Sample records for front zip pockets

  1. Services provided by community pharmacies in Wayne County, Michigan: a comparison by ZIP code characteristics.

    PubMed

    Erickson, Steven R; Workman, Paul

    2014-01-01

    To document the availability of selected pharmacy services and out-of-pocket cost of medication throughout a diverse county in Michigan and to assess possible associations between availability of services and price of medication and characteristics of residents of the ZIP codes in which the pharmacies were located. Cross-sectional telephone survey of pharmacies coupled with ZIP code-level census data. 503 pharmacies throughout the 63 ZIP codes of Wayne County, MI. The out-of-pocket cost for a 30 days' supply of levothyroxine 50 mcg and brand-name atorvastatin (Lipitor-Pfizer) 20 mg, availability of discount generic drug programs, home delivery of medications, hours of pharmacy operation, and availability of pharmacy-based immunization services. Census data aggregated at the ZIP code level included race, annual household income, age, and number of residents per pharmacy. The overall results per ZIP code showed that the average cost for levothyroxine was $10.01 ± $2.29 and $140.45 + $14.70 for Lipitor. Per ZIP code, the mean (± SD) percentages of pharmacies offering discount generic drug programs was 66.9% ± 15.0%; home delivery of medications was 44.5% ± 22.7%; and immunization for influenza was 46.7% ± 24.3% of pharmacies. The mean (± SD) hours of operation per pharmacy per ZIP code was 67.0 ± 25.2. ZIP codes with higher household income as well as higher percentage of residents being white had lower levothyroxine price, greater percentage of pharmacies offering discount generic drug programs, more hours of operation per week, and more pharmacy-based immunization services. The cost of Lipitor was not associated with any ZIP code characteristic. Disparities in the cost of generic levothyroxine, the availability of services such as discount generic drug programs, hours of operation, and pharmacy-based immunization services are evident based on race and household income within this diverse metropolitan county.

  2. Accuracy of piezoelectric pedometer and accelerometer step counts.

    PubMed

    Cruz, Joana; Brooks, Dina; Marques, Alda

    2017-04-01

    This study aimed to assess step-count accuracy of a piezoeletric pedometer (Yamax PW/EX-510), when worn at different body parts, and a triaxial accelerometer (GT3X+), and to compare device accuracy; and identify the preferred location(s) to wear a pedometer. Sixty-three healthy adults (45.8±20.6 years old) wore 7 pedometers (neck, lateral right and left of the waist, front right and left of the waist, front pockets of the trousers) and 1 accelerometer (over the right hip), while walking 120 m at slow, self-preferred/normal and fast paces. Steps were recorded. Participants identified their preferred location(s) to wear the pedometer. Absolute percent error (APE) and Bland and Altman (BA) method were used to assess device accuracy (criterion measure: manual counts) and BA method for device comparisons. Pedometer APE was below 3% at normal and fast paces despite wearing location, but higher at slow pace (4.5-9.1%). Pedometers were more accurate at the front waist and inside the pockets. Accelerometer APE was higher than pedometer APE (P<0.05); nevertheless, limits of agreement between devices were relatively small. Preferred wearing locations were inside the front right (N.=25) and left (N.=20) pockets of the trousers. Yamax PW/EX-510 pedometers may be preferable than GT3X+ accelerometers to count steps, as they provide more accurate results. These pedometers should be worn at the front right or left positions of the waist or inside the front pockets of the trousers.

  3. Availability and variation of publicly reported prescription drug prices.

    PubMed

    Kullgren, Jeffrey T; Segel, Joel E; Peterson, Timothy A; Fendrick, A Mark; Singh, Simone

    2017-07-01

    To examine how often retail prices for prescription drugs are available on state public reporting websites, the variability of these reported prices, and zip code characteristics associated with greater price variation. Searches of state government-operated websites in Michigan, Missouri, New York, and Pennsylvania for retail prices for Advair Diskus (250/50 fluticasone propionate/salmeterol), Lyrica (pregabalin 50 mg), Nasonex (mometasone 50 mcg nasal spray), Spiriva (tiotropium 18 mcg cp-handihaler), Zetia (ezetimibe 10 mg), atorvastatin 20 mg, and metoprolol 50 mg. Data were collected for a 25% random sample of 1330 zip codes. For zip codes with at least 1 pharmacy, we used χ2 tests to compare how often prices were reported. For zip codes with at least 2 reported prices, we used Kruskal-Wallis tests to compare the median difference between the highest and lowest prices and a generalized linear model to identify zip code characteristics associated with greater price variation. Price availability varied significantly (P <.001) across states and drugs, ranging from 52% for metoprolol in Michigan to 1% for atorvastatin in Michigan. Price variation also varied significantly (P <.001) across states and drugs, ranging from a median of $159 for atorvastatin in Pennsylvania to a median of $24 for Nasonex in Missouri. The mean price variation was $52 greater (P <.001) for densely populated zip codes and $60 greater (P <.001) for zip codes with mostly nonwhite residents. Publicly reported information on state prescription drug price websites is often deficient. When prices are reported, there can be significant variation in the prices of prescriptions, which could translate into substantial savings for consumers who pay out-of-pocket for prescription drugs.

  4. OHD - OHD Staff

    Science.gov Websites

    Site Map News Organization Search NWS All NOAA Go Local forecast by "City, St" Search by city or zip code. Press enter or select the go button to submit request City, St Go Front Office OWP

  5. OHD - Data Systems

    Science.gov Websites

    Site Map News Organization Search NWS All NOAA Go Local forecast by "City, St" Search by city or zip code. Press enter or select the go button to submit request City, St Go Front Office OWP

  6. OHD - Additional Links

    Science.gov Websites

    Site Map News Organization Search NWS All NOAA Go Local forecast by "City, St" Search by city or zip code. Press enter or select the go button to submit request City, St Go Front Office OWP

  7. OHD - Current history

    Science.gov Websites

    Site Map News Organization Search NWS All NOAA Go Local forecast by "City, St" Search by city or zip code. Press enter or select the go button to submit request City, St Go Front Office OWP

  8. OHD - Field Support

    Science.gov Websites

    Site Map News Organization Search NWS All NOAA Go Local forecast by "City, St" Search by city or zip code. Press enter or select the go button to submit request City, St Go Front Office OWP

  9. Validity and reliability of the Fitbit Zip as a measure of preschool children’s step count

    PubMed Central

    Sharp, Catherine A; Mackintosh, Kelly A; Erjavec, Mihela; Pascoe, Duncan M; Horne, Pauline J

    2017-01-01

    Objectives Validation of physical activity measurement tools is essential to determine the relationship between physical activity and health in preschool children, but research to date has not focused on this priority. The aims of this study were to ascertain inter-rater reliability of observer step count, and interdevice reliability and validity of Fitbit Zip accelerometer step counts in preschool children. Methods Fifty-six children aged 3–4 years (29 girls) recruited from 10 nurseries in North Wales, UK, wore two Fitbit Zip accelerometers while performing a timed walking task in their childcare settings. Accelerometers were worn in secure pockets inside a custom-made tabard. Video recordings enabled two observers to independently code the number of steps performed in 3 min by each child during the walking task. Intraclass correlations (ICCs), concordance correlation coefficients, Bland-Altman plots and absolute per cent error were calculated to assess the reliability and validity of the consumer-grade device. Results An excellent ICC was found between the two observer codings (ICC=1.00) and the two Fitbit Zips (ICC=0.91). Concordance between the Fitbit Zips and observer counts was also high (r=0.77), with an acceptable absolute per cent error (6%–7%). Bland-Altman analyses identified a bias for Fitbit 1 of 22.8±19.1 steps with limits of agreement between −14.7 and 60.2 steps, and a bias for Fitbit 2 of 25.2±23.2 steps with limits of agreement between −20.2 and 70.5 steps. Conclusions Fitbit Zip accelerometers are a reliable and valid method of recording preschool children’s step count in a childcare setting. PMID:29081984

  10. 20. Living room, view to east wall and pocket doors ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. Living room, view to east wall and pocket doors to front parlor; view to east; 65mm lens with electronic flash illumination. - Warner Hutton House, 13495 Sousa Lane, Saratoga, Santa Clara County, CA

  11. Accelerometer's position independent physical activity recognition system for long-term activity monitoring in the elderly.

    PubMed

    Khan, Adil Mehmood; Lee, Young-Koo; Lee, Sungyoung; Kim, Tae-Seong

    2010-12-01

    Mobility is a good indicator of health status and thus objective mobility data could be used to assess the health status of elderly patients. Accelerometry has emerged as an effective means for long-term physical activity monitoring in the elderly. However, the output of an accelerometer varies at different positions on a subject's body, even for the same activity, resulting in high within-class variance. Existing accelerometer-based activity recognition systems thus require firm attachment of the sensor to a subject's body. This requirement makes them impractical for long-term activity monitoring during unsupervised free-living as it forces subjects into a fixed life pattern and impede their daily activities. Therefore, we introduce a novel single-triaxial-accelerometer-based activity recognition system that reduces the high within-class variance significantly and allows subjects to carry the sensor freely in any pocket without its firm attachment. We validated our system using seven activities: resting (lying/sitting/standing), walking, walking-upstairs, walking-downstairs, running, cycling, and vacuuming, recorded from five positions: chest pocket, front left trousers pocket, front right trousers pocket, rear trousers pocket, and inner jacket pocket. Its simplicity, ability to perform activities unimpeded, and an average recognition accuracy of 94% make our system a practical solution for continuous long-term activity monitoring in the elderly.

  12. Structure–kinetic relationship study of CDK8/CycC specific compounds

    PubMed Central

    Schneider, Elisabeth V.; Böttcher, Jark; Huber, Robert; Maskos, Klaus; Neumann, Lars

    2013-01-01

    In contrast with the very well explored concept of structure–activity relationship, similar studies are missing for the dependency between binding kinetics and compound structure of a protein ligand complex, the structure–kinetic relationship. Here, we present a structure–kinetic relationship study of the cyclin-dependent kinase 8 (CDK8)/cyclin C (CycC) complex. The scaffold moiety of the compounds is anchored in the kinase deep pocket and extended with diverse functional groups toward the hinge region and the front pocket. These variations can cause the compounds to change from fast to slow binding kinetics, resulting in an improved residence time. The flip of the DFG motif (“DMG” in CDK8) to the inactive DFG-out conformation appears to have relatively little influence on the velocity of binding. Hydrogen bonding with the kinase hinge region contributes to the residence time but has less impact than hydrophobic complementarities within the kinase front pocket. PMID:23630251

  13. Boko Haram’s Strategy Deconstructed: A Case Study Comparison Between Boko Haram and the Algerian National Liberation Front

    DTIC Science & Technology

    2015-06-12

    of wealth and political ‘ pocket -lining.’ Nigeria is the “thirteenth largest supplier of oil to the global market and the second largest destination......intermixed with pockets of uniformed ALN fighters, launched a series of assaults on unarmed European colonists of all ages, from Bone to south of

  14. Octanol-assisted liposome assembly on chip

    PubMed Central

    Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E. C.; Dekker, Cees

    2016-01-01

    Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5–20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells. PMID:26794442

  15. Octanol-assisted liposome assembly on chip.

    PubMed

    Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E C; Dekker, Cees

    2016-01-22

    Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5-20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells.

  16. Octanol-assisted liposome assembly on chip

    NASA Astrophysics Data System (ADS)

    Deshpande, Siddharth; Caspi, Yaron; Meijering, Anna E. C.; Dekker, Cees

    2016-01-01

    Liposomes are versatile supramolecular assemblies widely used in basic and applied sciences. Here we present a novel microfluidics-based method, octanol-assisted liposome assembly (OLA), to form monodisperse, cell-sized (5-20 μm), unilamellar liposomes with excellent encapsulation efficiency. Akin to bubble blowing, an inner aqueous phase and a surrounding lipid-carrying 1-octanol phase is pinched off by outer fluid streams. Such hydrodynamic flow focusing results in double-emulsion droplets that spontaneously develop a side-connected 1-octanol pocket. Owing to interfacial energy minimization, the pocket splits off to yield fully assembled solvent-free liposomes within minutes. This solves the long-standing fundamental problem of prolonged presence of residual oil in the liposome bilayer. We demonstrate the unilamellarity of liposomes with functional α-haemolysin protein pores in the membrane and validate the biocompatibility by inner leaflet localization of bacterial divisome proteins (FtsZ and ZipA). OLA offers a versatile platform for future analytical tools, delivery systems, nanoreactors and synthetic cells.

  17. Sidewall crystallization and saturation front formation in silicic magma chambers

    NASA Astrophysics Data System (ADS)

    Lake, E. T.

    2012-12-01

    The cooling and crystallization style of silicic magma bodies in the upper crust falls on a continuum between whole-chamber processes of convection, crystal settling, and cumulate formation and interface driven processes of conduction and crystallization front migration. In the former case, volatile saturation occurs uniformly chamber wide, in the latter volatile saturation occurs along an inward propagating front. Ambient thermal gradient primarily controls the propagation rate; warm (> 30 °C / km) geothermal gradients promote 1000m+ thick crystal mush zones but slow crystallization front propagation. Cold geothermal gradients support the opposite. Magma chamber geometry plays a second order role in controlling propagation rates; bodies with high surface to magma ratio and large Earth's surface parallel faces exhibit more rapid propagation and smaller mush zones. Crystallization front propagation occurs at speeds of up to 6 cm/year (rhyolitic magma, thin sill geometry, 10 °C / km geotherm), far faster than diffusion of volatiles in magma and faster than bubbles can nucleate and ascend under certain conditions. Saturation front propagation is fixed by pressure and magma crystal content; above certain modest initial water contents (4.4 wt% in a dacite) mobile magma above 10 km depth always contains a saturation front. Saturation fronts propagate down from the magma chamber roof at lower water contents (3.3 wt% in a dacite at 5 km depth), creating an upper saturated interface for most common (4 - 6 wt%) magma water contents. This upper interface promotes the production of a fluid pocket underneath the apex of the magma chamber. Magma de-densification by bubble nucleation promotes convection and homogenization in dacitic systems. If the fluid pocket grew rapidly without draining, hydro-fracturing and eruption would result. The combination of fluid escape pathways and metal scavenging would generate economic vein or porphyry deposits.

  18. ZIP3D: An elastic and elastic-plastic finite-element analysis program for cracked bodies

    NASA Technical Reports Server (NTRS)

    Shivakumar, K. N.; Newman, J. C., Jr.

    1990-01-01

    ZIP3D is an elastic and an elastic-plastic finite element program to analyze cracks in three dimensional solids. The program may also be used to analyze uncracked bodies or multi-body problems involving contacting surfaces. For crack problems, the program has several unique features including the calculation of mixed-mode strain energy release rates using the three dimensional virtual crack closure technique, the calculation of the J integral using the equivalent domain integral method, the capability to extend the crack front under monotonic or cyclic loading, and the capability to close or open the crack surfaces during cyclic loading. The theories behind the various aspects of the program are explained briefly. Line-by-line data preparation is presented. Input data and results for an elastic analysis of a surface crack in a plate and for an elastic-plastic analysis of a single-edge-crack-tension specimen are also presented.

  19. Repression of transcriptional activity of C/EBPalpha by E2F-dimerization partner complexes.

    PubMed

    Zaragoza, Katrin; Bégay, Valérie; Schuetz, Anja; Heinemann, Udo; Leutz, Achim

    2010-05-01

    The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, keratinocytes, and cells of the lung and placenta. C/EBPalpha transactivates lineage-specific differentiation genes and inhibits proliferation by repressing E2F-regulated genes. The myeloproliferative C/EBPalpha BRM2 mutant serves as a paradigm for recurrent human C-terminal bZIP C/EBPalpha mutations that are involved in acute myeloid leukemogenesis. BRM2 fails to repress E2F and to induce adipogenesis and granulopoiesis. The data presented here show that, independently of pocket proteins, C/EBPalpha interacts with the dimerization partner (DP) of E2F and that C/EBPalpha-E2F/DP interaction prevents both binding of C/EBPalpha to its cognate sites on DNA and transactivation of C/EBP target genes. The BRM2 mutant, in addition, exhibits enhanced interaction with E2F-DP and reduced affinity toward DNA and yet retains transactivation potential and differentiation competence that becomes exposed when E2F/DP levels are low. Our data suggest a tripartite balance between C/EBPalpha, E2F/DP, and pocket proteins in the control of proliferation, differentiation, and tumorigenesis.

  20. A Comparison of the Nutritional Quality of Food Products Advertised in Grocery Store Circulars of High- versus Low-Income New York City Zip Codes

    PubMed Central

    Ethan, Danna; Basch, Corey H.; Rajan, Sonali; Samuel, Lalitha; Hammond, Rodney N.

    2013-01-01

    Grocery stores can be an important resource for health and nutrition with the variety and economic value of foods offered. Weekly circulars are a means of promoting foods at a sale price. To date, little is known about the extent that nutritious foods are advertised and prominently placed in circulars. This study’s aim was to compare the nutritional quality of products advertised on the front page of online circulars from grocery stores in high- versus low-income neighborhoods in New York City (NYC). Circulars from grocery stores in the five highest and five lowest median household income NYC zip codes were analyzed. Nutrition information for food products was collected over a two-month period with a total of 805 products coded. The study found no significant difference between the nutritional quality of products advertised on the front page of online circulars from grocery stores in high- versus low-income neighborhoods in New York City (NYC). In both groups, almost two-thirds of the products advertised were processed, one-quarter were high in carbohydrates, and few to no products were low-sodium, high-fiber, or reduced-, low- or zero fat. Through innovative partnerships with health professionals, grocery stores are increasingly implementing in-store and online health promotion strategies. Weekly circulars can be used as a means to regularly advertise and prominently place more healthful and seasonal foods at an affordable price, particularly for populations at higher risk for nutrition-related chronic disease. PMID:24384775

  1. A comparison of the nutritional quality of food products advertised in grocery store circulars of high- versus low-income New York City zip codes.

    PubMed

    Ethan, Danna; Basch, Corey H; Rajan, Sonali; Samuel, Lalitha; Hammond, Rodney N

    2013-12-31

    Grocery stores can be an important resource for health and nutrition with the variety and economic value of foods offered. Weekly circulars are a means of promoting foods at a sale price. To date, little is known about the extent that nutritious foods are advertised and prominently placed in circulars. This study's aim was to compare the nutritional quality of products advertised on the front page of online circulars from grocery stores in high- versus low-income neighborhoods in New York City (NYC). Circulars from grocery stores in the five highest and five lowest median household income NYC zip codes were analyzed. Nutrition information for food products was collected over a two-month period with a total of 805 products coded. The study found no significant difference between the nutritional quality of products advertised on the front page of online circulars from grocery stores in high- versus low-income neighborhoods in New York City (NYC). In both groups, almost two-thirds of the products advertised were processed, one-quarter were high in carbohydrates, and few to no products were low-sodium, high-fiber, or reduced-, low- or zero fat. Through innovative partnerships with health professionals, grocery stores are increasingly implementing in-store and online health promotion strategies. Weekly circulars can be used as a means to regularly advertise and prominently place more healthful and seasonal foods at an affordable price, particularly for populations at higher risk for nutrition-related chronic disease.

  2. A Fortunate Story of an Unusual AK-47 Bullet Trajectory: Always Keep a Smartphone in Your Pocket.

    PubMed

    Thabouillot, Oscar; Perrier, Pierre; Roche, Nicolas-Charles; Agard, David; Barbier, Olivier; Martin, Guillaume; Viant, Eric; Leclere, Jean-Baptiste

    2016-06-01

    This is a report of a fortunate story of an unusual AK-47 bullet trajectory which took place during the Paris (France) attack of November 13th, 2015. A young man, trying to protect his girlfriend, interfered between her and a shooter. He had been wounded in the posterior compartment of the thigh. The bullet penetrated him and, instead of exiting, rebound against his Smartphone, which was in the front pocket of his pants. Thanks to that, the missile bullet did not injure his girlfriend but ended its trajectory in the fat tissue of his thigh. Thabouillot O , Perrier P , Roche NC , Agard D , Barbier O , Martin G , Viant E , Leclere JB . A fortunate story of an unusual AK-47 bullet trajectory: always keep a Smartphone in your pocket. Prehosp Disaster Med, 2016;31(3):343-345.

  3. The Contents of My Backpack

    ERIC Educational Resources Information Center

    Goldman, Arthur

    2004-01-01

    As Mr. Goldman empties his backpack, his philosophy of teaching spills out, along with an interesting assortment of odds and ends. In this article Mr. Goldman describes the contents of his L.L. Bean daypack with two large compartments in the back, a smaller forward compartment, and a little zippered pocket in the very front, along with his…

  4. A ZIP6-ZIP10 heteromer controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition.

    PubMed

    Brethour, Dylan; Mehrabian, Mohadeseh; Williams, Declan; Wang, Xinzhu; Ghodrati, Farinaz; Ehsani, Sepehr; Rubie, Elizabeth A; Woodgett, James R; Sevalle, Jean; Xi, Zhengrui; Rogaeva, Ekaterina; Schmitt-Ulms, Gerold

    2017-01-18

    The prion protein (PrP) evolved from the subbranch of ZIP metal ion transporters comprising ZIPs 5, 6 and 10, raising the prospect that the study of these ZIPs may reveal insights relevant for understanding the function of PrP. Building on data which suggested PrP and ZIP6 are critical during epithelial-to-mesenchymal transition (EMT), we investigated ZIP6 in an EMT paradigm using ZIP6 knockout cells, mass spectrometry and bioinformatic methods. Reminiscent of PrP, ZIP6 levels are five-fold upregulated during EMT and the protein forms a complex with NCAM1. ZIP6 also interacts with ZIP10 and the two ZIP transporters exhibit interdependency during their expression. ZIP6 contributes to the integration of NCAM1 in focal adhesion complexes but, unlike cells lacking PrP, ZIP6 deficiency does not abolish polysialylation of NCAM1. Instead, ZIP6 mediates phosphorylation of NCAM1 on a cluster of cytosolic acceptor sites. Substrate consensus motif features and in vitro phosphorylation data point toward GSK3 as the kinase responsible, and interface mapping experiments identified histidine-rich cytoplasmic loops within the ZIP6/ZIP10 heteromer as a novel scaffold for GSK3 binding. Our data suggests that PrP and ZIP6 inherited the ability to interact with NCAM1 from their common ZIP ancestors but have since diverged to control distinct posttranslational modifications of NCAM1.

  5. Two Cassava Basic Leucine Zipper (bZIP) Transcription Factors (MebZIP3 and MebZIP5) Confer Disease Resistance against Cassava Bacterial Blight.

    PubMed

    Li, Xiaolin; Fan, Shuhong; Hu, Wei; Liu, Guoyin; Wei, Yunxie; He, Chaozu; Shi, Haitao

    2017-01-01

    Basic domain-leucine zipper (bZIP) transcription factor, one type of conserved gene family, plays an important role in plant development and stress responses. Although 77 MebZIPs have been genome-wide identified in cassava, their in vivo roles remain unknown. In this study, we analyzed the expression pattern and the function of two MebZIPs ( MebZIP3 and MebZIP5 ) in response to pathogen infection. Gene expression analysis indicated that MebZIP3 and MebZIP5 were commonly regulated by flg22, Xanthomonas axonopodis pv. manihotis ( Xam ), salicylic acid (SA), and hydrogen peroxide (H 2 O 2 ). Subcellular localization analysis showed that MebZIP3 and MebZIP5 are specifically located in cell nucleus. Through overexpression in tobacco, we found that MebZIP3 and MebZIP5 conferred improved disease resistance against cassava bacterial blight, with more callose depositions. On the contrary, MebZIP3- and MebZIP5 -silenced plants by virus-induced gene silencing (VIGS) showed disease sensitive phenotype, lower transcript levels of defense-related genes and less callose depositions. Taken together, this study highlights the positive role of MebZIP3 and MebZIP5 in disease resistance against cassava bacterial blight for further utilization in genetic improvement of cassava disease resistance.

  6. A conserved proline residue in the leucine zipper region of AtbZIP34 and AtbZIP61 in Arabidopsis thaliana interferes with the formation of homodimer.

    PubMed

    Shen, Huaishun; Cao, Kaiming; Wang, Xiping

    2007-10-19

    Two putative Arabidopsis E group bZIP transcript factors, AtbZIP34 and AtbZIP61, are nuclear-localized and their transcriptional activation domain is in their N-terminal region. By searching GenBank, we found other eight plant homologues of AtbZIP34 and AtbZIP61. All of them have a proline residue in the third heptad of zipper region. Yeast two-hybrid assay and EMSA showed that AtbZIP34 and AtbZIP61 could not form homodimer while their mutant forms, AtbZIP34m and AtbZIP61m, which the proline residue was replaced by an alanine residue in the zipper region, could form homodimer and bind G-box element. These results suggest that the conserved proline residue interferes with the homodimer formation. However, both AtbZIP34 and AtbZIP61 could form heterodimers with members of I group and S group transcription factors in which some members involved in vascular development. So we speculate that AtbZIP34 and AtbZIP61 may participate in plant development via interacting with other group bZIP transcription factors.

  7. Passive microwave detection of river-plume fronts in the German Bight

    NASA Technical Reports Server (NTRS)

    Blume, H.-J. C.

    1982-01-01

    The NASA P-3 aircraft with the L- and S-band radiometer system on board participated in the MARSEN experiments carried out between August 30 and September 23, 1979. Measurements of surface temperature and salinity were concentrated on freshwater outflows of the Rivers Weser and Elbe in the German Bight. Three missions were carried out, on September 19, 22, and 23. The values of salinity are plotted as a function of geographic position, and contour maps of the salinity distribution are generated from the value plots. It is noted that on September 22, during a noon flood-tide, two river-plume salinity fronts were detected when a body of water with higher salinity existed in front of the Weser delta near Bremerhaven generating with the river outflow of lower saline waters a front of delta-S equals 5 per thousand. Another pocket of lower saline waters was found in front of the Elbe delta at Cuxhaven, which in turn set up a strong front of delta-S equals 6 per thousand. The morning low tide of September 23 did not exhibit this extreme condition.

  8. Bioinformatic analyses implicate the collaborating meiotic crossover/chiasma proteins Zip2, Zip3, and Spo22/Zip4 in ubiquitin labeling

    PubMed Central

    Perry, Jason; Kleckner, Nancy; Börner, G. Valentin

    2005-01-01

    Zip2 and Zip3 are meiosis-specific proteins that, in collaboration with several partners, act at the sites of crossover-designated, axis-associated recombinational interactions to mediate crossover/chiasma formation. Here, Spo22 (also called Zip4) is identified as a probable functional collaborator of Zip2/3. The molecular roles of Zip2, Zip3, and Spo22/Zip4 are unknown. All three proteins are part of a small evolutionary cohort comprising similar homologs in four related yeasts. Zip3 is shown to contain a RING finger whose structural features most closely match those of known ubiquitin E3s. Further, Zip3 exhibits major domainal homologies to Rad18, a known DNA-binding ubiquitin E3. Also described is an approach to the identification and mapping of repeated protein sequence motifs, Alignment Based Repeat Annotation (ABRA), that we have developed. When ABRA is applied to Zip2 and Spo22/Zip4, they emerge as a 14-blade WD40-like repeat protein and a 22-unit tetratricopeptide repeat protein, respectively. WD40 repeats of Cdc20, Cdh1, and Cdc16 and tetratricopeptide repeats of Cdc16, Cdc23, and Cdc27, all components of the anaphase-promoting complex, are also analyzed. These and other findings suggest that Zip2, Zip3, and Zip4 act together to mediate a process that involves Zip3-mediated ubiquitin labeling, potentially as a unique type of ubiquitin-conjugating complex. PMID:16314568

  9. HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP

    PubMed Central

    Maudet, Claire; Sourisce, Adèle; Dragin, Loïc; Lahouassa, Hichem; Rain, Jean-Christophe; Bouaziz, Serge; Ramirez, Bertha Cécilia; Margottin-Goguet, Florence

    2013-01-01

    The Vpr protein from type 1 and type 2 Human Immunodeficiency Viruses (HIV-1 and HIV-2) is thought to inactivate several host proteins through the hijacking of the DCAF1 adaptor of the Cul4A ubiquitin ligase. Here, we identified two transcriptional regulators, ZIP and sZIP, as Vpr-binding proteins degraded in the presence of Vpr. ZIP and sZIP have been shown to act through the recruitment of the NuRD chromatin remodeling complex. Strikingly, chromatin is the only cellular fraction where Vpr is present together with Cul4A ubiquitin ligase subunits. Components of the NuRD complex and exogenous ZIP and sZIP were also associated with this fraction. Several lines of evidence indicate that Vpr induces ZIP and sZIP degradation by hijacking DCAF1: (i) Vpr induced a drastic decrease of exogenously expressed ZIP and sZIP in a dose-dependent manner, (ii) this decrease relied on the proteasome activity, (iii) ZIP or sZIP degradation was impaired in the presence of a DCAF1-binding deficient Vpr mutant or when DCAF1 expression was silenced. Vpr-mediated ZIP and sZIP degradation did not correlate with the growth-related Vpr activities, namely G2 arrest and G2 arrest-independent cytotoxicity. Nonetheless, infection with HIV-1 viruses expressing Vpr led to the degradation of the two proteins. Altogether our results highlight the existence of two host transcription factors inactivated by Vpr. The role of Vpr-mediated ZIP and sZIP degradation in the HIV-1 replication cycle remains to be deciphered. PMID:24116224

  10. Characterization of pollen-expressed bZIP protein interactions and the role of ATbZIP18 in the male gametophyte.

    PubMed

    Gibalová, Antónia; Steinbachová, Lenka; Hafidh, Said; Bláhová, Veronika; Gadiou, Zuzana; Michailidis, Christos; Műller, Karel; Pleskot, Roman; Dupľáková, Nikoleta; Honys, David

    2017-03-01

    KEY MESSAGE : bZIP TF network in pollen. Transcriptional control of gene expression represents an important mechanism guiding organisms through developmental processes and providing plasticity towards environmental stimuli. Because of their sessile nature, plants require effective gene regulation for rapid response to variation in environmental and developmental conditions. Transcription factors (TFs) provide such control ensuring correct gene expression in spatial and temporal manner. Our work reports the interaction network of six bZIP TFs expressed in Arabidopsis thaliana pollen and highlights the potential functional role for AtbZIP18 in pollen. AtbZIP18 was shown to interact with three other pollen-expressed bZIP TFs-AtbZIP34, AtbZIP52, and AtbZIP61 in yeast two-hybrid assays. AtbZIP18 transcripts are highly expressed in pollen, and at the subcellular level, an AtbZIP18-GFP fusion protein was located in the nucleus and cytoplasm/ER. To address the role of AtbZIP18 in the male gametophyte, we performed phenotypic analysis of a T-DNA knockout allele, which showed slightly reduced transmission through the male gametophyte. Some of the phenotype defects in atbzip18 pollen, although observed at low penetrance, were similar to those seen at higher frequency in the T-DNA knockout of the interacting partner, AtbZIP34. To gain deeper insight into the regulatory role of AtbZIP18, we analysed atbzip18/- pollen microarray data. Our results point towards a potential repressive role for AtbZIP18 and its functional redundancy with AtbZIP34 in pollen.

  11. A Ramie bZIP Transcription Factor BnbZIP2 Is Involved in Drought, Salt, and Heavy Metal Stress Response.

    PubMed

    Huang, Chengjian; Zhou, Jinghua; Jie, Yucheng; Xing, Hucheng; Zhong, Yingli; Yu, Weilin; She, Wei; Ma, Yushen; Liu, Zehang; Zhang, Ying

    2016-12-01

    bZIP transcription factors play key roles in plant growth, development, and stress signaling. A bZIP gene BnbZIP2 (GenBank accession number: KP642148) was cloned from ramie. BnbZIP2 has a 1416 base pair open reading frame, encoding a 471 amino acid protein containing a characteristic bZIP domain and a leucine zipper. BnbZIP2 shares high sequence similarity with bZIP factors from other plants. The BnbZIP2 protein is localized to both nuclei and cytoplasm. Transcripts of BnbZIP2 were found in various tissues in ramie, with significantly higher levels in female and male flowers. Its expression was induced by drought, high salinity, and abscisic acid treatments. Analysis of the cis-elements in promoters of BnbZIP2 identified cis-acting elements involved in growth, developmental processes, and a variety of stress responses. Transgenic Arabidopsis plants' overexpression of BnbZIP2 exhibited more sensitivity to drought and heavy metal Cd stress during seed germination, whereas more tolerance to high-salinity stress than the wild type during both seed germination and plant development. Thus, BnbZIP2 may act as a positive regulator in plants' response to high-salinity stress and be an important candidate gene for molecular breeding of salt-tolerant plants.

  12. Overexpression of a wheat (Triticum aestivum L.) bZIP transcription factor gene, TabZIP6, decreased the freezing tolerance of transgenic Arabidopsis seedlings by down-regulating the expression of CBFs.

    PubMed

    Cai, Wangting; Yang, Yaling; Wang, Weiwei; Guo, Guangyan; Liu, Wei; Bi, Caili

    2018-03-01

    The basic leucine zipper (bZIP) proteins play important roles against abiotic stress in plants, including cold stress. However, most bZIPs involved in plant freezing tolerance are positive regulators. Only a few bZIPs function negatively in cold stress response. In this study, TabZIP6, a Group C bZIP transcription factor gene from common wheat (Triticum aestivum L.), was cloned and characterized. The transcript of TabZIP6 was strongly induced by cold treatment (4 °C). TabZIP6 is a nuclear-localized protein with transcriptional activation activity. Arabidopsis plants overexpressing TabZIP6 showed decreased tolerance to freezing stress. Microarray as well as quantitative real-time PCR (qRT-PCR) analysis showed that CBFs and some key COR genes, including COR47 and COR15B, were down-regulated by cold treatment in TabZIP6-overexpressing Arabidopsis lines. TabZIP6 was capable of binding to the G-box motif and the CBF1 and CBF3 promoters in yeast cells. A yeast two-hybrid assay revealed that TabZIP6, as well as the other two Group S bZIP proteins involved in cold stress tolerance in wheat, Wlip19 and TaOBF1, can form homodimers by themselves and heterodimers with each other. These results suggest that TabZIP6 may function negatively in the cold stress response by binding to the promoters of CBFs, and thereby decreasing the expression of downstream COR genes in TabZIP6-overexpressing Arabidopsis seedlings. Copyright © 2018. Published by Elsevier Masson SAS.

  13. The ZIP family zinc transporters support the virulence of Cryptococcus neoformans

    PubMed Central

    Do, Eunsoo; Hu, Guanggan; Caza, Mélissa; Kronstad, James W.; Jung, Won Hee

    2016-01-01

    Zinc is an essential element in living organisms and a cofactor for various metalloproteins. To disseminate and survive, a pathogenic microbe must obtain zinc from the host, which is an environment with extremely limited zinc availability. In this study, we investigated the roles of the ZIP family zinc transporters Zip1 and Zip2 in the human pathogenic fungus Cryptococcus neoformans. Zip1 and Zip2 are homologous to Zrt1 and Zrt2 of the model fungus, Saccharomyces cerevisiae, respectively. We found that the expression of ZIP1 was regulated by the zinc concentration in the environment. Furthermore, the mutant lacking ZIP1 displayed a severe growth defect under zinc-limited conditions, while the mutant lacking ZIP2 displayed normal growth. Inductively coupled plasma–atomic emission spectroscopy analysis showed that the absence of Zip1 expression significantly reduced total cellular zinc levels relative to that in the wild type, while overexpression of Zip1 was associated with increased cellular zinc levels. These findings suggested that Zip1 plays roles in zinc uptake in C. neoformans. We also constructed a Zip1-FLAG fusion protein and found, by immunofluorescence, not only that the protein was localized to the periphery implying it is a membrane transporter, but also that the protein was N-glycosylated. Furthermore, the mutant lacking ZIP1 showed attenuated virulence in a murine inhalation model of cryptococcosis and reduced survival within murine macrophages. Overall, our data suggest that Zip1 plays essential roles in zinc transport and the virulence of C. neoformans. PMID:27118799

  14. Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: a potential novel strategy to enhance zinc absorption by ZIP4 targeting.

    PubMed

    Hashimoto, Ayako; Ohkura, Katsuma; Takahashi, Masakazu; Kizu, Kumiko; Narita, Hiroshi; Enomoto, Shuichi; Miyamae, Yusaku; Masuda, Seiji; Nagao, Masaya; Irie, Kazuhiro; Ohigashi, Hajime; Andrews, Glen K; Kambe, Taiho

    2015-12-01

    Dietary zinc deficiency puts human health at risk, so we explored strategies for enhancing zinc absorption. In the small intestine, the zinc transporter ZIP4 functions as an essential component of zinc absorption. Overexpression of ZIP4 protein increases zinc uptake and thereby cellular zinc levels, suggesting that food components with the ability to increase ZIP4 could potentially enhance zinc absorption via the intestine. In the present study, we used mouse Hepa cells, which regulate mouse Zip4 (mZip4) in a manner indistinguishable from that in intestinal enterocytes, to screen for suitable food components that can increase the abundance of ZIP4. Using this ZIP4-targeting strategy, two such soybean extracts were identified that were specifically able to decrease mZip4 endocytosis in response to zinc. These soybean extracts also effectively increased the abundance of apically localized mZip4 in transfected polarized Caco2 and Madin-Darby canine kidney cells and, moreover, two apically localized mZip4 acrodermatitis enteropathica mutants. Soybean components were purified from one extract and soyasaponin Bb was identified as an active component that increased both mZip4 protein abundance and zinc levels in Hepa cells. Finally, we confirmed that soyasaponin Bb is capable of enhancing cell surface endogenous human ZIP4 in human cells. Our results suggest that ZIP4 targeting may represent a new strategy to improve zinc absorption in humans. © 2015 Authors; published by Portland Press Limited.

  15. Wetting transition on patterned surfaces: transition states and energy barriers.

    PubMed

    Ren, Weiqing

    2014-03-18

    We study the wetting transition on microstructured hydrophobic surfaces. We use the string method [J. Chem. Phys. 2007, 126, 164103; J. Chem. Phys. 2013, 138, 134105] to accurately compute the transition states, the energy barriers, and the minimum energy paths for the wetting transition from the Cassie-Baxter state to the Wenzel state. Numerical results are obtained for the wetting of a hydrophobic surface textured with a square lattice of pillars. It is found that the wetting of the solid substrate occurs via infiltration of the liquid in a single groove, followed by lateral propagation of the liquid front. The propagation of the liquid front proceeds in a stepwise manner, and a zipping mechanism is observed during the infiltration of each layer. The minimum energy path for the wetting transition goes through a sequence of intermediate metastable states, whose wetted areas reflect the microstructure of the patterned surface. We also study the dependence of the energy barrier on the drop size and the gap between the pillars.

  16. SlbZIP38, a Tomato bZIP Family Gene Downregulated by Abscisic Acid, Is a Negative Regulator of Drought and Salt Stress Tolerance

    PubMed Central

    Pan, Yanglu; Hu, Xin; Li, Chunyan; Xu, Xing; Su, Chenggang; Li, Jinhua; Song, Hongyuan; Zhang, Xingguo; Pan, Yu

    2017-01-01

    The basic leucine zipper (bZIP) transcription factors have crucial roles in plant stress responses. In this study, the bZIP family gene SlbZIP38 (GenBank accession No: XM004239373) was isolated from a tomato (Solanum lycopersicum cv. Ailsa Craig) mature leaf cDNA library. The DNA sequence of SlbZIP38 encodes a protein of 484 amino acids, including a highly conserved bZIP DNA-binding domain in the C-terminal region. We found that SlbZIP38 was differentially expressed in various organs of the tomato plant and was downregulated by drought, salt stress, and abscisic acid (ABA). However, overexpression of SlbZIP38 significantly decreased drought and salt stress tolerance in tomatoes (Ailsa Craig). The findings that SlbZIP38 overexpression reduced the chlorophyll and free proline content in leaves but increased the malondialdehyde content may explain the reduced drought and salt tolerance observed in these lines. These results suggest that SlbZIP38 is a negative regulator of drought and salt resistance that acts by modulating ABA signaling. PMID:29261143

  17. Structure and function of homodomain-leucine zipper (HD-Zip) proteins.

    PubMed

    Elhiti, Mohamed; Stasolla, Claudio

    2009-02-01

    Homeodomain-leucine zipper (HD-Zip) proteins are transcription factors unique to plants and are encoded by more than 25 genes in Arabidopsis thaliana. Based on sequence analyses these proteins have been classified into four distinct groups: HD-Zip I-IV. HD-Zip proteins are characterized by the presence of two functional domains; a homeodomain (HD) responsible for DNA binding and a leucine zipper domain (Zip) located immediately C-terminal to the homeodomain and involved in protein-protein interaction. Despite sequence similarities HD-ZIP proteins participate in a variety of processes during plant growth and development. HD-Zip I proteins are generally involved in responses related to abiotic stress, abscisic acid (ABA), blue light, de-etiolation and embryogenesis. HD-Zip II proteins participate in light response, shade avoidance and auxin signalling. Members of the third group (HD-Zip III) control embryogenesis, leaf polarity, lateral organ initiation and meristem function. HD-Zip IV proteins play significant roles during anthocyanin accumulation, differentiation of epidermal cells, trichome formation and root development.

  18. Genome-wide characterization and analysis of bZIP transcription factor gene family related to abiotic stress in cassava.

    PubMed

    Hu, Wei; Yang, Hubiao; Yan, Yan; Wei, Yunxie; Tie, Weiwei; Ding, Zehong; Zuo, Jiao; Peng, Ming; Li, Kaimian

    2016-03-07

    The basic leucine zipper (bZIP) transcription factor family plays crucial roles in various aspects of biological processes. Currently, no information is available regarding the bZIP family in the important tropical crop cassava. Herein, 77 bZIP genes were identified from cassava. Evolutionary analysis indicated that MebZIPs could be divided into 10 subfamilies, which was further supported by conserved motif and gene structure analyses. Global expression analysis suggested that MebZIPs showed similar or distinct expression patterns in different tissues between cultivated variety and wild subspecies. Transcriptome analysis of three cassava genotypes revealed that many MebZIP genes were activated by drought in the root of W14 subspecies, indicating the involvement of these genes in the strong resistance of cassava to drought. Expression analysis of selected MebZIP genes in response to osmotic, salt, cold, ABA, and H2O2 suggested that they might participate in distinct signaling pathways. Our systematic analysis of MebZIPs reveals constitutive, tissue-specific and abiotic stress-responsive candidate MebZIP genes for further functional characterization in planta, yields new insights into transcriptional regulation of MebZIP genes, and lays a foundation for understanding of bZIP-mediated abiotic stress response.

  19. Membrane androgen receptor characteristics of human ZIP9 (SLC39A) zinc transporter in prostate cancer cells: Androgen-specific activation and involvement of an inhibitory G protein in zinc and MAP kinase signaling.

    PubMed

    Thomas, Peter; Pang, Yefei; Dong, Jing

    2017-05-15

    Characteristics of novel human membrane androgen receptor (mAR), ZIP9 (SLC39A9), were investigated in ZIP9-transfected PC-3 cells (PC3-ZIP9). Ligand blot analysis showed plasma membrane [ 3 H]-T binding corresponds to the position of ZIP9 on Western blots which suggests ZIP9 can bind [ 3 H]-T alone, without a protein partner. Progesterone antagonized testosterone actions, blocking increases in zinc, Erk phosphorylation and apoptosis, further evidence that ZIP9 is specifically activated by androgens. Pre-treatment with GTPγS and pertussis toxin decreased plasma membrane [ 3 H]-T binding and blocked testosterone-induced increases in Erk phosphorylation and intracellular zinc, indicating ZIP9 is coupled to an inhibitory G protein (Gi) that mediates both MAP kinase and zinc signaling. Testosterone treatment of nuclei and mitochondria which express ZIP9 decreased their zinc contents, suggesting ZIP9 also regulates free zinc through releasing it from these intracellular organelles. The results show ZIP9 is a specific Gi coupled-mAR mediating testosterone-induced MAP kinase and zinc signaling in PC3-ZIP9 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Comparative Genomic Analysis of slc39a12/ZIP12: Insight into a Zinc Transporter Required for Vertebrate Nervous System Development

    PubMed Central

    Chowanadisai, Winyoo

    2014-01-01

    The zinc transporter ZIP12, which is encoded by the gene slc39a12, has previously been shown to be important for neuronal differentiation in mouse Neuro-2a neuroblastoma cells and primary mouse neurons and necessary for neurulation during Xenopus tropicalis embryogenesis. However, relatively little is known about the biochemical properties, cellular regulation, or the physiological role of this gene. The hypothesis that ZIP12 is a zinc transporter important for nervous system function and development guided a comparative genetics approach to uncover the presence of ZIP12 in various genomes and identify conserved sequences and expression patterns associated with ZIP12. Ortholog detection of slc39a12 was conducted with reciprocal BLAST hits with the amino acid sequence of human ZIP12 in comparison to the human paralog ZIP4 and conserved local synteny between genomes. ZIP12 is present in the genomes of almost all vertebrates examined, from humans and other mammals to most teleost fish. However, ZIP12 appears to be absent from the zebrafish genome. The discrimination of ZIP12 compared to ZIP4 was unsuccessful or inconclusive in other invertebrate chordates and deuterostomes. Splice variation, due to the inclusion or exclusion of a conserved exon, is present in humans, rats, and cows and likely has biological significance. ZIP12 also possesses many putative di-leucine and tyrosine motifs often associated with intracellular trafficking, which may control cellular zinc uptake activity through the localization of ZIP12 within the cell. These findings highlight multiple aspects of ZIP12 at the biochemical, cellular, and physiological levels with likely biological significance. ZIP12 appears to have conserved function as a zinc uptake transporter in vertebrate nervous system development. Consequently, the role of ZIP12 may be an important link to reported congenital malformations in numerous animal models and humans that are caused by zinc deficiency. PMID:25375179

  1. Tissue-Specific Induction of Mouse ZIP8 and ZIP14 Divalent Cation/Bicarbonate Symporters by, and Cytokine Response to, Inflammatory Signals

    PubMed Central

    Gálvez-Peralta, Marina; Wang, Zhifang; Bao, Shengying; Knoell, Daren L; Nebert, Daniel W

    2014-01-01

    Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are ubiquitous divalent cation/(HCO3−)2 symporters responsible for uptake of Zn2+, Fe2+ and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a single protein, Slc39a14 has two exons 4 which, via alternative splicing, give rise to ZIP14A and ZIP14B; why differences exist in cell-type-specific expression of ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with ZIP8 and ZIP14 up-regulation, but a systematic study of many tissues simultaneously in a laboratory animal following inflammatory cytokine exposure has not yet been reported. Herein we show that C57BL/6J male mice—treated intraperitoneally with lipopolysaccharide (LPS), or the proinflammatory cytokines tumor necrosis factor (TNF) or interleukin-6 (IL6)—exhibited quantatively very different, highly tissue-specific, and markedly time-dependent up- and down-regulation of ZIP8, ZIP14A and ZIP14B mRNA levels in twelve tissues. Magnitude of the inflammatory response was confirmed by measuring the proinflammatory cytokine TNF, IL6 and interleukin-1β (IL1B) mRNA levels in the same tissues of these animals. Our data suggest that most if not all tissues use ZIP8, ZIP14A and/or ZIP14B) for Zn2+ uptake, some tissues under basal conditions and others moreso when inflammatory stressors are present; collectively, this might lead to substantial alterations in plasma Zn2+ levels, due to Zn2+ redistribution not just in liver, but across many vital organs. In the context of cadmium-mediated toxicity, our data suggest that tissues other than liver, kidney and lung should also be considered. PMID:24728862

  2. The role of ZIP transporters and group F bZIP transcription factors in the Zn-deficiency response of wheat (Triticum aestivum).

    PubMed

    Evens, Nicholas P; Buchner, Peter; Williams, Lorraine E; Hawkesford, Malcolm J

    2017-10-01

    Understanding the molecular basis of zinc (Zn) uptake and transport in staple cereal crops is critical for improving both Zn content and tolerance to low-Zn soils. This study demonstrates the importance of group F bZIP transcription factors and ZIP transporters in responses to Zn deficiency in wheat (Triticum aestivum). Seven group F TabZIP genes and 14 ZIPs with homeologs were identified in hexaploid wheat. Promoter analysis revealed the presence of Zn-deficiency-response elements (ZDREs) in a number of the ZIPs. Functional complementation of the zrt1/zrt2 yeast mutant by TaZIP3, -6, -7, -9 and -13 supported an ability to transport Zn. Group F TabZIPs contain the group-defining cysteine-histidine-rich motifs, which are the predicted binding site of Zn 2+ in the Zn-deficiency response. Conservation of these motifs varied between the TabZIPs suggesting that individual TabZIPs may have specific roles in the wheat Zn-homeostatic network. Increased expression in response to low Zn levels was observed for several of the wheat ZIPs and bZIPs; this varied temporally and spatially suggesting specific functions in the response mechanism. The ability of the group F TabZIPs to bind to specific ZDREs in the promoters of TaZIPs indicates a conserved mechanism in monocots and dicots in responding to Zn deficiency. In support of this, TabZIPF1-7DL and TabZIPF4-7AL afforded a strong level of rescue to the Arabidopsis hypersensitive bzip19 bzip23 double mutant under Zn deficiency. These results provide a greater understanding of Zn-homeostatic mechanisms in wheat, demonstrating an expanded repertoire of group F bZIP transcription factors, adding to the complexity of Zn homeostasis. © 2017 The Authors The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.

  3. Selective inhibition of c-Myc/Max dimerization and DNA binding by small molecules.

    PubMed

    Kiessling, Anke; Sperl, Bianca; Hollis, Angela; Eick, Dirk; Berg, Thorsten

    2006-07-01

    bZip and bHLHZip protein family members comprise a large fraction of eukaryotic transcription factors and need to bind DNA in order to exert most of their fundamental biological roles. Their binding to DNA requires homo- or heterodimerization via alpha-helical domains, which generally do not contain obvious binding sites for small molecules. We have identified two small molecules, dubbed Mycro1 and Mycro2, which inhibit the protein-protein interactions between the bHLHZip proteins c-Myc and Max. Mycros are the first inhibitors of c-Myc/Max dimerization, which have been demonstrated to inhibit DNA binding of c-Myc with preference over other dimeric transcription factors in vitro. Mycros inhibit c-Myc-dependent proliferation, gene transcription, and oncogenic transformation in the low micromolar concentration range. Our data support the idea that dimeric transcription factors can be druggable even in the absence of obvious small-molecule binding pockets.

  4. Interplay of HD-Zip II and III transcription factors in auxin-regulated plant development.

    PubMed

    Turchi, L; Baima, S; Morelli, G; Ruberti, I

    2015-08-01

    The homeodomain-leucine zipper (HD-Zip) class of transcription factors is unique to plants. HD-Zip proteins bind to DNA exclusively as dimers recognizing dyad symmetric sequences and act as positive or negative regulators of gene expression. On the basis of sequence homology in the HD-Zip DNA-binding domain, HD-Zip proteins have been grouped into four families (HD-Zip I-IV). Each HD-Zip family can be further divided into subfamilies containing paralogous genes that have arisen through genome duplication. Remarkably, all the members of the HD-Zip IIγ and -δ clades are regulated by light quality changes that induce in the majority of the angiosperms the shade-avoidance response, a process regulated at multiple levels by auxin. Intriguingly, it has recently emerged that, apart from their function in shade avoidance, the HD-Zip IIγ and -δ transcription factors control several auxin-regulated developmental processes, including apical embryo patterning, lateral organ polarity, and gynoecium development, in a white-light environment. This review presents recent advances in our understanding of HD-Zip II protein function in plant development, with particular emphasis on the impact of loss-of-function HD-Zip II mutations on auxin distribution and response. The review also describes evidence demonstrating that HD-Zip IIγ and -δ genes are directly and positively regulated by HD-Zip III transcription factors, primary determinants of apical shoot development, known to control the expression of several auxin biosynthesis, transport, and response genes. Finally, the interplay between HD-Zip II and III transcription factors in embryo apical patterning and organ polarity is discussed. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Isolation and expression analysis of EcbZIP17 from different finger millet genotypes shows conserved nature of the gene.

    PubMed

    Chopperla, Ramakrishna; Singh, Sonam; Mohanty, Sasmita; Reddy, Nanja; Padaria, Jasdeep C; Solanke, Amolkumar U

    2017-10-01

    Basic leucine zipper (bZIP) transcription factors comprise one of the largest gene families in plants. They play a key role in almost every aspect of plant growth and development and also in biotic and abiotic stress tolerance. In this study, we report isolation and characterization of EcbZIP17 , a group B bZIP transcription factor from a climate smart cereal, finger millet ( Eleusine coracana L.). The genomic sequence of EcbZIP17 is 2662 bp long encompassing two exons and one intron with ORF of 1722 bp and peptide length of 573 aa. This gene is homologous to AtbZIP17 ( Arabidopsis ), ZmbZIP17 (maize) and OsbZIP60 (rice) which play a key role in endoplasmic reticulum (ER) stress pathway. In silico analysis confirmed the presence of basic leucine zipper (bZIP) and transmembrane (TM) domains in the EcbZIP17 protein. Allele mining of this gene in 16 different genotypes by Sanger sequencing revealed no variation in nucleotide sequence, including the 618 bp long intron. Expression analysis of EcbZIP17 under heat stress exhibited similar pattern of expression in all the genotypes across time intervals with highest upregulation after 4 h. The present study established the conserved nature of EcbZIP17 at nucleotide and expression level.

  6. Evolutionary and Expression Analyses of the Apple Basic Leucine Zipper Transcription Factor Family

    PubMed Central

    Zhao, Jiao; Guo, Rongrong; Guo, Chunlei; Hou, Hongmin; Wang, Xiping; Gao, Hua

    2016-01-01

    Transcription factors (TFs) play essential roles in the regulatory networks controlling many developmental processes in plants. Members of the basic leucine (Leu) zipper (bZIP) TF family, which is unique to eukaryotes, are involved in regulating diverse processes, including flower and vascular development, seed maturation, stress signaling, and defense responses to pathogens. The bZIP proteins have a characteristic bZIP domain composed of a DNA-binding basic region and a Leu zipper dimerization region. In this study, we identified 112 apple (Malus domestica Borkh) bZIP TF-encoding genes, termed MdbZIP genes. Synteny analysis indicated that segmental and tandem duplication events, as well as whole genome duplication, have contributed to the expansion of the apple bZIP family. The family could be divided into 11 groups based on structural features of the encoded proteins, as well as on the phylogenetic relationship of the apple bZIP proteins to those of the model plant Arabidopsis thaliana (AtbZIP genes). Synteny analysis revealed that several paired MdbZIP genes and AtbZIP gene homologs were located in syntenic genomic regions. Furthermore, expression analyses of group A MdbZIP genes showed distinct expression levels in 10 different organs. Moreover, changes in these expression profiles in response to abiotic stress conditions and various hormone treatments identified MdbZIP genes that were responsive to high salinity and drought, as well as to different phytohormones. PMID:27066030

  7. Evolutionary and Expression Analyses of the Apple Basic Leucine Zipper Transcription Factor Family.

    PubMed

    Zhao, Jiao; Guo, Rongrong; Guo, Chunlei; Hou, Hongmin; Wang, Xiping; Gao, Hua

    2016-01-01

    Transcription factors (TFs) play essential roles in the regulatory networks controlling many developmental processes in plants. Members of the basic leucine (Leu) zipper (bZIP) TF family, which is unique to eukaryotes, are involved in regulating diverse processes, including flower and vascular development, seed maturation, stress signaling, and defense responses to pathogens. The bZIP proteins have a characteristic bZIP domain composed of a DNA-binding basic region and a Leu zipper dimerization region. In this study, we identified 112 apple (Malus domestica Borkh) bZIP TF-encoding genes, termed MdbZIP genes. Synteny analysis indicated that segmental and tandem duplication events, as well as whole genome duplication, have contributed to the expansion of the apple bZIP family. The family could be divided into 11 groups based on structural features of the encoded proteins, as well as on the phylogenetic relationship of the apple bZIP proteins to those of the model plant Arabidopsis thaliana (AtbZIP genes). Synteny analysis revealed that several paired MdbZIP genes and AtbZIP gene homologs were located in syntenic genomic regions. Furthermore, expression analyses of group A MdbZIP genes showed distinct expression levels in 10 different organs. Moreover, changes in these expression profiles in response to abiotic stress conditions and various hormone treatments identified MdbZIP genes that were responsive to high salinity and drought, as well as to different phytohormones.

  8. Bioinformatic Analyses of Subgroup-A Members of the Wheat bZIP Transcription Factor Family and Functional Identification of TabZIP174 Involved in Drought Stress Response

    PubMed Central

    Li, Xueyin; Feng, Biane; Zhang, Fengjie; Tang, Yimiao; Zhang, Liping; Ma, Lingjian; Zhao, Changping; Gao, Shiqing

    2016-01-01

    Extensive studies in Arabidopsis and rice have demonstrated that Subgroup-A members of the bZIP transcription factor family play important roles in plant responses to multiple abiotic stresses. Although common wheat (Triticum aestivum) is one of the most widely cultivated and consumed food crops in the world, there are limited investigations into Subgroup A of the bZIP family in wheat. In this study, we performed bioinformatic analyses of the 41 Subgroup-A members of the wheat bZIP family. Phylogenetic and conserved motif analyses showed that most of the Subgroup-A bZIP proteins involved in abiotic stress responses of wheat, Arabidopsis, and rice clustered in Clade A1 of the phylogenetic tree, and shared a majority of conserved motifs, suggesting the potential importance of Clade-A1 members in abiotic stress responses. Gene structure analysis showed that TabZIP genes with close phylogenetic relationships tended to possess similar exon–intron compositions, and the positions of introns in the hinge regions of the bZIP domains were highly conserved, whereas introns in the leucine zipper regions were at variable positions. Additionally, eleven groups of homologs and two groups of tandem paralogs were also identified in Subgroup A of the wheat bZIP family. Expression profiling analysis indicated that most Subgroup-A TabZIP genes were responsive to abscisic acid and various abiotic stress treatments. TabZIP27, TabZIP74, TabZIP138, and TabZIP174 proteins were localized in the nucleus of wheat protoplasts, whereas TabZIP9-GFP fusion protein was simultaneously present in the nucleus, cytoplasm, and cell membrane. Transgenic Arabidopsis overexpressing TabZIP174 displayed increased seed germination rates and primary root lengths under drought treatments. Overexpression of TabZIP174 in transgenic Arabidopsis conferred enhanced drought tolerance, and transgenic plants exhibited lower water loss rates, higher survival rates, higher proline, soluble sugar, and leaf chlorophyll contents, as well as more stable osmotic potential under drought conditions. Additionally, overexpression of TabZIP174 increased the expression of stress-responsive genes (RD29A, RD29B, RAB18, DREB2A, COR15A, and COR47). The improved drought resistance might be attributed to the increased osmotic adjustment capacity. Our results indicate that TabZIP174 may participate in regulating plant response to drought stress and holds great potential for genetic improvement of abiotic stress tolerance in crops. PMID:27899926

  9. Characteristics of flash initiations in a supercell cluster with tornadoes

    NASA Astrophysics Data System (ADS)

    Zheng, Dong; MacGorman, Donald R.

    2016-01-01

    Flash initiations within a supercell cluster during 10-11 May 2010 in Oklahoma were investigated based on observations from the Oklahoma Lightning Mapping Array and the Norman, Oklahoma, polarimetric radar (KOUN). The flash initiations at positions dominated by graupel, dry snow, small hail and crystals accounted for 44.3%, 44.1%, 8.0% and 3.0% of the total flashes, respectively. During the tornadic stage of the southern supercell in the cluster, flash initiations associated with graupel occupied the main body, the right flank and the forward flank of the supercell, while those associated with dry snow dominated the outskirts of the adjacent forward anvil, right anvil and rear anvil. The flash initiations associated with small hail were concentrated around the main updraft, particularly toward its front side. Highly dense flash initiations were located in the regions overlying the differential reflectivity (ZDR) arc and right anvil. The average initial height of the flashes decreased gradually from the rear to the front and from the right to the left flanks, while the height range over which initiations occurred reached a maximum at the front of the updraft. The flashes that were initiated in the adjacent forward anvils were largest on average, followed by those in the regions ahead of the updraft and near the ZDR arc. This study supports the concept of charge pockets and further deduces that the pockets in the right anvil are the most abundant and compact due to the frequent flash initiations, small-sized flashes and thin layers including flash initiations.

  10. [Cloning and expression analysis of a zinc-regulated transporters (ZRT), iron-regulated transporter (IRT)-like protein encoding gene in Dendrobium officinale].

    PubMed

    Zhang, Gang; Li, Yi-Min; Li, Biao; Zhang, Da-Wei; Guo, Shun-Xing

    2015-01-01

    The zinc-regulated transporters (ZRT), iron-regulated transporter (IRT)-like protein (ZIP) plays an important role in the growth and development of plant. In this study, a full length cDNA of ZIP encoding gene, designed as DoZIP1 (GenBank accession KJ946203), was identified from Dendrobium officinale using RT-PCR and RACE. Bioinformatics analysis showed that DoZIP1 consisted of a 1,056 bp open reading frame (ORF) encoded a 351-aa protein with a molecular weight of 37.57 kDa and an isoelectric point (pI) of 6.09. The deduced DoZIP1 protein contained the conserved ZIP domain, and its secondary structure was composed of 50.71% alpha helix, 11.11% extended strand, 36.18% random coil, and beta turn 1.99%. DoZIP1 protein exhibited a signal peptide and eight transmembrane domains, presumably locating in cell membrane. The amino acid sequence had high homology with ZIP proteins from Arabidopsis, alfalfa and rice. A phylogenetic tree analysis demonstrated that DoZIP1 was closely related to AtZIP10 and OsZIP3, and they were clustered into one clade. Real time quantitative PCR analysis demonstrated that the transcription level of DoZIP1 in D. officinale roots was the highest (4.19 fold higher than that of stems), followed by that of leaves (1.12 fold). Molecular characters of DoZIP1 will be useful for further functional determination of the gene involving in the growth and development of D. officinale.

  11. ZIP8 expression in human proximal tubule cells, human urothelial cells transformed by Cd+2 and As+3 and in specimens of normal human urothelium and urothelial cancer

    PubMed Central

    2012-01-01

    Background ZIP8 functions endogenously as a Zn+2/HCO3- symporter that can also bring cadmium (Cd+2) into the cell. It has also been proposed that ZIP8 participates in Cd-induced testicular necrosis and renal disease. In this study real-time PCR, western analysis, immunostaining and fluorescent localization were used to define the expression of ZIP8 in human kidney, cultured human proximal tubule (HPT) cells, normal and malignant human urothelium and Cd+2 and arsenite (As+3) transformed urothelial cells. Results It was shown that in the renal system both the non-glycosylated and glycosylated form of ZIP8 was expressed in the proximal tubule cells with localization of ZIP8 to the cytoplasm and cell membrane; findings in line with previous studies on ZIP8. The studies in the bladder were the first to show that ZIP8 was expressed in normal urothelium and that ZIP8 could be localized to the paranuclear region. Studies in the UROtsa cell line confirmed a paranuclear localization of ZIP8, however addition of growth medium to the cells increased the expression of the protein in the UROtsa cells. In archival human samples of the normal urothelium, the expression of ZIP8 was variable in intensity whereas in urothelial cancers ZIP8 was expressed in 13 of 14 samples, with one high grade invasive urothelial cancer showing no expression. The expression of ZIP8 was similar in the Cd+2 and As+3 transformed UROtsa cell lines and their tumor transplants. Conclusion This is the first study which shows that ZIP8 is expressed in the normal urothelium and in bladder cancer. In addition the normal UROtsa cell line and its transformed counterparts show similar expression of ZIP8 compared to the normal urothelium and the urothelial cancers suggesting that the UROtsa cell line could serve as a model system to study the expression of ZIP8 in bladder disease. PMID:22550998

  12. Salt and drought stress and ABA responses related to bZIP genes from V. radiata and V. angularis.

    PubMed

    Wang, Lanfen; Zhu, Jifeng; Li, Xiaoming; Wang, Shumin; Wu, Jing

    2018-04-20

    Mung bean and adzuki bean are warm-season legumes widely cultivated in China. However, bean production in major producing regions is limited by biotic and abiotic stress, such as drought and salt stress. Basic leucine zipper (bZIP) genes play key roles in responses to various biotic and abiotic stresses. However, only several bZIP genes involved in drought and salt stress in legumes, especially Vigna radiata and Vigna angularis, have been identified. In this study, we identified 54 and 50 bZIP proteins from whole-genome sequences of V. radiata and V. angularis, respectively. First, we comprehensively surveyed the characteristics of all bZIP genes, including their gene structure, chromosome distribution and motif composition. Phylogenetic trees showed that VrbZIP and VabZIP proteins were divided into ten clades comprising nine known and one unknown subgroup. The results of the nucleotide substitution rate of the orthologous gene pairs showed that bZIP proteins have undergone strong purifying selection: V. radiata and V. angularis diverged 1.25 million years ago (mya) to 9.20 mya (average of 4.95 mya). We also found that many cis-acting regulatory elements (CAREs) involved in abiotic stress and plant hormone responses were detected in the putative promoter regions of the bZIP genes. Finally, using the quantitative real-time PCR (qRT-PCR) method, we performed expression profiling of the bZIP genes in response to drought, salt and abscisic acid (ABA). We identified several bZIP genes that may be involved in drought and salt responses. Generally, our results provided useful and rich resources of VrbZIP and VabZIP genes for the functional characterization and understanding of bZIP transcription factors (TFs) in warm-season legumes. In addition, our results revealed important and interesting data - a subset of VrbZIP and VabZIP gene expression profiles in response to drought, salt and ABA stress. These results provide gene expression evidence for the selection of candidate genes under drought and salt stress for future study. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Genome-wide analysis of the homeodomain-leucine zipper (HD-ZIP) gene family in peach (Prunus persica).

    PubMed

    Zhang, C H; Ma, R J; Shen, Z J; Sun, X; Korir, N K; Yu, M L

    2014-04-08

    In this study, 33 homeodomain-leucine zipper (HD-ZIP) genes were identified in peach using the HD-ZIP amino acid sequences of Arabidopsis thaliana as a probe. Based on the phylogenetic analysis and the individual gene or protein characteristics, the HD-ZIP gene family in peach can be classified into 4 subfamilies, HD-ZIP I, II, III, and IV, containing 14, 7, 4, and 8 members, respectively. The most closely related peach HD-ZIP members within the same subfamilies shared very similar gene structure in terms of either intron/exon numbers or lengths. Almost all members of the same subfamily shared common motif compositions, thereby implying that the HD-ZIP proteins within the same subfamily may have functional similarity. The 33 peach HD-ZIP genes were distributed across scaffolds 1 to 7. Although the primary structure varied among HD-ZIP family proteins, their tertiary structures were similar. The results from this study will be useful in selecting candidate genes from specific subfamilies for functional analysis.

  14. In vivo binding of hot pepper bZIP transcription factor CabZIP1 to the G-box region of pathogenesis-related protein 1 promoter

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

    Lee, Boo-Ja; Park, Chang-Jin; Kim, Sung-Kyu

    2006-05-26

    We find that salicylic acid and ethephon treatment in hot pepper increases the expression of a putative basic/leucine zipper (bZIP) transcription factor gene, CabZIP1. CabZIP1 mRNA is expressed ubiquitously in various organs. The green fluorescent protein-fused transcription factor, CabZIP1::GFP, can be specifically localized to the nucleus, an action that is consistent with the presence of a nuclear localization signal in its protein sequence. Transient overexpression of the CabZIP1 transcription factor results in an increase in PR-1 transcripts level in Nicotiana benthamiana leaves. Using chromatin immunoprecipitation, we demonstrate that CabZIP1 binds to the G-box elements in native promoter of the hotmore » pepper pathogenesis-related protein 1 (CaPR-1) gene in vivo. Taken together, our results suggest that CabZIP1 plays a role as a transcriptional regulator of the CaPR-1 gene.« less

  15. Characterization of zinc transport by divalent metal transporters of the ZIP family from the model legume medicago truncatula

    USDA-ARS?s Scientific Manuscript database

    To understand how plants from the Fabaceae family maintain zinc (Zn) homeostasis, we have characterized the kinetics of the Zn transporting proteins from the ZIP family of divalent metal transporters in the model legume Medicago truncatula. MtZIP1, MtZIP5, and MtZIP6 were the only members from this ...

  16. Genome-wide analyses of the bZIP family reveal their involvement in the development, ripening and abiotic stress response in banana

    PubMed Central

    Hu, Wei; Wang, Lianzhe; Tie, Weiwei; Yan, Yan; Ding, Zehong; Liu, Juhua; Li, Meiying; Peng, Ming; Xu, Biyu; Jin, Zhiqiang

    2016-01-01

    The leucine zipper (bZIP) transcription factors play important roles in multiple biological processes. However, less information is available regarding the bZIP family in the important fruit crop banana. In this study, 121 bZIP transcription factor genes were identified in the banana genome. Phylogenetic analysis showed that MabZIPs were classified into 11 subfamilies. The majority of MabZIP genes in the same subfamily shared similar gene structures and conserved motifs. The comprehensive transcriptome analysis of two banana genotypes revealed the differential expression patterns of MabZIP genes in different organs, in various stages of fruit development and ripening, and in responses to abiotic stresses, including drought, cold, and salt. Interaction networks and co-expression assays showed that group A MabZIP-mediated networks participated in various stress signaling, which was strongly activated in Musa ABB Pisang Awak. This study provided new insights into the complicated transcriptional control of MabZIP genes and provided robust tissue-specific, development-dependent, and abiotic stress-responsive candidate MabZIP genes for potential applications in the genetic improvement of banana cultivars. PMID:27445085

  17. Functional Analysis of Maize Silk-Specific ZmbZIP25 Promoter.

    PubMed

    Li, Wanying; Yu, Dan; Yu, Jingjuan; Zhu, Dengyun; Zhao, Qian

    2018-03-12

    ZmbZIP25 ( Zea mays bZIP (basic leucine zipper) transcription factor 25) is a function-unknown protein that belongs to the D group of the bZIP transcription factor family. RNA-seq data showed that the expression of ZmbZIP25 was tissue-specific in maize silks, and this specificity was confirmed by RT-PCR (reverse transcription-polymerase chain reaction). In situ RNA hybridization showed that ZmbZIP25 was expressed exclusively in the xylem of maize silks. A 5' RACE (rapid amplification of cDNA ends) assay identified an adenine residue as the transcription start site of the ZmbZIP25 gene. To characterize this silk-specific promoter, we isolated and analyzed a 2450 bp (from -2083 to +367) and a 2600 bp sequence of ZmbZIP25 (from -2083 to +517, the transcription start site was denoted +1). Stable expression assays in Arabidopsis showed that the expression of the reporter gene GUS driven by the 2450 bp ZmbZIP25 5'-flanking fragment occurred exclusively in the papillae of Arabidopsis stigmas. Furthermore, transient expression assays in maize indicated that GUS and GFP expression driven by the 2450 bp ZmbZIP25 5'-flanking sequences occurred only in maize silks and not in other tissues. However, no GUS or GFP expression was driven by the 2600 bp ZmbZIP25 5'-flanking sequences in either stable or transient expression assays. A series of deletion analyses of the 2450 bp ZmbZIP25 5'-flanking sequence was performed in transgenic Arabidopsis plants, and probable elements prediction analysis revealed the possible presence of negative regulatory elements within the 161 bp region from -1117 to -957 that were responsible for the specificity of the ZmbZIP25 5'-flanking sequence.

  18. Functional Analysis of Maize Silk-Specific ZmbZIP25 Promoter

    PubMed Central

    Li, Wanying; Yu, Dan; Yu, Jingjuan; Zhu, Dengyun; Zhao, Qian

    2018-01-01

    ZmbZIP25 (Zea mays bZIP (basic leucine zipper) transcription factor 25) is a function-unknown protein that belongs to the D group of the bZIP transcription factor family. RNA-seq data showed that the expression of ZmbZIP25 was tissue-specific in maize silks, and this specificity was confirmed by RT-PCR (reverse transcription-polymerase chain reaction). In situ RNA hybridization showed that ZmbZIP25 was expressed exclusively in the xylem of maize silks. A 5′ RACE (rapid amplification of cDNA ends) assay identified an adenine residue as the transcription start site of the ZmbZIP25 gene. To characterize this silk-specific promoter, we isolated and analyzed a 2450 bp (from −2083 to +367) and a 2600 bp sequence of ZmbZIP25 (from −2083 to +517, the transcription start site was denoted +1). Stable expression assays in Arabidopsis showed that the expression of the reporter gene GUS driven by the 2450 bp ZmbZIP25 5′-flanking fragment occurred exclusively in the papillae of Arabidopsis stigmas. Furthermore, transient expression assays in maize indicated that GUS and GFP expression driven by the 2450 bp ZmbZIP25 5′-flanking sequences occurred only in maize silks and not in other tissues. However, no GUS or GFP expression was driven by the 2600 bp ZmbZIP25 5′-flanking sequences in either stable or transient expression assays. A series of deletion analyses of the 2450 bp ZmbZIP25 5′-flanking sequence was performed in transgenic Arabidopsis plants, and probable elements prediction analysis revealed the possible presence of negative regulatory elements within the 161 bp region from −1117 to −957 that were responsible for the specificity of the ZmbZIP25 5′-flanking sequence. PMID:29534529

  19. A specific role for the ZipA protein in cell division: stabilization of the FtsZ protein.

    PubMed

    Pazos, Manuel; Natale, Paolo; Vicente, Miguel

    2013-02-01

    In Escherichia coli, the cell division protein FtsZ is anchored to the cytoplasmic membrane by the action of the bitopic membrane protein ZipA and the cytoplasmic protein FtsA. Although the presence of both ZipA and FtsA is strictly indispensable for cell division, an FtsA gain-of-function mutant FtsA* (R286W) can bypass the ZipA requirement for cell division. This observation casts doubts on the role of ZipA and its need for cell division. Maxicells are nucleoid-free bacterial cells used as a whole cell in vitro system to probe protein-protein interactions without the need of protein purification. We show that ZipA protects FtsZ from the ClpXP-directed degradation observed in E. coli maxicells and that ZipA-stabilized FtsZ forms membrane-attached spiral-like structures in the bacterial cytoplasm. The overproduction of the FtsZ-binding ZipA domain is sufficient to protect FtsZ from degradation, whereas other C-terminal ZipA partial deletions lacking it are not. Individual overproduction of the proto-ring component FtsA or its gain-of-function mutant FtsA* does not result in FtsZ protection. Overproduction of FtsA or FtsA* together with ZipA does not interfere with the FtsZ protection. Moreover, neither FtsA nor FtsA* protects FtsZ when overproduced together with ZipA mutants lacking the FZB domain. We propose that ZipA protects FtsZ from degradation by ClpP by making the FtsZ site of interaction unavailable to the ClpX moiety of the ClpXP protease. This role cannot be replaced by either FtsA or FtsA*, suggesting a unique function for ZipA in proto-ring stability.

  20. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response

    PubMed Central

    Liuzzi, Juan P.; Lichten, Louis A.; Rivera, Seth; Blanchard, Raymond K.; Aydemir, Tolunay Beker; Knutson, Mitchell D.; Ganz, Tomas; Cousins, Robert J.

    2005-01-01

    Infection and inflammation produce systemic responses that include hypozincemia and hypoferremia. The latter involves regulation of the iron transporter ferroportin 1 by hepcidin. The mechanism of reduced plasma zinc is not known. Transcripts of the two zinc transporter gene families (ZnT and Zip) were screened for regulation in mouse liver after turpentine-induced inflammation and LPS administration. Zip14 mRNA was the transporter transcript most up-regulated by inflammation and LPS. IL-6 knockout (IL-6–/–) mice did not exhibit either hypozincemia or the induction of Zip14 with turpentine inflammation. However, in IL-6–/– mice, LPS produced a milder hypozincemic response but no Zip14 induction. Northern analysis showed Zip14 up-regulation was specific for the liver, with one major transcript. Immunohistochemistry, using an antibody to an extracellular Zip14 epitope, showed both LPS and turpentine increased abundance of Zip14 at the plasma membrane of hepatocytes. IL-6 produced increased expression of Zip14 in primary hepatocytes cultures and localization of the protein to the plasma membrane. Transfection of mZip14 cDNA into human embryonic kidney cells increased zinc uptake as measured by both a fluorescent probe for free Zn2+ and 65Zn accumulation, as well as by metallothionein mRNA induction, all indicating that Zip14 functions as a zinc importer. Zip14 was localized in plasma membrane of the transfected cells. These in vivo and in vitro experiments demonstrate that Zip14 expression is up-regulated through IL-6, and that this zinc transporter most likely plays a major role in the mechanism responsible for hypozincemia that accompanies the acute-phase response to inflammation and infection. PMID:15863613

  1. Functional analysis RaZIP1 transporter of the ZIP family from the ectomycorrhizal Zn-accumulating Russula atropurpurea.

    PubMed

    Leonhardt, Tereza; Sácký, Jan; Kotrba, Pavel

    2018-04-01

    A search of R. atropurpurea transcriptome for sequences encoding the transporters of the Zrt-, Irt-like Protein (ZIP) family, which are in eukaryotes integral to Zn supply into cytoplasm, allowed the identification of RaZIP1 cDNA with a predicted product belonging to ZIP I subfamily; it was subjected to functional studies in mutant Saccharomyces cerevisiae strains. The expression of RaZIP1, but not RaZIP1 H208A or RaZIP1 H232A mutants lacking conserved-among-ZIPs transmembrane histidyls, complemented Zn uptake deficiency in zrt1Δzrt2Δ yeasts. RaZIP1 substantially increased cellular Zn uptake in this strain and added to Zn sensitivity in zrc1Δcot1Δ mutant. The Fe uptake deficiency in ftr1Δ strain was not rescued and Mn uptake was insufficient for toxicity in Mn-sensitive pmr1Δ yeasts. By contrast, RaZIP1 increased Cd sensitivity in yap1Δ strain and conferred Cd transport activity in yeasts, albeit with substantially lower efficiency compared to Zn transport. In metal uptake assays, the accumulation of Zn in zrt1Δzrt2Δ strain remained unaffected by Cd, Fe, and Mn present in 20-fold molar excess over Zn. Immunofluorescence microscopy detected functional hemagglutinin-tagged HA::RaZIP1 on the yeast cell protoplast periphery. Altogether, these data indicate that RaZIP1 is a high-affinity plasma membrane transporter specialized in Zn uptake, and improve the understanding of the cellular and molecular biology of Zn in R. atropurpurea that is known for its ability to accumulate remarkably high concentrations of Zn.

  2. Expression Profile Analysis of Zinc Transporters (ZIP4, ZIP9, ZIP11, ZnT9) in Gliomas and their Correlation with IDH1 Mutation Status.

    PubMed

    Kang, Xing; Chen, Rong; Zhang, Jie; Li, Gang; Dai, Peng-Gao; Chen, Chao; Wang, Hui-Juan

    2015-01-01

    Zinc transporters have been considered as essential regulators in many cancers; however, their mechanisms remain unknown, especially in gliomas. Isocitrate dehydrogenase 1(IDH1) mutation is crucial to glioma. This study aimed to investigate whether zinc transporters are correlated with glioma grade and IDH1 mutation status. IDH1 mutation status and mRNA expression of four zinc transporters (ZIP4, ZIP9, ZIP11, and ZnT9) were determined by subjecting a panel of 74 glioma tissue samples to quantitative real-time PCR and pyrosequencing. The correlations between the expression levels of these zinc transporter genes and the grade of glioma, as well as IDH1 mutation status, were investigated. Among the four zinc transporter genes, high ZIP4 expression and low ZIP11 expression were significantly associated with higher grade (grades III and IV) tumors compared with lower grade (grades I and II) counterparts (p<0.0001). However, only ZIP11 exhibited weak correlation with IDH1 mutation status (p=0.045). Samples with mutations in IDH1 displayed higher ZIP11 expression than those without IDH1 mutations. This finding indicated that zinc transporters may interact with IDH1 mutation by direct modulation or action in some shared pathways or genes to promote the development of glioma. Zinc transporters may play an important role in glioma. ZIP4 and ZIP11 are promising molecular diagnostic markers and novel therapeutic targets. Nevertheless, the detailed biological function of zinc transporters and the mechanism of the potential interaction between ZIP11 and IDH1 mutation in gliomagenesis should be further investigated.

  3. Genome-wide analysis and expression profile of the bZIP transcription factor gene family in grapevine (Vitis vinifera)

    PubMed Central

    2014-01-01

    Background Basic leucine zipper (bZIP) transcription factor gene family is one of the largest and most diverse families in plants. Current studies have shown that the bZIP proteins regulate numerous growth and developmental processes and biotic and abiotic stress responses. Nonetheless, knowledge concerning the specific expression patterns and evolutionary history of plant bZIP family members remains very limited. Results We identified 55 bZIP transcription factor-encoding genes in the grapevine (Vitis vinifera) genome, and divided them into 10 groups according to the phylogenetic relationship with those in Arabidopsis. The chromosome distribution and the collinearity analyses suggest that expansion of the grapevine bZIP (VvbZIP) transcription factor family was greatly contributed by the segment/chromosomal duplications, which may be associated with the grapevine genome fusion events. Nine intron/exon structural patterns within the bZIP domain and the additional conserved motifs were identified among all VvbZIP proteins, and showed a high group-specificity. The predicted specificities on DNA-binding domains indicated that some highly conserved amino acid residues exist across each major group in the tree of land plant life. The expression patterns of VvbZIP genes across the grapevine gene expression atlas, based on microarray technology, suggest that VvbZIP genes are involved in grapevine organ development, especially seed development. Expression analysis based on qRT-PCR indicated that VvbZIP genes are extensively involved in drought- and heat-responses, with possibly different mechanisms. Conclusions The genome-wide identification, chromosome organization, gene structures, evolutionary and expression analyses of grapevine bZIP genes provide an overall insight of this gene family and their potential involvement in growth, development and stress responses. This will facilitate further research on the bZIP gene family regarding their evolutionary history and biological functions. PMID:24725365

  4. Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters

    PubMed Central

    Schmitt-Ulms, Gerold; Ehsani, Sepehr; Watts, Joel C.; Westaway, David; Wille, Holger

    2009-01-01

    In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transporters of the ZIP family, ZIP6 and ZIP10, to mammalian prion proteins in vivo. A subsequent bioinformatic analysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species place the split from the ZIP-like ancestor gene at the base of the chordate lineage. This relationship explains structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The phylogenetic and spatial connection to ZIP proteins is expected to open new avenues of research to elucidate the biology of the prion protein in health and disease. PMID:19784368

  5. Design of a Novel Low Cost Point of Care Tampon (POCkeT) Colposcope for Use in Resource Limited Settings

    PubMed Central

    Lam, Christopher T.; Krieger, Marlee S.; Gallagher, Jennifer E.; Asma, Betsy; Muasher, Lisa C.; Schmitt, John W.; Ramanujam, Nimmi

    2015-01-01

    Introduction Current guidelines by WHO for cervical cancer screening in low- and middle-income countries involves visual inspection with acetic acid (VIA) of the cervix, followed by treatment during the same visit or a subsequent visit with cryotherapy if a suspicious lesion is found. Implementation of these guidelines is hampered by a lack of: trained health workers, reliable technology, and access to screening facilities. A low cost ultra-portable Point of Care Tampon based digital colposcope (POCkeT Colposcope) for use at the community level setting, which has the unique form factor of a tampon, can be inserted into the vagina to capture images of the cervix, which are on par with that of a state of the art colposcope, at a fraction of the cost. A repository of images to be compiled that can be used to empower front line workers to become more effective through virtual dynamic training. By task shifting to the community setting, this technology could potentially provide significantly greater cervical screening access to where the most vulnerable women live. The POCkeT Colposcope’s concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes. Evaluation with standard optical imaging targets to assess the POCkeT Colposcope against the state of the art digital colposcope and other VIAM technologies. Results Our POCkeT Colposcope has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our POCkeT Colposcope capturing comparable quality images to commercial systems. Conclusion The POCkeT Colposcope is capable of capturing images suitable for cervical lesion analysis. Our portable low cost system could potentially increase access to cervical cancer screening in limited resource settings through task shifting to community health workers. PMID:26332673

  6. The Zinc Transporter Zip5 (Slc39a5) Regulates Intestinal Zinc Excretion and Protects the Pancreas against Zinc Toxicity

    PubMed Central

    Geiser, Jim; De Lisle, Robert C.; Andrews, Glen K.

    2013-01-01

    Background ZIP5 localizes to the baso-lateral membranes of intestinal enterocytes and pancreatic acinar cells and is internalized and degraded coordinately in these cell-types during periods of dietary zinc deficiency. These cell-types are thought to control zinc excretion from the body. The baso-lateral localization and zinc-regulation of ZIP5 in these cells are unique among the 14 members of the Slc39a family and suggest that ZIP5 plays a role in zinc excretion. Methods/Principal Findings We created mice with floxed Zip5 genes and deleted this gene in the entire mouse or specifically in enterocytes or acinar cells and then examined the effects on zinc homeostasis. We found that ZIP5 is not essential for growth and viability but total knockout of ZIP5 led to increased zinc in the liver in mice fed a zinc-adequate (ZnA) diet but impaired accumulation of pancreatic zinc in mice fed a zinc-excess (ZnE) diet. Loss-of-function of enterocyte ZIP5, in contrast, led to increased pancreatic zinc in mice fed a ZnA diet and increased abundance of intestinal Zip4 mRNA. Finally, loss-of-function of acinar cell ZIP5 modestly reduced pancreatic zinc in mice fed a ZnA diet but did not impair zinc uptake as measured by the rapid accumulation of 67zinc. Retention of pancreatic 67zinc was impaired in these mice but the absence of pancreatic ZIP5 sensitized them to zinc-induced pancreatitis and exacerbated the formation of large cytoplasmic vacuoles containing secretory protein in acinar cells. Conclusions These studies demonstrate that ZIP5 participates in the control of zinc excretion in mice. Specifically, they reveal a paramount function of intestinal ZIP5 in zinc excretion but suggest a role for pancreatic ZIP5 in zinc accumulation/retention in acinar cells. ZIP5 functions in acinar cells to protect against zinc-induced acute pancreatitis and attenuate the process of zymophagy. This suggests that it may play a role in autophagy. PMID:24303081

  7. High affinity receptor labeling based on basic leucine zipper domain peptides conjugated with pH-sensitive fluorescent dye: Visualization of AMPA-type glutamate receptor endocytosis in living neurons.

    PubMed

    Hayashi, Ayako; Asanuma, Daisuke; Kamiya, Mako; Urano, Yasuteru; Okabe, Shigeo

    2016-01-01

    Techniques to visualize receptor trafficking in living neurons are important, but currently available methods are limited in their labeling efficiency, specificity and reliability. Here we report a method for receptor labeling with a basic leucine zipper domain peptide (ZIP) and a binding cassette specific to ZIP. Receptors are tagged with a ZIP-binding cassette at their extracellular domain. Tagged receptors expressed in cultured cells were labeled with exogenously applied fluorescently labeled ZIP with low background and high affinity. To test if ZIP labeling is useful in monitoring endocytosis and intracellular trafficking, we next conjugated ZIP with a pH-sensitive dye RhP-M (ZIP-RhP-M). ZIP binding to its binding cassette was pH-resistant and RhP-M fluorescence dramatically increased in acidic environment. Thus AMPA-type glutamate receptors (AMPARs) labeled by ZIP-RhP-M can report receptor endocytosis and subsequent intracellular trafficking. Application of ZIP-RhP-M to cultured hippocampal neurons expressing AMPARs tagged with a ZIP-binding cassette resulted in appearance of fluorescent puncta in PSD-95-positive large spines, suggesting local endocytosis and acidification of AMPARs in individual mature spines. This spine pool of AMPARs in acidic environment was distinct from the early endosomes labeled by transferrin uptake. These results suggest that receptor labeling by ZIP-RhP-M is a useful technique for monitoring endocytosis and intracellular trafficking. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. A Novel Wheat C-bZIP Gene, TabZIP14-B, Participates in Salt and Freezing Tolerance in Transgenic Plants

    PubMed Central

    Zhang, Lina; Zhang, Lichao; Xia, Chuan; Gao, Lifeng; Hao, Chenyang; Zhao, Guangyao; Jia, Jizeng; Kong, Xiuying

    2017-01-01

    The group C-bZIP transcription factors (TFs) are involved in diverse biological processes, such as the regulation of seed storage protein (SSP) production and the responses to pathogen challenge and abiotic stress. However, our knowledge of the abiotic functions of group C-bZIP genes in wheat remains limited. Here, we present the function of a novel TabZIP14-B gene in wheat. This gene belongs to the group C-bZIP TFs and contains six exons and five introns; three haplotypes were identified among accessions of tetraploid and hexaploid wheat. A subcellular localization analysis indicated that TabZIP14-B was targeted to the nucleus of tobacco epidermal cells. A transactivation assay demonstrated that TabZIP14-B showed transcriptional activation ability and was capable of binding the abscisic acid (ABA) responsive element (ABRE) in yeast. RT-qPCR revealed that TabZIP14-B was expressed in the roots, stems, leaves, and young spikes and was up-regulated by exogenous ABA, salt, low-temperature, and polyethylene glycol (PEG) stress treatments. Furthermore, Arabidopsis plants overexpressing TabZIP14-B exhibited enhanced tolerance to salt, freezing stresses and ABA sensitivity. Overexpression of TabZIP14-B resulted in increased expression of the AtRD29A, AtCOR47, AtRD20, AtGSTF6, and AtRAB18 genes and changes in several physiological characteristics. These results suggest that TabZIP14-B could function as a positive regulator in mediating the abiotic stress response. PMID:28536588

  9. 39 CFR Appendix A to Part 121 - Tables Depicting Service Standard Day Ranges

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (Days) Alaska Hawaii, Guam, & American Samoa Puerto Rico & USVI Periodicals 1 1-3 1 1-3 1-4 (AK)11 (JNU... 2-3 12 11 11 AK = Alaska 3-digit ZIP Codes 995-997; JNU = Juneau AK 3-digit ZIP Code 998; KTN = Ketchikan AK 3-digit ZIP Code 999; HI = Hawaii 3-digit ZIP Codes 967 and 968; GU = Guam 3-digit ZIP Code 969...

  10. N-terminal segments modulate the α-helical propensities of the intrinsically disordered basic regions of bZIP proteins.

    PubMed

    Das, Rahul K; Crick, Scott L; Pappu, Rohit V

    2012-02-17

    Basic region leucine zippers (bZIPs) are modular transcription factors that play key roles in eukaryotic gene regulation. The basic regions of bZIPs (bZIP-bRs) are necessary and sufficient for DNA binding and specificity. Bioinformatic predictions and spectroscopic studies suggest that unbound monomeric bZIP-bRs are uniformly disordered as isolated domains. Here, we test this assumption through a comparative characterization of conformational ensembles for 15 different bZIP-bRs using a combination of atomistic simulations and circular dichroism measurements. We find that bZIP-bRs have quantifiable preferences for α-helical conformations in their unbound monomeric forms. This helicity varies from one bZIP-bR to another despite a significant sequence similarity of the DNA binding motifs (DBMs). Our analysis reveals that intramolecular interactions between DBMs and eight-residue segments directly N-terminal to DBMs are the primary modulators of bZIP-bR helicities. We test the accuracy of this inference by designing chimeras of bZIP-bRs to have either increased or decreased overall helicities. Our results yield quantitative insights regarding the relationship between sequence and the degree of intrinsic disorder within bZIP-bRs, and might have general implications for other intrinsically disordered proteins. Understanding how natural sequence variations lead to modulation of disorder is likely to be important for understanding the evolution of specificity in molecular recognition through intrinsically disordered regions (IDRs). Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Feedback Regulation of ABA Signaling and Biosynthesis by a bZIP Transcription Factor Targets Drought-Resistance-Related Genes1[OPEN

    PubMed Central

    Tang, Ning; Yang, Jun; Peng, Lei; Ma, Siqi; Xu, Yan; Li, Guoliang

    2016-01-01

    The OsbZIP23 transcription factor has been characterized for its essential role in drought resistance in rice (Oryza sativa), but the mechanism is unknown. In this study, we first investigated the transcriptional activation of OsbZIP23. A homolog of SnRK2 protein kinase (SAPK2) was found to interact with and phosphorylate OsbZIP23 for its transcriptional activation. SAPK2 also interacted with OsPP2C49, an ABI1 homolog, which deactivated the SAPK2 to inhibit the transcriptional activation activity of OsbZIP23. Next, we performed genome-wide identification of OsbZIP23 targets by immunoprecipitation sequencing and RNA sequencing analyses in the OsbZIP23-overexpression, osbzip23 mutant, and wild-type rice under normal and drought stress conditions. OsbZIP23 directly regulates a large number of reported genes that function in stress response, hormone signaling, and developmental processes. Among these targets, we found that OsbZIP23 could positively regulate OsPP2C49, and overexpression of OsPP2C49 in rice resulted in significantly decreased sensitivity of the abscisic acid (ABA) response and rapid dehydration. Moreover, OsNCED4 (9-cis-epoxycarotenoid dioxygenase4), a key gene in ABA biosynthesis, was also positively regulated by OsbZIP23. Together, our results suggest that OsbZIP23 acts as a central regulator in ABA signaling and biosynthesis, and drought resistance in rice. PMID:27325665

  12. Genome-Wide Analysis of bZIP-Encoding Genes in Maize

    PubMed Central

    Wei, Kaifa; Chen, Juan; Wang, Yanmei; Chen, Yanhui; Chen, Shaoxiang; Lin, Yina; Pan, Si; Zhong, Xiaojun; Xie, Daoxin

    2012-01-01

    In plants, basic leucine zipper (bZIP) proteins regulate numerous biological processes such as seed maturation, flower and vascular development, stress signalling and pathogen defence. We have carried out a genome-wide identification and analysis of 125 bZIP genes that exist in the maize genome, encoding 170 distinct bZIP proteins. This family can be divided into 11 groups according to the phylogenetic relationship among the maize bZIP proteins and those in Arabidopsis and rice. Six kinds of intron patterns (a–f) within the basic and hinge regions are defined. The additional conserved motifs have been identified and present the group specificity. Detailed three-dimensional structure analysis has been done to display the sequence conservation and potential distribution of the bZIP domain. Further, we predict the DNA-binding pattern and the dimerization property on the basis of the characteristic features in the basic and hinge regions and the leucine zipper, respectively, which supports our classification greatly and helps to classify 26 distinct subfamilies. The chromosome distribution and the genetic analysis reveal that 58 ZmbZIP genes are located in the segmental duplicate regions in the maize genome, suggesting that the segment chromosomal duplications contribute greatly to the expansion of the maize bZIP family. Across the 60 different developmental stages of 11 organs, three apparent clusters formed represent three kinds of different expression patterns among the ZmbZIP gene family in maize development. A similar but slightly different expression pattern of bZIPs in two inbred lines displays that 22 detected ZmbZIP genes might be involved in drought stress. Thirteen pairs and 143 pairs of ZmbZIP genes show strongly negative and positive correlations in the four distinct fungal infections, respectively, based on the expression profile and Pearson's correlation coefficient analysis. PMID:23103471

  13. Systematic Analysis of Sequences and Expression Patterns of Drought-Responsive Members of the HD-Zip Gene Family in Maize

    PubMed Central

    Zhao, Yang; Zhou, Yuqiong; Jiang, Haiyang; Li, Xiaoyu; Gan, Defang; Peng, Xiaojian; Zhu, Suwen; Cheng, Beijiu

    2011-01-01

    Background Members of the homeodomain-leucine zipper (HD-Zip) gene family encode transcription factors that are unique to plants and have diverse functions in plant growth and development such as various stress responses, organ formation and vascular development. Although systematic characterization of this family has been carried out in Arabidopsis and rice, little is known about HD-Zip genes in maize (Zea mays L.). Methods and Findings In this study, we described the identification and structural characterization of HD-Zip genes in the maize genome. A complete set of 55 HD-Zip genes (Zmhdz1-55) were identified in the maize genome using Blast search tools and categorized into four classes (HD-Zip I-IV) based on phylogeny. Chromosomal location of these genes revealed that they are distributed unevenly across all 10 chromosomes. Segmental duplication contributed largely to the expansion of the maize HD-ZIP gene family, while tandem duplication was only responsible for the amplification of the HD-Zip II genes. Furthermore, most of the maize HD-Zip I genes were found to contain an overabundance of stress-related cis-elements in their promoter sequences. The expression levels of the 17 HD-Zip I genes under drought stress were also investigated by quantitative real-time PCR (qRT-PCR). All of the 17 maize HD-ZIP I genes were found to be regulated by drought stress, and the duplicated genes within a sister pair exhibited the similar expression patterns, suggesting their conserved functions during the process of evolution. Conclusions Our results reveal a comprehensive overview of the maize HD-Zip gene family and provide the first step towards the selection of Zmhdz genes for cloning and functional research to uncover their roles in maize growth and development. PMID:22164299

  14. Systematic analysis of sequences and expression patterns of drought-responsive members of the HD-Zip gene family in maize.

    PubMed

    Zhao, Yang; Zhou, Yuqiong; Jiang, Haiyang; Li, Xiaoyu; Gan, Defang; Peng, Xiaojian; Zhu, Suwen; Cheng, Beijiu

    2011-01-01

    Members of the homeodomain-leucine zipper (HD-Zip) gene family encode transcription factors that are unique to plants and have diverse functions in plant growth and development such as various stress responses, organ formation and vascular development. Although systematic characterization of this family has been carried out in Arabidopsis and rice, little is known about HD-Zip genes in maize (Zea mays L.). In this study, we described the identification and structural characterization of HD-Zip genes in the maize genome. A complete set of 55 HD-Zip genes (Zmhdz1-55) were identified in the maize genome using Blast search tools and categorized into four classes (HD-Zip I-IV) based on phylogeny. Chromosomal location of these genes revealed that they are distributed unevenly across all 10 chromosomes. Segmental duplication contributed largely to the expansion of the maize HD-ZIP gene family, while tandem duplication was only responsible for the amplification of the HD-Zip II genes. Furthermore, most of the maize HD-Zip I genes were found to contain an overabundance of stress-related cis-elements in their promoter sequences. The expression levels of the 17 HD-Zip I genes under drought stress were also investigated by quantitative real-time PCR (qRT-PCR). All of the 17 maize HD-ZIP I genes were found to be regulated by drought stress, and the duplicated genes within a sister pair exhibited the similar expression patterns, suggesting their conserved functions during the process of evolution. Our results reveal a comprehensive overview of the maize HD-Zip gene family and provide the first step towards the selection of Zmhdz genes for cloning and functional research to uncover their roles in maize growth and development.

  15. An efficient and extensible approach for compressing phylogenetic trees

    PubMed Central

    2011-01-01

    Background Biologists require new algorithms to efficiently compress and store their large collections of phylogenetic trees. Our previous work showed that TreeZip is a promising approach for compressing phylogenetic trees. In this paper, we extend our TreeZip algorithm by handling trees with weighted branches. Furthermore, by using the compressed TreeZip file as input, we have designed an extensible decompressor that can extract subcollections of trees, compute majority and strict consensus trees, and merge tree collections using set operations such as union, intersection, and set difference. Results On unweighted phylogenetic trees, TreeZip is able to compress Newick files in excess of 98%. On weighted phylogenetic trees, TreeZip is able to compress a Newick file by at least 73%. TreeZip can be combined with 7zip with little overhead, allowing space savings in excess of 99% (unweighted) and 92%(weighted). Unlike TreeZip, 7zip is not immune to branch rotations, and performs worse as the level of variability in the Newick string representation increases. Finally, since the TreeZip compressed text (TRZ) file contains all the semantic information in a collection of trees, we can easily filter and decompress a subset of trees of interest (such as the set of unique trees), or build the resulting consensus tree in a matter of seconds. We also show the ease of which set operations can be performed on TRZ files, at speeds quicker than those performed on Newick or 7zip compressed Newick files, and without loss of space savings. Conclusions TreeZip is an efficient approach for compressing large collections of phylogenetic trees. The semantic and compact nature of the TRZ file allow it to be operated upon directly and quickly, without a need to decompress the original Newick file. We believe that TreeZip will be vital for compressing and archiving trees in the biological community. PMID:22165819

  16. An efficient and extensible approach for compressing phylogenetic trees.

    PubMed

    Matthews, Suzanne J; Williams, Tiffani L

    2011-10-18

    Biologists require new algorithms to efficiently compress and store their large collections of phylogenetic trees. Our previous work showed that TreeZip is a promising approach for compressing phylogenetic trees. In this paper, we extend our TreeZip algorithm by handling trees with weighted branches. Furthermore, by using the compressed TreeZip file as input, we have designed an extensible decompressor that can extract subcollections of trees, compute majority and strict consensus trees, and merge tree collections using set operations such as union, intersection, and set difference. On unweighted phylogenetic trees, TreeZip is able to compress Newick files in excess of 98%. On weighted phylogenetic trees, TreeZip is able to compress a Newick file by at least 73%. TreeZip can be combined with 7zip with little overhead, allowing space savings in excess of 99% (unweighted) and 92%(weighted). Unlike TreeZip, 7zip is not immune to branch rotations, and performs worse as the level of variability in the Newick string representation increases. Finally, since the TreeZip compressed text (TRZ) file contains all the semantic information in a collection of trees, we can easily filter and decompress a subset of trees of interest (such as the set of unique trees), or build the resulting consensus tree in a matter of seconds. We also show the ease of which set operations can be performed on TRZ files, at speeds quicker than those performed on Newick or 7zip compressed Newick files, and without loss of space savings. TreeZip is an efficient approach for compressing large collections of phylogenetic trees. The semantic and compact nature of the TRZ file allow it to be operated upon directly and quickly, without a need to decompress the original Newick file. We believe that TreeZip will be vital for compressing and archiving trees in the biological community.

  17. Recovery from temporary endoplasmic reticulum stress in plants relies on the tissue-specific and largely independent roles of bZIP28 and bZIP60, as well as an antagonizing function of BAX-Inhibitor 1 upon the pro-adaptive signaling mediated by bZIP28.

    PubMed

    Ruberti, Cristina; Lai, YaShiuan; Brandizzi, Federica

    2018-01-01

    The unfolded protein response (UPR) is an ancient signaling pathway that commits to life-or-death outcomes in response to proteotoxic stress in the endoplasmic reticulum (ER). In plants, the membrane-tethered transcription factor bZIP28 and the ribonuclease-kinase IRE1 along with its splicing target, bZIP60, govern the two cytoprotective UPR signaling pathways known to date. The conserved ER membrane-associated BAX inhibitor 1 (BI1) modulates ER stress-induced programmed cell death through yet-unknown mechanisms. Despite the significance of the UPR for cell homeostasis, in plants the regulatory circuitry underlying ER stress resolution is still largely unmapped. To gain insights into the coordination of plant UPR strategies, we analyzed the functional relationship of the UPR modulators through the analysis of single and higher order mutants of IRE1, bZIP60, bZIP28 and BI1 in experimental conditions causing either temporary or chronic ER stress. We established a functional duality of bZIP28 and bZIP60, as they exert partially independent tissue-specific roles in recovery from ER stress, but redundantly actuate survival strategies in chronic ER stress. We also discovered that BI1 attenuates the pro-survival function of bZIP28 in ER stress resolution and, differently to animal cells, it does not temper the ribonuclease activity of inositol-requiring enzyme 1 (IRE1) under temporary ER stress. Together these findings reveal a functional independence of bZIP28 and bZIP60 in plant UPR, and identify an antagonizing role of BI1 in the pro-adaptive signaling mediated by bZIP28, bringing to light the distinctive complexity of the unfolded protein response (UPR) in plants. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  18. Molecular pathogenesis of Spondylocheirodysplastic Ehlers-Danlos syndrome caused by mutant ZIP13 proteins

    PubMed Central

    Bin, Bum-Ho; Hojyo, Shintaro; Hosaka, Toshiaki; Bhin, Jinhyuk; Kano, Hiroki; Miyai, Tomohiro; Ikeda, Mariko; Kimura-Someya, Tomomi; Shirouzu, Mikako; Cho, Eun-Gyung; Fukue, Kazuhisa; Kambe, Taiho; Ohashi, Wakana; Kim, Kyu-Han; Seo, Juyeon; Choi, Dong-Hwa; Nam, Yeon-Ju; Hwang, Daehee; Fukunaka, Ayako; Fujitani, Yoshio; Yokoyama, Shigeyuki; Superti-Furga, Andrea; Ikegawa, Shiro; Lee, Tae Ryong; Fukada, Toshiyuki

    2014-01-01

    The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mutant ZIP13 proteins found in human patients: ZIP13G64D, in which Gly at amino acid position 64 is replaced by Asp, and ZIP13ΔFLA, which contains a deletion of Phe-Leu-Ala. We demonstrated that both the ZIP13G64D and ZIP13ΔFLA protein levels are decreased by degradation via the valosin-containing protein (VCP)-linked ubiquitin proteasome pathway. The inhibition of degradation pathways rescued the protein expression levels, resulting in improved intracellular Zn homeostasis. Our findings uncover the pathogenic mechanisms elicited by mutant ZIP13 proteins. Further elucidation of these degradation processes may lead to novel therapeutic targets for SCD-EDS. PMID:25007800

  19. Structural insights of ZIP4 extracellular domain critical for optimal zinc transport

    NASA Astrophysics Data System (ADS)

    Zhang, Tuo; Sui, Dexin; Hu, Jian

    2016-06-01

    The ZIP zinc transporter family is responsible for zinc uptake from the extracellular milieu or intracellular vesicles. The LIV-1 subfamily, containing nine out of the 14 human ZIP proteins, is featured with a large extracellular domain (ECD). The critical role of the ECD is manifested by disease-causing mutations on ZIP4, a representative LIV-1 protein. Here we report the first crystal structure of a mammalian ZIP4-ECD, which reveals two structurally independent subdomains and an unprecedented dimer centred at the signature PAL motif. Structure-guided mutagenesis, cell-based zinc uptake assays and mapping of the disease-causing mutations indicate that the two subdomains play pivotal but distinct roles and that the bridging region connecting them is particularly important for ZIP4 function. These findings lead to working hypotheses on how ZIP4-ECD exerts critical functions in zinc transport. The conserved dimeric architecture in ZIP4-ECD is also demonstrated to be a common structural feature among the LIV-1 proteins.

  20. Genome-Wide Identification and Structural Analysis of bZIP Transcription Factor Genes in Brassica napus.

    PubMed

    Zhou, Yan; Xu, Daixiang; Jia, Ledong; Huang, Xiaohu; Ma, Guoqiang; Wang, Shuxian; Zhu, Meichen; Zhang, Aoxiang; Guan, Mingwei; Lu, Kun; Xu, Xinfu; Wang, Rui; Li, Jiana; Qu, Cunmin

    2017-10-24

    The basic region/leucine zipper motif (bZIP) transcription factor family is one of the largest families of transcriptional regulators in plants. bZIP genes have been systematically characterized in some plants, but not in rapeseed ( Brassica napus ). In this study, we identified 247 BnbZIP genes in the rapeseed genome, which we classified into 10 subfamilies based on phylogenetic analysis of their deduced protein sequences. The BnbZIP genes were grouped into functional clades with Arabidopsis genes with similar putative functions, indicating functional conservation. Genome mapping analysis revealed that the BnbZIPs are distributed unevenly across all 19 chromosomes, and that some of these genes arose through whole-genome duplication and dispersed duplication events. All expression profiles of 247 bZIP genes were extracted from RNA-sequencing data obtained from 17 different B . napus ZS11 tissues with 42 various developmental stages. These genes exhibited different expression patterns in various tissues, revealing that these genes are differentially regulated. Our results provide a valuable foundation for functional dissection of the different BnbZIP homologs in B . napus and its parental lines and for molecular breeding studies of bZIP genes in B . napus .

  1. Genome-Wide Identification and Structural Analysis of bZIP Transcription Factor Genes in Brassica napus

    PubMed Central

    Zhou, Yan; Xu, Daixiang; Jia, Ledong; Huang, Xiaohu; Ma, Guoqiang; Wang, Shuxian; Zhu, Meichen; Zhang, Aoxiang; Guan, Mingwei; Xu, Xinfu; Wang, Rui; Li, Jiana

    2017-01-01

    The basic region/leucine zipper motif (bZIP) transcription factor family is one of the largest families of transcriptional regulators in plants. bZIP genes have been systematically characterized in some plants, but not in rapeseed (Brassica napus). In this study, we identified 247 BnbZIP genes in the rapeseed genome, which we classified into 10 subfamilies based on phylogenetic analysis of their deduced protein sequences. The BnbZIP genes were grouped into functional clades with Arabidopsis genes with similar putative functions, indicating functional conservation. Genome mapping analysis revealed that the BnbZIPs are distributed unevenly across all 19 chromosomes, and that some of these genes arose through whole-genome duplication and dispersed duplication events. All expression profiles of 247 bZIP genes were extracted from RNA-sequencing data obtained from 17 different B. napus ZS11 tissues with 42 various developmental stages. These genes exhibited different expression patterns in various tissues, revealing that these genes are differentially regulated. Our results provide a valuable foundation for functional dissection of the different BnbZIP homologs in B. napus and its parental lines and for molecular breeding studies of bZIP genes in B. napus. PMID:29064393

  2. Basic leucine zipper transcription factor SlbZIP1 mediates salt and drought stress tolerance in tomato.

    PubMed

    Zhu, Mingku; Meng, Xiaoqing; Cai, Jing; Li, Ge; Dong, Tingting; Li, Zongyun

    2018-05-08

    Basic region/leucine zipper (bZIP) transcription factors perform as crucial regulators in ABA-mediated stress response in plants. Nevertheless, the functions for most bZIP family members in tomato remain to be deciphered. Here we examined the functional characterization of SlbZIP1 under salt and drought stresses in tomato. Silencing of SlbZIP1 in tomato resulted in reduced expression of multiple ABA biosynthesis- and signal transduction-related genes in transgenic plants. In stress assays, SlbZIP1-RNAi transgenic plants exhibited reduced tolerance to salt and drought stresses compared with WT plants, as are evaluated by multiple physiological parameters associated with stress responses, such as decreased ABA, chlorophyll contents and CAT activity, and increased MDA content. In addition, RNA-seq analysis of transgenic plants revealed that the transcription levels of multiple genes encoding defense proteins related to responses to abiotic stress (e.g. endochitinase, peroxidases, and lipid transfer proteins) and biotic stress (e.g. pathogenesis-related proteins) were downregulated in SlbZIP1-RNAi plants, suggesting that SlbZIP1 plays a role in regulating the genes related to biotic and abiotic stress response. Collectively, the data suggest that SlbZIP1 exerts an essential role in salt and drought stress tolerance through modulating an ABA-mediated pathway, and SlbZIP1 may hold potential applications in the engineering of salt- and drought-tolerant tomato cultivars.

  3. A role for the Drosophila zinc transporter Zip88E in protecting against dietary zinc toxicity.

    PubMed

    Richards, Christopher D; Warr, Coral G; Burke, Richard

    2017-01-01

    Zinc absorption in animals is thought to be regulated in a local, cell autonomous manner with intestinal cells responding to dietary zinc content. The Drosophila zinc transporter Zip88E shows strong sequence similarity to Zips 42C.1, 42C.2 and 89B as well as mammalian Zips 1, 2 and 3, suggesting that it may act in concert with the apically-localised Drosophila zinc uptake transporters to facilitate dietary zinc absorption by importing ions into the midgut enterocytes. However, the functional characterisation of Zip88E presented here indicates that Zip88E may instead play a role in detecting and responding to zinc toxicity. Larvae homozygous for a null Zip88E allele are viable yet display heightened sensitivity to elevated levels of dietary zinc. This decreased zinc tolerance is accompanied by an overall decrease in Metallothionein B transcription throughout the larval midgut. A Zip88E reporter gene is expressed only in the salivary glands, a handful of enteroendocrine cells at the boundary between the anterior and middle midgut regions, and in two parallel strips of sensory cell projections connecting to the larval ventral ganglion. Zip88E expression solely in this restricted subset of cells is sufficient to rescue the Zip88E mutant phenotype. Together, our data suggest that Zip88E may be functioning in a small subset of cells to detect excessive zinc levels and induce a systemic response to reduce dietary zinc absorption and hence protect against toxicity.

  4. The regulatory network of ThbZIP1 in response to abscisic acid treatment

    PubMed Central

    Ji, Xiaoyu; Liu, Guifeng; Liu, Yujia; Nie, Xianguang; Zheng, Lei; Wang, Yucheng

    2015-01-01

    Previously, a bZIP transcription factor from Tamarix hispida, ThbZIP1, was characterized: plants overexpressing ThbZIP1 displayed improved salt stress tolerance but were sensitive to abscisic acid (ABA). In the current study, we further characterized the regulatory network of ThbZIP1 and the mechanism of ABA sensitivity mediated by ThbZIP1. An ABF transcription factor from T. hispida, ThABF1, directly regulates the expression of ThbZIP1. Microarray analysis identified 1662 and 1609 genes that were respectively significantly upregulated or downregulated by ThbZIP1 when exposed to ABA. Gene ontology (GO) analysis showed that the processes including “response to stimulus,” “catalytic activity,” “binding function,” and “metabolic process” were highly altered in ThbZIP1 expressing plants exposed to ABA. The gene expression in ThbZIP1 transformed plants were compared between exposed to ABA and salt on the genome scale. Genes differentially regulated by both salt and ABA treatment only accounted for 9.75% of total differentially regulated genes. GO analysis showed that structural molecule activity, organelle part, membrane-enclosed lumen, reproduction, and reproductive process are enhanced by ABA but inhibited by salt stress. Conversely, immune system and multi-organism process were improved by salt but inhibited by ABA. Transcription regulator activity, enzyme regulator activity, and developmental process were significantly altered by ABA but were not affected by salt stress. Our study provides insights into how ThbZIP1 mediates ABA and salt stress response at the molecular level. PMID:25713576

  5. 39 CFR Appendix A to Part 121 - Tables Depicting Service Standard Day Ranges

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 1-3 (AK)7 (JNU) 7 (KTN) 1 (HI)7 (GU) 1-2 1-2 6-7 5-6 Standard Mail 2 3 3 3-4 10 10 9 Package Services 1 2 2 2-3 8 8 7 AK = Alaska 3-digit ZIP Codes 995-997; JNU = Juneau AK 3-digit ZIP Code 998; KTN = Ketchikan AK 3-digit ZIP Code 999; HI = Hawaii 3-digit ZIP Codes 967 and 968; GU = Guam 3-digit ZIP Code 969...

  6. 39 CFR Appendix A to Part 121 - Tables Depicting Service Standard Day Ranges

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 1-3 (AK)7 (JNU) 7 (KTN) 1 (HI)7 (GU) 1-2 1-2 6-7 5-6 Standard Mail 2 3 3 3-4 10 10 9 Package Services 1 2 2 2-3 8 8 7 AK = Alaska 3-digit ZIP Codes 995-997; JNU = Juneau AK 3-digit ZIP Code 998; KTN = Ketchikan AK 3-digit ZIP Code 999; HI = Hawaii 3-digit ZIP Codes 967 and 968; GU = Guam 3-digit ZIP Code 969...

  7. A Petunia Homeodomain-Leucine Zipper Protein, PhHD-Zip, Plays an Important Role in Flower Senescence

    PubMed Central

    Chang, Xiaoxiao; Donnelly, Linda; Sun, Daoyang; Rao, Jingping; Reid, Michael S.; Jiang, Cai-Zhong

    2014-01-01

    Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence. PMID:24551088

  8. A Petunia homeodomain-leucine zipper protein, PhHD-Zip, plays an important role in flower senescence.

    PubMed

    Chang, Xiaoxiao; Donnelly, Linda; Sun, Daoyang; Rao, Jingping; Reid, Michael S; Jiang, Cai-Zhong

    2014-01-01

    Flower senescence is initiated by developmental and environmental signals, and regulated by gene transcription. A homeodomain-leucine zipper transcription factor, PhHD-Zip, is up-regulated during petunia flower senescence. Virus-induced gene silencing of PhHD-Zip extended flower life by 20% both in unpollinated and pollinated flowers. Silencing PhHD-Zip also dramatically reduced ethylene production and the abundance of transcripts of genes involved in ethylene (ACS, ACO), and ABA (NCED) biosynthesis. Abundance of transcripts of senescence-related genes (SAG12, SAG29) was also dramatically reduced in the silenced flowers. Over-expression of PhHD-Zip accelerated petunia flower senescence. Furthermore, PhHD-Zip transcript abundance in petunia flowers was increased by application of hormones (ethylene, ABA) and abiotic stresses (dehydration, NaCl and cold). Our results suggest that PhHD-Zip plays an important role in regulating petunia flower senescence.

  9. Conditional mouse models support the role of SLC39A14 (ZIP14) in Hyperostosis Cranialis Interna and in bone homeostasis

    PubMed Central

    Steenackers, Ellen; Yorgan, Timur A.; Hermans, Christophe; Boudin, Eveline; Waterval, Jérôme J.; Jansen, Ineke D. C.; Aydemir, Tolunay Beker; Kamerling, Niels; Plumeyer, Christine; D’Haese, Patrick C.; Everts, Vincent; Lammens, Martin; Mortier, Geert; Cousins, Robert J.; Schinke, Thorsten; Stokroos, Robert J.; Manni, Johannes J.; Van Hul, Wim

    2018-01-01

    Hyperostosis Cranialis Interna (HCI) is a rare bone disorder characterized by progressive intracranial bone overgrowth at the skull. Here we identified by whole-exome sequencing a dominant mutation (L441R) in SLC39A14 (ZIP14). We show that L441R ZIP14 is no longer trafficked towards the plasma membrane and excessively accumulates intracellular zinc, resulting in hyper-activation of cAMP-CREB and NFAT signaling. Conditional knock-in mice overexpressing L438R Zip14 in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients. Remarkably, L438R Zip14 also generates an osteoporotic trabecular bone phenotype. The effects of osteoblastic overexpression of L438R Zip14 therefore mimic the disparate actions of estrogen on cortical and trabecular bone through osteoblasts. Collectively, we reveal ZIP14 as a novel regulator of bone homeostasis, and that manipulating ZIP14 might be a therapeutic strategy for bone diseases. PMID:29621230

  10. Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus

    PubMed Central

    Evuarherhe, Obaro; Barker, Gareth R. I.; Savalli, Giorgia; Warburton, Elizabeth C.; Brown, Malcolm W.

    2014-01-01

    Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesised to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluR2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluR2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluR2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. PMID:24729442

  11. Hippocampal Infusion of Zeta Inhibitory Peptide Impairs Recent, but Not Remote, Recognition Memory in Rats

    PubMed Central

    Hales, Jena B.; Ocampo, Amber C.; Broadbent, Nicola J.; Clark, Robert E.

    2015-01-01

    Spatial memory in rodents can be erased following the infusion of zeta inhibitory peptide (ZIP) into the dorsal hippocampus via indwelling guide cannulas. It is believed that ZIP impairs spatial memory by reversing established late-phase long-term potentiation (LTP). However, it is unclear whether other forms of hippocampus-dependent memory, such as recognition memory, are also supported by hippocampal LTP. In the current study, we tested recognition memory in rats following hippocampal ZIP infusion. In order to combat the limited targeting of infusions via cannula, we implemented a stereotaxic approach for infusing ZIP throughout the dorsal, intermediate, and ventral hippocampus. Rats infused with ZIP 3–7 days after training on the novel object recognition task exhibited impaired object recognition memory compared to control rats (those infused with aCSF). In contrast, rats infused with ZIP 1 month after training performed similar to control rats. The ability to form new memories after ZIP infusions remained intact. We suggest that enhanced recognition memory for recent events is supported by hippocampal LTP, which can be reversed by hippocampal ZIP infusion. PMID:26380123

  12. Knockdown of Zinc Transporter ZIP5 by RNA Interference Inhibits Esophageal Cancer Growth In Vivo.

    PubMed

    Li, Qian; Jin, Jing; Liu, Jianghui; Wang, Liqun; He, Yutong

    2016-01-01

    We recently found that SLC39A5 (ZIP5), a zinc transporter, is overexpressed in esophageal cancer. Downregulation of ZIP5 inhibited the proliferation, migration, and invasion of the esophageal cancer cell line KYSE170 in vitro. In this study, we found that downregulation of SLC39A5 (ZIP5) by interference resulted in a significant reduction in esophageal cancer tumor volume and weight in vivo. COX2 (cyclooxygenase 2) expression was decreased and E-cadherin expression was increased in the KYSE170K xenografts, which was caused by the downregulation of ZIP5. However, we did not find that the downregulation of ZIP5 caused a change in the relative expressions of cyclin D1, VEGF (vascular endothelial growth factor), MMP9 (matrix metalloprotein 9), and Bcl-2 (B-cell lymphoma/leukmia-2) mRNA or an alteration in the average level of zinc in the peripheral blood and xenografts in vivo. Collectively, these findings indicate that knocking down ZIP5 by small interfering RNA (siRNA) might be a novel treatment strategy for esophageal cancer with ZIP5 overexpression.

  13. Knockdown of zinc transporter ZIP8 expression inhibits neuroblastoma progression and metastasis in vitro.

    PubMed

    Mei, Zhengrong; Yan, Pengke; Wang, Ying; Liu, Shaozhi; He, Fang

    2018-05-02

    Neuroblastoma is one of the leading causes of cancer‑associated mortality worldwide, particularly in children, partially due to the absence of effective therapeutic targets and diagnostic biomarkers. Therefore, novel molecular targets are critical to the development of therapeutic approaches for neuroblastoma. In the present study, the functions of zinc transporter ZIP8 (Zip8), a member of the zinc transporting protein family, were investigated as novel molecular targets in neuroblastoma cancer cells. The proliferation rates of neuroblastoma cancer cells were significantly decreased when Zip8 was knocked down by lentiviral‑mediated RNA interference. Study of the molecular mechanism suggested that Zip8 modulated the expression of key genes involved in the nuclear factor‑κB signaling pathway. Furthermore, Zip8 depletion suppressed the migratory potential of neuroblastoma cancer cells by reducing the expression levels of matrix metalloproteinases. In conclusion, the results of the present study suggested that Zip8 was an important regulator of neuroblastoma cell proliferation and migration, indicating that Zip8 may be a potential anticancer therapeutic target and a promising diagnostic biomarker for human neuroblastoma.

  14. Zinc Transporter SLC39A7/ZIP7 Promotes Intestinal Epithelial Self-Renewal by Resolving ER Stress

    PubMed Central

    Ohashi, Wakana; Kimura, Shunsuke; Iwanaga, Toshihiko; Furusawa, Yukihiro; Irié, Tarou; Izumi, Hironori; Watanabe, Takashi; Hara, Takafumi; Ohara, Osamu; Koseki, Haruhiko; Sato, Toshiro; Robine, Sylvie; Mori, Hisashi; Hattori, Yuichi; Mishima, Kenji; Ohno, Hiroshi; Hase, Koji; Fukada, Toshiyuki

    2016-01-01

    Zinc transporters play a critical role in spatiotemporal regulation of zinc homeostasis. Although disruption of zinc homeostasis has been implicated in disorders such as intestinal inflammation and aberrant epithelial morphology, it is largely unknown which zinc transporters are responsible for the intestinal epithelial homeostasis. Here, we show that Zrt-Irt-like protein (ZIP) transporter ZIP7, which is highly expressed in the intestinal crypt, is essential for intestinal epithelial proliferation. Mice lacking Zip7 in intestinal epithelium triggered endoplasmic reticulum (ER) stress in proliferative progenitor cells, leading to significant cell death of progenitor cells. Zip7 deficiency led to the loss of Olfm4+ intestinal stem cells and the degeneration of post-mitotic Paneth cells, indicating a fundamental requirement for Zip7 in homeostatic intestinal regeneration. Taken together, these findings provide evidence for the importance of ZIP7 in maintenance of intestinal epithelial homeostasis through the regulation of ER function in proliferative progenitor cells and maintenance of intestinal stem cells. Therapeutic targeting of ZIP7 could lead to effective treatment of gastrointestinal disorders. PMID:27736879

  15. Basic leucine zipper family in barley: genome-wide characterization of members and expression analysis.

    PubMed

    Pourabed, Ehsan; Ghane Golmohamadi, Farzan; Soleymani Monfared, Peyman; Razavi, Seyed Morteza; Shobbar, Zahra-Sadat

    2015-01-01

    The basic leucine zipper (bZIP) family is one of the largest and most diverse transcription factors in eukaryotes participating in many essential plant processes. We identified 141 bZIP proteins encoded by 89 genes from the Hordeum vulgare genome. HvbZIPs were classified into 11 groups based on their DNA-binding motif. Amino acid sequence alignment of the HvbZIPs basic-hinge regions revealed some highly conserved residues within each group. The leucine zipper heptads were analyzed predicting their dimerization properties. 34 conserved motifs were identified outside the bZIP domain. Phylogenetic analysis indicated that major diversification within the bZIP family predated the monocot/dicot divergence, although intra-species duplication and parallel evolution seems to be occurred afterward. Localization of HvbZIPs on the barley chromosomes revealed that different groups have been distributed on seven chromosomes of barley. Six types of intron pattern were detected within the basic-hinge regions. Most of the detected cis-elements in the promoter and UTR sequences were involved in seed development or abiotic stress response. Microarray data analysis revealed differential expression pattern of HvbZIPs in response to ABA treatment, drought, and cold stresses and during barley grain development and germination. This information would be helpful for functional characterization of bZIP transcription factors in barley.

  16. LiZIP3 is a cellular zinc transporter that mediates the tightly regulated import of zinc in Leishmania infantum parasites

    PubMed Central

    Carvalho, Sandra; da Silva, Rosa Barreira; Shawki, Ali; Castro, Helena; Lamy, Márcia; Eide, David; Costa, Vítor; Mackenzie, Bryan; Tomás, Ana M.

    2016-01-01

    Summary Cellular zinc homeostasis ensures that the intracellular concentration of this element is kept within limits that enable its participation in critical physiological processes without exerting toxic effects. We report here the identification and characterization of the first mediator of zinc homeostasis in Leishmania infantum, LiZIP3, a member of the ZIP family of divalent metal-ion transporters. The zinc transporter activity of LiZIP3 was first disclosed by its capacity to rescue the growth of Saccharomyces cerevisiae strains deficient in zinc acquisition. Subsequent expression of LiZIP3 in Xenopus laevis oocytes was shown to stimulate the uptake of a broad range of metal ions, among which Zn2+ was the preferred LiZIP3 substrate (K0.5 ≈ 0.1 μM). Evidence that LiZIP3 functions as a zinc importer in L. infantum came from the observations that the protein locates to the cell membrane and that its overexpression leads to augmented zinc internalization. Importantly, expression and cell-surface location of LiZIP3 are lost when parasites face high zinc bioavailability. LiZIP3 decline in response to zinc is regulated at the mRNA level in a process involving (a) short-lived protein(s). Collectively, our data reveal that LiZIP3 enables L. infantum to acquire zinc in a highly regulated manner, hence contributing to zinc homeostasis. PMID:25644708

  17. Generation of a Slc39a8 hypomorph mouse: Markedly decreased ZIP8 Zn{sup 2+}/(HCO{sub 3}{sup -}){sub 2} transporter expression

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

    Wang, Bin; He, Lei; Dong, Hongbin

    2011-07-01

    Highlights: {yields} The mouse Slc39a8 gene encodes the ZIP8 transporter. {yields} ZIP8 functions endogenously as a electroneutral Zn{sup 2+}/(HCO{sub 3}{sup -}){sub 2} symporter. {yields} A Slc39a8(neo/neo) hypomorph mouse, due to retention of the neo mini-gene, has been created. {yields} ZIP8 expression in utero is {approx}90% decreased in all tissues examined. {yields} This mouse model will be useful for studying developmental and in utero physiological functions of ZIP8. -- Abstract: Previously this laboratory has identified the mouse Slc39a8 gene encoding the ZIP8 transporter, important in cadmium uptake. ZIP8 functions endogenously as a electroneutral Zn{sup 2+}/(HCO{sub 3}{sup -}){sub 2} symporter, moving bothmore » ions into the cell. The overall physiological importance of ZIP8 remains unclear. Herein we describe generation of a mouse line carrying the Slc39a8(neo) allele, containing the Frt-flanked neomycin-resistance (neo) mini-cassette in intron 3 and loxP sites in introns 3 and 6. Cre recombinase functions correctly in Escherichia coli and in adeno-Cre-infected mouse fetal fibroblasts, but does not function in the intact mouse for reasons not clear. Slc39a8(neo) is a hypomorphic allele, because Slc39a8(neo/neo) homozygotes exhibit dramatically decreased ZIP8 expression in embryo, fetus, and visceral yolk sac - in comparison to their littermate wild-type controls. This ZIP8 hypomorph will be instrumental in studying developmental and in utero physiological functions of the ZIP8 transporter.« less

  18. Genome-wide analysis of soybean HD-Zip gene family and expression profiling under salinity and drought treatments.

    PubMed

    Chen, Xue; Chen, Zhu; Zhao, Hualin; Zhao, Yang; Cheng, Beijiu; Xiang, Yan

    2014-01-01

    Homeodomain-leucine zipper (HD-Zip) proteins, a group of homeobox transcription factors, participate in various aspects of normal plant growth and developmental processes as well as environmental responses. To date, no overall analysis or expression profiling of the HD-Zip gene family in soybean (Glycine max) has been reported. An investigation of the soybean genome revealed 88 putative HD-Zip genes. These genes were classified into four subfamilies, I to IV, based on phylogenetic analysis. In each subfamily, the constituent parts of gene structure and motif were relatively conserved. A total of 87 out of 88 genes were distributed unequally on 20 chromosomes with 36 segmental duplication events, indicating that segmental duplication is important for the expansion of the HD-Zip family. Analysis of the Ka/Ks ratios showed that the duplicated genes of the HD-Zip family basically underwent purifying selection with restrictive functional divergence after the duplication events. Analysis of expression profiles showed that 80 genes differentially expressed across 14 tissues, and 59 HD-Zip genes are differentially expressed under salinity and drought stress, with 20 paralogous pairs showing nearly identical expression patterns and three paralogous pairs diversifying significantly under drought stress. Quantitative real-time RT-PCR (qRT-PCR) analysis of six paralogous pairs of 12 selected soybean HD-Zip genes under both drought and salinity stress confirmed their stress-inducible expression patterns. This study presents a thorough overview of the soybean HD-Zip gene family and provides a new perspective on the evolution of this gene family. The results indicate that HD-Zip family genes may be involved in many plant responses to stress conditions. Additionally, this study provides a solid foundation for uncovering the biological roles of HD-Zip genes in soybean growth and development.

  19. Pepper CabZIP63 acts as a positive regulator during Ralstonia solanacearum or high temperature-high humidity challenge in a positive feedback loop with CaWRKY40.

    PubMed

    Shen, Lei; Liu, Zhiqin; Yang, Sheng; Yang, Tong; Liang, Jiaqi; Wen, Jiayu; Liu, Yanyan; Li, Jiazhi; Shi, Lanping; Tang, Qian; Shi, Wei; Hu, Jiong; Liu, Cailing; Zhang, Yangwen; Lin, Wei; Wang, Rongzhang; Yu, Huanxin; Mou, Shaoliang; Hussain, Ansar; Cheng, Wei; Cai, Hanyang; He, Li; Guan, Deyi; Wu, Yang; He, Shuilin

    2016-04-01

    CaWRKY40 is known to act as a positive regulator in the response of pepper (Capsicum annuum) to Ralstonia solanacearum inoculation (RSI) or high temperature-high humidity (HTHH), but the underlying mechanism remains elusive. Herein, we report that CabZIP63, a pepper bZIP family member, participates in this process by regulating the expression of CaWRKY40. CabZIP63 was found to localize in the nuclei, be up-regulated by RSI or HTHH, bind to promoters of both CabZIP63(pCabZIP63) and CaWRKY40(pCaWRKY40), and activate pCabZIP63- and pCaWRKY40-driven β-glucuronidase expression in a C- or G-box-dependent manner. Silencing of CabZIP63 by virus-induced gene silencing (VIGS) in pepper plants significantly attenuated their resistance to RSI and tolerance to HTHH, accompanied by down-regulation of immunity- or thermotolerance-associated CaPR1, CaNPR1, CaDEF1, and CaHSP24. Hypersensitive response-mediated cell death and expression of the tested immunity- and thermotolerance-associated marker genes were induced by transient overexpression (TOE) of CabZIP63, but decreased by that of CabZIP63-SRDX. Additionally, binding of CabZIP63 to pCaWRKY40 was up-regulated by RSI or HTHH, and the transcript level of CaWRKY40 and binding of CaWRKY40 to the promoters of CaPR1, CaNPR1, CaDEF1 and CaHSP24 were up-regulated by TOE of CabZIP63. On the other hand, CabZIP63 was also up-regulated transcriptionally by TOE of CaWRKY40. The data suggest collectively that CabZIP63 directly or indirectly regulates the expression of CaWRKY40 at both the transcriptional and post-transcriptional level, forming a positive feedback loop with CaWRKY40 during pepper's response to RSI or HTHH. Altogether, our data will help to elucidate the underlying mechanism of crosstalk between pepper's response to RSI and HTHH. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Memory Retrieval Has a Dynamic Influence on the Maintenance Mechanisms That Are Sensitive to ζ-Inhibitory Peptide (ZIP).

    PubMed

    Levitan, David; Fortis-Santiago, Yaihara; Figueroa, Joshua A; Reid, Emily E; Yoshida, Takashi; Barry, Nicholas C; Russo, Abigail; Katz, Donald B

    2016-10-12

    In neuroscientists' attempts to understand the long-term storage of memory, topics of particular importance and interest are the cellular and system mechanisms of maintenance (e.g., those sensitive to ζ-inhibitory peptide, ZIP) and those induced by memory retrieval (i.e., reconsolidation). Much is known about each of these processes in isolation, but less is known concerning how they interact. It is known that ZIP sensitivity and memory retrieval share at least some molecular targets (e.g., recycling α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, AMPA, receptors to the plasma membrane); conversely, the fact that sensitivity to ZIP emerges only after consolidation ends suggests that consolidation (and by extension reconsolidation) and maintenance might be mutually exclusive processes, the onset of one canceling the other. Here, we use conditioned taste aversion (CTA) in rats, a cortically dependent learning paradigm, to test this hypothesis. First, we demonstrate that ZIP infusions into gustatory cortex begin interfering with CTA memory 43-45 h after memory acquisition-after consolidation ends. Next, we show that a retrieval trial administered after this time point interrupts the ability of ZIP to induce amnesia and that ZIP's ability to induce amnesia is reengaged only 45 h after retrieval. This pattern of results suggests that memory retrieval and ZIP-sensitive maintenance mechanisms are mutually exclusive and that the progression from one to the other are similar after acquisition and retrieval. They also reveal concrete differences between ZIP-sensitive mechanisms induced by acquisition and retrieval: the latency with which ZIP-sensitive mechanisms are expressed differ for the two processes. Memory retrieval and the molecular mechanisms that are sensitive to ζ-inhibitory peptide (ZIP) are the few manipulations that have been shown to effect memory maintenance. Although much is known about their effect on maintenance separately, it is unknown how they interact. Here, we describe a model for the interaction between memory retrieval and ZIP-sensitive mechanisms, showing that retrieval trials briefly (i.e., for 45 h) interrupt these mechanisms. ZIP sensitivity emerges across a similar time window after memory acquisition and retrieval; the maintenance mechanisms that follow acquisition and retrieval differ, however, in the latency with which the impact of ZIP is expressed. Copyright © 2016 the authors 0270-6474/16/3610654-09$15.00/0.

  1. Invariance of wearing location of Omron-BI pedometers: a validation study.

    PubMed

    Zhu, Weimo; Lee, Miyoung

    2010-11-01

    The purpose of this study was to investigate the validity and reliability evidences of the Omron BI pedometer, which could count steps taken even when worn at different locations on the body. Forty (20 males and 20 females) adults were recruited to walk wearing 5 sets, 1 set at a time, of 10 BI pedometers during testing, 1 each at 10 different locations. For comparison, they also wore 2 Yamax Digi-Walker SW-200 pedometers and a Dynastream AMP 331 activity monitor. The subjects walked in 3 free-living conditions: a flat sidewalk, stairs, and mixed conditions. Except for a slight decrease in accuracy in the pant pocket locations, Omron BI pedometers counted steps accurately across other locations when subjects walked on the flat sidewalk, and the performance was consistent across devices and trials. When the subjects climbed up stairs, however, the absolute error % of the pant pocket locations increased significantly (P < .05) and similar or higher error rates were found in the AMP 331 and SW-200s. The Omron BI pedometer can accurately count steps when worn at various locations on the body in free-living conditions except for front pant pocket locations, especially when climbing stairs.

  2. High Resolution WENO Simulation of 3D Detonation Waves

    DTIC Science & Technology

    2012-02-27

    pocket behind the detonation front was not observed in their results because the rotating transverse detonation completely consumed the unburned gas. Dou...three-dimensional detonations We add source terms (functions of x, y, z and t) to the PDE system so that the following functions are exact solutions to... detonation rotates counter-clockwise, opposite to that in [48]. It can be seen that, the triple lines and transverse waves collide with the walls, and strong

  3. Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress

    PubMed Central

    Kim, Min-Hyun; Aydemir, Tolunay B.; Kim, Jinhee; Cousins, Robert J.

    2017-01-01

    Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet–induced ER stress using Zip14−/− (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders. PMID:28673968

  4. Evolution and expression analysis reveal the potential role of the HD-Zip gene family in regulation of embryo abortion in grapes (Vitis vinifera L.).

    PubMed

    Li, Zhiqian; Zhang, Chen; Guo, Yurui; Niu, Weili; Wang, Yuejin; Xu, Yan

    2017-09-21

    The HD-Zip family has a diversity of functions during plant development. In this study, we identify 33 HD-Zip transcription factors in grape and detect their expressions in ovules and somatic embryos, as well as in various vegetative organs. A genome-wide survey for HD-Zip transcription factors in Vitis was conducted based on the 12 X grape genome (V. vinifera L.). A total of 33 members were identified and classified into four subfamilies (I-IV) based on phylogeny analysis with Arabidopsis, rice and maize. VvHDZs in the same subfamily have similar protein motifs and intron/exon structures. An evaluation of duplication events suggests several HD-Zip genes arose before the divergence of the grape and Arabidopsis lineages. The 33 members of HD-Zip were differentially expressed in ovules of the stenospermic grape, Thompson Seedless and of the seeded grape, Pinot noir. Most have higher expressions during ovule abortion in Thompson Seedless. In addition, transcripts of the HD-Zip family were also detected in somatic embryogenesis of Thompson Seedless and in different vegetative organs of Thompson Seedless at varying levels. Additionally, VvHDZ28 is located in the nucleus and had transcriptional activity consistent with the typical features of the HD-Zip family. Our results provide a foundation for future grape HD-Zip gene function research. The identification and expression profiles of the HD-Zip transcription factors in grape, reveal their diverse roles during ovule abortion and organ development. Our results lay a foundation for functional analysis of grape HDZ genes.

  5. Hepatic ZIP14-mediated zinc transport is required for adaptation to endoplasmic reticulum stress.

    PubMed

    Kim, Min-Hyun; Aydemir, Tolunay B; Kim, Jinhee; Cousins, Robert J

    2017-07-18

    Extensive endoplasmic reticulum (ER) stress damages the liver, causing apoptosis and steatosis despite the activation of the unfolded protein response (UPR). Restriction of zinc from cells can induce ER stress, indicating that zinc is essential to maintain normal ER function. However, a role for zinc during hepatic ER stress is largely unknown despite important roles in metabolic disorders, including obesity and nonalcoholic liver disease. We have explored a role for the metal transporter ZIP14 during pharmacologically and high-fat diet-induced ER stress using Zip14 -/- (KO) mice, which exhibit impaired hepatic zinc uptake. Here, we report that ZIP14-mediated hepatic zinc uptake is critical for adaptation to ER stress, preventing sustained apoptosis and steatosis. Impaired hepatic zinc uptake in Zip14 KO mice during ER stress coincides with greater expression of proapoptotic proteins. ER stress-induced Zip14 KO mice show greater levels of hepatic steatosis due to higher expression of genes involved in de novo fatty acid synthesis, which are suppressed in ER stress-induced WT mice. During ER stress, the UPR-activated transcription factors ATF4 and ATF6α transcriptionally up-regulate Zip14 expression. We propose ZIP14 mediates zinc transport into hepatocytes to inhibit protein-tyrosine phosphatase 1B (PTP1B) activity, which acts to suppress apoptosis and steatosis associated with hepatic ER stress. Zip14 KO mice showed greater hepatic PTP1B activity during ER stress. These results show the importance of zinc trafficking and functional ZIP14 transporter activity for adaptation to ER stress associated with chronic metabolic disorders.

  6. PpHB22, a member of HD-Zip proteins, activates PpDAM1 to regulate bud dormancy transition in 'Suli' pear (Pyrus pyrifolia White Pear Group).

    PubMed

    Yang, Qinsong; Niu, Qingfeng; Li, Jianzhao; Zheng, Xiaoyan; Ma, Yunjing; Bai, Songling; Teng, Yuanwen

    2018-06-01

    Homeodomain-leucine zipper (HD-Zip) proteins, which form one of the largest and most diverse families, regulate many biological processes in plants, including differentiation, flowering, vascular development, and stress signaling. Abscisic acid (ABA) has been proved to be one of the key regulators of bud dormancy and to influence several HD-Zip genes expression. However, the role of HD-Zip genes in regulating bud dormancy remains unclear. We identified 47 pear (P. pyrifolia White Pear Group) HD-Zip genes, which were classified into four subfamilies (HD-Zip I-IV). We further revealed that gene expression levels of some HD-Zip members were closely related to ABA concentrations in flower buds during dormancy transition. Exogenous ABA treatment confirmed that PpHB22 and several other HD-Zip genes responded to ABA. Yeast one-hybrid and dual luciferase assay results combining subcellular localization showed that PpHB22 was present in nucleus and directly induced PpDAM1 (dormancy associated MADS-box 1) expression. Thus, PpHB22 is a negative regulator of plant growth associated with the ABA response pathway and functions upstream of PpDAM1. These findings enrich our understanding of the function of HD-Zip genes related to the bud dormancy transition. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  7. Genome-Wide Identification, Evolutionary Expansion, and Expression Profile of Homeodomain-Leucine Zipper Gene Family in Poplar (Populus trichocarpa)

    PubMed Central

    Hu, Ruibo; Chi, Xiaoyuan; Chai, Guohua; Kong, Yingzhen; He, Guo; Wang, Xiaoyu; Shi, Dachuan; Zhang, Dongyuan; Zhou, Gongke

    2012-01-01

    Background Homeodomain-leucine zipper (HD-ZIP) proteins are plant-specific transcriptional factors known to play crucial roles in plant development. Although sequence phylogeny analysis of Populus HD-ZIPs was carried out in a previous study, no systematic analysis incorporating genome organization, gene structure, and expression compendium has been conducted in model tree species Populus thus far. Principal Findings In this study, a comprehensive analysis of Populus HD-ZIP gene family was performed. Sixty-three full-length HD-ZIP genes were found in Populus genome. These Populus HD-ZIP genes were phylogenetically clustered into four distinct subfamilies (HD-ZIP I–IV) and predominately distributed across 17 linkage groups (LG). Fifty genes from 25 Populus paralogous pairs were located in the duplicated blocks of Populus genome and then preferentially retained during the sequential evolutionary courses. Genomic organization analyses indicated that purifying selection has played a pivotal role in the retention and maintenance of Populus HD-ZIP gene family. Microarray analysis has shown that 21 Populus paralogous pairs have been differentially expressed across different tissues and under various stresses, with five paralogous pairs showing nearly identical expression patterns, 13 paralogous pairs being partially redundant and three paralogous pairs diversifying significantly. Quantitative real-time RT-PCR (qRT-PCR) analysis performed on 16 selected Populus HD-ZIP genes in different tissues and under both drought and salinity stresses confirms their tissue-specific and stress-inducible expression patterns. Conclusions Genomic organizations indicated that segmental duplications contributed significantly to the expansion of Populus HD-ZIP gene family. Exon/intron organization and conserved motif composition of Populus HD-ZIPs are highly conservative in the same subfamily, suggesting the members in the same subfamilies may also have conservative functionalities. Microarray and qRT-PCR analyses showed that 89% (56 out of 63) of Populus HD-ZIPs were duplicate genes that might have been retained by substantial subfunctionalization. Taken together, these observations may lay the foundation for future functional analysis of Populus HD-ZIP genes to unravel their biological roles. PMID:22359569

  8. Genome-wide analysis of the basic leucine zipper (bZIP) transcription factor gene family in six legume genomes.

    PubMed

    Wang, Zhihui; Cheng, Ke; Wan, Liyun; Yan, Liying; Jiang, Huifang; Liu, Shengyi; Lei, Yong; Liao, Boshou

    2015-12-10

    Plant bZIP proteins characteristically harbor a highly conserved bZIP domain with two structural features: a DNA-binding basic region and a leucine (Leu) zipper dimerization region. They have been shown to be diverse transcriptional regulators, playing crucial roles in plant development, physiological processes, and biotic/abiotic stress responses. Despite the availability of six completely sequenced legume genomes, a comprehensive investigation of bZIP family members in legumes has yet to be presented. In this study, we identified 428 bZIP genes encoding 585 distinct proteins in six legumes, Glycine max, Medicago truncatula, Phaseolus vulgaris, Cicer arietinum, Cajanus cajan, and Lotus japonicus. The legume bZIP genes were categorized into 11 groups according to their phylogenetic relationships with genes from Arabidopsis. Four kinds of intron patterns (a-d) within the basic and hinge regions were defined and additional conserved motifs were identified, both presenting high group specificity and supporting the group classification. We predicted the DNA-binding patterns and the dimerization properties, based on the characteristic features in the basic and hinge regions and the Leu zipper, respectively, which indicated that some highly conserved amino acid residues existed across each major group. The chromosome distribution and analysis for WGD-derived duplicated blocks revealed that the legume bZIP genes have expanded mainly by segmental duplication rather than tandem duplication. Expression data further revealed that the legume bZIP genes were expressed constitutively or in an organ-specific, development-dependent manner playing roles in multiple seed developmental stages and tissues. We also detected several key legume bZIP genes involved in drought- and salt-responses by comparing fold changes of expression values in drought-stressed or salt-stressed roots and leaves. In summary, this genome-wide identification, characterization and expression analysis of legume bZIP genes provides valuable information for understanding the molecular functions and evolution of the legume bZIP transcription factor family, and highlights potential legume bZIP genes involved in regulating tissue development and abiotic stress responses.

  9. Characterization of a putative grapevine Zn transporter, VvZIP3, suggests its involvement in early reproductive development in Vitis vinifera L

    PubMed Central

    2012-01-01

    Background Zinc (Zn) deficiency is one of the most widespread mineral nutritional problems that affect normal development in plants. Because Zn cannot passively diffuse across cell membranes, it must be transported into intracellular compartments for all biological processes where Zn is required. Several members of the Zinc-regulated transporters, Iron-regulated transporter-like Protein (ZIP) gene family have been characterized in plants, and have shown to be involved in metal uptake and transport. This study describes the first putative Zn transporter in grapevine. Unravelling its function may explain an important symptom of Zn deficiency in grapevines, which is the production of clusters with fewer and usually smaller berries than normal. Results We identified and characterized a putative Zn transporter from berries of Vitis vinifera L., named VvZIP3. Compared to other members of the ZIP family identified in the Vitis vinifera L. genome, VvZIP3 is mainly expressed in reproductive tissue - specifically in developing flowers - which correlates with the high Zn accumulation in these organs. Contrary to this, the low expression of VvZIP3 in parthenocarpic berries shows a relationship with the lower Zn accumulation in this tissue than in normal seeded berries where its expression is induced by Zn. The predicted protein sequence indicates strong similarity with several members of the ZIP family from Arabidopsis thaliana and other species. Moreover, VvZIP3 complemented the growth defect of a yeast Zn-uptake mutant, ZHY3, and is localized in the plasma membrane of plant cells, suggesting that VvZIP3 has the function of a Zn uptake transporter. Conclusions Our results suggest that VvZIP3 encodes a putative plasma membrane Zn transporter protein member of the ZIP gene family that might play a role in Zn uptake and distribution during the early reproductive development in Vitis vinifera L., indicating that the availability of this micronutrient may be relevant for reproductive development. PMID:22824090

  10. A basic leucine zipper transcription factor, AabZIP1, connects abscisic acid signaling with artemisinin biosynthesis in Artemisia annua.

    PubMed

    Zhang, Fangyuan; Fu, Xueqing; Lv, Zongyou; Lu, Xu; Shen, Qian; Zhang, Ling; Zhu, Mengmeng; Wang, Guofeng; Sun, Xiaofen; Liao, Zhihua; Tang, Kexuan

    2015-01-01

    Artemisinin is a sesquiterpenoid especially synthesized in the Chinese herbal plant, Artemisia annua, which is widely used in the treatment of malaria. Artemisinin accumulation can be enhanced by exogenous abscisic acid (ABA) treatment. However, it is not known how ABA signaling regulates artemisinin biosynthesis. A global expression profile and phylogenetic analysis as well as the dual-LUC screening revealed that a basic leucine zipper family transcription factor from A. annua (namely AabZIP1) was involved in ABA signaling to regulate artemisinin biosynthesis. AabZIP1 had a higher expression level in the inflorescences than in other tissues; ABA treatment, drought, and salt stress strongly induced the expression of AabZIP1. Yeast one-hybrid assay and electrophoretic mobility shift assay (EMSA) showed that AabZIP1 bound to the ABA-responsive elements (ABRE) in the promoter regions of the amorpha-4,11-diene synthase (ADS) gene and CYP71AV1, which are two key structural genes of the artemisinin biosynthetic pathway. A mutagenesis assay showed that the C1 domain in the N-terminus of AabZIP1 was important for its transactivation activity. Furthermore, the activation of ADS and CYP71AV1 promoters by AabZIP1 was enhanced by ABA treatment in transient dual-LUC analysis. The AabZIP1 variant with C1 domain deletion lost the ability to activate ADS and CYP71AV1 promoters regardless of ABA treatment. Notably, overexpression of AabZIP1 in A. annua resulted in significantly increased accumulation of artemisinin. Our results indicate that ABA promotes artemisinin biosynthesis, likely through 1 activation of ADS and CYP71AV1 expression by AabZIP in A. annua. Meanwhile, our findings reveal the potential value of AabZIP1 in genetic engineering of artemisinin production. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  11. PSD-Zip70 Deficiency Causes Prefrontal Hypofunction Associated with Glutamatergic Synapse Maturation Defects by Dysregulation of Rap2 Activity.

    PubMed

    Mayanagi, Taira; Yasuda, Hiroki; Sobue, Kenji

    2015-10-21

    Dysregulation of synapse formation and plasticity is closely related to the pathophysiology of psychiatric and neurodevelopmental disorders. The prefrontal cortex (PFC) is particularly important for executive functions such as working memory, cognition, and emotional control, which are impaired in the disorders. PSD-Zip70 (Lzts1/FEZ1) is a postsynaptic density (PSD) protein predominantly expressed in the frontal cortex, olfactory bulb, striatum, and hippocampus. Here we found that PSD-Zip70 knock-out (PSD-Zip70KO) mice exhibit working memory and cognitive defects, and enhanced anxiety-like behaviors. These abnormal behaviors are caused by impaired glutamatergic synapse transmission accompanied by tiny-headed immature dendritic spines in the PFC, due to aberrant Rap2 activation, which has roles in synapse formation and plasticity. PSD-Zip70 modulates the Rap2 activity by interacting with SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) in the postsynapse. Furthermore, suppression of the aberrant Rap2 activation in the PFC rescued the behavioral defects in PSD-Zip70KO mice. Our data demonstrate a critical role for PSD-Zip70 in Rap2-dependent spine synapse development in the PFC and underscore the importance of this regulation in PFC-dependent behaviors. PSD-Zip70 deficiency causes behavioral defects in working memory and cognition, and enhanced anxiety due to prefrontal hypofunction. This study revealed that PSD-Zip70 plays essential roles in glutamatergic synapse maturation via modulation of the Rap2 activity in the PFC. PSD-Zip70 interacts with both SPAR (spine-associated RapGAP) and PDZ-GEF1 (RapGEF) and modulates the Rap2 activity in postsynaptic sites. Our results provide a novel Rap2-specific regulatory mechanism in synaptic maturation involving PSD-Zip70. Copyright © 2015 the authors 0270-6474/15/3514327-14$15.00/0.

  12. Reassessment of the transport mechanism of the human zinc transporter SLC39A2.

    PubMed

    Franz, Marie Christine; Pujol-Gimenez, Jonai; Montalbetti, Nicolas; Fernandez-Tenorio, Miguel; DeGrado, Timothy R; Niggli, Ernst; Romero, Michael F; Hediger, Matthias A

    2018-05-23

    The human zinc transporter SLC39A2, also known as ZIP2, was shown to mediate zinc transport that could be inhibited at pH values below 7.0 and stimulated by HCO3-, suggesting a Zn2+/HCO3- cotransport mechanism (1). In contrast, recent experiments in our laboratory indicated that the functional activity of ZIP2 increases at acidic pH (2). The present study was therefore designed to reexamine the findings on the pH-dependence and to extend the functional characterization of ZIP2. Our current results show that ZIP2-mediated transport is modulated by extracellular pH, but independent of the H+ driving force. Also, in our experiments, ZIP2-mediated transport is not modulated by extracellular HCO3-. Moreover, high extracellular [K+], which induces depolarization, inhibited ZIP2-mediated transport, indicating that the transport mechanism is voltage-dependent. We also show that ZIP2-mediates the uptake of Cd2+ (Km~ 1.57 µM) in a pH-dependent manner (KH+ of ~66 nM). Cd2+ transport is inhibited by extracellular [Zn2+] (IC50~ 0.32 µM), [Cu2+] (IC50~ 1.81 µM) and to a lower extend by [Co2+], but not by [Mn2+] or [Ba2+]. Fe2+ is not transported by ZIP2. Accordingly, the substrate selectivity of ZIP2 decreases in the order Zn2+ > Cd2+ ≥ Cu2+ > Co2+. Altogether, we propose that ZIP2 is a facilitated divalent metal ion transporter that can be modulated by extracellular pH and membrane potential. Given that ZIP2 expression has been reported in acidic environments (3-5), we suggest that the herein described H+-mediated regulatory mechanism might be important to determine the velocity and direction of the transport process.

  13. Genome-Wide Analysis of Soybean HD-Zip Gene Family and Expression Profiling under Salinity and Drought Treatments

    PubMed Central

    Chen, Xue; Chen, Zhu; Zhao, Hualin; Zhao, Yang; Cheng, Beijiu; Xiang, Yan

    2014-01-01

    Background Homeodomain-leucine zipper (HD-Zip) proteins, a group of homeobox transcription factors, participate in various aspects of normal plant growth and developmental processes as well as environmental responses. To date, no overall analysis or expression profiling of the HD-Zip gene family in soybean (Glycine max) has been reported. Methods and Findings An investigation of the soybean genome revealed 88 putative HD-Zip genes. These genes were classified into four subfamilies, I to IV, based on phylogenetic analysis. In each subfamily, the constituent parts of gene structure and motif were relatively conserved. A total of 87 out of 88 genes were distributed unequally on 20 chromosomes with 36 segmental duplication events, indicating that segmental duplication is important for the expansion of the HD-Zip family. Analysis of the Ka/Ks ratios showed that the duplicated genes of the HD-Zip family basically underwent purifying selection with restrictive functional divergence after the duplication events. Analysis of expression profiles showed that 80 genes differentially expressed across 14 tissues, and 59 HD-Zip genes are differentially expressed under salinity and drought stress, with 20 paralogous pairs showing nearly identical expression patterns and three paralogous pairs diversifying significantly under drought stress. Quantitative real-time RT-PCR (qRT-PCR) analysis of six paralogous pairs of 12 selected soybean HD-Zip genes under both drought and salinity stress confirmed their stress-inducible expression patterns. Conclusions This study presents a thorough overview of the soybean HD-Zip gene family and provides a new perspective on the evolution of this gene family. The results indicate that HD-Zip family genes may be involved in many plant responses to stress conditions. Additionally, this study provides a solid foundation for uncovering the biological roles of HD-Zip genes in soybean growth and development. PMID:24498296

  14. Characterization of a putative grapevine Zn transporter, VvZIP3, suggests its involvement in early reproductive development in Vitis vinifera L.

    PubMed

    Gainza-Cortés, Felipe; Pérez-Dïaz, Ricardo; Pérez-Castro, Ramón; Tapia, Jaime; Casaretto, José A; González, Sebastián; Peña-Cortés, Hugo; Ruiz-Lara, Simón; González, Enrique

    2012-07-23

    Zinc (Zn) deficiency is one of the most widespread mineral nutritional problems that affect normal development in plants. Because Zn cannot passively diffuse across cell membranes, it must be transported into intracellular compartments for all biological processes where Zn is required. Several members of the Zinc-regulated transporters, Iron-regulated transporter-like Protein (ZIP) gene family have been characterized in plants, and have shown to be involved in metal uptake and transport. This study describes the first putative Zn transporter in grapevine. Unravelling its function may explain an important symptom of Zn deficiency in grapevines, which is the production of clusters with fewer and usually smaller berries than normal. We identified and characterized a putative Zn transporter from berries of Vitis vinifera L., named VvZIP3. Compared to other members of the ZIP family identified in the Vitis vinifera L. genome, VvZIP3 is mainly expressed in reproductive tissue - specifically in developing flowers - which correlates with the high Zn accumulation in these organs. Contrary to this, the low expression of VvZIP3 in parthenocarpic berries shows a relationship with the lower Zn accumulation in this tissue than in normal seeded berries where its expression is induced by Zn. The predicted protein sequence indicates strong similarity with several members of the ZIP family from Arabidopsis thaliana and other species. Moreover, VvZIP3 complemented the growth defect of a yeast Zn-uptake mutant, ZHY3, and is localized in the plasma membrane of plant cells, suggesting that VvZIP3 has the function of a Zn uptake transporter. Our results suggest that VvZIP3 encodes a putative plasma membrane Zn transporter protein member of the ZIP gene family that might play a role in Zn uptake and distribution during the early reproductive development in Vitis vinifera L., indicating that the availability of this micronutrient may be relevant for reproductive development.

  15. Properties of Zip4 accumulation during zinc deficiency and its usefulness to evaluate zinc status: a study of the effects of zinc deficiency during lactation.

    PubMed

    Hashimoto, Ayako; Nakagawa, Miki; Tsujimura, Natsuki; Miyazaki, Shiho; Kizu, Kumiko; Goto, Tomoko; Komatsu, Yusuke; Matsunaga, Ayu; Shirakawa, Hitoshi; Narita, Hiroshi; Kambe, Taiho; Komai, Michio

    2016-03-01

    Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely. Copyright © 2016 the American Physiological Society.

  16. Expression of a grape (Vitis vinifera) bZIP transcription factor, VlbZIP36, in Arabidopsis thaliana confers tolerance of drought stress during seed germination and seedling establishment.

    PubMed

    Tu, Mingxing; Wang, Xianhang; Feng, Tongying; Sun, Xiaomeng; Wang, Yaqiong; Huang, Li; Gao, Min; Wang, Yuejin; Wang, Xiping

    2016-11-01

    Drought is one of the most serious factors that limit agricultural productivity and there is considerable interest in understanding the molecular bases of drought responses and their regulation. While numbers of basic leucine zipper (bZIP) transcription factors (TFs) are known to play key roles in response of plants to various abiotic stresses, only a few group K bZIP TFs have been functionally characterized in the context of stress signaling. In this study, we characterized the expression of the grape (Vitis vinifera) group K bZIP gene, VlbZIP36, and found evidence for its involvement in response to drought and the stress-associated phytohormone abscisic acid (ABA). Transgenic Arabidopsis thaliana lines over-expressing VlbZIP36 under the control of a constitutive promoter showed enhanced dehydration tolerance during the seed germination stage, as well as in the seedling and mature plant stages. The results indicated that VlbZIP36 plays a role in drought tolerance by improving the water status, through limiting water loss, and mitigating cellular damage. The latter was evidenced by reduced cell death, lower electrolyte leakage in the transgenic plants, as well as by increased activities of antioxidant enzymes. We concluded that VlbZIP36 enhances drought tolerance through the transcriptional regulation of ABA-/stress-related genes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Poplar PtabZIP1-like enhances lateral root formation and biomass growth under drought stress

    DOE PAGES

    Dash, Madhumita; Yordanov, Yordan S.; Georgieva, Tatyana; ...

    2017-02-10

    Developing drought-resistance varieties is a major goal for bioenergy crops, such as poplar (Populus), which will be grown on marginal lands with little or no water input. Root architecture can affect drought resistance, but few genes that affect root architecture in relation to water availability have been identified. Here in this study, using activation tagging in the prime bioenergy crop poplar, we have identified a mutant that overcomes the block of lateral root (LR) formation under osmotic stress. Positioning of the tag, validation of the activation and recapitulation showed that the phenotype is caused by the poplar PtabZIP1-like (PtabZIP1L) genemore » with highest homology to bZIP1 from Arabidopsis. PtabZIP1L is predominantly expressed in roots, particularly in zones where lateral root primordia (LRP) initiate and LR differentiate and emerge. Transgenics overexpressing PtabZIP1L showed precocious LRP and LR development, while PtabZIP1L suppression significantly delayed both LRP and LR formation. Transgenic overexpression and suppression of PtabZIP1L also resulted in modulation of key metabolites like proline, asparagine, valine and several flavonoids. Consistently, expression of both of the poplar Proline Dehydrogenase orthologs and two of the Flavonol Synthases genes was also increased and decreased in overexpressed and suppressed transgenics, respectively. These findings suggest that PtabZIP1L mediates LR development and drought resistance through modulation of multiple metabolic pathways.« less

  18. Poplar PtabZIP1-like enhances lateral root formation and biomass growth under drought stress

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

    Dash, Madhumita; Yordanov, Yordan S.; Georgieva, Tatyana

    Developing drought-resistance varieties is a major goal for bioenergy crops, such as poplar (Populus), which will be grown on marginal lands with little or no water input. Root architecture can affect drought resistance, but few genes that affect root architecture in relation to water availability have been identified. Here in this study, using activation tagging in the prime bioenergy crop poplar, we have identified a mutant that overcomes the block of lateral root (LR) formation under osmotic stress. Positioning of the tag, validation of the activation and recapitulation showed that the phenotype is caused by the poplar PtabZIP1-like (PtabZIP1L) genemore » with highest homology to bZIP1 from Arabidopsis. PtabZIP1L is predominantly expressed in roots, particularly in zones where lateral root primordia (LRP) initiate and LR differentiate and emerge. Transgenics overexpressing PtabZIP1L showed precocious LRP and LR development, while PtabZIP1L suppression significantly delayed both LRP and LR formation. Transgenic overexpression and suppression of PtabZIP1L also resulted in modulation of key metabolites like proline, asparagine, valine and several flavonoids. Consistently, expression of both of the poplar Proline Dehydrogenase orthologs and two of the Flavonol Synthases genes was also increased and decreased in overexpressed and suppressed transgenics, respectively. These findings suggest that PtabZIP1L mediates LR development and drought resistance through modulation of multiple metabolic pathways.« less

  19. Residential Segregation and the Availability of Primary Care Physicians

    PubMed Central

    Gaskin, Darrell J; Dinwiddie, Gniesha Y; Chan, Kitty S; McCleary, Rachael R

    2012-01-01

    Objective To examine the association between residential segregation and geographic access to primary care physicians (PCPs) in metropolitan statistical areas (MSAs). Data Sources We combined zip code level data on primary care physicians from the 2006 American Medical Association master file with demographic, socioeconomic, and segregation measures from the 2000 U.S. Census. Our sample consisted of 15,465 zip codes located completely or partially in an MSA. Methods We defined PCP shortage areas as those zip codes with no PCP or a population to PCP ratio of >3,500. Using logistic regressions, we estimated the association between a zip code's odds of being a PCP shortage area and its minority composition and degree of segregation in its MSA. Principal Findings We found that odds of being a PCP shortage area were 67 percent higher for majority African American zip codes but 27 percent lower for majority Hispanic zip codes. The association varied with the degree of segregation. As the degree of segregation increased, the odds of being a PCP shortage area increased for majority African American zip codes; however, the converse was true for majority Hispanic and Asian zip codes. Conclusions Efforts to address PCP shortages should target African American communities especially in segregated MSAs. PMID:22524264

  20. Requirement of Zinc Transporter SLC39A7/ZIP7 for Dermal Development to Fine-Tune Endoplasmic Reticulum Function by Regulating Protein Disulfide Isomerase.

    PubMed

    Bin, Bum-Ho; Bhin, Jinhyuk; Seo, Juyeon; Kim, Se-Young; Lee, Eunyoung; Park, Kyuhee; Choi, Dong-Hwa; Takagishi, Teruhisa; Hara, Takafumi; Hwang, Daehee; Koseki, Haruhiko; Asada, Yoshinobu; Shimoda, Shinji; Mishima, Kenji; Fukada, Toshiyuki

    2017-08-01

    Skin is the first area that manifests zinc deficiency. However, the molecular mechanisms by which zinc homeostasis affects skin development remain largely unknown. Here, we show that zinc-regulation transporter-/iron-regulation transporter-like protein 7 (ZIP7) localized to the endoplasmic reticulum plays critical roles in connective tissue development. Mice lacking the Slc39a7/Zip7 gene in collagen 1-expressing tissue exhibited dermal dysplasia. Ablation of ZIP7 in mesenchymal stem cells inhibited cell proliferation thereby preventing proper dermis formation, indicating that ZIP7 is required for dermal development. We also found that mesenchymal stem cells lacking ZIP7 accumulated zinc in the endoplasmic reticulum, which triggered zinc-dependent aggregation and inhibition of protein disulfide isomerase, leading to endoplasmic reticulum dysfunction. These results suggest that ZIP7 is necessary for endoplasmic reticulum function in mesenchymal stem cells and, as such, is essential for dermal development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Efficient Proximity Computation Techniques Using ZIP Code Data for Smart Cities †

    PubMed Central

    Murdani, Muhammad Harist; Hong, Bonghee

    2018-01-01

    In this paper, we are interested in computing ZIP code proximity from two perspectives, proximity between two ZIP codes (Ad-Hoc) and neighborhood proximity (Top-K). Such a computation can be used for ZIP code-based target marketing as one of the smart city applications. A naïve approach to this computation is the usage of the distance between ZIP codes. We redefine a distance metric combining the centroid distance with the intersecting road network between ZIP codes by using a weighted sum method. Furthermore, we prove that the results of our combined approach conform to the characteristics of distance measurement. We have proposed a general and heuristic approach for computing Ad-Hoc proximity, while for computing Top-K proximity, we have proposed a general approach only. Our experimental results indicate that our approaches are verifiable and effective in reducing the execution time and search space. PMID:29587366

  2. ZIP4 silencing improves bone loss in pancreatic cancer

    PubMed Central

    Yang, Jingxuan; Ding, Hao; LeBrun, Drake; Ding, Kai; Houchen, Courtney W.; Postier, Russell G.; Ambrose, Catherine G.; Li, Zhaoshen; Bi, Xiaohong; Li, Min

    2015-01-01

    Metabolic bone disorders are associated with several types of human cancers. Pancreatic cancer patients usually suffer from severe nutrition deficiency, muscle wasting, and loss of bone mass. We have previously found that silencing of a zinc transporter ZIP4 prolongs the survival and reduces the severity of the cachexia in vivo. However, the role of ZIP4 in the pancreatic cancer related bone loss remains unknown. In this study we investigated the effect of ZIP4 knockdown on the bone structure, composition and mechanical properties of femurs in an orthotopic xenograft mouse model. Our data showed that silencing of ZIP4 resulted in increased bone tissue mineral density, decreased bone crystallinity and restoration of bone strength through the RANK/RANKL pathway. The results further support the impact of ZIP4 on the progression of pancreatic cancer, and suggest its potential significance as a therapeutic target for treating patients with such devastating disease and cancer related disorders. PMID:26305676

  3. Indianapolis emergency medical service and the Indiana Network for Patient Care: evaluating the patient match algorithm.

    PubMed

    Park, Seong C; Finnell, John T

    2012-01-01

    In 2009, Indianapolis launched an electronic medical record system within their ambulances1 and started to exchange patient data with the Indiana Network for Patient Care (INPC) This unique system allows EMS personnel to get important information prior to the patient's arrival to the hospital. In this descriptive study, we found EMS personnel requested patient data on 14% of all transports, with a "success" match rate of 46%, and a match "failure" rate of 17%. The three major factors for causing match "failure" were ZIP code 55%, Patient Name 22%, and Birth date 12%. We conclude that the ZIP code matching process needs to be improved by applying a limitation of 5 digits in ZIP code instead of using ZIP+4 code. Non-ZIP code identifiers may be a better choice due to inaccuracies and changes of the ZIP code in a patient's record.

  4. Efficient Proximity Computation Techniques Using ZIP Code Data for Smart Cities †.

    PubMed

    Murdani, Muhammad Harist; Kwon, Joonho; Choi, Yoon-Ho; Hong, Bonghee

    2018-03-24

    In this paper, we are interested in computing ZIP code proximity from two perspectives, proximity between two ZIP codes ( Ad-Hoc ) and neighborhood proximity ( Top-K ). Such a computation can be used for ZIP code-based target marketing as one of the smart city applications. A naïve approach to this computation is the usage of the distance between ZIP codes. We redefine a distance metric combining the centroid distance with the intersecting road network between ZIP codes by using a weighted sum method. Furthermore, we prove that the results of our combined approach conform to the characteristics of distance measurement. We have proposed a general and heuristic approach for computing Ad-Hoc proximity, while for computing Top-K proximity, we have proposed a general approach only. Our experimental results indicate that our approaches are verifiable and effective in reducing the execution time and search space.

  5. Basic leucine zipper domain transcription factors: the vanguards in plant immunity.

    PubMed

    Noman, Ali; Liu, Zhiqin; Aqeel, Muhammad; Zainab, Madiha; Khan, Muhammad Ifnan; Hussain, Ansar; Ashraf, Muhammad Furqan; Li, Xia; Weng, Yahong; He, Shuilin

    2017-12-01

    Regulation of spatio-temporal expression patterns of stress tolerance associated plant genes is an essential component of the stress responses. Eukaryotes assign a large amount of their genome to transcription with multiple transcription factors (TFs). Often, these transcription factors fit into outsized gene groups which, in several cases, exclusively belong to plants. Basic leucine zipper domain (bZIP) transcription factors regulate vital processes in plants and animals. In plants, bZIPs are implicated in numerous fundamental processes like seed development, energy balance, and responses to abiotic or biotic stresses. Systematic analysis of the information obtained over the last two decades disclosed a constitutive role of bZIPs against biotic stress. bZIP TFs are vital players in plant innate immunity due to their ability to regulate genes associated with PAMP-triggered immunity, effector-triggered immunity, and hormonal signaling networks. Expression analysis of studied bZIP genes suggests that exploration and functional characterization of novel bZIP TFs in planta is helpful in improving crop resistance against pathogens and environmental stresses. Our review focuses on major advancements in bZIP TFs and plant responses against different pathogens. The integration of genomics information with the functional studies provides new insights into the regulation of plant defense mechanisms and engineering crops with improved resistance to invading pathogens. Conclusively, succinct functions of bZIPs as positive or negative regulator mediate resistance to the plant pathogens and lay a foundation for understanding associated genes and TFs regulating different pathways. Moreover, bZIP TFs may offer a comprehensive transgenic gizmo for engineering disease resistance in plant breeding programs.

  6. hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer

    PubMed Central

    Franklin, Renty B; Feng, Pei; Milon, B; Desouki, Mohamed M; Singh, Keshav K; Kajdacsy-Balla, André; Bagasra, Omar; Costello, Leslie C

    2005-01-01

    Background The genetic and molecular mechanisms responsible for and associated with the development and progression of prostate malignancy are largely unidentified. The peripheral zone is the major region of the human prostate gland where malignancy develops. The normal peripheral zone glandular epithelium has the unique function of accumulating high levels of zinc. In contrast, the ability to accumulate zinc is lost in the malignant cells. The lost ability of the neoplastic epithelial cells to accumulate zinc is a consistent factor in their development of malignancy. Recent studies identified ZIP1 (SLC39A1) as an important zinc transporter involved in zinc accumulation in prostate cells. Therefore, we investigated the possibility that down-regulation of hZIP1 gene expression might be involved in the inability of malignant prostate cells to accumulate zinc. To address this issue, the expression of hZIP1 and the depletion of zinc in malignant versus non-malignant prostate glands of prostate cancer tissue sections were analyzed. hZIP1 expression was also determined in malignant prostate cell lines. Results hZIP1 gene expression, ZIP1 transporter protein, and cellular zinc were prominent in normal peripheral zone glandular epithelium and in benign hyperplastic glands (also zinc accumulating glands). In contrast, hZIP1 gene expression and transporter protein were markedly down-regulated and zinc was depleted in adenocarcinomatous glands and in prostate intra-epithelial neoplastic foci (PIN). These changes occur early in malignancy and are sustained during its progression in the peripheral zone. hZIP1 is also expressed in the malignant cell lines LNCaP, PC-3, DU-145; and in the nonmalignant cell lines HPr-1 and BPH-1. Conclusion The studies clearly establish that hZIP1 gene expression is down regulated and zinc is depleted in adenocarcinomatous glands. The fact that all the malignant cell lines express hZIP1 indicates that the down-regulation in adenocarcinomatous glands is likely due to in situ gene silencing. These observations, coupled with the numerous and consistent reports of loss of zinc accumulation in malignant cells in prostate cancer, lead to the plausible proposal that down regulation of hZIP1 is a critical early event in the development prostate cancer. PMID:16153295

  7. Using ZIP Code Business Patterns Data to Measure Alcohol Outlet Density

    PubMed Central

    Matthews, Stephen A.; McCarthy, John D.; Rafail, Patrick S.

    2014-01-01

    Some states maintain high-quality alcohol outlet databases but quality varies by state, making comprehensive comparative analysis across US communities difficult. This study assesses the adequacy of using ZIP Code Business Patterns (ZIP-BP) data on establishments as estimates of the number of alcohol outlets by ZIP code. Specifically we compare ZIP-BP alcohol outlet counts with high-quality data from state and local records surrounding 44 college campus communities across 10 states plus the District of Columbia. Results show that a composite measure is strongly correlated (R=0.89) with counts of alcohol outlets generated from official state records. Analyses based on Generalized Estimation Equation models show that community and contextual factors have little impact on the concordance between the two data sources. There are also minimal inter-state differences in the level of agreement. To validate the use of a convenient secondary data set (ZIP-BP) it is important to have a high correlation with the more complex, high quality and more costly data product (i.e., datasets based on the acquisition and geocoding of state and local records) and then to clearly demonstrate that the discrepancy between the two to be unrelated to relevant explanatory variables. Thus our overall findings support the adequacy of using a conveniently available data set (ZIP-BP data) to estimate alcohol outlet densities in ZIP code areas in future research. PMID:21411233

  8. Using ZIP code business patterns data to measure alcohol outlet density.

    PubMed

    Matthews, Stephen A; McCarthy, John D; Rafail, Patrick S

    2011-07-01

    Some states maintain high-quality alcohol outlet databases but quality varies by state, making comprehensive comparative analysis across US communities difficult. This study assesses the adequacy of using ZIP Code Business Patterns (ZIP-BP) data on establishments as estimates of the number of alcohol outlets by ZIP code. Specifically we compare ZIP-BP alcohol outlet counts with high-quality data from state and local records surrounding 44 college campus communities across 10 states plus the District of Columbia. Results show that a composite measure is strongly correlated (R=0.89) with counts of alcohol outlets generated from official state records. Analyses based on Generalized Estimation Equation models show that community and contextual factors have little impact on the concordance between the two data sources. There are also minimal inter-state differences in the level of agreement. To validate the use of a convenient secondary data set (ZIP-BP) it is important to have a high correlation with the more complex, high quality and more costly data product (i.e., datasets based on the acquisition and geocoding of state and local records) and then to clearly demonstrate that the discrepancy between the two to be unrelated to relevant explanatory variables. Thus our overall findings support the adequacy of using a conveniently available data set (ZIP-BP data) to estimate alcohol outlet densities in ZIP code areas in future research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Genome Wide Identification of Orthologous ZIP Genes Associated with Zinc and Iron Translocation in Setaria italica.

    PubMed

    Alagarasan, Ganesh; Dubey, Mahima; Aswathy, Kumar S; Chandel, Girish

    2017-01-01

    Genes in the ZIP family encode transcripts to store and transport bivalent metal micronutrient, particularly iron (Fe) and or zinc (Zn). These transcripts are important for a variety of functions involved in the developmental and physiological processes in many plant species, including most, if not all, Poaceae plant species and the model species Arabidopsis. Here, we present the report of a genome wide investigation of orthologous ZIP genes in Setaria italica and the identification of 7 single copy genes. RT-PCR shows 4 of them could be used to increase the bio-availability of zinc and iron content in grains. Of 36 ZIP members, 25 genes have traces of signal peptide based sub-cellular localization, as compared to those of plant species studied previously, yet translocation of ions remains unclear. In silico analysis of gene structure and protein nature suggests that these two were preeminent in shaping the functional diversity of the ZIP gene family in S. italica . NAC, bZIP and bHLH are the predominant Fe and Zn responsive transcription factors present in SiZIP genes. Together, our results provide new insights into the signal peptide based/independent iron and zinc translocation in the plant system and allowed identification of ZIP genes that may be involved in the zinc and iron absorption from the soil, and thus transporting it to the cereal grain underlying high micronutrient accumulation.

  10. Crosstalk between Two bZIP Signaling Pathways Orchestrates Salt-Induced Metabolic Reprogramming in Arabidopsis Roots

    PubMed Central

    Hartmann, Laura; Pedrotti, Lorenzo; Weiste, Christoph; Fekete, Agnes; Schierstaedt, Jasper; Göttler, Jasmin; Kempa, Stefan; Krischke, Markus; Dietrich, Katrin; Mueller, Martin J.; Vicente-Carbajosa, Jesus; Hanson, Johannes; Dröge-Laser, Wolfgang

    2015-01-01

    Soil salinity increasingly causes crop losses worldwide. Although roots are the primary targets of salt stress, the signaling networks that facilitate metabolic reprogramming to induce stress tolerance are less understood than those in leaves. Here, a combination of transcriptomic and metabolic approaches was performed in salt-treated Arabidopsis thaliana roots, which revealed that the group S1 basic leucine zipper transcription factors bZIP1 and bZIP53 reprogram primary C- and N-metabolism. In particular, gluconeogenesis and amino acid catabolism are affected by these transcription factors. Importantly, bZIP1 expression reflects cellular stress and energy status in roots. In addition to the well-described abiotic stress response pathway initiated by the hormone abscisic acid (ABA) and executed by SnRK2 (Snf1-RELATED-PROTEIN-KINASE2) and AREB-like bZIP factors, we identify a structurally related ABA-independent signaling module consisting of SnRK1s and S1 bZIPs. Crosstalk between these signaling pathways recruits particular bZIP factor combinations to establish at least four distinct gene expression patterns. Understanding this signaling network provides a framework for securing future crop productivity. PMID:26276836

  11. Role of Homeodomain leucine zipper (HD-Zip) IV transcription factors in plant development and plant protection from deleterious environmental factors.

    PubMed

    Chew, William; Hrmova, Maria; Lopato, Sergiy

    2013-04-12

    Homeobox genes comprise an important group of genes that are responsible for regulation of developmental processes. These genes determine cell differentiation and cell fate in all eukaryotic organisms, starting from the early stages of embryo development. Homeodomain leucine zipper (HD-Zip) transcription factors are unique to the plant kingdom. Members of the HD-Zip IV subfamily have a complex domain topology and can bind several cis-elements with overlapping sequences. Many of the reported HD-Zip IV genes were shown to be specifically or preferentially expressed in plant epidermal or sub-epidermal cells. HD-Zip IV TFs were found to be associated with differentiation and maintenance of outer cell layers, and regulation of lipid biosynthesis and transport. Insights about the role of these proteins in plant cuticle formation, and hence their possible involvement in plant protection from pathogens and abiotic stresses has just started to emerge. These roles make HD-Zip IV proteins an attractive tool for genetic engineering of crop plants. To this end, there is a need for in-depth studies to further clarify the function of each HD-Zip IV subfamily member in commercially important plant species.

  12. Role of Homeodomain Leucine Zipper (HD-Zip) IV Transcription Factors in Plant Development and Plant Protection from Deleterious Environmental Factors

    PubMed Central

    Chew, William; Hrmova, Maria; Lopato, Sergiy

    2013-01-01

    Homeobox genes comprise an important group of genes that are responsible for regulation of developmental processes. These genes determine cell differentiation and cell fate in all eukaryotic organisms, starting from the early stages of embryo development. Homeodomain leucine zipper (HD-Zip) transcription factors are unique to the plant kingdom. Members of the HD-Zip IV subfamily have a complex domain topology and can bind several cis-elements with overlapping sequences. Many of the reported HD-Zip IV genes were shown to be specifically or preferentially expressed in plant epidermal or sub-epidermal cells. HD-Zip IV TFs were found to be associated with differentiation and maintenance of outer cell layers, and regulation of lipid biosynthesis and transport. Insights about the role of these proteins in plant cuticle formation, and hence their possible involvement in plant protection from pathogens and abiotic stresses has just started to emerge. These roles make HD-Zip IV proteins an attractive tool for genetic engineering of crop plants. To this end, there is a need for in-depth studies to further clarify the function of each HD-Zip IV subfamily member in commercially important plant species. PMID:23584027

  13. 39 CFR Appendix A to Part 121 - Tables Depicting Service Standard Day Ranges

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... & USVI Periodicals 1 1-3 1 1-3 1-4 (AK) 11 (JNU) 11 (KTN) 1 (HI) 2 (GU) 1-4 10-11 10 8-10 Standard Mail 2 3 3-4 3-4 14 13 12 Package Services 1 2 2-3 2-3 12 11 11 AK = Alaska 3-digit ZIP Codes 995-997; JNU = Juneau AK 3-digit ZIP Code 998; KTN = Ketchikan AK 3-digit ZIP Code 999; HI = Hawaii 3-digit ZIP Codes...

  14. 39 CFR Appendix A to Part 121 - Tables Depicting Service Standard Day Ranges

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... & USVI Periodicals 1 1-3 1 1-3 1-4 (AK) 11 (JNU) 11 (KTN) 1 (HI) 2 (GU) 1-4 10-11 10 8-10 Standard Mail 2 3 3-4 3-4 14 13 12 Package Services 1 2 2-3 2-3 12 11 11 AK = Alaska 3-digit ZIP Codes 995-997; JNU = Juneau AK 3-digit ZIP Code 998; KTN = Ketchikan AK 3-digit ZIP Code 999; HI = Hawaii 3-digit ZIP Codes...

  15. Arabidopsis HD-Zip II transcription factors control apical embryo development and meristem function.

    PubMed

    Turchi, Luana; Carabelli, Monica; Ruzza, Valentino; Possenti, Marco; Sassi, Massimiliano; Peñalosa, Andrés; Sessa, Giovanna; Salvi, Sergio; Forte, Valentina; Morelli, Giorgio; Ruberti, Ida

    2013-05-01

    The Arabidopsis genome encodes ten Homeodomain-Leucine zipper (HD-Zip) II proteins. ARABIDOPSIS THALIANA HOMEOBOX 2 (ATHB2), HOMEOBOX ARABIDOPSIS THALIANA 1 (HAT1), HAT2, HAT3 and ATHB4 are regulated by changes in the red/far red light ratio that induce shade avoidance in most of the angiosperms. Here, we show that progressive loss of HAT3, ATHB4 and ATHB2 activity causes developmental defects from embryogenesis onwards in white light. Cotyledon development and number are altered in hat3 athb4 embryos, and these defects correlate with changes in auxin distribution and response. athb2 gain-of-function mutation and ATHB2 expression driven by its promoter in hat3 athb4 result in significant attenuation of phenotypes, thus demonstrating that ATHB2 is functionally redundant to HAT3 and ATHB4. In analogy to loss-of-function mutations in HD-Zip III genes, loss of HAT3 and ATHB4 results in organ polarity defects, whereas triple hat3 athb4 athb2 mutants develop one or two radialized cotyledons and lack an active shoot apical meristem (SAM). Consistent with overlapping expression pattern of HD-Zip II and HD-Zip III gene family members, bilateral symmetry and SAM defects are enhanced when hat3 athb4 is combined with mutations in PHABULOSA (PHB), PHAVOLUTA (PHV) or REVOLUTA (REV). Finally, we show that ATHB2 is part of a complex regulatory circuit directly involving both HD-Zip II and HD-Zip III proteins. Taken together, our study provides evidence that a genetic system consisting of HD-Zip II and HD-Zip III genes cooperates in establishing bilateral symmetry and patterning along the adaxial-abaxial axis in the embryo as well as in controlling SAM activity.

  16. Find a Podiatrist

    MedlinePlus

    ... Carolina South Dakota Tennessee Texas Utah Vermont Virgin Islands Virginia Washington West Virginia Wisconsin Wyoming Yukon Territory Zip / Postal Code: The closest podiatrist may not be in your zip code. Please use the mile radius search OR enter just the first 3 digits of your zip code to find the ...

  17. Molecular cloning and characterization of a tomato cDNA encoding a systemically wound-inducible bZIP DNA-binding protein

    NASA Technical Reports Server (NTRS)

    Stankovic, B.; Vian, A.; Henry-Vian, C.; Davies, E.

    2000-01-01

    Localized wounding of one leaf in intact tomato (Lycopersicon esculentum Mill.) plants triggers rapid systemic transcriptional responses that might be involved in defense. To better understand the mechanism(s) of intercellular signal transmission in wounded tomatoes, and to identify the array of genes systemically up-regulated by wounding, a subtractive cDNA library for wounded tomato leaves was constructed. A novel cDNA clone (designated LebZIP1) encoding a DNA-binding protein was isolated and identified. This clone appears to be encoded by a single gene, and belongs to the family of basic leucine zipper domain (bZIP) transcription factors shown to be up-regulated by cold and dark treatments. Analysis of the mRNA levels suggests that the transcript for LebZIP1 is both organ-specific and up-regulated by wounding. In wounded wild-type tomatoes, the LebZIP1 mRNA levels in distant tissue were maximally up-regulated within only 5 min following localized wounding. Exogenous abscisic acid (ABA) prevented the rapid wound-induced increase in LebZIP1 mRNA levels, while the basal levels of LebZIP1 transcripts were higher in the ABA mutants notabilis (not), sitiens (sit), and flacca (flc), and wound-induced increases were greater in the ABA-deficient mutants. Together, these results suggest that ABA acts to curtail the wound-induced synthesis of LebZIP1 mRNA.

  18. Variation in Drug Prices at Pharmacies: Are Prices Higher in Poorer Areas?

    PubMed Central

    Gellad, Walid F; Choudhry, Niteesh K; Friedberg, Mark W; Brookhart, M Alan; Haas, Jennifer S; Shrank, William H

    2009-01-01

    Objective To determine whether retail prices for prescription drugs are higher in poorer areas. Data Sources The MyFloridarx.com website, which provides retail prescription prices at Florida pharmacies, and median ZIP code income from the 2000 Census. Study Design We compared mean pharmacy prices for each of the four study drugs across ZIP code income groups. Pharmacies were classified as either chain pharmacies or independent pharmacies. Data Collection Prices were downloaded in November 2006. Principal Findings Across the four study drugs, mean prices were highest in the poorest ZIP codes: 9 percent above the statewide average. Independent pharmacies in the poorest ZIP codes charged the highest mean prices. Conclusions Retail prescription prices appear to be higher in poorer ZIP codes of Florida. PMID:19178584

  19. Interleukin-1beta contributes via nitric oxide to the upregulation and functional activity of the zinc transporter Zip14 (Slc39a14) in murine hepatocytes.

    PubMed

    Lichten, Louis A; Liuzzi, Juan P; Cousins, Robert J

    2009-04-01

    Zinc metabolism during chronic disease is dysregulated by inflammatory cytokines. Experiments with IL-6 knockout mice show that LPS regulates expression of the zinc transporter, Zip14, by a mechanism that is partially independent of IL-6. The LPS-induced model of sepsis may occur by a mechanism signaled by nitric oxide (NO) as a secondary messenger. To address the hypothesis that NO can modulate Zip14 expression, we treated primary hepatocytes from wild-type mice with the NO donor S-nitroso N-acetyl penicillamine (SNAP). After treatment with SNAP, steady-state Zip14 mRNA levels displayed a maximal increase after 8 h and a concomitant increase in the transcriptional activity of the gene. Chromatin immunoprecipitation documented the kinetics of activator protein (AP)-1 and RNA polymerase II association with the Zip14 promoter after NO exposure, indicating a role of AP-1 in transcription of Zip14. We then stimulated the primary murine hepatocytes with IL-1beta, an LPS-induced proinflammatory cytokine and a potent activator of inducible NO synthase (iNOS) and NO production. In support of our hypothesis, IL-1beta treatment led to a threefold increase in Zip14 mRNA and enhanced zinc transport, as measured with a zinc fluorophore, in wild-type but not iNOS-/- hepatocytes. These data suggest that signaling pathways activated by NO are factors in the upregulation of Zip14, which in turn mediates hepatic zinc accumulation and hypozincemia during inflammation and sepsis.

  20. OsbZIP58, a basic leucine zipper transcription factor, regulates starch biosynthesis in rice endosperm.

    PubMed

    Wang, Jie-Chen; Xu, Heng; Zhu, Ying; Liu, Qiao-Quan; Cai, Xiu-Ling

    2013-08-01

    Starch composition and the amount in endosperm, both of which contribute dramatically to seed yield, cooking quality, and taste in cereals, are determined by a series of complex biochemical reactions. However, the mechanism regulating starch biosynthesis in cereal seeds is not well understood. This study showed that OsbZIP58, a bZIP transcription factor, is a key transcriptional regulator controlling starch synthesis in rice endosperm. OsbZIP58 was expressed mainly in endosperm during active starch synthesis. osbzip58 null mutants displayed abnormal seed morphology with altered starch accumulation in the white belly region and decreased amounts of total starch and amylose. Moreover, osbzip58 had a higher proportion of short chains and a lower proportion of intermediate chains of amylopectin. Furthermore, OsbZIP58 was shown to bind directly to the promoters of six starch-synthesizing genes, OsAGPL3, Wx, OsSSIIa, SBE1, OsBEIIb, and ISA2, and to regulate their expression. These findings indicate that OsbZIP58 functions as a key regulator of starch synthesis in rice seeds and provide new insights into seed quality control.

  1. Zipping dielectric elastomer actuators: characterization, design and modeling

    NASA Astrophysics Data System (ADS)

    Maffli, L.; Rosset, S.; Shea, H. R.

    2013-10-01

    We report on miniature dielectric elastomer actuators (DEAs) operating in zipping mode with an analytical model that predicts their behavior. Electrostatic zipping is a well-known mechanism in silicon MEMS to obtain large deformations and forces at lower voltages than for parallel plate electrostatic actuation. We extend this concept to DEAs, which allows us to obtain much larger out-of-plane displacements compared to silicon thanks to the softness of the elastomer membrane. We study experimentally the effect of sidewall angles and elastomer prestretch on 2.3 mm diameter actuators with PDMS membranes. With 15° and 22.5° sidewall angles, the devices zip in a bistable manner down 300 μm to the bottom of the chambers. The highly tunable bistable behavior is controllable by both chamber geometry and membrane parameters. Other specific characteristics of zipping DEAs include well-controlled deflected shape, tunable displacement versus voltage characteristics to virtually any shape, including multi-stable modes, sealing of embedded holes or channels for valving action and the reduction of the operating voltage. These properties make zipping DEAs an excellent candidate for applications such as integrated microfluidics actuators or Braille displays.

  2. A genome-wide survey of homeodomain-leucine zipper genes and analysis of cold-responsive HD-Zip I members' expression in tomato.

    PubMed

    Zhang, Zhenzhu; Chen, Xiuling; Guan, Xin; Liu, Yang; Chen, Hongyu; Wang, Tingting; Mouekouba, Liana Dalcantara Ongouya; Li, Jingfu; Wang, Aoxue

    2014-01-01

    Homeodomain-leucine zipper (HD-Zip) proteins are a kind of transcriptional factors that play a vital role in plant growth and development. However, no detailed information of HD-Zip family in tomato has been reported till now. In this study, 51 HD-Zip genes (SlHZ01-51) in this family were identified and categorized into 4 classes by exon-intron and protein structure in tomato (Solanum lycopersicum) genome. The synthetical phylogenetic tree of tomato, Arabidopsis and rice HD-Zip genes were established for an insight into their evolutionary relationships and putative functions. The results showed that the contribution of segmental duplication was larger than that of tandem duplication for expansion and evolution of genes in this family of tomato. The expression profile results under abiotic stress suggested that all SlHZ I genes were responsive to cold stress. This study will provide a clue for the further investigation of functional identification and the role of tomato HD-Zip I subfamily in plant cold stress responses and developmental events.

  3. The bZIP transcription factor PfZipA regulates secondary metabolism and oxidative stress response in the plant endophytic fungus Pestalotiopsis fici.

    PubMed

    Wang, Xiuna; Wu, Fan; Liu, Ling; Liu, Xingzhong; Che, Yongsheng; Keller, Nancy P; Guo, Liyun; Yin, Wen-Bing

    2015-08-01

    The bZIP transcription factors are conserved in all eukaryotes and play critical roles in organismal responses to environmental challenges. In filamentous fungi, several lines of evidence indicate that secondary metabolism (SM) is associated with oxidative stress mediated by bZIP proteins. Here we uncover a connection with a bZIP protein and oxidative stress induction of SM in the plant endophytic fungus Pestalotiopsis fici. A homology search of the P. fici genome with the bZIP protein RsmA, involved in SM and the oxidative stress response in Aspergillus nidulans, identified PfZipA. Deletion of PfzipA resulted in a strain that displayed resistant to the oxidative reagents tert-butylhydroperoxide (tBOOH), diamide, and menadione sodium bisulfite (MSB), but increased sensitivity to H2O2 as compared to wild type (WT). Secondary metabolite production presented a complex pattern dependent on PfzipA and oxidative reagents. Without oxidative treatment, the ΔPfzipA strain produced less isosulochrin and ficipyroneA than WT; addition of tBOOH further decreased production of iso-A82775C and pestaloficiol M in ΔPfzipA; diamide treatment resulted in equivalent production of isosulochrin and ficipyroneA in the two strains; MSB treatment further decreased production of RES1214-1 and iso-A82775C but increased pestaloficiol M production in the mutant; and H2O2 treatment resulted in enhanced production of isosulochrin, RES1214-1 and pestheic acid but decreased ficipyroneA and pestaloficiol M in ΔPfzipA compared to WT. Our results suggest that PfZipA regulation of SM is modified by oxidative stress pathways and provide insights into a possible role of PfZipA in mediating SM synthesis in the endophytic lifestyle of P. fici. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Comprehensive characterization and RNA-Seq profiling of the HD-Zip transcription factor family in soybean (Glycine max) during dehydration and salt stress

    USDA-ARS?s Scientific Manuscript database

    The homeodomain leucine zipper (HD-Zip) transcription factor family is one of the largest plant specific superfamilies, and includes genes with roles in modulation of plant growth and response to environmental stresses. Many HD-Zip genes are well characterized in Arabidopsis (Arabidopsis thaliana), ...

  5. Genomic identification of bZIP family genes involved in drought and heat stresses in strawberry (Fragaria vesca)

    USDA-ARS?s Scientific Manuscript database

    Basic leucine zipper (bZIP) genes are known to play dominant roles in plant response to development signals, as well as abiotic or biotic stress stimuli. Fifty bZIP genes across the woodland strawberry (Fragaria vesca) genome were identified and analyzed. They can be divided into 10 clades according...

  6. Expression Patterns and Correlations with Metabolic Markers of Zinc Transporters ZIP14 and ZNT1 in Obesity and Polycystic Ovary Syndrome

    PubMed Central

    Maxel, Trine; Svendsen, Pernille Fog; Smidt, Kamille; Lauridsen, Jesper Krogh; Brock, Birgitte; Pedersen, Steen Bønlykke; Rungby, Jørgen; Larsen, Agnete

    2017-01-01

    Polycystic ovary syndrome (PCOS) is associated with infertility, increased androgen levels, and insulin resistance. In adipose tissue, zinc facilitates insulin signaling. Circulating zinc levels are altered in obesity, diabetes, and PCOS; and zinc supplementation can ameliorate metabolic disturbances in PCOS. In adipose tissue, expression of zinc influx transporter ZIP14 varies with body mass index (BMI), clinical markers of metabolic syndrome, and peroxisome proliferator-activated receptor gamma (PPARG). In this study, we investigated expression levels of ZIP14 and PPARG in subcutaneous adipose tissue of 36 PCOS women (17 lean and 19 obese women) compared with 23 healthy controls (7 lean and 16 obese women). Further, expression levels of zinc transporter ZIP9, a recently identified androgen receptor, and zinc efflux transporter ZNT1 were investigated, alongside lipid profile and markers of glucose metabolism [insulin degrading enzyme, retinol-binding protein 4 (RBP4), and glucose transporter 4 (GLUT4)]. We find that ZIP14 expression is reduced in obesity and positively correlates with PPARG expression, which is downregulated with increasing BMI. ZNT1 is upregulated in obesity, and both ZIP14 and ZNT1 expression significantly correlates with clinical markers of altered glucose metabolism. In addition, RBP4 and GLUT4 associate with obesity, but an association with PCOS as such was present only for PPARG and RBP4. ZIP14 and ZNT1 does not relate to clinical androgen status and ZIP9 is unaffected by all parameters investigated. In conclusion, our findings support the existence of a zinc dyshomeostasis in adipose tissue in metabolic disturbances including PCOS-related obesity. PMID:28303117

  7. Hyperglycemia-Induced Changes in ZIP7 and ZnT7 Expression Cause Zn2+ Release From the Sarco(endo)plasmic Reticulum and Mediate ER Stress in the Heart.

    PubMed

    Tuncay, Erkan; Bitirim, Verda C; Durak, Aysegul; Carrat, Gaelle R J; Taylor, Kathryn M; Rutter, Guy A; Turan, Belma

    2017-05-01

    Changes in cellular free Zn 2+ concentration, including those in the sarco(endo)plasmic reticulum [S(E)R], are primarily coordinated by Zn 2+ transporters (ZnTs) whose identity and role in the heart are not well established. We hypothesized that ZIP7 and ZnT7 transport Zn 2+ in opposing directions across the S(E)R membrane in cardiomyocytes and that changes in their activity play an important role in the development of ER stress during hyperglycemia. The subcellular S(E)R localization of ZIP7 and ZnT7 was determined in cardiomyocytes and in isolated S(E)R preparations. Markedly increased mRNA and protein levels of ZIP7 were observed in ventricular cardiomyocytes from diabetic rats or high-glucose-treated H9c2 cells while ZnT7 expression was low. In addition, we observed increased ZIP7 phosphorylation in response to high glucose in vivo and in vitro. By using recombinant-targeted Förster resonance energy transfer sensors, we show that hyperglycemia induces a marked redistribution of cellular free Zn 2+ , increasing cytosolic free Zn 2+ and lowering free Zn 2+ in the S(E)R. These changes involve alterations in ZIP7 phosphorylation and were suppressed by small interfering RNA-mediated silencing of CK2α. Opposing changes in the expression of ZIP7 and ZnT7 were also observed in hyperglycemia. We conclude that subcellular free Zn 2+ redistribution in the hyperglycemic heart, resulting from altered ZIP7 and ZnT7 activity, contributes to cardiac dysfunction in diabetes. © 2017 by the American Diabetes Association.

  8. How Accurate Is Your Activity Tracker? A Comparative Study of Step Counts in Low-Intensity Physical Activities

    PubMed Central

    2017-01-01

    Background As commercially available activity trackers are being utilized in clinical trials, the research community remains uncertain about reliability of the trackers, particularly in studies that involve walking aids and low-intensity activities. While these trackers have been tested for reliability during walking and running activities, there has been limited research on validating them during low-intensity activities and walking with assistive tools. Objective The aim of this study was to (1) determine the accuracy of 3 Fitbit devices (ie, Zip, One, and Flex) at different wearing positions (ie, pants pocket, chest, and wrist) during walking at 3 different speeds, 2.5, 5, and 8 km/h, performed by healthy adults on a treadmill; (2) determine the accuracy of the mentioned trackers worn at different sites during activities of daily living; and (3) examine whether intensity of physical activity (PA) impacts the choice of optimal wearing site of the tracker. Methods We recruited 15 healthy young adults to perform 6 PAs while wearing 3 Fitbit devices (ie, Zip, One, and Flex) on their chest, pants pocket, and wrist. The activities include walking at 2.5, 5, and 8 km/h, pushing a shopping cart, walking with aid of a walker, and eating while sitting. We compared the number of steps counted by each tracker with gold standard numbers. We performed multiple statistical analyses to compute descriptive statistics (ie, ANOVA test), intraclass correlation coefficient (ICC), mean absolute error rate, and correlation by comparing the tracker-recorded data with that of the gold standard. Results All the 3 trackers demonstrated good-to-excellent (ICC>0.75) correlation with the gold standard step counts during treadmill experiments. The correlation was poor (ICC<0.60), and the error rate was significantly higher in walker experiment compared to other activities. There was no significant difference between the trackers and the gold standard in the shopping cart experiment. The wrist worn tracker, Flex, counted several steps when eating (P<.01). The chest tracker was identified as the most promising site to capture steps in more intense activities, while the wrist was the optimal wearing site in less intense activities. Conclusions This feasibility study focused on 6 PAs and demonstrated that Fitbit trackers were most accurate when walking on a treadmill and least accurate during walking with a walking aid and for low-intensity activities. This may suggest excluding participants with assistive devices from studies that focus on PA interventions using commercially available trackers. This study also indicates that the wearing site of the tracker is an important factor impacting the accuracy performance. A larger scale study with a more diverse population, various activity tracker vendors, and a larger activity set are warranted to generalize our results. PMID:28801304

  9. The Populus Class III HD ZIP transcription factor POPCORONA affects cell differentiation during secondary growth of woody stems

    Treesearch

    Juan Du; Eriko Miura; Marcel Robischon; Ciera Martinez; Andrew Groover

    2011-01-01

    The developmental mechanisms regulating cell differentiation and patterning during the secondary growth of woody tissues are poorly understood. Class III HD ZIP transcription factors are evolutionarily ancient and play fundamental roles in various aspects of plant development. Here we investigate the role of a Class III HD ZIP transcription factor, ...

  10. Does it really matter that people zip through ads? Testing the effectiveness of simultaneous presentation advertising in an IDTV environment.

    PubMed

    Nam, Yoonjae; Kwon, Kyonghee H; Lee, Sungjoon

    2010-04-01

    In an IDTV environment, which facilitates self-scheduling, skipping advertisements by zipping is an emerging ad-avoidance behavior. This study explores whether an alternative ad format, called simultaneous presentation advertising (SPA), may overcome the limitations of classical sequential advertising (CSA) in controlling zipping behavior and increasing the effectiveness of ads. The experiment revealed that SPA is more effective than CSA in reducing zipping and increasing recall, but SPA was more intrusive and produced a negative product image. There was no difference regarding cognitive avoidance. This work discusses the implications of these findings in the interactive media environment.

  11. Mechanism of DNA binding enhancement by hepatitis B virus protein pX.

    PubMed

    Palmer, C R; Gegnas, L D; Schepartz, A

    1997-12-09

    At least three hundred million people worldwide are infected with the hepatitis B virus (HBV), and epidemiological studies show a clear correlation between chronic HBV infection and the development of hepatocellular carcinoma. HBV encodes a protein, pX, which abducts the cellular transcriptional machinery in several ways including direct interactions with bZIP transcription factors. These interactions increase the DNA affinities of target bZIP proteins in a DNA sequence-dependent manner. Here we use a series of bZIP peptide models to explore the mechanism by which pX interacts with bZIP proteins. Our results suggest that pX increases bZIP.DNA stability by increasing the stability of the bZIP dimer as well as the affinity of the dimer for DNA. Additional experiments provide evidence for a mechanism in which pX recognizes the composite structure of the peptide.DNA complex, not simply the primary peptide sequence. These experiments provide a framework for understanding how pX alters the patterns of transcription within the nucleus. The similarities between the mechanism proposed for pX and the mechanism previously proposed for the human T-cell leukemia virus protein Tax are discussed.

  12. Engineering of a novel zipFv using leucine zipper motif against rabies virus glycoprotein G with improved protection potency in vivo.

    PubMed

    Xi, Hualong; Zhang, Kaixin; Yin, Yanchun; Gu, Tiejun; Sun, Qing; Li, Zhuang; Cheng, Yue; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2017-06-01

    Rabies is an acute zoonotic infectious disease with a high fatality rate but is preventable with vaccination and rabies immunoglobulin (RIG). The single-chain Fv fragment (scFv), a small engineered antigen-binding protein derived from antibody variable heavy (V H ) and light (V L ) chains connected by a peptide linker, can potentially be used to replace RIG. Here, we produced two peptides V H -JUN-HIS and V L -FOS-HA separately in Escherichia coli and assembled them to form zipFv successfully in vitro. The new zipFv utilizes FOS and JUN leucine zippers to form an antibody structure similar to the IgG counterpart with two free N-terminal ends of V H and V L . The zipFv protein showed notable improvement in binding ability and affinity over its corresponding scFv. The zipFv also demonstrated greater stability in serum and the same protective rate as RIG against challenge with a standard rabies virus (CVS-24) in mice. Our results indicated zipFv as a novel and efficient antibody form with enhanced neutralizing potency. Copyright © 2017. Published by Elsevier B.V.

  13. Unfolded protein response activation compensates endoplasmic reticulum-associated degradation deficiency in Arabidopsis.

    PubMed

    Li, Qingliang; Wei, Hai; Liu, Lijing; Yang, Xiaoyuan; Zhang, Xiansheng; Xie, Qi

    2017-07-01

    Abiotic stresses often disrupt protein folding and induce endoplasmic reticulum (ER) stress. There is a sophisticated ER quality control (ERQC) system to mitigate the effects of malfunctioning proteins and maintain ER homeostasis. The accumulation of misfolded proteins in the ER activates the unfolded protein response (UPR) to enhance ER protein folding and the degradation of misfolded proteins mediate by ER-associated degradation (ERAD). That ERQC reduces abiotic stress damage has been well studied in mammals and yeast. However, in plants, both ERAD and UPR have been studied separately and found to be critical for plant abiotic stress tolerance. In this study, we discovered that UPR-associated transcription factors AtbZIP17, AtbZIP28 and AtbZIP60 responded to tunicamycin (TM) and NaCl induced ER stress and subsequently enhanced Arabidopsis thaliana abiotic stress tolerance. They regulated the expression level of ER chaperones and the HRD1-complex components. Moreover, overexpression of AtbZIP17, AtbZIP28 and AtbZIP60 could restore stress tolerance via ERAD in the HRD1-complex mutant hrd3a-2, which suggested that UPR and ERAD have an interactive mechanism in Arabidopsis. © 2017 Institute of Botany, Chinese Academy of Sciences.

  14. bZIP17 regulates the expression of genes related to seed storage and germination, reducing seed susceptibility to osmotic stress.

    PubMed

    Cifuentes-Esquivel, Nicolás; Celiz-Balboa, Jonathan; Henriquez-Valencia, Carlos; Mitina, Irina; Arraño-Salinas, Paulina; Moreno, Adrián A; Meneses, Claudio; Blanco-Herrera, Francisca; Orellana, Ariel

    2018-04-25

    Low temperatures, salinity, and drought cause significant crop losses. These conditions involve osmotic stress, triggering transcriptional remodeling, and consequently, the restitution of cellular homeostasis and growth recovery. Protein transcription factors regulate target genes, thereby mediating plant responses to stress. bZIP17 is a transcription factor involved in cellular responses to salinity and the unfolded protein response. Because salinity can also produce osmotic stress, the role of bZIP17 in response to osmotic stress was assessed. Mannitol treatments induced the transcript accumulation and protein processing of bZIP17. Transcriptomic analyses showed that several genes associated with seed storage and germination showed lower expression in bzip17 mutants than in wild-type plants. Interestingly, bZIP17 transcript was more abundant in seeds, and germination analyses revealed that wild-type plants germinated later than bzip17 mutants in the presence of mannitol, but no effects were observed when the seeds were exposed to ABA. Finally, the transcript levels of bZIP17 target genes that control seed storage and germination were assessed in seeds exposed to mannitol treatments, which showed lower expression levels in bzip17 mutants compared to the wild-type seeds. These results suggest that bZIP17 plays a role in osmotic stress, acting as a negative regulator of germination through the regulation of genes involved in seed storage and germination. © 2018 Wiley Periodicals, Inc.

  15. DNA Methylation Influences Chlorogenic Acid Biosynthesis in Lonicera japonica by Mediating LjbZIP8 to Regulate Phenylalanine Ammonia-Lyase 2 Expression.

    PubMed

    Zha, Liangping; Liu, Shuang; Liu, Juan; Jiang, Chao; Yu, Shulin; Yuan, Yuan; Yang, Jian; Wang, Yaolong; Huang, Luqi

    2017-01-01

    The content of active compounds differ in buds and flowers of Lonicera japonica (FLJ) and L. japonica var. chinensis (rFLJ). Chlorogenic acid (CGAs) were major active compounds of L. japonica and regarded as measurements for quality evaluation. However, little is known concerning the formation of active compounds at the molecular level. We quantified the major CGAs in FLJ and rFLJ, and found the concentrations of CGAs were higher in the buds of rFLJ than those of FLJ. Further analysis of CpG methylation of CGAs biosynthesis genes showed differences between FLJ and rFLJ in the 5'-UTR of phenylalanine ammonia-lyase 2 ( PAL2 ). We identified 11 LjbZIP proteins and 24 rLjbZIP proteins with conserved basic leucine zipper domains, subcellular localization, and electrophoretic mobility shift assay showed that the transcription factor LjbZIP8 is a nuclear-localized protein that specifically binds to the G-box element of the LjPAL2 5'-UTR. Additionally, a transactivation assay and LjbZIP8 overexpression in transgenic tobacco indicated that LjbZIP8 could function as a repressor of transcription. Finally, treatment with 5-azacytidine decreased the transcription level of LjPAL2 and CGAs content in FLJ leaves. These results raise the possibility that DNA methylation might influence the recruitment of LjbZIP8, regulating PAL2 expression level and CGAs content in L. japonica .

  16. DNA Methylation Influences Chlorogenic Acid Biosynthesis in Lonicera japonica by Mediating LjbZIP8 to Regulate Phenylalanine Ammonia-Lyase 2 Expression

    PubMed Central

    Zha, Liangping; Liu, Shuang; Liu, Juan; Jiang, Chao; Yu, Shulin; Yuan, Yuan; Yang, Jian; Wang, Yaolong; Huang, Luqi

    2017-01-01

    The content of active compounds differ in buds and flowers of Lonicera japonica (FLJ) and L. japonica var. chinensis (rFLJ). Chlorogenic acid (CGAs) were major active compounds of L. japonica and regarded as measurements for quality evaluation. However, little is known concerning the formation of active compounds at the molecular level. We quantified the major CGAs in FLJ and rFLJ, and found the concentrations of CGAs were higher in the buds of rFLJ than those of FLJ. Further analysis of CpG methylation of CGAs biosynthesis genes showed differences between FLJ and rFLJ in the 5′-UTR of phenylalanine ammonia-lyase 2 (PAL2). We identified 11 LjbZIP proteins and 24 rLjbZIP proteins with conserved basic leucine zipper domains, subcellular localization, and electrophoretic mobility shift assay showed that the transcription factor LjbZIP8 is a nuclear-localized protein that specifically binds to the G-box element of the LjPAL2 5′-UTR. Additionally, a transactivation assay and LjbZIP8 overexpression in transgenic tobacco indicated that LjbZIP8 could function as a repressor of transcription. Finally, treatment with 5-azacytidine decreased the transcription level of LjPAL2 and CGAs content in FLJ leaves. These results raise the possibility that DNA methylation might influence the recruitment of LjbZIP8, regulating PAL2 expression level and CGAs content in L. japonica. PMID:28740500

  17. Tryptophan-dependent auxin biosynthesis is required for HD-ZIP III-mediated xylem patterning.

    PubMed

    Ursache, Robertas; Miyashima, Shunsuke; Chen, Qingguo; Vatén, Anne; Nakajima, Keiji; Carlsbecker, Annelie; Zhao, Yunde; Helariutta, Ykä; Dettmer, Jan

    2014-03-01

    The development and growth of higher plants is highly dependent on the conduction of water and minerals throughout the plant by xylem vessels. In Arabidopsis roots the xylem is organized as an axis of cell files with two distinct cell fates: the central metaxylem and the peripheral protoxylem. During vascular development, high and low expression levels of the class III HD-ZIP transcription factors promote metaxylem and protoxylem identities, respectively. Protoxylem specification is determined by both mobile, ground tissue-emanating miRNA165/6 species, which downregulate, and auxin concentrated by polar transport, which promotes HD-ZIP III expression. However, the factors promoting high HD-ZIP III expression for metaxylem identity have remained elusive. We show here that auxin biosynthesis promotes HD-ZIP III expression and metaxylem specification. Several auxin biosynthesis genes are expressed in the outer layers surrounding the vascular tissue in Arabidopsis root and downregulation of HD-ZIP III expression accompanied by specific defects in metaxylem development is seen in auxin biosynthesis mutants, such as trp2-12, wei8 tar2 or a quintuple yucca mutant, and in plants treated with L-kynurenine, a pharmacological inhibitor of auxin biosynthesis. Some of the patterning defects can be suppressed by synthetically elevated HD-ZIP III expression. Taken together, our results indicate that polar auxin transport, which was earlier shown to be required for protoxylem formation, is not sufficient to establish a proper xylem axis but that root-based auxin biosynthesis is additionally required.

  18. A modified detector concept for SuperCDMS: The HiZIP and its charge performance

    NASA Astrophysics Data System (ADS)

    Page, Kedar Mohan

    SuperCDMS is a leading direct dark matter search experiment which uses solid state detectors (Ge crystals) at milliKelvin temperatures to look for nuclear recoils caused by dark matter interactions in the detector. 'Weakly Interacting Massive Particles' (WIMPs) are the most favoured dark matter candidate particles. SuperCDMS, like many other direct dark matter search experiments, primarily looks for WIMPs. The measurement of both the ionization and the lattice vibration (phonon) signals from an interaction in the detector allow it to discriminate against electron recoils which are the main source of background for WIMP detection. SuperCDMS currently operates about 9 kgs worth of germanium detectors at the Soudan underground lab in northern Minnesota. In its next phase, SuperCDMS SNOLAB, it plans to use 100-200 kg of target mass (Ge) which would allow it to probe more of the interesting and unexplored parameter space for WIMPs predicted by theoretical models. The SuperCDMS Queen's Test Facility is a detector testing facility which is intended to serve detector testing and detector research and development purposes for the SuperCDMS experiment. A modified detector called the 'HiZIP' (Half-iZIP), which is reduced in complexity in comparison to the currently used iZIP (interleaved Z-sensitive Ionization and Phonon mediated) detectors, is studied in this thesis. The HiZIP detector design also serves to discriminate against background from multiple scatter events occurring close to the surfaces in a single detector. Studies carried out to compare the surface event leakage in the HiZIP detector using limited information from iZIP data taken at SuperCDMS test facility at UC Berkley produce a highly conservative upper limit of 5 out of 10,000 events at 90% confidence level. This upper limit is the best among many different HiZIP configurations that were investigated and is comparable to the upper limit calculated for an iZIP detector in the same way using the same data. A real HiZIP device operated at Queen's Test Facility produced an exposure limited 90% upper limit of about 1 in 100 events for surface event leakage. The data used in these studies contain true nuclear recoil events from cosmogenic and ambient neutrons. This background was not subtracted in the calculation of the upper limits stated above and hence they are highly conservative. A surface event source was produced by depositing lead-210 from radon exposure onto a copper plate. This source was then used to take data for a surface event discrimination study of the HiZIP detector operated at Queen's Test Facility. A study of the contribution of the noise from capacitive crosstalk between charge sensors in a HiZIP detector configuration was investigated, confirming the expectation that no significant drop in performance is to be expected due to this effect.

  19. Geographic variation and effect of area-level poverty rate on colorectal cancer screening.

    PubMed

    Lian, Min; Schootman, Mario; Yun, Shumei

    2008-10-16

    With a secular trend of increasing colorectal cancer (CRC) screening, concerns about disparities in CRC screening also have been rising. It is unclear if CRC screening varies geographically, if area-level poverty rate affects CRC screening, and if individual-level characteristics mediate the area-level effects on CRC screening. Using 2006 Missouri Behavioral Risk Factor Surveillance System (BRFSS) data, a multilevel study was conducted to examine geographic variation and the effect of area-level poverty rate on CRC screening use among persons age 50 or older. Individuals were nested within ZIP codes (ZIP5 areas), which in turn, were nested within aggregations of ZIP codes (ZIP3 areas). Six groups of individual-level covariates were considered as potential mediators. An estimated 51.8% of Missourians aged 50 or older adhered to CRC screening recommendations. Nearly 15% of the total variation in CRC screening lay between ZIP5 areas. Persons residing in ZIP5 areas with > or = 10% of poverty rate had lower odds of CRC screening use than those residing in ZIP5 areas with <10% poverty rate (unadjusted odds ratio [OR], 0.69; 95% confidence interval [95% CI], 0.58-0.81; adjusted OR, 0.81; 95% CI, 0.67-0.98). Persons who resided in ZIP3 areas with > or = 20% poverty rate also had lower odds of following CRC screening guidelines than those residing in ZIP3 areas with <20% poverty rate (unadjusted OR, 0.66; 95% CI, 0.52-0.83; adjusted OR, 0.64; 95% CI, 0.50-0.83). Obesity, history of depression/anxiety and access to care were associated with CRC screening, but did not mediate the effect of area-level poverty on CRC screening. Large geographic variation of CRC screening exists in Missouri. Area-level poverty rate, independent of individual-level characteristics, is a significant predictor of CRC screening, but it only explains a small portion of the geographic heterogeneity of CRC screening. Individual-level factors we examined do not mediate the effect of the area-level poverty rate on CRC screening. Future studies should identify other area- and individual-level characteristics associated with CRC screening in Missouri.

  20. Molecular evolution of the HD-ZIP I gene family in legume genomes.

    PubMed

    Li, Zhen; Jiang, Haiyang; Zhou, Lingyan; Deng, Lin; Lin, Yongxiang; Peng, Xiaojian; Yan, Hanwei; Cheng, Beijiu

    2014-01-01

    Homeodomain leucine zipper I (HD-ZIP I) genes were used to increase the plasticity of plants by mediating external signals and regulating growth in response to environmental conditions. The way genomic histories drove the evolution of the HD-ZIP I family in legume species was described; HD-ZIP I genes were searched in Lotus japonicus, Medicago truncatula, Cajanus cajan and Phaseolus vulgaris, and then divided into five clades through phylogenetic analysis. Microsynteny analysis was made based on genomic segments containing the HD-ZIP I genes. Some pairs turned out to conform with syntenic genome regions, while others corresponded to those that were inverted, expanded, or contracted after the divergence of legumes. Besides, we dated their duplications by Ks analysis and demonstrated that all the blocks were formed after the monocot-dicot split; we observed Ka/Ks ratios representing strong purifying selections in the four legume species which might have been followed by gene loss and rearrangement. © 2014 Elsevier B.V. All rights reserved.

  1. Employment and residential characteristics in relation to automated external defibrillator locations

    PubMed Central

    Griffis, Heather M.; Band, Roger A; Ruther, Matthew; Harhay, Michael; Asch, David A.; Hershey, John C.; Hill, Shawndra; Nadkarni, Lindsay; Kilaru, Austin; Branas, Charles C.; Shofer, Frances; Nichol, Graham; Becker, Lance B.; Merchant, Raina M.

    2015-01-01

    Background Survival from out-of-hospital cardiac arrest (OHCA) is generally poor and varies by geography. Variability in automated external defibrillator (AED) locations may be a contributing factor. To inform optimal placement of AEDs, we investigated AED access in a major US city relative to demographic and employment characteristics. Methods and Results This was a retrospective analysis of a Philadelphia AED registry (2,559 total AEDs). The 2010 US Census and the Local Employment Dynamics (LED) database by ZIP code was used. AED access was calculated as the weighted areal percentage of each ZIP code covered by a 400 meter radius around each AED. Of 47 ZIP codes, only 9%(4) were high AED service areas. In 26%(12) of ZIP codes, less than 35% of the area was covered by AED service areas. Higher AED access ZIP codes were more likely to have a moderately populated residential area (p=0.032), higher median household income (p=0.006), and higher paying jobs (p=008). Conclusions The locations of AEDs vary across specific ZIP codes; select residential and employment characteristics explain some variation. Further work on evaluating OHCA locations, AED use and availability, and OHCA outcomes could inform AED placement policies. Optimizing the placement of AEDs through this work may help to increase survival. PMID:26856232

  2. Tubular iron deposition and iron handling proteins in human healthy kidney and chronic kidney disease.

    PubMed

    Raaij, Sanne van; Swelm, Rachel van; Bouman, Karlijn; Cliteur, Maaike; Heuvel, Marius van den; Pertijs, Jeanne; Patel, Dominic; Bass, Paul; Goor, Harry van; Unwin, Robert; Srai, Surjit Kaila; Swinkels, Dorine

    2018-06-19

    Iron is suggested to play a detrimental role in the progression of chronic kidney disease (CKD). The kidney recycles iron back into the circulation. However, the localization of proteins relevant for physiological tubular iron handling and their potential role in CKD remain unclear. We examined associations between iron deposition, expression of iron handling proteins and tubular injury in kidney biopsies from CKD patients and healthy controls using immunohistochemistry. Iron was deposited in proximal (PT) and distal tubules (DT) in 33% of CKD biopsies, predominantly in pathologies with glomerular dysfunction, but absent in controls. In healthy kidney, PT contained proteins required for iron recycling including putative iron importers ZIP8, ZIP14, DMT1, iron storage proteins L- and H-ferritin and iron exporter ferroportin, while DT only contained ZIP8, ZIP14, and DMT1. In CKD, iron deposition associated with increased intensity of iron importers (ZIP14, ZIP8), storage proteins (L-, H-ferritin), and/or decreased ferroportin abundance. This demonstrates that tubular iron accumulation may result from increased iron uptake and/or inadequate iron export. Iron deposition associated with oxidative injury as indicated by heme oxygenase-1 abundance. In conclusion, iron deposition is relatively common in CKD, and may result from altered molecular iron handling and may contribute to renal injury.

  3. Increasing the affinity of selective bZIP-binding peptides through surface residue redesign.

    PubMed

    Kaplan, Jenifer B; Reinke, Aaron W; Keating, Amy E

    2014-07-01

    The coiled-coil dimer is a prevalent protein interaction motif that is important for many cellular processes. The basic leucine-zipper (bZIP) transcription factors are one family of proteins for which coiled-coil mediated dimerization is essential for function, and misregulation of bZIPs can lead to disease states including cancer. This makes coiled coils attractive protein-protein interaction targets to disrupt using engineered molecules. Previous work designing peptides to compete with native coiled-coil interactions focused primarily on designing the core residues of the interface to achieve affinity and specificity. However, folding studies on the model bZIP GCN4 show that coiled-coil surface residues also contribute to binding affinity. Here we extend a prior study in which peptides were designed to bind tightly and specifically to representative members of each of 20 human bZIP families. These "anti-bZIP" peptides were designed with an emphasis on target-binding specificity, with contributions to design-target specificity and affinity engineered considering only the coiled-coil core residues. High-throughput testing using peptide arrays indicated many successes. We have now measured the binding affinities and specificities of anti-bZIPs that bind to FOS, XBP1, ATF6, and CREBZF in solution and tested whether redesigning the surface residues can increase design-target affinity. Incorporating residues that favor helix formation into the designs increased binding affinities in all cases, providing low-nanomolar binders of each target. However, changes in surface electrostatic interactions sometimes changed the binding specificity of the designed peptides. © 2014 The Protein Society.

  4. Tobacco outlet density and converted versus native non-daily cigarette use in a national US sample

    PubMed Central

    Kirchner, Thomas R; Anesetti-Rothermel, Andrew; Bennett, Morgane; Gao, Hong; Carlos, Heather; Scheuermann, Taneisha S; Reitzel, Lorraine R; Ahluwalia, Jasjit S

    2017-01-01

    Objective Investigate whether non-daily smokers’ (NDS) cigarette price and purchase preferences, recent cessation attempts, and current intentions to quit are associated with the density of the retail cigarette product landscape surrounding their residential address. Participants Cross-sectional assessment of N=904 converted NDS (CNDS). who previously smoked every day, and N=297 native NDS (NNDS) who only smoked non-daily, drawn from a national panel. Outcome measures Kernel density estimation was used to generate a nationwide probability surface of tobacco outlets linked to participants’ residential ZIP code. Hierarchically nested log-linear models were compared to evaluate associations between outlet density, non-daily use patterns, price sensitivity and quit intentions. Results Overall, NDS in ZIP codes with greater outlet density were less likely than NDS in ZIP codes with lower outlet density to hold 6-month quit intentions when they also reported that price affected use patterns (G2=66.1, p<0.001) and purchase locations (G2=85.2, p<0.001). CNDS were more likely than NNDS to reside in ZIP codes with higher outlet density (G2=322.0, p<0.001). Compared with CNDS in ZIP codes with lower outlet density, CNDS in high-density ZIP codes were more likely to report that price influenced the amount they smoke (G2=43.9, p<0.001), and were more likely to look for better prices (G2=59.3, p<0.001). NDS residing in high-density ZIP codes were not more likely to report that price affected their cigarette brand choice compared with those in ZIP codes with lower density. Conclusions This paper provides initial evidence that the point-of-sale cigarette environment may be differentially associated with the maintenance of CNDS versus NNDS patterns. Future research should investigate how tobacco control efforts can be optimised to both promote cessation and curb the rising tide of non-daily smoking in the USA. PMID:26969172

  5. Where Do Freestanding Emergency Departments Choose to Locate? A National Inventory and Geographic Analysis in Three States.

    PubMed

    Schuur, Jeremiah D; Baker, Olesya; Freshman, Jaclyn; Wilson, Michael; Cutler, David M

    2017-04-01

    We determine the number and location of freestanding emergency departments (EDs) across the United States and determine the population characteristics of areas where freestanding EDs are located. We conducted a systematic inventory of US freestanding EDs. For the 3 states with the highest number of freestanding EDs, we linked demographic, insurance, and health services data, using the 5-digit ZIP code corresponding to the freestanding ED's location. To create a comparison nonfreestanding ED group, we matched 187 freestanding EDs to 1,048 nonfreestanding ED ZIP codes on land and population within state. We compared differences in demographic, insurance, and health services factors between matched ZIP codes with and without freestanding EDs, using univariate regressions with weights. We identified 360 freestanding EDs located in 30 states; 54.2% of freestanding EDs were hospital satellites, 36.6% were independent, and 9.2% were not classifiable. The 3 states with the highest number of freestanding EDs accounted for 66% of all freestanding EDs: Texas (181), Ohio (34), and Colorado (24). Across all 3 states, freestanding EDs were located in ZIP codes that had higher incomes and a lower proportion of the population with Medicaid. In Texas and Ohio, freestanding EDs were located in ZIP codes with a higher proportion of the population with private insurance. In Texas, freestanding EDs were located in ZIP codes that had fewer Hispanics, had a greater number of hospital-based EDs and physician offices, and had more physician visits and medical spending per year than ZIP codes without a freestanding ED. In Ohio, freestanding EDs were located in ZIP codes with fewer hospital-based EDs. In Texas, Ohio, and Colorado, freestanding EDs were located in areas with a better payer mix. The location of freestanding EDs in relation to other health care facilities and use and spending on health care varied between states. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  6. The sonic window: second generation results

    NASA Astrophysics Data System (ADS)

    Walker, William F.; Fuller, Michael I.; Brush, Edward V.; Eames, Matthew D. C.; Owen, Kevin; Ranganathan, Karthik; Blalock, Travis N.; Hossack, John A.

    2006-03-01

    Medical Ultrasound Imaging is widely used clinically because of its relatively low cost, portability, lack of ionizing radiation, and real-time nature. However, even with these advantages ultrasound has failed to permeate the broad array of clinical applications where its use could be of value. A prime example of this untapped potential is the routine use of ultrasound to guide intravenous access. In this particular application existing systems lack the required portability, low cost, and ease-of-use required for widespread acceptance. Our team has been working for a number of years to develop an extremely low-cost, pocket-sized, and intuitive ultrasound imaging system that we refer to as the "Sonic Window." We have previously described the first generation Sonic Window prototype that was a bench-top device using a 1024 element, fully populated array operating at a center frequency of 3.3 MHz. Through a high degree of custom front-end integration combined with multiplexing down to a 2 channel PC based digitizer this system acquired a full set of RF data over a course of 512 transmit events. While initial results were encouraging, this system exhibited limitations resulting from low SNR, relatively coarse array sampling, and relatively slow data acquisition. We have recently begun assembling a second-generation Sonic Window system. This system uses a 3600 element fully sampled array operating at 5.0 MHz with a 300 micron element pitch. This system extends the integration of the first generation system to include front-end protection, pre-amplification, a programmable bandpass filter, four sample and holds, and four A/D converters for all 3600 channels in a set of custom integrated circuits with a combined area smaller than the 1.8 x 1.8 cm footprint of the transducer array. We present initial results from this front-end and present benchmark results from a software beamformer implemented on the Analog Devices BF-561 DSP. We discuss our immediate plans for further integration and testing. This second prototype represents a major reduction in size and forms the foundation of a fully functional, fully integrated, pocket sized prototype.

  7. Light Infantry in the Defense of Urban Europe.

    DTIC Science & Technology

    1986-12-14

    if applicable) 6c. ADDRESS (City, State, and ZIP Code ) 7b. ADDRESS (City, State, and ZIP Code ) Fort Leavenworth, Kansas 66027-6900 Ba. NAME OF FUNDING...SPONSORING 8b. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If applicable) Sc. ADDRESS (City, State, and ZIP Code ) 10...PAGE COUNT wo - EFROM TO144 16. SUPPLEMENTARY NOTATION 17. COSATI CODES A*SUBJECT TERMS (Continue on reverse if necessary and identify by block

  8. Mechanism of autophosphorylation of mycobacterial PknB explored by molecular dynamics simulations.

    PubMed

    Damle, Nikhil P; Mohanty, Debasisa

    2014-07-22

    Mycobacterial Ser/Thr kinase, PknB, is essential for the growth of the pathogen. Unphosphorylated PknB is catalytically inactive, and its activation requires autophosphorylation of Thr residues on the activation loop. Autophosphorylation can in principle take place via two distinct mechanisms. Intermolecular trans autophosphorylation involves dimerization and phosphorylation of the activation loop of one chain in the catalytic pocket of the other chain. On the other hand, intramolecular cis autophosphorylation involves phosphorylation of the activation loop of the kinases in its own catalytic pocket within a monomer. On the basis of the crystal structure of PknB in the front-to-front dimeric form, it is currently believed that activation of PknB involves trans autophosphorylation. However, because of the lack of coordinates of the activation loop in the crystal structures, atomic details of the conformational changes associated with activation are yet to be deciphered. Therefore, to understand the conformational transitions associated with activation via autophosphorylation, a series of explicit solvent molecular dynamics simulations with a duration of 1 μs have been performed on each of the phosphorylated and nonphosphorylated forms of the PknB catalytic domain in monomeric and dimeric states. Simulations on phosphorylated PknB revealed a differential network of crucial electrostatic and hydrophobic residues that stabilize the phosphorylated form in the active conformation. Interestingly, in our simulations on nonphosphorylated monomers, the activation loop was observed to fold into its own active site, thereby opening the novel possibility of activation through intramolecular cis autophosphorylation. Thus, our simulations suggest that autophosphorylation of PknB might also involve cis initiation followed by trans amplification as reported for other eukaryotic kinases based on recent reaction kinetics studies.

  9. Enhanced Gene Expression Rather than Natural Polymorphism in Coding Sequence of the OsbZIP23 Determines Drought Tolerance and Yield Improvement in Rice Genotypes

    PubMed Central

    Dey, Avishek; Samanta, Milan Kumar; Gayen, Srimonta; Sen, Soumitra K.; Maiti, Mrinal K.

    2016-01-01

    Drought is one of the major limiting factors for productivity of crops including rice (Oryza sativa L.). Understanding the role of allelic variations of key regulatory genes involved in stress-tolerance is essential for developing an effective strategy to combat drought. The bZIP transcription factors play a crucial role in abiotic-stress adaptation in plants via abscisic acid (ABA) signaling pathway. The present study aimed to search for allelic polymorphism in the OsbZIP23 gene across selected drought-tolerant and drought-sensitive rice genotypes, and to characterize the new allele through overexpression (OE) and gene-silencing (RNAi). Analyses of the coding DNA sequence (CDS) of the cloned OsbZIP23 gene revealed single nucleotide polymorphism at four places and a 15-nucleotide deletion at one place. The single-copy OsbZIP23 gene is expressed at relatively higher level in leaf tissues of drought-tolerant genotypes, and its abundance is more in reproductive stage. Cloning and sequence analyses of the OsbZIP23-promoter from drought-tolerant O. rufipogon and drought-sensitive IR20 cultivar showed variation in the number of stress-responsive cis-elements and a 35-nucleotide deletion at 5’-UTR in IR20. Analysis of the GFP reporter gene function revealed that the promoter activity of O. rufipogon is comparatively higher than that of IR20. The overexpression of any of the two polymorphic forms (1083 bp and 1068 bp CDS) of OsbZIP23 improved drought tolerance and yield-related traits significantly by retaining higher content of cellular water, soluble sugar and proline; and exhibited decrease in membrane lipid peroxidation in comparison to RNAi lines and non-transgenic plants. The OE lines showed higher expression of target genes-OsRab16B, OsRab21 and OsLEA3-1 and increased ABA sensitivity; indicating that OsbZIP23 is a positive transcriptional-regulator of the ABA-signaling pathway. Taken together, the present study concludes that the enhanced gene expression rather than natural polymorphism in coding sequence of OsbZIP23 is accountable for improved drought tolerance and yield performance in rice genotypes. PMID:26959651

  10. Geographic Discordance Between Patient Residence and Incident Location in Emergency Medical Services Responses.

    PubMed

    Hsia, Renee Y; Dai, Mengtao; Wei, Ran; Sabbagh, Sarah; Mann, N Clay

    2017-01-01

    The location of a patient's residence is often used for emergency medical services (EMS) system planning. Our objective is to evaluate the association between patient residence and emergency incident zip codes for 911 calls. We used data from the 2013 National Emergency Medical Services Information System (NEMSIS) Public-Release Research Dataset. We studied all 911 calls with a valid complaint by dispatch, identifying zip codes for both the residence and incident locations (n=12,376,784). The primary outcomes were geographic and distance discordances between patient residence and incident zip codes. We used a multivariate logistic regression model to determine geographic discordance between residence and incident zip codes by dispatch complaint, age, and sex. We also measured distances between locations with geospatial processing. The overall proportion of geographic discordance for all 911 calls was 27.7% (95% confidence interval [CI] 27.7% to 27.8%) and the median distance discordance was 11.5 miles (95% CI 11.5 to 11.5 miles). Lower geographic discordance rates were found among patients aged 65 to 79 years (20.2%; 95% CI 20.1% to 20.2%) and 80 years and older (14.5%; 95% CI 14.5% to 14.6%). Motor vehicle crashes (63.5%; 95% CI 63.5% to 63.6%), industrial accidents (59.3%; 95% CI 58.0% to 60.6%), and mass casualty incidents (50.6%; 95% CI 49.6% to 51.5%) were more likely to occur outside a patient's residence zip code. Median network distance between home and incident zip centroid codes ranged from 8.6 to 23.5 miles. In NEMSIS, there was geographic discordance between patient residence zip code and call location zip code in slightly more than one quarter of EMS responses records. The geographic discordance rates between residence and incident zip codes were associated with dispatch complaints and age. Although a patient's residence might be a valid proxy for incident location for elderly patients, this relationship holds less true for other age groups and among different complaints. Our findings have important implications for EMS system planning, resource allocation, and injury surveillance. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  11. The Zinc Concentration in the Diet and the Length of the Feeding Period Affect the Methylation Status of the ZIP4 Zinc Transporter Gene in Piglets

    PubMed Central

    Karweina, Diana; Kreuzer-Redmer, Susanne; Müller, Uwe; Franken, Tobias; Pieper, Robert; Baron, Udo; Olek, Sven; Zentek, Jürgen; Brockmann, Gudrun A.

    2015-01-01

    High doses of zinc oxide are commonly used in weaned pig diets to improve performance and health. Recent reports show that this may also lead to an imbalanced zinc homeostasis in the animal. For a better understanding of the regulatory mechanisms of different zinc intakes, we performed a feeding experiment to assess potential epigenetic regulation of the ZIP4 gene expression via DNA methylation in the small intestine of piglets. Fifty-four piglets were fed diets with 57 (LZn), 164 (NZn) or 2,425 (HZn) mg Zn/kg feed for one or four weeks. The ZIP4 expression data provided significant evidence for counter-regulation of zinc absorption with higher dietary zinc concentrations. The CpG +735 in the second exon had a 56% higher methylation in the HZn group compared to the others after one week of feeding (8.0·10-4 < p < 0.035); the methylation of this CpG was strongly negatively associated with the expression of the long ZIP4 transcripts (p < 0.007). In the LZn and NZn diets, the expression of the long ZIP4 transcripts were lower after four vs. one week of feeding (2.9·10-4 < p < 0.017). The strongest switch leading to high DNA methylation in nearly all analysed regions was dependent on feeding duration or age in all diet groups (3.7·10-10 < p < 0.099). The data suggest that DNA methylation serves as a fine-tuning mechanism of ZIP4 gene regulation to maintain zinc homeostasis. Methylation of the ZIP4 gene may play a minor role in the response to very high dietary zinc concentration, but may affect binding of alternate zinc-responsive transcription factors. PMID:26599865

  12. Isolation and expression analysis of four HD-ZIP III family genes targeted by microRNA166 in peach.

    PubMed

    Zhang, C H; Zhang, B B; Ma, R J; Yu, M L; Guo, S L; Guo, L

    2015-10-30

    MicroRNA166 (miR166) is known to have highly conserved targets that encode proteins of the class III homeodomain-leucine zipper (HD-ZIP III) family, in a broad range of plant species. To further understand the relationship between HD-ZIP III genes and miR166, four HD-ZIP III family genes (PpHB14, PpHB15, PpHB8, and PpREV) were isolated from peach (Prunus persica) tissue and characterized. Spatio-temporal expression profiles of the genes were analyzed. Genes of the peach HD-ZIP III family were predicted to encode five conserved domains. Deduced amino acid sequences and tertiary structures of the four peach HD-ZIP III genes were highly conserved, with corresponding genes in Arabidopsis thaliana. The expression level of four targets displayed the opposite trend to that of miR166 throughout fruit development, with the exception of PpHB14 from 35 to 55 days after full bloom (DAFB). This finding indicates that miR166 may negatively regulate its four targets throughout fruit development. As for leaf and phloem, the same trend in expression level was observed between four targets and miR166 from 75 to 105 DAFB. However, the opposite trend was observed for the transcript level between four targets and miR166 from 35 to 55 DAFB. miRNA166 may negatively regulate four targets in some but not all developmental stages for a given tissue. The four genes studied were observed to have, exactly or generally, the same change tendency as individual tissue development, a finding that suggests genes of the HD-ZIP III family in peach may have complementary or cooperative functions in various tissues.

  13. Residential exposure to aircraft noise and hospital admissions for cardiovascular diseases: multi-airport retrospective study.

    PubMed

    Correia, Andrew W; Peters, Junenette L; Levy, Jonathan I; Melly, Steven; Dominici, Francesca

    2013-10-08

    To investigate whether exposure to aircraft noise increases the risk of hospitalization for cardiovascular diseases in older people (≥ 65 years) residing near airports. Multi-airport retrospective study of approximately 6 million older people residing near airports in the United States. We superimposed contours of aircraft noise levels (in decibels, dB) for 89 airports for 2009 provided by the US Federal Aviation Administration on census block resolution population data to construct two exposure metrics applicable to zip code resolution health insurance data: population weighted noise within each zip code, and 90th centile of noise among populated census blocks within each zip code. 2218 zip codes surrounding 89 airports in the contiguous states. 6 027 363 people eligible to participate in the national medical insurance (Medicare) program (aged ≥ 65 years) residing near airports in 2009. Percentage increase in the hospitalization admission rate for cardiovascular disease associated with a 10 dB increase in aircraft noise, for each airport and on average across airports adjusted by individual level characteristics (age, sex, race), zip code level socioeconomic status and demographics, zip code level air pollution (fine particulate matter and ozone), and roadway density. Averaged across all airports and using the 90th centile noise exposure metric, a zip code with 10 dB higher noise exposure had a 3.5% higher (95% confidence interval 0.2% to 7.0%) cardiovascular hospital admission rate, after controlling for covariates. Despite limitations related to potential misclassification of exposure, we found a statistically significant association between exposure to aircraft noise and risk of hospitalization for cardiovascular diseases among older people living near airports.

  14. Expression of a Truncated ATHB17 Protein in Maize Increases Ear Weight at Silking

    PubMed Central

    Creelman, Robert A.; Griffith, Cara; Ahrens, Jeffrey E.; Taylor, J. Philip; Murphy, Lesley R.; Manjunath, Siva; Thompson, Rebecca L.; Lingard, Matthew J.; Back, Stephanie L.; Larue, Huachun; Brayton, Bonnie R.; Burek, Amanda J.; Tiwari, Shiv; Adam, Luc; Morrell, James A.; Caldo, Rico A.; Huai, Qing; Kouadio, Jean-Louis K.; Kuehn, Rosemarie; Sant, Anagha M.; Wingbermuehle, William J.; Sala, Rodrigo; Foster, Matt; Kinser, Josh D.; Mohanty, Radha; Jiang, Dongming; Ziegler, Todd E.; Huang, Mingya G.; Kuriakose, Saritha V.; Skottke, Kyle; Repetti, Peter P.; Reuber, T. Lynne; Ruff, Thomas G.; Petracek, Marie E.; Loida, Paul J.

    2014-01-01

    ATHB17 (AT2G01430) is an Arabidopsis gene encoding a member of the α-subclass of the homeodomain leucine zipper class II (HD-Zip II) family of transcription factors. The ATHB17 monomer contains four domains common to all class II HD-Zip proteins: a putative repression domain adjacent to a homeodomain, leucine zipper, and carboxy terminal domain. However, it also possesses a unique N-terminus not present in other members of the family. In this study we demonstrate that the unique 73 amino acid N-terminus is involved in regulation of cellular localization of ATHB17. The ATHB17 protein is shown to function as a transcriptional repressor and an EAR-like motif is identified within the putative repression domain of ATHB17. Transformation of maize with an ATHB17 expression construct leads to the expression of ATHB17Δ113, a truncated protein lacking the first 113 amino acids which encodes a significant portion of the repression domain. Because ATHB17Δ113 lacks the repression domain, the protein cannot directly affect the transcription of its target genes. ATHB17Δ113 can homodimerize, form heterodimers with maize endogenous HD-Zip II proteins, and bind to target DNA sequences; thus, ATHB17Δ113 may interfere with HD-Zip II mediated transcriptional activity via a dominant negative mechanism. We provide evidence that maize HD-Zip II proteins function as transcriptional repressors and that ATHB17Δ113 relieves this HD-Zip II mediated transcriptional repression activity. Expression of ATHB17Δ113 in maize leads to increased ear size at silking and, therefore, may enhance sink potential. We hypothesize that this phenotype could be a result of modulation of endogenous HD-Zip II pathways in maize. PMID:24736658

  15. Expression of a truncated ATHB17 protein in maize increases ear weight at silking.

    PubMed

    Rice, Elena A; Khandelwal, Abha; Creelman, Robert A; Griffith, Cara; Ahrens, Jeffrey E; Taylor, J Philip; Murphy, Lesley R; Manjunath, Siva; Thompson, Rebecca L; Lingard, Matthew J; Back, Stephanie L; Larue, Huachun; Brayton, Bonnie R; Burek, Amanda J; Tiwari, Shiv; Adam, Luc; Morrell, James A; Caldo, Rico A; Huai, Qing; Kouadio, Jean-Louis K; Kuehn, Rosemarie; Sant, Anagha M; Wingbermuehle, William J; Sala, Rodrigo; Foster, Matt; Kinser, Josh D; Mohanty, Radha; Jiang, Dongming; Ziegler, Todd E; Huang, Mingya G; Kuriakose, Saritha V; Skottke, Kyle; Repetti, Peter P; Reuber, T Lynne; Ruff, Thomas G; Petracek, Marie E; Loida, Paul J

    2014-01-01

    ATHB17 (AT2G01430) is an Arabidopsis gene encoding a member of the α-subclass of the homeodomain leucine zipper class II (HD-Zip II) family of transcription factors. The ATHB17 monomer contains four domains common to all class II HD-Zip proteins: a putative repression domain adjacent to a homeodomain, leucine zipper, and carboxy terminal domain. However, it also possesses a unique N-terminus not present in other members of the family. In this study we demonstrate that the unique 73 amino acid N-terminus is involved in regulation of cellular localization of ATHB17. The ATHB17 protein is shown to function as a transcriptional repressor and an EAR-like motif is identified within the putative repression domain of ATHB17. Transformation of maize with an ATHB17 expression construct leads to the expression of ATHB17Δ113, a truncated protein lacking the first 113 amino acids which encodes a significant portion of the repression domain. Because ATHB17Δ113 lacks the repression domain, the protein cannot directly affect the transcription of its target genes. ATHB17Δ113 can homodimerize, form heterodimers with maize endogenous HD-Zip II proteins, and bind to target DNA sequences; thus, ATHB17Δ113 may interfere with HD-Zip II mediated transcriptional activity via a dominant negative mechanism. We provide evidence that maize HD-Zip II proteins function as transcriptional repressors and that ATHB17Δ113 relieves this HD-Zip II mediated transcriptional repression activity. Expression of ATHB17Δ113 in maize leads to increased ear size at silking and, therefore, may enhance sink potential. We hypothesize that this phenotype could be a result of modulation of endogenous HD-Zip II pathways in maize.

  16. Transcription Factors Responding to Pb Stress in Maize

    PubMed Central

    Zhang, Yanling; Ge, Fei; Hou, Fengxia; Sun, Wenting; Zheng, Qi; Zhang, Xiaoxiang; Ma, Langlang; Fu, Jun; He, Xiujing; Peng, Huanwei; Pan, Guangtang; Shen, Yaou

    2017-01-01

    Pb can damage the physiological function of human organs by entering the human body via food-chain enrichment. Revealing the mechanisms of maize tolerance to Pb is critical for preventing this. In this study, a Pb-tolerant maize inbred line, 178, was used to analyse transcription factors (TFs) expressed under Pb stress based on RNA sequencing data. A total of 464 genes expressed in control check (CK) or Pb treatment samples were annotated as TFs. Among them, 262 differentially expressed transcription factors (DETs) were identified that responded to Pb treatment. Furthermore, the DETs were classified into 4 classes according to their expression patterns, and 17, 12 and 2 DETs were significantly annotated to plant hormone signal transduction, basal transcription factors and base excision repair, respectively. Seventeen DETs were found to participate in the plant hormone signal transduction pathway, where basic leucine zippers (bZIPs) were the most significantly enriched TFs, with 12 members involved. We further obtained 5 Arabidopsis transfer DNA (T-DNA) mutants for 6 of the maize bZIPs, among which the mutants atbzip20 and atbzip47, representing ZmbZIP54 and ZmbZIP107, showed obviously inhibited growth of roots and above-ground parts, compared with wild type. Five highly Pb-tolerant and 5 highly Pb-sensitive in maize lines were subjected to DNA polymorphism and expression level analysis of ZmbZIP54 and ZmbZIP107. The results suggested that differences in bZIPs expression partially accounted for the differences in Pb-tolerance among the maize lines. Our results contribute to the understanding of the molecular regulation mechanisms of TFs in maize under Pb stress. PMID:28927013

  17. The bZIP dimer localizes at DNA full-sites where each basic region can alternately translocate and bind to subsites at the half-site.

    PubMed

    Chan, I-San; Al-Sarraj, Taufik; Shahravan, S Hesam; Fedorova, Anna V; Shin, Jumi A

    2012-08-21

    Crystal structures of the GCN4 bZIP (basic region/leucine zipper) with the AP-1 or CRE site show how each GCN4 basic region binds to a 4 bp cognate half-site as a single DNA target; however, this may not always fully describe how bZIP proteins interact with their target sites. Previously, we showed that the GCN4 basic region interacts with all 5 bp in half-site TTGCG (termed 5H-LR) and that 5H-LR comprises two 4 bp subsites, TTGC and TGCG, which individually are also target sites of the basic region. In this work, we explore how the basic region interacts with 5H-LR when the bZIP dimer localizes to full-sites. Using AMBER molecular modeling, we simulated GCN4 bZIP complexes with full-sites containing 5H-LR to investigate in silico the interface between the basic region and 5H-LR. We also performed in vitro investigation of bZIP-DNA interactions at a number of full-sites that contain 5H-LR versus either subsite: we analyzed results from DNase I footprinting and electrophoretic mobility shift assay (EMSA) and from EMSA titrations to quantify binding affinities. Our computational and experimental results together support a highly dynamic DNA-binding model: when a bZIP dimer localizes to its target full-site, the basic region can alternately recognize either subsite as a distinct target at 5H-LR and translocate between the subsites, potentially by sliding and hopping. This model provides added insights into how α-helical DNA-binding domains of transcription factors can localize to their gene regulatory sequences in vivo.

  18. ZIP2DL: An Elastic-Plastic, Large-Rotation Finite-Element Stress Analysis and Crack-Growth Simulation Program

    NASA Technical Reports Server (NTRS)

    Deng, Xiaomin; Newman, James C., Jr.

    1997-01-01

    ZIP2DL is a two-dimensional, elastic-plastic finte element program for stress analysis and crack growth simulations, developed for the NASA Langley Research Center. It has many of the salient features of the ZIP2D program. For example, ZIP2DL contains five material models (linearly elastic, elastic-perfectly plastic, power-law hardening, linear hardening, and multi-linear hardening models), and it can simulate mixed-mode crack growth for prescribed crack growth paths under plane stress, plane strain and mixed state of stress conditions. Further, as an extension of ZIP2D, it also includes a number of new capabilities. The large-deformation kinematics in ZIP2DL will allow it to handle elastic problems with large strains and large rotations, and elastic-plastic problems with small strains and large rotations. Loading conditions in terms of surface traction, concentrated load, and nodal displacement can be applied with a default linear time dependence or they can be programmed according to a user-defined time dependence through a user subroutine. The restart capability of ZIP2DL will make it possible to stop the execution of the program at any time, analyze the results and/or modify execution options and resume and continue the execution of the program. This report includes three sectons: a theoretical manual section, a user manual section, and an example manual secton. In the theoretical secton, the mathematics behind the various aspects of the program are concisely outlined. In the user manual section, a line-by-line explanation of the input data is given. In the example manual secton, three types of examples are presented to demonstrate the accuracy and illustrate the use of this program.

  19. Residential exposure to aircraft noise and hospital admissions for cardiovascular diseases: multi-airport retrospective study

    PubMed Central

    Correia, Andrew W; Peters, Junenette L; Levy, Jonathan I; Melly, Steven

    2013-01-01

    Objective To investigate whether exposure to aircraft noise increases the risk of hospitalization for cardiovascular diseases in older people (≥65 years) residing near airports. Design Multi-airport retrospective study of approximately 6 million older people residing near airports in the United States. We superimposed contours of aircraft noise levels (in decibels, dB) for 89 airports for 2009 provided by the US Federal Aviation Administration on census block resolution population data to construct two exposure metrics applicable to zip code resolution health insurance data: population weighted noise within each zip code, and 90th centile of noise among populated census blocks within each zip code. Setting 2218 zip codes surrounding 89 airports in the contiguous states. Participants 6 027 363 people eligible to participate in the national medical insurance (Medicare) program (aged ≥65 years) residing near airports in 2009. Main outcome measures Percentage increase in the hospitalization admission rate for cardiovascular disease associated with a 10 dB increase in aircraft noise, for each airport and on average across airports adjusted by individual level characteristics (age, sex, race), zip code level socioeconomic status and demographics, zip code level air pollution (fine particulate matter and ozone), and roadway density. Results Averaged across all airports and using the 90th centile noise exposure metric, a zip code with 10 dB higher noise exposure had a 3.5% higher (95% confidence interval 0.2% to 7.0%) cardiovascular hospital admission rate, after controlling for covariates. Conclusions Despite limitations related to potential misclassification of exposure, we found a statistically significant association between exposure to aircraft noise and risk of hospitalization for cardiovascular diseases among older people living near airports. PMID:24103538

  20. Dysregulation of hepatic zinc transporters in a mouse model of alcoholic liver disease

    PubMed Central

    Sun, Qian; Li, Qiong; Zhong, Wei; Zhang, Jiayang; Sun, Xiuhua; Tan, Xiaobing; Yin, Xinmin; Sun, Xinguo; Zhang, Xiang

    2014-01-01

    Zinc deficiency is a consistent phenomenon observed in patients with alcoholic liver disease, but the mechanisms have not been well defined. The objective of this study was to determine if alcohol alters hepatic zinc transporters in association with reduction of hepatic zinc levels and if oxidative stress mediates the alterations of zinc transporters. C57BL/6 mice were pair-fed with the Lieber-DeCarli control or ethanol diets for 2, 4, or 8 wk. Chronic alcohol exposure reduced hepatic zinc levels, but increased plasma and urine zinc levels, at all time points. Hepatic zinc finger proteins, peroxisome proliferator-activated receptor-α (PPAR-α) and hepatocyte nuclear factor 4α (HNF-4α), were downregulated in ethanol-fed mice. Four hepatic zinc transporter proteins showed significant alterations in ethanol-fed mice compared with the controls. ZIP5 and ZIP14 proteins were downregulated, while ZIP7 and ZnT7 proteins were upregulated, by ethanol exposure at all time points. Immunohistochemical staining demonstrated that chronic ethanol exposure upregulated cytochrome P-450 2E1 and caused 4-hydroxynonenal accumulation in the liver. For the in vitro study, murine FL-83B hepatocytes were treated with 5 μM 4-hydroxynonenal or 100 μM hydrogen peroxide for 72 h. The results from in vitro studies demonstrated that 4-hydroxynonenal treatment altered ZIP5 and ZIP7 protein abundance, and hydrogen peroxide treatment changed ZIP7, ZIP14, and ZnT7 protein abundance. These results suggest that chronic ethanol exposure alters hepatic zinc transporters via oxidative stress, which might account for ethanol-induced hepatic zinc deficiency. PMID:24924749

  1. Wartime Tracking of Class I Surface Shipments from Production or Procurement to Destination

    DTIC Science & Technology

    1992-04-01

    Armed Forces I ICAF-FAP National Defense University 6c. ADDRESS (City, State, ard ZIP Code ) 7b. ADDRESS (City, State, and ZIP Code ) Fort Lesley J...INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If applicable) 9c. ADDRESS (City, State, and ZIP Code ) 10. SOURCE OF FUNDING NUMBERS PROGRAM PROJECT TASK...COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP 19. ABSTRACT (Continue on reverse

  2. Force Identification from Structural Response

    DTIC Science & Technology

    1999-12-01

    STUDENT AT (If applicable) AFIT/CIA Univ of New Mexico A 6c. ADDRESS (City, State, and ZIP Code ) 7b. ADDRESS (City, State, and ZIP Code ) Wright...ADDRESS (City, State, and ZIP Code ) 10. SOURCE OF FUNDING NUMBERS PROGRAM PROJECT TASK WORK UNIT ELEMENT NO. NO. NO. ACCESSION NO. 11. TITLE (h,,clude...FOR PUBLIC RELEASE IAW AFR 190-1 ERNEST A. HAYGOOD, 1st Lt, USAF Executive Officer, Civilian Institution Programs 17. COSATI CODES 18. SUBJECT TERMS

  3. The validation of Fibit Zip™ physical activity monitor as a measure of free-living physical activity.

    PubMed

    Tully, Mark A; McBride, Cairmeal; Heron, Leonnie; Hunter, Ruth F

    2014-12-23

    The new generation of activity monitors allow users to upload their data to the internet and review progress. The aim of this study is to validate the Fitbit Zip as a measure of free-living physical activity. Participants wore a Fitbit Zip, ActiGraph GT3X accelerometer and a Yamax CW700 pedometer for seven days. Participants were asked their opinion on the utility of the Fitbit Zip. Validity was assessed by comparing the output using Spearman's rank correlation coefficients, Wilcoxon signed rank tests and Bland-Altman plots. 59.5% (25/47) of the cohort were female. There was a high correlation in steps/day between the Fitbit Zip and the two reference devices (r = 0.91, p < 0.001). No statistically significant difference between the Fitbit and Yamax steps/day was observed (Median (IQR) 7477 (3597) vs 6774 (3851); p = 0.11). The Fitbit measured significantly more steps/day than the Actigraph (7477 (3597) vs 6774 (3851); p < 0.001). Bland-Altman plots revealed no systematic differences between the devices. Given the high level of correlation and no apparent systematic biases in the Bland Altman plots, the use of Fitbit Zip as a measure of physical activity. However the Fitbit Zip recorded a significantly higher number of steps per day than the Actigraph.

  4. Genome-Wide Investigation and Expression Profiling of HD-Zip Transcription Factors in Foxtail Millet (Setaria italica L.).

    PubMed

    Chai, Wenbo; Si, Weina; Ji, Wei; Qin, Qianqian; Zhao, Manli; Jiang, Haiyang

    2018-01-01

    HD-Zip proteins represent the major transcription factors in higher plants, playing essential roles in plant development and stress responses. Foxtail millet is a crop to investigate the systems biology of millet and biofuel grasses and the HD-Zip gene family has not been studied in foxtail millet. For further investigation of the expression profile of the HD-Zip gene family in foxtail millet, a comprehensive genome-wide expression analysis was conducted in this study. We found 47 protein-encoding genes in foxtail millet using BLAST search tools; the putative proteins were classified into four subfamilies, namely, subfamilies I, II, III, and IV. Gene structure and motif analysis indicate that the genes in one subfamily were conserved. Promotor analysis showed that HD-Zip gene was involved in abiotic stress. Duplication analysis revealed that 8 (~17%) hdz genes were tandemly duplicated and 28 (58%) were segmentally duplicated; purifying duplication plays important roles in gene expansion. Microsynteny analysis revealed the maximum relationship in foxtail millet-sorghum and foxtail millet-rice. Expression profiling upon the abiotic stresses of drought and high salinity and the biotic stress of ABA revealed that some genes regulated responses to drought and salinity stresses via an ABA-dependent process, especially sihdz29 and sihdz45. Our study provides new insight into evolutionary and functional analyses of HD-Zip genes involved in environmental stress responses in foxtail millet.

  5. Community Alcohol Outlet Density and Underage Drinking

    PubMed Central

    Chen, Meng-Jinn; Grube, Joel W.; Gruenewald, Paul J.

    2009-01-01

    Aim This study examined how community alcohol outlet density may be associated with drinking among youths. Methods Longitudinal data were collected from 1091 adolescents (aged 14–16 at baseline) recruited from 50 zip codes in California with varying levels of alcohol outlet density and median household income. Hierarchical linear models were used to examine the associations between zip code alcohol outlet density and frequency rates of general alcohol use and excessive drinking, taking into account zip code median household income and individual-level variables (age, gender, race/ethnicity, personal income, mobility, and perceived drinking by parents and peers). Findings When all other factors were controlled, higher initial levels of drinking and excessive drinking were observed among youths residing in zip codes with higher alcohol outlet densities. Growth in drinking and excessive drinking was on average more rapid in zip codes with lower alcohol outlet densities. The relation of zip code alcohol outlet density with drinking appeared to be mitigated by having friends with access to a car. Conclusion Alcohol outlet density may play a significant role in initiation of underage drinking during early teen ages, especially when youths have limited mobility. Youth who reside in areas with low alcohol outlet density may overcome geographic constraints through social networks that increase their mobility and the ability to seek alcohol and drinking opportunities beyond the local community. PMID:20078485

  6. Computing travel time when the exact address is unknown: a comparison of point and polygon ZIP code approximation methods.

    PubMed

    Berke, Ethan M; Shi, Xun

    2009-04-29

    Travel time is an important metric of geographic access to health care. We compared strategies of estimating travel times when only subject ZIP code data were available. Using simulated data from New Hampshire and Arizona, we estimated travel times to nearest cancer centers by using: 1) geometric centroid of ZIP code polygons as origins, 2) population centroids as origin, 3) service area rings around each cancer center, assigning subjects to rings by assuming they are evenly distributed within their ZIP code, 4) service area rings around each center, assuming the subjects follow the population distribution within the ZIP code. We used travel times based on street addresses as true values to validate estimates. Population-based methods have smaller errors than geometry-based methods. Within categories (geometry or population), centroid and service area methods have similar errors. Errors are smaller in urban areas than in rural areas. Population-based methods are superior to the geometry-based methods, with the population centroid method appearing to be the best choice for estimating travel time. Estimates in rural areas are less reliable.

  7. Mm-size bistable zipping dielectric elastomer actuators for integrated microfluidics

    NASA Astrophysics Data System (ADS)

    Maffli, Luc; Rosset, Samuel; Shea, Herbert R.

    2013-04-01

    We report on a new structure of Dielectric Elastomer Actuators (DEAs) called zipping DEAs, which have a set of unique characteristics that are a good match for the requirements of electrically-powered integrated microfluidic pumping and/or valving units as well as Braille displays. The zipping DEAs operate by pulling electrostatically an elastomer membrane in contact with the rigid sidewalls of a sloped chamber. In this work, we report on fully functional mm-size zipping DEAs that demonstrate a complete sealing of the chamber sidewalls and a tunable bistable behavior, and compare the measurements with an analytical model. Compared to our first generation of devices, we are able vary the sidewall angle and benefit therefore from more flexibility to study the requirements to make fully functional actuators. In particular, we show that with Nusil CF19 as membrane material (1.2 MPa Young's modulus), it is possible to zip completely 2.3 mm diameter chambers with 15° and 21° sidewalls angle equibiaxially prestretched to λ0=1.12 and 15° chambers with λ0=1.27.

  8. An Assessment of Potential Soviet Responses to Evolving Theater Nuclear Systems.

    DTIC Science & Technology

    1987-06-05

    ORGANIZATION REPORT NUMIBER(S) 5 MONITORING ORGANIZAODN REPORT NUMNBER(S) 6a NAM OFPERFORMING ORGANIZATION fib OFFICE SYMBOL 7& NAME OF MONITORING... ORGANIZATION 6C. ADDRESS (Oty. State, and ZIP Cod.) 7b ADDRESSC,ty, State, and ZIP Cod.) Vicksburg, MS 39180-0631 Ba AMEOF UNDNG SPOSORNG8b OFFICE SYMBOL...9 PROCuREMENT INSR~UMENT IDENTiCICATtON N%BER ORGANIZATION (If appliabe USAm op fEgnes DN’o~)1 Bk. ADDRESS (City, State, and ZIP Code) 10 SOURCE OF

  9. Tobacco outlet density and converted versus native non-daily cigarette use in a national US sample.

    PubMed

    Kirchner, Thomas R; Anesetti-Rothermel, Andrew; Bennett, Morgane; Gao, Hong; Carlos, Heather; Scheuermann, Taneisha S; Reitzel, Lorraine R; Ahluwalia, Jasjit S

    2017-01-01

    Investigate whether non-daily smokers' (NDS) cigarette price and purchase preferences, recent cessation attempts, and current intentions to quit are associated with the density of the retail cigarette product landscape surrounding their residential address. Cross-sectional assessment of N=904 converted NDS (CNDS). who previously smoked every day, and N=297 native NDS (NNDS) who only smoked non-daily, drawn from a national panel. Kernel density estimation was used to generate a nationwide probability surface of tobacco outlets linked to participants' residential ZIP code. Hierarchically nested log-linear models were compared to evaluate associations between outlet density, non-daily use patterns, price sensitivity and quit intentions. Overall, NDS in ZIP codes with greater outlet density were less likely than NDS in ZIP codes with lower outlet density to hold 6-month quit intentions when they also reported that price affected use patterns (G 2 =66.1, p<0.001) and purchase locations (G 2 =85.2, p<0.001). CNDS were more likely than NNDS to reside in ZIP codes with higher outlet density (G 2 =322.0, p<0.001). Compared with CNDS in ZIP codes with lower outlet density, CNDS in high-density ZIP codes were more likely to report that price influenced the amount they smoke (G 2 =43.9, p<0.001), and were more likely to look for better prices (G 2 =59.3, p<0.001). NDS residing in high-density ZIP codes were not more likely to report that price affected their cigarette brand choice compared with those in ZIP codes with lower density. This paper provides initial evidence that the point-of-sale cigarette environment may be differentially associated with the maintenance of CNDS versus NNDS patterns. Future research should investigate how tobacco control efforts can be optimised to both promote cessation and curb the rising tide of non-daily smoking in the USA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  10. Hepatitis C: Treatment

    MedlinePlus

    ... Public Home » Hepatitis C » Hepatitis C Treatment Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For ... Enter ZIP code here Enter ZIP code here Hepatitis C Treatment for Veterans and the Public Treatment ...

  11. Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes.

    PubMed

    Roskoski, Robert

    2016-01-01

    Because dysregulation and mutations of protein kinases play causal roles in human disease, this family of enzymes has become one of the most important drug targets over the past two decades. The X-ray crystal structures of 21 of the 27 FDA-approved small molecule inhibitors bound to their target protein kinases are depicted in this paper. The structure of the enzyme-bound antagonist complex is used in the classification of these inhibitors. Type I inhibitors bind to the active protein kinase conformation (DFG-Asp in, αC-helix in). Type I½ inhibitors bind to a DFG-Asp in inactive conformation while Type II inhibitors bind to a DFG-Asp out inactive conformation. Type I, I½, and type II inhibitors occupy part of the adenine binding pocket and form hydrogen bonds with the hinge region connecting the small and large lobes of the enzyme. Type III inhibitors bind next to the ATP-binding pocket and type IV inhibitors do not bind to the ATP or peptide substrate binding sites. Type III and IV inhibitors are allosteric in nature. Type V inhibitors bind to two different regions of the protein kinase domain and are therefore bivalent inhibitors. The type I-V inhibitors are reversible. In contrast, type VI inhibitors bind covalently to their target enzyme. Type I, I½, and II inhibitors are divided into A and B subtypes. The type A inhibitors bind in the front cleft, the back cleft, and near the gatekeeper residue, all of which occur within the region separating the small and large lobes of the protein kinase. The type B inhibitors bind in the front cleft and gate area but do not extend into the back cleft. An analysis of the limited available data indicates that type A inhibitors have a long residence time (minutes to hours) while the type B inhibitors have a short residence time (seconds to minutes). The catalytic spine includes residues from the small and large lobes and interacts with the adenine ring of ATP. Nearly all of the approved protein kinase inhibitors occupy the adenine-binding pocket; thus it is not surprising that these inhibitors interact with nearby catalytic spine (CS) residues. Moreover, a significant number of approved drugs also interact with regulatory spine (RS) residues. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Find a Diabetes Prevention Program Near You

    MedlinePlus

    ... throughout the country. Find an In-person Class Select From List Find a class near you by ... some locations. Search by ZIP ZIP Code: Distance: Select Location Location: Find an Online Program Online programs ...

  13. Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones

    PubMed Central

    Chao, Lily; Marcus-Samuels, Bernice; Mason, Mark M.; Moitra, Jaideep; Vinson, Charles; Arioglu, Elif; Gavrilova, Oksana; Reitman, Marc L.

    2000-01-01

    There is uncertainty about the site(s) of action of the antidiabetic thiazolidinediones (TZDs). These drugs are agonist ligands of the transcription factor PPARγ, which is abundant in adipose tissue but is normally present at very low levels in liver and muscle. We have studied the effects of TZDs in A-ZIP/F-1 mice, which lack white adipose tissue. The A-ZIP/F-1 phenotype strikingly resembles that of humans with severe lipoatrophic diabetes, including the lack of fat, marked insulin resistance and hyperglycemia, hyperlipidemia, and fatty liver. Rosiglitazone or troglitazone treatment did not reduce glucose or insulin levels, suggesting that white adipose tissue is required for the antidiabetic effects of TZDs. However, TZD treatment was effective in lowering circulating triglycerides and increasing whole body fatty acid oxidation in the A-ZIP/F-1 mice, indicating that this effect occurs via targets other than white adipose tissue. A-ZIP/F-1 mice have markedly increased liver PPARγ mRNA levels, which may be a general property of fatty livers. Rosiglitazone treatment increased the triglyceride content of the steatotic livers of A-ZIP/F-1 and ob/ob mice, but not the “lean” livers of fat-transplanted A-ZIP/F-1 mice. In light of this evidence that rosiglitazone acts differently in steatotic livers, the effects of rosiglitazone, particularly on hepatic triglyceride levels, should be examined in humans with hepatic steatosis. PMID:11086023

  14. Transcriptome-Wide Survey and Expression Profile Analysis of Putative Chrysanthemum HD-Zip I and II Genes

    PubMed Central

    Song, Aiping; Li, Peiling; Xin, Jingjing; Chen, Sumei; Zhao, Kunkun; Wu, Dan; Fan, Qingqing; Gao, Tianwei; Chen, Fadi; Guan, Zhiyong

    2016-01-01

    The homeodomain-leucine zipper (HD-Zip) transcription factor family is a key transcription factor family and unique to the plant kingdom. It consists of a homeodomain and a leucine zipper that serve in combination as a dimerization motif. The family can be classified into four subfamilies, and these subfamilies participate in the development of hormones and mediation of hormone action and are involved in plant responses to environmental conditions. However, limited information on this gene family is available for the important chrysanthemum ornamental species (Chrysanthemum morifolium). Here, we characterized 17 chrysanthemum HD-Zip genes based on transcriptome sequences. Phylogenetic analyses revealed that 17 CmHB genes were distributed in the HD-Zip subfamilies I and II and identified two pairs of putative orthologous proteins in Arabidopsis and chrysanthemum and four pairs of paralogous proteins in chrysanthemum. The software MEME was used to identify 7 putative motifs with E values less than 1e-3 in the chrysanthemum HD-Zip factors, and they can be clearly classified into two groups based on the composition of the motifs. A bioinformatics analysis predicted that 8 CmHB genes could be targeted by 10 miRNA families, and the expression of these 17 genes in response to phytohormone treatments and abiotic stresses was characterized. The results presented here will promote research on the various functions of the HD-Zip gene family members in plant hormones and stress responses. PMID:27196930

  15. How Accurate Is Your Activity Tracker? A Comparative Study of Step Counts in Low-Intensity Physical Activities.

    PubMed

    Alinia, Parastoo; Cain, Chris; Fallahzadeh, Ramin; Shahrokni, Armin; Cook, Diane; Ghasemzadeh, Hassan

    2017-08-11

    As commercially available activity trackers are being utilized in clinical trials, the research community remains uncertain about reliability of the trackers, particularly in studies that involve walking aids and low-intensity activities. While these trackers have been tested for reliability during walking and running activities, there has been limited research on validating them during low-intensity activities and walking with assistive tools. The aim of this study was to (1) determine the accuracy of 3 Fitbit devices (ie, Zip, One, and Flex) at different wearing positions (ie, pants pocket, chest, and wrist) during walking at 3 different speeds, 2.5, 5, and 8 km/h, performed by healthy adults on a treadmill; (2) determine the accuracy of the mentioned trackers worn at different sites during activities of daily living; and (3) examine whether intensity of physical activity (PA) impacts the choice of optimal wearing site of the tracker. We recruited 15 healthy young adults to perform 6 PAs while wearing 3 Fitbit devices (ie, Zip, One, and Flex) on their chest, pants pocket, and wrist. The activities include walking at 2.5, 5, and 8 km/h, pushing a shopping cart, walking with aid of a walker, and eating while sitting. We compared the number of steps counted by each tracker with gold standard numbers. We performed multiple statistical analyses to compute descriptive statistics (ie, ANOVA test), intraclass correlation coefficient (ICC), mean absolute error rate, and correlation by comparing the tracker-recorded data with that of the gold standard. All the 3 trackers demonstrated good-to-excellent (ICC>0.75) correlation with the gold standard step counts during treadmill experiments. The correlation was poor (ICC<0.60), and the error rate was significantly higher in walker experiment compared to other activities. There was no significant difference between the trackers and the gold standard in the shopping cart experiment. The wrist worn tracker, Flex, counted several steps when eating (P<.01). The chest tracker was identified as the most promising site to capture steps in more intense activities, while the wrist was the optimal wearing site in less intense activities. This feasibility study focused on 6 PAs and demonstrated that Fitbit trackers were most accurate when walking on a treadmill and least accurate during walking with a walking aid and for low-intensity activities. This may suggest excluding participants with assistive devices from studies that focus on PA interventions using commercially available trackers. This study also indicates that the wearing site of the tracker is an important factor impacting the accuracy performance. A larger scale study with a more diverse population, various activity tracker vendors, and a larger activity set are warranted to generalize our results. ©Parastoo Alinia, Chris Cain, Ramin Fallahzadeh, Armin Shahrokni, Diane Cook, Hassan Ghasemzadeh. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 11.08.2017.

  16. Future Research Needs for Dredgeability of Rock: Rock Dredging Workshop Held in Jacksonville, Florida on 25-26 July 1985.

    DTIC Science & Technology

    1986-09-01

    ORGANIZATION Gjeoteehnical Laborator WESGR-M 6c ADDRESS (City, Slate, and ZIP Code ) 7b ADDRESS(City, State. and ZIP Code ) PO Box 631 Vicksburg, MS 39180...of Engineers 8< ADDRESS(City, State, and ZIP Code ) 10 SOURCE OF FUNDING NUMBERS PROGRAM PROJECT TASK WORK UNIT.. ", 1 :, • ; I, - u It ., " ’ ~f...Springfield, VA 22161 17 COSATI CODES 18 SUBJECT TERMS (Continue-On revprse of necessary and identify by block number) " FIELD GROUP SUB GROUP

  17. Migration of Hazardous Substances through Soil. Part 4. Development of a Serial Batch Extraction Method and Application to the Accelerated Testing of Seven Industrial Wastes

    DTIC Science & Technology

    1987-09-01

    Evaluation Commnand &_. ADMASS Coly, 1W~., and ZIP Code ) 7b. ADDRESS (C01y, State, wid ZIP Code ) Dugwiay, Utahi 84022-5000 Aberdeen Proving Ground...Aency_________________________ 9L AoOMS(CRY, 0to, and ZIP Code ) 10. SOURCE OF FUNDING NUMBERS Hazardous Waste Environmental RLsearch Lab PROGRAM PROJECT TASK...CLASSIFICATION 0 UNO.ASSIFIEDAIJNLIMITED 0l SAME AS RPT. 03 OTIC USERS UNCLA.SSIFIED 22a. RAWE OF RESPONSIBLE INDIVIDUAL 22b TELEPHONE (Include Area Code ) I

  18. Zeta Inhibitory Peptide Disrupts Electrostatic Interactions That Maintain Atypical Protein Kinase C in Its Active Conformation on the Scaffold p62.

    PubMed

    Tsai, Li-Chun Lisa; Xie, Lei; Dore, Kim; Xie, Li; Del Rio, Jason C; King, Charles C; Martinez-Ariza, Guillermo; Hulme, Christopher; Malinow, Roberto; Bourne, Philip E; Newton, Alexandra C

    2015-09-04

    Atypical protein kinase C (aPKC) enzymes signal on protein scaffolds, yet how they are maintained in an active conformation on scaffolds is unclear. A myristoylated peptide based on the autoinhibitory pseudosubstrate fragment of the atypical PKCζ, zeta inhibitory peptide (ZIP), has been extensively used to inhibit aPKC activity; however, we have previously shown that ZIP does not inhibit the catalytic activity of aPKC isozymes in cells (Wu-Zhang, A. X., Schramm, C. L., Nabavi, S., Malinow, R., and Newton, A. C. (2012) J. Biol. Chem. 287, 12879-12885). Here we sought to identify a bona fide target of ZIP and, in so doing, unveiled a novel mechanism by which aPKCs are maintained in an active conformation on a protein scaffold. Specifically, we used protein-protein interaction network analysis, structural modeling, and protein-protein docking to predict that ZIP binds an acidic surface on the Phox and Bem1 (PB1) domain of p62, an interaction validated by peptide array analysis. Using a genetically encoded reporter for PKC activity fused to the p62 scaffold, we show that ZIP inhibits the activity of wild-type aPKC, but not a construct lacking the pseudosubstrate. These data support a model in which the pseudosubstrate of aPKCs is tethered to the acidic surface on p62, locking aPKC in an open, signaling-competent conformation. ZIP competes for binding to the acidic surface, resulting in displacement of the pseudosubstrate of aPKC and re-engagement in the substrate-binding cavity. This study not only identifies a cellular target for ZIP, but also unveils a novel mechanism by which scaffolded aPKC is maintained in an active conformation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The Proliferating Cell Nuclear Antigen (PCNA)-interacting Protein (PIP) Motif of DNA Polymerase η Mediates Its Interaction with the C-terminal Domain of Rev1*

    PubMed Central

    Boehm, Elizabeth M.; Powers, Kyle T.; Kondratick, Christine M.; Spies, Maria; Houtman, Jon C. D.; Washington, M. Todd

    2016-01-01

    Y-family DNA polymerases, such as polymerase η, polymerase ι, and polymerase κ, catalyze the bypass of DNA damage during translesion synthesis. These enzymes are recruited to sites of DNA damage by interacting with the essential replication accessory protein proliferating cell nuclear antigen (PCNA) and the scaffold protein Rev1. In most Y-family polymerases, these interactions are mediated by one or more conserved PCNA-interacting protein (PIP) motifs that bind in a hydrophobic pocket on the front side of PCNA as well as by conserved Rev1-interacting region (RIR) motifs that bind in a hydrophobic pocket on the C-terminal domain of Rev1. Yeast polymerase η, a prototypical translesion synthesis polymerase, binds both PCNA and Rev1. It possesses a single PIP motif but not an RIR motif. Here we show that the PIP motif of yeast polymerase η mediates its interactions both with PCNA and with Rev1. Moreover, the PIP motif of polymerase η binds in the hydrophobic pocket on the Rev1 C-terminal domain. We also show that the RIR motif of human polymerase κ and the PIP motif of yeast Msh6 bind both PCNA and Rev1. Overall, these findings demonstrate that PIP motifs and RIR motifs have overlapping specificities and can interact with both PCNA and Rev1 in structurally similar ways. These findings also suggest that PIP motifs are a more versatile protein interaction motif than previously believed. PMID:26903512

  20. Seasonal Abscisic Acid Signal and a Basic Leucine Zipper Transcription Factor, DkbZIP5, Regulate Proanthocyanidin Biosynthesis in Persimmon Fruit1[C][W][OA

    PubMed Central

    Akagi, Takashi; Katayama-Ikegami, Ayako; Kobayashi, Shozo; Sato, Akihiko; Kono, Atsushi; Yonemori, Keizo

    2012-01-01

    Proanthocyanidins (PAs) are secondary metabolites that contribute to plant protection and crop quality. Persimmon (Diospyros kaki) has a unique characteristic of accumulating large amounts of PAs, particularly in its fruit. Normal astringent-type and mutant nonastringent-type fruits show different PA accumulation patterns depending on the seasonal expression patterns of DkMyb4, which is a Myb transcription factor (TF) regulating many PA pathway genes in persimmon. In this study, attempts were made to identify the factors involved in DkMyb4 expression and the resultant PA accumulation in persimmon fruit. Treatment with abscisic acid (ABA) and an ABA biosynthesis inhibitor resulted in differential changes in the expression patterns of DkMyb4 and PA biosynthesis in astringent-type and nonastringent-type fruits depending on the development stage. To obtain an ABA-signaling TF, we isolated a full-length basic leucine zipper (bZIP) TF, DkbZIP5, which is highly expressed in persimmon fruit. We also showed that ectopic DkbZIP5 overexpression in persimmon calluses induced the up-regulation of DkMyb4 and the resultant PA biosynthesis. In addition, a detailed molecular characterization using the electrophoretic mobility shift assay and transient reporter assay indicated that DkbZIP5 recognized ABA-responsive elements in the promoter region of DkMyb4 and acted as a direct regulator of DkMyb4 in an ABA-dependent manner. These results suggest that ABA signals may be involved in PA biosynthesis in persimmon fruit via DkMyb4 activation by DkbZIP5. PMID:22190340

  1. Accuracy of a step counter during treadmill and daily life walking by healthy adults and patients with cardiac disease

    PubMed Central

    Thorup, Charlotte Brun; Grønkjær, Mette; Dinesen, Birthe Irene

    2017-01-01

    Background Step counters have been used to observe activity and support physical activity, but there is limited evidence on their accuracy. Objective The purpose was to investigate the step accuracy of the Fitbit Zip (Zip) in healthy adults during treadmill walking and in patients with cardiac disease while hospitalised at home. Methods Twenty healthy adults aged 39±13.79 (mean ±SD) wore four Zips while walking on a treadmill at different speeds (1.7–6.1 km/hour), and 24 patients with cardiac disease (age 67±10.03) wore a Zip for 24 hours during hospitalisation and for 4 weeks thereafter at home. A Shimmer3 device was used as a criterion standard. Results At a treadmill speed of 3.6 km/hour, the relative error (±SD) for the Zips on the upper body was −0.02±0.67 on the right side and −0.09 (0.67) on the left side. For the Zips on the waist, this was 0.08±0.71 for the right side and -0.08 (0.47) on the left side. At a treadmill speed of 3.6 km/hour and higher, the average per cent of relative error was <3%. The 24-hour test for the hospitalised patients showed a relative error of −47.15±24.11 (interclass correlation coefficient (ICC): 0.60), and for the 24-hour test at home, the relative error was −27.51±28.78 (ICC: 0.87). Thus, none of the 24-hour tests had less than the expected 20% error. In time periods of evident walking during the 24 h test, the Zip had an average per cent relative error of <3% at 3.6 km/hour and higher speeds. Conclusions A speed of 3.6 km/hour or higher is required to expect acceptable accuracy in step measurement using a Zip, on a treadmill and in real life. Inaccuracies are directly related to slow speeds, which might be a problem for patients with cardiac disease who walk at a slow pace. PMID:28363918

  2. Biomass Data | Geospatial Data Science | NREL

    Science.gov Websites

    Biomass Data Biomass Data These datasets detail the biomass resources available in the United Coverage File Last Updated Metadata Biomethane Zip 72.2 MB 10/30/2014 Biomethane.xml Solid Biomass Zip 69.5

  3. Formal Models of Hardware and Their Applications to VLSI Design Automation.

    DTIC Science & Technology

    1986-12-24

    ORGANIZATION Universitv of Southern’iaplcbe ralifnrni Offico of ’,aval "esearch 6c. ADDRESS (City. State and ZIP Code) 7b. ADDRESS (City. Stote and ZIP Code...Di’f-i2C-33-K-O147 8.ADESS IXity, State and ZIP Coda, 10 SOURCE OF FUNDING NODS US fr-," esearch C-f-ice PORM POET TS OKUI 2..Fc 2~1ELEMENT No NO. NO...are classified as belonging to one of six different types. The dimensions of the routing channel are defined as functions of these random variables

  4. The prion-ZIP connection: From cousins to partners in iron uptake

    PubMed Central

    Singh, Neena; Asthana, Abhishek; Baksi, Shounak; Desai, Vilok; Haldar, Swati; Hari, Sahi; Tripathi, Ajai K

    2015-01-01

    ABSTRACT Converging observations from disparate lines of inquiry are beginning to clarify the cause of brain iron dyshomeostasis in sporadic Creutzfeldt-Jakob disease (sCJD), a neurodegenerative condition associated with the conversion of prion protein (PrPC), a plasma membrane glycoprotein, from α-helical to a β-sheet rich PrP-scrapie (PrPSc) isoform. Biochemical evidence indicates that PrPC facilitates cellular iron uptake by functioning as a membrane-bound ferrireductase (FR), an activity necessary for the transport of iron across biological membranes through metal transporters. An entirely different experimental approach reveals an evolutionary link between PrPC and the Zrt, Irt-like protein (ZIP) family, a group of proteins involved in the transport of zinc, iron, and manganese across the plasma membrane. Close physical proximity of PrPC with certain members of the ZIP family on the plasma membrane and increased uptake of extracellular iron by cells that co-express PrPC and ZIP14 suggest that PrPC functions as a FR partner for certain members of this family. The connection between PrPC and ZIP proteins therefore extends beyond common ancestry to that of functional cooperation. Here, we summarize evidence supporting the facilitative role of PrPC in cellular iron uptake, and implications of this activity on iron metabolism in sCJD brains. PMID:26689487

  5. Spatial relationships among dairy farms, drinking water quality, and maternal-child health outcomes in the San Joaquin Valley.

    PubMed

    Blake, Sarah Brown

    2014-01-01

    Access to clean and affordable water is a significant public health issue globally, in the United States, and in California where land is heavily used for agriculture and dairy operations. The purpose of this study was to explore the geographic relationships among dairy farms, nitrate levels in drinking water, low birth weight, and socioeconomic data at the ZIP code level in the San Joaquin Valley. This ecological study used a Geographic Information System (GIS) to explore and analyze secondary data. A total of 211 ZIP codes were analyzed using spatial autocorrelation and regression analysis methods in ArcGIS version 10.1. ZIP codes with dairies had a higher percentage of Hispanic births (p = .001). Spatial statistics revealed that ZIP codes with more dairy farms and a higher dairy cow density had higher levels of nitrate contamination. No correlation was detected between LBW and unsafe nitrate levels at the ZIP code level. Further research examining communities that use private and small community wells in the San Joaquin Valley should be conducted. Birth data from smaller geographic areas should be used to continue exploring the relationship between birth outcomes and nitrate contamination in drinking water. © 2014 Wiley Periodicals, Inc.

  6. The Populus class III HD ZIP, popREVOLUTA, influences cambium initiation and patterning of woody stems.

    PubMed

    Robischon, Marcel; Du, Juan; Miura, Eriko; Groover, Andrew

    2011-03-01

    The secondary growth of a woody stem requires the formation of a vascular cambium at an appropriate position and proper patterning of the vascular tissues derived from the cambium. Class III homeodomain-leucine zipper (HD ZIP) transcription factors have been implicated in polarity determination and patterning in lateral organs and primary vascular tissues and in the initiation and function of shoot apical meristems. We report here the functional characterization of a Populus class III HD ZIP gene, popREVOLUTA (PRE), that demonstrates another role for class III HD ZIPs in regulating the development of cambia and secondary vascular tissues. PRE is orthologous to Arabidopsis (Arabidopsis thaliana) REVOLUTA and is expressed in both the shoot apical meristem and in the cambial zone and secondary vascular tissues. Transgenic Populus expressing a microRNA-resistant form of PRE presents unstable phenotypic abnormalities affecting both primary and secondary growth. Surprisingly, phenotypic changes include abnormal formation of cambia within cortical parenchyma that can produce secondary vascular tissues in reverse polarity. Genes misexpressed in PRE mutants include transcription factors and auxin-related genes previously implicated in class III HD ZIP functions during primary growth. Together, these results suggest that PRE plays a fundamental role in the initiation of the cambium and in regulating the patterning of secondary vascular tissues.

  7. Heterogeneous Compression of Large Collections of Evolutionary Trees.

    PubMed

    Matthews, Suzanne J

    2015-01-01

    Compressing heterogeneous collections of trees is an open problem in computational phylogenetics. In a heterogeneous tree collection, each tree can contain a unique set of taxa. An ideal compression method would allow for the efficient archival of large tree collections and enable scientists to identify common evolutionary relationships over disparate analyses. In this paper, we extend TreeZip to compress heterogeneous collections of trees. TreeZip is the most efficient algorithm for compressing homogeneous tree collections. To the best of our knowledge, no other domain-based compression algorithm exists for large heterogeneous tree collections or enable their rapid analysis. Our experimental results indicate that TreeZip averages 89.03 percent (72.69 percent) space savings on unweighted (weighted) collections of trees when the level of heterogeneity in a collection is moderate. The organization of the TRZ file allows for efficient computations over heterogeneous data. For example, consensus trees can be computed in mere seconds. Lastly, combining the TreeZip compressed (TRZ) file with general-purpose compression yields average space savings of 97.34 percent (81.43 percent) on unweighted (weighted) collections of trees. Our results lead us to believe that TreeZip will prove invaluable in the efficient archival of tree collections, and enables scientists to develop novel methods for relating heterogeneous collections of trees.

  8. Evaluating area-based socioeconomic status indicators for monitoring disparities within health care systems: results from a primary care network.

    PubMed

    Berkowitz, Seth A; Traore, Carine Y; Singer, Daniel E; Atlas, Steven J

    2015-04-01

    To determine which area-based socioeconomic status (SES) indicator is best suited to monitor health care disparities from a delivery system perspective. 142,659 adults seen in a primary care network from January 1, 2009 to December 31, 2011. Cross-sectional, comparing associations between area-based SES indicators and patient outcomes. Address data were geocoded to construct area-based SES indicators at block group (BG), census tract (CT), and ZIP code (ZIP) levels. Data on health outcomes were abstracted from electronic records. Relative indices of inequality (RIIs) were calculated to quantify disparities detected by area-based SES indicators and compared to RIIs from self-reported educational attainment. ZIP indicators had less missing data than BG or CT indicators (p < .0001). Area-based SES indicators were strongly associated with self-report educational attainment (p < .0001). ZIP, BG, and CT indicators all detected expected SES gradients in health outcomes similarly. Single-item, cut point defined indicators performed as well as multidimensional indices and quantile indicators. Area-based SES indicators detected health outcome differences well and may be useful for monitoring disparities within health care systems. Our preferred indicator was ZIP-level median household income or percent poverty, using cut points. © Health Research and Educational Trust.

  9. Estimating sources of Valley Fever pathogen propagation in southern Arizona: A remote sensing approach

    NASA Astrophysics Data System (ADS)

    Pianalto, Frederick S.

    Coccidioidomycosis (Valley Fever) is an environmentally-mediated respiratory disease caused by the inhalation of airborne spores from the fungi Coccidioides spp. The fungi reside in arid and semi-arid soils of the Americas. The disease has increased epidemically in Arizona and other areas within the last two decades. Despite this increase, the ecology of the fungi remains obscure, and environmental antecedents of the disease are largely unstudied. Two sources of soil disturbance, hypothesized to affect soil ecology and initiate spore dissemination, are investigated. Nocturnal desert rodents interact substantially with the soil substrate. Rodents are hypothesized to act as a reservoir of coccidioidomycosis, a mediator of soil properties, and a disseminator of fungal spores. Rodent distributions are poorly mapped for the study area. We build automated multi-linear regression models and decision tree models for ten rodent species using rodent trapping data from the Organ Pipe Cactus National Monument (ORPI) in southwest Arizona with a combination of surface temperature, a vegetation index and its texture, and a suite of topographic rasters. Surface temperature, derived from Landsat TM thermal images, is the most widely selected predictive variable in both automated methods. Construction-related soil disturbance (e.g. road construction, trenching, land stripping, and earthmoving) is a significant source of fugitive dust, which decreases air quality and may carry soil pathogens. Annual differencing of Landsat Thematic Mapper (TM) mid-infrared images is used to create change images, and thresholded change areas are associated with coordinates of local dust inspections. The output metric identifies source areas of soil disturbance, and it estimates the annual amount of dust-producing surface area for eastern Pima County spanning 1994 through 2009. Spatially explicit construction-related soil disturbance and rodent abundance data are compared with coccidioidomycosis incidence data using rank order correlation and regression methods. Construction-related soil disturbance correlates strongly with annual county-wide incidence. It also correlates with Tucson periphery incidence aggregated to zip codes. Abundance values for the desert pocket mouse (Chaetodipus penicillatus), derived from a soil-adjusted vegetation index, aspect (northing) and thermal radiance, correlate with total study period incidence aggregated to zip code.

  10. Cryogenic Optical Performance of a Lightweighted Mirror Assembly for Future Space Astronomical Telescopes: Correlating Optical Test Results and Thermal Optical Model

    NASA Technical Reports Server (NTRS)

    Eng, Ron; Arnold, William R.; Baker, Marcus A.; Bevan, Ryan M.; Burdick, Gregory; Effinger, Michael R.; Gaddy, Darrell E.; Goode, Brian K.; Hanson, Craig; Hogue, William D.; hide

    2013-01-01

    A 43cm diameter stacked core mirror demonstrator was interferometrically tested at room temperature down to 250 degrees Kelvin for thermal deformation. The 2.5m radius of curvature spherical mirror assembly was constructed by low temperature fusing three abrasive waterjet core sections between two CNC pocket milled face sheets. The 93% lightweighted Corning ULE® mirror assembly represents the current state of the art for future UV, optical, near IR space telescopes. During the multiple thermal test cycles, test results of interferometric test, thermal IR images of the front face were recorded in order to validate thermal optical model.

  11. WASHINGTON DAIRIES

    EPA Science Inventory

    The dairy_wa.zip file is a zip file containing an Arc/Info export file and a text document. Note the DISCLAIM.TXT file as these data are not verified. Map extent: statewide. Input Source: Address database obtained from Wa Dept of Agriculture. Data was originally developed und...

  12. Abscisic-acid-dependent basic leucine zipper (bZIP) transcription factors in plant abiotic stress.

    PubMed

    Banerjee, Aditya; Roychoudhury, Aryadeep

    2017-01-01

    One of the major causes of significant crop loss throughout the world is the myriad of environmental stresses including drought, salinity, cold, heavy metal toxicity, and ultraviolet-B (UV-B) rays. Plants as sessile organisms have evolved various effective mechanism which enable them to withstand this plethora of stresses. Most of such regulatory mechanisms usually follow the abscisic-acid (ABA)-dependent pathway. In this review, we have primarily focussed on the basic leucine zipper (bZIP) transcription factors (TFs) activated by the ABA-mediated signalosome. Upon perception of ABA by specialized receptors, the signal is transduced via various groups of Ser/Thr kinases, which phosphorylate the bZIP TFs. Following such post-translational modification of TFs, they are activated so that they bind to specific cis-acting sequences called abscisic-acid-responsive elements (ABREs) or GC-rich coupling elements (CE), thereby influencing the expression of their target downstream genes. Several in silico techniques have been adopted so far to predict the structural features, recognize the regulatory modification sites, undergo phylogenetic analyses, and facilitate genome-wide survey of TF under multiple stresses. Current investigations on the epigenetic regulation that controls greater accessibility of the inducible regions of DNA of the target gene to the bZIP TFs exclusively under stress situations, along with the evolved stress memory responses via genomic imprinting mechanism, have been highlighted. The potentiality of overexpression of bZIP TFs, either in a homologous or in a heterologous background, in generating transgenic plants tolerant to various abiotic stressors have also been addressed by various groups. The present review will provide a coherent documentation on the functional characterization and regulation of bZIP TFs under multiple environmental stresses, with the major goal of generating multiple-stress-tolerant plant cultivars in near future.

  13. The Arabidopsis bZIP11 transcription factor links low-energy signalling to auxin-mediated control of primary root growth

    PubMed Central

    Weiste, Christoph; Pedrotti, Lorenzo; Muralidhara, Prathibha; Ljung, Karin; Dröge-Laser, Wolfgang

    2017-01-01

    Plants have to tightly control their energy homeostasis to ensure survival and fitness under constantly changing environmental conditions. Thus, it is stringently required that energy-consuming stress-adaptation and growth-related processes are dynamically tuned according to the prevailing energy availability. The evolutionary conserved SUCROSE NON-FERMENTING1 RELATED KINASES1 (SnRK1) and the downstream group C/S1 basic leucine zipper (bZIP) transcription factors (TFs) are well-characterised central players in plants’ low-energy management. Nevertheless, mechanistic insights into plant growth control under energy deprived conditions remains largely elusive. In this work, we disclose the novel function of the low-energy activated group S1 bZIP11-related TFs as regulators of auxin-mediated primary root growth. Whereas transgenic gain-of-function approaches of these bZIPs interfere with the activity of the root apical meristem and result in root growth repression, root growth of loss-of-function plants show a pronounced insensitivity to low-energy conditions. Based on ensuing molecular and biochemical analyses, we propose a mechanistic model, in which bZIP11-related TFs gain control over the root meristem by directly activating IAA3/SHY2 transcription. IAA3/SHY2 is a pivotal negative regulator of root growth, which has been demonstrated to efficiently repress transcription of major auxin transport facilitators of the PIN-FORMED (PIN) gene family, thereby restricting polar auxin transport to the root tip and in consequence auxin-driven primary root growth. Taken together, our results disclose the central low-energy activated SnRK1-C/S1-bZIP signalling module as gateway to integrate information on the plant’s energy status into root meristem control, thereby balancing plant growth and cellular energy resources. PMID:28158182

  14. A cross-sectional prevalence study of ethnically targeted and general audience outdoor obesity-related advertising.

    PubMed

    Yancey, Antronette K; Cole, Brian L; Brown, Rochelle; Williams, Jerome D; Hillier, Amy; Kline, Randolph S; Ashe, Marice; Grier, Sonya A; Backman, Desiree; McCarthy, William J

    2009-03-01

    Commercial marketing is a critical but understudied element of the sociocultural environment influencing Americans' food and beverage preferences and purchases. This marketing also likely influences the utilization of goods and services related to physical activity and sedentary behavior. A growing literature documents the targeting of racial/ethnic and income groups in commercial advertisements in magazines, on billboards, and on television that may contribute to sociodemographic disparities in obesity and chronic disease risk and protective behaviors. This article examines whether African Americans, Latinos, and people living in low-income neighborhoods are disproportionately exposed to advertisements for high-calorie, low nutrient-dense foods and beverages and for sedentary entertainment and transportation and are relatively underexposed to advertising for nutritious foods and beverages and goods and services promoting physical activities. Outdoor advertising density and content were compared in zip code areas selected to offer contrasts by area income and ethnicity in four cities: Los Angeles, Austin, New York City, and Philadelphia. Large variations were observed in the amount, type, and value of advertising in the selected zip code areas. Living in an upper-income neighborhood, regardless of its residents' predominant ethnicity, is generally protective against exposure to most types of obesity-promoting outdoor advertising (food, fast food, sugary beverages, sedentary entertainment, and transportation). The density of advertising varied by zip code area race/ethnicity, with African American zip code areas having the highest advertising densities, Latino zip code areas having slightly lower densities, and white zip code areas having the lowest densities. The potential health and economic implications of differential exposure to obesity-related advertising are substantial. Although substantive legal questions remain about the government's ability to regulate advertising, the success of limiting tobacco advertising offers lessons for reducing the marketing contribution to the obesigenicity of urban environments.

  15. The Arabidopsis bZIP11 transcription factor links low-energy signalling to auxin-mediated control of primary root growth.

    PubMed

    Weiste, Christoph; Pedrotti, Lorenzo; Selvanayagam, Jebasingh; Muralidhara, Prathibha; Fröschel, Christian; Novák, Ondřej; Ljung, Karin; Hanson, Johannes; Dröge-Laser, Wolfgang

    2017-02-01

    Plants have to tightly control their energy homeostasis to ensure survival and fitness under constantly changing environmental conditions. Thus, it is stringently required that energy-consuming stress-adaptation and growth-related processes are dynamically tuned according to the prevailing energy availability. The evolutionary conserved SUCROSE NON-FERMENTING1 RELATED KINASES1 (SnRK1) and the downstream group C/S1 basic leucine zipper (bZIP) transcription factors (TFs) are well-characterised central players in plants' low-energy management. Nevertheless, mechanistic insights into plant growth control under energy deprived conditions remains largely elusive. In this work, we disclose the novel function of the low-energy activated group S1 bZIP11-related TFs as regulators of auxin-mediated primary root growth. Whereas transgenic gain-of-function approaches of these bZIPs interfere with the activity of the root apical meristem and result in root growth repression, root growth of loss-of-function plants show a pronounced insensitivity to low-energy conditions. Based on ensuing molecular and biochemical analyses, we propose a mechanistic model, in which bZIP11-related TFs gain control over the root meristem by directly activating IAA3/SHY2 transcription. IAA3/SHY2 is a pivotal negative regulator of root growth, which has been demonstrated to efficiently repress transcription of major auxin transport facilitators of the PIN-FORMED (PIN) gene family, thereby restricting polar auxin transport to the root tip and in consequence auxin-driven primary root growth. Taken together, our results disclose the central low-energy activated SnRK1-C/S1-bZIP signalling module as gateway to integrate information on the plant's energy status into root meristem control, thereby balancing plant growth and cellular energy resources.

  16. Extreme Population Differences in the Human Zinc Transporter ZIP4 (SLC39A4) Are Explained by Positive Selection in Sub-Saharan Africa

    PubMed Central

    Pybus, Marc; Andrews, Glen K.; Lalueza-Fox, Carles; Comas, David; Sekler, Israel; de la Rasilla, Marco; Rosas, Antonio; Stoneking, Mark; Valverde, Miguel A.; Vicente, Rubén; Bosch, Elena

    2014-01-01

    Extreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution (Leu372Val) in the human intestinal zinc uptake transporter, ZIP4, yet no further evidence was found for a selective sweep around the ZIP4 gene (SLC39A4). By interrogating allele frequencies in more than 100 diverse human populations and resequencing Neanderthal DNA, we confirmed the ancestral state of this locus and found a strong geographical gradient for the derived allele (Val372), with near fixation in West Africa. In extensive coalescent simulations, we show that the extreme differences in allele frequency, yet absence of a classical sweep signature, can be explained by the effect of a local recombination hotspot, together with directional selection favoring the Val372 allele in Sub-Saharan Africans. The possible functional effect of the Leu372Val substitution, together with two pathological mutations at the same codon (Leu372Pro and Leu372Arg) that cause acrodermatitis enteropathica (a disease phenotype characterized by extreme zinc deficiency), was investigated by transient overexpression of human ZIP4 protein in HeLa cells. Both acrodermatitis mutations cause absence of the ZIP4 transporter cell surface expression and nearly absent zinc uptake, while the Val372 variant displayed significantly reduced surface protein expression, reduced basal levels of intracellular zinc, and reduced zinc uptake in comparison with the Leu372 variant. We speculate that reduced zinc uptake by the ZIP4-derived Val372 isoform may act by starving certain pathogens of zinc, and hence may have been advantageous in Sub-Saharan Africa. Moreover, these functional results may indicate differences in zinc homeostasis among modern human populations with possible relevance for disease risk. PMID:24586184

  17. The bZIP dimer localizes at DNA full-sites where each basic region can alternately translocate and bind to subsites at the half-site

    PubMed Central

    Chan, I-San; Al-Sarraj, Taufik; Shahravan, S. Hesam; Fedorova, Anna V.; Shin, Jumi A.

    2012-01-01

    Crystal structures of the GCN4 bZIP (basic region/leucine zipper) with the AP-1 or CRE site show how each GCN4 basic region binds to a 4-bp cognate half-site as a single DNA target; however, this may not always fully describe how bZIP proteins interact with their target sites. Previously, we showed that the GCN4 basic region interacts with all 5 bp in half-site TTGCG (termed 5H-LR), and that 5H-LR comprises two 4-bp subsites, TTGC and TGCG, which individually are also target sites of the basic region. In this work, we explored how the basic region interacts with 5H-LR when the bZIP dimer localizes to full-sites. Using AMBER molecular modeling, we simulated GCN4 bZIP complexes with full-sites containing 5H-LR to investigate in silico the interface between the basic region and 5H-LR. We also performed in vitro investigation of bZIP–DNA interactions at a number of full-sites that contain 5H-LR vs. either subsite: we analyzed results from DNase I footprinting and electrophoretic mobility shift assay (EMSA) and from EMSA titrations to quantify binding affinities. Our computational and experimental results together support a highly dynamic DNA-binding model: when a bZIP dimer localizes to its target full-site, the basic region can alternately recognize either subsite as a distinct target at 5H-LR and translocate between the subsites, potentially by sliding and hopping. This model provides added insights into how α-helical DNA-binding domains of transcription factors can localize to their gene regulatory sequences in vivo. PMID:22856882

  18. OsLOL1, a C2C2-type zinc finger protein, interacts with OsbZIP58 to promote seed germination through the modulation of gibberellin biosynthesis in Oryza sativa.

    PubMed

    Wu, Jiahe; Zhu, Chuanfeng; Pang, Jinhuan; Zhang, Xiangrong; Yang, Chunlin; Xia, Guixian; Tian, Yingchuan; He, Chaozu

    2014-12-01

    Seed germination is a key developmental process in the plant life cycle that is influenced by various environmental cues and phytohormones through gene expression and a series of metabolism pathways. In the present study, we investigated a C2C2-type finger protein, OsLOL1, which promotes gibberellin (GA) biosynthesis and affects seed germination in Oryza sativa (rice). We used OsLOL1 antisense and sense transgenic lines to explore OsLOL1 functions. Seed germination timing in antisense plants was restored to wild type when exogenous GA3 was applied. The reduced expression of the GA biosynthesis gene OsKO2 and the accumulation of ent-kaurene were observed during germination in antisense plants. Based on yeast two-hybrid and firefly luciferase complementation analyses, OsLOL1 interacted with the basic leucine zipper protein OsbZIP58. The results from electrophoretic mobility shift and dual-luciferase reporter assays showed that OsbZIP58 binds the G-box cis-element of the OsKO2 promoter and activates LUC reporter gene expression, and that interaction between OsLOL1 and OsbZIP58 activates OsKO2 gene expression. In addition, OsLOL1 decreased SOD1 gene expression and accelerated programmed cell death (PCD) in the aleurone layer of rice grains. These findings demonstrate that the interaction between OsLOL1 and OsbZIP58 influences GA biosynthesis through the activation of OsKO2 via OsbZIP58, thereby stimulating aleurone PCD and seed germination. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  19. Oxidative stress upregulates zinc uptake activity via Zrt/Irt-like protein 1 (ZIP1) in cultured mouse astrocytes.

    PubMed

    Furuta, Takahiro; Ohshima, Chiaki; Matsumura, Mayu; Takebayashi, Naoto; Hirota, Emi; Mawaribuchi, Toshiki; Nishida, Kentaro; Nagasawa, Kazuki

    2016-04-15

    Zinc released from glutamatergic boutons and astrocytes acts as neuro- and glio-transmitters, and thus its extracellular level has to be strictly regulated. We previously revealed that uptake of zinc by astrocytes plays a critical role in its clearance, and zinc transporter Zrt/Irt-like protein 1 (ZIP1) is the molecule responsible for the uptake. However, it is unknown whether or not the functionality of the zinc clearance system is altered under oxidative stress-loaded conditions. Here, we characterized zinc uptake by oxidative stress-loaded astrocytes. Cultured mouse astrocytes were treated with hydrogen peroxide (H2O2) to load oxidative stress. Functional expression of ZIP1 in astrocytes was evaluated by means of (65)Zn uptake, Western blotting and immunocytochemical analysis. Treatment of astrocytes with 0.4mM H2O2 for 24h increased the expression levels of glial fibrillary acidic protein and 4-hydroxynonenal without significant decreases in their viability, indicating that induction of oxidative stress in astrocytes. Under oxidative stress-loaded conditions, astrocytes exhibited increased (65)Zn uptake activity, and the maximum uptake velocity for the uptake was significantly increased compared to that in the control group, while there was no change in the Michaelis constants, which were almost identical to that of mouse ZIP1. In the H2O2-treated astrocytes, the expression levels of ZIP1 were significantly increased in the cellular and plasma membrane fractions. It appears that under oxidative stress-loaded conditions, astrocytes exhibit increased zinc clearance activity and this is due, at least in part, to increased ZIP1 expression. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 77 FR 12764 - POSTNET Barcode Discontinuation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-02

    ... routing code appears in the lower right corner. * * * * * [Delete current 5.6, DPBC Numeric Equivalent, in... correct ZIP Code, ZIP+4 code, or numeric equivalent to the delivery point routing code and which meets... equivalent to the delivery point routing code is formed by [[Page 12766

  1. Homolog of protein kinase Mζ maintains context aversive memory and underlying long-term facilitation in terrestrial snail Helix

    PubMed Central

    Balaban, Pavel M.; Roshchin, Matvey; Timoshenko, Alia Kh.; Zuzina, Alena B.; Lemak, Maria; Ierusalimsky, Victor N.; Aseyev, Nikolay A.; Malyshev, Aleksey Y.

    2015-01-01

    It has been shown that a variety of long-term memories in different regions of the brain and in different species are quickly erased by local inhibition of protein kinase Mζ (PKMζ), a persistently active protein kinase. Using antibodies to mammalian PKMζ, we describe in the present study the localization of immunoreactive molecules in the nervous system of the terrestrial snail Helix lucorum. Presence of a homolog of PKMζ was confirmed with transcriptomics. We have demonstrated in behavioral experiments that contextual fear memory disappeared under a blockade of PKMζ with a selective peptide blocker of PKMζ zeta inhibitory peptide (ZIP), but not with scrambled ZIP. If ZIP was combined with a “reminder” (20 min in noxious context), no impairment of the long-term contextual memory was observed. In electrophysiological experiments we investigated whether PKMζ takes part in the maintenance of long-term facilitation (LTF) in the neural circuit mediating tentacle withdrawal. LTF of excitatory synaptic inputs to premotor interneurons was induced by high-frequency nerve stimulation combined with serotonin bath applications and lasted at least 4 h. We found that bath application of 2 × 10−6 M ZIP at the 90th min after the tetanization reduced the EPSP amplitude to the non-tetanized EPSP values. Applications of the scrambled ZIP peptide at a similar time and concentration didn’t affect the EPSP amplitudes. In order to test whether effects of ZIP are specific to the synapses, we performed experiments with LTF of somatic membrane responses to local glutamate applications. It was shown earlier that serotonin application in such an “artificial synapse” condition elicits LTF of responses to glutamate. It was found that ZIP had no effect on LTF in these conditions, which may be explained by the very low concentration of PKMζ molecules in somata of these identified neurons, as evidenced by immunochemistry. Obtained results suggest that the Helix homolog of PKMζ might be involved in post-induction maintenance of long-term changes in the nervous system of the terrestrial snail. PMID:26157359

  2. Intercellular communication in plants: evidence for two rapidly transmitted systemic signals generated in response to electromagnetic field stimulation in tomato.

    PubMed

    Beaubois, Elisabeth; Girard, Sebastien; Lallechere, Sebastien; Davies, Eric; Paladian, Françoise; Bonnet, Pierre; Ledoigt, Gerard; Vian, Alain

    2007-07-01

    Exposing all of a wild-type tomato plant to electromagnetic radiation evoked rapid and substantial accumulation of basic leucine-zipper transcription factor (bZIP) mRNA in the terminal leaf (#4) with kinetics very similar to that seen in response to wounding, while in the abscisic acid (ABA) mutant (Sitiens), the response was more rapid, but transient. Submitting just the oldest leaf (#1) of a wild-type plant to irradiation evoked bZIP mRNA accumulation both locally in the exposed leaf and systemically in the unexposed (distant) leaf #4, although systemic accumulation was delayed somewhat. Accumulation of Pin2 mRNA was less than bZIP in both the exposed and distant leaves in wild type, but there was no delay in the systemic response. In Sitiens, bZIP mRNA accumulation was far less than in wild type in both local and distant leaves, while Pin2 mRNA accumulation was stronger in the exposed leaf, but totally prevented in the systemic leaf. In the jasmonic acid (JA) mutant (JL-5) and in wild-type plants treated with the ABA biosynthesis inhibitor, naproxen, responses were similar to those in the ABA mutant, while treatment of the exposed leaf with calcium antagonists totally abolished both local and systemic increases in bZIP transcript accumulation.

  3. Evaluating Area-Based Socioeconomic Status Indicators for Monitoring Disparities within Health Care Systems: Results from a Primary Care Network

    PubMed Central

    Berkowitz, Seth A; Traore, Carine Y; Singer, Daniel E; Atlas, Steven J

    2015-01-01

    Objective To determine which area-based socioeconomic status (SES) indicator is best suited to monitor health care disparities from a delivery system perspective. Data Sources/Study Setting 142,659 adults seen in a primary care network from January 1, 2009 to December 31, 2011. Study Design Cross-sectional, comparing associations between area-based SES indicators and patient outcomes. Data Collection Address data were geocoded to construct area-based SES indicators at block group (BG), census tract (CT), and ZIP code (ZIP) levels. Data on health outcomes were abstracted from electronic records. Relative indices of inequality (RIIs) were calculated to quantify disparities detected by area-based SES indicators and compared to RIIs from self-reported educational attainment. Principal Findings ZIP indicators had less missing data than BG or CT indicators (p < .0001). Area-based SES indicators were strongly associated with self-report educational attainment (p < .0001). ZIP, BG, and CT indicators all detected expected SES gradients in health outcomes similarly. Single-item, cut point defined indicators performed as well as multidimensional indices and quantile indicators. Conclusions Area-based SES indicators detected health outcome differences well and may be useful for monitoring disparities within health care systems. Our preferred indicator was ZIP-level median household income or percent poverty, using cut points. PMID:25219917

  4. 48 CFR 52.204-7 - System for Award Management.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... for Award Manangement (JUL 2013) (a) Definitions. As used in this provision— Data Universal Numbering... information, including the DUNS number or the DUNS+4 number, the Contractor and Government Entity (CAGE) code... Zip Code. (iv) Company Mailing Address, City, State and Zip Code (if separate from physical). (v...

  5. 48 CFR 52.204-7 - System for Award Management.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... for Award Manangement (JUL 2013) (a) Definitions. As used in this provision— Data Universal Numbering... information, including the DUNS number or the DUNS+4 number, the Contractor and Government Entity (CAGE) code... Zip Code. (iv) Company Mailing Address, City, State and Zip Code (if separate from physical). (v...

  6. Fundamental Studies in the Molecular Basis of Laser Induced Retinal Damage

    DTIC Science & Technology

    1988-01-01

    Cornell University .LECT l School of Applied & Engineering PhysicsIthaca, NY 14853 0 JAN 198D DOD DISTRIBUTION STATEMENT Approved for public release...State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) School of Applied & Engineering Physics Ithaca, NY 14853 Ba. NAME OF FUNDING/ SPONSORING

  7. 77 FR 18716 - Transportation Security Administration Postal Zip Code Change; Technical Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... organizational changes and it has no substantive effect on the public. DATES: Effective March 28, 2012. FOR... No. 1572-9] Transportation Security Administration Postal Zip Code Change; Technical Amendment AGENCY: Transportation Security Administration, DHS. ACTION: Final rule. SUMMARY: This rule is a technical change to...

  8. 76 FR 75939 - ZipGlobal Holdings, Inc., Symbollon Pharmaceuticals, Inc., Microholdings US, Inc., ComCam...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ... SECURITIES AND EXCHANGE COMMISSION [ File No. 500-1] ZipGlobal Holdings, Inc., Symbollon Pharmaceuticals, Inc., Microholdings US, Inc., ComCam International, Inc., Outfront Companies, Augrid Global... periodic reports since the period ended March 31, 2011. 3. Microholdings US, Inc. is an Oklahoma...

  9. Using wireless (Pocket)PCs in Large Introductory Courses to Expand Discourse and Interactivity

    NASA Astrophysics Data System (ADS)

    van der Pluijm, B. A.; Knoop, P. A.; Samson, P. J.; Teasley, S. D.

    2005-12-01

    Teaching methods in introductory, undergraduate courses traditionally rely on static textbooks and/or course packs, with presentation delivered as a monologue in front of a mostly passive, large audience. The concepts presented in class are often best illustrated using visualizations and/or demonstrations, but even the most stunning of images or spectacular exhibits, while motivating, offer students only passive participation in the learning process. Add to this the advent of course websites with lecture notes and PowerPoint presentations and the students are left with little incentive to attend, much less participate. Clearly this model does not provide much opportunity or motivation for today's students to learn and think more critically about the arguments being developed. What is needed is a coupling of the rich imagery of many fields with advances in technology and in learning, toward revitalizing pedagogical approaches in survey-level courses and student-instructor interaction. Our IT-enhanced classroom project couples the use of peer instruction techniques in large classes (as originally described by Mazur, 1997) with the use of interactive spatial concept challenges, utilizing wireless PocketPCs (handhelds) or student-owned wireless-enabled laptops. The technologies employed (web, PocketPC/laptop, WiFi) are off-the-shelf technologies and the Peer Instruction technique is increasingly documented in undergraduate science classes. However, the combination is not employed due to its initial cost, wrongly perceived level of effort to implement, availability of engaging activities and modest volume of data on student learning. We'll show our development, implementation and preliminary cognitive assessment efforts of this IT-enhanced classroom experience, involving interactive image quizzes and data manipulation in large introductory classes at the University of Michigan.

  10. Methods of affecting nitrogen assimilation in plants

    DOEpatents

    Coruzzi, Gloria; Gutierrez, Rodrigo A.; Nero, Damion C.

    2016-10-11

    Provided herein are compositions and methods for producing transgenic plants. In specific embodiments, transgenic plants comprise a construct comprising a polynucleotide encoding CCA1, GLK1 or bZIP1, operably linked to a plant-specific promote, wherein the CCA1, GLK1 or bZIP1 is ectopically overexpressed in the transgenic plants, and wherein the promoter is optionally a constitutive or inducible promoter. In other embodiments, transgenic plants in which express a lower level of CCA1, GLK1 or bZIP1 are provided. Also provided herein are commercial products (e.g., pulp, paper, paper products, or lumber) derived from the transgenic plants (e.g., transgenic trees) produced using the methods provided herein.

  11. Community measures of low-fat milk consumption: comparing store shelves with households.

    PubMed

    Fisher, B D; Strogatz, D S

    1999-02-01

    This study examined the relationship between the proportion of milk in food stores that is low-fat and consumption of low-fat milk in the community. Data were gathered from 503 stores across 53 New York State zip codes. In 19 zip codes, a telephone survey measured household low-fat milk use. Census data were obtained to examine sociodemographic predictors of the percentage of low-fat milk in stores. The proportion of low-fat milk in stores was directly related to low-fat milk consumption in households and to the median income and urban level of the zip code. These results support using food store shelf-space observations to estimate low-fat milk consumption.

  12. Selection and Evaluation of a Real Time Monitoring System for the Bigeye Bomb Fill/Close Production Facility. Phase 2

    DTIC Science & Technology

    1989-06-01

    and ZIP Code ) 10 SOURCE OF FUNDING NU MBERS I O KUI PROGRAM PRO ECCT TASKWOKUI E L E M E N T N O . N O .I 1 2 0 N O A 5 A C C E S S I O N N OlI I1 TITLE... source of by-products formation. Generating Data for Mathematical Modeling of Real Vapor Phase Reaction Systems (tremendously speeds multi -level, multi ...SMCC-RI1 6c AD RS(Ciry,. State, and ZIP Code ) SCRRI 7b. ADDRESS (City, State, and ZIP Code ) IA!hrueýýt Proving Ground, MD 21010-54213 a.NMOFFUNI.DNG

  13. Inertial Pocket Navigation System: Unaided 3D Positioning

    PubMed Central

    Munoz Diaz, Estefania

    2015-01-01

    Inertial navigation systems use dead-reckoning to estimate the pedestrian's position. There are two types of pedestrian dead-reckoning, the strapdown algorithm and the step-and-heading approach. Unlike the strapdown algorithm, which consists of the double integration of the three orthogonal accelerometer readings, the step-and-heading approach lacks the vertical displacement estimation. We propose the first step-and-heading approach based on unaided inertial data solving 3D positioning. We present a step detector for steps up and down and a novel vertical displacement estimator. Our navigation system uses the sensor introduced in the front pocket of the trousers, a likely location of a smartphone. The proposed algorithms are based on the opening angle of the leg or pitch angle. We analyzed our step detector and compared it with the state-of-the-art, as well as our already proposed step length estimator. Lastly, we assessed our vertical displacement estimator in a real-world scenario. We found that our algorithms outperform the literature step and heading algorithms and solve 3D positioning using unaided inertial data. Additionally, we found that with the pitch angle, five activities are distinguishable: standing, sitting, walking, walking up stairs and walking down stairs. This information complements the pedestrian location and is of interest for applications, such as elderly care. PMID:25897501

  14. Experimental investigation of water distribution in a two-phase zone during gravity-dominated evaporation

    NASA Astrophysics Data System (ADS)

    Cejas, Cesare M.; Castaing, Jean-Christophe; Hough, Larry; Frétigny, Christian; Dreyfus, Rémi

    2017-12-01

    We characterize the water repartition within the partially saturated (two-phase) zone (PSZ) during evaporation from mixed wettable porous media by controlling the wettability of glass beads, their sizes, and as well the surrounding relative humidity. Here, capillary numbers are low and under these conditions, the percolating front is stabilized by gravity. Using experimental and numerical analyses, we find that the PSZ saturation decreases with the Bond number, where packing of smaller particles have higher saturation values than packing made of larger particles. Results also reveal that the extent (height) of the PSZ, as well as water saturation in the PSZ, both increase with wettability. We also numerically calculate the saturation exclusively contained in connected liquid films and results show that values are less than the expected PSZ saturation. These results strongly reflect that the two-phase zone is not solely made up of connected capillary networks but also made of disconnected water clusters or pockets. Moreover, we also find that global saturation (PSZ + full wet zone) decreases with wettability, confirming that greater quantity of water is lost via evaporation with increasing hydrophilicity. These results show that connected liquid films are favored in more-hydrophilic systems while disconnected water pockets are favored in less-hydrophilic systems.

  15. Zinc and its transporters, pancreatic beta cells, and insulin metabolism

    USDA-ARS?s Scientific Manuscript database

    Zinc is an essential trace metal for life. Two families of zinc transporters, SLC30A (ZnT) and SLC39A (ZIP) are required for maintaining cellular zinc homeostasis. ZnTs function to decrease cytoplasmic zinc concentrations whereas ZIPs do the opposite. Expression of zinc transporters can be tissue/ce...

  16. Dermal Sensitization Potential of DIGL-RP Solid Propellant in Guinea Pigs

    DTIC Science & Technology

    1989-10-01

    y ’,c. ADM$$S (ft, SWOt , &Wd ZIP Cod 7b. ADDRESS (City, State, arid ZIP Code) Letterman Army Institute of Research Fort Detrick Presidio of San...for contact sensitization. Toxicol Appl Pharmacol 1969; Suppl 3:90-102. 7. Buehler EV, Griffith JF. Experimental skin sensitization in the guinea pig

  17. IRT-ZIP Modeling for Multivariate Zero-Inflated Count Data

    ERIC Educational Resources Information Center

    Wang, Lijuan

    2010-01-01

    This study introduces an item response theory-zero-inflated Poisson (IRT-ZIP) model to investigate psychometric properties of multiple items and predict individuals' latent trait scores for multivariate zero-inflated count data. In the model, two link functions are used to capture two processes of the zero-inflated count data. Item parameters are…

  18. Interactions among the early Escherichia coli divisome proteins revealed by bimolecular fluorescence complementation.

    PubMed

    Pazos, Manuel; Natale, Paolo; Margolin, William; Vicente, Miguel

    2013-12-01

    We used bimolecular fluorescence complementation (BiFC) assays to detect protein-protein interactions of all possible pairs of the essential Escherichia coli proto-ring components, FtsZ, FtsA and ZipA, as well as the non-essential FtsZ-associated proteins ZapA and ZapB. We found an unexpected interaction between ZipA and ZapB at potential cell division sites, and when co-overproduced, they induced long narrow constrictions at division sites that were dependent on FtsZ. These assays also uncovered an interaction between ZipA and ZapA that was mediated by FtsZ. BiFC with ZapA and ZapB showed that in addition to their expected interaction at midcell, they also interact at the cell poles. BiFC detected interaction between FtsZ and ZapB at midcell and close to the poles. Results from the remaining pairwise combinations confirmed known interactions between FtsZ and ZipA, and ZapB with itself. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  19. Mechanism of DNA-binding enhancement by the human T-cell leukaemia virus transactivator Tax.

    PubMed

    Baranger, A M; Palmer, C R; Hamm, M K; Giebler, H A; Brauweiler, A; Nyborg, J K; Schepartz, A

    1995-08-17

    Tax protein activates transcription of the human T-cell leukaemia virus type I (HTLV-I) genome through three imperfect cyclic AMP-responsive element (CRE) target sites located within the viral promoter. Previous work has shown that Tax interacts with the bZIP element of proteins that bind the CRE target site to promote peptide dimerization, suggesting an association between Tax and bZIP coiled coil. Here we show that the site of interaction with Tax is not the coiled coil, but the basic segment. This interaction increases the stability of the GCN4 bZIP dimer by 1.7 kcal mol-1 and the DNA affinity of the dimer by 1.9 kcal mol-1. The differential effect of Tax on several bZip-DNA complexes that differ in peptide sequence or DNA conformation suggests a model for Tax action based on stabilization of a distinct DNA-bound protein structure. This model may explain how Tax interacts with transcription factors of considerable sequence diversity to alter patterns of gene expression.

  20. Zinc Up-Regulates Insulin Secretion from β Cell-Like Cells Derived from Stem Cells from Human Exfoliated Deciduous Tooth (SHED).

    PubMed

    Kim, Gyuyoup; Shin, Ki-Hyuk; Pae, Eung-Kwon

    2016-12-13

    Stem cells from human exfoliated deciduous tooth (SHED) offer several advantages over other stem cell sources. Using SHED, we examined the roles of zinc and the zinc uptake transporter ZIP8 (Zrt- and irt-like protein 8) while inducing SHED into insulin secreting β cell-like stem cells (i.e., SHED-β cells). We observed that ZIP8 expression increased as SHED differentiated into SHED-β cells, and that zinc supplementation at day 10 increased the levels of most pancreatic β cell markers-particularly Insulin and glucose transporter 2 (GLUT2). We confirmed that SHED-β cells produce insulin successfully. In addition, we note that zinc supplementation significantly increases insulin secretion with a significant elevation of ZIP8 transporters in SHED-β cells. We conclude that SHED can be converted into insulin-secreting β cell-like cells as zinc concentration in the cytosol is elevated. Insulin production by SHED-β cells can be regulated via modulation of zinc concentration in the media as ZIP8 expression in the SHED-β cells increases.

  1. A new cable-tie based sternal closure system: description of the device, technique of implantation and first clinical evaluation

    PubMed Central

    2012-01-01

    Background Wire closure still remains the preferred technique despite reasonable disadvantages. Associated complications, such as infection and sternal instability, cause time- and cost-consuming therapies. We present a new tool for sternal closure with its first clinical experience and results. Methods The sternal ZipFixTM System is based on the cable-tie principle. It primarily consists of biocompatible Poly-Ether-Ether-Ketone implants and is predominantly used peristernally through the intercostal space. The system provides a large implant-to-bone contact for better force distribution and for avoiding bone cut through. Results 50 patients were closed with the ZipFixTM system. No sternal instability was observed at 30 days. Two patients developed a mediastinitis that necessitated the removal of the device; however, the ZipFixTM were intact and the sternum remained stable. Conclusions In our initial evaluation, the short-term results have shown that the sternal ZipFixTM can be used safely and effectively. It is fast, easy to use and serves as a potential alternative for traditional wire closure. PMID:22731778

  2. Abscisic acid-dependent regulation of small rubber particle protein gene expression in Taraxacum brevicorniculatum is mediated by TbbZIP1.

    PubMed

    Fricke, Julia; Hillebrand, Andrea; Twyman, Richard M; Prüfer, Dirk; Schulze Gronover, Christian

    2013-04-01

    Natural rubber is a high-molecular-mass biopolymer found in the latex of >2,500 plant species, including Hevea brasiliensis, Parthenium argentatum and Taraxacum spp. The active sites of rubber biosynthesis are rubber particles, which comprise a hydrophobic rubber core surrounded by a phospholipid monolayer membrane containing species-dependent lipids and associated proteins. Small rubber particle proteins are the most abundant rubber particle-associated proteins in Taraxacum brevicorniculatum (TbSRPPs) and may promote rubber biosynthesis by stabilizing the rubber particle architecture. We investigated the transcriptional regulation of genes encoding SRPPs and identified a bZIP transcription factor (TbbZIP.1) similar to the Arabidopsis thaliana ABI5-ABF-AREB subfamily, which is thought to include downstream targets of ABA and/or abiotic stress-inducible protein kinases. The TbbZIP.1 gene was predominantly expressed in laticifers and regulates the expression of TbSRPP genes in an ABA-dependent manner. The individual TbSRPP genes showed distinct induction profiles, suggesting diverse roles in rubber biosynthesis and stress adaptation. The potential involvement of TbSRPPs in the adaptation of T. brevicorniculatum plants to environmental stress is discussed based on our current knowledge of the stress-response roles of SRPPs and their homologs, and the protective function of latex and rubber against pathogens. Our data suggest that TbSRPPs contribute to stress tolerance in T. brevicorniculatum and that their effects are mediated by TbbZIP.1.

  3. Implications of Supermarket Access, Neighborhood Walkability, and Poverty Rates for Diabetes Risk in an Employee Population

    PubMed Central

    Herrick, Cynthia J.; Yount, Byron W.; Eyler, Amy A.

    2016-01-01

    Objective Diabetes is a growing public health problem, and the environment in which people live and work may affect diabetes risk. The goal of this study was to examine the association between multiple aspects of environment and diabetes risk in an employee population. Design This was a retrospective cross-sectional analysis. Home environment variables were derived using employee zip code. Descriptive statistics were run on all individual and zip code level variables, stratified by diabetes risk and worksite. A multivariable logistic regression analysis was then conducted to determine the strongest associations with diabetes risk. Setting Data was collected from employee health fairs in a Midwestern health system 2009–2012. Subjects The dataset contains 25,227 unique individuals across four years of data. From this group, using an individual’s first entry into the database, 15,522 individuals had complete data for analysis. Results The prevalence of high diabetes risk in this population was 2.3%. There was significant variability in individual and zip code level variables across worksites. From the multivariable analysis, living in a zip code with higher percent poverty and higher walk score was positively associated with high diabetes risk, while living in a zip code with higher supermarket density was associated with a reduction in high diabetes risk. Conclusions Our study underscores the important relationship between poverty, home neighborhood environment, and diabetes risk, even in a relatively healthy employed population, and suggests a role for the employer in promoting health. PMID:26638995

  4. Implications of supermarket access, neighbourhood walkability and poverty rates for diabetes risk in an employee population.

    PubMed

    Herrick, Cynthia J; Yount, Byron W; Eyler, Amy A

    2016-08-01

    Diabetes is a growing public health problem, and the environment in which people live and work may affect diabetes risk. The goal of the present study was to examine the association between multiple aspects of environment and diabetes risk in an employee population. This was a retrospective cross-sectional analysis. Home environment variables were derived using employees' zip code. Descriptive statistics were run on all individual- and zip-code-level variables, stratified by diabetes risk and worksite. A multivariable logistic regression analysis was then conducted to determine the strongest associations with diabetes risk. Data were collected from employee health fairs in a Midwestern health system, 2009-2012. The data set contains 25 227 unique individuals across four years of data. From this group, using an individual's first entry into the database, 15 522 individuals had complete data for analysis. The prevalence of high diabetes risk in this population was 2·3 %. There was significant variability in individual- and zip-code-level variables across worksites. From the multivariable analysis, living in a zip code with higher percentage of poverty and higher walk score was positively associated with high diabetes risk, while living in a zip code with higher supermarket density was associated with a reduction in high diabetes risk. Our study underscores the important relationship between poverty, home neighbourhood environment and diabetes risk, even in a relatively healthy employed population, and suggests a role for the employer in promoting health.

  5. Chromatin Immunoprecipitation and Microarray Analysis Suggest Functional Cooperation between Kaposi's Sarcoma-Associated Herpesvirus ORF57 and K-bZIP

    PubMed Central

    Hunter, Olga V.; Sei, Emi; Richardson, R. Blake

    2013-01-01

    The Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 57 (ORF57)-encoded protein (Mta) is a multifunctional regulator of viral gene expression. ORF57 is essential for viral replication, so elucidation of its molecular mechanisms is important for understanding KSHV infection. ORF57 has been implicated in nearly every aspect of viral gene expression, including transcription, RNA stability, splicing, export, and translation. Here we demonstrate that ORF57 interacts with the KSHV K-bZIP protein in vitro and in cell extracts from lytically reactivated infected cells. To further test the biological relevance of the interaction, we performed a chromatin immunoprecipitation and microarray (ChIP-chip) analysis using anti-ORF57 antibodies and a KSHV tiling array. The results revealed four specific areas of enrichment, including the ORF4 and K8 (K-bZIP) promoters, as well as oriLyt, all of which interact with K-bZIP. In addition, ORF57 associated with DNA corresponding to the PAN RNA transcribed region, a known posttranscriptional target of ORF57. All of the peaks were RNase insensitive, demonstrating that ORF57 association with the viral genome is unlikely to be mediated exclusively by an RNA tether. Our data demonstrate that ORF57 associates with the viral genome by using at least two modes of recruitment, and they suggest that ORF57 and K-bZIP coregulate viral gene expression during lytic infection. PMID:23365430

  6. Mitochondrial AtTrxo1 is transcriptionally regulated by AtbZIP9 and AtAZF2 and affects seed germination under saline conditions

    PubMed Central

    Ortiz-Espín, Ana; Iglesias-Fernández, Raquel; Calderón, Aingeru; Carbonero, Pilar; Sevilla, Francisca

    2017-01-01

    Abstract Mitochondrial thioredoxin-o (AtTrxo1) was characterized and its expression examined in different organs of Arabidopsis thaliana. AtTrxo1 transcript levels were particularly high in dry seeds and cotyledons where they reached a maximum 36 h after imbibition with water, coinciding with 50% germination. Expression was lower in seeds germinating in 100 mM NaCl. To gain insight into the transcriptional regulation of the AtTrxo1 gene, a phylogenomic analysis was coupled with the screening of an arrayed library of Arabidopsis transcription factors in yeast. The basic leucine zipper AtbZIP9 and the zinc finger protein AZF2 were identified as putative transcriptional regulators. Transcript regulation of AtbZIP9 and AtAFZ2 during germination was compatible with the proposed role in transcriptional regulation of AtTrxo1. Transient over-expression of AtbZIP9 and AtAZF2 in Nicotiana benthamiana leaves demonstrated an activation effect of AtbZIP9 and a repressor effect of AtAZF2 on AtTrxo1 promoter-driven reporter expression. Although moderate concentrations of salt delayed germination in Arabidopsis wild-type seeds, those of two different AtTrxo1 knock-out mutants germinated faster and accumulated higher H2O2 levels than the wild-type. All these data indicate that AtTrxo1 has a role in redox homeostasis during seed germination under salt conditions. PMID:28184497

  7. Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.

    PubMed

    Mutai, Hideki; Miya, Fuyuki; Fujii, Masato; Tsunoda, Tatsuhiko; Matsunaga, Tatsuo

    2015-01-01

    Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (-)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing.

  8. Influence of DNA-methylation on zinc homeostasis in myeloid cells: Regulation of zinc transporters and zinc binding proteins.

    PubMed

    Kessels, Jana Elena; Wessels, Inga; Haase, Hajo; Rink, Lothar; Uciechowski, Peter

    2016-09-01

    The distribution of intracellular zinc, predominantly regulated through zinc transporters and zinc binding proteins, is required to support an efficient immune response. Epigenetic mechanisms such as DNA methylation are involved in the expression of these genes. In demethylation experiments using 5-Aza-2'-deoxycytidine (AZA) increased intracellular (after 24 and 48h) and total cellular zinc levels (after 48h) were observed in the myeloid cell line HL-60. To uncover the mechanisms that cause the disturbed zinc homeostasis after DNA demethylation, the expression of human zinc transporters and zinc binding proteins were investigated. Real time PCR analyses of 14 ZIP (solute-linked carrier (SLC) SLC39A; Zrt/IRT-like protein), and 9 ZnT (SLC30A) zinc transporters revealed significantly enhanced mRNA expression of the zinc importer ZIP1 after AZA treatment. Because ZIP1 protein was also enhanced after AZA treatment, ZIP1 up-regulation might be the mediator of enhanced intracellular zinc levels. The mRNA expression of ZIP14 was decreased, whereas zinc exporter ZnT3 mRNA was also significantly increased; which might be a cellular reaction to compensate elevated zinc levels. An enhanced but not significant chromatin accessibility of ZIP1 promoter region I was detected by chromatin accessibility by real-time PCR (CHART) assays after demethylation. Additionally, DNA demethylation resulted in increased mRNA accumulation of zinc binding proteins metallothionein (MT) and S100A8/S100A9 after 48h. MT mRNA was significantly enhanced after 24h of AZA treatment also suggesting a reaction of the cell to restore zinc homeostasis. These data indicate that DNA methylation is an important epigenetic mechanism affecting zinc binding proteins and transporters, and, therefore, regulating zinc homeostasis in myeloid cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

  9. Growth Arrest by Trehalose-6-Phosphate: An Astonishing Case of Primary Metabolite Control over Growth by Way of the SnRK1 Signaling Pathway1[C][W][OA

    PubMed Central

    Delatte, Thierry L.; Sedijani, Prapti; Kondou, Youichi; Matsui, Minami; de Jong, Gerhardus J.; Somsen, Govert W.; Wiese-Klinkenberg, Anika; Primavesi, Lucia F.; Paul, Matthew J.; Schluepmann, Henriette

    2011-01-01

    The strong regulation of plant carbon allocation and growth by trehalose metabolism is important for our understanding of the mechanisms that determine growth and yield, with obvious applications in crop improvement. To gain further insight on the growth arrest by trehalose feeding, we first established that starch-deficient seedlings of the plastidic phosphoglucomutase1 mutant were similarly affected as the wild type on trehalose. Starch accumulation in the source cotyledons, therefore, did not cause starvation and consequent growth arrest in the growing zones. We then screened the FOX collection of Arabidopsis (Arabidopsis thaliana) expressing full-length cDNAs for seedling resistance to 100 mm trehalose. Three independent transgenic lines were identified with dominant segregation of the trehalose resistance trait that overexpress the bZIP11 (for basic region/leucine zipper motif) transcription factor. The resistance of these lines to trehalose could not be explained simply through enhanced trehalase activity or through inhibition of bZIP11 translation. Instead, trehalose-6-phosphate (T6P) accumulation was much increased in bZIP11-overexpressing lines, suggesting that these lines may be insensitive to the effects of T6P. T6P is known to inhibit the central stress-integrating kinase SnRK1 (KIN10) activity. We confirmed that this holds true in extracts from seedlings grown on trehalose, then showed that two independent transgenic lines overexpressing KIN10 were insensitive to trehalose. Moreover, the expression of marker genes known to be jointly controlled by SnRK1 activity and bZIP11 was consistent with low SnRK1 or bZIP11 activity in seedlings on trehalose. These results reveal an astonishing case of primary metabolite control over growth by way of the SnRK1 signaling pathway involving T6P, SnRK1, and bZIP11. PMID:21753116

  10. A Cross-Sectional Prevalence Study of Ethnically Targeted and General Audience Outdoor Obesity-Related Advertising

    PubMed Central

    Yancey, Antronette K; Cole, Brian L; Brown, Rochelle; Williams, Jerome D; Hillier, Amy; Kline, Randolph S; Ashe, Marice; Grier, Sonya A; Backman, Desiree; McCarthy, William J

    2009-01-01

    Context: Commercial marketing is a critical but understudied element of the sociocultural environment influencing Americans' food and beverage preferences and purchases. This marketing also likely influences the utilization of goods and services related to physical activity and sedentary behavior. A growing literature documents the targeting of racial/ethnic and income groups in commercial advertisements in magazines, on billboards, and on television that may contribute to sociodemographic disparities in obesity and chronic disease risk and protective behaviors. This article examines whether African Americans, Latinos, and people living in low-income neighborhoods are disproportionately exposed to advertisements for high-calorie, low nutrient–dense foods and beverages and for sedentary entertainment and transportation and are relatively underexposed to advertising for nutritious foods and beverages and goods and services promoting physical activities. Methods: Outdoor advertising density and content were compared in zip code areas selected to offer contrasts by area income and ethnicity in four cities: Los Angeles, Austin, New York City, and Philadelphia. Findings: Large variations were observed in the amount, type, and value of advertising in the selected zip code areas. Living in an upper-income neighborhood, regardless of its residents' predominant ethnicity, is generally protective against exposure to most types of obesity-promoting outdoor advertising (food, fast food, sugary beverages, sedentary entertainment, and transportation). The density of advertising varied by zip code area race/ethnicity, with African American zip code areas having the highest advertising densities, Latino zip code areas having slightly lower densities, and white zip code areas having the lowest densities. Conclusions: The potential health and economic implications of differential exposure to obesity-related advertising are substantial. Although substantive legal questions remain about the government's ability to regulate advertising, the success of limiting tobacco advertising offers lessons for reducing the marketing contribution to the obesigenicity of urban environments. PMID:19298419

  11. Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US.

    PubMed

    Des Jarlais, D C; Cooper, H L F; Arasteh, K; Feelemyer, J; McKnight, C; Ross, Z

    2018-01-01

    We identified potential geographic "hotspots" for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an "end of the epidemic" stage, while HCV is in a continuing, high prevalence (> 50%) stage. We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011-2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential "hotspots" for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk-passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk-injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years. Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation. For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US.

  12. Issues in Performance Measurement for Military Aviation with Applications to Air Combat Maneuvering

    DTIC Science & Technology

    1986-04-04

    Systems Center 6c. ADDRESS (City, State, and ZIP Co*e) 7b. ADDRESS (City. State, and ZIP Code) 1040 Woodcock Road, Suite 227 Orlando, FL 32813-7100...NTSC TR-86-008 Vreuls, D., Obermayer, R. W., Goldstein, I. & Lauber, J. K. (1973). Measurement of trainee performance in a captive rotary- wing device

  13. Application of Microgravity to the Assessment of Existing Structures and Structural Foundations.

    DTIC Science & Technology

    1988-04-29

    UADGU Geophysique Francafse IUSRSU 6c. ADDRESS (City, State. and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) 20, Rue des Pavilions Box 65 92800...r (2.8 - 2.4) 286 AM~TCT f eldo f6 YOUOUVT 4. EXISTING STRUCTURES AND (U) CONPAGNIE DE PROSPECTION GEOPHYSIQUE FRANCAISE RUEIL-MALNAISO J LAKSHNRNRN

  14. A Field Trip without Buses: Connecting Your Students to Scientists through a Virtual Visit

    ERIC Educational Resources Information Center

    Adedokun, Omolola; Parker, Loran Carleton; Loizzo, Jamie; Burgess, Wilella; Robinson, J. Paul

    2011-01-01

    One school offers zipTrips as an alternative to actual field trips taken outside of school. ZipTrips are web- and broadcast-delivered electronic field trips that include online videos, lesson plans, and a live, 45-minute interactive program consisting of four core components: an in-studio audience, live interaction with scientists, prerecorded…

  15. Response, Emergency Staging, Communications, Uniform Management, and Evacuation (R.E.S.C.U.M.E.) : Concept of Operations. [supporting datasets

    DOT National Transportation Integrated Search

    2012-10-31

    This zip file contains 45 files of data to support FHWA-JPO-13-063 Response, Emergency Staging, Communications, Uniform Management, and Evacuation (R.E.S.C.U.M.E.) : Concept of Operations. Zip size is 9.9 MB. The files have been uploaded as-is; no fu...

  16. 76 FR 54931 - Post Office (PO) Box Fee Groups for Merged Locations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... POSTAL SERVICE 39 CFR Part 111 Post Office (PO) Box Fee Groups for Merged Locations AGENCY: Postal... different ZIP Code TM location because of a merger of two or more ZIP Code locations into a single location... merged with a location whose box section is more than one fee group level different, the location would...

  17. 76 FR 40849 - Post Office (PO) Box Fee Groups for Merged Locations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-12

    ... POSTAL SERVICE 39 CFR Part 111 Post Office (PO) Box Fee Groups for Merged Locations AGENCY: Postal... Locations.'' Faxed comments are not accepted. FOR FURTHER INFORMATION CONTACT: Nan McKenzie at 202-268-3089... boxes move to a different ZIP Code location because of a merger of two or more ZIP Code locations into a...

  18. Transgenic plants expressing GLK1 and CCA1 having increased nitrogen assimilation capacity

    DOEpatents

    Coruzzi, Gloria [New York, NY; Gutierrez, Rodrigo A [Santiago, CL; Nero, Damion C [Woodside, NY

    2012-04-10

    Provided herein are compositions and methods for producing transgenic plants. In specific embodiments, transgenic plants comprise a construct comprising a polynucleotide encoding CCA1, GLK1 or bZIP1, operably linked to a plant-specific promote, wherein the CCA1, GLK1 or bZIP1 is ectopically overexpressed in the transgenic plants, and wherein the promoter is optionally a constitutive or inducible promoter. In other embodiments, transgenic plants in which express a lower level of CCA1, GLK1 or bZIP1 are provided. Also provided herein are commercial products (e.g., pulp, paper, paper products, or lumber) derived from the transgenic plants (e.g., transgenic trees) produced using the methods provided herein.

  19. Community measures of low-fat milk consumption: comparing store shelves with households.

    PubMed Central

    Fisher, B D; Strogatz, D S

    1999-01-01

    OBJECTIVES: This study examined the relationship between the proportion of milk in food stores that is low-fat and consumption of low-fat milk in the community. METHODS: Data were gathered from 503 stores across 53 New York State zip codes. In 19 zip codes, a telephone survey measured household low-fat milk use. Census data were obtained to examine sociodemographic predictors of the percentage of low-fat milk in stores. RESULTS: The proportion of low-fat milk in stores was directly related to low-fat milk consumption in households and to the median income and urban level of the zip code. CONCLUSIONS: These results support using food store shelf-space observations to estimate low-fat milk consumption. PMID:9949755

  20. Bow Shocks in Space

    NASA Image and Video Library

    2016-01-05

    Bow shocks thought to mark the paths of massive, speeding stars are highlighted in these images from NASA's Spitzer Space Telescope and Wide-field Infrared Survey Explorer, or WISE. Cosmic bow shocks occur when massive stars zip through space, pushing material ahead of them in the same way that water piles up in front of a race boat. The stars also produce high-speed winds that smack into this compressed material. The end result is pile-up of heated material that glows in infrared light. In these images, infrared light has been assigned the colored red. Green shows wispy dust in the region and blue shows stars. The two images at left are from Spitzer, and the one on the right is from WISE. The speeding stars thought to be creating the bow shocks can be seen at the center of each arc-shaped feature. The image at right actually consists of two bow shocks and two speeding stars. All the speeding stars are massive, ranging from about 8 to 30 times the mass of our sun. http://photojournal.jpl.nasa.gov/catalog/PIA20062

  1. Investigating the Importance of the Pocket-estimation Method in Pocket-based Approaches: An Illustration Using Pocket-ligand Classification.

    PubMed

    Caumes, Géraldine; Borrel, Alexandre; Abi Hussein, Hiba; Camproux, Anne-Claude; Regad, Leslie

    2017-09-01

    Small molecules interact with their protein target on surface cavities known as binding pockets. Pocket-based approaches are very useful in all of the phases of drug design. Their first step is estimating the binding pocket based on protein structure. The available pocket-estimation methods produce different pockets for the same target. The aim of this work is to investigate the effects of different pocket-estimation methods on the results of pocket-based approaches. We focused on the effect of three pocket-estimation methods on a pocket-ligand (PL) classification. This pocket-based approach is useful for understanding the correspondence between the pocket and ligand spaces and to develop pharmacological profiling models. We found pocket-estimation methods yield different binding pockets in terms of boundaries and properties. These differences are responsible for the variation in the PL classification results that can have an impact on the detected correspondence between pocket and ligand profiles. Thus, we highlighted the importance of the pocket-estimation method choice in pocket-based approaches. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Assessment of BRAC 133 Final Environmental Assessment of July 2008 and Transportation Management Plan of July 2010

    DTIC Science & Technology

    2011-04-20

    car - sharing vehicles on-site or within walking distance of BRAC 133,” as there currently is one ZipCar®. Second, the Transportation Coordinator will...for obtaining additional car - sharing vehicles on-site or within walking distance of BRAC 133,” as there currently is one ZipCar® located at 2001 N

  3. Development of a Run Time Math Library for the 1750A Airborne Microcomputer.

    DTIC Science & Technology

    1985-12-01

    premiue CWUTLDK Is R: Integer :a 0; 0: Integer :ul; LNMM: UEM; -Compute the Lado (alpii) for J In 0..Ol.K-1) loop Itf 0(14 1)/ 0. 0...ORGANIZATION (If appiicable) * School of Engineering AFIT/ ENC 6c. ADDRESS (City, State and ZIP Code) 7b. ADDRESS (City. State and ZIP Code) Air Force

  4. Boundary Conditions for the Maintenance of Memory by PKM[zeta] in Neocortex

    ERIC Educational Resources Information Center

    Shema, Reul; Hazvi, Shoshi; Sacktor, Todd C.; Dudai, Yadin

    2009-01-01

    We report here that ZIP, a selective inhibitor of the atypical protein kinase C isoform PKM[zeta], abolishes very long-term conditioned taste aversion (CTA) associations in the insular cortex of the behaving rat, at least 3 mo after encoding. The effect of ZIP is not replicated by a general serine/threonine protein kinase inhibitor that is…

  5. Analysis of Champus Per Capita Mental Health Expenditures and Utilization for Beneficiaries Less Than Eighteen Years

    DTIC Science & Technology

    1991-04-01

    and (If applicable) Clinical Investigation Icty HSAD -A HQ HSC/HSCL-M 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code...NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (Include Area Code) 22c. OFFICE SYMBOL Dr. Scott A. Optenberg, GM-14 (512) 221-5880 HSAD -A DD Form

  6. The Design and Implementation of a Read Prediction Buffer

    DTIC Science & Technology

    1992-12-01

    City, State, and ZIP Code) 7b ADDRESS (City, State. and ZIP Code) 8a. NAME OF FUNDING /SPONSORING 8b. OFFICE SYMBOL 9 PROCUREMENT INSTRUMENT... 9 E. THESIS STRUCTURE.. . .... ............... 9 II. READ PREDICTION ALGORITHM AND BUFFER DESIGN 10 A. THE READ PREDICTION ALGORITHM...29 Figure 9 . Basic Multiplexer Cell .... .......... .. 30 Figure 10. Block Diagram Simulation Labels ......... 38 viii I. INTRODUCTION A

  7. Critical Habitat :: NOAA Fisheries

    Science.gov Websites

    82 FR 51186 (comments close 1/02/18) Beluga Whale Cook Inlet 2011 76 FR 20180 Go to Data Hawaiian Monk Seal 1988, 1986, 2015 53 FR 18988, 51 FR 16047, 80 FR 50925 Go to Data [zip] (excluded areas Revise (Feb 2015) 2006 71 FR 69054 Go To Data [zip] North Atlantic Right Whale Northeast Southeast 1994

  8. Zip Pak (Boys) for Third Reader Level.

    ERIC Educational Resources Information Center

    Scott, Norval C., Comp.

    Aim of the Zip Pak is to improve the migrant child's interest in reading. Behavioral objectives are to have the migrant child indicate 10 percent happier faces on the posttest; to have an equal number of blame-self, blame-others on the posttest; and to have 25 percent more praise-self on the posttest. The workbook for boys includes a story about…

  9. SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants

    PubMed Central

    Mair, Andrea; Pedrotti, Lorenzo; Wurzinger, Bernhard; Anrather, Dorothea; Simeunovic, Andrea; Weiste, Christoph; Valerio, Concetta; Dietrich, Katrin; Kirchler, Tobias; Nägele, Thomas; Vicente Carbajosa, Jesús; Hanson, Johannes; Baena-González, Elena; Chaban, Christina; Weckwerth, Wolfram; Dröge-Laser, Wolfgang; Teige, Markus

    2015-01-01

    Metabolic adjustment to changing environmental conditions, particularly balancing of growth and defense responses, is crucial for all organisms to survive. The evolutionary conserved AMPK/Snf1/SnRK1 kinases are well-known metabolic master regulators in the low-energy response in animals, yeast and plants. They act at two different levels: by modulating the activity of key metabolic enzymes, and by massive transcriptional reprogramming. While the first part is well established, the latter function is only partially understood in animals and not at all in plants. Here we identified the Arabidopsis transcription factor bZIP63 as key regulator of the starvation response and direct target of the SnRK1 kinase. Phosphorylation of bZIP63 by SnRK1 changed its dimerization preference, thereby affecting target gene expression and ultimately primary metabolism. A bzip63 knock-out mutant exhibited starvation-related phenotypes, which could be functionally complemented by wild type bZIP63, but not by a version harboring point mutations in the identified SnRK1 target sites. DOI: http://dx.doi.org/10.7554/eLife.05828.001 PMID:26263501

  10. Structural zeroes and zero-inflated models.

    PubMed

    He, Hua; Tang, Wan; Wang, Wenjuan; Crits-Christoph, Paul

    2014-08-01

    In psychosocial and behavioral studies count outcomes recording the frequencies of the occurrence of some health or behavior outcomes (such as the number of unprotected sexual behaviors during a period of time) often contain a preponderance of zeroes because of the presence of 'structural zeroes' that occur when some subjects are not at risk for the behavior of interest. Unlike random zeroes (responses that can be greater than zero, but are zero due to sampling variability), structural zeroes are usually very different, both statistically and clinically. False interpretations of results and study findings may result if differences in the two types of zeroes are ignored. However, in practice, the status of the structural zeroes is often not observed and this latent nature complicates the data analysis. In this article, we focus on one model, the zero-inflated Poisson (ZIP) regression model that is commonly used to address zero-inflated data. We first give a brief overview of the issues of structural zeroes and the ZIP model. We then given an illustration of ZIP with data from a study on HIV-risk sexual behaviors among adolescent girls. Sample codes in SAS and Stata are also included to help perform and explain ZIP analyses.

  11. NUCLEAR FACTOR Y Transcription Factors Have Both Opposing and Additive Roles in ABA-Mediated Seed Germination

    PubMed Central

    Kumimoto, Roderick W.; Siriwardana, Chamindika L.; Gayler, Krystal K.; Risinger, Jan R.; Siefers, Nicholas; Holt, Ben F.

    2013-01-01

    In the model organism Arabidopsis thaliana the heterotrimeric transcription factor NUCLEAR FACTOR Y (NF-Y) has been shown to play multiple roles in facilitating plant growth and development. Although NF-Y itself represents a multi-protein transcriptional complex, recent studies have shown important interactions with other transcription factors, especially those in the bZIP family. Here we add to the growing evidence that NF-Y and bZIP form common complexes to affect many processes. We carried out transcriptional profiling on nf-yc mutants and through subsequent analyses found an enrichment of bZIP binding sites in the promoter elements of misregulated genes. Using NF-Y as bait, yeast two hybrid assays yielded interactions with bZIP proteins that are known to control ABA signaling. Accordingly, we find that plants mutant for several NF-Y subunits show characteristic phenotypes associated with the disruption of ABA signaling. While previous reports have shown additive roles for NF-YC family members in photoperiodic flowering, we found that they can have opposing roles in ABA signaling. Collectively, these results demonstrated the importance and complexity of NF-Y in the integration of environmental and hormone signals. PMID:23527203

  12. The unfolded protein response and programmed cell death are induced by expression of Garlic virus X p11 in Nicotiana benthamiana.

    PubMed

    Lu, Yuwen; Yin, Mingyuan; Wang, Xiaodan; Chen, Binghua; Yang, Xue; Peng, Jiejun; Zheng, Hongying; Zhao, Jinping; Lin, Lin; Yu, Chulang; MacFarlane, Stuart; He, Jianqing; Liu, Yong; Chen, Jianping; Dai, Liangying; Yan, Fei

    2016-06-01

    Garlic virus X (GarVX) ORF3 encodes a p11 protein, which contributes to virus cell-to-cell movement and forms granules on the endoplasmic reticulum (ER) in Nicotiana benthamiana. Expression of p11 either from a binary vector, PVX or TMV induced ER stress and the unfolded protein response (UPR), as demonstrated by an increase in transcription of the ER luminal binding protein (BiP) and bZIP60 genes. UPR-related programmed cell death (PCD) was elicited by PVX : p11 or TMV : p11 in systemic infected leaves. Examination of p11 mutants with deletions of two transmembrane domains (TM) revealed that both were required for generating granules and for inducing necrosis. TRV-based VIGS was used to investigate the correlation between bZIP60 expression and p11-induced UPR-related PCD. Less necrosis was observed on local and systemic leaves of bZIP60 knockdown plants when infected with PVXp11, suggesting that bZIP60 plays an important role in the UPR-related PCD response to p11 in N. benthamiana.

  13. [Improvement in zinc nutrition due to zinc transporter-targeting strategy].

    PubMed

    Kambe, Taiho

    2016-07-01

    Adequate intake of zinc from the daily diet is indispensable to maintain health. However, the dietary zinc content often fails to fulfill the recommended daily intake, leading to zinc deficiency and also increases the risk of developing chronic diseases, particularly in elderly individuals. Therefore, increased attention is required to overcome zinc deficiency and it is important to improve zinc nutrition in daily life. In the small intestine, the zinc transporter, ZIP4, functions as a component that is essential for zinc absorption. In this manuscript, we present a brief overview regarding zinc deficiency. Moreover, we review a novel strategy, called "ZIP4-targeting", which has the potential to enable efficient zinc absorption from the diet. ZIP4-targeting strategy is possibly a major step in preventing zinc deficiency and improving human health.

  14. Poverty, wealth, and health care utilization: a geographic assessment.

    PubMed

    Cooper, Richard A; Cooper, Matthew A; McGinley, Emily L; Fan, Xiaolin; Rosenthal, J Thomas

    2012-10-01

    Geographic variation has been of interest to both health planners and social epidemiologists. However, while the major focus of interest of planners has been on variation in health care spending, social epidemiologists have focused on health; and while social epidemiologists have observed strong associations between poor health and poverty, planners have concluded that income is not an important determinant of variation in spending. These different conclusions stem, at least in part, from differences in approach. Health planners have generally studied variation among large regions, such as states, counties, or hospital referral regions (HRRs), while epidemiologists have tended to study local areas, such as ZIP codes and census tracts. To better understand the basis for geographic variation in hospital utilization, we drew upon both approaches. Counties and HRRs were disaggregated into their constituent ZIP codes and census tracts and examined the interrelationships between income, disability, and hospital utilization that were examined at both the regional and local levels, using statistical and geomapping tools. Our studies centered on the Milwaukee and Los Angeles HRRs, where per capita health care utilization has been greater than elsewhere in their states. We compared Milwaukee to other HRRs in Wisconsin and Los Angeles to the other populous counties of California and to a region in California of comparable size and diversity, stretching from San Francisco to Sacramento (termed "San-Framento"). When studied at the ZIP code level, we found steep, curvilinear relationships between lower income and both increased hospital utilization and increasing percentages of individuals reporting disabilities. These associations were also evident on geomaps. They were strongest among populations of working-age adults but weaker among seniors, for whom income proved to be a poor proxy for poverty and whose residential locations deviated from the major underlying income patterns. Among working-age adults, virtually all of the excess utilization in Milwaukee was attributable to very high utilization in Milwaukee's segregated "poverty corridor." Similarly, the greater rate of hospital use in Los Angeles than in San-Framento could be explained by proportionately more low-income ZIP codes in Los Angeles and fewer in San-Framento. Indeed, when only high-income ZIP codes were assessed, there was little variation in hospital utilization among California's 18 most populous counties. We estimated that had utilization within each region been at the rate of its high-income ZIP codes, overall utilization would have been 35 % less among working-age adults and 20 % less among seniors. These studies reveal the importance of disaggregating large geographic units into their constituent ZIP codes in order to understand variation in health care utilization among them. They demonstrate the strong association between low ZIP code income and both higher percentages of disability and greater hospital utilization. And they suggest that, given the large contribution of the poorest neighborhoods to aggregate utilization, it will be difficult to curb the growth of health care spending without addressing the underlying social determinants of health.

  15. Intra-Amygdala ZIP Injections Impair the Memory of Learned Active Avoidance Responses and Attenuate Conditioned Taste-Aversion Acquisition in Rats

    ERIC Educational Resources Information Center

    Gamiz, Fernando; Gallo, Milagros

    2011-01-01

    We have investigated the effect of protein kinase Mzeta (PKM[zeta]) inhibition in the basolateral amygdala (BLA) upon the retention of a nonspatial learned active avoidance response and conditioned taste-aversion (CTA) acquisition in rats. ZIP (10 nmol/[mu]L) injected into the BLA 24 h after training impaired retention of a learned…

  16. The Populus Class III HD ZIP, popREVOLUTA, influences cambium initiation and patterning of woody stems

    Treesearch

    Marcel Robischon; Juan Du; Eriko Miura; Andrew Groover

    2011-01-01

    The secondary growth of a woody stem requires the formation of a vascular cambium at an appropriate position and proper patterning of the vascular tissues derived from the cambium. Class III homeodomain-leucine zipper (HD ZIP) transcription factors have been implicated in polarity determination and patterning in lateral organs and primary vascular tissues and in the...

  17. The IRE1/bZIP60 pathway and Bax inhibitor 1 suppress systemic accumulation of potyviruses and potexviruses in Arabidopsis and Nicotiana benthamiana plants

    USDA-ARS?s Scientific Manuscript database

    The inositol requiring enzyme (IRE1) is an endoplasmic reticulum (ER) stress sensor and when activated it splices the bZIP60 mRNA producing a truncated transcription factor that upregulates expression of genes involved in the unfolded protein response (UPR). Bax inhibitor 1 (BI-1) is another ER stre...

  18. Determining Market Categorization of United States Zip Codes for Purposes of Army Recruiting

    DTIC Science & Technology

    2016-06-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited DETERMINING MARKET ...2016 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE DETERMINING MARKET CATEGORIZATION OF UNITED STATES ZIP CODES FOR...Army uses commercial market segmentation data to analyze markets and past accessions to assign recruiters and quotas to maximize production. We use

  19. Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US

    PubMed Central

    Cooper, H. L. F.; Arasteh, K.; Feelemyer, J.; McKnight, C.; Ross, Z.

    2018-01-01

    Objective We identified potential geographic “hotspots” for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an “end of the epidemic” stage, while HCV is in a continuing, high prevalence (> 50%) stage. Methods We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011–2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential “hotspots” for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk—passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk—injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years. Results Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation. Discussion For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US. PMID:29596464

  20. Hexokinase 1 is required for glucose-induced repression of bZIP63, At5g22920, and BT2 in Arabidopsis

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

    Kunz, Sabine; Gardestrom, Per; Pesquet, Edouard

    Simple sugars, like glucose (Glc) and sucrose (Suc), act as signals to modulate the expression of hundreds of genes in plants. Frequently, however, it remains unclear whether this regulation is induced by the sugars themselves or by their derivatives generated in the course of carbohydrate (CH) metabolism. In the present study, we tested the relevance of different CH metabolism and allocation pathways affecting expression patterns of five selected sugar-responsive genes ( bZIP63, At5g22920, BT2, MGD2, and TPS9) in Arabidopsis thaliana. In general, the expression followed diurnal changes in the overall sugar availability. However, under steady growth conditions, this response wasmore » hardly impaired in the mutants for CH metabolizing/ transporting proteins ( adg1, sex1, sus1-4, sus5/6, and tpt2), including also hexokinase1 (HXK1) loss- and gain-of-function plants— gin2.1 and oe3.2, respectively. In addition, transgenic plants carrying pbZIP63::GUS showed no changes in reporter-gene-expression when grown on sugar under steady-state conditions. In contrast, short-term treatments of agar-grown seedlings with 1% Glc or Suc induced pbZIP63::GUS repression, which became even more apparent in seedlings grown in liquid media. Subsequent analyses of liquid-grown gin2.1 and oe3.2 seedlings revealed that Glc -dependent regulation of the five selected genes was not affected in gin2.1, whereas it was enhanced in oe3.2 plants for bZIP63, At5g22920, and BT. The sugar treatments had no effect on ATP/ADP ratio, suggesting that changes in gene expression were not linked to cellular energy status. Altogether, the data suggest that HXK1 does not act as Glc sensor controlling bZIP63, At5g22920, and BT2 expression, but it is nevertheless required for the production of a downstream metabolic signal regulating their expression« less

  1. Hexokinase 1 is required for glucose-induced repression of bZIP63, At5g22920, and BT2 in Arabidopsis

    DOE PAGES

    Kunz, Sabine; Gardestrom, Per; Pesquet, Edouard; ...

    2015-07-14

    Simple sugars, like glucose (Glc) and sucrose (Suc), act as signals to modulate the expression of hundreds of genes in plants. Frequently, however, it remains unclear whether this regulation is induced by the sugars themselves or by their derivatives generated in the course of carbohydrate (CH) metabolism. In the present study, we tested the relevance of different CH metabolism and allocation pathways affecting expression patterns of five selected sugar-responsive genes ( bZIP63, At5g22920, BT2, MGD2, and TPS9) in Arabidopsis thaliana. In general, the expression followed diurnal changes in the overall sugar availability. However, under steady growth conditions, this response wasmore » hardly impaired in the mutants for CH metabolizing/ transporting proteins ( adg1, sex1, sus1-4, sus5/6, and tpt2), including also hexokinase1 (HXK1) loss- and gain-of-function plants— gin2.1 and oe3.2, respectively. In addition, transgenic plants carrying pbZIP63::GUS showed no changes in reporter-gene-expression when grown on sugar under steady-state conditions. In contrast, short-term treatments of agar-grown seedlings with 1% Glc or Suc induced pbZIP63::GUS repression, which became even more apparent in seedlings grown in liquid media. Subsequent analyses of liquid-grown gin2.1 and oe3.2 seedlings revealed that Glc -dependent regulation of the five selected genes was not affected in gin2.1, whereas it was enhanced in oe3.2 plants for bZIP63, At5g22920, and BT. The sugar treatments had no effect on ATP/ADP ratio, suggesting that changes in gene expression were not linked to cellular energy status. Altogether, the data suggest that HXK1 does not act as Glc sensor controlling bZIP63, At5g22920, and BT2 expression, but it is nevertheless required for the production of a downstream metabolic signal regulating their expression« less

  2. Attenuation of Progressive Hearing Loss in DBA/2J Mice by Reagents that Affect Epigenetic Modifications Is Associated with Up-Regulation of the Zinc Importer Zip4

    PubMed Central

    Mutai, Hideki; Miya, Fuyuki; Fujii, Masato; Tsunoda, Tatsuhiko; Matsunaga, Tatsuo

    2015-01-01

    Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (–)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing. PMID:25875282

  3. Manifestations of poverty and birthrates among young teenagers in California zip code areas.

    PubMed

    Kirby, D; Coyle, K; Gould, J B

    2001-01-01

    Given that many communities are implementing community-wide initiatives to reduce teenage pregnancy or childbearing, it is important to understand the effects of a community's characteristics on adolescent birthrates. Data from the 1990 census and from California birth certificates were obtained for zip codes in California. Regression analyses were conducted on data from zip code areas with at least 200 females aged 15-17 between 1991 and 1996, to predict the effects of race and ethnicity marital status, education, employment, income and poverty, and housing on birthrates among young teenagers. In bivariate analyses, the proportion of families living below poverty level within a zip code was highly related to the birthrate among young teenagers in that zip code (r=.80, p<.001). In multivariate analyses, which controlled for some of the correlates of family poverty level, the proportion of families living below poverty level remained by far the most important predictor of the birthrate among young teenagers (b=1.54), followed by the proportion of adults aged 25 or older who have a college education (b=-0.80). Race and ethnicity were only weakly related to birthrate. In all three racial and ethnic groups, poverty and education were significantly related to birthrate, but the effect of college education was greater among Hispanics (b=-2.98) than among either non-Hispanic whites (b=-0.53) or blacks (b=-1.12). Male employment and unemployment and female unemployment were highly related to the birthrate among young teenagers in some racial or ethnic groups, but not in others. Multiple manifestations of poverty, including poverty itself, low levels of education and employment, and high levels of unemployment, may have a large impact upon birthrates among young teenagers. Addressing some of these issues could substantially reduce childbearing among young adolescents.

  4. Manganese Transport and Toxicity in Polarized WIF-B Hepatocytes.

    PubMed

    Thompson, Khristy J; Hein, Jennifer; Baez, Andrew; Sosa, Jose Carlo; Wessling-Resnick, Marianne

    2018-05-24

    Mn toxicity arises from nutritional problems, community and occupational exposures, and genetic risks. Mn blood levels are controlled by hepatobiliary clearance. The goals of this study were to determine the cellular distribution of Mn transporters in polarized hepatocytes, to establish an in vitro assay for hepatocyte Mn efflux, and to examine possible roles the Mn transporters would play in metal import and export. For these experiments, hepatocytoma WIF-B cells were grown for 12-14 days to achieve maximal polarity. Immunoblots showed that Mn transporters ZIP8, ZnT10, ferroportin (Fpn), and ZIP14 were present. Indirect immunofluorescence microscopy localized Fpn and ZIP14 to WIF-B cell basolateral domains while ZnT10 and ZIP8 associated with intracellular vesicular compartments. ZIP8-positive structures were distributed uniformly throughout the cytoplasm, but ZnT10-positive vesicles were adjacent to apical bile compartments. WIF-B cells were sensitive to Mn toxicity, showing decreased viability after 16 h exposure to > 250 M MnCl2. However, the hepatocytes were resistant to 4 h exposures of up to 500 M MnCl2 despite 50-fold increased Mn content. Washout experiments showed time-dependent efflux with 80% Mn released after a 4 h chase period. Hepcidin reduced levels of Fpn in WIF-B cells, clearing Fpn from the cell surface, but Mn efflux was unaffected. The secretory inhibitor brefeldin A did block release of Mn from WIF-B cells, suggesting vesicle fusion may be involved in export. These results point to a possible role of ZnT10 to import Mn into vesicles that subsequently fuse with the apical membrane and empty their contents into bile.

  5. Nanocarrier-mediated foliar zinc fertilization influences expression of metal homeostasis related genes in flag leaves and enhances gluten content in durum wheat.

    PubMed

    Deshpande, Paresh; Dapkekar, Ashwin; Oak, Manoj; Paknikar, Kishore; Rajwade, Jyutika

    2018-01-01

    Wheat is the staple food for most of the world's population; however, it is a poor source of zinc. Foliar fertilization of zinc via zinc loaded chitosan nanocarriers (Zn-CNP) post-anthesis has proved to be a promising approach for grain zinc enhancement in durum wheat as evidenced in our earlier study. However, the molecular mechanism of uptake of zinc via Zn-CNP remains unclear. Foliar application of Zn-CNP was performed at post anthesis stages in two durum wheat cultivars (MACS 3125 and UC1114, containing the Gpc-B1 gene), and expression levels of several metal-related genes were analyzed during early senescence. Zn-CNP application indeed caused changes in gene expression as revealed by qPCR data on representative genes involved in metal homeostasis, phloem transporters, and leaf senescence. Furthermore, zinc-regulated transporters and iron (Fe)-regulated transporter-like protein (ZIP) family [ZIP1, ZIP7, ZIP15], CA (carbonic anhydrase), and DMAS (2'-deoxymugineic acid synthase) in flag leaves exhibited significant correlation with zinc content in the seeds. The analysis of grain endosperm proteins showed enhancement of gamma gliadins while other gluten subunits decreased. Gene expression within ZIP family members varied with the type of cultivar mostly attributed to the Gpc-B1, concentration of external zinc ions as well as the type of tissue analyzed. Correlation analysis revealed the involvement of the selected genes in zinc enhancement. At the molecular level, uptake of zinc via Zn-CNP nanocarrier was comparable to the uptake of zinc via common zinc fertilizers i.e. ZnSO4.

  6. The management of amputations of the leg using a new rigid foam plaster for prosthetic fitting.

    PubMed

    Hölter, W; Echterhoff, M; Blömer, A; Verfürden, H

    1980-01-01

    This paper describes the use of a rigid polyurethane foam to construct a stump socket for immediate or early prosthetic fitting in 15 patients with amputation through the leg. The foam plaster is poured into a prepared cotton sleeve, with a zip incorporated, and rolled out to a layer 4 mm thick. The filled sleeve is put around the stump and the zip closed, moulding the sleeve firmly to the stump. The closed sleeve hardens into a rigid polyurethane shell within 20 min. Aferwards the skeletal prosthetic components are fixed with the same rigid foam. The polyurethane foam socket is quickly and cleanly prepared, only one third of the weight of a plaster of Paris cast and is easily removed by means of the zip, allowing access to the stump.

  7. Estimating the Depth of the Navy Recruiting Market

    DTIC Science & Technology

    2016-09-01

    recommend that NRC make use of the Poisson regression model in order to determine high-yield ZIP codes for market depth. 14. SUBJECT...recommend that NRC make use of the Poisson regression model in order to determine high-yield ZIP codes for market depth. vi THIS PAGE INTENTIONALLY LEFT...DEPTH OF THE NAVY RECRUITING MARKET by Emilie M. Monaghan September 2016 Thesis Advisor: Lyn R. Whitaker Second Reader: Jonathan K. Alt

  8. A Continuum Diffusion Model for Viscoelastic Materials

    DTIC Science & Technology

    1988-11-01

    ZIP Code) 7b. ADDRESS (CJI. Slow, and ZIP Code) Mechanics Div isi on Office of Naval Research; Code 432 Collge Satio, T as 7843800 Quincy Ave. Collge ...these studies, which involved experimental, analytical, and materials science aspects, were conducted by researchers in the fields of physical and...thermodynamics, with irreversibility stemming from the foregoing variables yr through "growth laws" that correspond to viscous resistance. The physical ageing of

  9. Mechanisms of Temporal Pattern Discrimination by Human Observers

    DTIC Science & Technology

    1994-02-15

    Research Center Department of Psychology University of Florida Gainesville, Florida 32611 15 February 1994 Final Technical Report for Period 1 October 1990...Center tfpdCbE Department of Psychology ________ AFOSR/NL Gr. &OORESS (City. Stteco and ZIP Code) 7b. ADDRESS (City’. State and ZIP Code) University of...contrasting novice and experienced performance. Journal of Experimental Psychology : Human Perception and Performance, 18, 50-71. Berg, B. G. (1989). Analysis

  10. Planned Monolayer Assemblies by Adsorption

    DTIC Science & Technology

    1988-09-01

    RESEARCH OFFICE OF TBE U.S. ARMY Xcndn, Engan aONRAcM NUMBE DAJA45-84-C-0055 acntractor: The Weizmn InstituteAttn: Ms. N. Guter Office of Research ...ORGANIZATION The Weizmann Inst’,a#. of (if appficable) European Research office ScienceUSARDSG-UK) Sk. ADDRESS (Wiy State, and ZIP Code) 7b. ADDRESS (City...State. and ZIP Code) Department of Isotope Research Box 65 76100 Rehoyot FPO NY 09510-1500 IsraelJ

  11. The effect of long-term relocation on child and adolescent survivors of Hurricane Katrina.

    PubMed

    Hansel, Tonya C; Osofsky, Joy D; Osofsky, Howard J; Friedrich, Patricia

    2013-10-01

    The current study is designed to increase knowledge of the effects of relocation and its association with longer-term psychological symptoms following disaster. Following clinical observations and in discussions held with school officials expressing concerns about relocated students, it was hypothesized that students who relocated to a different city following Hurricane Katrina in 2005 would have more symptoms of posttraumatic stress compared to students who returned to New Orleans. The effect of Hurricane Katrina relocation was assessed on a sample of child and adolescent survivors in 5th through 12th grades (N = 795). Students with Orleans Parish zip codes prior to Hurricane Katrina were categorized into relocation groupings: (a) relocated to Baton Rouge, (b) returned to prior zip code, and (c) moved to a different zip code within Orleans Parish. Overall results revealed more trauma symptoms for relocated students. Results also revealed that younger relocated students had fewer symptoms compared to older students. The opposite was found for students who returned to their same zip code, with older students having fewer symptoms. This study supports the need for school-based services not only in disaster areas, but also in schools where survivors tend to migrate. Copyright © 2013 International Society for Traumatic Stress Studies.

  12. A comparison between Poisson and zero-inflated Poisson regression models with an application to number of black spots in Corriedale sheep

    PubMed Central

    Naya, Hugo; Urioste, Jorge I; Chang, Yu-Mei; Rodrigues-Motta, Mariana; Kremer, Roberto; Gianola, Daniel

    2008-01-01

    Dark spots in the fleece area are often associated with dark fibres in wool, which limits its competitiveness with other textile fibres. Field data from a sheep experiment in Uruguay revealed an excess number of zeros for dark spots. We compared the performance of four Poisson and zero-inflated Poisson (ZIP) models under four simulation scenarios. All models performed reasonably well under the same scenario for which the data were simulated. The deviance information criterion favoured a Poisson model with residual, while the ZIP model with a residual gave estimates closer to their true values under all simulation scenarios. Both Poisson and ZIP models with an error term at the regression level performed better than their counterparts without such an error. Field data from Corriedale sheep were analysed with Poisson and ZIP models with residuals. Parameter estimates were similar for both models. Although the posterior distribution of the sire variance was skewed due to a small number of rams in the dataset, the median of this variance suggested a scope for genetic selection. The main environmental factor was the age of the sheep at shearing. In summary, age related processes seem to drive the number of dark spots in this breed of sheep. PMID:18558072

  13. Conformation of Tax-response elements in the human T-cell leukemia virus type I promoter.

    PubMed

    Cox, J M; Sloan, L S; Schepartz, A

    1995-12-01

    HTLV-I Tax is believed to activate viral gene expression by binding bZIP proteins (such as CREB) and increasing their affinities for proviral TRE target sites. Each 21 bp TRE target site contains an imperfect copy of the intrinsically bent CRE target site (the TRE core) surrounded by highly conserved flanking sequences. These flanking sequences are essential for maximal increases in DNA affinity and transactivation, but they are not, apparently, contacted by protein. Here we employ non-denaturing gel electrophoresis to evaluate TRE conformation in the presence and absence of bZIP proteins, and to explore the role of DNA conformation in viral transactivation. Our results show that the TRE-1 flanking sequences modulate the structure and modestly increase the affinity of a CREB bZIP peptide for the TRE-1 core recognition sequence. These flanking sequences are also essential for a maximal increase in stability of the CREB-DNA complex in the presence of Tax. The CRE-like TRE core and the TRE flanking sequences are both essential for formation of stable CREB-TRE-1 and Tax-CREB-TRE-1 complexes. These two DNA segments may have co-evolved into a unique structure capable of recognizing Tax and a bZIP protein.

  14. Bias with respect to socioeconomic status: A closer look at zip code matching in a pneumococcal vaccine effectiveness study.

    PubMed

    Link-Gelles, Ruth; Westreich, Daniel; Aiello, Allison E; Shang, Nong; Weber, David J; Holtzman, Corinne; Scherzinger, Karen; Reingold, Arthur; Schaffner, William; Harrison, Lee H; Rosen, Jennifer B; Petit, Susan; Farley, Monica; Thomas, Ann; Eason, Jeffrey; Wigen, Christine; Barnes, Meghan; Thomas, Ola; Zansky, Shelley; Beall, Bernard; Whitney, Cynthia G; Moore, Matthew R

    2016-12-01

    In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geo-coding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8-91.9%; adjusted estimate: 82.5%, 95% CI 65.6-91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

  15. Structure of homeodomain-leucine zipper/DNA complexes studied using hydroxyl radical cleavage of DNA and methylation interference.

    PubMed

    Tron, Adriana E; Comelli, Raúl N; Gonzalez, Daniel H

    2005-12-27

    Homeodomain-leucine zipper (HD-Zip) proteins, unlike most homeodomain proteins, bind a pseudopalindromic DNA sequence as dimers. We have investigated the structure of the DNA complexes formed by two HD-Zip proteins with different nucleotide preferences at the central position of the binding site using footprinting and interference methods. The results indicate that the respective complexes are not symmetric, with the strand bearing a central purine (top strand) showing higher protection around the central region and the bottom strand protected toward the 3' end. Binding to a sequence with a nonpreferred central base pair produces a decrease in protection in either the top or the bottom strand, depending upon the protein. Modeling studies derived from the complex formed by the monomeric Antennapedia homeodomain with DNA indicate that in the HD-Zip/DNA complex the recognition helix of one of the monomers is displaced within the major groove respective to the other one. This monomer seems to lose contacts with a part of the recognition sequence upon binding to the nonpreferred site. The results show that the structure of the complex formed by HD-Zip proteins with DNA is dependent upon both protein intrinsic characteristics and the nucleotides present at the central position of the recognition sequence.

  16. Medicago truncatula Zinc-Iron Permease6 provides zinc to rhizobia-infected nodule cells.

    PubMed

    Abreu, Isidro; Saéz, Ángela; Castro-Rodríguez, Rosario; Escudero, Viviana; Rodríguez-Haas, Benjamín; Senovilla, Marta; Larue, Camille; Grolimund, Daniel; Tejada-Jiménez, Manuel; Imperial, Juan; González-Guerrero, Manuel

    2017-11-01

    Zinc is a micronutrient required for symbiotic nitrogen fixation. It has been proposed that in model legume Medicago truncatula, zinc is delivered by the root vasculature into the nodule and released in the infection/differentiation zone. There, transporters must introduce this element into rhizobia-infected cells to metallate the apoproteins that use zinc as a cofactor. MtZIP6 (Medtr4g083570) is an M. truncatula Zinc-Iron Permease (ZIP) that is expressed only in roots and nodules, with the highest expression levels in the infection/differentiation zone. Immunolocalization studies indicate that it is located in the plasma membrane of nodule rhizobia-infected cells. Down-regulating MtZIP6 expression levels with RNAi does not result in any strong phenotype when plants are fed mineral nitrogen. However, these plants displayed severe growth defects when they depended on nitrogen fixed by their nodules, losing of 80% of their nitrogenase activity. The reduction of this activity was likely an indirect effect of zinc being retained in the infection/differentiation zone and not reaching the cytosol of rhizobia-infected cells. These data are consistent with a model in which MtZIP6 would be responsible for zinc uptake by rhizobia-infected nodule cells in the infection/differentiation zone. © 2017 John Wiley & Sons Ltd.

  17. Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

    PubMed Central

    Han, Jeongsoo; Kwon, Minjee; Cha, Myeounghoon; Tanioka, Motomasa; Hong, Seong-Karp; Bai, Sun Joon; Lee, Bae Hwan

    2015-01-01

    The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain. PMID:26457205

  18. Localization, Weakening and Fluid-rock Coupling Mechanisms in Gypsum: Development and Initial Data From a New, Combined, Rotary Shear and Acoustic Emission Apparatus.

    NASA Astrophysics Data System (ADS)

    Benson, P. M.; Pozzi, G.; Guerin-Marthe, S.; De Paola, N.; Nielsen, S. B.; Tomas, R.

    2017-12-01

    We present initial pilot data from a newly developed apparatus designed to measure Acoustic Emissions (AE) during the shear of fault gouges to 25 MPa normal stress and up to a maximum speed of 1 m/s, simulating dynamic earthquake processes. The sample assembly consists of a titanium-vanadium alloy (Ti-alloy, Ti90Al6V4) anvil fitted with 6 ports on the lower (stationary) section for AE sensors that record the activity of the shearing occurring in the gouge layer above. AE data are amplified from between 6 to 70 dB and recorded to disk continuously at a sampling rate of 10 MHz; calibration tests with Teflon shims confirm that the machine noise is negligible. Gouge thicknesses of approximately 2 mm are used, confined with a Teflon ring. Here we focus on Gypsum gouge from the Volterra region of Italy, sieved to give a constant gouge range of between 63 to 90 micrometers. Mechanical data show the onset of weakening after a slip of 1-3 cm for velocities of v = 100 to 1 cm s-1 respectively. Microstructural observations reveal a shear zone bounded by sharp mirror surfaces, and the development of a dehydration front, which is likely to have produced small pockets of water. We also record a characteristic `pulsing' AE signal generated after shearing is arrested, manifested as a series of energy spikes occurring at regular intervals. However, these signals are only generally seen for shear tests conducted on gypsum gouges (not in anhydrite) at 10cm per second or higher. Taken together, we interpret these observations as evidence that the initial shearing generated a thin slip zone that heats up rapidly, generating the dehydration front. Once motion ceases, pockets of trapped pressurized water combined with thermal stress generates distributed micro-fracturing detected as an initial swarm of high energy AE, and allows fluids to vent in pulses to the ambient atmosphere. An initial seismic -b value analysis of the continuous AE waveform also supports these initial findings.

  19. ESTCP UXO Discrimination Study. MTADS Demonstration at Camp Sibert Magnetometer / EM61 MkII / GEM-3 Arrays, Gadsden, AL, April 2007

    DTIC Science & Technology

    2008-08-21

    Yuma Proving Ground Open Field ............................................................................... 76 B.3.1 Response Stage... Yuma Proving Ground ZIP (250) Iomega ZIP disk (250 MB version) xv ACKNOWLEDGEMENTS Glenn Harbaugh and Daniel Steinhurst (P.I.) of Nova Research...sites at Aberdeen Proving Ground and Yuma Proving Ground in 2003 and 2004 [6]. At each of the sites, the Calibration Lanes, the Blind Test Grid

  20. Return Difference Feedback Design for Robust Uncertainty Tolerance in Stochastic Multivariable Control Systems.

    DTIC Science & Technology

    1982-11-01

    D- R136 495 RETURN DIFFERENCE FEEDBACK DESIGN FOR ROBUSTj/ UNCERTAINTY TOLERANCE IN STO..(U) UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES DEPT OF...State and ZIP Code) 7. b6 ADORESS (City. Staft and ZIP Code) Department of Electrical Engineering -’M Directorate of Mathematical & Information Systems ...13. SUBJECT TERMS Continur on rverse ineeesaty and identify by block nmber) FIELD GROUP SUE. GR. Systems theory; control; feedback; automatic control

  1. Aircraft Observations of the Atmospheric Boundary Layer in the Vicinity of the Marginal Ice Zone Under Conditions of Flow Parallel to the Ice Edge

    DTIC Science & Technology

    1990-09-01

    iNaval P’ostgraduate School (if applicable) MIR Naval l’ostgraduate School 6c Address (city, stair’. and ZIP codr) 7b Address (elty, stai, and ZIP’ codr...Lieutenant, United States Navy B.A., Ithaca College, 1975 Submitted in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN

  2. Solar Data | Geospatial Data Science | NREL

    Science.gov Websites

    System Name: WGS_1984 Coverage File Last Updated Metadata KMZ File Lower 48 and Hawaii DNI 10-km Resolution 1998-2009 Zip 9.6 MB 09/12/2012 Direct Normal.xml Direct Normal.kmz Lower 48 and Hawaii GHI 10-km : GCS_North_American_1983 Coverage File Last Updated Metadata KMZ File Lower 48 DNI 10-km Resolution 1998-2005 Zip 9.1 MB 12

  3. Analysis of Enrollment by Zip Codes Fall 1982 to Fall 1984. Research Monograph IV [and] Student Enrollment by Majors and Educational Intent. Research Monograph VI.

    ERIC Educational Resources Information Center

    Shirazi, Annmarie

    These two reports analyze enrollments at Oklahoma City Community College (OCCC) by zip code between fall 1982 and fall 1984, by student major between spring 1981 and spring 1985, and by student educational goals for spring 1985. Highlighted findings include the following: (1) the enrollment from Oklahoma City showed a steady decline in terms of…

  4. Seismic Data from Roosevelt Hot Springs, Utah FORGE Study Area

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

    Miller, John

    This set of data contains raw and processed 2D and 3D seismic data from the Utah FORGE study area near Roosevelt Hot Springs. The zipped archives numbered from 1-100 to 1001-1122 contain 3D seismic uncorrelated shot gatherers SEG-Y files. The zipped archives numbered from 1-100C to 1001-1122C contain 3D seismic correlated shot gatherers SEG-Y files. Other data have intuitive names.

  5. ARES: A System for Real-Time Operational and Tactical Decision Support

    DTIC Science & Technology

    1986-12-01

    In B]LE LCLGf. 9 NAVAL POSTGRADUATE SCHOOL Monterey, California Vi,-. %*.. THESIS - ’ A RE S A SYSTEM -OR REAL- 1I I .-.. --- OPERATIONAL AND...able) aval Postgraduate School 54 Naval Postgraduate School NN DRESS (City,. State,. and ZIP Code) 7b ADDRESS (City,. State,. and ZIP Code...SUBJECT TERMS (Continue on reverse if necessaty and identify by block number) LD GROUP SUB-GROUP Decision Support System, Logistics Model, Operational

  6. Unfolding and melting of DNA (RNA) hairpins: the concept of structure-specific 2D dynamic landscapes.

    PubMed

    Lin, Milo M; Meinhold, Lars; Shorokhov, Dmitry; Zewail, Ahmed H

    2008-08-07

    A 2D free-energy landscape model is presented to describe the (un)folding transition of DNA/RNA hairpins, together with molecular dynamics simulations and experimental findings. The dependence of the (un)folding transition on the stem sequence and the loop length is shown in the enthalpic and entropic contributions to the free energy. Intermediate structures are well defined by the two coordinates of the landscape during (un)zipping. Both the free-energy landscape model and the extensive molecular dynamics simulations totaling over 10 mus predict the existence of temperature-dependent kinetic intermediate states during hairpin (un)zipping and provide the theoretical description of recent ultrafast temperature-jump studies which indicate that hairpin (un)zipping is, in general, not a two-state process. The model allows for lucid prediction of the collapsed state(s) in simple 2D space and we term it the kinetic intermediate structure (KIS) model.

  7. Ergonomic assessment of enhanced protection under body armour combat shirt neck collars.

    PubMed

    Breeze, John; Granger, C J; Pearkes, T D; Clasper, J C

    2014-03-01

    Combat neck injury due to explosively propelled fragments is a significant cause of mortality and long-term morbidity in UK soldiers deployed on current operations. Reinforcing the collar of the existing under body armour combat shirt (UBACS) has been suggested as a potential method for reducing the incidence of combat neck injury. 20 soldiers serving in Afghanistan objectively compared three designs of enhanced protection UBACS (EP-UBACS) using 10 representative military tasks against a baseline of a standard UBACS. Each EP-UBACS design was trialled using three constituent materials: two layers of para-aramid felt, one layer of ultra high molecule weight polyethylene (UHMWPE) felt or two layers of a silk fabric. Subjective assessment of these nine configurations in terms of comfort, heat dissipation and overall acceptability were compared with the standard UBACS using a χ² test. All military tasks could be performed with all nine configurations of EP-UBACS. Although silk was the most comfortable material, it was not functionally practical in any of the three designs. Crossover collars incorporating UHMWPE or para-aramid were the only two of the nine configurations to demonstrate similar user acceptability to a standard UBACS. The EP-UBACS has the potential to provide neck protection without reducing performance incorporating materials analogous to either of the felts assessed in this study. The collar should provide stand-off from the skin to improve heat dissipation and comfort, which can be maximised by changing the current UBACS collar shape to one that crosses over at the front. Should a zip be desired, it should be moved to one side of the midline to reduce rubbing on the chin and be covered with ballistic protective material. Additional semi-circles of silk beneath the collar at the front and back would improve protection without affecting comfort.

  8. Pesticide exposure and hepatocellular carcinoma risk: A case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data.

    PubMed

    VoPham, Trang; Brooks, Maria M; Yuan, Jian-Min; Talbott, Evelyn O; Ruddell, Darren; Hart, Jaime E; Chang, Chung-Chou H; Weissfeld, Joel L

    2015-11-01

    Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. U.S. studies examining self-reported pesticide exposure in relation to HCC have demonstrated inconclusive results. We aimed to clarify the association between pesticide exposure and HCC by implementing a novel data linkage between Surveillance, Epidemiology, and End Results (SEER)-Medicare and California Pesticide Use Report (PUR) data using a geographic information system (GIS). Controls were frequency-matched to HCC cases diagnosed between 2000 and 2009 in California by year, age, race, sex, and duration of residence in California. Potential confounders were extracted from Medicare claims. From 1974 to 2008, pounds (1 pound represents 0.45 kg) of applied organophosphate, organochlorine, and carbamate pesticides provided in PURs were aggregated to the ZIP Code level using area weighting in a GIS. ZIP Code exposure estimates were linked to subjects using Medicare-provided ZIP Codes to calculate pesticide exposure. Agricultural residents were defined as living in ZIP Codes with a majority area intersecting agricultural land cover according to the 1992, 2001, and 2006 National Land Cover Database (NLCD) rasters. Multivariable conditional logistic regression was used to estimate the association between pesticide exposure and HCC. Among California residents of agriculturally intensive areas, previous annual ZIP Code-level exposure to over 14.53 kg/km(2) of organochlorine pesticides (75(th) percentile among controls) was associated with an increased risk of HCC after adjusting for liver disease and diabetes (adjusted odds ratio [OR] 1.87, 95% confidence interval [CI] 1.17, 2.99; p=0.0085). ZIP Code-level organochlorines were significantly associated with an increased risk of HCC among males (adjusted OR 2.76, 95% CI 1.58, 4.82; p=0.0004), but not associated with HCC among females (adjusted OR 0.83, 95% CI 0.35, 1.93; p=0.6600) (interaction p=0.0075). This is the first epidemiologic study to use GIS-based exposure estimates to study pesticide exposure and HCC. Our results suggest that organochlorine pesticides are associated with an increase in HCC risk among males but not females. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. K-bZIP Mediated SUMO-2/3 Specific Modification on the KSHV Genome Negatively Regulates Lytic Gene Expression and Viral Reactivation

    PubMed Central

    Yang, Wan-Shan; Hsu, Hung-Wei; Campbell, Mel; Cheng, Chia-Yang; Chang, Pei-Ching

    2015-01-01

    SUMOylation is associated with epigenetic regulation of chromatin structure and transcription. Epigenetic modifications of herpesviral genomes accompany the transcriptional switch of latent and lytic genes during the virus life cycle. Here, we report a genome-wide comparison of SUMO paralog modification on the KSHV genome. Using chromatin immunoprecipitation in conjunction with high-throughput sequencing, our study revealed highly distinct landscape changes of SUMO paralog genomic modifications associated with KSHV reactivation. A rapid and widespread deposition of SUMO-2/3, compared with SUMO-1, modification across the KSHV genome upon reactivation was observed. Interestingly, SUMO-2/3 enrichment was inversely correlated with H3K9me3 mark after reactivation, indicating that SUMO-2/3 may be responsible for regulating the expression of viral genes located in low heterochromatin regions during viral reactivation. RNA-sequencing analysis showed that the SUMO-2/3 enrichment pattern positively correlated with KSHV gene expression profiles. Activation of KSHV lytic genes located in regions with high SUMO-2/3 enrichment was enhanced by SUMO-2/3 knockdown. These findings suggest that SUMO-2/3 viral chromatin modification contributes to the diminution of viral gene expression during reactivation. Our previous study identified a SUMO-2/3-specific viral E3 ligase, K-bZIP, suggesting a potential role of this enzyme in regulating SUMO-2/3 enrichment and viral gene repression. Consistent with this prediction, higher K-bZIP binding on SUMO-2/3 enrichment region during reactivation was observed. Moreover, a K-bZIP SUMO E3 ligase dead mutant, K-bZIP-L75A, in the viral context, showed no SUMO-2/3 enrichment on viral chromatin and higher expression of viral genes located in SUMO-2/3 enriched regions during reactivation. Importantly, virus production significantly increased in both SUMO-2/3 knockdown and KSHV K-bZIP-L75A mutant cells. These results indicate that SUMO-2/3 modification of viral chromatin may function to counteract KSHV reactivation. As induction of herpesvirus reactivation may activate cellular antiviral regimes, our results suggest that development of viral SUMO E3 ligase specific inhibitors may be an avenue for anti-virus therapy. PMID:26197391

  10. Pesticide exposure and hepatocellular carcinoma risk: a case-control study using a geographic information system (GIS) to link SEER-Medicare and California pesticide data

    PubMed Central

    VoPham, Trang; Brooks, Maria M.; Yuan, Jian-Min; Talbott, Evelyn O.; Ruddell, Darren; Hart, Jaime E.; Chang, Chung-Chou H.; Weissfeld, Joel L.

    2015-01-01

    Background Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is associated with low survival. U.S. studies examining self-reported pesticide exposure in relation to HCC have demonstrated inconclusive results. We aimed to clarify the association between pesticide exposure and HCC by implementing a novel data linkage between Surveillance, Epidemiology, and End Results (SEER)-Medicare and California Pesticide Use Report (PUR) data using a geographic information system (GIS). Methods Controls were frequency-matched to HCC cases diagnosed between 2000 and 2009 in California by year, age, race, sex, and duration of residence in California. Potential confounders were extracted from Medicare claims. From 1974 to 2008, pounds (1 pound represents 0.45 kg) of applied organophosphate, organochlorine, and carbamate pesticides provided in PURs were aggregated to the ZIP Code level using area weighting in a GIS. ZIP Code exposure estimates were linked to subjects using Medicare-provided ZIP Codes to calculate pesticide exposure. Agricultural residents were defined as living in ZIP Codes with a majority area intersecting agricultural land cover according to the 1992, 2001, and 2006 National Land Cover Database (NLCD) rasters. Multivariable conditional logistic regression was used to estimate the association between pesticide exposure and HCC. Results Among California residents of agriculturally intensive areas, previous annual ZIP Code-level exposure to over 14.53 kg/km2 of organochlorine pesticides (75th percentile among controls) was associated with an increased risk of HCC after adjusting for liver disease and diabetes (adjusted odds ratio [OR] 1.87, 95% confidence interval [CI] 1.17, 2.99; p=0.0085). ZIP Code-level organochlorines were significantly associated with an increased risk of HCC among males (adjusted OR 2.76, 95% CI 1.58, 4.82; p=0.0004), but not associated with HCC among females (adjusted OR 0.83, 95% CI 0.35, 1.93; p=0.6600) (interaction p=0.0075). Conclusions This is the first epidemiologic study to use GIS-based exposure estimates to study pesticide exposure and HCC. Our results suggest that organochlorine pesticides are associated with an increase in HCC risk among males but not females. PMID:26451881

  11. PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins

    PubMed Central

    Hussein, Hiba Abi; Borrel, Alexandre; Geneix, Colette; Petitjean, Michel; Regad, Leslie; Camproux, Anne-Claude

    2015-01-01

    Predicting protein pocket's ability to bind drug-like molecules with high affinity, i.e. druggability, is of major interest in the target identification phase of drug discovery. Therefore, pocket druggability investigations represent a key step of compound clinical progression projects. Currently computational druggability prediction models are attached to one unique pocket estimation method despite pocket estimation uncertainties. In this paper, we propose ‘PockDrug-Server’ to predict pocket druggability, efficient on both (i) estimated pockets guided by the ligand proximity (extracted by proximity to a ligand from a holo protein structure) and (ii) estimated pockets based solely on protein structure information (based on amino atoms that form the surface of potential binding cavities). PockDrug-Server provides consistent druggability results using different pocket estimation methods. It is robust with respect to pocket boundary and estimation uncertainties, thus efficient using apo pockets that are challenging to estimate. It clearly distinguishes druggable from less druggable pockets using different estimation methods and outperformed recent druggability models for apo pockets. It can be carried out from one or a set of apo/holo proteins using different pocket estimation methods proposed by our web server or from any pocket previously estimated by the user. PockDrug-Server is publicly available at: http://pockdrug.rpbs.univ-paris-diderot.fr. PMID:25956651

  12. PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins.

    PubMed

    Hussein, Hiba Abi; Borrel, Alexandre; Geneix, Colette; Petitjean, Michel; Regad, Leslie; Camproux, Anne-Claude

    2015-07-01

    Predicting protein pocket's ability to bind drug-like molecules with high affinity, i.e. druggability, is of major interest in the target identification phase of drug discovery. Therefore, pocket druggability investigations represent a key step of compound clinical progression projects. Currently computational druggability prediction models are attached to one unique pocket estimation method despite pocket estimation uncertainties. In this paper, we propose 'PockDrug-Server' to predict pocket druggability, efficient on both (i) estimated pockets guided by the ligand proximity (extracted by proximity to a ligand from a holo protein structure) and (ii) estimated pockets based solely on protein structure information (based on amino atoms that form the surface of potential binding cavities). PockDrug-Server provides consistent druggability results using different pocket estimation methods. It is robust with respect to pocket boundary and estimation uncertainties, thus efficient using apo pockets that are challenging to estimate. It clearly distinguishes druggable from less druggable pockets using different estimation methods and outperformed recent druggability models for apo pockets. It can be carried out from one or a set of apo/holo proteins using different pocket estimation methods proposed by our web server or from any pocket previously estimated by the user. PockDrug-Server is publicly available at: http://pockdrug.rpbs.univ-paris-diderot.fr. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Signal Processing with Degenerate Four-Wave Mixing.

    DTIC Science & Technology

    1987-12-07

    MONITORING ORGANIZATION Optical Sciences Center j (i applicable) 6c. ADDRESS (City, State, and ZIPCode) 7b. ADDRESS (City, State, and ZIP Cod...apOliable) AFOSR I j AFOSR-84-0277 I, ADDRESS (City, State and ZIP Code) 10. SOURCE OF FUNDING NUMBERS Bulig40PROGRAM IPROJECT TASK I WORK UNIT Buling...5 Accesson Fo I - __ 0 4.Z- NTIS GRA. D__t _______r_!_ ________I,,* k AccessiondFor Dist.~~ .ipe i 45 rix’ _ _____ _____ __ j

  14. Determination of SPEAR-1 Rocket Body Potential during High-Voltage Experiments

    DTIC Science & Technology

    1990-06-01

    California at San Diego La Jolla, CA 92093 10 . Dr. C. E. McIlwain Center for Astrophysics and Space Science University of California at San Diego La Jolla...Postgraduate School 39 Naval Postgraduate School 6c. ADDRESS (City, S:are, and ZIP Code) 7b. ADDRESS (Ciy, State, and ZIP Code) Monterey. CA 93943-5000...Monterey. CA 93943-5000 8a. NAME OF FUNDING.SPONSORING 80. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If applicable

  15. European Science Notes. Volume 40, Number 4.

    DTIC Science & Technology

    1986-04-01

    OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (if applicable) 8c. ADDRESS (City, State, and ZIP Code ) 10. SOURCE OF...Office, London ONRL 6c. ADDRESS (City, State, and ZIP Code ) 7b. ADDRESS (City, State, and ZIPCode) Box 39 FPO, NY 09510 Ba. NAME OF FUNDING/SPONSORING 8b...13..TYPj9 REPORT13bTIECVRD1.DTOFRPT(YaMnhDy)1.AGCUNMonthly FROM TO _ April 1986 32 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18. SUBJECT TERMS

  16. Verifying the Chemical Weapons Convention: The Case for a United Nations Verification Agency

    DTIC Science & Technology

    1991-12-01

    ORGANIZATION REPORT NUMBER(S) 6&. NAME OF PERFORMING ORGANIZATION j6b. OFFICE SYMBOL 7&. NAME OF MONITORING ORGANIZATION Naval Postgraduate School J(if applicaip...Naval Postgraduate School 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Monterey. CA 93943-5000 Monterey, CA 93943...Governinent. 17. COSATI CODES 18. SUBJECT TERMS (continue on reverse if necessaty and identify by black number) -FIELD GROUP SUBGROUP Chemical

  17. Pullout of a Rigid Insert Adhesively Bonded to an Elastic Half Plane.

    DTIC Science & Technology

    1983-12-01

    COMMAND UNITED STATES AIR FORCE C-= °84 02 13 071. C,, W % d 6 This document was prepared by the Department of Engineering Mechanics, USAF Academy Faculty...THOMAS E. KULLGREN, Lt Col, USAF Project Engineer /Scientist Professor and Acting Head, Department of Engineering Mechanics KENNETH E. SIEGETH Lt Col...Department of Engineering (Ifapphicable) Mechanics USAFA/DFEM 6c. ADDRESS (City. State and ZIP Code) 7b. ADDRESS (City, Slate and ZIP Code) USAF Academy

  18. USAF Presence in Latin America in the 21st Century.

    DTIC Science & Technology

    1988-04-01

    faculty in partial fulfillment of requirements for graduation. AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY MAXWELL AFB, AL 36112 UNCLASSIFIED SECURITY...ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Maxwell AFB AL 36112-5542 Ba. NAME OF FUNDING /SPONSORING 8 b. OFFICE SYMBOL... Servicio Multimodal Transistmico across the Isthmus of Tehuantepec (11:28). It does, however. *%4 row:n militaiy importance. The U.S. Atlantic Command’s

  19. Mechanism of Cytotoxicity of the AIDS Virus, HTLV-III/LAV

    DTIC Science & Technology

    1989-05-21

    distribution unlimited 4. PERFORMING OR3ANIZATION REPORT NUMBER(S) S. MONITORING ORGANIZATION REPORT NUMBER($) 143-065-3611-Al 6s. NAME OF PERFORMING... ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME Of MONITORING ORGANIZATIONj (I aI cb) Washinton University k€. ADORESS (City, State, and ZIP Code) 7b. ADDRESS...IDENTIFICATION NUMBER ORGANIZATiON U.S. Army Medical (if awible) Resch. & Development Command DArJM-17-87-C-7101 Sc. ADDRESS (Oil, State, and ZIP Code

  20. IGG Subclass and Isotype Specific Immunoglobulin Responses to Lassa Fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunization

    DTIC Science & Technology

    1990-09-30

    EQUINE N ENCEPHALOMYELITIS: NATURAL INFECTION AND IMMUNIZATION , I PRINCIPAL INVESTIGATOR: Renata J. Engler, LTC, MC CONTRACTING ORGANIZATION: Uniformed...Services University of the Health Sciences Department of Medicine Bethesda, MD 20814-4799 REPORT DATE: September 30, 1990 ELECTEO 0CT 3 11990 TYPE OF...Uniformed Services University (If applicable) of Health Sciences I 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code

  1. Developmental Role and Auxin Responsiveness of Class III Homeodomain Leucine Zipper Gene Family Members in Rice1[C][W][OA

    PubMed Central

    Itoh, Jun-Ichi; Hibara, Ken-Ichiro; Sato, Yutaka; Nagato, Yasuo

    2008-01-01

    Members of the Class III homeodomain leucine zipper (Class III HD-Zip) gene family are central regulators of crucial aspects of plant development. To better understand the roles of five Class III HD-Zip genes in rice (Oryza sativa) development, we investigated their expression patterns, ectopic expression phenotypes, and auxin responsiveness. Four genes, OSHB1 to OSHB4, were expressed in a localized domain of the shoot apical meristem (SAM), the adaxial cells of leaf primordia, the leaf margins, and the xylem tissue of vascular bundles. In contrast, expression of OSHB5 was observed only in phloem tissue. Plants ectopically expressing microRNA166-resistant versions of the OSHB3 gene exhibited severe defects, including the ectopic production of leaf margins, shoots, and radialized leaves. The treatment of seedlings with auxin quickly induced ectopic OSHB3 expression in the entire region of the SAM, but not in other tissues. Furthermore, this ectopic expression of OSHB3 was correlated with leaf initiation defects. Our findings suggest that rice Class III HD-Zip genes have conserved functions with their homologs in Arabidopsis (Arabidopsis thaliana), but have also acquired specific developmental roles in grasses or monocots. In addition, some Class III HD-Zip genes may regulate the leaf initiation process in the SAM in an auxin-dependent manner. PMID:18567825

  2. Variation Analysis of Physiological Traits in Betula platyphylla Overexpressing TaLEA-ThbZIP Gene under Salt Stress

    PubMed Central

    Xiao, Zhenhai; Wang, Fuwei; Li, Shuchun; Zang, Lina; Zheng, Mi; Li, Ying; Qu, Guan-Zheng

    2016-01-01

    The aim of this study was to determine whether transgenic birch (Betula platyphylla) ectopic overexpressing a late embryogenesis abundant (LEA) gene and a basic leucine zipper (bZIP) gene from the salt-tolerant genus Tamarix (salt cedar) show increased tolerance to salt (NaCl) stress. Co-transfer of TaLEA and ThbZIP in birch under the control of two independent CaMV 35S promoters significantly enhanced salt stress. PCR and northern blot analyses indicated that the two genes were ectopically overexpressed in several dual-gene transgenic birch lines. We compared the effects of salt stress among three transgenic birch lines (L-4, L-5, and L-8) and wild type (WT). In all lines, the net photosynthesis values were higher before salt stress treatment than afterwards. After the salt stress treatment, the transgenic lines L-4 and L-8 showed higher values for photosynthetic traits, chlorophyll fluorescence, peroxidase and superoxide dismutase activities, and lower malondialdehyde and Na+ contents, compared with those in WT and L-5. These different responses to salt stress suggested that the transcriptional level of the TaLEA and ThbZIP genes differed among the transgenic lines, resulting in a variety of genetic and phenotypic effects. The results of this research can provide a theoretical basis for the genetic engineering of salt-tolerant trees. PMID:27802286

  3. The membrane tethered transcription factor EcbZIP17 from finger millet promotes plant growth and enhances tolerance to abiotic stresses.

    PubMed

    Ramakrishna, Chopperla; Singh, Sonam; Raghavendrarao, Sangala; Padaria, Jasdeep C; Mohanty, Sasmita; Sharma, Tilak Raj; Solanke, Amolkumar U

    2018-02-01

    The occurrence of various stresses, as the outcome of global climate change, results in the yield losses of crop plants. Prospecting of genes in stress tolerant plant species may help to protect and improve their agronomic performance. Finger millet (Eleusine coracana L.) is a valuable source of superior genes and alleles for stress tolerance. In this study, we isolated a novel endoplasmic reticulum (ER) membrane tethered bZIP transcription factor from finger millet, EcbZIP17. Transgenic tobacco plants overexpressing this gene showed better vegetative growth and seed yield compared with wild type (WT) plants under optimal growth conditions and confirmed upregulation of brassinosteroid signalling genes. Under various abiotic stresses, such as 250 mM NaCl, 10% PEG6000, 400 mM mannitol, water withdrawal, and heat stress, the transgenic plants showed higher germination rate, biomass, primary and secondary root formation, and recovery rate, compared with WT plants. The transgenic plants exposed to an ER stress inducer resulted in greater leaf diameter and plant height as well as higher expression of the ER stress-responsive genes BiP, PDIL, and CRT1. Overall, our results indicated that EcbZIP17 improves plant growth at optimal conditions through brassinosteroid signalling and provide tolerance to various environmental stresses via ER signalling pathways.

  4. PockDrug: A Model for Predicting Pocket Druggability That Overcomes Pocket Estimation Uncertainties.

    PubMed

    Borrel, Alexandre; Regad, Leslie; Xhaard, Henri; Petitjean, Michel; Camproux, Anne-Claude

    2015-04-27

    Predicting protein druggability is a key interest in the target identification phase of drug discovery. Here, we assess the pocket estimation methods' influence on druggability predictions by comparing statistical models constructed from pockets estimated using different pocket estimation methods: a proximity of either 4 or 5.5 Å to a cocrystallized ligand or DoGSite and fpocket estimation methods. We developed PockDrug, a robust pocket druggability model that copes with uncertainties in pocket boundaries. It is based on a linear discriminant analysis from a pool of 52 descriptors combined with a selection of the most stable and efficient models using different pocket estimation methods. PockDrug retains the best combinations of three pocket properties which impact druggability: geometry, hydrophobicity, and aromaticity. It results in an average accuracy of 87.9% ± 4.7% using a test set and exhibits higher accuracy (∼5-10%) than previous studies that used an identical apo set. In conclusion, this study confirms the influence of pocket estimation on pocket druggability prediction and proposes PockDrug as a new model that overcomes pocket estimation variability.

  5. Reliability and validity of ten consumer activity trackers.

    PubMed

    Kooiman, Thea J M; Dontje, Manon L; Sprenger, Siska R; Krijnen, Wim P; van der Schans, Cees P; de Groot, Martijn

    2015-01-01

    Activity trackers can potentially stimulate users to increase their physical activity behavior. The aim of this study was to examine the reliability and validity of ten consumer activity trackers for measuring step count in both laboratory and free-living conditions. Healthy adult volunteers (n = 33) walked twice on a treadmill (4.8 km/h) for 30 min while wearing ten different activity trackers (i.e. Lumoback, Fitbit Flex, Jawbone Up, Nike+ Fuelband SE, Misfit Shine, Withings Pulse, Fitbit Zip, Omron HJ-203, Yamax Digiwalker SW-200 and Moves mobile application). In free-living conditions, 56 volunteers wore the same activity trackers for one working day. Test-retest reliability was analyzed with the Intraclass Correlation Coefficient (ICC). Validity was evaluated by comparing each tracker with the gold standard (Optogait system for laboratory and ActivPAL for free-living conditions), using paired samples t-tests, mean absolute percentage errors, correlations and Bland-Altman plots. Test-retest analysis revealed high reliability for most trackers except for the Omron (ICC .14), Moves app (ICC .37) and Nike+ Fuelband (ICC .53). The mean absolute percentage errors of the trackers in laboratory and free-living conditions respectively, were: Lumoback (-0.2, -0.4), Fibit Flex (-5.7, 3.7), Jawbone Up (-1.0, 1.4), Nike+ Fuelband (-18, -24), Misfit Shine (0.2, 1.1), Withings Pulse (-0.5, -7.9), Fitbit Zip (-0.3, 1.2), Omron (2.5, -0.4), Digiwalker (-1.2, -5.9), and Moves app (9.6, -37.6). Bland-Altman plots demonstrated that the limits of agreement varied from 46 steps (Fitbit Zip) to 2422 steps (Nike+ Fuelband) in the laboratory condition, and 866 steps (Fitbit Zip) to 5150 steps (Moves app) in the free-living condition. The reliability and validity of most trackers for measuring step count is good. The Fitbit Zip is the most valid whereas the reliability and validity of the Nike+ Fuelband is low.

  6. Characterization of a new family of metal transport proteins. 1998 annual progress report

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

    Guerinot, M.L.

    1998-06-01

    'Soils at many DOE sites are contaminated with metals and radionuclides. Such soils obviously pose a risk to human and animal health. Unlike organic wastes which can be metabolized, metals are immutable and cannot be degraded into harmless constituents. Phytoremediation, the use of plants to remove toxic materials from soil and water, may prove to be an environmentally friendly and cost effective solution for cleaning up metal-contaminated sites. The success of phytoremediation will rely on the availability of plants that absorb, translocate, and tolerate the contaminating metals. However, before the authors can engineer such plants, they need more basic informationmore » on how plants acquire metals. An important long term goal of the research program is to understand how metals such as zinc, cadmium and copper are transported across membranes. The research is focused on a new family of metal transporters which they have identified through combined studies in the yeast Saccharomyces cerevisiae and in the model plant Arabidopsis thaliana. They have identified a family of 19 presumptive metal transport genes in a variety of organisms including yeast, trypanosomes, plants, nematodes, and humans. This family, which the authors have designated the ZIP genes, provides a rich source of material with which to undertake studies on metal transport in eukaryotes. The project has three main objectives: Objective 1: Determine the sub-cellular location of the ZIP proteins in Arabidopsis. Objective 2: Carry out a structure/function analysis of the proteins encoded by the ZIP gene family to identify regions of the protein responsible for substrate specificity and affinity. Objective 3: Engineer plants to overexpress and underexpress members of the ZIP gene family and analyze these transgenic plants for alterations in metal accumulation. They now know that manipulation of transporter levels will also require an understanding of post-transcriptional control of ZIP gene expression. They are currently in year one of a three-year project.'« less

  7. Operation CeaseFire-New Orleans: an infectious disease model for addressing community recidivism from penetrating trauma.

    PubMed

    McVey, Erin; Duchesne, Juan C; Sarlati, Siavash; O'Neal, Michael; Johnson, Kelly; Avegno, Jennifer

    2014-07-01

    CeaseFire, using an infectious disease approach, addresses violence by partnering hospital resources with the community by providing violence interruption and community-based services for an area roughly composed of a single city zip code (70113). Community-based violence interrupters start in the trauma center from the moment penetrating trauma occurs, through hospital stay, and in the community after release. This study interprets statistics from this pilot program, begun May 2012. We hypothesize a decrease in penetrating trauma rates in the target area compared with others after program implementation. This was a 3-year prospective data collection of trauma registry from May 2010 to May 2013. All intentional, target area, penetrating trauma treated at our Level I trauma center received immediate activation of CeaseFire personnel. Incidences of violent trauma and rates of change, by zip code, were compared with the same period for 2 years before implementation. During this period, the yearly incidence of penetrating trauma in Orleans Parish increased. Four of the highest rates were found in adjacent zip codes: 70112, 70113, 70119, and 70125. Average rates per 100,000 were 722.7, 523.6, 286.4, and 248, respectively. These areas represent four of the six zip codes citywide that saw year-to-year increases in violent trauma during this period. Zip 70113 saw a lower rate of rise in trauma compared with 70112 and a higher but comparable rise compared with that of 70119 and 70125. Hospital-based intervention programs that partner with culturally appropriate personnel and resources outside the institution walls have potential to have meaningful impact over the long term. While few conclusions of the effect of such a program can be drawn in a 12-month period, we anticipate long-term changes in the numbers of penetrating injuries in the target area and in the rest of the city as this program expands. Therapeutic study, level IV.

  8. Functional studies of Drosophila zinc transporters reveal the mechanism for dietary zinc absorption and regulation

    PubMed Central

    2013-01-01

    Background Zinc is key to the function of many proteins, but the process of dietary zinc absorption is not well clarified. Current knowledge about dietary zinc absorption is fragmented, and mostly derives from incomplete mammalian studies. To gain a comprehensive picture of this process, we systematically characterized all zinc transporters (that is, the Zip and ZnT family members) for their possible roles in dietary zinc absorption in a genetically amenable model organism, Drosophila melanogaster. Results A set of plasma membrane-resident zinc transporters was identified to be responsible for absorbing zinc from the lumen into the enterocyte and the subsequent exit of zinc to the circulation. dZip1 and dZip2, two functionally overlapping zinc importers, are responsible for absorbing zinc from the lumen into the enterocyte. Exit of zinc to the circulation is mediated through another two functionally overlapping zinc exporters, dZnT1, and its homolog CG5130 (dZnT77C). Somewhat surprisingly, it appears that the array of intracellular ZnT proteins, including the Golgi-resident dZnT7, is not directly involved in dietary zinc absorption. By modulating zinc status in different parts of the body, we found that regulation of dietary zinc absorption, in contrast to that of iron, is unresponsive to bodily needs or zinc status outside the gut. The zinc transporters that are involved in dietary zinc absorption, including the importers dZip1 and dZip2, and the exporter dZnT1, are respectively regulated at the RNA and protein levels by zinc in the enterocyte. Conclusions Our study using the model organism Drosophila thus starts to reveal a comprehensive sketch of dietary zinc absorption and its regulatory control, a process that is still incompletely understood in mammalian organisms. The knowledge gained will act as a reference for future mammalian studies, and also enable an appreciation of this important process from an evolutionary perspective. PMID:24063361

  9. Association between community socioeconomic factors, animal feeding operations, and campylobacteriosis incidence rates: Foodborne Diseases Active Surveillance Network (FoodNet), 2004-2010.

    PubMed

    Rosenberg Goldstein, Rachel E; Cruz-Cano, Raul; Jiang, Chengsheng; Palmer, Amanda; Blythe, David; Ryan, Patricia; Hogan, Brenna; White, Benjamin; Dunn, John R; Libby, Tanya; Tobin-D'Angelo, Melissa; Huang, Jennifer Y; McGuire, Suzanne; Scherzinger, Karen; Lee, Mei-Ling Ting; Sapkota, Amy R

    2016-07-22

    Campylobacter is a leading cause of foodborne illness in the United States. Campylobacter infections have been associated with individual risk factors, such as the consumption of poultry and raw milk. Recently, a Maryland-based study identified community socioeconomic and environmental factors that are also associated with campylobacteriosis rates. However, no previous studies have evaluated the association between community risk factors and campylobacteriosis rates across multiple U.S. states. We obtained Campylobacter case data (2004-2010; n = 40,768) from the Foodborne Diseases Active Surveillance Network (FoodNet) and socioeconomic and environmental data from the 2010 Census of Population and Housing, the 2011 American Community Survey, and the 2007 U.S. Census of Agriculture. We linked data by zip code and derived incidence rate ratios using negative binomial regression models. Community socioeconomic and environmental factors were associated with both lower and higher campylobacteriosis rates. Zip codes with higher percentages of African Americans had lower rates of campylobacteriosis (incidence rate ratio [IRR]) = 0.972; 95 % confidence interval (CI) = 0.970,0.974). In Georgia, Maryland, and Tennessee, three leading broiler chicken producing states, zip codes with broiler operations had incidence rates that were 22 % (IRR = 1.22; 95 % CI = 1.03,1.43), 16 % (IRR = 1.16; 95 % CI = 0.99,1.37), and 35 % (IRR = 1.35; 95 % CI = 1.18,1.53) higher, respectively, than those of zip codes without broiler operations. In Minnesota and New York FoodNet counties, two top dairy producing areas, zip codes with dairy operations had significantly higher campylobacteriosis incidence rates (IRR = 1.37; 95 % CI = 1.22, 1.55; IRR = 1.19; 95 % CI = 1.04,1.36). Community socioeconomic and environmental factors are important to consider when evaluating the relationship between possible risk factors and Campylobacter infection.

  10. Fire, Lava Flows, and Human Evolution

    NASA Astrophysics Data System (ADS)

    Medler, M. J.

    2015-12-01

    Richard Wrangham and others argue that cooked food has been obligate for our ancestors since the time of Homo erectus. This hypothesis provides a particularly compelling explanation for the smaller mouths and teeth, shorter intestines, and larger brains that separate us from other hominins. However, natural ignitions are infrequent and it is unclear how earlier hominins may have adapted to cooked food and fire before they developed the necessary intelligence to make or control fire. To address this conundrum, we present cartographical evidence that the massive and long lasting lava flows in the African Rift could have provided our ancestors with episodic access to heat and fire as the front edges of these flows formed ephemeral pockets of heat and ignition and other geothermal features. For the last several million years major lava flows have been infilling the African Rift. After major eruptions there were likely more slowly advancing lava fronts creating small areas with very specific adaptive pressures and opportunities for small isolated groups of hominins. Some of these episodes of isolation may have extended for millennia allowing these groups of early hominins to develop the adaptations Wrangham links to fire and cooked food. To examine the potential veracity of this proposal, we developed a series of maps that overlay the locations of prominent hominin dig sites with contemporaneous lava flows. These maps indicate that many important developments in hominin evolution were occurring in rough spatial and temporal proximity to active lava flows. These maps indicate it is worth considering that over the last several million years small isolated populations of hominins may have experienced unique adaptive conditions while living near the front edges of these slowly advancing lava flows.

  11. Robust Control of Multivariable and Large Scale Systems.

    DTIC Science & Technology

    1986-03-14

    AD-A175 $5B ROBUST CONTROL OF MULTIVRRIALE AND LARG SCALE SYSTEMS V2 R75 (U) HONEYWELL SYSTEMS AND RESEARCH CENTER MINNEAPOLIS MN J C DOYLE ET AL...ONIJQ 86 R alFS ja ,.AMIECFOEPF:ORMING ORGANIZATION So OFFICE SYMBOL 7a NAME OF MONITORING ORGANIZATI ON jonevwell Systems & Research If 4000c" Air...Force Office of Scientific Research .~ C :AE S C.rv. Stare arma ZIP Code) 7C ADDRESS (Crty. Stare. am ZIP Code, *3660 Marshall Street NE Building 410

  12. Model of Dredging Impact on Dungeness Crab in Grays Harbor, Washington

    DTIC Science & Technology

    1987-06-01

    Washington. 43 pp. Barry, Steve. 1986. Personal communication . Washington Dept. of Fisheries , Montesano, Washington. Bella, D.A. and K.J. Williamson. 1980... FISHERIES 18SHERIES RESEARCH INSTITUTE *~~ ~~~~~~~ Z *;r. .’."*,* U.-~0 SECURITY CLASSIFICATION OF THIS PAGE REPORT DOCUMENTATION PAGE Form Approved...School of Fisheries U.S.Ary Corps of Engineers, Seattle District 6c. ADDRESS (Cty, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code

  13. Technology Evaluation for Treatment/Disposal of TNT Red Water

    DTIC Science & Technology

    1990-04-01

    U.S. Army Toxic and Hazardous Materials Agency Aberdeen Proving Ground , MD 21010-5423 __ E=4N DISTRIBUTION UNLIMITED I I TECHNOLOGY EVALUATION FOR...ABERDEEN PROVING GROUND , MARYLAND 21010-5423 April 1990 I I SECURITY CLASSIFICATION OF T-HI5 PA iiREPORT DOCUMENTATION PAGE W 7"f 4 I. REPORT SECURITY...and ZIP Code) 7b, ADDRESS (City, State, and ZIP Code) ATTN: CETHA-TE-D Aberdeen Proving Ground , MD 21010-5401 BaG. NAME OF FUNDING /SPONSORING 8b

  14. Identification (ID) Cards for Members of the Uniformed Services, Their Dependents, and Other Eligible Individuals

    DTIC Science & Technology

    1992-12-30

    Encl 5) Cayman Islands CJ Central African Republic CT Chad CD Chile CI China CH Christmas Island KT Clipperton Islands IP Cocos (Keeling) Islands CK...PA Puerto Rico PR Rhode Island RI South Carolina SC South Dakota SD Tennessee TN Federated States of Marshall Islands , Palau TT Texas TX Utah UT...Vermont VT Virginia VA Virgin Islands VI Washington WA West Virginia WV Wisconsin WI Wyoming WY Block 17. ZIP Code. Enter the correct nine-digit ZIP Code

  15. Applications of Functional Analytic and Martingale Methods to Problems in Queueing Network Theory.

    DTIC Science & Technology

    1983-05-14

    8217’") Air Force Office of Scientific Research Sf. ADDRESS (Cllty. State and ZIP Code) 7b. ADDRESS (City. State and ZIP Code) Directorate of Mathematical... Scientific Report on Air Force Grant #82-0167 Principal Investigator: Professor Walter A. Rosenkrantz I. Publications (1) Calculation of the LaPlace transform...whether or not a protocol for accessing a comunications channel is stable. In AFOSR 82-0167, Report No. 3 we showed that the SLOTTED ALOHA Multi access

  16. Thermospray Liquid Chromatography/Mass Spectrometry of Mustard and Its Metabolites

    DTIC Science & Technology

    1989-05-01

    MONITORING ORGANIZATION REPORT NUMBER(S) CRDEC-TR-066 6a. NAME OF PERFORMING ORGANIZATION 6b OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION (If applicable...see reverse 6c- ADDRESS (Cty, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Ba. NAME OF FUNDING/SPONSORING 8b OFFICE SYMBOL 9...Ather und Thioather in Dioxan- Wasser -Gemischen," Chem, Ber. Vol. 81, p 123 (1948). 2. Capon, B., and McManus, S. P., Neighboring Group Participation

  17. Preparation and Use of Liposomes in Immunological Studies

    DTIC Science & Technology

    1993-01-01

    SYMBOL MFI RO W 0 E FANIZATION Division of Bioctmnistry El O9V09W399 6c. ADDRESS (City, State, and ZIP Code). DRESS(Ci State, and ZIP Code) "Walter Reed...Anuv Institute of Research 1 A Washington. DC 20307-5100 oC" 8a. NAME OF FUNDING/SPONSORING 8b. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION...12a NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (Include Area Code) 22c. OFFICE SYMBOL OD Form 1473, JUN 86 Previous editions are obsolete

  18. The Telecommunications Emergency Decision Support System as a Crisis Management Decision Support System

    DTIC Science & Technology

    1991-09-01

    NAVAL POSTGRADUATE SCHOOL Monterey, California AD-A246 188 7 R DTIC fl ELECTE FEB2 1992 U THESIS THE TELECOMMUNICATIONS EMERGENCY DECISION SUPPORT...ORGANIZATION REPORT NUMBER(S) a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOl 7a. NAME OF MONITORING ORGANIZATION Naval Postgraduate School J ""X...s Naval Postgraduate School c. ADDRESS (City, State and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Monterey, CA 93943-5000 Monterey, CA 93943

  19. Problem-Solving Under Time Constraints: Alternatives for the Commander’s Estimate

    DTIC Science & Technology

    1990-03-26

    CHOOL OF ADVANCED MILITAR (If applicable) STUDIES, USAC&GSC IATZL-SWV 6. ADDRESS (City, State, and ZIP Code ) 7b. ADDRESS (City, State, and ZIP Code ...NOTATION 17. COSATI CODES 18. SUBJECT TERMS (Continue on reverse if necessary and identify by block number) FIELD GROUP SUB-GROUP DECISIONJ*MAKING...OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (Include Area Code ) 122c. OFFICE SYMBOL MAJ TIMOTHY D. LYNCH 9 684-3437 1 AT71-.qWV DO Form 1473, JUN 86

  20. Bibliography on Metrication, January 1977 to August 1989

    DTIC Science & Technology

    1990-08-01

    X.L. 109 Guist, Althea R . 460 Gutmann, Fredrick T. 14,291 Hager. Mary 306 Halstead, Bruce B. 188 Hamilton, A.B. 21,303 Hanley, Charles J. 417 Hart, K.C...Scientific Info. Cent IAMSMI-RD-cs- R 6c. ADDRESS (CIty, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Commander, U.S. Army Missile Command...Redstone Scientific Information Center AMSMI-RD-CS- R Redstone Arsenal, AL 35898-5241 8a. NAME OF FUNDING/SPONSORING 18b. OFFICE SYMBOL 9. PROCUREMENT

  1. Fiber Optic Microsensor for Receptor-Based Assays

    DTIC Science & Technology

    1988-09-01

    MONITORING ORGANIZATION ORDInc.(if applicable ) 6c. ADDRESS (CWty Sta~te, and ZIP code) 7b. ADDRESS (City, State, an~d ZIP=Cd) Nahant, MA 019081 Sa, NAME OF...yield B-PE B-phycoerythrin 545 575 2,410,000 0.98 R-PE R-phycoerythrin 565 578 11960,000 0.68 CPC C- phycocyanine 620 650 1,690,000 0.51 A-PC...efficient transfer occurred for unit magnification. Figure 3 shows the optical design. Evaluation of the instrument was done with both A- phycocyanine

  2. Proceedings of Workshop 15 of the COSPAR Meetings Held in Toulouse, France on 30 June-12 July 1986. Chapter 2. Reference Atmospheres and Thermospheric Mapping,

    DTIC Science & Technology

    1988-01-21

    DISTRIBUTION/AVAILABILITY OF REPORT Approved for public release; 2b. DECLASSIFICATION /’DOWNGRADING SCHEDULE Distribution unlimited 4. PERFORMING ORGANIZATION ...REPORT NUMBER(S) 5. MONITORING ORGANIZATION REPORT NUMBER(S) AFGL-TR-88-0016 6a, NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF...MONITORING ORGANIZATION Air Force Geophysics (If applicable) Laboratory I oc. ADDRESS (City, State, and ZIP Code) 7b ADDRESS (City, Stare, and ZIP Code

  3. Signal Transduction Pathway in Maspin-induced Tumor Suppression of Prostate Cancer

    DTIC Science & Technology

    2002-03-01

    the zip Ebr allele is tested in similar assays with BR-C or Sb-sbd mutants. The zipEbr mutation is associated with a missense alteration in the myosin ...cytoskeletal dynamics in elongating legs via by inducing contraction of the apical actin- myosin belt. 8 Recent evidence has shown that mutations in...the RhoA mutations used in these studies have been characterized at a molecular level (Table 2). RhoAE3 °o is a CAAX box missense mutation (C to Y

  4. IGG Subclass and Isotype Specific Immunoglobulin Responses to LASSA fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunication

    DTIC Science & Technology

    1989-03-01

    VENEZUELAN EQUINE ENCEPHALOMYELITIS: NATURAL INFECTION AND IMMUNIZATION PRINCIPAL INVESTIGATOR: Renata J. Engler CONTRACTING ORGANIZATION: Uniformed Services...University of Health Sciences 4301 Jones Bridges Road Bethesda, MD 20814-4799 DTIC REPORT DATE: March 1, 1989 E T E MAR0 6 1990 TYPE OF REPORT...University (if applicable) of Health Sciences I 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) 4301 Jones Bridges Road

  5. Travelling Wave Concepts for the Modeling and Control of Space Structures

    DTIC Science & Technology

    1988-01-31

    ZIP Code) 77 Massachusetts Avenue AFOSR / L \\\\ 0 Cambridge, MA 02139 Bolling Air Force Base , DC 20332-6448 8a. NAME OF FUNDING/SPONSORING 8b OFFICE...FQ8671-88-00398 8c. ADDRESS (City, State, and ZIP Code) 10 SOURCE OF FUNDING NUMBERS Building 410 PROGRAM PROJECT tASK WORK UNIT Bolling Air Force Base ...at the Jet Propulsion Laboratories, and is writing two further papers for journal publication based on his PhD dissertation. In the winter of 1987

  6. Miller Cave (23PU2), Fort Leonard Wood, Pulaski County, Missouri: Report of Archaeological Testing and Assessment of Damage

    DTIC Science & Technology

    1993-01-01

    SECURITY CLASSIFICATION AUTHORITY 3. DISTRIBUTION JAVAILABIUITY OF REPORT 2b. DECLASSIFICATION I OWNGRAD)ING SCHEDULE I4. PERFORMING ORGANIZATION ...REPORT NUMBER(S) 5. MONITORING ORGANIZATION REPORT NUMBER(S) RESEARCH REPORT NO. 9 6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF...MONITORING ORGANIZATION Markman & Associates, Inc.(I plcbe 6c. ADDRESS (City. State. and ZIP Code) 7b. ADDRESS (City. State. and ZIP Code) 824 N. Bl

  7. Selective electrodiffusion of zinc ions in a Zrt-, Irt-like protein, ZIPB

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

    Lin, W.; Fu, D.; Chai, J.

    2010-12-10

    All living cells need zinc ions to support cell growth. Zrt-, Irt-like proteins (ZIPs) represent a major route for entry of zinc ions into cells, but how ZIPs promote zinc uptake has been unclear. Here we report the molecular characterization of ZIPB from Bordetella bronchiseptica, the first ZIP homolog to be purified and functionally reconstituted into proteoliposomes. Zinc flux through ZIPB was found to be nonsaturable and electrogenic, yielding membrane potentials as predicted by the Nernst equation. Conversely, membrane potentials drove zinc fluxes with a linear voltage-flux relationship. Direct measurements of metal uptake by inductively coupled plasma mass spectroscopy demonstratedmore » that ZIPB is selective for two group 12 transition metal ions, Zn{sup 2+} and Cd{sup 2+}, whereas rejecting transition metal ions in groups 7 through 11. Our results provide the molecular basis for cellular zinc acquisition by a zinc-selective channel that exploits in vivo zinc concentration gradients to move zinc ions into the cytoplasm.« less

  8. Abscisic acid signaling is controlled by a BRANCHED1/HD-ZIP I cascade in Arabidopsis axillary buds.

    PubMed

    González-Grandío, Eduardo; Pajoro, Alice; Franco-Zorrilla, José M; Tarancón, Carlos; Immink, Richard G H; Cubas, Pilar

    2017-01-10

    Shoot-branching patterns determine key aspects of plant life and are important targets for crop breeding. However, we are still largely ignorant of the genetic networks controlling locally the most important decision during branch development: whether the axillary bud, or branch primordium, grows out to give a lateral shoot or remains dormant. Here we show that, inside the buds, the TEOSINTE BRANCHED1, CYCLOIDEA, PCF (TCP) transcription factor BRANCHED1 (BRC1) binds to and positively regulates the transcription of three related Homeodomain leucine zipper protein (HD-ZIP)-encoding genes: HOMEOBOX PROTEIN 21 (HB21), HOMEOBOX PROTEIN 40 (HB40), and HOMEOBOX PROTEIN 53 (HB53). These three genes, together with BRC1, enhance 9-CIS-EPOXICAROTENOID DIOXIGENASE 3 (NCED3) expression, lead to abscisic acid accumulation, and trigger hormone response, thus causing suppression of bud development. This TCP/HD-ZIP genetic module seems to be conserved in dicot and monocotyledonous species to prevent branching under light-limiting conditions.

  9. Decryption-decompression of AES protected ZIP files on GPUs

    NASA Astrophysics Data System (ADS)

    Duong, Tan Nhat; Pham, Phong Hong; Nguyen, Duc Huu; Nguyen, Thuy Thanh; Le, Hung Duc

    2011-10-01

    AES is a strong encryption system, so decryption-decompression of AES encrypted ZIP files requires very large computing power and techniques of reducing the password space. This makes implementations of techniques on common computing system not practical. In [1], we reduced the original very large password search space to a much smaller one which surely containing the correct password. Based on reduced set of passwords, in this paper, we parallel decryption, decompression and plain text recognition for encrypted ZIP files by using CUDA computing technology on graphics cards GeForce GTX295 of NVIDIA, to find out the correct password. The experimental results have shown that the speed of decrypting, decompressing, recognizing plain text and finding out the original password increases about from 45 to 180 times (depends on the number of GPUs) compared to sequential execution on the Intel Core 2 Quad Q8400 2.66 GHz. These results have demonstrated the potential applicability of GPUs in this cryptanalysis field.

  10. Conformationally Constrained Analogues of Diacylglycerol. 29. Cells Sort Diacylglycerol-Lactone Chemical Zip Codes to Produce Diverse and Selective Biological Activities

    PubMed Central

    Duan, Dehui; Sigano, Dina M.; Kelley, James A.; Lai, Christopher C.; Lewin, Nancy E.; Kedei, Noemi; Peach, Megan L.; Lee, Jeewoo; Abeyweera, Thushara P.; Rotenberg, Susan A.; Kim, Hee; Kim, Young Ho; Kazzouli, Saïd El; Chung, Jae-Uk; Young, Howard A.; Young, Matthew R.; Baker, Alyson; Colburn, Nancy H.; Haimovitz-Friedman, Adriana; Truman, Jean-Philip; Parrish, Damon A.; Deschamps, Jeffrey R.; Perry, Nicholas A.; Surawski, Robert J.; Blumberg, Peter M.; Marquez, Victor E.

    2008-01-01

    Diacylglycerol-lactone (DAG-lactone) libraries generated by a solid-phase approach using IRORI technology produced a variety of unique biological activities. Subtle differences in chemical diversity in two areas of the molecule, the combination of which generates what we have termed “chemical zip codes”, are able to transform a relatively small chemical space into a larger universe of biological activities, as membrane-containing organelles within the cell appear to be able to decode these “chemical zip codes”. It is postulated that after binding to protein kinase C (PKC) isozymes or other non-kinase target proteins that contain diacylglycerol responsive, membrane interacting domains (C1 domains), the resulting complexes are directed to diverse intracellular sites where different sets of substrates are accessed. Multiple cellular bioassays show that DAG-lactones, which bind in vitro to PKCα to varying degrees, expand their biological repertoire into a larger domain, eliciting distinct cellular responses. PMID:18698758

  11. VIP1 is very important/interesting protein 1 regulating touch responses of Arabidopsis.

    PubMed

    Tsugama, Daisuke; Liu, Shenkui; Takano, Tetsuo

    2016-06-02

    VIP1 (VIRE2-INTERACTING PROTEIN 1) is a bZIP transcription factor in Arabidopsis thaliana. VIP1 and its close homologs (i.e., Arabidopsis group I bZIP proteins) are present in the cytoplasm under steady conditions, but are transiently localized to the nucleus when cells are exposed to hypo-osmotic conditions, which mimic mechanical stimuli such as touch. Recently we have reported that overexpression of a repression domain-fused form of VIP1 represses the expression of some touch-responsive genes, changes structures and/or local auxin responses of the root cap cells, and enhances the touch-induced root waving. This raises the possibility that VIP1 suppresses touch-induced responses. VIP1 should be useful to further characterize touch responses of plants. Here we discuss 2 seemingly interesting perspectives about VIP1: (1) What factors are involved in regulating the nuclear localization of VIP1?; (2) What can be done to further characterize the physiological functions of VIP1 and other Arabidopsis group I bZIP proteins?

  12. Cavity Versus Ligand Shape Descriptors: Application to Urokinase Binding Pockets.

    PubMed

    Cerisier, Natacha; Regad, Leslie; Triki, Dhoha; Camproux, Anne-Claude; Petitjean, Michel

    2017-11-01

    We analyzed 78 binding pockets of the human urokinase plasminogen activator (uPA) catalytic domain extracted from a data set of crystallized uPA-ligand complexes. These binding pockets were computed with an original geometric method that does NOT involve any arbitrary parameter, such as cutoff distances, angles, and so on. We measured the deviation from convexity of each pocket shape with the pocket convexity index (PCI). We defined a new pocket descriptor called distributional sphericity coefficient (DISC), which indicates to which extent the protein atoms of a given pocket lie on the surface of a sphere. The DISC values were computed with the freeware PCI. The pocket descriptors and their high correspondences with ligand descriptors are crucial for polypharmacology prediction. We found that the protein heavy atoms lining the urokinases binding pockets are either located on the surface of their convex hull or lie close to this surface. We also found that the radii of the urokinases binding pockets and the radii of their ligands are highly correlated (r = 0.9).

  13. Interplay between Magnetism, Superconductivity, and Orbital Order in 5-Pocket Model for Iron-Based Superconductors: Parquet Renormalization Group Study.

    PubMed

    Classen, Laura; Xing, Rui-Qi; Khodas, Maxim; Chubukov, Andrey V

    2017-01-20

    We report the results of the parquet renormalization group (RG) analysis of the phase diagram of the most general 5-pocket model for Fe-based superconductors. We use as an input the orbital structure of excitations near the five pockets made out of d_{xz}, d_{yz}, and d_{xy} orbitals and argue that there are 40 different interactions between low-energy fermions in the orbital basis. All interactions flow under the RG, as one progressively integrates out fermions with higher energies. We find that the low-energy behavior is amazingly simple, despite the large number of interactions. Namely, at low energies the full 5-pocket model effectively reduces either to a 3-pocket model made of one d_{xy} hole pocket and two electron pockets or a 4-pocket model made of two d_{xz}/d_{yz} hole pockets and two electron pockets. The leading instability in the effective 4-pocket model is a spontaneous orbital (nematic) order, followed by s^{+-} superconductivity. In the effective 3-pocket model, orbital fluctuations are weaker, and the system develops either s^{+-} superconductivity or a stripe spin-density wave. In the latter case, nematicity is induced by composite spin fluctuations.

  14. Use of Medicaid and housing data may help target areas of ...

    EPA Pesticide Factsheets

    Objective: To determine if there was a significant difference between mold contamination and asthma prevalence in Detroit and non-Detroit Michigan homes, between newer and older homes, and if there is a correlation between mold contamination and measures of Medicaid use for asthma in the 25 Detroit zip codes. Methods: Settled dust was collected from homes (n = 113) of Detroit asthmatic children and from a representative group of Michigan homes (n = 43). The mold contamination for each home was measured using the Environmental Relative Moldiness Index (ERMI) scale and the mean ERMI values in Detroit and non-Detroit homes were statistically compared. Michigan Medicaid data (13 measures related to asthma) in each of the 25 zip codes in Detroit were tested for correlation to ERMI values for homes in those zip codes. Results: The mean ERMI value (14.5 ± 8.0) for Detroit asthmatic childrens' homes was significantly (Student's t-test, p 60 years old had significantly (p = 0.01) greater mean ERMI values than Detroit homes ≤ 60 years old (15.87 vs. 11.25). The percentage of children that underwent spirometry testing for their persistent asthma (based on Medicaid data) was significantly, positively correlated with the mean ERMI values of the homes in the 25 zip codes. Conclusions: Applying Medicaid-use data for spirometry testing and locating a city's older housing stock might help find foci of homes with high ERMI values. To further define the relationship between mo

  15. Geographic Variation in Susceptibility to Ventilator-Associated Pneumonia After Traumatic Injury

    PubMed Central

    Zarzaur, Ben L.; Bell, Teresa; Croce, Martin A.; Fabian, Timothy C.

    2013-01-01

    Background Emphasis on prevention of healthcare-associated infections (HAI) including ventilator-associated pneumonia (VAP) has increased as hospitals are beginning to be held financially accountable for such infections. HAIs are often represented as being avoidable; however, the literature indicates that complete preventability may not be possible. The vast majority of research on risk factors for VAP concerns individual level factors. No studies have investigated the role of the patient's environment prior to admission. In this study we aim to investigate the potential role pre-hospital environment plays in VAP etiology. Methods In a retrospective cohort study, a sample of 5,031 trauma patients treated with mechanical ventilation between 1996–2010 was analyzed to determine the effect of neighborhood on the probability of developing VAP. We evaluated the effect of zip code using multilevel logistic regression analysis adjusting for individual level factors associated with VAP. Results We identified three zip codes with rates of ventilator-associated pneumonia that differed significantly from the mean. Logistic regression indicated that zip code, age, gender, race, injury severity, paralysis, head injury, and number of days on the ventilator were significantly associated with VAP. However, median zip code income was not. Conclusions Spatial factors that are independent of health care quality may potentiate the likelihood of a patient developing VAP and possibly other types of healthcare acquired infections. Un-modifiable environmental patient characteristics may predispose certain populations to developing infections in the setting of trauma. Level of Evidence III PMID:23823609

  16. Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates.

    PubMed

    Jemielita, Thomas; Gerton, George L; Neidell, Matthew; Chillrud, Steven; Yan, Beizhan; Stute, Martin; Howarth, Marilyn; Saberi, Pouné; Fausti, Nicholas; Penning, Trevor M; Roy, Jason; Propert, Kathleen J; Panettieri, Reynold A

    2015-01-01

    Over the past ten years, unconventional gas and oil drilling (UGOD) has markedly expanded in the United States. Despite substantial increases in well drilling, the health consequences of UGOD toxicant exposure remain unclear. This study examines an association between wells and healthcare use by zip code from 2007 to 2011 in Pennsylvania. Inpatient discharge databases from the Pennsylvania Healthcare Cost Containment Council were correlated with active wells by zip code in three counties in Pennsylvania. For overall inpatient prevalence rates and 25 specific medical categories, the association of inpatient prevalence rates with number of wells per zip code and, separately, with wells per km2 (separated into quantiles and defined as well density) were estimated using fixed-effects Poisson models. To account for multiple comparisons, a Bonferroni correction with associations of p<0.00096 was considered statistically significant. Cardiology inpatient prevalence rates were significantly associated with number of wells per zip code (p<0.00096) and wells per km2 (p<0.00096) while neurology inpatient prevalence rates were significantly associated with wells per km2 (p<0.00096). Furthermore, evidence also supported an association between well density and inpatient prevalence rates for the medical categories of dermatology, neurology, oncology, and urology. These data suggest that UGOD wells, which dramatically increased in the past decade, were associated with increased inpatient prevalence rates within specific medical categories in Pennsylvania. Further studies are necessary to address healthcare costs of UGOD and determine whether specific toxicants or combinations are associated with organ-specific responses.

  17. Exploring the bZIP transcription factor regulatory network in Neurospora crassa

    PubMed Central

    Tian, Chaoguang; Li, Jingyi; Glass, N. Louise

    2011-01-01

    Transcription factors (TFs) are key nodes of regulatory networks in eukaryotic organisms, including filamentous fungi such as Neurospora crassa. The 178 predicted DNA-binding TFs in N. crassa are distributed primarily among six gene families, which represent an ancient expansion in filamentous ascomycete genomes; 98 TF genes show detectable expression levels during vegetative growth of N. crassa, including 35 that show a significant difference in expression level between hyphae at the periphery versus hyphae in the interior of a colony. Regulatory networks within a species genome include paralogous TFs and their respective target genes (TF regulon). To investigate TF network evolution in N. crassa, we focused on the basic leucine zipper (bZIP) TF family, which contains nine members. We performed baseline transcriptional profiling during vegetative growth of the wild-type and seven isogenic, viable bZIP deletion mutants. We further characterized the regulatory network of one member of the bZIP family, NCU03905. NCU03905 encodes an Ap1-like protein (NcAp-1), which is involved in resistance to multiple stress responses, including oxidative and heavy metal stress. Relocalization of NcAp-1 from the cytoplasm to the nucleus was associated with exposure to stress. A comparison of the NcAp-1 regulon with Ap1-like regulons in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Aspergillus fumigatus showed both conservation and divergence. These data indicate how N. crassa responds to stress and provide information on pathway evolution. PMID:21081763

  18. Exploring the bZIP transcription factor regulatory network in Neurospora crassa.

    PubMed

    Tian, Chaoguang; Li, Jingyi; Glass, N Louise

    2011-03-01

    Transcription factors (TFs) are key nodes of regulatory networks in eukaryotic organisms, including filamentous fungi such as Neurospora crassa. The 178 predicted DNA-binding TFs in N. crassa are distributed primarily among six gene families, which represent an ancient expansion in filamentous ascomycete genomes; 98 TF genes show detectable expression levels during vegetative growth of N. crassa, including 35 that show a significant difference in expression level between hyphae at the periphery versus hyphae in the interior of a colony. Regulatory networks within a species genome include paralogous TFs and their respective target genes (TF regulon). To investigate TF network evolution in N. crassa, we focused on the basic leucine zipper (bZIP) TF family, which contains nine members. We performed baseline transcriptional profiling during vegetative growth of the wild-type and seven isogenic, viable bZIP deletion mutants. We further characterized the regulatory network of one member of the bZIP family, NCU03905. NCU03905 encodes an Ap1-like protein (NcAp-1), which is involved in resistance to multiple stress responses, including oxidative and heavy metal stress. Relocalization of NcAp-1 from the cytoplasm to the nucleus was associated with exposure to stress. A comparison of the NcAp-1 regulon with Ap1-like regulons in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans and Aspergillus fumigatus showed both conservation and divergence. These data indicate how N. crassa responds to stress and provide information on pathway evolution.

  19. Stage-specific regulation of four HD-ZIP III transcription factors during polar pattern formation in Larix leptolepis somatic embryos.

    PubMed

    Li, Shui-gen; Li, Wan-feng; Han, Su-ying; Yang, Wen-hua; Qi, Li-wang

    2013-06-15

    Polar auxin transport provides a developmental signal for cell fate specification during somatic embryogenesis. Some members of the HD-ZIP III transcription factors participate in regulation of auxin transport, but little is known about this regulation in somatic embryogenesis. Here, four HD-ZIP III homologues from Larix leptolepis were identified and designated LaHDZ31, 32, 33 and 34. The occurrence of a miR165/166 target sequence in all four cDNA sequences indicated that they might be targets of miR165/166. Identification of the cleavage products of LaHDZ31 and LaHDZ32 in vivo confirmed that they were regulated by miRNA. Their mRNA accumulation patterns during somatic embryogenesis and the effects of 1-N-naphthylphthalamic acid (NPA) on their transcript levels and somatic embryo maturation were investigated. The results showed that the four genes had higher transcript levels at mature stages than at the proliferation stage, and that NPA treatment down-regulated the mRNA abundance of LaHDZ31, 32 and 33 at cotyledonary embryo stages, but had no effect on the mRNA abundance of LaHDZ34. We concluded that these four members of Larix HD-ZIP III family might participate in polar auxin transport and the development of somatic embryos, providing new insights into the regulatory mechanisms of somatic embryogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Zinc Transport Differs in Rat Spermatogenic Cell Types and Is Affected by Treatment with Cyclophosphamide1

    PubMed Central

    Downey, Anne Marie; Hales, Barbara F.; Robaire, Bernard

    2016-01-01

    Adequate zinc levels are required for proper cellular functions and for male germ cell development. Zinc transport is accomplished by two families of zinc transporters, the ZIPs and the ZnTs, that increase and decrease cytosolic zinc levels, respectively. However, very little is known about zinc transport in the testis. Furthermore, whether cytotoxic agents such as cyclophosphamide (CPA), a known male germ cell toxicant, can affect zinc transport and homeostasis is unknown. We examined zinc transporter expression and zinc transport in pachytene spermatocytes (PS) and round spermatids (RS) in a normal state and after exposure to CPA. We observed differences in the expression of members of the ZnT and ZIP families in purified populations of PS and RS. We also observed that RS accumulate more zinc over time than PS. The expression of many zinc binding genes was altered after CPA treatment. Interestingly, we found that the expression levels of ZIP5 and ZIP14 were increased in PS from animals treated daily with 6 mg/kg CPA for 4 wk but not in RS. This up-regulation led to an increase in zinc uptake in PS but not in RS from treated animals compared to controls. These data suggest that CPA treatment may alter zinc homeostasis in male germ cells leading to an increased need for zinc. Altered zinc homeostasis may disrupt proper germ cell development and contribute to infertility and effects on progeny. PMID:27281708

  1. Assessment of Drug Binding Potential of Pockets in the NS2B/NS3 Dengue Virus Protein

    NASA Astrophysics Data System (ADS)

    Amelia, F.; Iryani; Sari, P. Y.; Parikesit, A. A.; Bakri, R.; Toepak, E. P.; Tambunan, U. S. F.

    2018-04-01

    Every year an endemic dengue fever estimated to affect over 390 million cases in over 128 countries occurs. However, the antigen types which stimulate the human immune response are variable, as a result, neither effective vaccines nor antiviral treatments have been successfully developed for this disease. The NS2B/NS3 protease of the dengue virus (DENV) responsible for viral replication is a potential drug target. The ligand-enzyme binding site determination is a key role in the success of virtual screening of new inhibitors. The NS2B/NS3 protease of DENV (PDB ID: 2FOM) has two pockets consisting of 37 (Pocket 1) and 27 (Pocket 2) amino acid residues in each pocket. In this research, we characterized the amino acid residues for binding sites in NS3/NS2B based on the hydrophobicity, the percentage of charged residues, volume, depth, ΔGbinding, hydrogen bonding and bond length. The hydrophobic percentages of both pockets are high, 59 % (Pocket 1) and 41% (Pocket 2) and the percentage of charged residues in Pocket 1 and 2 are 22% and 48%, and the pocket volume is less than 700 Å3. An interaction analysis using molecular docking showed that interaction between the ligand complex and protein in Pocket 1 is more negative than Pocket 2. As a result, Pocket 1 is the better potential target for a ligand to inhibit the action of NS2B/NS3 DENV.

  2. Presence of animal feeding operations and community socioeconomic factors impact salmonellosis incidence rates: An ecological analysis using data from the Foodborne Diseases Active Surveillance Network (FoodNet), 2004-2010.

    PubMed

    Shaw, Kristi S; Cruz-Cano, Raul; Jiang, Chengsheng; Malayil, Leena; Blythe, David; Ryan, Patricia; Sapkota, Amy R

    2016-10-01

    Nontyphoidal Salmonella spp. are a leading cause of foodborne illness. Risk factors for salmonellosis include the consumption of contaminated chicken, eggs, pork and beef. Agricultural, environmental and socioeconomic factors also have been associated with rates of Salmonella infection. However, to our knowledge, these factors have not been modeled together at the community-level to improve our understanding of whether rates of salmonellosis are variable across communities defined by differing factors. To address this knowledge gap, we obtained data on culture-confirmed Salmonella Typhimurium, S. Enteritidis, S. Newport and S. Javiana cases (2004-2010; n=14,297) from the Foodborne Diseases Active Surveillance Network (FoodNet), and socioeconomic, environmental and agricultural data from the 2010 Census of Population and Housing, the 2011 American Community Survey, and the 2007 U.S. Census of Agriculture. We linked data by zip code and derived incidence rate ratios using negative binomial regressions. Multiple community-level factors were associated with salmonellosis rates; however, our findings varied by state. For example, in Georgia (Incidence Rate Ratio (IRR)=1.01; 95% Confidence Interval (CI)=1.005-1.015) Maryland (IRR=1.01; 95% CI=1.003-1.015) and Tennessee (IRR=1.01; 95% CI=1.002-1.012), zip codes characterized by greater rurality had higher rates of S. Newport infections. The presence of broiler chicken operations, dairy operations and cattle operations in a zip code also was associated with significantly higher rates of infection with at least one serotype in states that are leading producers of these animal products. For instance, in Georgia and Tennessee, rates of S. Enteritidis infection were 48% (IRR=1.48; 95% CI=1.12-1.95) and 46% (IRR=1.46; 95% CI=1.17-1.81) higher in zip codes with broiler chicken operations compared to those without these operations. In Maryland, New Mexico and Tennessee, higher poverty levels in zip codes were associated with higher rates of infection with one or more Salmonella serotypes. In Georgia and Tennessee, zip codes with higher percentages of the population composed of African Americans had significantly higher rates of infection with one or more Salmonella serotypes. In summary, our findings show that community-level agricultural, environmental and socioeconomic factors may be important with regard to rates of infection with Salmonella Typhimurium, Enteritidis, Newport and Javiana. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Changes in zinc status and zinc transporters expression in whole blood of patients with Systemic Inflammatory Response Syndrome (SIRS).

    PubMed

    Florea, Daniela; Molina-López, Jorge; Hogstrand, Christer; Lengyel, Imre; de la Cruz, Antonio Pérez; Rodríguez-Elvira, Manuel; Planells, Elena

    2018-09-01

    Critically ill patients develop severe stress, inflammation and a clinical state that may raise the utilization and metabolic replacement of many nutrients and especially zinc, depleting their body reserves. This study was designed to assess the zinc status in critical care patients with systemic inflammatory response syndrome (SIRS), comparing them with a group of healthy people, and studying the association with expression of zinc transporters. This investigation was a prospective, multicentre, comparative, observational and analytic study. Twelve critically ill patients from different hospitals and 12 healthy subjects from Granada, Spain, all with informed consent were recruited. Data on daily nutritional assessment, ICU severity scores, inflammation, clinical and nutritional parameters, plasma and blood cell zinc concentrations, and levels of transcripts for zinc transporters in whole blood were taken at admission and at the seventh day of the ICU stay. Zinc levels on critical ill patient are diminish comparing with the healthy control (HS: 0.94 ± 0.19; CIPF: 0.67 ± 0.16 mg/dL). The 58% of critical ill patients showed zinc plasma deficiency at beginning of study while 50.0% of critical ill after 7 days of ICU stay. ZnT7, ZIP4 and ZIP9 were the zinc transporters with highest expression in whole blood. In general, all zinc transporters were significantly down-regulated (P < 0.05) in the critical ill population at admission in comparison with healthy subjects. Severity scores and inflammation were significantly associated (P < 0.05) with zinc plasma levels, and zinc transporters ZIP3, ZIP4, ZIP8, ZnT6, ZnT7. Expression of 11 out of 24 zinc transporters was analysed, and ZnT1, ZnT4, ZnT5 and ZIP4, which were downregulated by more than 3-fold in whole blood of patients. In summary, in our study an alteration of zinc status was related with the severity-of-illness scores and inflammation in critical ill patients since admission in ICU stay. SIRS caused a general shut-down of expression of zinc transporters in whole blood. That behavior was associated with severity and inflammation of patients at ICU admission regardless zinc status. We conclude that zinc transporters in blood might be useful indicators of severity of systemic inflammation and outcome for critically ill patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. An Amino Acid Code to Define a Protein’s Tertiary Packing Surface

    PubMed Central

    Fraga, Keith J.; Joo, Hyun; Tsai, Jerry

    2015-01-01

    One difficult aspect of the protein-folding problem is characterizing the non-specific interactions that define packing in protein tertiary structure. To better understand tertiary structure, this work extends the knob-socket model by classifying the interactions of a single knob residue packed into a set of contiguous sockets, or a pocket made up of 4 or more residues. The knob-socket construct allows for a symbolic two-dimensional mapping of pockets. The two-dimensional mapping of pockets provides a simple method to investigate the variety of pocket shapes in order to understand the geometry of protein tertiary surfaces. The diversity of pocket geometries can be organized into groups of pockets that share a common core, which suggests that some interactions in pockets are ancillary to packing. Further analysis of pocket geometries displays a preferred configuration that is right-handed in α-helices and left-handed in β-sheets. The amino acid composition of pockets illustrates the importance of non-polar amino acids in packing as well as position specificity. As expected, all pocket shapes prefer to pack with hydrophobic knobs; however, knobs are not selective for the pockets they pack. Investigating side-chain rotamer preferences for certain pocket shapes uncovers no strong correlations. These findings allow a simple vocabulary based on knobs and sockets to describe protein tertiary packing that supports improved analysis, design and prediction of protein structure. PMID:26575337

  5. Cavity Versus Ligand Shape Descriptors: Application to Urokinase Binding Pockets

    PubMed Central

    Cerisier, Natacha; Regad, Leslie; Triki, Dhoha; Camproux, Anne-Claude

    2017-01-01

    Abstract We analyzed 78 binding pockets of the human urokinase plasminogen activator (uPA) catalytic domain extracted from a data set of crystallized uPA–ligand complexes. These binding pockets were computed with an original geometric method that does NOT involve any arbitrary parameter, such as cutoff distances, angles, and so on. We measured the deviation from convexity of each pocket shape with the pocket convexity index (PCI). We defined a new pocket descriptor called distributional sphericity coefficient (DISC), which indicates to which extent the protein atoms of a given pocket lie on the surface of a sphere. The DISC values were computed with the freeware PCI. The pocket descriptors and their high correspondences with ligand descriptors are crucial for polypharmacology prediction. We found that the protein heavy atoms lining the urokinases binding pockets are either located on the surface of their convex hull or lie close to this surface. We also found that the radii of the urokinases binding pockets and the radii of their ligands are highly correlated (r = 0.9). PMID:28570103

  6. Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

    PubMed

    Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket properties for ligand binding.

  7. Insights into an Original Pocket-Ligand Pair Classification: A Promising Tool for Ligand Profile Prediction

    PubMed Central

    Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A.; Villoutreix, Bruno O.; Camproux, Anne-Claude

    2013-01-01

    Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket properties for ligand binding. PMID:23840299

  8. When to Pull the Trigger for the Counterattack: Simplicity versus Sophistication.

    DTIC Science & Technology

    1985-12-02

    ADA1I67 705 WHNEN TO PULL THE TRIGGER FOR THE CO$JNTERRTTRCK: vi1 SIMPLICITY VERSUS SOPHISTICATION(U) ARMY COMMAND AND, GENERAL STAFF COLL FORT...Adv’affied Military Studie SU.S. Army Command and General Staff College Fort Leavenworth, Kansas 2 December 1985 Approved ror Public Release: Distribution...OF MONITORING ORGANIZAl ION O~US ARMY CMD1AN’D AN𔃻D GENERAL If JT -10ab 6C. ADD)RESS (City. State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP

  9. SAC (Strategic Air Command) Needs a Few Good Men and Women’ - A Guide to ICBM (Intercontinental Ballistic Missile) Operations Duty

    DTIC Science & Technology

    1988-04-01

    Ditribufion is unlimited. 4 PERFORMING ORGANIZATION REPORT NUMBER(S) 5. MONITORING ORGANIZATION REPORT NUMBER(S) 88-0825 6a NAME OF PERFORMING ORGANIZATION 6b...OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION ACS C/EDC (If applicable) 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and...ZIP Code) MAXWELL AFB AL 36112-5542 8a. NAME OF FUNDING/SPONSORING 8b. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If

  10. Dispersion Strengthening of High Temperature Niobium Alloys

    DTIC Science & Technology

    1988-05-31

    Fig. 2 for the alloys containing ZrC and Ta6 Si3 respectively. The former shows classical age .hardening response with hardening followed by softening...tILE COP) ION STRENGTH’ENING OF HIGH TEMATURE NIOBIUM ALLOYS Prepared by D.L. Anton 00 D.B. Snow In) A.F. Giamei ANNUAL REPORT Contract F49620486-C...Center / ni .’ - k- ADDRESS (Ciy, State, and ZIP Code) 7b ADDRESS (City, State, and ZIP Code) East Hartford, CT 06108 7-Jc\\ 4 0 _ .F3 A.C 8a. NAME OF

  11. Development of the Pipe Loop System for Determining Effectiveness of Corrosion Control Chemicals in Potable Water Systems

    DTIC Science & Technology

    1988-08-01

    OFFICE SYMBOL 7a NAME OF MONITORING ORGANIZATION U.S. Army Construction (if applicable) Engr Research Laboratory CECER-EN 6c. ADDRESS (City, State...and ZIP Code) 7b ADDRESS (City, State, and ZIP Code) P.O. Box 4005 Champaign, IL 61821 8a. NAME OF FUNDING/SPONSORING 8b OFFICE SYMBOL 9 PROCUREMENT...NAME OF RESPONSIBLE INDIVIDUAL 22b TELEPHONE (Include Area Code) 22c OFFICE SYMBOL Jane Andrew 1(217) 352-6511, x388 CECER-IMT DD FORM 1473. 84 MAR 83

  12. The Roots of Social Protest in the Philippines and Their Effects on U.S. -R.P. Relations

    DTIC Science & Technology

    1990-12-01

    the nation to follow; attain self-sufficiency for the nation in food, clothing and shelter ; create jobs so Filipinos could earn the money to secure...I AD-A242 312 NAVAL POSTGRADUATE SCHOOL Monterey, California DTIC OCT 3 THESIS THE ROOTS OF SOCIAL PROTEST IN THE PHILIPPINES AND THEIR EFFECTS ON... and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code) Monterey. CA 93943-5100 MontereyCA 93943-5100 8a NAME OF FUNDING/SPONSORING 8b OFFICE SYMBOL 9

  13. Vertical Windshear Below 5.5 Kilometers in the Vicinity of Berlin, Germany.

    DTIC Science & Technology

    1986-08-01

    DIRECTORATE- L LEVITT ET AL . UNCL~ASSFE UG 66 AMSMI/TR-RD-RE-96-9 SBIAD-E951 031 F/G 4/2 N smmmmhhhhhm moommhmhhhuo im -~ L L0 MICROCOPY RESOLUTION TEST...AD-RI82 432 VERTICAL NINDSHEAR BELOW 55 KILOMETERS IN THE VICINITY 1/1 OF BERLIN GERMANY..(U) ARMY MISSILE COMMAND REDSTONE ARSENAL AL RESEARCH...ADDRESS (City, State, an ZIP Code) 7b ADDRESS (City, State, and ZIP Code) Comunder US Army Missile Coeypini ATTN4: AISMI-RO-RE Redstone Arsenal,* AL 35898

  14. Collaborative Studies of Polar Cap Ionospheric Dynamics.

    DTIC Science & Technology

    1987-10-12

    AQOIIRISS ICity. State ed Zip Code , 10. SOURCE OF PUNOING NOS. PROGRAM PROJECT TASK WORK .jNir ILE MgtNT NO. NO. NO. NO I TTL fneud ScuryCjMf,4,0...housing and the 3- stage thermoelectric cooler for the image plane detector. The operational principles that govern the application of the instrument are...Force Geophysics Laboratory 6c AOAGS J~iy. Sart A4 Z’P Cdol b. ADDRIESS (City. fE t ad ZIP Code , Anti Arbor, Mic higa n 4819HncmAFB Massachusetts 01731 A

  15. Differential Equations, Related Problems of Pade Approximations and Computer Applications

    DTIC Science & Technology

    1988-01-01

    x e X : d(x,A) Unfortunately. for moderate primes (p < 10,000) 1). Expanders have the property that every A c none of these Ramanujan graphs have a...and for every A c X, Card(A) :< n/2, the graphs of relataively small diameter can be boundary aA has at least c • Card(A) elements. Ramanujan graphs...State, and ZIP,ode) 7b. ADDRESS (City, State, and ZIP Code) - _ - - " Building 410 - C x ,, -Boiling, AFB DC 20332-6448 11a. NAME OF FUNDING

  16. Dosimetric Effects of Air Pockets Around High-Dose Rate Brachytherapy Vaginal Cylinders

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

    Richardson, Susan, E-mail: srichardson@radonc.wustl.ed; Palaniswaamy, Geethpriya; Grigsby, Perry W.

    2010-09-01

    Purpose: Most physicians use a single-channel vaginal cylinder for postoperative endometrial cancer brachytherapy. Recent published data have identified air pockets between the vaginal cylinders and the vaginal mucosa. The purpose of this research was to evaluate the incidence, size, and dosimetric effects of these air pockets. Methods and Materials: 25 patients receiving postoperative vaginal cuff brachytherapy with a high-dose rate vaginal cylinders were enrolled in this prospective data collection study. Patients were treated with 6 fractions of 200 to 400 cGy per fraction prescribed at 5 mm depth. Computed tomography simulation for brachytherapy treatment planning was performed for each fraction.more » The quantity, volume, and dosimetric impact of the air pockets surrounding the cylinder were quantified. Results: In 25 patients, a total of 90 air pockets were present in 150 procedures (60%). Five patients had no air pockets present during any of their treatments. The average number of air pockets per patient was 3.6, with the average total air pocket volume being 0.34 cm{sup 3} (range, 0.01-1.32 cm{sup 3}). The average dose reduction to the vaginal mucosa at the air pocket was 27% (range, 9-58%). Ten patients had no air pockets on their first fraction but air pockets occurred in subsequent fractions. Conclusion: Air pockets between high-dose rate vaginal cylinder applicators and the vaginal mucosa are present in the majority of fractions of therapy, and their presence varies from patient to patient and fraction to fraction. The existence of air pockets results in reduced radiation dose to the vaginal mucosa.« less

  17. Form and deformity: the trouble with Victorian pockets.

    PubMed

    Matthews, Christopher Todd

    2010-01-01

    This essay explores the Victorian debate about the place of pockets in men's and women's clothing. By studying the representation of men as naturally pocketed creatures and the general denial of useful pockets to middle-class women, the essay demonstrates the tenacious cultural logic by which men's and women's pockets were imagined to correspond to sexual differences and to index access, or lack thereof, to public mobility and financial agency. Interconnected readings of visual art, essays, and novels show how the common sense about gendered pockets was utilized and promulgated in Victorian narratives. The question of who gets pockets is thus positioned as part of the history of gendered bodies in public space.

  18. "Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run".

    PubMed

    Doidy, Joan; Li, Ying; Neymotin, Benjamin; Edwards, Molly B; Varala, Kranthi; Gresham, David; Coruzzi, Gloria M

    2016-02-03

    Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking. Here, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity-labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of-principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run"). Our findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read-out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control.

  19. Pocket money, eating behaviors, and weight status among Chinese children: The Childhood Obesity Study in China mega-cities.

    PubMed

    Li, Miao; Xue, Hong; Jia, Peng; Zhao, Yaling; Wang, Zhiyong; Xu, Fei; Wang, Youfa

    2017-07-01

    Both the obesity rate and pocket money are rising among children in China. This study examined family correlates of children's pocket money, associations of pocket money with eating behaviors and weight status, and how the associations may be modified by schools' unhealthy food restrictions in urban China. Data were collected in 2015 from 1648 students in 16 primary and middle schools in four mega-cities in China (4 schools/city): Beijing, Shanghai, Nanjing, and Xi'an. Cluster robust negative binomial regression models were fit to assess family correlates of pocket money, associations of pocket money with child eating behaviors and weight outcomes, and possible modifying effects of schools' unhealthy food restrictions. Sixty-nine percent of students received pocket money weekly. Students received more pocket money if mothers frequently ate out of home (IRR=2.28 [1.76, 2.94]) and/or family rarely had dinner together (IRR=1.42, 95%=[1.01, 1.99]). Students got less pocket money if parents were concerned about child's future health due to unhealthy eating (IRR=0.56 [0.32,0.98]). Students with more pocket money more frequently consumed (by 25-89%) sugary beverages, snacks, fast food, or at street food stalls, and were 45-90% more likely to be overweight/obese. Associations of pocket money with unhealthy eating and overweight/obesity were weaker in schools with unhealthy food restrictions. Pocket money is a risk factor for unhealthy eating and obesity in urban China. School policies may buffer pocket money's negative influence on students' eating and weight status. Copyright © 2017. Published by Elsevier Inc.

  20. Increased Rate of Hospitalization for Diabetes and Residential Proximity of Hazardous Waste Sites

    PubMed Central

    Kouznetsova, Maria; Huang, Xiaoyu; Ma, Jing; Lessner, Lawrence; Carpenter, David O.

    2007-01-01

    Background Epidemiologic studies suggest that there may be an association between environmental exposure to persistent organic pollutants (POPs) and diabetes. Objective The aim of this study was to test the hypothesis that residential proximity to POP-contaminated waste sites result in increased rates of hospitalization for diabetes. Methods We determined the number of hospitalized patients 25–74 years of age diagnosed with diabetes in New York State exclusive of New York City for the years 1993–2000. Descriptive statistics and negative binomial regression were used to compare diabetes hospitalization rates in individuals who resided in ZIP codes containing or abutting hazardous waste sites containing POPs (“POP” sites); ZIP codes containing hazardous waste sites but with wastes other than POPs (“other” sites); and ZIP codes without any identified hazardous waste sites (“clean” sites). Results Compared with the hospitalization rates for diabetes in clean sites, the rate ratios for diabetes discharges for people residing in POP sites and “other” sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32] and 1.25 (95% CI, 1.16–1.34), respectively. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites. Conclusions After controlling for major confounders, we found a statistically significant increase in the rate of hospitalization for diabetes among the population residing in the ZIP codes containing toxic waste sites. PMID:17366823

  1. Lossless compression techniques for maskless lithography data

    NASA Astrophysics Data System (ADS)

    Dai, Vito; Zakhor, Avideh

    2002-07-01

    Future lithography systems must produce more dense chips with smaller feature sizes, while maintaining the throughput of one wafer per sixty seconds per layer achieved by today's optical lithography systems. To achieve this throughput with a direct-write maskless lithography system, using 25 nm pixels for 50 nm feature sizes, requires data rates of about 10 Tb/s. In a previous paper, we presented an architecture which achieves this data rate contingent on consistent 25 to 1 compression of lithography data, and on implementation of a decoder-writer chip with a real-time decompressor fabricated on the same chip as the massively parallel array of lithography writers. In this paper, we examine the compression efficiency of a spectrum of techniques suitable for lithography data, including two industry standards JBIG and JPEG-LS, a wavelet based technique SPIHT, general file compression techniques ZIP and BZIP2, our own 2D-LZ technique, and a simple list-of-rectangles representation RECT. Layouts rasterized both to black-and-white pixels, and to 32 level gray pixels are considered. Based on compression efficiency, JBIG, ZIP, 2D-LZ, and BZIP2 are found to be strong candidates for application to maskless lithography data, in many cases far exceeding the required compression ratio of 25. To demonstrate the feasibility of implementing the decoder-writer chip, we consider the design of a hardware decoder based on ZIP, the simplest of the four candidate techniques. The basic algorithm behind ZIP compression is Lempel-Ziv 1977 (LZ77), and the design parameters of LZ77 decompression are optimized to minimize circuit usage while maintaining compression efficiency.

  2. Neighborhood walkability and active travel (walking and cycling) in New York City.

    PubMed

    Freeman, Lance; Neckerman, Kathryn; Schwartz-Soicher, Ofira; Quinn, James; Richards, Catherine; Bader, Michael D M; Lovasi, Gina; Jack, Darby; Weiss, Christopher; Konty, Kevin; Arno, Peter; Viola, Deborah; Kerker, Bonnie; Rundle, Andrew G

    2013-08-01

    Urban planners have suggested that built environment characteristics can support active travel (walking and cycling) and reduce sedentary behavior. This study assessed whether engagement in active travel is associated with neighborhood walkability measured for zip codes in New York City. Data were analyzed on engagement in active travel and the frequency of walking or biking ten blocks or more in the past month, from 8,064 respondents to the New York City 2003 Community Health Survey (CHS). A neighborhood walkability scale that measures: residential, intersection, and subway stop density; land use mix; and the ratio of retail building floor area to retail land area was calculated for each zip code. Data were analyzed using zero-inflated negative binomial regression incorporating survey sample weights and adjusting for respondents' sociodemographic characteristics. Overall, 44 % of respondents reported no episodes of active travel and among those who reported any episode, the mean number was 43.2 episodes per month. Comparing the 75th to the 25th percentile of zip code walkability, the odds ratio for reporting zero episodes of active travel was 0.71 (95 % CI 0.61, 0.83) and the exponentiated beta coefficient for the count of episodes of active travel was 1.13 (95 % CI 1.06, 1.21). Associations between lower walkability and reporting zero episodes of active travel were significantly stronger for non-Hispanic Whites as compared to non-Hispanic Blacks and to Hispanics and for those living in higher income zip codes. The results suggest that neighborhood walkability is associated with higher engagement in active travel.

  3. Need for and Access to Supportive Services in the Child Welfare System

    PubMed Central

    Freisthler, Bridget

    2011-01-01

    Objective The purpose of this paper is to examine how geographical availability of social services is related to foster care entry rates and referrals for child maltreatment investigations. The primary concerns are to (1) determine locations across Los Angeles County where the availability of social services is low but display a high need for those services and (2) begin to examine how the geographic distribution of social services is related to rates of referrals and foster care entries in child maltreatment. Methods Archival data for all 288 zip codes within Los Angeles County were collected on rates of referrals, foster care entries, location and types of social service agencies, and zip code demographics. Data were analyzed using point process models and spatial regressions. Results Higher densities of child welfare services in local areas (for referrals) and lagged areas (for referrals and foster care entries) were related to lower rates of child maltreatment. The density of housing and housing-related services was negatively related to referrals in local areas and foster care entry rates in lagged areas. Areas with higher densities of substance abuse and domestic violence service agencies had significantly higher rates of both Child Protective Services (CPS) referrals and entries into foster care in local areas. Conclusions While the total density of child welfare services within and surrounding zip code areas is related to lower rates of referrals and foster care entries, the findings are less clear about what those specific services are. Living in and around “resource rich” zip codes may reduce rates of child maltreatment. PMID:23788827

  4. Structure-function analysis of HKE4, a member of the new LIV-1 subfamily of zinc transporters.

    PubMed Central

    Taylor, Kathryn M; Morgan, Helen E; Johnson, Andrea; Nicholson, Robert I

    2004-01-01

    The KE4 proteins are an emerging group of proteins with little known functional data. In the present study, we report the first characterization of the recombinant human KE4 protein in mammalian cells. The KE4 sequences are included in the subfamily of ZIP (Zrt-, Irt-like Proteins) zinc transporters, which we have termed LZT (LIV-1 subfamily of ZIP zinc Transporters). All these LZT sequences contain similarities to ZIP transporters, including the consensus sequence in transmembrane domain IV, which is essential for zinc transport. However, the new LZT subfamily can be separated from other ZIP transporters by the presence of a highly conserved potential metalloprotease motif (HEXPHEXGD) in transmembrane domain V. Here we report the location of HKE4 on intracellular membranes, including the endoplasmic reticulum, and its ability to increase the intracellular free zinc as measured with the zinc-specific fluorescent dye, Newport Green, in a time-, temperature- and concentration-dependent manner. This is in contrast with the zinc influx ability of another LZT protein, LIV-1, which was due to its plasma membrane location. Therefore we have added to the functionality of LZT proteins by reporting their ability to increase intracellular-free zinc, whether they are located on the plasma membrane or on intracellular membranes. This result, in combination with the crucial role that zinc plays in cell growth, emphasizes the importance of this new LZT subfamily, including the KE4 sequences, in the control of intracellular zinc homoeostasis, aberrations of which can lead to diseases such as cancer, immunological disorders and neurological dysfunction. PMID:14525538

  5. The impacts of marijuana dispensary density and neighborhood ecology on marijuana abuse and dependence

    PubMed Central

    Mair, Christina; Freisthler, Bridget; Ponicki, William R.; Gaidus, Andrew

    2015-01-01

    Background As an increasing number of states liberalize cannabis use and develop laws and local policies, it is essential to better understand the impacts of neighborhood ecology and marijuana dispensary density on marijuana use, abuse, and dependence. We investigated associations between marijuana abuse/dependence hospitalizations and community demographic and environmental conditions from 2001–2012 in California, as well as cross-sectional associations between local and adjacent marijuana dispensary densities and marijuana hospitalizations. Methods We analyzed panel population data relating hospitalizations coded for marijuana abuse or dependence and assigned to residential ZIP codes in California from 2001 through 2012 (20,219 space-time units) to ZIP code demographic and ecological characteristics. Bayesian space-time misalignment models were used to account for spatial variations in geographic unit definitions over time, while also accounting for spatial autocorrelation using conditional autoregressive priors. We also analyzed cross-sectional associations between marijuana abuse/dependence and the density of dispensaries in local and spatially adjacent ZIP codes in 2012. Results An additional one dispensary per square mile in a ZIP code was cross-sectionally associated with a 6.8% increase in the number of marijuana hospitalizations (95% credible interval 1.033, 1.105) with a marijuana abuse/dependence code. Other local characteristics, such as the median household income and age and racial/ethnic distributions, were associated with marijuana hospitalizations in cross-sectional and panel analyses. Conclusions Prevention and intervention programs for marijuana abuse and dependence may be particularly essential in areas of concentrated disadvantage. Policy makers may want to consider regulations that limit the density of dispensaries. PMID:26154479

  6. Practice Location Characteristics of Non-Traditional Dental Practices.

    PubMed

    Solomon, Eric S; Jones, Daniel L

    2016-04-01

    Current and future dental school graduates are increasingly likely to choose a non-traditional dental practice-a group practice managed by a dental service organization or a corporate practice with employed dentists-for their initial practice experience. In addition, the growth of non-traditional practices, which are located primarily in major urban areas, could accelerate the movement of dentists to those areas and contribute to geographic disparities in the distribution of dental services. To help the profession understand the implications of these developments, the aim of this study was to compare the location characteristics of non-traditional practices and traditional dental practices. After identifying non-traditional practices across the United States, the authors located those practices and traditional dental practices geographically by zip code. Non-traditional dental practices were found to represent about 3.1% of all dental practices, but they had a greater impact on the marketplace with almost twice the average number of staff and annual revenue. Virtually all non-traditional dental practices were located in zip codes that also had a traditional dental practice. Zip codes with non-traditional practices had significant differences from zip codes with only a traditional dental practice: the populations in areas with non-traditional practices had higher income levels and higher education and were slightly younger and proportionally more Hispanic; those practices also had a much higher likelihood of being located in a major metropolitan area. Dental educators and leaders need to understand the impact of these trends in the practice environment in order to both prepare graduates for practice and make decisions about planning for the workforce of the future.

  7. Association between Residential Proximity to Fuel-Fired Power Plants and Hospitalization Rate for Respiratory Diseases

    PubMed Central

    Liu, Xiaopeng; Lessner, Lawrence

    2012-01-01

    Background: Air pollution is known to cause respiratory disease. Unlike motor vehicle sources, fuel-fired power plants are stationary. Objective: Using hospitalization data, we examined whether living near a fuel-fired power plant increases the likelihood of hospitalization for respiratory disease. Methods: Rates of hospitalization for asthma, acute respiratory infection (ARI), and chronic obstructive pulmonary disease (COPD) were estimated using hospitalization data for 1993–2008 from New York State in relation to data for residences near fuel-fired power plants. We also explored data for residential proximity to hazardous waste sites. Results: After adjusting for age, sex, race, median household income, and rural/urban residence, there were significant 11%, 15%, and 17% increases in estimated rates of hospitalization for asthma, ARI, and COPD, respectively, among individuals > 10 years of age living in a ZIP code containing a fuel-fired power plant compared with one that had no power plant. Living in a ZIP code with a fuel-fired power plant was not significantly associated with hospitalization for asthma or ARI among children < 10 years of age. Living in a ZIP code with a hazardous waste site was associated with hospitalization for all outcomes in both age groups, and joint effect estimates were approximately additive for living in a ZIP code that contained a fuel-fired power plant and a hazardous waste site. Conclusions: Our results are consistent with the hypothesis that exposure to air pollution from fuel-fired power plants and volatile compounds coming from hazardous waste sites increases the risk of hospitalization for respiratory diseases. PMID:22370087

  8. Programs and Place: Risk and Asset Mapping for Fall Prevention

    PubMed Central

    Smith, Matthew Lee; Towne, Samuel D.; Motlagh, Audry S.; Smith, Donald R.; Boolani, Ali; Horel, Scott A.; Ory, Marcia G.

    2017-01-01

    Identifying ways to measure access, availability, and utilization of health-care services, relative to at-risk areas or populations, is critical in providing practical and actionable information to key stakeholders. This study identified the prevalence and geospatial distribution of fall-related emergency medical services (EMS) calls in relation to the delivery of an evidence-based fall prevention program in Tarrant County, Texas over a 3-year time period. It aims to educate public health professionals and EMS first respondents about the application of geographic information system programs to identify risk-related “hot spots,” service gaps, and community assets to reduce falls among older adults. On average, 96.09 (±108.65) calls were received per ZIP Code (ranging from 0 calls to 386 calls). On average, EMS calls per ZIP Code increased from 30.80 (±34.70) calls in 2009 to 33.75 (±39.58) calls in 2011, which indicate a modest annual call increase over the 3-year study period. The percent of ZIP Codes offering A Matter of Balance/Volunteer Lay Leader Model (AMOB/VLL) workshops increased from 27.3% in 2009 to 34.5% in 2011. On average, AMOB/VLL workshops were offered in ZIP Codes with more fall-related EMS calls over the 3-year study period. Findings suggest that the study community was providing evidence-based fall prevention programming (AMOB/VLL workshops) in higher-risk areas. Opportunities for strategic service expansion were revealed through the identification of fall-related hot spots and asset mapping. PMID:28361049

  9. The bZIP repressor proteins, c-Jun dimerization protein 2 and activating transcription factor 3, recruit multiple HDAC members to the ATF3 promoter.

    PubMed

    Darlyuk-Saadon, Ilona; Weidenfeld-Baranboim, Keren; Yokoyama, Kazunari K; Hai, Tsonwin; Aronheim, Ami

    2012-01-01

    JDP2, is a basic leucine zipper (bZIP) protein displaying a high degree of homology with the stress inducible transcription factor, ATF3. Both proteins bind to cAMP and TPA response elements and repress transcription by multiple mechanisms. Histone deacetylases (HDACs) play a key role in gene inactivation by deacetylating lysine residues on histones. Here we describe the association of JDP2 and ATF3 with HDACs 1, 2-6 and 10. Association of HDAC3 and HDAC6 with JDP2 and ATF3 occurs via direct protein-protein interactions. Only part of the N-terminal bZIP motif of JDP2 and ATF3 basic domain is necessary and sufficient for the interaction with HDACs in a manner that is independent of coiled-coil dimerization. Class I HDACs associate with the bZIP repressors via the DAC conserved domain whereas the Class IIb HDAC6 associates through its C-terminal unique binder of ubiquitin Zn finger domain. Both JDP2 and ATF3 are known to bind and repress the ATF3 promoter. MEF cells treated with histone deacetylase inhibitor, trichostatin A (TSA) display enhanced ATF3 transcription. ATF3 enhanced transcription is significantly reduced in MEF cells lacking both ATF3 and JDP2. Collectively, we propose that the recruitment of multiple HDAC members to JDP2 and ATF3 is part of their transcription repression mechanism. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Zinc Fortification Decreases ZIP1 Gene Expression of Some Adolescent Females with Appropriate Plasma Zinc Levels

    PubMed Central

    Méndez, Rosa O.; Santiago, Alejandra; Yepiz-Plascencia, Gloria; Peregrino-Uriarte, Alma B.; de la Barca, Ana M. Calderón; García, Hugo S.

    2014-01-01

    Zinc homeostasis is achieved after intake variation by changes in the expression levels of zinc transporters. The aim of this study was to evaluate dietary intake (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24 adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc intake increased (p < 0.001) from 10.5 ± 3.9 mg/day to 17.6 ± 4.4 mg/day, and its estimated absorption from 3.1 ± 1.2 to 5.3 ± 1.3 mg/day. Mean plasma zinc concentration remained unchanged (p > 0.05) near 150 µg/dL, but increased by 31 µg/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 µg/dL (p < 0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression of ZnT1 there was no difference after intervention (p = 0.39). An increase of dietary zinc after 27-days consumption of fortified-milk did not increase (p > 0.05) the plasma level of adolescent girls but for 6/24 participants from group A in spite of the formerly appropriation, which cellular zinc uptake decreased as assessed by reduction of the expression of ZIP1. PMID:24922175

  11. Unconventional Gas and Oil Drilling Is Associated with Increased Hospital Utilization Rates

    PubMed Central

    Neidell, Matthew; Chillrud, Steven; Yan, Beizhan; Stute, Martin; Howarth, Marilyn; Saberi, Pouné; Fausti, Nicholas; Penning, Trevor M.; Roy, Jason; Propert, Kathleen J.; Panettieri, Reynold A.

    2015-01-01

    Over the past ten years, unconventional gas and oil drilling (UGOD) has markedly expanded in the United States. Despite substantial increases in well drilling, the health consequences of UGOD toxicant exposure remain unclear. This study examines an association between wells and healthcare use by zip code from 2007 to 2011 in Pennsylvania. Inpatient discharge databases from the Pennsylvania Healthcare Cost Containment Council were correlated with active wells by zip code in three counties in Pennsylvania. For overall inpatient prevalence rates and 25 specific medical categories, the association of inpatient prevalence rates with number of wells per zip code and, separately, with wells per km2 (separated into quantiles and defined as well density) were estimated using fixed-effects Poisson models. To account for multiple comparisons, a Bonferroni correction with associations of p<0.00096 was considered statistically significant. Cardiology inpatient prevalence rates were significantly associated with number of wells per zip code (p<0.00096) and wells per km2 (p<0.00096) while neurology inpatient prevalence rates were significantly associated with wells per km2 (p<0.00096). Furthermore, evidence also supported an association between well density and inpatient prevalence rates for the medical categories of dermatology, neurology, oncology, and urology. These data suggest that UGOD wells, which dramatically increased in the past decade, were associated with increased inpatient prevalence rates within specific medical categories in Pennsylvania. Further studies are necessary to address healthcare costs of UGOD and determine whether specific toxicants or combinations are associated with organ-specific responses. PMID:26176544

  12. Comparison of Deterministic and Probabilistic Radial Distribution Systems Load Flow

    NASA Astrophysics Data System (ADS)

    Gupta, Atma Ram; Kumar, Ashwani

    2017-12-01

    Distribution system network today is facing the challenge of meeting increased load demands from the industrial, commercial and residential sectors. The pattern of load is highly dependent on consumer behavior and temporal factors such as season of the year, day of the week or time of the day. For deterministic radial distribution load flow studies load is taken as constant. But, load varies continually with a high degree of uncertainty. So, there is a need to model probable realistic load. Monte-Carlo Simulation is used to model the probable realistic load by generating random values of active and reactive power load from the mean and standard deviation of the load and for solving a Deterministic Radial Load Flow with these values. The probabilistic solution is reconstructed from deterministic data obtained for each simulation. The main contribution of the work is: Finding impact of probable realistic ZIP load modeling on balanced radial distribution load flow. Finding impact of probable realistic ZIP load modeling on unbalanced radial distribution load flow. Compare the voltage profile and losses with probable realistic ZIP load modeling for balanced and unbalanced radial distribution load flow.

  13. Isolation and functional characterisation of two new bZIP maize regulators of the ABA responsive gene rab28.

    PubMed

    Nieva, Claudia; Busk, Peter K; Domínguez-Puigjaner, Eva; Lumbreras, Victoria; Testillano, Pilar S; Risueño, Maria-Carmen; Pagès, Montserrat

    2005-08-01

    The plant hormone abscisic acid regulates gene expression in response to growth stimuli and abiotic stress. Previous studies have implicated members of the bZIP family of transcription factors as mediators of abscisic acid dependent gene expression through the ABRE cis-element. Here, we identify two new maize bZIP transcription factors, EmBP-2 and ZmBZ-1 related to EmBP-1 and OsBZ-8 families. They are differentially expressed during embryo development; EmBP-2 is constitutive, whereas ZmBZ-1 is abscisic acid-inducible and accumulates during late embryogenesis. Both factors are nuclear proteins that bind to ABREs and activate transcription of the abscisic acid-inducible gene rab28 from maize. EmBP-2 and ZmBZ-1 are phosphorylated by protein kinase CK2 and phosphorylation alters their DNA binding properties. Our data suggest that EmBP-2 and ZmBZ-1 are involved in the expression of abscisic acid inducible genes such as rab28 and their activity is modulated by ABA and by phosphorylation.

  14. An Augmented Pocketome: Detection and Analysis of Small-Molecule Binding Pockets in Proteins of Known 3D Structure.

    PubMed

    Bhagavat, Raghu; Sankar, Santhosh; Srinivasan, Narayanaswamy; Chandra, Nagasuma

    2018-03-06

    Protein-ligand interactions form the basis of most cellular events. Identifying ligand binding pockets in proteins will greatly facilitate rationalizing and predicting protein function. Ligand binding sites are unknown for many proteins of known three-dimensional (3D) structure, creating a gap in our understanding of protein structure-function relationships. To bridge this gap, we detect pockets in proteins of known 3D structures, using computational techniques. This augmented pocketome (PocketDB) consists of 249,096 pockets, which is about seven times larger than what is currently known. We deduce possible ligand associations for about 46% of the newly identified pockets. The augmented pocketome, when subjected to clustering based on similarities among pockets, yielded 2,161 site types, which are associated with 1,037 ligand types, together providing fold-site-type-ligand-type associations. The PocketDB resource facilitates a structure-based function annotation, delineation of the structural basis of ligand recognition, and provides functional clues for domains of unknown functions, allosteric proteins, and druggable pockets. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Economics of Malignant Gliomas: A Critical Review

    PubMed Central

    Raizer, Jeffrey J.; Fitzner, Karen A.; Jacobs, Daniel I.; Bennett, Charles L.; Liebling, Dustin B.; Luu, Thanh Ha; Trifilio, Steven M.; Grimm, Sean A.; Fisher, Matthew J.; Haleem, Meraaj S.; Ray, Paul S.; McKoy, Judith M.; DeBoer, Rebecca; Tulas, Katrina-Marie E.; Deeb, Mohammed; McKoy, June M.

    2015-01-01

    Purpose: Approximately 18,500 persons are diagnosed with malignant glioma in the United States annually. Few studies have investigated the comprehensive economic costs. We reviewed the literature to examine costs to patients with malignant glioma and their families, payers, and society. Methods: A total of 18 fully extracted studies were included. Data were collected on direct and indirect costs, and cost estimates were converted to US dollars using the conversion rate calculated from the study's publication date, and updated to 2011 values after adjustment for inflation. A standardized data abstraction form was used. Data were extracted by one reviewer and checked by another. Results: Before approval of effective chemotherapeutic agents for malignant gliomas, estimated total direct medical costs in the United States for surgery and radiation therapy per patient ranged from $50,600 to $92,700. The addition of temozolomide (TMZ) and bevacizumab to glioblastoma treatment regimens has resulted in increased overall costs for glioma care. Although health care costs are now less front-loaded, they have increased over the course of illness. Analysis using a willingness-to-pay threshold of $50,000 per quality-adjusted life-year suggests that the benefits of TMZ fall on the edge of acceptable therapies. Furthermore, indirect medical costs, such as productivity losses, are not trivial. Conclusion: With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve. Larger out-of-pocket costs may influence the choice of chemotherapeutic agents, the economic implications of which should be evaluated prospectively. PMID:25466707

  16. Economics of Malignant Gliomas: A Critical Review.

    PubMed

    Raizer, Jeffrey J; Fitzner, Karen A; Jacobs, Daniel I; Bennett, Charles L; Liebling, Dustin B; Luu, Thanh Ha; Trifilio, Steven M; Grimm, Sean A; Fisher, Matthew J; Haleem, Meraaj S; Ray, Paul S; McKoy, Judith M; DeBoer, Rebecca; Tulas, Katrina-Marie E; Deeb, Mohammed; McKoy, June M

    2015-01-01

    Approximately 18,500 persons are diagnosed with malignant glioma in the United States annually. Few studies have investigated the comprehensive economic costs. We reviewed the literature to examine costs to patients with malignant glioma and their families, payers, and society. A total of 18 fully extracted studies were included. Data were collected on direct and indirect costs, and cost estimates were converted to US dollars using the conversion rate calculated from the study's publication date, and updated to 2011 values after adjustment for inflation. A standardized data abstraction form was used. Data were extracted by one reviewer and checked by another. Before approval of effective chemotherapeutic agents for malignant gliomas, estimated total direct medical costs in the United States for surgery and radiation therapy per patient ranged from $50,600 to $92,700. The addition of temozolomide (TMZ) and bevacizumab to glioblastoma treatment regimens has resulted in increased overall costs for glioma care. Although health care costs are now less front-loaded, they have increased over the course of illness. Analysis using a willingness-to-pay threshold of $50,000 per quality-adjusted life-year suggests that the benefits of TMZ fall on the edge of acceptable therapies. Furthermore, indirect medical costs, such as productivity losses, are not trivial. With increased chemotherapy use for malignant glioma, the paradigm for treatment and associated out-of-pocket and total medical costs continue to evolve. Larger out-of-pocket costs may influence the choice of chemotherapeutic agents, the economic implications of which should be evaluated prospectively. Copyright © 2015 by American Society of Clinical Oncology.

  17. Investigation of Super*Zip separation joint

    NASA Technical Reports Server (NTRS)

    Bement, Laurence J.; Schimmel, Morry L.

    1988-01-01

    An investigation to determine the most likely cause of two failures of five tests on 79 inch diameter Lockheed Super*Zip spacecraft separation joints being used for the development of a Shuttle/Centaur propulsion system. This joint utilizes an explosively expanded tube to fracture surrounding prenotched aluminum plates to achieve planar separation. A test method was developed and more than 300 tests firings were made to provide an understanding of severance mechanisms and the functional performance effects of system variables. An approach for defining functional margin was developed, and specific recommendations were made for improving existing and future systems.

  18. Visualizing electron pockets in cuprate superconductors

    NASA Astrophysics Data System (ADS)

    Das, Tanmoy; Markiewicz, R. S.; Bansil, A.; Balatsky, A. V.

    2012-06-01

    Fingerprints of the electron pocket in cuprates have been obtained only in numerous magnetotransport measurements, but its absence in spectroscopic observations poses a long-standing mystery. We develop a theoretical tool to provide ways to detect electron pockets via spectroscopies including scanning tunneling microscopy (STM) spectra, inelastic neutron scattering (INS), and angle-resolved photoemission spectroscopy (ARPES). We show that the quasiparticle-interference (QPI) pattern, measured by STM, shows an additional seven q vectors associated with the scattering on the electron pocket than that on the hole pocket. Furthermore, the Bogolyubov quasiparticle scatterings of the electron pocket lead to a second magnetic resonance mode in the INS spectra at a higher resonance energy. Finally, we reanalyze some STM, INS, and ARPES experimental data of several cuprates which dictates the direct fingerprints of electron pockets in these systems.

  19. Visualisation of variable binding pockets on protein surfaces by probabilistic analysis of related structure sets.

    PubMed

    Ashford, Paul; Moss, David S; Alex, Alexander; Yeap, Siew K; Povia, Alice; Nobeli, Irene; Williams, Mark A

    2012-03-14

    Protein structures provide a valuable resource for rational drug design. For a protein with no known ligand, computational tools can predict surface pockets that are of suitable size and shape to accommodate a complementary small-molecule drug. However, pocket prediction against single static structures may miss features of pockets that arise from proteins' dynamic behaviour. In particular, ligand-binding conformations can be observed as transiently populated states of the apo protein, so it is possible to gain insight into ligand-bound forms by considering conformational variation in apo proteins. This variation can be explored by considering sets of related structures: computationally generated conformers, solution NMR ensembles, multiple crystal structures, homologues or homology models. It is non-trivial to compare pockets, either from different programs or across sets of structures. For a single structure, difficulties arise in defining particular pocket's boundaries. For a set of conformationally distinct structures the challenge is how to make reasonable comparisons between them given that a perfect structural alignment is not possible. We have developed a computational method, Provar, that provides a consistent representation of predicted binding pockets across sets of related protein structures. The outputs are probabilities that each atom or residue of the protein borders a predicted pocket. These probabilities can be readily visualised on a protein using existing molecular graphics software. We show how Provar simplifies comparison of the outputs of different pocket prediction algorithms, of pockets across multiple simulated conformations and between homologous structures. We demonstrate the benefits of use of multiple structures for protein-ligand and protein-protein interface analysis on a set of complexes and consider three case studies in detail: i) analysis of a kinase superfamily highlights the conserved occurrence of surface pockets at the active and regulatory sites; ii) a simulated ensemble of unliganded Bcl2 structures reveals extensions of a known ligand-binding pocket not apparent in the apo crystal structure; iii) visualisations of interleukin-2 and its homologues highlight conserved pockets at the known receptor interfaces and regions whose conformation is known to change on inhibitor binding. Through post-processing of the output of a variety of pocket prediction software, Provar provides a flexible approach to the analysis and visualization of the persistence or variability of pockets in sets of related protein structures.

  20. 24 CFR 570.466 - Additional application submission requirements for Pockets of Poverty-employment opportunities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... requirements for Pockets of Poverty-employment opportunities. 570.466 Section 570.466 Housing and Urban... application submission requirements for Pockets of Poverty—employment opportunities. Applicants for Action Grants under the Pockets of Poverty provision must describe the number and, to the extent possible, the...

  1. 24 CFR 570.466 - Additional application submission requirements for Pockets of Poverty-employment opportunities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... requirements for Pockets of Poverty-employment opportunities. 570.466 Section 570.466 Housing and Urban... application submission requirements for Pockets of Poverty—employment opportunities. Applicants for Action Grants under the Pockets of Poverty provision must describe the number and, to the extent possible, the...

  2. 24 CFR 570.466 - Additional application submission requirements for Pockets of Poverty-employment opportunities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... requirements for Pockets of Poverty-employment opportunities. 570.466 Section 570.466 Housing and Urban... application submission requirements for Pockets of Poverty—employment opportunities. Applicants for Action Grants under the Pockets of Poverty provision must describe the number and, to the extent possible, the...

  3. 24 CFR 570.466 - Additional application submission requirements for Pockets of Poverty-employment opportunities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... requirements for Pockets of Poverty-employment opportunities. 570.466 Section 570.466 Housing and Urban... application submission requirements for Pockets of Poverty—employment opportunities. Applicants for Action Grants under the Pockets of Poverty provision must describe the number and, to the extent possible, the...

  4. 24 CFR 570.466 - Additional application submission requirements for Pockets of Poverty-employment opportunities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements for Pockets of Poverty-employment opportunities. 570.466 Section 570.466 Housing and Urban... application submission requirements for Pockets of Poverty—employment opportunities. Applicants for Action Grants under the Pockets of Poverty provision must describe the number and, to the extent possible, the...

  5. The Association Between Neighborhood Poverty and HIV Diagnoses Among Males and Females in New York City, 2010-2011.

    PubMed

    Wiewel, Ellen W; Bocour, Angelica; Kersanske, Laura S; Bodach, Sara D; Xia, Qiang; Braunstein, Sarah L

    2016-01-01

    We assessed the association of neighborhood poverty with HIV diagnosis rates for males and females in New York City. We calculated annual HIV diagnosis rates by ZIP Code, sex, and neighborhood poverty level using 2010-2011 New York City (NYC) HIV surveillance data and data from the U.S. Census 2010 and American Community Survey 2007-2011. Neighborhood poverty levels were percentage of residents in a ZIP Code with incomes below the federal poverty threshold, categorized as 0%-<10% (low poverty), 10%-<20% (medium poverty), 20%-<30% (high poverty), and 30%-100% (very high poverty). We used sex-stratified negative binomial regression models to measure the association between neighborhood-level poverty and HIV diagnosis rates, controlling for neighborhood-level education, race/ethnicity, age, and percentage of men who have sex with men. In 2010-2011, 6,184 people were newly diagnosed with HIV. Median diagnosis rates per 100,000 population increased by neighborhood poverty level overall (13.7, 34.3, 50.6, and 75.6 for low-, medium-, high-, and very high-poverty ZIP Codes, respectively), for males, and for females. In regression models, higher neighborhood poverty remained associated with higher diagnosis rates among males (adjusted rate ratio [ARR] = 1.63, 95% confidence interval [CI] 1.34, 1.97) and females (ARR=2.14, 95% CI 1.46, 3.14) for very high- vs. low-poverty ZIP Codes. Living in very high- vs. low-poverty urban neighborhoods was associated with increased HIV diagnosis rates. After controlling for other factors, the association between poverty and diagnosis rates was stronger among females than among males. Alleviating poverty may help decrease HIV-related disparities.

  6. The price may not be right: the value of comparison shopping for prescription drugs.

    PubMed

    Arora, Sanjay; Sood, Neeraj; Terp, Sophie; Joyce, Geoffrey

    2017-07-01

    To measure variations in drug prices across and within zip codes that may reveal simple strategies to improve patients' access to prescribed medications. We compared drug prices at different types of pharmacies across and within local markets. In-store prices were compared with a Web-based service providing discount coupons for prescription medications. Prices were collected for 2 generic antibiotics because most patients have limited experience with them and are less likely to know the price ranges for them. Drug prices were obtained via telephone from 528 pharmacies in Los Angeles (LA) County, California, from July to August 2014. Online prices were collected from GoodRx, a popular Web-based service that aggregates available discounts and directly negotiates with retail outlets. Drug prices found at independent pharmacies and by using discount coupons available online were lower on average than at grocery, big-box, or chain drug stores for 2 widely prescribed antibiotics. The lowest-price prescription was offered at a grocery, big-box, or chain drug store in 6% of zip codes within the LA County area. Drug prices varied dramatically within a zip code, however, and were less expensive in lower-income areas. The average price difference within a zip code was $52 for levofloxacin and $17 for azithromycin. Price shopping for medications within a small geographic area can yield considerable cost savings for the uninsured and consumers in high-deductible health plans with high negotiated prices. Clinicians and patient advocates have an incentive to convey this information to patients to improve adherence to prescribed medicines and lower the financial burden of purchasing prescription drugs.

  7. Impact of Medicaid disenrollment in Tennessee on breast cancer stage at diagnosis and treatment.

    PubMed

    Tarazi, Wafa W; Bradley, Cathy J; Bear, Harry D; Harless, David W; Sabik, Lindsay M

    2017-09-01

    States routinely may consider rollbacks of Medicaid expansions to address statewide economic conditions. To the authors' knowledge, little is known regarding the effects of public insurance contractions on health outcomes. The current study examined the effects of the 2005 Medicaid disenrollment in Tennessee on breast cancer stage at the time of diagnosis and delays in treatment among nonelderly women. The authors used Tennessee Cancer Registry data from 2002 through 2008 and estimated a difference-in-difference model comparing women diagnosed with breast cancer who lived in low-income zip codes (and therefore were more likely to be subject to disenrollment) with a similar group of women who lived in high-income zip codes before and after the 2005 Medicaid disenrollment. The study outcomes were changes in stage of disease at the time of diagnosis and delays in treatment of >60 days and >90 days. Overall, nonelderly women in Tennessee were diagnosed at later stages of disease and experienced more delays in treatment in the period after disenrollment. Disenrollment was found to be associated with a 3.3-percentage point increase in late stage of disease at the time of diagnosis (P = .024), a 1.9-percentage point decrease in having a delay of >60 days in surgery (P = .024), and a 1.4-percentage point decrease in having a delay of >90 days in treatment (P = .054) for women living in low-income zip codes compared with women residing in high-income zip codes. The results of the current study indicate that Medicaid disenrollment is associated with a later stage of disease at the time of breast cancer diagnosis, thereby providing evidence of the potential negative health impacts of Medicaid contractions. Cancer 2017;123:3312-9. © 2017 American Cancer Society. © 2017 American Cancer Society.

  8. Radar - 449MHz - Forks, WA (FKS) - Raw Data

    DOE Data Explorer

    Gottas, Daniel

    2018-06-25

    **Winds.** A radar wind profiler measures the Doppler shift of electromagnetic energy scattered back from atmospheric turbulence and hydrometeors along 3-5 vertical and off-vertical point beam directions. Back-scattered signal strength and radial-component velocities are remotely sensed along all beam directions and are combined to derive the horizontal wind field over the radar. These data typically are sampled and averaged hourly and usually have 6-m and/or 100-m vertical resolutions up to 4 km for the 915 MHz and 8 km for the 449 MHz systems. **Temperature.** To measure atmospheric temperature, a radio acoustic sounding system (RASS) is used in conjunction with the wind profile. These data typically are sampled and averaged for five minutes each hour and have a 60-m vertical resolution up to 1.5 km for the 915 MHz and 60 m up to 3.5 km for the 449 MHz. **Moments and Spectra.** The raw spectra and moments data are available for all dwells along each beam and are stored in daily files. For each day, there are files labeled "header" and "data." These files are generated by the radar data acquisition system (LAP-XM) and are encoded in a proprietary binary format. Values of spectral density at each Doppler velocity (FFT point), as well as the radial velocity, signal-to-noise ratio, and spectra width for the selected signal peak are included in these files. Attached zip files, *449mhz-spectra-data-extraction.zip* and *449mhz-moment-data-extraction.zip*, include executables to unpack the spectra, (GetSpectra32.exe) and moments (GetMomSp32.exe), respectively. Documentation on usage and output file formats also are included in the zip files.

  9. Radar - 449MHz - North Bend, OR (OTH) - Raw Data

    DOE Data Explorer

    Gottas, Daniel

    2018-06-25

    **Winds.** A radar wind profiler measures the Doppler shift of electromagnetic energy scattered back from atmospheric turbulence and hydrometeors along 3-5 vertical and off-vertical point beam directions. Back-scattered signal strength and radial-component velocities are remotely sensed along all beam directions and are combined to derive the horizontal wind field over the radar. These data typically are sampled and averaged hourly and usually have 6-m and/or 100-m vertical resolutions up to 4 km for the 915 MHz and 8 km for the 449 MHz systems. **Temperature.** To measure atmospheric temperature, a radio acoustic sounding system (RASS) is used in conjunction with the wind profile. These data typically are sampled and averaged for five minutes each hour and have a 60-m vertical resolution up to 1.5 km for the 915 MHz and 60 m up to 3.5 km for the 449 MHz. **Moments and Spectra.** The raw spectra and moments data are available for all dwells along each beam and are stored in daily files. For each day, there are files labeled "header" and "data." These files are generated by the radar data acquisition system (LAP-XM) and are encoded in a proprietary binary format. Values of spectral density at each Doppler velocity (FFT point), as well as the radial velocity, signal-to-noise ratio, and spectra width for the selected signal peak are included in these files. Attached zip files, *449mhz-spectra-data-extraction.zip* and *449mhz-moment-data-extraction.zip*, include executables to unpack the spectra, (GetSpectra32.exe) and moments (GetMomSp32.exe), respectively. Documentation on usage and output file formats also are included in the zip files.

  10. Radar - 449MHz - North Bend, OR (OTH) - Reviewed Data

    DOE Data Explorer

    Gottas, Daniel

    2018-06-25

    **Winds.** A radar wind profiler measures the Doppler shift of electromagnetic energy scattered back from atmospheric turbulence and hydrometeors along 3-5 vertical and off-vertical point beam directions. Back-scattered signal strength and radial-component velocities are remotely sensed along all beam directions and are combined to derive the horizontal wind field over the radar. These data typically are sampled and averaged hourly and usually have 6-m and/or 100-m vertical resolutions up to 4 km for the 915 MHz and 8 km for the 449 MHz systems. **Temperature.** To measure atmospheric temperature, a radio acoustic sounding system (RASS) is used in conjunction with the wind profile. These data typically are sampled and averaged for five minutes each hour and have a 60-m vertical resolution up to 1.5 km for the 915 MHz and 60 m up to 3.5 km for the 449 MHz. **Moments and Spectra.** The raw spectra and moments data are available for all dwells along each beam and are stored in daily files. For each day, there are files labeled "header" and "data." These files are generated by the radar data acquisition system (LAP-XM) and are encoded in a proprietary binary format. Values of spectral density at each Doppler velocity (FFT point), as well as the radial velocity, signal-to-noise ratio, and spectra width for the selected signal peak are included in these files. Attached zip files, *449mhz-spectra-data-extraction.zip* and *449mhz-moment-data-extraction.zip*, include executables to unpack the spectra, (GetSpectra32.exe) and moments (GetMomSp32.exe), respectively. Documentation on usage and output file formats also are included in the zip files.

  11. Radar - 449MHz - Forks, WA (FKS) - Reviewed Data

    DOE Data Explorer

    Gottas, Daniel

    2018-06-25

    **Winds.** A radar wind profiler measures the Doppler shift of electromagnetic energy scattered back from atmospheric turbulence and hydrometeors along 3-5 vertical and off-vertical point beam directions. Back-scattered signal strength and radial-component velocities are remotely sensed along all beam directions and are combined to derive the horizontal wind field over the radar. These data typically are sampled and averaged hourly and usually have 6-m and/or 100-m vertical resolutions up to 4 km for the 915 MHz and 8 km for the 449 MHz systems. **Temperature.** To measure atmospheric temperature, a radio acoustic sounding system (RASS) is used in conjunction with the wind profile. These data typically are sampled and averaged for five minutes each hour and have a 60-m vertical resolution up to 1.5 km for the 915 MHz and 60 m up to 3.5 km for the 449 MHz. **Moments and Spectra.** The raw spectra and moments data are available for all dwells along each beam and are stored in daily files. For each day, there are files labeled "header" and "data." These files are generated by the radar data acquisition system (LAP-XM) and are encoded in a proprietary binary format. Values of spectral density at each Doppler velocity (FFT point), as well as the radial velocity, signal-to-noise ratio, and spectra width for the selected signal peak are included in these files. Attached zip files, *449mhz-spectra-data-extraction.zip* and *449mhz-moment-data-extraction.zip*, include executables to unpack the spectra, (GetSpectra32.exe) and moments (GetMomSp32.exe), respectively. Documentation on usage and output file formats also are included in the zip files.

  12. Radar - 449MHz - Astoria, OR (AST) - Reviewed Data

    DOE Data Explorer

    Gottas, Daniel

    2018-06-25

    **Winds.** A radar wind profiler measures the Doppler shift of electromagnetic energy scattered back from atmospheric turbulence and hydrometeors along 3-5 vertical and off-vertical point beam directions. Back-scattered signal strength and radial-component velocities are remotely sensed along all beam directions and are combined to derive the horizontal wind field over the radar. These data typically are sampled and averaged hourly and usually have 6-m and/or 100-m vertical resolutions up to 4 km for the 915 MHz and 8 km for the 449 MHz systems. **Temperature.** To measure atmospheric temperature, a radio acoustic sounding system (RASS) is used in conjunction with the wind profile. These data typically are sampled and averaged for five minutes each hour and have a 60-m vertical resolution up to 1.5 km for the 915 MHz and 60 m up to 3.5 km for the 449 MHz. **Moments and Spectra.** The raw spectra and moments data are available for all dwells along each beam and are stored in daily files. For each day, there are files labeled "header" and "data." These files are generated by the radar data acquisition system (LAP-XM) and are encoded in a proprietary binary format. Values of spectral density at each Doppler velocity (FFT point), as well as the radial velocity, signal-to-noise ratio, and spectra width for the selected signal peak are included in these files. Attached zip files, *449mhz-spectra-data-extraction.zip* and *449mhz-moment-data-extraction.zip*, include executables to unpack the spectra, (GetSpectra32.exe) and moments (GetMomSp32.exe), respectively. Documentation on usage and output file formats also are included in the zip files.

  13. Radar - 449MHz - Astoria, OR (AST) - Raw Data

    DOE Data Explorer

    Gottas, Daniel

    2018-06-25

    **Winds.** A radar wind profiler measures the Doppler shift of electromagnetic energy scattered back from atmospheric turbulence and hydrometeors along 3-5 vertical and off-vertical point beam directions. Back-scattered signal strength and radial-component velocities are remotely sensed along all beam directions and are combined to derive the horizontal wind field over the radar. These data typically are sampled and averaged hourly and usually have 6-m and/or 100-m vertical resolutions up to 4 km for the 915 MHz and 8 km for the 449 MHz systems. **Temperature.** To measure atmospheric temperature, a radio acoustic sounding system (RASS) is used in conjunction with the wind profile. These data typically are sampled and averaged for five minutes each hour and have a 60-m vertical resolution up to 1.5 km for the 915 MHz and 60 m up to 3.5 km for the 449 MHz. **Moments and Spectra.** The raw spectra and moments data are available for all dwells along each beam and are stored in daily files. For each day, there are files labeled "header" and "data." These files are generated by the radar data acquisition system (LAP-XM) and are encoded in a proprietary binary format. Values of spectral density at each Doppler velocity (FFT point), as well as the radial velocity, signal-to-noise ratio, and spectra width for the selected signal peak are included in these files. Attached zip files, *449mhz-spectra-data-extraction.zip* and *449mhz-moment-data-extraction.zip*, include executables to unpack the spectra, (GetSpectra32.exe) and moments (GetMomSp32.exe), respectively. Documentation on usage and output file formats also are included in the zip files.

  14. Improving Hospital Reporting of Patient Race and Ethnicity--Approaches to Data Auditing.

    PubMed

    Zingmond, David S; Parikh, Punam; Louie, Rachel; Lichtensztajn, Daphne Y; Ponce, Ninez; Hasnain-Wynia, Romana; Gomez, Scarlett Lin

    2015-08-01

    To investigate new metrics to improve the reporting of patient race and ethnicity (R/E) by hospitals. California Patient Discharge Database (PDD) and birth registry, 2008-2009, Healthcare and Cost Utilization Project's State Inpatient Database, 2008-2011, cancer registry 2000-2008, and 2010 US Census Summary File 2. We examined agreement between hospital reported R/E versus self-report among mothers delivering babies and a cancer cohort in California. Metrics were created to measure root mean squared differences (RMSD) by hospital between reported R/E distribution and R/E estimates using R/E distribution within each patient's zip code of residence. RMSD comparisons were made to corresponding "gold standard" facility-level measures within the maternal cohort for California and six comparison states. Maternal birth hospitalization (linked to the state birth registry) and cancer cohort records linked to preceding and subsequent hospitalizations. Hospital discharges were linked to the corresponding Census zip code tabulation area using patient zip code. Overall agreement between the PDD and the gold standard for the maternal cohort was 86 percent for the combined R/E measure and 71 percent for race alone. The RMSD measure is modestly correlated with the summary level gold standard measure for R/E (r = 0.44). The RMSD metric revealed general improvement in data agreement and completeness across states. "Other" and "unknown" categories were inconsistently applied within inpatient databases. Comparison between reported R/E and R/E estimates using zip code level data may be a reasonable first approach to evaluate and track hospital R/E reporting. Further work should focus on using more granular geocoded data for estimates and tracking data to improve hospital collection of R/E data. © Health Research and Educational Trust.

  15. The impacts of marijuana dispensary density and neighborhood ecology on marijuana abuse and dependence.

    PubMed

    Mair, Christina; Freisthler, Bridget; Ponicki, William R; Gaidus, Andrew

    2015-09-01

    As an increasing number of states liberalize cannabis use and develop laws and local policies, it is essential to better understand the impacts of neighborhood ecology and marijuana dispensary density on marijuana use, abuse, and dependence. We investigated associations between marijuana abuse/dependence hospitalizations and community demographic and environmental conditions from 2001 to 2012 in California, as well as cross-sectional associations between local and adjacent marijuana dispensary densities and marijuana hospitalizations. We analyzed panel population data relating hospitalizations coded for marijuana abuse or dependence and assigned to residential ZIP codes in California from 2001 through 2012 (20,219 space-time units) to ZIP code demographic and ecological characteristics. Bayesian space-time misalignment models were used to account for spatial variations in geographic unit definitions over time, while also accounting for spatial autocorrelation using conditional autoregressive priors. We also analyzed cross-sectional associations between marijuana abuse/dependence and the density of dispensaries in local and spatially adjacent ZIP codes in 2012. An additional one dispensary per square mile in a ZIP code was cross-sectionally associated with a 6.8% increase in the number of marijuana hospitalizations (95% credible interval 1.033, 1.105) with a marijuana abuse/dependence code. Other local characteristics, such as the median household income and age and racial/ethnic distributions, were associated with marijuana hospitalizations in cross-sectional and panel analyses. Prevention and intervention programs for marijuana abuse and dependence may be particularly essential in areas of concentrated disadvantage. Policy makers may want to consider regulations that limit the density of dispensaries. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Waterborne Zn influenced Zn uptake and lipid metabolism in two intestinal regions of juvenile goby Synechogobius hasta.

    PubMed

    Ling, Shi-Cheng; Luo, Zhi; Chen, Guang-Hui; Zhang, Dian-Guang; Liu, Xu

    2018-02-01

    The present study explored the influence of Zn addition in the water on Zn transport and lipid metabolism of two intestinal regions in goby Synechogobius hasta. Zn contents in water were 0.004 (control), 0.181 and 0.361mg Zn L -1 , respectively. The experiment lasted for 28 days. TG and Zn contents, mRNA contents of genes of Zn transport and lipid metabolism, and enzyme activity from anterior and mid-intestine tissues were analyzed. In anterior intestine, Zn addition in the water increased Zn contents, and mRNA concentrations of ZIP4, ZIP5, ATGL, PPARα, ZNF202 and KLF7, decreased TG contents, 6PGD and G6PD activities, and mRNA contents of 6PGD, G6PD, FAS, PPARγ, ICDH and KLF4. In mid-intestine tissue, the highest Zn and TG contents were observed for 0.18mg Zn/l group, in parallel with the highest expressions of ZnT1, ZIP4, ZIP5, 6PGD, FAS, ICDH, PPARγ, PPARα, ZNF202, KLF4 and KLF7, and with the highest FAS, 6PGD and G6PD activities. Thus, in the anterior intestine, Zn addition increased lipolysis and decreased lipogenesis, and accordingly reduced TG content. However, the highest mid-intestinal TG content in 0.18mg Zn/l group was due to the up-regulated lipogenesis. Although lipolysis was also increased, the incremental lipid synthesis was enough to compensate for lipid degradation, which led TG accumulation. Our results, for the first time, show an anterior/mid functional regionalization of the intestine in lipid metabolism and Zn transport of S. hasta following Zn exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Differences in prescription opioid analgesic availability: comparing minority and white pharmacies across Michigan.

    PubMed

    Green, Carmen R; Ndao-Brumblay, S Khady; West, Brady; Washington, Tamika

    2005-10-01

    Little is known about physical barriers to adequate pain treatment for minorities. This investigation explored sociodemographic determinants of pain medication availability in Michigan pharmacies. A cross-sectional survey-based study with census data and data provided by Michigan community retail pharmacists was designed. Sufficient opioid analgesic supplies was defined as stocking at least one long-acting, short-acting, and combination opioid analgesic. Pharmacies located in minority (or=70% white residents) zip code areas were randomly selected by using a 2-stage sampling selection process (response rate, 80%). For the 190 pharmacies surveyed, most were located in white areas (51.6%) and had sufficient supplies (84.1%). After accounting for zip code median age and stratifying by income, pharmacies in white areas (odds ratio, 13.36 high income vs 54.42 low income) and noncorporate pharmacies (odds ratio, 24.92 high income vs 3.61 low income) were more likely to have sufficient opioid analgesic supplies (P < .005). Racial differences in the odds of having a sufficient supply were significantly higher in low income areas when compared with high income areas. Having a pharmacy located near a hospital did not change the availability for opioid analgesics. Persons living in predominantly minority areas experienced significant barriers to accessing pain medication, with greater disparities in low income areas regardless of ethnic composition. Differences were also found on the basis of pharmacy type, suggesting variability in pharmacist's decision making. Michigan pharmacies in minority zip codes were 52 times less likely to carry sufficient opioid analgesics than pharmacies in white zip codes regardless of income. Lower income areas and corporate pharmacies were less likely to carry sufficient opioid analgesics. This study illustrates barriers to pain care and has public health implications.

  18. Poverty, Transportation Access, and Medication Nonadherence.

    PubMed

    Hensley, Caroline; Heaton, Pamela C; Kahn, Robert S; Luder, Heidi R; Frede, Stacey M; Beck, Andrew F

    2018-04-01

    Variability in primary medication nonadherence (PMN), or failure to fill a new prescription, influences disparities and widens equity gaps. This study sought to evaluate PMN across 1 metropolitan area and assess relationships with underlying zip code-level measures. This was a retrospective observational study using data extracted from 1 regional community pharmacy market-share leader (October 2016-April 2017). Data included patient age, sex, payer, medication type, and home zip code. This zip code was connected to US census measures enumerating poverty and vehicle access, which were treated as continuous variables and within quintiles. The prescription-level outcome was whether prescriptions were not filled within 30 days of reaching the pharmacy. The ecological-level outcome was PMN calculated for each zip code (numerator, unfilled prescriptions; denominator, received prescriptions). There were 213 719 prescriptions received by 54 included pharmacies; 12.2% were unfilled. Older children, boys, and those with public insurance were more likely to have prescriptions not filled. Prescriptions originating from the highest poverty quintile were significantly more likely to not be filled than those from the lowest poverty quintile (adjusted odds ratio 1.60; 95% confidence interval 1.52-1.69); a similar pattern was noted for vehicle access (adjusted odds ratio 1.77; 95% confidence interval 1.68-1.87). At the ecological level, there were significant, graded relationships between PMN rates and poverty and vehicle access (both P < .0001); these gradients extended across all medication classes. Poverty and vehicle access are related to significant differences in prescription- and ecological-level PMN across 1 metropolitan area. Pharmacists and pharmacies can be key partners in population health efforts. Copyright © 2018 by the American Academy of Pediatrics.

  19. Major zircon megacryst suites of the Indo-Pacific lithospheric margin (ZIP) and their petrogenetic and regional implications

    NASA Astrophysics Data System (ADS)

    Sutherland, Lin; Graham, Ian; Yaxley, Gregory; Armstrong, Richard; Giuliani, Gaston; Hoskin, Paul; Nechaev, Victor; Woodhead, Jon

    2016-04-01

    Zircon megacrysts (± gem corundum) appear in basalt fields of Indo-Pacific origin over a 12,000 km zone (ZIP) along West Pacific continental margins. Age-dating, trace element, oxygen and hafnium isotope studies on representative zircons (East Australia-Asia) indicate diverse magmatic sources. The U-Pb (249 to 1 Ma) and zircon fission track (ZFT) ages (65 to 1 Ma) suggest thermal annealing during later basalt transport, with < 1 to 203 Ma gaps between the U-Pb and ZFT ages. Magmatic growth zonation and Zr/Hf ratios (0.01-0.02) suggest alkaline magmatic sources, while Ti—in—zircon thermometry suggests that most zircons crystallized within ranges between 550 and 830 °C. Chondrite-normalised multi-element plots show variable enrichment patterns, mostly without marked Eu depletion, indicating little plagioclase fractionation in source melts. Key elements and ratios matched against zircons from magmatic rocks suggest a range of ultramafic to felsic source melts. Zircon O-isotope ratios (δ18O in the range 4 to 11‰) and initial Hf isotope ratios (ɛHf in the range +2 to +14) encompass ranges for both mantle and crustal melts. Calculated Depleted Mantle (TDM 0.03-0.56 Ga) and Crustal Residence (0.20-1.02 Ga) model ages suggest several mantle events, continental break-ups (Rodinia and Gondwana) and convergent margin collisions left imprints in the zircon source melts. East Australian ZIP sites reflect prolonged intraplate magmatism (~85 Ma), often during times of fast-migrating lithosphere. In contrast, East Asian-Russian ZIP sites reflect later basaltic magmatism (<40 Ma), often linked to episodes of back-arc rifting and spreading, slow-migrating lithosphere and slab subduction.

  20. The Association Between Neighborhood Poverty and HIV Diagnoses Among Males and Females in New York City, 2010–2011

    PubMed Central

    Bocour, Angelica; Kersanske, Laura S.; Bodach, Sara D.; Xia, Qiang; Braunstein, Sarah L.

    2016-01-01

    Objective We assessed the association of neighborhood poverty with HIV diagnosis rates for males and females in New York City. Methods We calculated annual HIV diagnosis rates by ZIP Code, sex, and neighborhood poverty level using 2010–2011 New York City (NYC) HIV surveillance data and data from the U.S. Census 2010 and American Community Survey 2007–2011. Neighborhood poverty levels were percentage of residents in a ZIP Code with incomes below the federal poverty threshold, categorized as 0%–<10% (low poverty), 10%–<20% (medium poverty), 20%–<30% (high poverty), and 30%–100% (very high poverty). We used sex-stratified negative binomial regression models to measure the association between neighborhood-level poverty and HIV diagnosis rates, controlling for neighborhood-level education, race/ethnicity, age, and percentage of men who have sex with men. Results In 2010–2011, 6,184 people were newly diagnosed with HIV. Median diagnosis rates per 100,000 population increased by neighborhood poverty level overall (13.7, 34.3, 50.6, and 75.6 for low-, medium-, high-, and very high-poverty ZIP Codes, respectively), for males, and for females. In regression models, higher neighborhood poverty remained associated with higher diagnosis rates among males (adjusted rate ratio [ARR] = 1.63, 95% confidence interval [CI] 1.34, 1.97) and females (ARR=2.14, 95% CI 1.46, 3.14) for very high- vs. low-poverty ZIP Codes. Conclusion Living in very high- vs. low-poverty urban neighborhoods was associated with increased HIV diagnosis rates. After controlling for other factors, the association between poverty and diagnosis rates was stronger among females than among males. Alleviating poverty may help decrease HIV-related disparities. PMID:26957664

  1. POVME 2.0: An Enhanced Tool for Determining Pocket Shape and Volume Characteristics

    PubMed Central

    2015-01-01

    Analysis of macromolecular/small-molecule binding pockets can provide important insights into molecular recognition and receptor dynamics. Since its release in 2011, the POVME (POcket Volume MEasurer) algorithm has been widely adopted as a simple-to-use tool for measuring and characterizing pocket volumes and shapes. We here present POVME 2.0, which is an order of magnitude faster, has improved accuracy, includes a graphical user interface, and can produce volumetric density maps for improved pocket analysis. To demonstrate the utility of the algorithm, we use it to analyze the binding pocket of RNA editing ligase 1 from the unicellular parasite Trypanosoma brucei, the etiological agent of African sleeping sickness. The POVME analysis characterizes the full dynamics of a potentially druggable transient binding pocket and so may guide future antitrypanosomal drug-discovery efforts. We are hopeful that this new version will be a useful tool for the computational- and medicinal-chemist community. PMID:25400521

  2. Current switching ratio optimization using dual pocket doping engineering

    NASA Astrophysics Data System (ADS)

    Dash, Sidhartha; Sahoo, Girija Shankar; Mishra, Guru Prasad

    2018-01-01

    This paper presents a smart idea to maximize current switching ratio of cylindrical gate tunnel FET (CGT) by growing pocket layers in both source and channel region. The pocket layers positioned in the source and channel of the device provides significant improvement in ON-state and OFF-state current respectively. The dual pocket doped cylindrical gate TFET (DP-CGT) exhibits much superior performance in term of drain current, transconductance and current ratio as compared to conventional CGT, channel pocket doped CGT (CP-CGT) and source pocket doped CGT (SP-CGT). Further, the current ratio has been optimized w.r.t. width and instantaneous position both the pocket layers. The much improved current ratio and low power consumption makes the proposed device suitable for low-power and high speed application. The simulation work of DP-CGT is done using 3D Sentaurus TCAD device simulator from Synopsys.

  3. CALUTRON STRUCTURE

    DOEpatents

    Price, D.

    1958-09-01

    An improved means is described for removably installing and supporting a collector pocket in a calutron. The salient feature of the invention is the support of the collector pocket by means of suspension bolts engaging the pocket at a point intermediate the top and bottom of the pocket, and having nuts so arranged that by turing the desired predetermined position.

  4. What induces pocket openings on protein surface patches involved in protein-protein interactions?

    PubMed

    Eyrisch, Susanne; Helms, Volkhard

    2009-02-01

    We previously showed for the proteins BCL-X(L), IL-2, and MDM2 that transient pockets at their protein-protein binding interfaces can be identified by applying the PASS algorithm to molecular dynamics (MD) snapshots. We now investigated which aspects of the natural conformational dynamics of proteins induce the formation of such pockets. The pocket detection protocol was applied to three different conformational ensembles for the same proteins that were extracted from MD simulations of the inhibitor bound crystal conformation in water and the free crystal/NMR structure in water and in methanol. Additional MD simulations studied the impact of backbone mobility. The more efficient CONCOORD or normal mode analysis (NMA) techniques gave significantly smaller pockets than MD simulations, whereas tCONCOORD generated pockets comparable to those observed in MD simulations for two of the three systems. Our findings emphasize the influence of solvent polarity and backbone rearrangements on the formation of pockets on protein surfaces and should be helpful in future generation of transient pockets as putative ligand binding sites at protein-protein interfaces.

  5. What induces pocket openings on protein surface patches involved in protein-protein interactions?

    NASA Astrophysics Data System (ADS)

    Eyrisch, Susanne; Helms, Volkhard

    2009-02-01

    We previously showed for the proteins BCL-XL, IL-2, and MDM2 that transient pockets at their protein-protein binding interfaces can be identified by applying the PASS algorithm to molecular dynamics (MD) snapshots. We now investigated which aspects of the natural conformational dynamics of proteins induce the formation of such pockets. The pocket detection protocol was applied to three different conformational ensembles for the same proteins that were extracted from MD simulations of the inhibitor bound crystal conformation in water and the free crystal/NMR structure in water and in methanol. Additional MD simulations studied the impact of backbone mobility. The more efficient CONCOORD or normal mode analysis (NMA) techniques gave significantly smaller pockets than MD simulations, whereas tCONCOORD generated pockets comparable to those observed in MD simulations for two of the three systems. Our findings emphasize the influence of solvent polarity and backbone rearrangements on the formation of pockets on protein surfaces and should be helpful in future generation of transient pockets as putative ligand binding sites at protein-protein interfaces.

  6. Validity of a Smartphone-Based Fall Detection Application on Different Phones Worn on a Belt or in a Trouser Pocket.

    PubMed

    Vermeulen, Joan; Willard, Sarah; Aguiar, Bruno; De Witte, Luc P

    2015-01-01

    The objective of this study was to evaluate the sensitivity and specificity of a smartphone-based fall detection application when different smartphone models are worn on a belt or in a trouser pocket. Eight healthy adults aged between 18 and 24 years old simulated 10 different types of true falls, 5 different types of falls with recovery, and 11 daily activities, five consecutive times. Participants wore one smartphone in a pocket that was attached to their belt and another one in their trouser pocket. All smartphones were equipped with a built-in accelerometer and the fall detection application. Four participants tested the application on a Samsung S3 and four tested the application on a Samsung S3 mini. Sensitivity scores were .75 (Samsung S3 belt), .88 (Samsung S3 mini trouser pocket), and .90 (Samsung S3 mini belt/Samsung S3 trouser pocket). Specificity scores were .87 (Samsung S3 trouser pocket), .91 (Samsung S3 mini trouser pocket), .97 (Samsung S3 belt), and .99 (Samsung S3 mini belt). These results suggest that an application on a smartphone can generate valid fall alarms when worn on a belt or in a trouser pocket. However, sensitivity should be improved before implementation of the application in practice.

  7. Exploitation of pocket gophers and their food caches by grizzly bears

    USGS Publications Warehouse

    Mattson, D.J.

    2004-01-01

    I investigated the exploitation of pocket gophers (Thomomys talpoides) by grizzly bears (Ursus arctos horribilis) in the Yellowstone region of the United States with the use of data collected during a study of radiomarked bears in 1977-1992. My analysis focused on the importance of pocket gophers as a source of energy and nutrients, effects of weather and site features, and importance of pocket gophers to grizzly bears in the western contiguous United States prior to historical extirpations. Pocket gophers and their food caches were infrequent in grizzly bear feces, although foraging for pocket gophers accounted for about 20-25% of all grizzly bear feeding activity during April and May. Compared with roots individually excavated by bears, pocket gopher food caches were less digestible but more easily dug out. Exploitation of gopher food caches by grizzly bears was highly sensitive to site and weather conditions and peaked during and shortly after snowmelt. This peak coincided with maximum success by bears in finding pocket gopher food caches. Exploitation was most frequent and extensive on gently sloping nonforested sites with abundant spring beauty (Claytonia lanceolata) and yampah (Perdieridia gairdneri). Pocket gophers are rare in forests, and spring beauty and yampah roots are known to be important foods of both grizzly bears and burrowing rodents. Although grizzly bears commonly exploit pocket gophers only in the Yellowstone region, this behavior was probably widespread in mountainous areas of the western contiguous United States prior to extirpations of grizzly bears within the last 150 years.

  8. Gophers as geomorphic agents in the Colorado Front Range subalpine zone

    NASA Astrophysics Data System (ADS)

    Winchell, Eric W.; Anderson, Robert S.; Lombardi, Elizabeth M.; Doak, Daniel F.

    2016-07-01

    Gophers are significant geomorphic agents in many landscapes. We document activity of the northern pocket gopher (Thomomys talpoides) in two small subalpine meadows (1050-1800 m2) of the Front Range, Colorado, USA. We tracked locations and volumes of mounds and subnivean infilled tunnels over one year and probed the thickness of the biomantle within one meadow. We infer that only 5-7 gophers occupied each meadow, implying a gopher density of 28-67 ha- 1. Fractional areal coverage of the meadows by diggings suggests that within 49-95 years gophers would fully resurface the meadows. Annual volumes of excavated soil correspond to the equivalent of 1 mm of material spread evenly over the meadows. Probed meadow resistance depths reveal a pattern we interpret to be stone lines at roughly 15 cm depths; implied vertical turnover times are therefore roughly 150 years. These spatial and temporal patterns imply that gophers should be able to churn the biomantle on approximately century timescales and should fully resurface the meadow areas in similar timescales. These field data also contribute to an investigation of lateral sediment transport; given the local slope of the landscape, gopher-driven sediment transport within our two study sites suggests a landscape diffusivity of 0.008 m2y- 1. At no time do gophers occupy the forest. As evidenced by subnivean infilled tunnels, winter activity is restricted to the upslope (and hence upwind) meadow edges, which correspond to high snow cover and warm (> 0 °C) shallow subsurface soil temperatures. Subsequent activity expands downhill into the meadows and shows a distinct pulse of mound activity in late summer through early fall prior to snowfall. Local forest fire history has led to much more extensive meadows in the past, suggesting that the geomorphic influence of gophers in the landscape is much more widespread than the present distribution of meadows and may cover the entire subalpine region of the Front Range on millennial timescales.

  9. Proton pump inhibitors reduce the size and acidity of the acid pocket in the stomach.

    PubMed

    Rohof, Wout O; Bennink, Roelof J; Boeckxstaens, Guy E

    2014-07-01

    The gastric acid pocket is believed to be the reservoir from which acid reflux events originate. Little is known about how changes in position, size, and acidity of the acid pocket contribute to the therapeutic effect of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD). Thirty-six patients with GERD (18 not taking PPIs, 18 taking PPIs; 19 men; age, 55 ± 2.1 y) were analyzed by concurrent high-resolution manometry and pH-impedance monitoring after a standardized meal. The acid pocket was visualized using scintigraphy after intravenous administration of (99m)technetium-pertechnetate. The size of the acid pocket was measured and its position was determined, relative to the diaphragm, using radionuclide markers on a high-resolution manometry catheter. At the end of the study, the acid pocket was aspirated, and its pH level was measured. The number of reflux episodes was comparable between patients on and off PPIs, but the number of acid reflux episodes was reduced significantly in patients on PPIs. In patients on PPIs, the acid pocket was smaller and more frequently located below the diaphragm. The mean pH of the acid pocket was significantly lower in patients not taking PPIs (n = 6) than in those who were (n = 16) (0.9; range, 0.7-1.2 vs 4.0; range, 1.6-5.9; P < .001). The pH of acid pockets correlated significantly with the lowest pH values measured for refluxate (r = 0.72; P < .01). Based on analyses of acid pockets in patients with GERD, the acid pocket appears to be a reservoir from which reflux occurs when patients are receiving PPIs. PPIs might affect the size, acidity, or position of the acid pocket, which contributes to the efficacy in patients with GERD. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. GPFA-AB_Phase1ReservoirTask2DataUpload

    DOE Data Explorer

    Teresa E. Jordan

    2015-10-22

    This submission to the Geothermal Data Repository (GDR) node of the National Geothermal Data System (NGDS) in support of Phase 1 Low Temperature Geothermal Play Fairway Analysis for the Appalachian Basin. The files included in this zip file contain all data pertinent to the methods and results of this task’s output, which is a cohesive multi-state map of all known potential geothermal reservoirs in our region, ranked by their potential favorability. Favorability is quantified using a new metric, Reservoir Productivity Index, as explained in the Reservoirs Methodology Memo (included in zip file). Shapefile and images of the Reservoir Productivity and Reservoir Uncertainty are included as well.

  11. Brain model of text animation as a data mining strategy.

    PubMed

    Astakhova, Tamara; Astakhov, Vadim

    2009-01-01

    Imagination is the critical point in developing of realistic intelligence (AI) systems. One way to approach imagination would be simulation of its properties and operations. We developed two models "Brain Network Hierarchy of Languages," and "Semantical Holographic Calculus" and simulation system ScriptWriter that emulate the process of imagination through an automatic animation of English texts. The purpose of this paper is to demonstrate the model and present "ScriptWriter" system http://nvo.sdsc.edu/NVO/JCSG/get_SRB_mime_file2.cgi//home/tamara.sdsc/test/demo.zip?F=/home/tamara.sdsc/test/demo.zip&M=application/x-gtar for simulation of the imagination.

  12. Why Wars End: An Expected Utility War Termination Model

    DTIC Science & Technology

    1992-04-15

    any o( I, qelei. Thk document may not be rMeed for ope pubjckdoa untu it huA been deared by de appropriate militUay e r "e r aovsmment agency. WHY WARS...MONITORING ORGANIZATION 4I r U11f (if applicable) 6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City. State, and ZIP Code) /Z OCT HfuL.I(i RL...Classification) ~ LA.’ 7Z f/ ’YA 479 , 12. PERSONAL AUTHOR(S) 𔃾 M70?’ 7- 04ŝ’- r -71 on6, .13 . TYPE OF REPORT 113b. TIME COVERED 14- DATE OF REPORT

  13. Privacy protection versus cluster detection in spatial epidemiology.

    PubMed

    Olson, Karen L; Grannis, Shaun J; Mandl, Kenneth D

    2006-11-01

    Patient data that includes precise locations can reveal patients' identities, whereas data aggregated into administrative regions may preserve privacy and confidentiality. We investigated the effect of varying degrees of address precision (exact latitude and longitude vs the center points of zip code or census tracts) on detection of spatial clusters of cases. We simulated disease outbreaks by adding supplementary spatially clustered emergency department visits to authentic hospital emergency department syndromic surveillance data. We identified clusters with a spatial scan statistic and evaluated detection rate and accuracy. More clusters were identified, and clusters were more accurately detected, when exact locations were used. That is, these clusters contained at least half of the simulated points and involved few additional emergency department visits. These results were especially apparent when the synthetic clustered points crossed administrative boundaries and fell into multiple zip code or census tracts. The spatial cluster detection algorithm performed better when addresses were analyzed as exact locations than when they were analyzed as center points of zip code or census tracts, particularly when the clustered points crossed administrative boundaries. Use of precise addresses offers improved performance, but this practice must be weighed against privacy concerns in the establishment of public health data exchange policies.

  14. Local variations in the timing of RSV epidemics.

    PubMed

    Noveroske, Douglas B; Warren, Joshua L; Pitzer, Virginia E; Weinberger, Daniel M

    2016-11-11

    Respiratory syncytial virus (RSV) is a primary cause of hospitalizations in children worldwide. The timing of seasonal RSV epidemics needs to be known in order to administer prophylaxis to high-risk infants at the appropriate time. We used data from the Connecticut State Inpatient Database to identify RSV hospitalizations based on ICD-9 diagnostic codes. Harmonic regression analyses were used to evaluate RSV epidemic timing at the county level and ZIP code levels. Linear regression was used to investigate associations between the socioeconomic status of a locality and RSV epidemic timing. 9,740 hospitalizations coded as RSV occurred among children less than 2 years old between July 1, 1997 and June 30, 2013. The earliest ZIP code had a seasonal RSV epidemic that peaked, on average, 4.64 weeks earlier than the latest ZIP code. Earlier epidemic timing was significantly associated with demographic characteristics (higher population density and larger fraction of the population that was black). Seasonal RSV epidemics in Connecticut occurred earlier in areas that were more urban (higher population density and larger fraction of the population that was). These findings could be used to better time the administration of prophylaxis to high-risk infants.

  15. The Functions of Metallothionein and ZIP and ZnT Transporters: An Overview and Perspective

    PubMed Central

    Kimura, Tomoki; Kambe, Taiho

    2016-01-01

    Around 3000 proteins are thought to bind zinc in vivo, which corresponds to ~10% of the human proteome. Zinc plays a pivotal role as a structural, catalytic, and signaling component that functions in numerous physiological processes. It is more widely used as a structural element in proteins than any other transition metal ion, is a catalytic component of many enzymes, and acts as a cellular signaling mediator. Thus, it is expected that zinc metabolism and homeostasis have sophisticated regulation, and elucidating the underlying molecular basis of this is essential to understanding zinc functions in cellular physiology and pathogenesis. In recent decades, an increasing amount of evidence has uncovered critical roles of a number of proteins in zinc metabolism and homeostasis through influxing, chelating, sequestrating, coordinating, releasing, and effluxing zinc. Metallothioneins (MT) and Zrt- and Irt-like proteins (ZIP) and Zn transporters (ZnT) are the proteins primarily involved in these processes, and their malfunction has been implicated in a number of inherited diseases such as acrodermatitis enteropathica. The present review updates our current understanding of the biological functions of MTs and ZIP and ZnT transporters from several new perspectives. PMID:26959009

  16. The zygomatic implant perforated (ZIP) flap: a new technique for combined surgical reconstruction and rapid fixed dental rehabilitation following low-level maxillectomy.

    PubMed

    Butterworth, C J; Rogers, S N

    2017-12-01

    This aim of this report is to describe the development and evolution of a new surgical technique for the immediate surgical reconstruction and rapid post-operative prosthodontic rehabilitation with a fixed dental prosthesis following low-level maxillectomy for malignant disease.The technique involves the use of a zygomatic oncology implant perforated micro-vascular soft tissue flap (ZIP flap) for the primary management of maxillary malignancy with surgical closure of the resultant maxillary defect and the installation of osseointegrated support for a zygomatic implant-supported maxillary fixed dental prosthesis.The use of this technique facilitates extremely rapid oral and dental rehabilitation within a few weeks of resective surgery, providing rapid return to function and restoring appearance following low-level maxillary resection, even in cases where radiotherapy is required as an adjuvant treatment post-operatively. The ZIP flap technique has been adopted as a standard procedure in the unit for the management of low-level maxillary malignancy, and this report provides a detailed step-by-step approach to treatment and discusses modifications developed over the treatment of an initial cohort of patients.

  17. GhABF2, a bZIP transcription factor, confers drought and salinity tolerance in cotton (Gossypium hirsutum L.).

    PubMed

    Liang, Chengzhen; Meng, Zhaohong; Meng, Zhigang; Malik, Waqas; Yan, Rong; Lwin, Khin Myat; Lin, Fazhuang; Wang, Yuan; Sun, Guoqing; Zhou, Tao; Zhu, Tao; Li, Jianying; Jin, Shuangxia; Guo, Sandui; Zhang, Rui

    2016-10-07

    The bZIP transcription factor (TF) act as an important regulator for the abscisic acid (ABA) mediated abiotic stresses signaling pathways in plants. Here, we reported the cloning and characterization of GhABF2, encoding for typical cotton bZIP TF. Overexpression of GhABF2 significantly improved drought and salt stress tolerance both in Arabidopsis and cotton. However, silencing of GhABF2 made transgenic cotton sensitive to PEG osmotic and salt stress. Expression of GhABF2 was induced by drought and ABA treatments but repressed by high salinity. Transcriptome analysis indicated that GhABF2 increases drought and salt tolerance by regulating genes related to ABA, drought and salt response. The proline contents, activity of superoxide dismutase (SOD) and catalase (CAT) were also significantly increased in GhABF2-overexpression cottons in comparison to wild type after drought and salt treatment. Further, an increase in fiber yield under drought and saline-alkali wetland exhibited the important role of GhABF2 in enhancing the drought and salt tolerance in transgenic lines. In conclusion, manipulation of GhABF2 by biotechnological tools could be a sustainable strategy to deploy drought and salt tolerance in cotton.

  18. Possible etiologies of increased incidence of gastroschisis.

    PubMed

    Souther, Christina; Puapong, Devin P; Woo, Russell; Johnson, Sidney M

    2017-11-01

    Gastroschisis incidence has increased over the past decade nationally and in Hawaii. Pesticides have been implicated as potential causative factors for gastroschisis, and use of restricted use pesticides (RUPs) is widespread in Hawaii. This study was conducted to characterize gastroschisis cases in Hawaii and determine whether RUP application correlates with gastroschisis incidence. Gastroschisis patients treated in Hawaii between September, 2008 and August, 2015 were mapped by zip code along with RUP use. Spatial analysis software was used to identify patients' homes located within the pesticide application zone and agricultural land use areas. 71 gastroschisis cases were identified. 2.8% of patients were from Kauai, 64.8% from Oahu, 16.9% from Hawaii, 14.1% from Maui, and 1.4% from Molokai. RUPs have been used on all of these islands. 78.9% of patients lived in zip codes overlapping agricultural land use areas. 85.9% of patients shared zip codes with RUP-use areas. The majority of gastroschisis patients were from RUP-use areas, supporting the idea that pesticides may contribute to the development of gastroschisis, although limited data on specific releases make it difficult to apply these findings. As more RUP-use data become available to the public, these important research questions can be investigated further.

  19. A kMC-MD method with generalized move-sets for the simulation of folding of α-helical and β-stranded peptides.

    PubMed

    Peter, Emanuel K; Pivkin, Igor V; Shea, Joan-Emma

    2015-04-14

    In Monte-Carlo simulations of protein folding, pathways and folding times depend on the appropriate choice of the Monte-Carlo move or process path. We developed a generalized set of process paths for a hybrid kinetic Monte Carlo-Molecular dynamics algorithm, which makes use of a novel constant time-update and allows formation of α-helical and β-stranded secondary structures. We apply our new algorithm to the folding of 3 different proteins: TrpCage, GB1, and TrpZip4. All three systems are seen to fold within the range of the experimental folding times. For the β-hairpins, we observe that loop formation is the rate-determining process followed by collapse and formation of the native core. Cluster analysis of both peptides reveals that GB1 folds with equal likelihood along a zipper or a hydrophobic collapse mechanism, while TrpZip4 follows primarily a zipper pathway. The difference observed in the folding behavior of the two proteins can be attributed to the different arrangements of their hydrophobic core, strongly packed, and dry in case of TrpZip4, and partially hydrated in the case of GB1.

  20. Programmable optical microshutter arrays for large aspect ratio microslits

    NASA Astrophysics Data System (ADS)

    Ilias, S.; Picard, F.; Larouche, C.; Kruzelecky, R.; Jamroz, W.; Le Noc, L.; Topart, P.

    2008-06-01

    Design, fabrication and characterization of a 16x1 programmable microshutter array are described. Each shutter controls the light transmitted through a microslit defined on the transparent substrate supporting the array. Two approaches were considered for the shutter array implementation: sweeping blades and zipping actuators. Simulation results and fabrication constraints led to the selection of the zipping actuators. The device was fabricated using a surface micromachining process. Each microshutter is basically an electrostatic zipping actuator having a curved shape induced by a stress gradient throughout the actuator thickness. When a sufficient voltage is applied between the microshutter and an actuation electrode surrounding the microslit area, the generated electrostatic force pulls the actuator down to the substrate which closes the microslit. Opening the slit relies on the restoring force due to the actuator deformation. Microshutter arrays were fabricated successfully. High light transmission through the slit area is obtained with the actuator in the open position and excellent light blocking is observed when the shutter is closed. Static and dynamic responses of the device were determined. A pull-in voltage of about 110 V closes the microslit and the response times to close and open the microslit are about 2 and 7 ms, respectively.

  1. A MEMS sensor for AC electric current

    NASA Astrophysics Data System (ADS)

    Leland, Eli Sidney

    This manuscript describes the development of a new MEMS sensor for the measurement of AC electric current. The sensor is comprised of a MEMS piezoelectric cantilever with a microscale permanent magnet mounted to the cantilever's free end. When placed near a wire carrying AC current, the magnet couples to the oscillating magnetic field surrounding the wire, causing the cantilever to deflect, and piezoelectric coupling produces a sinusoidal voltage proportional to the current in the wire. The sensor is itself passive, requiring no power supply to operate. It also operates on proximity and need only be placed near a current carrier in order to function. The sensor does not need to encircle the current carrier and it therefore can measure current in two-wire zip-cords without necessitating the separation of the two conductors. Applications for tins sensor include measuring residential and commercial electricity use and monitoring electric power distribution networks. An analytical model describing the behavior of the current sensor was developed. This model was also adapted to describe the power output of an energy scavenger coupled to a wire carrying AC current. A mesoscale sensor exhibited a sensitivity of 75 mV/A when measuring AC electric current in a zip-cord. A mesoscale energy scavenger produced 345 muW when coupled to a zip-cord carrying 13 A. MEMS current sensors were fabricated from aluminum nitride piezoelectric cantilevers and composite permanent magnets. The cantilevers were fabricated using a four-mask process. Microscale permanent magnets were dispenser-printed using NdFeB magnetic powder with an epoxy binder. The MEMS AC current sensor was interfaced with amplification circuitry and packaged inside an almninum enclosure. The sensor was also integrated with a mesoscale energy scavenger and power conditioning circuitry to create a fully self-powered current sensor. Unamplified sensitivity of the sensor was 0.1-1.1 mV/A when measuring currents in single wires and zip-cords. The self-powered current sensor operated at a 0.6% duty cycle when coupled to the zip-cord of a 1500 W space heater drawing 13 A. The self-powered sensor's energy scavenger transferred energy to a 10 mF storage capacitor at a rate of 69 muJ/s.

  2. Zn2+-transporters ZIP7 and ZnT7 play important role in progression of cardiac dysfunction via affecting sarco(endo)plasmic reticulum-mitochondria coupling in hyperglycemic cardiomyocytes.

    PubMed

    Tuncay, Erkan; Bitirim, C Verda; Olgar, Yusuf; Durak, Aysegul; Rutter, Guy A; Turan, Belma

    2018-01-04

    Functional contribution of S(E)R-mitochondria coupling to normal cellular processes is crucial and any alteration in S(E)R-mitochondria axis may be responsible for the onset of diseases. Mitochondrial free Zn 2+ level in cardiomyocytes ([Zn 2+ ] Mit ) is lower comparison to either its cytosolic or S(E)R level under physiological condition. However, there is little information about distribution of Zn 2+ -transporters on mitochondria and role of Zn 2+ -dependent mitochondrial-function associated with [Zn 2+ ] Mit . Since we recently have shown how hyperglycemia (HG)-induced changes in ZIP7 and ZnT7 contribute to Zn 2+ -transport across S(E)R and contribute to S(E)R-stress in the heart, herein, we hypothesized that these transporters can also be localized to mitochondria and affect the S(E)R-mitochondria coupling, and thereby contribute to cellular Zn 2+ -muffling between S(E)R-mitochondria in HG-cells. Mitochondrial localizations of ZIP7 and ZnT7 were demonstrated using fluorescence technique while they were confirmed in isolated mitochondrial fractions using biochemical analysis. Markedly decreased ZIP7 and increased ZnT7 levels were measured in isolated mitochondrial fractions from either HG- or doxorubicin, DOX (as positive control)-treated cardiomyocytes. Significantly increases in [Zn 2+ ] Mit and ROS production levels and depolarized mitochondrial membrane potential were also measured in HG cells. The expression levels of some key proteins, responsible for proper S(E)R-mitochondria coupling such as Mfn-1, Fis-1, OPA1, BAP31, STIM1 and PML in either HG- or DOX-cells were supported our above hypothesis, strongly. Overall, this study provides an important description about the role of ZIP7 and ZnT7, localized to both mitochondria and S(E)R and contribute to cellular Zn 2+ -muffling between cellular-compartments in HG or hypertrophic cardiomyocytes via affecting S(E)R-mitochondria coupling. Any alteration in this axis and/or cellular [Zn 2+ ] may provide new insight for prevention/therapy of HF in diabetes and/or hypertrophy. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  3. A pocket of variability in Pinus rigida

    Treesearch

    F. Thomas Ledig; John H. Fryer

    1971-01-01

    Steady state gene frequencies around a pocket of differential fitness have been formulated by Hanson (1966) in a generalization of the work of Haldane (1948). A pocket of differential fitness would result in a pocket-of-variability, assuming that the radius of the area of contrasting fitness was large in relation to the vagility of the organism. Conversely, the absence...

  4. The 2.1Å Crystal Structure of an Acyl-CoA Synthetase from Methanosarcina acetivorans reveals an alternate acyl binding pocket for small branched acyl substrates†,‡

    PubMed Central

    Shah, Manish B.; Ingram-Smith, Cheryl; Cooper, Leroy L.; Qu, Jun; Meng, Yu; Smith, Kerry S.; Gulick, Andrew M.

    2009-01-01

    The acyl-AMP forming family of adenylating enzymes catalyze two-step reactions to activate a carboxylate with the chemical energy derived from ATP hydrolysis. X-ray crystal structures have been determined for multiple members of this family and, together with biochemical studies, provide insights into the active site and catalytic mechanisms used by these enzymes. These studies have shown that the enzymes use a domain rotation of 140° to reconfigure a single active site to catalyze the two partial reactions. We present here the crystal structure of a new medium chain acyl-CoA synthetase from Methanosarcina acetivorans. The binding pocket for the three substrates is analyzed, with many conserved residues present in the AMP binding pocket. The CoA binding pocket is compared to the pockets of both acetyl-CoA synthetase and 4-chlorobenzoate:CoA ligase. Most interestingly, the acyl binding pocket of the new structure is compared with other acyl- and aryl-CoA synthetases. A comparison of the acyl-binding pocket of the acyl-CoA synthetase from M. acetivorans with other structures identifies a shallow pocket that is used to bind the medium chain carboxylates. These insights emphasize the high sequence and structural diversity among this family in the area of the acyl binding pocket. PMID:19544569

  5. Detecting Local Ligand-Binding Site Similarity in Non-Homologous Proteins by Surface Patch Comparison

    PubMed Central

    Sael, Lee; Kihara, Daisuke

    2012-01-01

    Functional elucidation of proteins is one of the essential tasks in biology. Function of a protein, specifically, small ligand molecules that bind to a protein, can be predicted by finding similar local surface regions in binding sites of known proteins. Here, we developed an alignment free local surface comparison method for predicting a ligand molecule which binds to a query protein. The algorithm, named Patch-Surfer, represents a binding pocket as a combination of segmented surface patches, each of which is characterized by its geometrical shape, the electrostatic potential, the hydrophobicity, and the concaveness. Representing a pocket by a set of patches is effective to absorb difference of global pocket shape while capturing local similarity of pockets. The shape and the physicochemical properties of surface patches are represented using the 3D Zernike descriptor, which is a series expansion of mathematical 3D function. Two pockets are compared using a modified weighted bipartite matching algorithm, which matches similar patches from the two pockets. Patch-Surfer was benchmarked on three datasets, which consist in total of 390 proteins that bind to one of 21 ligands. Patch-Surfer showed superior performance to existing methods including a global pocket comparison method, Pocket-Surfer, which we have previously introduced. Particularly, as intended, the accuracy showed large improvement for flexible ligand molecules, which bind to pockets in different conformations. PMID:22275074

  6. Detecting local ligand-binding site similarity in nonhomologous proteins by surface patch comparison.

    PubMed

    Sael, Lee; Kihara, Daisuke

    2012-04-01

    Functional elucidation of proteins is one of the essential tasks in biology. Function of a protein, specifically, small ligand molecules that bind to a protein, can be predicted by finding similar local surface regions in binding sites of known proteins. Here, we developed an alignment free local surface comparison method for predicting a ligand molecule which binds to a query protein. The algorithm, named Patch-Surfer, represents a binding pocket as a combination of segmented surface patches, each of which is characterized by its geometrical shape, the electrostatic potential, the hydrophobicity, and the concaveness. Representing a pocket by a set of patches is effective to absorb difference of global pocket shape while capturing local similarity of pockets. The shape and the physicochemical properties of surface patches are represented using the 3D Zernike descriptor, which is a series expansion of mathematical 3D function. Two pockets are compared using a modified weighted bipartite matching algorithm, which matches similar patches from the two pockets. Patch-Surfer was benchmarked on three datasets, which consist in total of 390 proteins that bind to one of 21 ligands. Patch-Surfer showed superior performance to existing methods including a global pocket comparison method, Pocket-Surfer, which we have previously introduced. Particularly, as intended, the accuracy showed large improvement for flexible ligand molecules, which bind to pockets in different conformations. Copyright © 2011 Wiley Periodicals, Inc.

  7. The impact of health insurance programs on out-of-pocket expenditures in Indonesia: an increase or a decrease?

    PubMed

    Aji, Budi; De Allegri, Manuela; Souares, Aurelia; Sauerborn, Rainer

    2013-07-18

    We used panel data from the Indonesian Family Life Survey to investigate the impact of health insurance programs on reducing out-of-pocket expenditures. We employed three linear panel data models, two of which accounted for endogeneity: pooled ordinary least squares (OLS), pooled two-stage least squares (2SLS) for instrumental variable (IV), and fixed effects (FE). The study revealed that two health insurance programs had a significantly negative impact on out-of-pocket expenditures by using IV estimates. In the IV model, Askeskin decreased out-of-pocket expenditures by 34% and Askes by 55% compared with non-Askeskin and non-Askes, respectively, while Jamsostek was found to bear a nonsignificant effect on out-of-pocket expenditures. In the FE model, only Askeskin had a significant negative effect with an 11% reduction on out-of-pocket expenditures. This study showed that two large existing health insurance programs in Indonesia, Askeskin and Askes, effectively reduced household out-of-pocket expenditures. The ability of programs to offer financial protection by reducing out-of-pocket expenditures is likely to be a direct function of their benefits package and co-payment policies.

  8. The acid pocket: a target for treatment in reflux disease?

    PubMed

    Kahrilas, Peter J; McColl, Kenneth; Fox, Mark; O'Rourke, Lisa; Sifrim, Daniel; Smout, Andre J P M; Boeckxstaens, Guy

    2013-07-01

    The nadir esophageal pH of reflux observed during pH monitoring in the postprandial period is often more acidic than the concomitant intragastric pH. This paradox prompted the discovery of the "acid pocket", an area of unbuffered gastric acid that accumulates in the proximal stomach after meals and serves as the reservoir for acid reflux in healthy individuals and gastroesophageal reflux disease (GERD) patients. However, there are differentiating features between these populations in the size and position of the acid pocket, with GERD patients predisposed to upward migration of the proximal margin onto the esophageal mucosa, particularly when supine. This upward migration of acid, sometimes referred to as an "acid film", likely contributes to mucosal pathology in the region of the squamocolumnar junction. Furthermore, movement of the acid pocket itself to a supradiaphragmatic location with hiatus hernia increases the propensity for acid reflux by all conventional mechanisms. Consequently, the acid pocket is an attractive target for GERD therapy. It may be targeted in a global way with proton pump inhibitors that attenuate acid pocket development, or with alginate/antacid combinations that colocalize with the acid pocket and displace it distally, thereby demonstrating the potential for selective targeting of the acid pocket in GERD.

  9. The Impact of Health Insurance Programs on Out-of-Pocket Expenditures in Indonesia: An Increase or a Decrease?

    PubMed Central

    Aji, Budi; De Allegri, Manuela; Souares, Aurelia; Sauerborn, Rainer

    2013-01-01

    We used panel data from the Indonesian Family Life Survey to investigate the impact of health insurance programs on reducing out-of-pocket expenditures. We employed three linear panel data models, two of which accounted for endogeneity: pooled ordinary least squares (OLS), pooled two-stage least squares (2SLS) for instrumental variable (IV), and fixed effects (FE). The study revealed that two health insurance programs had a significantly negative impact on out-of-pocket expenditures by using IV estimates. In the IV model, Askeskin decreased out-of-pocket expenditures by 34% and Askes by 55% compared with non-Askeskin and non-Askes, respectively, while Jamsostek was found to bear a nonsignificant effect on out-of-pocket expenditures. In the FE model, only Askeskin had a significant negative effect with an 11% reduction on out-of-pocket expenditures. This study showed that two large existing health insurance programs in Indonesia, Askeskin and Askes, effectively reduced household out-of-pocket expenditures. The ability of programs to offer financial protection by reducing out-of-pocket expenditures is likely to be a direct function of their benefits package and co-payment policies. PMID:23873263

  10. Identification of Small Molecules against Botulinum Neurotoxin B Binding to Neuronal Cells at Ganglioside GT1b Binding Site with Low to Moderate Affinity

    DTIC Science & Technology

    2014-10-01

    BoNT serotype B (BoNT/B) for the trisaccharide GT1b were identified from the x-ray crystal structure of the BoNT/B/trisaccharide (GT1b) complex ( PDB ...trisaccharide and all the water from the structure and identified four potential binding pockets (Pocket-1, Pocket-2, and Pocket-4) as shown in...four potential binding sites or pockets on BoNT serotype B (BoNT/B) for the trisaccharide GT1b were identified from the x-ray crystal structure of the

  11. An integrated strategy for improving contrast, durability, and portability of a Pocket Colposcope for cervical cancer screening and diagnosis

    PubMed Central

    Mueller, Jenna; Asma, Betsy; Asiedu, Mercy; Krieger, Marlee S.; Chitalia, Rhea; Dahl, Denali; Taylor, Peyton; Schmitt, John W.; Ramanujam, Nimmi

    2018-01-01

    Introduction We have previously developed a portable Pocket Colposcope for cervical cancer screening in resource-limited settings. In this manuscript we report two different strategies (cross-polarization and an integrated reflector) to improve image contrast levels achieved with the Pocket Colposcope and evaluate the merits of each strategy compared to a standard-of-care digital colposcope. The desired outcomes included reduced specular reflection (glare), increased illumination beam pattern uniformity, and reduced electrical power budget. In addition, anti-fogging and waterproofing features were incorporated to prevent the Pocket Colposcope from fogging in the vaginal canal and to enable rapid disinfection by submersion in chemical agents. Methods Cross-polarization (Generation 3 Pocket Colposcope) and a new reflector design (Generation 4 Pocket Colposcope) were used to reduce glare and improve contrast. The reflector design (including the angle and height of the reflector sidewalls) was optimized through ray-tracing simulations. Both systems were characterized with a series of bench tests to assess specular reflection, beam pattern uniformity, and image contrast. A pilot clinical study was conducted to compare the Generation 3 and 4 Pocket Colposcopes to a standard-of-care colposcope (Leisegang Optik 2). Specifically, paired images of cervices were collected from the standard-of-care colposcope and either the Generation 3 (n = 24 patients) or the Generation 4 (n = 32 patients) Pocket Colposcopes. The paired images were blinded by device, randomized, and sent to an expert physician who provided a diagnosis for each image. Corresponding pathology was obtained for all image pairs. The primary outcome measures were the level of agreement (%) and κ (kappa) statistic between the standard-of-care colposcope and each Pocket Colposcope (Generation 3 and Generation 4). Results Both generations of Pocket Colposcope had significantly higher image contrast when compared to the standard-of-care colposcope. The addition of anti-fog and waterproofing features to the Generation 3 and 4 Pocket Colposcope did not impact image quality based on qualitative and quantitative metrics. The level of agreement between the Generation 3 Pocket Colposcope and the standard-of-care colposcope was 75.0% (kappa = 0.4000, p = 0.0028, n = 24). This closely matched the level of agreement between the Generation 4 Pocket Colposcope and the standard-of-care colposcope which was also 75.0% (kappa = 0.4941, p = 0.0024, n = 32). Conclusion Our results indicate that the Generation 3 and 4 Pocket Colposcopes perform comparably to the standard-of-care colposcope, with the added benefit of being low-cost and waterproof, which is ideal for use in resource-limited settings. Additionally, the reflector significantly reduces the electrical requirements of the Generation 4 Pocket Colposcope enhancing portability without altering performance compared to the Generation 3 system. PMID:29425225

  12. E-mail on the Move

    NASA Technical Reports Server (NTRS)

    1999-01-01

    PocketScience, Inc. was a member of the NASA Ames Technology Commercialization Center. Their PocketMail product is an email service that brings email capabilities to new hand-held devices. The PocketMail service uses technology originally developed at JPL. Through its involvement with the ATCC, PocketScience, Inc. was able to use this space probe communications technology and adapt it for advanced signal processing on Earth.

  13. Work of Breathing into Snow in the Presence versus Absence of an Artificial Air Pocket Affects Hypoxia and Hypercapnia of a Victim Covered with Avalanche Snow: A Randomized Double Blind Crossover Study.

    PubMed

    Roubík, Karel; Sieger, Ladislav; Sykora, Karel

    2015-01-01

    Presence of an air pocket and its size play an important role in survival of victims buried in the avalanche snow. Even small air pockets facilitate breathing. We hypothesize that the size of the air pocket significantly affects the airflow resistance and work of breathing. The aims of the study are (1) to investigate the effect of the presence of an air pocket on gas exchange and work of breathing in subjects breathing into the simulated avalanche snow and (2) to test whether it is possible to breathe with no air pocket. The prospective interventional double-blinded study involved 12 male volunteers, from which 10 completed the whole protocol. Each volunteer underwent two phases of the experiment in a random order: phase "AP"--breathing into the snow with a one-liter air pocket, and phase "NP"--breathing into the snow with no air pocket. Physiological parameters, fractions of oxygen and carbon dioxide in the airways and work of breathing expressed as pressure-time product were recorded continuously. The main finding of the study is that it is possible to breath in the avalanche snow even with no air pocket (0 L volume), but breathing under this condition is associated with significantly increased work of breathing. The significant differences were initially observed for end-tidal values of the respiratory gases (EtO2 and EtCO2) and peripheral oxygen saturation (SpO2) between AP and NP phases, whereas significant differences in inspiratory fractions occurred much later (for FIO2) or never (for FICO2). The limiting factor in no air pocket conditions is excessive increase in work of breathing that induces increase in metabolism accompanied by higher oxygen consumption and carbon dioxide production. The presence of even a small air pocket reduces significantly the work of breathing.

  14. Improved cardiovascular diagnostic accuracy by pocket size imaging device in non-cardiologic outpatients: the NaUSiCa (Naples Ultrasound Stethoscope in Cardiology) study

    PubMed Central

    2010-01-01

    Miniaturization has evolved in the creation of a pocket-size imaging device which can be utilized as an ultrasound stethoscope. This study assessed the additional diagnostic power of pocket size device by both experts operators and trainees in comparison with physical examination and its appropriateness of use in comparison with standard echo machine in a non-cardiologic population. Three hundred four consecutive non cardiologic outpatients underwent a sequential assessment including physical examination, pocket size imaging device and standard Doppler-echo exam. Pocket size device was used by both expert operators and trainees (who received specific training before the beginning of the study). All the operators were requested to give only visual, qualitative insights on specific issues. All standard Doppler-echo exams were performed by expert operators. One hundred two pocket size device exams were performed by experts and two hundred two by trainees. The time duration of the pocket size device exam was 304 ± 117 sec. Diagnosis of cardiac abnormalities was made in 38.2% of cases by physical examination and in 69.7% of cases by physical examination + pocket size device (additional diagnostic power = 31.5%, p < 0.0001). The overall K between pocket size device and standard Doppler-echo was 0.67 in the pooled population (0.84 by experts and 0.58 by trainees). K was suboptimal for trainees in the eyeball evaluation of ejection fraction, left atrial dilation and right ventricular dilation. Overall sensitivity was 91% and specificity 76%. Sensitivity and specificity were lower in trainees than in experts. In conclusion, pocket size device showed a relevant additional diagnostic value in comparison with physical examination. Sensitivity and specificity were good in experts and suboptimal in trainees. Specificity was particularly influenced by the level of experience. Training programs are needed for pocket size device users. PMID:21110840

  15. Epitympanum volume and tympanic isthmus area in temporal bones with retraction pockets.

    PubMed

    Monsanto, Rafael da Costa; Pauna, Henrique Furlan; Kaya, Serdar; Hızlı, Ömer; Kwon, Geeyoun; Paparella, Michael M; Cureoglu, Sebahattin

    2016-11-01

    To compare the volume of the epitympanic space, as well as the area of the tympanic isthmus, in human temporal bones with retraction pockets to those with chronic otitis media without retraction pockets and to those with neither condition. Comparative human temporal bone study. We generated a three-dimensional model of the bony epitympanum and measured the epitympanic space. We also compared the area of the tympanic isthmus. The mean total volume of the epitympanum was 40.55 ± 7.14 mm 3 in the retraction pocket group, 50.03 ± 8.49 mm 3 in the chronic otitis media group, and 48.03 ± 9.16 mm 3 in the neither condition group. The mean volume of the anterior, lateral, and medial compartments in temporal bones in the retraction pocket group was significantly smaller than in the two control groups (P < 0.05). Total epitympanic volume was also significantly smaller in the retraction pocket group than in both control groups (P < 0.05). The mean area of the tympanic isthmus was significantly smaller in the retraction pocket group (8.11 ± 2.44 mm 2 ) than in the chronic otitis media group (9.82 ± 2.06 mm 2 ) or the neither condition group (10.66 ± 1.78 mm 2 ) (P < 0.05). Our data indicate that temporal bones with retraction pockets have a smaller volume bony epitympanum and a smaller tympanic isthmus area as compared with temporal bones from both control groups. The smaller volume tympanic isthmus in the retraction pocket group may suggest that a blockage in the aeration pathways to the epitympanum could create dysventilation, resulting in negative pressure and ultimately in retraction pockets and cholesteatomas. NA Laryngoscope, 126:E369-E374, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Histological analysis of retraction pocket pars tensa of tympanic membrane in children.

    PubMed

    Urík, M; Hurník, P; Žiak, D; Machač, J; Šlapák, I; Motyka, O; Vaculová, J; Dvořáčková, J

    2016-07-01

    Histological and histochemical analysis of retraction pocket of pars tensa of tympanic membrane in children. Identification of morphological abnormalities in comparison with a healthy tympanic membrane as it is described in standard textbook. Identification of signs typical for cholesteatoma and support for a retraction theory of cholesteatoma formation. A prospective study analysing 31 samples of retraction pockets taken during surgery. University Hospital, Children's Medical Centre Samples of retraction pockets were processed by a standard process for light microscopy, stained by haematoxylin-eosin. Van Gieson's stain was used for differential staining of collagen, Verhoeff's stain for elastic fibre tissues, Alcian blue for acidic polysaccharides and PAS (Periodic Acid Schiff) method for basement membrane polysaccharides. The following findings were observed in the samples of retraction pockets: hyperkeratosis (100%), hypervascularisations (100%), subepithelial fragmented elastic fibres (96%), myxoid changes (87%), subepithelial inflammatory infiltration (84%), rete pegs (71%), papilomatosis (71%), intraepithelial inflammatory cellularizations, (48%), intraepithelial spongiosis (16%) and parakeratosis (3%). No basement membrane continuity interruptions were observed. Thickness of retraction pocket, thickness of epidermis, occurrence of rete pegs and frequency of fragmented elastic fibres was higher in a Grade III stage RP than Grade II stage RP (according to Charachon). Morphological abnormalities in the structure of retraction pockets in comparison with a healthy tympanic membrane were described. The changes are typical for a structure of cholesteatoma (these changes are common in matrix and perimatrix), supporting retraction theory of its origin. Our observations show that it is inflammation that probably plays a key role in the pathogenesis of retraction pocket. The frequency of some of the changes increases with the stage of retraction pocket (II-III according to Charachon). Basement membrane continuity interruptions are not typical for retraction pockets. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Alzheimer Disease and Related Disorders and Out-of-Pocket Health Care Spending and Burden Among Elderly Medicare Beneficiaries.

    PubMed

    Dwibedi, Nilanjana; Findley, Patricia A; Wiener R, Constance; Shen, Chan; Sambamoorthi, Usha

    2018-03-01

    To estimate the excess burden of out-of-pocket health care spending associated with Alzheimer disease and related disorders (ADRD) among older individuals (age 65 y and older). We adopted a retrospective, cross-sectional study design with data from 2012 Medicare Current Beneficiary Survey. The study sample comprised of elderly community-dwelling individuals who had positive total health care expenditures, and enrolled in Medicare throughout the calendar year (462 with ADRD, and 7160 without ADRD). We estimated the per-capita total annual out-of-pocket spending on health care and out-of-pocket spending by service type: inpatient, outpatient, home health, prescription drugs, and other services. We measured out-of-pocket spending burden by calculating the percentage of income spent on health care and defined high out-of-pocket spending burden as having this percentage above 10%. Multivariable analyses included ordinary least squares regressions and logistic regressions and these analyses adjusted for predisposing, enabling, need, personal health care practices and external environment characteristics. The average annual per-capita out-of-pocket health care spending was greater among individuals with ADRD compared with those without ADRD ($3285 vs. $1895); home health and prescription drugs accounted for 52% of total out-of-pocket spending among individuals with ADRD and 34% among individuals without ADRD. Elderly individuals with ADRD were more likely to have high out-of-pocket spending burden (adjusted odds ratio, 1.49; 95% confidence interval, 1.13-1.97) compared with those without ADRD. ADRD is associated with excess out-of-pocket health care spending, primarily driven by prescription drugs and home health care use.

  18. 3. DOWNHILL SIDE AND END ELEVATION OF COAL POCKETS, WITH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. DOWNHILL SIDE AND END ELEVATION OF COAL POCKETS, WITH RETAINING WALL IN BACKGROUND. VIEW LOOKING NORTHEAST. - Honesdale Coal Pockets, Main & Commercial Streets, between 700 & 800 blocks, Honesdale, Wayne County, PA

  19. Circadian periodicity of resistance to ionizing radiation in the pocket mouse.

    NASA Technical Reports Server (NTRS)

    Lindberg, R. G.; Hayden, P.; Gambino, J. J.

    1971-01-01

    Investigation of the response of pocket mice to Co 60 irradiation delivered at two times of day - namely, the predicted high and low points of the metabolic rate. The validity of torpor as an assay of the circadian period of body temperature in pocket mice and as a basis for selecting irradiation times is examined. A study is made of the mitotic activity in the pocket mouse intestinal epithelium as an example of a physiological rhythm which might influence radiation sensitivity. The results of tests in which pocket mice were exposed to ionizing radiation at two different times of day are cited. It is found that under the investigated conditions pocket mice irradiated during their metabolically active period (2330 hr) live significantly longer than those irradiated while their metabolic rate is low (0900 hr).

  20. Planview Geometry and morphological characteristics of pocket beaches on the Catalan coast (Spain)

    NASA Astrophysics Data System (ADS)

    Bowman, D.; Guillén, J.; López, L.; Pellegrino, V.

    2009-07-01

    Coastal planform studies are a relevant initial stage before launching detailed dynamic field experiments. The aim of this study is to define the planform characteristics of 72 Catalan pocket beaches, natural and man-made, and to determine their sheltering effect, embaymentization and their status of equilibrium. Planform measurements were performed on SIGPAC, 1:5000 orthophoto sets and wave climate was provided by Puertos del Estado (Wana model). Planform parameters were applied and coastal planview indexes were determined. The study shows that the Catalan pocket beaches display a wide range of indentation, suggesting that no single structural, tectonic or morphological control dominates their planform. The man-made pocket beaches typically display indentations which are smaller than those shown by natural pocket beaches. Headland spacing and beach area are positively correlated. The more indented bays are, the shorter their beaches become. Low-indented pocket beaches are the widest and the longest ones. Deep indentation contributes towards beach protection and energy dissipation which counteracts rip efficiency and inhibits the formation of mega-rips. Pocket beaches often show gradual and moderate alongshore changes in texture and beach morphology. One third of the Catalan pocket beaches are "sediment starved", i.e., 60% and more of their embayed shorelines are deprived of beach sediments. Examination of the status of equilibrium demonstrates that most of the Catalan pocket beaches are in an unstable mode, with indentation ratios that are unrelated to the wave obliquity.

  1. A Database Management System Application for the Graduate Programs Office of the School of Systems and Logistics. Volume 2. Technical Reference Manual

    DTIC Science & Technology

    1988-09-01

    CIT C 15 Name of local city. InCSrATE C 2 Name of local state as tw letter abbreviatiom. SIC ZIP C 10 Loa ZIP code. Five or nine digits . InC_ PHKtE C 15...record: 10 Database Dictimary for C: \\ BASE\\PAS1E.MF Field Nane Type Width Decimal Coments PMSCODE C 2 Third and fourth digits of PAS code. ON C 3...Version: 3.01 Date: 09/01/88 Time: 21:34 Report Libary : C: ASE\\GPO.RP1 Date: 08/28/88 Time: 11:32 PRMNT OFTICNS CflRL-PRINrM Nmber of copies: 1 Starting

  2. The Role of the Acid Pocket in Gastroesophageal Reflux Disease.

    PubMed

    Mitchell, David R; Derakhshan, Mohammad H; Robertson, Elaine V; McColl, Kenneth E L

    2016-02-01

    Gastroesophageal reflux disease is one of the commonest chronic conditions in the western world and its prevalence is increasing worldwide. The discovery of the acid pocket explained the paradox of acid reflux occurring more frequently in the postprandial period despite intragastric acidity being low due to the buffering effect of the meal. The acid pocket was first described in 2001 when it was detected as an area of low pH immediately distal to the cardia using dual pH electrode pull-through studies 15 minutes after a meal. It was hypothesized that there was a local pocket of acid close to the gastroesophageal junction that escapes the buffering effect of the meal, and that this is the source of postprandial acidic reflux. The presence of the acid pocket has been confirmed in other studies using different techniques including high-resolution pHmetry, Bravo capsule, magnetic resonance imaging, and scintigraphy. This review aims to describe what we know about the acid pocket including its length, volume, fluid constituents, and its relationship to the lower esophageal sphincter and squamocolumnar junction. We will discuss the possible mechanisms that lead to the formation of the acid pocket and examine what differences exist in patients who suffer from acid reflux. Treatments for reflux disease that affect the acid pocket will also be discussed.

  3. CONTROL SYSTEM FOR ISOTOPE SEPARATING APPARATUS

    DOEpatents

    Barnes, S.W.

    1960-01-26

    A method is described for controlling the position of the ion beams in a calutron used for isotope separation. The U/sup 238/ beams is centered over the U/sup 235/ receiving pocket, the operator monitoring the beam until a maximum reading is achieved on the meter connected to that pocket. Then both beams are simultaneously shifted by a preselected amount to move the U/sup 235/ beam over the U/sup 235/ pocket. A slotted door is placed over the entrance to that pocket during the U/sup 238/ beam centering to reduce the contamination to the pocket, while allowing enough beam to pass for monitoring purposes.

  4. Druggable pockets and binding site centric chemical space: a paradigm shift in drug discovery.

    PubMed

    Pérot, Stéphanie; Sperandio, Olivier; Miteva, Maria A; Camproux, Anne-Claude; Villoutreix, Bruno O

    2010-08-01

    Detection, comparison and analyses of binding pockets are pivotal to structure-based drug design endeavors, from hit identification, screening of exosites and de-orphanization of protein functions to the anticipation of specific and non-specific binding to off- and anti-targets. Here, we analyze protein-ligand complexes and discuss methods that assist binding site identification, prediction of druggability and binding site comparison. The full potential of pockets is yet to be harnessed, and we envision that better understanding of the pocket space will have far-reaching implications in the field of drug discovery, such as the design of pocket-specific compound libraries and scoring functions.

  5. Monte Carlo modeling of the MammoSite(Reg) treatments: Dose effects of air pockets

    NASA Astrophysics Data System (ADS)

    Huang, Yu-Huei Jessica

    In the treatment of early-stage breast cancer, MammoSiteRTM has been used as one of the partial breast irradiation techniques after breast-conserving surgery. The MammoSiteRTM applicator is a single catheter with an inflatable balloon at its distal end that can be placed in the resected cavity (tumor bed). The treatment is performed by delivering the Ir-192 high-dose-rate source through the center lumen of the catheter by a remote afterloader while the balloon is inflated in the tumor bed cavity. In the MammoSiteRTM treatment, it has been found that air pockets occasionally exist and can be seen and measured in CT images. Experiences have shown that about 90% of the patients have air pockets when imaged two days after the balloon placement. The criterion for the air pocket volume is less than or equal to 10% of the planning target volume in volume. The purpose of this study is to quantify dose errors occurring at the interface of the air pocket in MammoSiteRTM treatments with Monte Carlo calculations, so that the dosimetric effects from the air pocket can be fully understood. Modern brachytherapy treatment planning systems typically consider patient anatomy as a homogeneous water medium, and incorrectly model lateral and backscatter radiation during treatment delivery. Heterogeneities complicate the problem and may result in overdosage to the tissue located near the medium interface. This becomes a problem in MammoSiteRTM brachytherapy when air pocket appears during the treatment. The resulting percentage dose difference near the air-tissue interface is hypothesized to be greater than 10% when comparing Monte Carlo N-Particle (version 5) with current treatment planning systems. The specific aims for this study are: (1) Validate Monte Carlo N-Particle (Version 5) source modeling. (2) Develop phantom. (3) Calculate phantom doses with Monte Carlo N-Particle (Version 5) and investigate doses difference between thermoluminescent dosimeter measurement, treatment planning system, and Monte Carlo results. (4) Calculate dose differences for various treatment parameters. The results from thermoliminescent dosimeter phantom measurements proves that with correct geometric and source models, Monte Carlo method can be used to estimate homogeneity and heterogeneity doses in MammoSiteRTM treatment. The resulting dose differences at various points of interests in Monte Carlo calculations were presented and compared between different calculation methods. The air pocket doses were found to be underestimated by the treatment planning system. It was concluded that after correcting for inverse square law, the underestimation error from the treatment planning system will be less than +/- 2.0%, and +/- 3.5%, at the air pocket surface and air pocket planning target volume, respectively, when comparing Monte Carlo N-Particle (version 5) results. If the skin surface is located close to the air pocket, the underestimation effect at the air pocket surface and air pocket planning target volume doses becomes less because the air outside of the skin surface reduces the air pocket inhomogeneity effect. In order to maintain appropriate skin dose within tolerance, the skin surface criterion should be considered as the smallest thickness of the breast tissue located between the air pocket and the skin surface. The thickness should be at least 5 mm. In conclusion, the air pocket outside the balloon had less than 10% inhomogeneity effect based on the situations studied. It is recommended that at least an inverse square correction should be taken into consideration in order to relate clinical outcomes to actual delivered doses to the air pocket and surrounding tissues.

  6. Privacy Protection Versus Cluster Detection in Spatial Epidemiology

    PubMed Central

    Olson, Karen L.; Grannis, Shaun J.; Mandl, Kenneth D.

    2006-01-01

    Objectives. Patient data that includes precise locations can reveal patients’ identities, whereas data aggregated into administrative regions may preserve privacy and confidentiality. We investigated the effect of varying degrees of address precision (exact latitude and longitude vs the center points of zip code or census tracts) on detection of spatial clusters of cases. Methods. We simulated disease outbreaks by adding supplementary spatially clustered emergency department visits to authentic hospital emergency department syndromic surveillance data. We identified clusters with a spatial scan statistic and evaluated detection rate and accuracy. Results. More clusters were identified, and clusters were more accurately detected, when exact locations were used. That is, these clusters contained at least half of the simulated points and involved few additional emergency department visits. These results were especially apparent when the synthetic clustered points crossed administrative boundaries and fell into multiple zip code or census tracts. Conclusions. The spatial cluster detection algorithm performed better when addresses were analyzed as exact locations than when they were analyzed as center points of zip code or census tracts, particularly when the clustered points crossed administrative boundaries. Use of precise addresses offers improved performance, but this practice must be weighed against privacy concerns in the establishment of public health data exchange policies. PMID:17018828

  7. The Zinc Transporter SLC39A13/ZIP13 Is Required for Connective Tissue Development; Its Involvement in BMP/TGF-β Signaling Pathways

    PubMed Central

    Shimoda, Shinji; Mishima, Kenji; Higashiyama, Hiroyuki; Idaira, Yayoi; Asada, Yoshinobu; Kitamura, Hiroshi; Yamasaki, Satoru; Hojyo, Shintaro; Nakayama, Manabu; Ohara, Osamu; Koseki, Haruhiko; dos Santos, Heloisa G.; Bonafe, Luisa; Ha-Vinh, Russia; Zankl, Andreas; Unger, Sheila; Kraenzlin, Marius E.; Beckmann, Jacques S.; Saito, Ichiro; Rivolta, Carlo; Ikegawa, Shiro; Superti-Furga, Andrea; Hirano, Toshio

    2008-01-01

    Background Zinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. Methodology/Principal Findings Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS). The Slc39a13 knockout (Slc39a13-KO) mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP) and TGF-β signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. Conclusions/Significance Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-β signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-β signaling and connective tissue dysfunction. PMID:18985159

  8. Identifiability in N-mixture models: a large-scale screening test with bird data.

    PubMed

    Kéry, Marc

    2018-02-01

    Binomial N-mixture models have proven very useful in ecology, conservation, and monitoring: they allow estimation and modeling of abundance separately from detection probability using simple counts. Recently, doubts about parameter identifiability have been voiced. I conducted a large-scale screening test with 137 bird data sets from 2,037 sites. I found virtually no identifiability problems for Poisson and zero-inflated Poisson (ZIP) binomial N-mixture models, but negative-binomial (NB) models had problems in 25% of all data sets. The corresponding multinomial N-mixture models had no problems. Parameter estimates under Poisson and ZIP binomial and multinomial N-mixture models were extremely similar. Identifiability problems became a little more frequent with smaller sample sizes (267 and 50 sites), but were unaffected by whether the models did or did not include covariates. Hence, binomial N-mixture model parameters with Poisson and ZIP mixtures typically appeared identifiable. In contrast, NB mixtures were often unidentifiable, which is worrying since these were often selected by Akaike's information criterion. Identifiability of binomial N-mixture models should always be checked. If problems are found, simpler models, integrated models that combine different observation models or the use of external information via informative priors or penalized likelihoods, may help. © 2017 by the Ecological Society of America.

  9. Drinking Water Residence Time in Distribution Networks and Emergency Department Visits for Gastrointestinal Illness in Metro Atlanta, Georgia

    PubMed Central

    Moe, Christine L.; Klein, Mitchel; Flanders, W. Dana; Uber, Jim; Amirtharajah, Appiah; Singer, Philip; Tolbert, Paige E.

    2013-01-01

    We examined whether the average water residence time, the time it takes water to travel from the treatment plant to the user, for a zip code was related to the proportion of emergency department (ED) visits for gastrointestinal (GI) illness among residents of that zip code. Individual-level ED data were collected from all hospitals located in the five-county metro Atlanta area from 1993 to 2004. Two of the largest water utilities in the area, together serving 1.7 million people, were considered. People served by these utilities had almost three million total ED visits, 164,937 of them for GI illness. The relationship between water residence time and risk for GI illness was assessed using logistic regression, controlling for potential confounding factors, including patient age and markers of socioeconomic status (SES). We observed a modestly increased risk for GI illness for residents of zip codes with the longest water residence times compared to intermediate residence times (odds ratio (OR) for Utility 1 = 1.07, 95% confidence interval (CI) = 1.03, 1.10; OR for Utility 2 = 1.05, 95% CI = 1.02, 1.08). The results suggest that drinking water contamination in the distribution system may contribute to the burden of endemic GI illness. PMID:19240359

  10. Drinking water residence time in distribution networks and emergency department visits for gastrointestinal illness in Metro Atlanta, Georgia.

    PubMed

    Tinker, Sarah C; Moe, Christine L; Klein, Mitchel; Flanders, W Dana; Uber, Jim; Amirtharajah, Appiah; Singer, Philip; Tolbert, Paige E

    2009-06-01

    We examined whether the average water residence time, the time it takes water to travel from the treatment plant to the user, for a zip code was related to the proportion of emergency department (ED) visits for gastrointestinal (GI) illness among residents of that zip code. Individual-level ED data were collected from all hospitals located in the five-county metro Atlanta area from 1993 to 2004. Two of the largest water utilities in the area, together serving 1.7 million people, were considered. People served by these utilities had almost 3 million total ED visits, 164,937 of them for GI illness. The relationship between water residence time and risk for GI illness was assessed using logistic regression, controlling for potential confounding factors, including patient age and markers of socioeconomic status (SES). We observed a modestly increased risk for GI illness for residents of zip codes with the longest water residence times compared with intermediate residence times (odds ratio (OR) for Utility 1 = 1.07, 95% confidence interval (CI) = 1.03, 1.10; OR for Utility 2 = 1.05, 95% CI = 1.02, 1.08). The results suggest that drinking water contamination in the distribution system may contribute to the burden of endemic GI illness.

  11. Developmental and seasonal expression of PtaHB1, a Populus gene encoding a class III HD-Zip protein, is closely associated with secondary growth and inversely correlated with the level of microRNA (miR166).

    PubMed

    Ko, Jae-Heung; Prassinos, Constantinos; Han, Kyung-Hwan

    2006-01-01

    In contrast to our knowledge of the shoot apical meristem, our understanding of cambium meristem differentiation and maintenance is limited. Class III homeodomain leucine-zipper (HD-Zip) proteins have been shown to play a regulatory role in vascular differentiation. The hybrid aspen (Populus tremulaxPopulus alba) class III HD-Zip transcription factor (PtaHB1) and microRNA 166 (Pta-miR166) family were cloned from hybrid aspen using a combination of in silico and polymerase chain reaction methods. Expression analyses of PtaHB1 and Pta-miR166 were performed by Northern blot analysis. The expression of PtaHB1 was closely associated with wood formation and regulated both developmentally and seasonally, with the highest expression during the active growing season. Also, its expression was inversely correlated with the level of Pta-miR166. Pta-miR166-directed cleavage of PtaHB1 in vivo was confirmed using modified 5'-rapid amplification of cDNA ends (RACE). The expression of Pta-miR166 was much higher in the winter than in the growing seasons, suggesting seasonal and developmental regulation of microRNA in this perennial plant species.

  12. An exploratory study of the relationship between socioeconomic status and motor vehicle safety features.

    PubMed

    Girasek, Deborah C; Taylor, Brett

    2010-04-01

    The purpose of this study was to assess the association between motor vehicle owners' socioeconomic status (SES) and the safety of their motor vehicles. Truncated vehicle identification numbers (VINs) were obtained from the Maryland Motor Vehicle Administration office. ZIP code-level income and educational data were assigned to each VIN. Software was used to identify safety-related vehicle characteristics including crash test rating, availability of electronic stability control and side impact air bags, age, and weight. Correlations and analyses of variance were performed to assess whether a ZIP code's median household income and educational level were associated with its proportion of registered vehicles with safety features. For 13 of the 16 correlations performed, SES was significantly associated with the availability of vehicle safety features in a direction that favored upper-income individuals. Vehicle weight was not associated with income or education. When ZIP codes were divided into median household income quintiles, their mean proportions of safety features also differed significantly, in the same direction, for availability of electronic stability control, side impact air bags, vehicle age, and crash test ratings. Safer motor vehicles appear to be distributed along socioeconomic lines, with lower income groups experiencing more risk. This previously unidentified mechanism of disparity merits further study and the attention of policy makers.

  13. Chromosomal localization and cDNA cloning of the human DBP and TEF genes

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

    Khatib, Z.A.; Inaba, T.; Valentine, M.

    1994-09-15

    The authors have isolated cDNA and genomic clones and determined the human chromosome positions of two genes encoding transcription factors expressed in the liver and the pituitary gland: albumin D-site-binding protein (DBP) and thyrotroph embryonic factor (TEF). Both proteins have been identified as members of the PAR (proline and acidic amino acid-rich) subfamily of bZIP transcription factors in the rat, but human homologues have not been characterized. Using a fluorescence in situ hybridization technique, the DBP locus was assigned to chromosome 19q13, and TEF to chromosome 22q13. Each assignment was confirmed by means of human chromosome segregation in somatic cellmore » hybrids. Coding sequences of DBP and TEF, extending beyond the bZIP domain to the PAR region, were highly conserved in both human-human and interspecies comparisons. Conservation of the exon-intron boundaries of each bZIP domain-encoding exon suggested derivation from a common ancestral gene. DBP and TEF mRNAs were expressed in all tissues and cell lines examined, including brain, lung, liver, spleen, and kidney. Knowledge of the human chromosome locations of these PAR proteins will facilitate studies to assess their involvement in carcinogenesis and other fundamental biological processes. 37 refs., 5 figs., 1 tab.« less

  14. Small Maf proteins (MafF, MafG, MafK): History, structure and function.

    PubMed

    Katsuoka, Fumiki; Yamamoto, Masayuki

    2016-07-25

    The small Maf proteins (sMafs) are basic region leucine zipper (bZIP)-type transcription factors. The basic region of the Maf family is unique among the bZIP factors, and it contributes to the distinct DNA-binding mode of this class of proteins. MafF, MafG and MafK are the three vertebrate sMafs, and no functional differences have been observed among them in terms of their bZIP structures. sMafs form homodimers by themselves, and they form heterodimers with cap 'n' collar (CNC) proteins (p45 NF-E2, Nrf1, Nrf2, and Nrf3) and also with Bach proteins (Bach1 and Bach2). Because CNC and Bach proteins cannot bind to DNA as monomers, sMafs are indispensable partners that are required by CNC and Bach proteins to exert their functions. sMafs lack the transcriptional activation domain; hence, their homodimers act as transcriptional repressors. In contrast, sMafs participate in transcriptional activation or repression depending on their heterodimeric partner molecules and context. Mouse genetic analyses have revealed that various biological pathways are under the regulation of CNC-sMaf heterodimers. In this review, we summarize the history and current progress of sMaf studies in relation to their partners. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Multilevel built environment features and individual odds of overweight and obesity in Utah

    PubMed Central

    Xu, Yanqing; Wen, Ming; Wang, Fahui

    2015-01-01

    Based on the data from the Behavioral Risk Factor Surveillance System (BRFSS) in 2007, 2009 and 2011 in Utah, this research uses multilevel modeling (MLM) to examine the associations between neighborhood built environments and individual odds of overweight and obesity after controlling for individual risk factors. The BRFSS data include information on 21,961 individuals geocoded to zip code areas. Individual variables include BMI (body mass index) and socio-demographic attributes such as age, gender, race, marital status, education attainment, employment status, and whether an individual smokes. Neighborhood built environment factors measured at both zip code and county levels include street connectivity, walk score, distance to parks, and food environment. Two additional neighborhood variables, namely the poverty rate and urbanicity, are also included as control variables. MLM results show that at the zip code level, poverty rate and distance to parks are significant and negative covariates of the odds of overweight and obesity; and at the county level, food environment is the sole significant factor with stronger fast food presence linked to higher odds of overweight and obesity. These findings suggest that obesity risk factors lie in multiple neighborhood levels and built environment features need to be defined at a neighborhood size relevant to residents' activity space. PMID:26251559

  16. Genome-wide identification, expansion, and evolution analysis of homeobox genes and their expression profiles during root development in carrot.

    PubMed

    Que, Feng; Wang, Guang-Long; Li, Tong; Wang, Ya-Hui; Xu, Zhi-Sheng; Xiong, Ai-Sheng

    2018-06-16

    The homeobox gene family, a large family represented by transcription factors, has been implicated in secondary growth, early embryo patterning, and hormone response pathways in plants. However, reports about the information and evolutionary history of the homeobox gene family in carrot are limited. In the present study, a total of 130 homeobox family genes were identified in the carrot genome. Specific codomain and phylogenetic analyses revealed that the genes were classified into 14 subgroups. Whole genome and proximal duplication participated in the homeobox gene family expansion in carrot. Purifying selection also contributed to the evolution of carrot homeobox genes. In Gene Ontology (GO) analysis, most members of the HD-ZIP III and IV subfamilies were found to have a lipid binding (GO:0008289) term. Most HD-ZIP III and IV genes also harbored a steroidogenic acute regulatory protein-related lipid transfer (START) domain. These results suggested that the HD-ZIP III and IV subfamilies might be related to lipid transfer. Transcriptome and quantitative real-time PCR (RT-qPCR) data indicated that members of the WOX and KNOX subfamilies were likely implicated in carrot root development. Our study provided a useful basis for further studies on the complexity and function of the homeobox gene family in carrot.

  17. 1. Photocopy of photograph. ORIGINAL CANAL COAL POCKETS Source: Delaware ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Photocopy of photograph. ORIGINAL CANAL COAL POCKETS Source: Delaware and Hudson Railroad and Canal, by Wayne County Historical Society. - Honesdale Coal Pockets, Main & Commercial Streets, between 700 & 800 blocks, Honesdale, Wayne County, PA

  18. Pocket Guide to Transportation 2017

    DOT National Transportation Integrated Search

    2017-05-01

    The BTS Pocket Guide to Transportation is a quick reference guide to significant transportation statistics. All the previous seven sections plus a new Major Trends section are included. This year marks the 20th anniversary of the Pocket Guide, which ...

  19. Drug-like density: a method of quantifying the "bindability" of a protein target based on a very large set of pockets and drug-like ligands from the Protein Data Bank.

    PubMed

    Sheridan, Robert P; Maiorov, Vladimir N; Holloway, M Katharine; Cornell, Wendy D; Gao, Ying-Duo

    2010-11-22

    One approach to estimating the "chemical tractability" of a candidate protein target where we know the atomic resolution structure is to examine the physical properties of potential binding sites. A number of other workers have addressed this issue. We characterize ~290,000 "pockets" from ~42,000 protein crystal structures in terms of a three parameter "pocket space": volume, buriedness, and hydrophobicity. A metric DLID (drug-like density) measures how likely a pocket is to bind a drug-like molecule. This is calculated from the count of other pockets in its local neighborhood in pocket space that contain drug-like cocrystallized ligands and the count of total pockets in the neighborhood. Surprisingly, despite being defined locally, a global trend in DLID can be predicted by a simple linear regression on log(volume), buriedness, and hydrophobicity. Two levels of simplification are necessary to relate the DLID of individual pockets to "targets": taking the best DLID per Protein Data Bank (PDB) entry (because any given crystal structure can have many pockets), and taking the median DLID over all PDB entries for the same target (because different crystal structures of the same protein can vary because of artifacts and real conformational changes). We can show that median DLIDs for targets that are detectably homologous in sequence are reasonably similar and that median DLIDs correlate with the "druggability" estimate of Cheng et al. (Nature Biotechnology 2007, 25, 71-75).

  20. Prion protein functions as a ferrireductase partner for ZIP14 and DMT1

    PubMed Central

    Qian, Juan; Beserra, Amber; Suda, Srinivas; Singh, Ajay; Hopfer, Ulrich; Chen, Shu G.; Garrick, Michael D.; Turner, Jerrold R.; Knutson, Mitchell D.; Singh, Neena

    2015-01-01

    Excess circulating iron is stored in the liver, and requires reduction of non-Tf-bound-iron (NTBI) and transferrin (Tf)-iron at the plasma membrane and endosomes respectively by ferrireductase (FR) proteins for transport across biological membranes through divalent metal transporters. Here, we report that prion-protein (PrPC), a ubiquitously expressed glycoprotein most abundant on neuronal cells, functions as a FR partner for divalent-metal transporter-1 (DMT1) and ZIP14. Thus, absence of PrPC in PrP-knock-out (PrP−/−) mice resulted in markedly reduced liver iron stores, a deficiency that was not corrected by chronic or acute administration of iron by the oral or intra-peritoneal routes. Likewise, preferential radiolabeling of circulating NTBI with 59Fe revealed significantly reduced uptake and storage of NTBI by the liver of PrP−/− mice relative to matched PrP+/+ controls. However, uptake, storage, and utilization of ferritin-bound iron that does not require reduction for uptake was increased in PrP−/− mice, indicating a compensatory response to the iron-deficiency. Expression of exogenous PrPC in HepG2-cells increased uptake and storage of ferric-iron (Fe3+), not ferrous-iron (Fe2+) from the medium, supporting the function of PrPC as a plasma membrane FR. Co-expression of PrPC with ZIP14 and DMT1 in HepG2 cells increased uptake of Fe3+ significantly, and surprisingly, increased the ratio of N-terminally truncated PrPC forms lacking the FR domain relative to full-length PrPC. Together, these observations indicate that PrPC promotes, and possibly regulates the uptake of NTBI through DMT1 and Zip14 via its FR activity. Implications of these observations for neuronal iron homeostasis under physiological and pathological conditions are discussed. PMID:25862412

  1. Upregulation of Atrogin-1/FBXO32 is not necessary for cartilage destruction in mouse models of osteoarthritis.

    PubMed

    Kim, H-E; Rhee, J; Park, S; Yang, J; Chun, J-S

    2017-03-01

    In a preliminary study, we found that recently identified catabolic regulators of osteoarthritis (OA), including hypoxia-inducible factor (HIF)-2α and members of the zinc-ZIP8-MTF1 axis, upregulate the E3 ubiquitin ligase, Atrogin-1 (encoded by Fbxo32), in chondrocytes. As the ubiquitination/proteasomal degradation pathways are tightly regulated to modulate the expression of catabolic factors in chondrocytes, we examined the in vivo functions of Atrogin-1 in mouse models of OA. The mRNA and protein levels of Atrogin-1 and other regulators of OA were determined in primary cultured mouse chondrocytes, OA human cartilage, and OA cartilage from wild-type (WT) and Fbxo32-knockout (KO) mice subjected to destabilization of the medial meniscus or intra-articular (IA) injection of adenoviruses expressing HIF-2α (Ad-Epas1), ZIP8 (Ad-Zip8), or Atrogin-1 (Ad-Fbxo32). The effect of Atrogin-1 overexpression on the cartilage of WT mice was examined by IA injection of Ad-Fbxo32. Atrogin-1 mRNA levels in chondrocytes were markedly increased by treatment with interleukin-1β, HIF-2α, and members of the zinc-ZIP8-MTF1 axis. Atrogin-1 protein levels were also increased in OA cartilage from humans and various mouse OA models. However, the forced overexpression of Atrogin-1 in chondrocytes did not modulate the expression of cartilage matrix molecules or matrix-degrading enzymes. Moreover, overexpression of Atrogin-1 in the mouse joint tissues failed to cause OA pathogenesis, and Fbxo32 knockout failed to affect post-traumatic OA cartilage destruction in mice. Although Atrogin-1 is upregulated in OA cartilage, overexpression of Atrogin-1 in the joint tissues or knockout of Fbxo32 does not affect OA cartilage destruction in mice. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. Geospatial Analysis of Food Environment Demonstrates Associations with Gestational Diabetes

    PubMed Central

    KAHR, Maike K.; SUTER, Melissa A.; BALLAS, Jerasimos; RAMIN, Susan M.; MONGA, Manju; LEE, Wesley; HU, Min; SHOPE, Cindy D.; CHESNOKOVA, Arina; KRANNICH, Laura; GRIFFIN, Emily N.; MASTROBATTISTA, Joan; DILDY, Gary A.; STREHLOW, Stacy L.; RAMPHUL, Ryan; HAMILTON, Winifred J; AAGAARD, Kjersti M.

    2015-01-01

    Background Gestational diabetes mellitus (GDM) is one of most common complications of pregnancy, with incidence rates varying by maternal age, race/ethnicity, obesity, parity, and family history. Given its increasing prevalence in recent decades, co-variant environmental and sociodemographic factors may be additional determinants of GDM occurrence. Objectives We hypothesized that environmental risk factors, in particular measures of the food environment, may be a diabetes contributor. We employed geospatial modeling in a populous U.S. county to characterize the association of the relative availability of fast food restaurants and supermarkets to GDM. Study Design Utilizing a perinatal database with over 4900 encoded antenatal and outcome variables inclusive of zip code data, 8912 consecutive pregnancies were analyzed for correlations between GDM and food environment based on county-wide food permit registration data. Linkage between pregnancies and food environment was achieved on the basis of validated 5 digit zip code data. The prevalence of supermarkets and fast food restaurants per 100,000 inhabitants for each zip code were gathered from publicly available food permit sources. In order to independently authenticate our findings with objective data, we measured hemoglobin A1c (HbA1c) levels as a function of geospatial distribution of food environment in a matched subset (n=80). Results Residence in neighborhoods with a high prevalence of fast food restaurants (fourth quartile) was significantly associated with an increased risk of developing GDM (relative to first quartile, aOR: 1.63 [95% CI 1.21–2.19]). In multivariate analysis, this association held true after controlling for potential confounders (p=0.002). Measurement of HbA1c levels in a matched subset were significantly increased in association with residence in a zip code with a higher fast food/supermarket ratio (n=80, r=0.251 p<0.05). Conclusions As demonstrated by geospatial analysis, a relationship of food environment and risk for gestational diabetes was identified. PMID:26319053

  3. Interaction between C/EBPbeta and Tax down-regulates human T-cell leukemia virus type I transcription.

    PubMed

    Hivin, P; Gaudray, G; Devaux, C; Mesnard, J-M

    2004-01-20

    The human T-cell leukemia virus type I (HTLV-I) Tax protein trans-activates viral transcription through three imperfect tandem repeats of a 21-bp sequence called Tax-responsive element (TxRE). Tax regulates transcription via direct interaction with some members of the activating transcription factor/CRE-binding protein (ATF/CREB) family including CREM, CREB, and CREB-2. By interacting with their ZIP domain, Tax stimulates the binding of these cellular factors to the CRE-like sequence present in the TxREs. Recent observations have shown that CCAAT/enhancer binding protein beta (C/EBPbeta) forms stable complexes on the CRE site in the presence of CREB-2. Given that C/EBPbeta has also been found to interact with Tax, we analyzed the effects of C/EBPbeta on viral Tax-dependent transcription. We show here that C/EBPbeta represses viral transcription and that Tax is no more able to form a stable complex with CREB-2 on the TxRE site in the presence of C/EBPbeta. We also analyzed the physical interactions between Tax and C/EBPbeta and found that the central region of C/EBPbeta, excluding its ZIP domain, is required for direct interaction with Tax. It is the first time that Tax is described to interact with a basic leucine-zipper (bZIP) factor without recognizing its ZIP domain. Although unexpected, this result explains why C/EBPbeta would be unable to form a stable complex with Tax on the TxRE site and could then down-regulate viral transcription. Lastly, we found that C/EBPbeta was able to inhibit Tax expression in vivo from an infectious HTLV-I molecular clone. In conclusion, we propose that during cell activation events, which stimulate the Tax synthesis, C/EBPbeta may down-regulate the level of HTLV-I expression to escape the cytotoxic-T-lymphocyte response.

  4. Postsynaptic localization of PSD-95 is regulated by all three pathways downstream of TrkB signaling.

    PubMed

    Yoshii, Akira; Constantine-Paton, Martha

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate synaptic plasticity. TrkB triggers three downstream signaling pathways; Phosphatidylinositol 3-kinase (PI3K), Phospholipase Cγ (PLCγ) and Mitogen activated protein kinases/Extracellular signal-regulated kinases (MAPK/ERK). We previously showed two distinct mechanisms whereby BDNF-TrkB pathway controls trafficking of PSD-95, which is the major scaffold at excitatory synapses and is critical for synapse maturation. BDNF activates the PI3K-Akt pathway and regulates synaptic delivery of PSD-95 via vesicular transport (Yoshii and Constantine-Paton, 2007). BDNF-TrkB signaling also triggers PSD-95 palmitoylation and its transport to synapses through the phosphorylation of the palmitoylation enzyme ZDHHC8 by a protein kinase C (PKC; Yoshii etal., 2011). The second study used PKC inhibitors chelerythrine as well as a synthetic zeta inhibitory peptide (ZIP) which was originally designed to block the brain-specific PKC isoform protein kinase Mϖ (PKMϖ). However, recent studies raise concerns about specificity of ZIP. Here, we assessed the contribution of TrkB and its three downstream pathways to the synaptic distribution of endogenous PSD-95 in cultured neurons using chemical and genetic interventions. We confirmed that TrkB, PLC, and PI3K were critical for the postsynaptic distribution of PSD-95. Furthermore, suppression of MAPK/ERK also disrupted PSD-95 expression. Next, we examined the contribution of PKC. While both chelerythrine and ZIP suppressed the postsynaptic localization of PSD-95, RNA interference for PKMϖ did not have a significant effect. This result suggests that the ZIP peptide, widely used as the "specific" PKMϖ antagonist by many investigators may block a PKC variant other than PKMϖ such as PKCλ/ι. Our results indicate that TrkB regulates postsynaptic localization of PSD-95 through all three downstream pathways, but also recommend further work to identify other PKC variants that regulate palmitoylation and synaptic localization of PSD-95.

  5. Differential regulation of muscarinic M2 and M3 receptor signaling in gastrointestinal smooth muscle by caveolin-1.

    PubMed

    Bhattacharya, Sayak; Mahavadi, Sunila; Al-Shboul, Othman; Rajagopal, Senthilkumar; Grider, John R; Murthy, Karnam S

    2013-08-01

    Caveolae act as scaffolding proteins for several G protein-coupled receptor signaling molecules to regulate their activity. Caveolin-1, the predominant isoform in smooth muscle, drives the formation of caveolae. The precise role of caveolin-1 and caveolae as scaffolds for G protein-coupled receptor signaling and contraction in gastrointestinal muscle is unclear. Thus the aim of this study was to examine the role of caveolin-1 in the regulation of Gq- and Gi-coupled receptor signaling. RT-PCR, Western blot, and radioligand-binding studies demonstrated the selective expression of M2 and M3 receptors in gastric smooth muscle cells. Carbachol (CCh) stimulated phosphatidylinositol (PI) hydrolysis, Rho kinase and zipper-interacting protein (ZIP) kinase activity, induced myosin phosphatase 1 (MYPT1) phosphorylation (at Thr(696)) and 20-kDa myosin light chain (MLC20) phosphorylation (at Ser(19)) and muscle contraction, and inhibited cAMP formation. Stimulation of PI hydrolysis, Rho kinase, and ZIP kinase activity, phosphorylation of MYPT1 and MLC20, and muscle contraction in response to CCh were attenuated by methyl β-cyclodextrin (MβCD) or caveolin-1 small interfering RNA (siRNA). Similar inhibition of PI hydrolysis, Rho kinase, and ZIP kinase activity and muscle contraction in response to CCh and gastric emptying in vivo was obtained in caveolin-1-knockout mice compared with wild-type mice. Agonist-induced internalization of M2, but not M3, receptors was blocked by MβCD or caveolin-1 siRNA. Stimulation of PI hydrolysis, Rho kinase, and ZIP kinase activities in response to other Gq-coupled receptor agonists such as histamine and substance P was also attenuated by MβCD or caveolin-1 siRNA. Taken together, these results suggest that caveolin-1 facilitates signaling by Gq-coupled receptors and contributes to enhanced smooth muscle function.

  6. Are neighbourhood social capital and availability of sports facilities related to sports participation among Dutch adolescents?

    PubMed Central

    2012-01-01

    Background The aim of this study is to explore whether availability of sports facilities, parks, and neighbourhood social capital (NSC) and their interaction are associated with leisure time sports participation among Dutch adolescents. Methods Cross-sectional analyses were conducted on complete data from the last wave of the YouRAction evaluation trial. Adolescents (n = 852) completed a questionnaire asking for sports participation, perceived NSC and demographics. Ecometric methods were used to aggregate perceived NSC to zip code level. Availability of sports facilities and parks was assessed by means of geographic information systems within the zip-code area and within a 1600 meter buffer. Multilevel logistic regression analyses, with neighborhood and individual as levels, were conducted to examine associations between physical and social environmental factors and leisure time sports participation. Simple slopes analysis was conducted to decompose interaction effects. Results NSC was significantly associated with sports participation (OR: 3.51 (95%CI: 1.18;10.41)) after adjustment for potential confounders. Availability of sports facilities and availability of parks were not associated with sports participation. A significant interaction between NSC and density of parks within the neighbourhood area (OR: 1.22 (90%CI: 1.01;1.34)) was found. Decomposition of the interaction term showed that adolescents were most likely to engage in leisure time sports when both availability of parks and NSC were highest. Conclusions The results of this study indicate that leisure time sports participation is associated with levels of NSC, but not with availability of parks or sports facilities. In addition, NSC and availability of parks in the zip code area interacted in such a way that leisure time sports participation is most likely among adolescents living in zip code areas with higher levels of NSC, and higher availability of parks. Hence, availability of parks appears only to be important for leisure time sports participation when NSC is high. PMID:22849512

  7. Spatial panel analyses of alcohol outlets and motor vehicle crashes in California: 1999–2008

    PubMed Central

    Ponicki, William R.; Gruenewald, Paul J.; Remer, Lillian G.

    2014-01-01

    Although past research has linked alcohol outlet density to higher rates of drinking and many related social problems, there is conflicting evidence of density’s association with traffic crashes. An abundance of local alcohol outlets simultaneously encourages drinking and reduces driving distances required to obtain alcohol, leading to an indeterminate expected impact on alcohol-involved crash risk. This study separately investigates the effects of outlet density on (1) the risk of injury crashes relative to population and (2) the likelihood that any given crash is alcohol-involved, as indicated by police reports and single-vehicle nighttime status of crashes. Alcohol outlet density effects are estimated using Bayesian misalignment Poisson analyses of all California ZIP codes over the years 1999–2008. These misalignment models allow panel analysis of ZIP-code data despite frequent redefinition of postal-code boundaries, while also controlling for overdispersion and the effects of spatial autocorrelation. Because models control for overall retail density, estimated alcohol-outlet associations represent the extra effect of retail establishments selling alcohol. The results indicate a number of statistically well-supported associations between retail density and crash behavior, but the implied effects on crash risks are relatively small. Alcohol-serving restaurants have a greater impact on overall crash risks than on the likelihood that those crashes involve alcohol, whereas bars primarily affect the odds that crashes are alcohol-involved. Off-premise outlet density is negatively associated with risks of both crashes and alcohol involvement, while the presence of a tribal casino in a ZIP code is linked to higher odds of police-reported drinking involvement. Alcohol outlets in a given area are found to influence crash risks both locally and in adjacent ZIP codes, and significant spatial autocorrelation also suggests important relationships across geographical units. These results suggest that each type of alcohol outlet can have differing impacts on risks of crashing as well as the alcohol involvement of those crashes. PMID:23537623

  8. Expression of the ZNT1 Zinc Transporter from the Metal Hyperaccumulator Noccaea caerulescens Confers Enhanced Zinc and Cadmium Tolerance and Accumulation to Arabidopsis thaliana

    PubMed Central

    Schat, Henk; Aarts, Mark G. M.

    2016-01-01

    Prompt regulation of transition metal transporters is crucial for plant zinc homeostasis. NcZNT1 is one of such transporters, found in the metal hyperaccumulator Brassicaceae species Noccaea caerulescens. It is orthologous to AtZIP4 from Arabidopsis thaliana, an important actor in Zn homeostasis. We examined if the NcZNT1 function contributes to the metal hyperaccumulation of N. caerulescens. NcZNT1 was found to be a plasma-membrane located metal transporter. Constitutive overexpression of NcZNT1 in A. thaliana conferred enhanced tolerance to exposure to excess Zn and Cd supply, as well as increased accumulation of Zn and Cd and induction of the Fe deficiency response, when compared to non-transformed wild-type plants. Promoters of both genes were induced by Zn deficiency in roots and shoots of A. thaliana. In A. thaliana, the AtZIP4 and NcZNT1 promoters were mainly active in cortex, endodermis and pericycle cells under Zn deficient conditions. In N. caerulescens, the promoters were active in the same tissues, though the activity of the NcZNT1 promoter was higher and not limited to Zn deficient conditions. Common cis elements were identified in both promoters by 5’ deletion analysis. These correspond to the previously determined Zinc Deficiency Responsive Elements found in A. thaliana to interact with two redundantly acting transcription factors, bZIP19 and bZIP23, controlling the Zn deficiency response. In conclusion, these results suggest that NcZNT1 is an important factor in contributing to Zn and Cd hyperaccumulation in N. caerulescens. Differences in cis- and trans-regulators are likely to account for the differences in expression between A. thaliana and N. caerulescens. The high, constitutive NcZNT1 expression in the stele of N. caerulescens roots implicates its involvement in long distance root-to-shoot metal transport by maintaining a Zn/Cd influx into cells responsible for xylem loading. PMID:26930473

  9. Geospatial analysis of food environment demonstrates associations with gestational diabetes.

    PubMed

    Kahr, Maike K; Suter, Melissa A; Ballas, Jerasimos; Ramin, Susan M; Monga, Manju; Lee, Wesley; Hu, Min; Shope, Cindy D; Chesnokova, Arina; Krannich, Laura; Griffin, Emily N; Mastrobattista, Joan; Dildy, Gary A; Strehlow, Stacy L; Ramphul, Ryan; Hamilton, Winifred J; Aagaard, Kjersti M

    2016-01-01

    Gestational diabetes mellitus (GDM) is one of most common complications of pregnancy, with incidence rates varying by maternal age, race/ethnicity, obesity, parity, and family history. Given its increasing prevalence in recent decades, covariant environmental and sociodemographic factors may be additional determinants of GDM occurrence. We hypothesized that environmental risk factors, in particular measures of the food environment, may be a diabetes contributor. We employed geospatial modeling in a populous US county to characterize the association of the relative availability of fast food restaurants and supermarkets to GDM. Utilizing a perinatal database with >4900 encoded antenatal and outcome variables inclusive of ZIP code data, 8912 consecutive pregnancies were analyzed for correlations between GDM and food environment based on countywide food permit registration data. Linkage between pregnancies and food environment was achieved on the basis of validated 5-digit ZIP code data. The prevalence of supermarkets and fast food restaurants per 100,000 inhabitants for each ZIP code were gathered from publicly available food permit sources. To independently authenticate our findings with objective data, we measured hemoglobin A1c levels as a function of geospatial distribution of food environment in a matched subset (n = 80). Residence in neighborhoods with a high prevalence of fast food restaurants (fourth quartile) was significantly associated with an increased risk of developing GDM (relative to first quartile: adjusted odds ratio, 1.63; 95% confidence interval, 1.21-2.19). In multivariate analysis, this association held true after controlling for potential confounders (P = .002). Measurement of hemoglobin A1c levels in a matched subset were significantly increased in association with residence in a ZIP code with a higher fast food/supermarket ratio (n = 80, r = 0.251 P < .05). As demonstrated by geospatial analysis, a relationship of food environment and risk for gestational diabetes was identified. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Rupture of DNA aptamer: New insights from simulations

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

    Mishra, Rakesh Kumar; Nath, Shesh; Kumar, Sanjay

    2015-10-28

    Base-pockets (non-complementary base-pairs) in a double-stranded DNA play a crucial role in biological processes. Because of thermal fluctuations, it can lower the stability of DNA, whereas, in case of DNA aptamer, small molecules, e.g., adenosinemonophosphate and adenosinetriphosphate, form additional hydrogen bonds with base-pockets termed as “binding-pockets,” which enhance the stability. Using the Langevin dynamics simulations of coarse grained model of DNA followed by atomistic simulations, we investigated the influence of base-pocket and binding-pocket on the stability of DNA aptamer. Striking differences have been reported here for the separation induced by temperature and force, which require further investigation by single moleculemore » experiments.« less

  11. A salt bridge turns off the foot-pocket in class-II HDACs.

    PubMed

    Zhou, Jingwei; Yang, Zuolong; Zhang, Fan; Luo, Hai-Bin; Li, Min; Wu, Ruibo

    2016-08-21

    Histone Deacetylases (HDACs) are promising anticancer targets and several selective inhibitors have been created based on the architectural differences of foot-pockets among HDACs. However, the "gate-keeper" of foot-pockets is still controversial. Herein, it is for the first time revealed that a conserved R-E salt bridge plays a critical role in keeping foot-pockets closed in class-II HDACs by computational simulations. This finding is further substantiated by our mutagenesis experiments.

  12. A randomised crossover comparison of mouth-to-face-shield ventilation and mouth-to-pocket-mask ventilation by surf lifeguards in a manikin.

    PubMed

    Adelborg, K; Bjørnshave, K; Mortensen, M B; Espeseth, E; Wolff, A; Løfgren, B

    2014-07-01

    Thirty surf lifeguards (mean (SD) age: 25.1 (4.8) years; 21 male, 9 female) were randomly assigned to perform 2 × 3 min of cardiopulmonary resuscitation on a manikin using mouth-to-face-shield ventilation (AMBU LifeKey) and mouth-to-pocket-mask ventilation (Laerdal Pocket Mask). Interruptions in chest compressions, effective ventilation (visible chest rise) ratio, tidal volume and inspiratory time were recorded. Interruptions in chest compressions per cycle were increased with mouth-to-face-shield ventilation (mean (SD) 8.6 (1.7) s) compared with mouth-to-pocket-mask ventilation (6.9 (1.2) s, p < 0.0001). The proportion of effective ventilations was less using mouth-to-face-shield ventilation (199/242 (82%)) compared with mouth-to-pocket-mask ventilation (239/240 (100%), p = 0.0002). Tidal volume was lower using mouth-to-face-shield ventilation (mean (SD) 0.36 (0.20) l) compared with mouth-to-pocket-mask ventilation (0.45 (0.20) l, p = 0.006). No differences in inspiratory times were observed between mouth-to-face-shield ventilation and mouth-to-pocket-mask ventilation. In conclusion, mouth-to-face-shield ventilation increases interruptions in chest compressions, reduces the proportion of effective ventilations and decreases delivered tidal volumes compared with mouth-to-pocket-mask ventilation. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

  13. Cigarette smoking in Chinese adolescents: importance of controlling the amount of pocket money.

    PubMed

    Ma, J; Zhu, J; Li, N; He, Y; Cai, Y; Qiao, Y; Redmon, P; Wang, Z

    2013-07-01

    To estimate the proportion of smokers that could potentially have been prevented from smoking by limiting the amount of pocket money received by Chinese adolescents. Cross-sectional study. Current smoking, ever smoking and the amount of pocket money were determined through self-administered questionnaires among 12,708 adolescents (aged 12-18 years) from 21 schools in Shanghai, China. Adjusted odds ratios for current smoking ranged from 2.0 [95% confidence interval (CI) 1.5-2.7] for adolescents receiving 200-399 Reminbin (RMB)/month as pocket money to 6.5 (95% CI 3.3-12.7) for those receiving ≥1000 RMB/month, compared with those receiving <200 RMB/month. The crude population-attributable risk percentage (PAR%) due to higher pocket money (≥200 RMB/month) for current smoking was 50.4% (95% CI 42.2-57.4), and adjusted PAR% was 43.3% (95% CI 30.7-53.1). Approximately half of current smokers may have been prevented from smoking if pocket money was limited to <200 RMB/month among Chinese adolescents. An even larger proportion could have been prevented from smoking if pocket money was reduced further. It is recommended that future intervention programmes should target parents to reduce the amount of pocket money in China. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  14. Raf Kinase Inhibitory Protein Function Is Regulated via a Flexible Pocket and Novel Phosphorylation-Dependent Mechanism▿ †

    PubMed Central

    Granovsky, Alexey E.; Clark, Matthew C.; McElheny, Dan; Heil, Gary; Hong, Jia; Liu, Xuedong; Kim, Youngchang; Joachimiak, Grazyna; Joachimiak, Andrzej; Koide, Shohei; Rosner, Marsha Rich

    2009-01-01

    Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a loss or switch in the function of yeast or plant RKIP homologues. However, the mechanism by which the pocket influences RKIP function is unknown. Here we show that the pocket integrates two regulatory signals, phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf-1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally, ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance studies reveal that the pocket is highly dynamic, rationalizing its capacity to interact with distinct partners and be involved in allosteric regulation. Our results show that RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway. This mechanism is an example of an emerging theme involving the regulation of signaling proteins and their interaction with effectors at the level of protein dynamics. PMID:19103740

  15. Raf kinase inhibitory protein function is regulated via a flexible pocket and novel phosphorylation-dependent mechanism.

    PubMed

    Granovsky, Alexey E; Clark, Matthew C; McElheny, Dan; Heil, Gary; Hong, Jia; Liu, Xuedong; Kim, Youngchang; Joachimiak, Grazyna; Joachimiak, Andrzej; Koide, Shohei; Rosner, Marsha Rich

    2009-03-01

    Raf kinase inhibitory protein (RKIP/PEBP1), a member of the phosphatidylethanolamine binding protein family that possesses a conserved ligand-binding pocket, negatively regulates the mammalian mitogen-activated protein kinase (MAPK) signaling cascade. Mutation of a conserved site (P74L) within the pocket leads to a loss or switch in the function of yeast or plant RKIP homologues. However, the mechanism by which the pocket influences RKIP function is unknown. Here we show that the pocket integrates two regulatory signals, phosphorylation and ligand binding, to control RKIP inhibition of Raf-1. RKIP association with Raf-1 is prevented by RKIP phosphorylation at S153. The P74L mutation increases kinase interaction and RKIP phosphorylation, enhancing Raf-1/MAPK signaling. Conversely, ligand binding to the RKIP pocket inhibits kinase interaction and RKIP phosphorylation by a noncompetitive mechanism. Additionally, ligand binding blocks RKIP association with Raf-1. Nuclear magnetic resonance studies reveal that the pocket is highly dynamic, rationalizing its capacity to interact with distinct partners and be involved in allosteric regulation. Our results show that RKIP uses a flexible pocket to integrate ligand binding- and phosphorylation-dependent interactions and to modulate the MAPK signaling pathway. This mechanism is an example of an emerging theme involving the regulation of signaling proteins and their interaction with effectors at the level of protein dynamics.

  16. Exploration of the effect of sequence variations located inside the binding pocket of HIV-1 and HIV-2 proteases.

    PubMed

    Triki, Dhoha; Billot, Telli; Visseaux, Benoit; Descamps, Diane; Flatters, Delphine; Camproux, Anne-Claude; Regad, Leslie

    2018-04-10

    HIV-2 protease (PR2) is naturally resistant to most FDA (Food and Drug Administration)-approved HIV-1 protease inhibitors (PIs), a major antiretroviral class. In this study, we compared the PR1 and PR2 binding pockets extracted from structures complexed with 12 ligands. The comparison of PR1 and PR2 pocket properties showed that bound PR2 pockets were more hydrophobic with more oxygen atoms and fewer nitrogen atoms than PR1 pockets. The structural comparison of PR1 and PR2 pockets highlighted structural changes induced by their sequence variations and that were consistent with these property changes. Specifically, substitutions at residues 31, 46, and 82 induced structural changes in their main-chain atoms that could affect PI binding in PR2. In addition, the modelling of PR1 mutant structures containing V32I and L76M substitutions revealed a cooperative mechanism leading to structural deformation of flap-residue 45 that could modify PR2 flexibility. Our results suggest that substitutions in the PR1 and PR2 pockets can modify PI binding and flap flexibility, which could underlie PR2 resistance against PIs. These results provide new insights concerning the structural changes induced by PR1 and PR2 pocket variation changes, improving the understanding of the atomic mechanism of PR2 resistance to PIs.

  17. Dynamic water behaviour due to one trapped air pocket in a laboratory pipeline apparatus

    NASA Astrophysics Data System (ADS)

    Bergant, A.; Karadžić, U.; Tijsseling, A.

    2016-11-01

    Trapped air pockets may cause severe operational problems in hydropower and water supply systems. A locally isolated air pocket creates distinct amplitude, shape and timing of pressure pulses. This paper investigates dynamic behaviour of a single trapped air pocket. The air pocket is incorporated as a boundary condition into the discrete gas cavity model (DGCM). DGCM allows small gas cavities to form at computational sections in the method of characteristics (MOC). The growth of the pocket and gas cavities is described by the water hammer compatibility equation(s), the continuity equation for the cavity volume, and the equation of state of an ideal gas. Isentropic behaviour is assumed for the trapped gas pocket and an isothermal bath for small gas cavities. Experimental investigations have been performed in a laboratory pipeline apparatus. The apparatus consists of an upstream end high-pressure tank, a horizontal steel pipeline (total length 55.37 m, inner diameter 18 mm), four valve units positioned along the pipeline including the end points, and a downstream end tank. A trapped air pocket is captured between two ball valves at the downstream end of the pipeline. The transient event is initiated by rapid opening of the upstream end valve; the downstream end valve stays closed during the event. Predicted and measured results for a few typical cases are compared and discussed.

  18. The Effect of Pharmacy Benefit Design on Patient-Physician Communication About Costs

    PubMed Central

    Shrank, William H; Fox, Sarah A; Kirk, Adele; Ettner, Susan L; Cantrell, Clairessa H; Glassman, Peter; Asch, Steven M

    2006-01-01

    BACKGROUND Incentive-based formularies have been widely instituted to control the rising costs of prescription drugs. To work properly, such formularies depend on patients to be aware of financial incentives and communicate their cost preferences with prescribing physicians. The impact of financial incentives on patient awareness of and communication about those costs is unknown. OBJECTIVE To evaluate the relationship between enrollment in incentive-based pharmacy benefit plans and awareness of out-of-pocket costs and rates of communication about out-of-pocket costs. DESIGN A matched telephone survey of patients and their primary care physicians. SETTING Los Angeles County. PARTICIPANTS One thousand nine hundred and seventeen patients aged 53 to 82 (73% response rate). MEASUREMENTS Patient-reported pharmacy benefit design, knowledge of out-of-pocket costs, and discussion of out-of-pocket costs with physicians. RESULTS Sixty-two percent of patients who had prescription drug coverage and were aware of their pharmacy benefit design reported being enrolled in incentive-based plans. The majority of these (54%) were “never” or only “sometimes” aware of their out-of-pocket cost requirements at the time of the physician visit. After controlling for numerous physician and patient level variables, we found that patients enrolled in pharmacy benefit designs requiring no copayments were more likely to report they “never” discuss out-of-pocket costs with physicians compared with patients enrolled in incentive-based pharmacy benefit designs (81% vs 67%, P =.001) and patients with no prescription druginsurance (57%, P <.001). CONCLUSIONS Incentive-based pharmacy benefit plans and lack of insurance are associated with increased rates of discussions about out-of-pocket costs. Nonetheless, most incentive-based enrollees are unaware of out-of-pocket costswhen prescriptions are written and never discuss out-of-pocket costs with their physicians, likely mitigating the effectiveness of financial incentives to guide decision making. Considering that out-of-pocket costs are associated with adherence to medical therapy, interventions to improve patient access to out-of-pocket cost information and the frequency of patient-physician discussions about costs are needed. PMID:16686808

  19. Ultrasonic Abrasive Removal Of EDM Recast

    NASA Technical Reports Server (NTRS)

    Mandel, Johnny L.; Jacobson, Marlowe S.

    1990-01-01

    Ultrasonic abrasive process removes layer of recast material generated during electrical-discharge machining (EDM) of damper pocket on turbine blade. Form-fitted tool vibrated ultrasonically in damper pocket from which material removed. Vibrations activate abrasive in pocket. Amount of material removed controlled precisely.

  20. Periodontal Pocket Depth, Hyperglycemia, and Progression of Chronic Kidney Disease: A Population-Based Longitudinal Study.

    PubMed

    Chang, Jia-Feng; Yeh, Jih-Chen; Chiu, Ya-Lin; Liou, Jian-Chiun; Hsiung, Jing-Ru; Tung, Tao-Hsin

    2017-01-01

    No large epidemiological study has been conducted to investigate the interaction and joint effects of periodontal pocket depth and hyperglycemia on progression of chronic kidney disease in patients with periodontal diseases. Periodontal pocket depth was utilized for the grading severity of periodontal disease in 2831 patients from January 2002 to June 2013. Progression of chronic kidney disease was defined as progression of color intensity in glomerular filtration rate and albuminuria grid of updated Kidney Disease-Improving Global Outcomes guidelines. Multivariable-adjusted hazard ratios (aHR) in various models were presented across different levels of periodontal pocket depth and hemoglobin A1c (HbA1c) in forest plots and 3-dimensional histograms. During 7621 person-years of follow-up, periodontal pocket depth and HbA1C levels were robustly associated with incremental risks for progression of chronic kidney disease (aHR 3.1; 95% confidence interval [CI], 2.0-4.6 for periodontal pocket depth >4.5 mm, and 2.5; 95% CI, 1.1-5.4 for HbA1C >6.5%, respectively). The interaction between periodontal pocket depth and HbA1C on progression of chronic kidney disease was strong (P <.01). Patients with higher periodontal pocket depth (>4.5 mm) and higher HbA1C (>6.5%) had the greatest risk (aHR 4.2; 95% CI, 1.7-6.8) compared with the lowest aHR group (periodontal pocket depth ≤3.8 mm and HbA1C ≤6%). Our study identified combined periodontal pocket depth and HbA1C as a valuable predictor of progression of chronic kidney disease in patients with periodontal diseases. While considering the interaction between periodontal diseases and hyperglycemia, periodontal survey and optimizing glycemic control are warranted to minimize the risk of worsening renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

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