. PMID:19841138

Low concentrations of copper in drinking water increase AP-1 binding in the brain.

PubMed

Lung, Shyang; Li, Huihui; Bondy, Stephen C; Campbell, Arezoo

2015-12-01

Copper (Cu) in trace amounts is essential for biological organisms. However, dysregulation of the redox-active metal has been implicated in different neurological disorders such as Wilson's, Menkes', Alzheimer's, and Parkinson's diseases. Since many households use Cu tubing in the plumbing system, and corrosion causes the metal to leach into the drinking water, there may be adverse effects on the central nervous system connected with low-level chronic exposure. The present study demonstrates that treatment with a biologically relevant concentration of Cu for 3 months significantly increases activation of the redox-modulated transcription factor AP-1 in mouse brains. This was independent of an upstream kinase indicated in AP-1 activation. Another redox-active transcription factor, NF-κB, was not significantly modified by the Cu exposure. These results indicate that the effect of Cu on AP-1 is unique and may involve direct modulation of DNA binding. © The Author(s) 2012.

Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis.

PubMed

Guo, Rey-Ting; Chong, Yeeting E; Guo, Min; Yang, Xiang-Lei

2009-10-16

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs for protein synthesis. However, the aminoacylation reaction can be diverted to produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways. The only known mechanism for Ap4A production by a tRNA synthetase is through the aminoacylation reaction intermediate aminoacyl-AMP, thus making Ap4A synthesis amino acid-dependent. Here, we demonstrate a new mechanism for Ap4A synthesis. Crystal structures and biochemical analyses show that human glycyl-tRNA synthetase (GlyRS) produces Ap4A by direct condensation of two ATPs, independent of glycine concentration. Interestingly, whereas the first ATP-binding pocket is conserved for all class II tRNA synthetases, the second ATP pocket is formed by an insertion domain that is unique to GlyRS, suggesting that GlyRS is the only tRNA synthetase catalyzing direct Ap4A synthesis. A special role for GlyRS in Ap4A homeostasis is proposed.

Crystal Structures and Biochemical Analyses Suggest a Unique Mechanism and Role for Human Glycyl-tRNA Synthetase in Ap4A Homeostasis*

PubMed Central

Guo, Rey-Ting; Chong, Yeeting E.; Guo, Min; Yang, Xiang-Lei

2009-01-01

Aminoacyl-tRNA synthetases catalyze the attachment of amino acids to their cognate tRNAs for protein synthesis. However, the aminoacylation reaction can be diverted to produce diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways. The only known mechanism for Ap4A production by a tRNA synthetase is through the aminoacylation reaction intermediate aminoacyl-AMP, thus making Ap4A synthesis amino acid-dependent. Here, we demonstrate a new mechanism for Ap4A synthesis. Crystal structures and biochemical analyses show that human glycyl-tRNA synthetase (GlyRS) produces Ap4A by direct condensation of two ATPs, independent of glycine concentration. Interestingly, whereas the first ATP-binding pocket is conserved for all class II tRNA synthetases, the second ATP pocket is formed by an insertion domain that is unique to GlyRS, suggesting that GlyRS is the only tRNA synthetase catalyzing direct Ap4A synthesis. A special role for GlyRS in Ap4A homeostasis is proposed. PMID:19710017

Free factor XIII activation peptide (fAP-FXIII) is a regulator of factor XIII activity via factor XIII-B.

PubMed

Dodt, Johannes; Pasternack, Ralf; Seitz, Rainer; Volkers, Peter

2016-02-01

In a factor XIIIa (FXIIIa) generation assay with recombinant FXIII-A2 (rFXIII-A2 ) free FXIII activation peptide (fAP-FXII) prolonged the time to peak (TTP) but did not affect the area under the curve (AUC) or concentration at peak (CP). Addition of recombinant factorXIII-B2 (rFXIII-B2 ) restored the characteristics of the FXIIIa generation parameters (AUC, TTP and CP) to those observed for plasma FXIII (FXIII-A2 B2 ). FXIII-A2 B2 reconstituted from rFXIII-A2 and rFXIII-B2 showed a similar effect on AUC, TTP and CP in the presence of fAP-FXII as observed for plasma FXIII-A2 B2 , indicating a role for FXIII-B in this observation. An effect of fAP-FXIII on thrombin, the proteolytic activator of FXIII, was excluded by thrombin generation assays and clotting experiments. In a purified system, fAP-FXIII did not interfere with the FXIIIa activity development of thrombin-cleaved rFXIII-A2 (rFXIII-A2 ') also excluding direct inhibition of FXIIIa. However, FXIIIa activity development of FXIII-A2 'B2 was inhibited in a concentration-dependent manner by fAP-FXIII, indicating that an interaction between AP-FXIII and FXIII-B2 contributes to the overall stability of FXIII-A2 'B2 . In addition to its well-known role, FXIII-B also contributes to FXIII-A2 B2 stability or dissociation depending on fAP-FXIII and calcium concentrations. © 2015 John Wiley & Sons Ltd.

AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function.

PubMed

Hayashi, Hisamitsu; Inamura, Kaori; Aida, Kensuke; Naoi, Sotaro; Horikawa, Reiko; Nagasaka, Hironori; Takatani, Tomozumi; Fukushima, Tamio; Hattori, Asami; Yabuki, Takashi; Horii, Ikuo; Sugiyama, Yuichi

2012-06-01

The bile salt export pump (BSEP) mediates the biliary excretion of bile salts and its dysfunction induces intrahepatic cholestasis. Reduced canalicular expression of BSEP resulting from the promotion of its internalization is one of the causes of this disease state. However, the molecular mechanism underlying BSEP internalization from the canalicular membrane (CM) remains unknown. We have shown previously that 4-phenylbutyrate (4PBA), a drug used for ornithine transcarbamylase deficiency (OTCD), inhibited internalization and subsequent degradation of cell-surface-resident BSEP. The current study found that 4PBA treatment decreased significantly the expression of α- and μ2-adaptin, both of which are subunits of the AP2 adaptor complex (AP2) that mediates clathrin-dependent endocytosis, in liver specimens from rats and patients with OTCD, and that BSEP has potential AP2 recognition motifs in its cytosolic region. Based on this, the role of AP2 in BSEP internalization was explored further. In vitro analysis with 3×FLAG-human BSEP-expressing HeLa cells and human sandwich-culture hepatocytes indicates that the impairment of AP2 function by RNA interference targeting of α-adaptin inhibits BSEP internalization from the plasma membrane and increases its cell-surface expression and transport function. Studies using immunostaining, coimmunoprecipitation, glutathione S-transferase pulldown assay, and time-lapse imaging show that AP2 interacts with BSEP at the CM through a tyrosine motif at the carboxyl terminus of BSEP and mediates BSEP internalization from the CM of hepatocytes. AP2 mediates the internalization and subsequent degradation of CM-resident BSEP through direct interaction with BSEP and thereby modulates the canalicular expression and transport function of BSEP. This information should be useful for understanding the pathogenesis of severe liver diseases associated with intrahepatic cholestasis. Copyright © 2012 American Association for the Study of Liver

Lipopolysaccharide potentiates the effect of hepatocyte growth factor on hepatocyte replication in rats by augmenting AP-1 activity.

PubMed

Gao, C; Jokerst, R; Gondipalli, P; Cai, S R; Kennedy, S; Flye, M W; Ponder, K P

1999-12-01

The liver regenerates by replication of differentiated hepatocytes after damage or removal of part of the liver. Although several growth factors and signaling pathways are activated during regeneration, it is unclear as to which of these are essential for hepatocyte replication. We show here that low- (1 mg/kg) and high- (10 mg/kg) dose hepatocyte growth factor (HGF) induced replication of 2.1% and 11.1% of hepatocytes in rats, respectively. Lipopolysaccharide (LPS), an inducer of the acute phase response, augmented hepatocyte replication in response to low- and high-dose HGF by 4- and 2-fold, respectively. HGF alone induced moderate levels of c-Jun-N-terminal kinase (JNK) and p44/p42 mitogen-activated protein kinase (MAPK), resulting in moderate levels of AP-1-DNA binding activity. The combination of LPS + HGF increased JNK and AP-1-DNA binding activity more than levels seen with LPS or HGF alone. The activation of Stat3 that was observed after administration of LPS + HGF, but not HGF alone, could contribute to increased transcription of AP-1 components. Because phosphorylation of the c-Jun component of AP-1 by JNK increases its ability to activate transcription, the AP-1 in hepatocytes from animals treated with LPS + HGF may be more active than in rats treated with LPS or HGF alone. LPS may contribute to hepatocyte replication by potentiating the effect of HGF on the activation of both AP-1-DNA binding and transcriptional activity.

Renal haemodynamics and natriuretic responses to intravenous administration of diadenosine tetraphosphate (Ap4A) and nicotinamide adenine dinucleotide (NAD) in rat.

PubMed

Szczepańska-Konkel, M; Langner, G; Bednarczuk, G; Stiepanow-Trzeciak, A; Jankowski, M; Angielski, S

2003-06-01

Effects of Ap4A and NAD--precursor of adenosine, on renal plasma flow (RPF), glomerular filtration rate (GFR) and urine excretion were determined in the anaesthetised rats. Infusion of Ap4A or NAD (i.v., bolus--1 micromol/kg followed by 10 nmol/min/kg) decreased RPF and GFR (by 30 and 40%, respectively). In spite of GFR reduction during Ap4A infusion, the significant increase in sodium excretion and urine flow was noticed: fractional sodium (FENa) and urine excretion (FEurine) rose 15-fold and 2.5-fold in comparison with the control value, respectively. In contrast to Ap4A, NAD-induced decrease in GFR was associated with parallel decrease in sodium and urine excretion, thus the FENa and FEurine did not significantly change. Pretreatment with adenosine deaminase (adenosine degrading enzyme, 2 U/min/kg) or theophylline (P1-receptors antagonist, 0.2 mmol/min/kg) ceased responses to NAD, whereas Ap4A-induced changes were not affected. Pre-treatment with suramin (P2-receptors antagonist, (i.v., bolus--12 mg/kg followed by 1.2 mg/min/kg) completely abolished the renal effects of Ap4A. We conclude that Ap4A may exert specific action on renal function. It acts different from NAD that modified renal function through its hydrolysis product--adenosine. Ap4A might reduce glomerular filtration rate and evoke natriuresis and diuresis, and its effects are probably mediated through stimulation of P2-receptors.

Cardioprotective effect of diadenosine tetraphosphate (AP4A) preservation in hypothermic storage and its relation with mitochondrial ATP-sensitive potassium channels.

PubMed

Ahmet, I; Sawa, Y; Nishimura, M; Kitakaze, M; Matsuda, H

2000-01-15

The preconditioning effect of diadenosine tetraphosphate (AP4A) was reported in ischemia/reperfused hearts, but its effect in heart preservation was unknown. According to the possible role of mitochondrial ATP-sensitive potassium channel (mK(ATP) channel) in the effect of ischemic preconditioning, the contribution of mK(ATP) channel to the effect of AP4A was tested. Isolated rat hearts were arrested and preserved by Eurocollin's (EC) solution at 4 degrees C for 8 hr. AP4A (80 microM) or AP4A with the 5-hydroxydecanoic acid (100 microM), a selective inhibitor of the mK(ATP) channel, was added into the EC solution. The preischemic and postischemic cardiac functions were evaluated on a buffer-perfused Langendorff apparatus before storage and after 20 min of reperfusion. AP4A administration improved the recovery of poststorage cardiac functions (the rate-pressure production, left ventricular systolic pressure, heart rate, coronary flow rate, and derivative of left ventricular systolic pressure; P<0.05) and reduced the leakage of lactate dehydrate and creatine kinase during reperfusion, compared with EC alone. Those effects of AP4A were completely reversed by 5-hydroxydecanoic acid administration in combination subjects. AP4A administration protects the heart through opening of the mK(ATP) channel during hypothermic preservation. Thus, addition of AP4A into cardioplegia may be a novel method of ischemic preconditioning in the transplantation context.

Thioredoxin reductase regulates AP-1 activity as well as thioredoxin nuclear localization via active cysteines in response to ionizing radiation.

PubMed

Karimpour, Shervin; Lou, Junyang; Lin, Lilie L; Rene, Luis M; Lagunas, Lucio; Ma, Xinrong; Karra, Sreenivasu; Bradbury, C Matthew; Markovina, Stephanie; Goswami, Prabhat C; Spitz, Douglas R; Hirota, Kiichi; Kalvakolanu, Dhananjaya V; Yodoi, Junji; Gius, David

2002-09-12

A recently identified class of signaling factors uses critical cysteine motif(s) that act as redox-sensitive 'sulfhydryl switches' to reversibly modulate specific signal transduction cascades regulating downstream proteins with similar redox-sensitive sites. For example, signaling factors such as redox factor-1 (Ref-1) and transcription factors such as the AP-1 complex both contain redox-sensitive cysteine motifs that regulate activity in response to oxidative stress. The mammalian thioredoxin reductase-1 (TR) is an oxidoreductase selenocysteine-containing flavoprotein that also appears to regulate multiple downstream intracellular redox-sensitive proteins. Since ionizing radiation (IR) induces oxidative stress as well as increases AP-1 DNA-binding activity via the activation of Ref-1, the potential roles of TR and thioredoxin (TRX) in the regulation of AP-1 activity in response to IR were investigated. Permanently transfected cell lines that overexpress wild type TR demonstrated constitutive increases in AP-1 DNA-binding activity as well as AP-1-dependent reporter gene expression, relative to vector control cells. In contrast, permanently transfected cell lines expressing a TR gene with the active site cysteine motif deleted were unable to induce AP-1 activity or reporter gene expression in response to IR. Transient genetic overexpression of either the TR wild type or dominant-negative genes demonstrated similar results using a transient assay system. One mechanism through which TR regulates AP-1 activity appears to involve TRX sub-cellular localization, with no change in the total TRX content of the cell. These results identify a novel function of the TR enzyme as a signaling factor in the regulation of AP-1 activity via a cysteine motif located in the protein.

Association between Rare Variants in AP4E1, a Component of Intracellular Trafficking, and Persistent Stuttering.

PubMed

Raza, M Hashim; Mattera, Rafael; Morell, Robert; Sainz, Eduardo; Rahn, Rachel; Gutierrez, Joanne; Paris, Emily; Root, Jessica; Solomon, Beth; Brewer, Carmen; Basra, M Asim Raza; Khan, Shaheen; Riazuddin, Sheikh; Braun, Allen; Bonifacino, Juan S; Drayna, Dennis

2015-11-05

Stuttering is a common, highly heritable neurodevelopmental disorder characterized by deficits in the volitional control of speech. Whole-exome sequencing identified two heterozygous AP4E1 coding variants, c.1549G>A (p.Val517Ile) and c.2401G>A (p.Glu801Lys), that co-segregate with persistent developmental stuttering in a large Cameroonian family, and we observed the same two variants in unrelated Cameroonians with persistent stuttering. We found 23 other rare variants, including predicted loss-of-function variants, in AP4E1 in unrelated stuttering individuals in Cameroon, Pakistan, and North America. The rate of rare variants in AP4E1 was significantly higher in unrelated Pakistani and Cameroonian stuttering individuals than in population-matched control individuals, and coding variants in this gene are exceptionally rare in the general sub-Saharan West African, South Asian, and North American populations. Clinical examination of the Cameroonian family members failed to identify any symptoms previously reported in rare individuals carrying homozygous loss-of-function mutations in this gene. AP4E1 encodes the ε subunit of the heterotetrameric (ε-β4-μ4-σ4) AP-4 complex, involved in protein sorting at the trans-Golgi network. We found that the μ4 subunit of AP-4 interacts with NAGPA, an enzyme involved in the synthesis of the mannose 6-phosphate signal that targets acid hydrolases to the lysosome and the product of a gene previously associated with stuttering. These findings implicate deficits in intracellular trafficking in persistent stuttering. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

FIRST BEAM TESTS OF THE APS MBA UPGRADE ORBIT FEEDBACK CONTROLLER

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

Sereno, N. S.; Arnold, N.; Brill, A.

The new orbit feedback system required for the APS multi-bend acromat (MBA) ring must meet challenging beam stability requirements. The AC stability requirement is to correct rms beam motion to 10 % the rms beam size at the insertion device source points from 0.01 to 1000 Hz. The vertical plane represents the biggest challenge for AC stability which is required to be 400 nm rms for a 4 micron vertical beam size. In addition long term drift over a period of 7 days is required to be 1 micron or less at insertion de- vice BPMs and 2 microns formore » arc bpms. We present test re- sults of theMBA prototype orbit feedback controller (FBC) in the APS storage ring. In this test, four insertion device BPMs were configured to send data to the FBC for process- ing into four fast corrector setpoints. The configuration of four bpms and four fast correctors creates a 4-bump and the configuration of fast correctors is similar to what will be implemented in the MBA ring. We report on performance benefits of increasing the sampling rate by a factor of 15 to 22.6 kHz over the existing APS orbit feedback system, lim- itations due to existing storage ring hardware and extrapo- lation to theMBA orbit feedback design. FBC architecture, signal flow and processing design will also be discussed.« less

Multiplicity among chemically peculiar stars. II. Cool magnetic Ap stars

NASA Astrophysics Data System (ADS)

Carrier, F.; North, P.; Udry, S.; Babel, J.

2002-10-01

We present new orbits for sixteen Ap spectroscopic binaries, four of which might in fact be Am stars, and give their orbital elements. Four of them are SB2 systems: HD 5550, HD 22128, HD 56495 and HD 98088. The twelve other stars are: HD 9996, HD 12288, HD 40711, HD 54908, HD 65339, HD 73709, HD 105680, HD 138426, HD 184471, HD 188854, HD 200405 and HD 216533. Rough estimates of the individual masses of the components of HD 65339 (53 Cam) are given, combining our radial velocities with the results of speckle interferometry and with Hipparcos parallaxes. Considering the mass functions of 74 spectroscopic binaries from this work and from the literature, we conclude that the distribution of the mass ratio is the same for cool Ap stars and for normal G dwarfs. Therefore, the only differences between binaries with normal stars and those hosting an Ap star lie in the period distribution: except for the case of HD 200405, all orbital periods are longer than (or equal to) 3 days. A consequence of this peculiar distribution is a deficit of null eccentricities. There is no indication that the secondary has a special nature, like e.g. a white dwarf. Based on observations collected at the Observatoire de Haute-Provence (CNRS), France. Tables 1 to 3 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/394/151 Appendix B is only available in electronic form at http://www.edpsciences.org

Growth, optical, ICP and thermal studies of nonlinear optical single crystal: Sodium acid phthalate (NaAP)

NASA Astrophysics Data System (ADS)

Mahadevan, M.; Arivanandhan, M.; Elangovan, K.; Anandan, P.; Ramachandran, K.

2017-07-01

Good quality single crystals of sodium acid phthalate (NaAP) were grown by slow evaporation technique. Single crystal X-ray diffraction study of the grown crystal reveals that the crystal belongs to orthorhombic system with space group B2ab. Fourier transform infrared spectrum confirms the presence of the functional groups of the grown material. Inductively coupled plasma emission spectroscopy analysis is used to confirm the presence of Na element in the sample. Thermal analysis of the NaAP crystal shows that the crystal is stable up to 140°C. Optical transmittance of the grown crystal was recorded in the wavelength range from 200 and 800 nm using UV-Vis-NIR spectrophotometer. The second harmonic generation of NaAP was analysed using Kurtz powder technique.

Validation of the new trapped environment AE9/AP9/SPM at low Earth orbit

NASA Astrophysics Data System (ADS)

Badavi, Francis F.

2014-09-01

The completion of the international space station (ISS) in 2011 has provided the space research community an ideal proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the validation of radiation environmental models, nuclear transport codes and nuclear reaction cross sections. Indeed, prior measurements on the space transportation system (STS; shuttle) provided vital information impacting both the environmental models and the nuclear transport code developments by indicating the need for an improved dynamic model of the low Earth orbit (LEO) trapped environment. Additional studies using thermo-luminescent detector (TLD), tissue equivalent proportional counter (TEPC) area monitors, and computer aided design (CAD) model of earlier ISS configurations, confirmed STS observations that, as input, computational dosimetry requires an environmental model with dynamic and directional (anisotropic) behavior, as well as an accurate six degree of freedom (DOF) definition of the vehicle attitude and orientation along the orbit of ISS. At LEO, a vehicle encounters exposure from trapped particles and attenuated galactic cosmic rays (GCR). Within the trapped field, a challenge arises from properly estimating the amount of exposure acquired. There exist a number of models to define the intensities of the trapped particles during the solar quiet and active times. At active times, solar energetic particles (SEP) generated by solar flare or coronal mass ejection (CME) also contribute to the exposure at high northern and southern latitudes. Among the more established trapped models are the historic and popular AE8/AP8, dating back to the 1980s, the historic and less popular CRRES electron/proton, dating back to 1990s and the recently released AE9/AP9/SPM. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four

La implantacion del enfoque constructivista en el aula de ciencia: Estudio de caso multiple

NASA Astrophysics Data System (ADS)

Arroyo Betancourt, Luz I.

Esta investigacion estudia la implantacion del enfoque constructivista en tres aulas de ciencia del contexto puertorriqueno. Se auscultaron las practicas educativas que utilizan maestras consideradas constructivistas y la correspondencia de sus practicas educativas con los elementos esenciales de la didactica que proponen los teoricos de los planteamientos constructivistas. Se ausculto, ademas, a que vision del enfoque constructivista responden las expresiones de las maestras acerca de su practica educativa y como compara con su quehacer, a la luz de los elementos esenciales de las visiones constructivistas piagetiana, social y radical. Se utilizo el diseno de estudio descriptivo de caso multiple. El estudio se baso en entrevistas a profundidad, revision de documentos y observacion no participativa a la sala de clases. El contexto fueron tres escuelas publicas de la Region Educativa de San Juan, una elemental, una intermedia y una superior. Los resultados confirmaron que la transicion hacia el enfoque constructivista es un proceso que toma tiempo, dedicacion y la participacion en adiestramientos y readiestramientos acerca del nuevo enfoque. Las maestras coinciden en la mayoria de las practicas educativas que utilizan para implantar el enfoque constructivista de ensenanza y difieren en algunas debido, probablemente, a que han tenido que adaptarlas a los correspondientes niveles de ensenanza: elemental, intermedio y superior. Dos de las maestras planifican por conceptos generadores, mientras que una de ellas planifica siguiendo la guia que recibe del Departamento de Educacion. Difieren ademas, en el enfasis que confieren al inquirir cientifico. Con relacion a la correspondencia entre la vision manifestada por las maestras a la luz de las visiones piagetiana, social y radical, aparentemente, las preguntas del protocolo de entrevistas no lograron evocar la informacion con suficiente profundidad, por lo que la investigadora tuvo que inferir las visiones de las

75 FR 20398 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on AP1000...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-19

... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on AP1000; Notice of Meeting The ACRS Subcommittee on the AP1000 will hold a meeting on April 22... Loss of Large Areas due to Fire/Explosions, and by Westinghouse on the subject of Shield Building...

Genome-Wide Identification of AP2/ERF Transcription Factors in Cauliflower and Expression Profiling of the ERF Family under Salt and Drought Stresses

PubMed Central

Li, Hui; Wang, Yu; Wu, Mei; Li, Lihong; Li, Cong; Han, Zhanpin; Yuan, Jiye; Chen, Chengbin; Song, Wenqin; Wang, Chunguo

2017-01-01

The AP2/ERF transcription factors (TFs) comprise one of the largest gene superfamilies in plants. These TFs perform vital roles in plant growth, development, and responses to biotic and abiotic stresses. In this study, 171 AP2/ERF TFs were identified in cauliflower (Brassica oleracea L. var. botrytis), one of the most important horticultural crops in Brassica. Among these TFs, 15, 9, and 1 TFs were classified into the AP2, RAV, and Soloist family, respectively. The other 146 TFs belong to ERF family, which were further divided into the ERF and DREB subfamilies. The ERF subfamily contained 91 TFs, while the DREB subfamily contained 55 TFs. Phylogenetic analysis results indicated that the AP2/ERF TFs can be classified into 13 groups, in which 25 conserved motifs were confirmed. Some motifs were group- or subgroup- specific, implying that they are significant to the functions of the AP2/ERF TFs of these clades. In addition, 35 AP2/ERF TFs from the 13 groups were selected randomly and then used for expression pattern analysis under salt and drought stresses. The majority of these AP2/ERF TFs exhibited positive responses to these stress conditions. In specific, Bra-botrytis-ERF054a, Bra-botrytis-ERF056, and Bra-botrytis-CRF2a demonstrated rapid responses. By contrast, six AP2/ERF TFs were showed to delay responses to both stresses. The AP2/ERF TFs exhibiting specific expression patterns under salt or drought stresses were also confirmed. Further functional analysis indicated that ectopic overexpression of Bra-botrytis-ERF056 could increase tolerance to both salt and drought treatments. These findings provide new insights into the AP2/ERF TFs present in cauliflower, and offer candidate AP2/ERF TFs for further studies on their roles in salt and drought stress tolerance. PMID:28642765

TAK1 regulates NF-{Kappa}B and AP-1 activation in airway epithelial cells following RSV infection

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

Dey, Nilay; Liu Tianshuang; Garofalo, Roberto P.

2011-09-30

Respiratory syncytial virus (RSV) is the most common cause of epidemic respiratory diseases in infants and young children. RSV infection of airway epithelial cells induces the expression of immune/inflammatory genes through the activation of a subset of transcription factors, including Nuclear Factor-{kappa}B (NF-{kappa}B) and AP-1. In this study, we have investigated the signaling pathway leading to activation of these two transcription factors in response to RSV infection. Our results show that IKK{beta} plays a key role in viral-induced NF-{kappa}B activation, while JNK regulates AP-1-dependent gene transcription, as demonstrated by using kinase inactive proteins and chemical inhibitors of the two kinases.more » Inhibition of TAK1 activation, by overexpression of kinase inactive TAK1 or using cells lacking TAK1 expression, significantly reduced RSV-induced NF-{kappa}B and AP-1 nuclear translocation and DNA-binding activity, as well as NF-{kappa}B-dependent gene expression, identifying TAK1 as an important upstream signaling molecule regulating RSV-induced NF-{kappa}B and AP-1 activation. - Highlights: > IKK{beta} is a major kinase involved in RSV-induced NF-{kappa}B activation. > JNK regulates AP-1-dependent gene transcription in RSV infection. > TAK1 is a critical upstream signaling molecule for both pathways in infected cells.« less

Control of E-cadherin apical localisation and morphogenesis by a SOAP-1/AP-1/clathrin pathway in C. elegans epidermal cells.

PubMed

Gillard, Ghislain; Shafaq-Zadah, Massiullah; Nicolle, Ophélie; Damaj, Raghida; Pécréaux, Jacques; Michaux, Grégoire

2015-05-01

E-cadherin (E-cad) is the main component of epithelial junctions in multicellular organisms, where it is essential for cell-cell adhesion. The localisation of E-cad is often strongly polarised in the apico-basal axis. However, the mechanisms required for its polarised distribution are still largely unknown. We performed a systematic RNAi screen in vivo to identify genes required for the strict E-cad apical localisation in C. elegans epithelial epidermal cells. We found that the loss of clathrin, its adaptor AP-1 and the AP-1 interactor SOAP-1 induced a basolateral localisation of E-cad without affecting the apico-basal diffusion barrier. We further found that SOAP-1 controls AP-1 localisation, and that AP-1 is required for clathrin recruitment. Finally, we also show that AP-1 controls E-cad apical delivery and actin organisation during embryonic elongation, the final morphogenetic step of embryogenesis. We therefore propose that a molecular pathway, containing SOAP-1, AP-1 and clathrin, controls the apical delivery of E-cad and morphogenesis. © 2015. Published by The Company of Biologists Ltd.

Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP 3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy

DOE PAGES

Zhu, Xiaojie; Zhu, Yun; Ye, Sheng; ...

2015-08-19

Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP 3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neithermore » recognized AP 3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP 3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP 3 form a hook-like structure to stabilize interaction between AP 3 and NHR helices. Therefore, AP 3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.« less

Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP 3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy

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

Zhu, Xiaojie; Zhu, Yun; Ye, Sheng

Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP 3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neithermore » recognized AP 3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP 3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP 3 form a hook-like structure to stabilize interaction between AP 3 and NHR helices. Therefore, AP 3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.« less

Characterization of ApB73, a virulence factor important for colonization of Zea mays by the smut Ustilago maydis.

PubMed

Stirnberg, Alexandra; Djamei, Armin

2016-12-01

The biotrophic fungus Ustilago maydis, the causal agent of corn smut disease, uses numerous small secreted effector proteins to suppress plant defence responses and reshape the host metabolism. However, the role of specific effectors remains poorly understood. Here, we describe the identification of ApB73 (Apathogenic in B73), an as yet uncharacterized protein essential for the successful colonization of maize by U. maydis. We show that apB73 is transcriptionally induced during the biotrophic stages of the fungal life cycle. The deletion of the apB73 gene results in cultivar-specific loss of gall formation in the host. The ApB73 protein is conserved among closely related smut fungi. However, using virulence assays, we show that only the orthologue of the maize-infecting head smut Sporisorium reilianum can complement the mutant phenotype of U. maydis. Although microscopy shows that ApB73 is secreted into the biotrophic interface, it seems to remain associated with fungal cell wall components or the fungal plasma membrane. Taken together, the results show that ApB73 is a conserved and important virulence factor of U. maydis that localizes to the interface between the pathogen and its host Zea mays. © 2016 THE AUTHORS. MOLECULAR PLANT PATHOLOGY PUBLISHED BY BRITISH SOCIETY FOR PLANT PATHOLOGY AND JOHN WILEY & SONS LTD.

The state of Health in All policies (HiAP) in the European Union: potential and pitfalls.

PubMed

Koivusalo, Meri

2010-06-01

Health in All Policies (HiAP) was formally legitimated as a European Union (EU) approach in 2006. It resulted from more long-term efforts to enhance action on considering health and health policy implications of other policies, as well as recognition that European-level policies affect health systems and scope for health-related regulation at national level. However, implementation of HiAP has remained a challenge. European-level efforts to use health impact assessment to benefit public health and health systems have not become strengthened by the new procedures. And, as a result of the Lisbon Treaty, European-level policy-making is expected to become more important in shaping national policies. HiAP has at European level remained mostly as rhetoric, but legitimate health arguments and provides policy space for health articulation within EU policy-making. HiAP is a broader approach than health impact assessment and at European level requires consideration of mechanisms that recognise the nature of European policy-making, as well as extending from administrative tools to increased transparency, accountability and scope for health and health policy-related arguments within political decision-making in the EU.

Importin Beta Plays an Essential Role in the Regulation of the LysRS-Ap4A Pathway in Immunologically Activated Mast Cells ▿

PubMed Central

Carmi-Levy, Irit; Motzik, Alex; Ofir-Birin, Yifat; Yagil, Zohar; Yang, Christopher Maolin; Kemeny, David Michael; Han, Jung Min; Kim, Sunghoon; Kay, Gillian; Nechushtan, Hovav; Suzuki, Ryo; Rivera, Juan; Razin, Ehud

2011-01-01

We recently reported that diadenosine tetraphosphate hydrolase (Ap4A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap4A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap4A biochemical pathway that is triggered upon immunological challenge. Here we explored the mechanism of this enzyme's translocation into the nucleus and found its immunologically dependent association with importin beta. Silencing of importin beta prevented Ap4A hydrolase nuclear translocation and affected the local concentration of Ap4A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap4A hydrolase, which changed the hydrolytic activity of the enzyme. PMID:21402779

Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease

PubMed Central

Nakagawa, Naoki; Gomez, Ivan G.; Johnson, Bryce G.; Kameoka, Sei; Jack, Richard M.; Lupher, Mark L.; Gharib, Sina A.; Duffield, Jeremy S.

2016-01-01

Pentraxin-2 (PTX-2), also known as serum amyloid P component (SAP/APCS), is a constitutive, antiinflammatory, innate immune plasma protein whose circulating level is decreased in chronic human fibrotic diseases. Here we show that recombinant human PTX-2 (rhPTX-2) retards progression of chronic kidney disease in Col4a3 mutant mice with Alport syndrome, reducing blood markers of kidney failure, enhancing lifespan by 20%, and improving histological signs of disease. Exogenously delivered rhPTX-2 was detected in macrophages but also in tubular epithelial cells, where it counteracted macrophage activation and was cytoprotective for the epithelium. Computational analysis of genes regulated by rhPTX-2 identified the transcriptional regulator c-Jun along with its activator protein–1 (AP-1) binding partners as a central target for the function of rhPTX-2. Accordingly, PTX-2 attenuates c-Jun and AP-1 activity, and reduces expression of AP-1–dependent inflammatory genes in both monocytes and epithelium. Our studies therefore identify rhPTX-2 as a potential therapy for chronic fibrotic disease of the kidney and an important inhibitor of pathological c-Jun signaling in this setting. PMID:27942582

77 FR 74696 - Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on AP-1000...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

... NUCLEAR REGULATORY COMMISSION Advisory Committee on Reactor Safeguards (ACRS); Meeting of the ACRS Subcommittee on AP-1000; Notice of Meeting The ACRS Subcommittee on AP-1000 will hold a meeting on January 18, 2013, Room T-2B1, 11545 Rockville Pike, Rockville, Maryland. The entire meeting will be open to public...

The Advanced Placement Program Benefits Mainly Well-Prepared Students Who Pass AP Exams. Issues in College Readiness

ERIC Educational Resources Information Center

National Center for Educational Achievement, 2010

2010-01-01

Many policymakers and education leaders have embraced the Advanced Placement (AP) Program as a tool to strengthen the high school curriculum and prepare students for college. The popularity of the AP program among these policy leaders reflects their belief that the traditional high school curriculum has often failed to provide rigorous courses…

Reinforce: An Ensemble Approach for Inferring PPI Network from AP-MS Data.

PubMed

Tian, Bo; Duan, Qiong; Zhao, Can; Teng, Ben; He, Zengyou

2017-05-17

Affinity Purification-Mass Spectrometry (AP-MS) is one of the most important technologies for constructing protein-protein interaction (PPI) networks. In this paper, we propose an ensemble method, Reinforce, for inferring PPI network from AP-MS data set. The new algorithm named Reinforce is based on rank aggregation and false discovery rate control. Under the null hypothesis that the interaction scores from different scoring methods are randomly generated, Reinforce follows three steps to integrate multiple ranking results from different algorithms or different data sets. The experimental results show that Reinforce can get more stable and accurate inference results than existing algorithms. The source codes of Reinforce and data sets used in the experiments are available at: https://sourceforge.net/projects/reinforce/.

Sugary Kefir Strain Lactobacillus mali APS1 Ameliorated Hepatic Steatosis by Regulation of SIRT-1/Nrf-2 and Gut Microbiota in Rats.

PubMed

Chen, Yung-Tsung; Lin, Yu-Chun; Lin, Jin-Seng; Yang, Ning-Sun; Chen, Ming-Ju

2018-04-01

Non-alcoholic fatty liver disease (NAFLD) is a common disease that is concomitant with obesity, resulting in increased mortality. To date, the efficiency of NAFLD treatment still needs to be improved. Therefore, we aimed to evaluate the effect of Lactobacillus mali APS1, which was isolated from sugary kefir, on hepatic steatosis in rats fed a high-fat diet (HFD). Sprague Dawley rats were fed a control diet, a HFD with saline, and a HFD with APS1 intervention by gavage daily for 12 weeks. The results showed that APS1 significantly reduced body weight and body weight gain in HFD-fed rats. APS1 reduced hepatic lipid accumulation by regulating SIRT-1/PGC-1α/SREBP-1 expression. Moreover, APS1 increased hepatic antioxidant activity by modulating Nrf-2/HO-1 expression. Notably, APS1 manipulated the gut microbiota, resulting in increasing proportions of the phylum Bacteroidetes/Firmicutes and reducing the abundance of specific NAFLD-associated bacteria. These results suggested that APS1 ameliorated hepatic steatosis by modulating lipid metabolism and antioxidant activity via manipulating specific NAFLD-associated gut microbiota in vivo. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Incidence and Genetic Diversity of Apple Mosaic Virus (ApMV) and Prune Dwarf Virus (PDV) in Prunus Species in Australia

PubMed Central

Constable, Fiona E.; Nancarrow, Narelle; Rodoni, Brendan

2018-01-01

Apple mosaic virus (ApMV) and prune dwarf virus (PDV) are amongst the most common viruses infecting Prunus species worldwide but their incidence and genetic diversity in Australia is not known. In a survey of 127 Prunus tree samples collected from five states in Australia, ApMV and PDV occurred in 4 (3%) and 13 (10%) of the trees respectively. High-throughput sequencing (HTS) of amplicons from partial conserved regions of RNA1, RNA2, and RNA3, encoding the methyltransferase (MT), RNA-dependent RNA polymerase (RdRp), and the coat protein (CP) genes respectively, of ApMV and PDV was used to determine the genetic diversity of the Australian isolates of each virus. Phylogenetic comparison of Australian ApMV and PDV amplicon HTS variants and full length genomes of both viruses with isolates occurring in other countries identified genetic strains of each virus occurring in Australia. A single Australian Prunus infecting ApMV genetic strain was identified as all ApMV isolates sequence variants formed a single phylogenetic group in each of RNA1, RNA2, and RNA3. Two Australian PDV genetic strains were identified based on the combination of observed phylogenetic groups in each of RNA1, RNA2, and RNA3 and one Prunus tree had both strains. The accuracy of amplicon sequence variants phylogenetic analysis based on segments of each virus RNA were confirmed by phylogenetic analysis of full length genome sequences of Australian ApMV and PDV isolates and all published ApMV and PDV genomes from other countries. PMID:29562672

Baculovirus p35 gene is oppositely regulated by P53 and AP-1 like factors in Spodoptera frugiperda

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

Mohareer, Krishnaveni; Institute of Life Sciences, University of Hyderabad Campus, Prof. C.R. Rao Road, Gachibowli, Hyderabad 500046; Sahdev, Sudhir

2011-11-04

Highlights: Black-Right-Pointing-Pointer Baculovirus p35 is regulated by both viral and host factors. Black-Right-Pointing-Pointer Baculovirus p35 is negatively regulated by SfP53-like factor. Black-Right-Pointing-Pointer Baculovirus p35 is positively regulated by SfAP-1-like factor. -- Abstract: Baculovirus p35 belongs to the early class of genes of AcMNPV and requires viral factors like Immediate Early protein-1 for its transcription. To investigate the role of host factors in regulating p35 gene expression, the putative transcription factor binding sites were examined in silico and the role of these factors in influencing the transcription of p35 gene was assessed. We focused our studies on AP-1 and P53-like factors,more » which are activated under oxidative stress conditions. The AP-1 motif is located at -1401 while P53 motif is at -1912 relative to p35 translation start site. The predicted AP-1 and P53 elements formed specific complexes with Spodoptera frugiperda nuclear extracts. Both AP-1 and P53 motif binding proteins were down regulated as a function of AcMNPV infection in Spodoptera cells. To address the question whether during an oxidative outburst, the p35 transcription is enhanced; we investigated the role of these oxidative stress induced host transcription factors in influencing p35 gene transcription. Reporter assays revealed that AP-1 element enhances the transcription of p35 by a factor of two. Interestingly, P53 element appears to repress the transcription of p35 gene.« less

Pre-steady-state fluorescence analysis of damaged DNA transfer from human DNA glycosylases to AP endonuclease APE1.

PubMed

Kuznetsova, Alexandra A; Kuznetsov, Nikita A; Ishchenko, Alexander A; Saparbaev, Murat K; Fedorova, Olga S

2014-10-01

DNA glycosylases remove the modified, damaged or mismatched bases from the DNA by hydrolyzing the N-glycosidic bonds. Some enzymes can further catalyze the incision of a resulting abasic (apurinic/apyrimidinic, AP) site through β- or β,δ-elimination mechanisms. In most cases, the incision reaction of the AP-site is catalyzed by special enzymes called AP-endonucleases. Here, we report the kinetic analysis of the mechanisms of modified DNA transfer from some DNA glycosylases to the AP endonuclease, APE1. The modified DNA contained the tetrahydrofurane residue (F), the analogue of the AP-site. DNA glycosylases AAG, OGG1, NEIL1, MBD4(cat) and UNG from different structural superfamilies were used. We found that all DNA glycosylases may utilise direct protein-protein interactions in the transient ternary complex for the transfer of the AP-containing DNA strand to APE1. We hypothesize a fast "flip-flop" exchange mechanism of damaged and undamaged DNA strands within this complex for monofunctional DNA glycosylases like MBD4(cat), AAG and UNG. Bifunctional DNA glycosylase NEIL1 creates tightly specific complex with DNA containing F-site thereby efficiently competing with APE1. Whereas APE1 fast displaces other bifunctional DNA glycosylase OGG1 on F-site thereby induces its shifts to undamaged DNA regions. Kinetic analysis of the transfer of DNA between human DNA glycosylases and APE1 allows us to elucidate the critical step in the base excision repair pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

ACTIVATION OF AP-1 IN UROTSA CELLS BY METHYLATED ARSENICALS

EPA Science Inventory

ACTIVATION OF AP-1 IN UROTSA CELLS BY METHYLATED TRIVALENT ARSENICALS. Z Drobna1, I Jaspers2, D J Thomas3 and M Styblo1. 1Department of Pediatrics; 2Center for Environmental Medicine and Lung Biology, University of North Carolina at Chapel Hill, NC, USA; 3US EPA, RTP, NC, USA.

Dexamethasone inhibits inflammatory response via down regulation of AP-1 transcription factor in human lung epithelial cells.

PubMed

Patil, Rajeshwari H; Naveen Kumar, M; Kiran Kumar, K M; Nagesh, Rashmi; Kavya, K; Babu, R L; Ramesh, Govindarajan T; Chidananda Sharma, S

2018-03-01

The production of inflammatory mediators by epithelial cells in inflammatory lung diseases may represent an important target for the anti-inflammatory effects of glucocorticoids. Activator protein-1 is a major activator of inflammatory genes and has been proposed as a target for inhibition by glucocorticoids. We have used human pulmonary type-II A549 cells to examine the effect of dexamethasone on the phorbol ester (PMA)/Lipopolysaccharide (LPS) induced pro-inflammatory cytokines and AP-1 factors. A549 cells were treated with and without PMA or LPS or dexamethasone and the cell viability and nitric oxide production was measured by MTT assay and Griess reagent respectively. Expression of pro-inflammatory cytokines and AP-1 factors mRNA were measured using semi quantitative RT-PCR. The PMA/LPS treated cells show significant 2-3 fold increase in the mRNA levels of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-8 and TNF-α), cyclo‑oxygenase-2 (COX-2) and specific AP-1 factors (c-Jun, c-Fos and Jun-D). Whereas, pretreatment of cells with dexamethasone significantly inhibited the LPS induced nitric oxide production and PMA/LPS induced mRNAs expression of above pro-inflammatory cytokines, COX-2 and AP-1 factors. Cells treated with dexamethasone alone at both the concentrations inhibit the mRNAs expression of IL-1β, IL-6 and TNF-α compared to control. Our study reveals that dexamethasone decreased the mRNAs expression of c-Jun and c-Fos available for AP-1 formation suggested that AP-1 is the probable key transcription factor involved in the anti-inflammatory activity of dexamethasone. This may be an important molecular mechanism of steroid action in asthma and other chronic inflammatory lung diseases which may be useful for treatment of lung inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular and functional characterization of clathrin- and AP-2-binding determinants within a disordered domain of auxilin.

PubMed

Scheele, Urte; Alves, Jurgen; Frank, Ronald; Duwel, Michael; Kalthoff, Christoph; Ungewickell, Ernst

2003-07-11

Uncoating of clathrin-coated vesicles requires the J-domain protein auxilin for targeting hsc70 to the clathrin coats and for stimulating the hsc70 ATPase activity. This results in the release of hsc70-complexed clathrin triskelia and concomitant dissociation of the coat. To understand the complex role of auxilin in uncoating and clathrin assembly in more detail, we analyzed the molecular organization of its clathrin-binding domain (amino acids 547-813). CD spectroscopy of auxilin fragments revealed that the clathrin-binding domain is almost completely disordered in solution. By systematic mapping using synthetic peptides and by site-directed mutagenesis, we identified short peptide sequences involved in clathrin heavy chain and AP-2 binding and evaluated their significance for the function of auxilin. Some of the binding determinants, including those containing sequences 674DPF and 636WDW, showed dual specificity for both clathrin and AP-2. In contrast, the two DLL motifs within the clathrin-binding domain were exclusively involved in clathrin binding. Surprisingly, they interacted not only with the N-terminal domain of the heavy chain, but also with the distal domain. Moreover, both DLL peptides proved to be essential for clathrin assembly and uncoating. In addition, we found that the motif 726NWQ is required for efficient clathrin assembly activity. Auxilin shares a number of protein-protein interaction motifs with other endocytic proteins, including AP180. We demonstrate that AP180 and auxilin compete for binding to the alpha-ear domain of AP-2. Like AP180, auxilin also directly interacts with the ear domain of beta-adaptin. On the basis of our data, we propose a refined model for the uncoating mechanism of clathrin-coated vesicles.

CitAP2.10 activation of the terpene synthase CsTPS1 is associated with the synthesis of (+)-valencene in ‘Newhall’ orange

PubMed Central

Shen, Shu-ling; Yin, Xue-ren; Zhang, Bo; Xie, Xiu-lan; Jiang, Qian; Grierson, Donald; Chen, Kun-song

2016-01-01

Aroma is a vital characteristic that determines the quality and commercial value of citrus fruits, and characteristic volatiles have been analyzed in different citrus species. In sweet orange, Citrus sinensis, the sesquiterpene (+)-valencene is a key volatile compound in the fruit peel. Valencene synthesis is catalyzed by the terpene synthase CsTPS1, but the transcriptional mechanisms controlling its gene expression are unknown. Here, the AP2/ERF (APETALA2/ethylene response factor) transcription factor, CitAP2.10, is characterized as a regulator of (+)-valencene synthesis. The expression pattern of CitAP2.10 was positively correlated with (+)-valencene content and CsTPS1 expression. Dual-luciferase assays indicated that CitAP2.10 could trans-activate the CsTPS1 promoter. Ethylene enhanced expression of CitAP2.10 and this effect was abolished by the ethylene antagonist 1-methylcyclopropene. The role and function of CitAP2.10 in (+)-valencene biosynthesis were confirmed using the Arabidopsis homolog (AtWRI1), which also transiently activated the CsTPS1 promoter. Furthermore, transient over-expression of CitAP2.10 triggered (+)-valencene biosynthesis in sweet orange fruit. These results indicate that CitAP2.10 regulates (+)-valencene synthesis via induction of CsTPS1 mRNA accumulation. PMID:27194737

Overexpression of AtAP1M3 regulates flowering time and floral development in Arabidopsis and effects key flowering-related genes in poplar.

PubMed

Chen, Zhong; Ye, Meixia; Su, Xiaoxing; Liao, Weihua; Ma, Huandi; Gao, Kai; Lei, Bingqi; An, Xinmin

2015-08-01

APETALA1 plays a crucial role in the transition from vegetative to reproductive phase and in floral development. In this study, to determine the effect of AP1 expression on flowering time and floral organ development, transgenic Arabidopsis and poplar overexpressing of AtAP1M3 (Arabidopsis AP1 mutant by dominant negative mutation) were generated. Transgenic Arabidopsis with e35Spro::AtAP1M3 displayed phenotypes with delayed-flowering compared to wild-type and flowers with abnormal sepals, petals and stamens. In addition, transgenic Arabidopsis plants exhibited reduced growth vigor compared to the wild-type plants. Ectopic expression of AtAP1M3 in poplar resulted in up- or down-regulation of some endogenous key flowering-related genes, including floral meristems identity gene LFY, B-class floral organ identity genes AP3 and PI, flowering pathway integrator FT1 and flower repressors TFL1 and SVP. These results suggest that AtAP1M3 regulates flowering time and floral development in plants.

Incentivos para atraer y retener personal de salud de zonas rurales del Perú: un estudio cualitativo

PubMed Central

Huicho, Luis; Canseco, Francisco Díez; Lema, Claudia; Miranda, J. Jaime; Lescano, Andrés G.

2014-01-01

El objetivo fue identificar incentivos de atracción y retención en zonas rurales y distantes de Ayacucho, Perú. Fueron realizadas entrevistas en profundidad con 80 médicos, enfermeras, obstetras y técnicos (20 por grupo) de las zonas más pobres y con 11 funcionarios. No existen políticas sistemáticas de atracción y retención de personal de salud en Ayacucho. Los principales incentivos, en orden de importancia, fueron mejoras salariales, oportunidades de formación y capacitación, estabilidad laboral y nombramiento, mejoras en infraestructura y equipos, e incremento del personal. Se mencionaron también mejoras en la vivienda y alimentación, mayor cercanía con la familia y reconocimiento por el sistema de salud. Existen coincidencias y singularidades entre los distintos grupos sobre los incentivos clave para estimular el trabajo rural, que deben considerarse al diseñar políticas públicas. Las iniciativas del Estado deben comprender procesos rigurosos de monitoreo y evaluación, para asegurar que las mismas tengan el impacto deseado. PMID:22488318

X-ray performance of 0.18 µm CMOS APS test arrays for solar observation

NASA Astrophysics Data System (ADS)

Dryer, B. J.; Holland, A. D.; Jerram, P.; Sakao, Taro

2012-07-01

Solar-C is the third generation solar observatory led by JAXA. The accepted ‘Plan-B’ payload calls for a radiation-hard solar-staring photon-counting x-ray spectrometer. CMOS APS technology offers advantages over CCDs for such an application such as increased radiation hardness and high frame rate (instrument target of 1000 fps). Looking towards the solution of a bespoke CMOS APS, this paper reports the x-ray spectroscopy performance, concentrating on charge collection efficiency and split event analysis, of two baseline e2v CMOS APSs not designed for x-ray performance, the EV76C454 and the Ocean Colour Imager (OCI) test array. The EV76C454 is an industrial 5T APS designed for machine vision, available back and front illuminated. The OCI test arrays have varying pixel design across the chips, but are 4T, back illuminated and have thin low-resistivity and thick high-resistivity variants. The OCI test arrays’ pixel variants allow understanding of how pixel design can affect x-ray performance.

77 FR 50100 - AP&G Holdings LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-20

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER12-2430-000] AP&G Holdings LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes Request for Blanket Section 204 Authorization This is a supplemental notice in the above-referenced proceeding, of AP&G Holdings...

Characterization of diadenosine tetraphosphate (Ap4A) binding sites in cultured chromaffin cells: evidence for a P2y site.

PubMed Central

Pintor, J.; Torres, M.; Castro, E.; Miras-Portugal, M. T.

1991-01-01

1. Diadenosine tetraphosphate (Ap4A) a dinucleotide, which is stored in secretory granules, presents two types of high affinity binding sites in chromaffin cells. A Kd value of 8 +/- 0.65 x 10(-11) M and Bmax value of 5420 +/- 450 sites per cell were obtained for the high affinity binding site. A Kd value of 5.6 +/- 0.53 x 10(-9) M and a Bmax value close to 70,000 sites per cell were obtained for the second binding site with high affinity. 2. The diadenosine polyphosphates, Ap3A, Ap4A, Ap5A and Ap6A, displaced [3H]-Ap4A from the two binding sites, the Ki values being 1.0 nM, 0.013 nM, 0.013 nM and 0.013 nM for the very high affinity binding site and 0.5 microM, 0.13 microM, 0.062 microM and 0.75 microM for the second binding site. 3. The ATP analogues displaced [3H]-Ap4A with the potency order of the P2y receptors, adenosine 5'-O-(2 thiodiphosphate) (ADP-beta-S) greater than 5'-adenylyl imidodiphosphate (AMP-PNP) greater than alpha, beta-methylene ATP (alpha, beta-MeATP), in both binding sites. The Ki values were respectively 0.075 nM, 0.2 nM and 0.75 nM for the very high affinity binding site and 0.125 microM, 0.5 microM and 0.9 microM for the second binding site. PMID:1912985

CoAP-Based Mobility Management for the Internet of Things

PubMed Central

Chun, Seung-Man; Kim, Hyun-Su; Park, Jong-Tae

2015-01-01

Most of the current mobility management protocols such as Mobile IP and its variants standardized by the IETF may not be suitable to support mobility management for Web-based applications in an Internet of Things (IoT) environment. This is because the sensor nodes have limited power capacity, usually operating in sleep/wakeup mode in a constrained wireless network. In addition, sometimes the sensor nodes may act as the server using the CoAP protocol in an IoT environment. This makes it difficult for Web clients to properly retrieve the sensing data from the mobile sensor nodes in an IoT environment. In this article, we propose a mobility management protocol, named CoMP, which can effectively retrieve the sensing data of sensor nodes while they are moving. The salient feature of CoMP is that it makes use of the IETF CoAP protocol for mobility management, instead of using Mobile IP. Thus CoMP can eliminates the additional signaling overhead of Mobile IP, provides reliable mobility management, and prevents the packet loss. CoMP employs a separate location management server to keep track of the location of the mobile sensor nodes. In order to prevent the loss of important sensing data during movement, a holding mode of operation has been introduced. All the signaling procedures including discovery, registration, binding and holding have been designed by extending the IETF CoAP protocol. The numerical analysis and simulation have been done for performance evaluation in terms of the handover latency and packet loss. The results show that the proposed CoMP is superior to previous mobility management protocols, i.e., Mobile IPv4/v6 (MIPv4/v6), Hierarchical Mobile IPv4/v6 (HMIPv4/v6), in terms of the handover latency and packet loss. PMID:26151214

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes

PubMed Central

Marriott, Andrew S.; Vasieva, Olga; Fang, Yongxiang; Copeland, Nikki A.; McLennan, Alexander G.; Jones, Nigel J.

2016-01-01

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

PubMed

Marriott, Andrew S; Vasieva, Olga; Fang, Yongxiang; Copeland, Nikki A; McLennan, Alexander G; Jones, Nigel J

2016-01-01

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting

Structure of the E6/E6AP/p53 complex required for HPV-mediated degradation of p53

PubMed Central

Martinez-Zapien, Denise; Ruiz, Francesc Xavier; Poirson, Juline; Mitschler, André; Ramirez-Ramos, Juan; Forster, Anne; Cousido-Siah, Alexandra; Masson, Murielle; Pol, Scott Vande; Podjarny, Alberto; Travé, Gilles; Zanier, Katia

2015-01-01

Summary The p53 pro-apoptotic tumor suppressor is mutated or functionally altered in most cancers. In epithelial tumors induced by “high-risk” mucosal Human Papillomaviruses (hrm-HPVs), including human cervical carcinoma and a growing number of head-and-neck cancers 1, p53 is degraded by the viral oncoprotein E6 2. In this process, E6 binds to a short LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3. Subsequently, the E6/E6AP heterodimer recruits and degrades p53 4. Neither E6 nor E6AP are separately able to recruit p53 3,5, and the precise mode of assembly of E6, E6AP and p53 is unknown. Here, we solved the crystal structure of a ternary complex comprising full-length HPV16 E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6-p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumor suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against HPV-mediated oncogenesis. PMID:26789255

Diadenosine tetraphosphate (AP4A) mimics cardioprotective effect of ischemic preconditioning in the rat heart: contribution of KATP channel and PKC.

PubMed

Ahmet, I; Sawa, Y; Nishimura, M; Ichikawa, H; Matsuda, H

2000-06-01

Diadenosine tetraphosphate (AP4A) administration is reported to mimic the effect of ischemic preconditioning (PC) via purine 2y receptors (P2yR) and adenosine receptors. This study was designed to test the contributions of the ATP-sensitive potassium channel (KATP channel) and protein kinase C (PKC), two of the main regulator in PC, to the effect of AP4A. Isolated buffer-perfused rat hearts were subjected to 20 min of global ischemia (37 degrees C) and 20 min of reperfusion. Three cycles of 1-min ischemia and 3-min reperfusion induced PC. Chemicals were administrated for 2 min before 20 min of ischemia. AP4A (10 microM) administration was as effective as PC in improving the recovery of post-ischemic contractile function and reducing creatine kinase leakage after reperfusion, whereas adenosine (10 and 100 microM) have not effect. AP4A had not effect on reperfusion-induced arrhythmia, whereas PC significantly prevented it. These effects of AP4A and PC were reversed by co-administration of glibenclimade (KATP channel blocker, 100 microM) and GF109203X (PKC inhibitor, 10 microM); the effects of AP4A but not PC were reversed by co-administration of reactive blue (P2yR antagonist, 13 nM). AP4A appears to activate the KATP channel and PKC via P2yR mimic the effects of PC in part. The role of P2yR indicated that trigger mechanism of the effect of PC and AP4A administration might differ in rat hearts.

Diadenosine 5', 5'''-P(1),P(4)-tetraphosphate (Ap4A) is synthesized in response to DNA damage and inhibits the initiation of DNA replication.

PubMed

Marriott, Andrew S; Copeland, Nikki A; Cunningham, Ryan; Wilkinson, Mark C; McLennan, Alexander G; Jones, Nigel J

2015-09-01

The level of intracellular diadenosine 5', 5'''-P(1),P(4)-tetraphosphate (Ap4A) increases several fold in mammalian cells treated with non-cytotoxic doses of interstrand DNA-crosslinking agents such as mitomycin C. It is also increased in cells lacking DNA repair proteins including XRCC1, PARP1, APTX and FANCG, while >50-fold increases (up to around 25 μM) are achieved in repair mutants exposed to mitomycin C. Part of this induced Ap4A is converted into novel derivatives, identified as mono- and di-ADP-ribosylated Ap4A. Gene knockout experiments suggest that DNA ligase III is primarily responsible for the synthesis of damage-induced Ap4A and that PARP1 and PARP2 can both catalyze its ADP-ribosylation. Degradative proteins such as aprataxin may also contribute to the increase. Using a cell-free replication system, Ap4A was found to cause a marked inhibition of the initiation of DNA replicons, while elongation was unaffected. Maximum inhibition of 70-80% was achieved with 20 μM Ap4A. Ap3A, Ap5A, Gp4G and ADP-ribosylated Ap4A were without effect. It is proposed that Ap4A acts as an important inducible ligand in the DNA damage response to prevent the replication of damaged DNA. Copyright © 2015 Elsevier B.V. All rights reserved.

Lecithin-based microemulsions for targeted delivery of ceramide AP into the stratum corneum: formulation, characterizations, and in vitro release and penetration studies.

PubMed

Sahle, Fitsum F; Metz, Hendrik; Wohlrab, Johannes; Neubert, Reinhard H H

2013-02-01

To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.

Two tobacco AP1-like gene promoters with highly specific, tightly regulated and uniquely expressed activity during floral transition, initiation and development

USDA-ARS?s Scientific Manuscript database

Biotech engineering of agronomic traits requires an array of highly specific and tightly regulated promoters in flower or other tissues. In this study, we isolated and characterized two tobacco AP1-like promoters (termed NtAP1La and NtAP1Lb1) in transgenic plants using GUS reporter and tissue-speci...

Comparison of the SidePak personal monitor with the Aerosol Particle Sizer (APS).

PubMed

Sánchez Jiménez, Araceli; van Tongeren, Martie; Galea, Karen S; Steinsvåg, Kjersti; MacCalman, Laura; Cherrie, John W

2011-06-01

The aim of this study was to compare the performance of the TSI Aerodynamic Particle Sizer (APS) and the TSI portable photometer SidePak to measure airborne oil mist particulate matter (PM) with aerodynamic diameters below 10 μm, 2.5 μm and 1 μm (PM(10), PM(2.5) and PM(1)). Three SidePaks each fitted with either a PM(10), PM(2.5) or a PM(1) impactor and an APS were run side by side in a controlled chamber. Oil mist from two different mineral oils and two different drilling fluid systems commonly used in offshore drilling technologies were generated using a nebulizer. Compared to the APS, the SidePaks overestimated the concentration of PM(10) and PM(2.5) by one order of magnitude and PM(1) concentrations by two orders of magnitude after exposure to oil mist for 3.3-6.5 min at concentrations ranging from 0.003 to 18.1 mg m(-3) for PM(10), 0.002 to 3.96 mg m(-3) for PM(2.5) and 0.001 to 0.418 mg m(-3) for PM(1) (as measured by the APS). In a second experiment a SidePak monitor previously exposed to oil mist overestimated PM(10) concentrations by 27% compared to measurements from another SidePak never exposed to oil mist. This could be a result of condensation of oil mist droplets in the optical system of the SidePak. The SidePak is a very useful instrument for personal monitoring in occupational hygiene due to its light weight and quiet pump. However, it may not be suitable for the measurement of particle concentrations from oil mist.

Increased Ap4A levels and ecto-nucleotidase activity in glaucomatous mice retina.

PubMed

Pérez de Lara, María J; Guzmán-Aranguez, Ana; Gómez-Villafuertes, Rosa; Gualix, Javier; Miras-Portugal, María Teresa; Pintor, Jesús

2018-06-08

The pathogenesis of glaucoma involves numerous intracellular mechanisms including the purinergic system contribution. Furthermore, the presence and release of nucleotides and dinucleotides during the glaucomatous damage and the maintenance of degradation machinery through ecto-nucleotidase activity are participating in the modulation of the suitable extracellular complex balance. The aim of this study was to investigate the levels of diadenosine tetraphosphate (Ap 4 A) and the pattern of ecto-nucleotidase activity expression in glaucomatous retinas during the progress the pathology. Ap 4 A levels were analyzed by HPLC in glaucomatous retinas from the DBA/2J mice at 3, 9, 15, and 23 months of age. For that, retinas were dissected as flattened whole-mounts and stimulated in Ringer buffer with or without 59 mM KCl. NPP1 expression was analyzed by RT-PCR and western blot and its distribution was assessed by immunohistochemistry studies examined under confocal microscopy. Glaucomatous mice exhibited Ap 4 A values, which changed in stimulated retinas as long as the pathology progressed varying from 0.73 ± 0.04 (3 months) to 0.170 ± 0.05 pmol/mg retina (23 months). Concomitantly, NPP1 expression was significantly increased (82.15%) in the DBA/2J mice at 15 months. Furthermore, immunohistochemical studies showed that NPP1 labeling was stronger in OPL and IPL labeling tangentially in the vitreal part of the retina and was upregulated at 15 months of age. Our findings demonstrate that Ap 4 A decreased levels may be related with exacerbated activity of NPP1 protein in glaucomatous degeneration and in this way contributing to elucidate different mechanisms involved in retinal impairment in glaucomatous degeneration.

Transgenic expression of plant-specific insert of potato aspartic proteases (StAP-PSI) confers enhanced resistance to Botrytis cinerea in Arabidopsis thaliana.

PubMed