Science.gov

Sample records for acid family phytosiderophores

  1. Biosynthesis of Phytosiderophores 1

    PubMed Central

    Shojima, Shinsuke; Nishizawa, Naoko-Kishi; Fushiya, Shinji; Nozoe, Shigeo; Irifune, Tomohiro; Mori, Satoshi

    1990-01-01

    2′ -Deoxymugineic acid (DMA), one of mugineic acid-family phytosiderophores (MAs), was synthesized in vitro both from l-methionine and from nicotianamine (NA) with a cell-free system derived from root tips of iron-deficient barley (Hordeum vulgare L.). The reactions producing DMA from NA needed an amino group acceptor (i.e. 2-oxoglutarate, pyruvate, or oxalacetic acid) and a reductant (i.e. NADH or NADPH). The activity of the enzymes to produce NA from l-methionine was the highest at about pH 9. This biosynthetic activity was markedly induced by iron-deficiency stress. The synthesis of NA from S-adenosyl-l-methionine was more efficient than from l-methionine. From the results with the cell-free system reported here, we propose a revised biosynthetic pathway of MAs. Images Figure 5 PMID:16667646

  2. The Phytosiderophore Efflux Transporter TOM2 Is Involved in Metal Transport in Rice*

    PubMed Central

    Nozoye, Tomoko; Nagasaka, Seiji; Kobayashi, Takanori; Sato, Yuki; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K.

    2015-01-01

    Iron is an essential metal element for all living organisms. Graminaceous plants produce and secrete mugineic acid family phytosiderophores from their roots to acquire iron in the soil. Phytosiderophores chelate and solubilize insoluble iron hydroxide in the soil. Subsequently, plants take up iron-phytosiderophore complexes through specific transporters on the root cell membrane. Phytosiderophores are also thought to be important for the internal transport of various transition metals, including iron. In this study, we analyzed TOM2 and TOM3, rice homologs of transporter of mugineic acid family phytosiderophores 1 (TOM1), a crucial efflux transporter directly involved in phytosiderophore secretion into the soil. Transgenic rice analysis using promoter-β-glucuronidase revealed that TOM2 was expressed in tissues involved in metal translocation, whereas TOM3 was expressed only in restricted parts of the plant. Strong TOM2 expression was observed in developing tissues during seed maturation and germination, whereas TOM3 expression was weak during seed maturation. Transgenic rice in which TOM2 expression was repressed by RNA interference showed growth defects compared with non-transformants and TOM3-repressed rice. Xenopus laevis oocytes expressing TOM2 released 14C-labeled deoxymugineic acid, the initial phytosiderophore compound in the biosynthetic pathway in rice. In onion epidermal and rice root cells, the TOM2-GFP fusion protein localized to the cell membrane, indicating that the TOM2 protein is a transporter for phytosiderophore efflux to the cell exterior. Our results indicate that TOM2 is involved in the internal transport of deoxymugineic acid, which is required for normal plant growth. PMID:26432636

  3. Experimental Determination of Zinc Isotope Fractionation in Complexes with the Phytosiderophore 2'-Deoxymugeneic Acid (DMA) and Its Structural Analogues, and Implications for Plant Uptake Mechanisms.

    PubMed

    Marković, Tamara; Manzoor, Saba; Humphreys-Williams, Emma; Kirk, Guy Jd; Vilar, Ramon; Weiss, Dominik J

    2017-01-03

    The stable isotope signatures of zinc and other metals are increasingly used to study plant and soil processes. Complexation with phytosiderophores is a key reaction and understanding the controls of isotope fractionation is central to such studies. Here, we investigated isotope fractionation during complexation of Zn(2+) with the phytosiderophore 2'-deoxymugeneic acid (DMA), and with three commercially available structural analogues of DMA: EDTA, TmDTA, and CyDTA. We used ion exchange chromatography to separate free and complexed zinc, and identified appropriate cation exchange resins for the individual systems. These were Chelex-100 for EDTA and CyDTA, Amberlite CG50 for TmDTA and Amberlite IR120 for DMA. With all the ligands we found preferential partitioning of isotopically heavy zinc in the complexed form, and the extent of fractionation was independent of the Zn:ligand ratio used, indicating isotopic equilibrium and that the results were not significantly affected by artifacts during separation. The fractionations (in ‰) were +0.33 ± 0.07 (1σ, n = 3), + 0.45 ± 0.02 (1σ, n = 2), + 0.62 ± 0.05 (1σ, n = 3) and +0.30 ± 0.07 (1σ, n = 4) for EDTA, TmDTA, CyDTA, and DMA, respectively. Despite the similarity in Zn-coordinating donor groups, the fractionation factors are significantly different and extent of fractionation seems proportional to the complexation stability constant. The extent of fractionation with DMA agreed with observed fractionations in zinc uptake by paddy rice in field experiments, supporting the possible involvement of DMA in zinc uptake by rice.

  4. Phytosiderophore Efflux Transporters Are Crucial for Iron Acquisition in Graminaceous Plants*

    PubMed Central

    Nozoye, Tomoko; Nagasaka, Seiji; Kobayashi, Takanori; Takahashi, Michiko; Sato, Yuki; Sato, Yoko; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K.

    2011-01-01

    Eukaryotic organisms have developed diverse mechanisms for the acquisition of iron, which is required for their survival. Graminaceous plants use a chelation strategy. They secrete phytosiderophore compounds, which solubilize iron in the soil, and then take up the resulting iron-phytosiderophore complexes. Bacteria and mammals also secrete siderophores to acquire iron. Although phytosiderophore secretion is crucial for plant growth, its molecular mechanism remains unknown. Here, we show that the efflux of deoxymugineic acid, the primary phytosiderophore from rice and barley, involves the TOM1 and HvTOM1 genes, respectively. Xenopus laevis oocytes expressing TOM1 or HvTOM1 released 14C-labeled deoxymugineic acid but not 14C-labeled nicotianamine, a structural analog and biosynthetic precursor of deoxymugineic acid, indicating that the TOM1 and HvTOM1 proteins are the phytosiderophore efflux transporters. Under conditions of iron deficiency, rice and barley roots express high levels of TOM1 and HvTOM1, respectively, and the overexpression of these genes increased tolerance to iron deficiency. In rice roots, the efficiency of deoxymugineic acid secretion was enhanced by overexpression of TOM1 and decreased by its repression, providing further evidence that TOM1 encodes the efflux transporter of deoxymugineic acid. We have also identified two genes encoding efflux transporters of nicotianamine, ENA1 and ENA2. Our identification of phytosiderophore efflux transporters has revealed the final piece in the molecular machinery of iron acquisition in graminaceous plants. PMID:21156806

  5. Reduced Cd accumulation in Zea mays: a protective role for phytosiderophores?

    PubMed

    Hill, Koralie A; Lion, Leonard W; Ahner, Beth A

    2002-12-15

    Cadmium is a nonessential trace metal and a frequent soil contaminant. Because plants vary in their accumulation of Cd, an understanding of the specific processes that control uptake could reveal methods for reducing Cd levels in edible plant tissues and conversely increasing Cd accumulation in plants used for phytoremediation. Phytosiderophores are iron chelators excreted by graminaceous plants under conditions of iron limitation, but they also complex other metals including cadmium. Here we examine the influence of Cd exposure on phytosiderophore production by hydroponically grown maize. Cd increased the rate of the phytosiderophore 2'-deoxymugineic acid (DMA) release under both Fe-sufficient and Fe-limiting conditions (+/-Fe). In addition, the -Fe plants released more DMA while taking up less Cd than the +Fe plants. In other short-term Cd uptake experiments, plants exposed to Cd in the presence of root exudates in which the DMA-Cd complex was likely the dominant Cd species displayed reduced Cd accumulation in root tissue, and plants similarly exposed to strongly chelated Cd in the presence of EDTA (employed as a positive control) contained the least Cd. Collectively, these results indicate that Cd stress causes Fe deficiency symptoms that result in greater DMA production by maize roots, and then the DMA appears to reduce Cd accumulation.

  6. A sensitive LC-ESI-Q-TOF-MS method reveals novel phytosiderophores and phytosiderophore-iron complexes in barley.

    PubMed

    Tsednee, Munkhtsetseg; Mak, Yit-Wai; Chen, Yet-Ran; Yeh, Kuo-Chen

    2012-09-01

    The direct analysis of phytosiderophores (PSs) and their metal complexes in plants is critical to understanding the biological functions of different PSs. Here we report on a rapid and highly sensitive liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (LC-ESI-Q-TOF-MS) method for the direct and simultaneous determination of free PSs and their ferric complexes in plants. In addition to previously reported PSs--deoxymugineic acid (DMA), mugineic acid (MA) and epihydroxymugineic acid (epi-HMA)--two more PSs, avenic acid (AVA) and hydroxyavenic acid (HAVA), were identified by this method in roots of Hordeum vulgare cv Himalaya and in root exudates under iron (Fe) deficiency. The two identified PSs could be responsible for Fe acquisition under Fe deficiency because of their relative abundance and ability to form ferric complexes in secreted root exudates. This LC-ESI-Q-TOF-MS method greatly facilitates the identification of free PSs and PS-Fe complexes in one plant sample. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  7. Yellow Stripe1. Expanded Roles for the Maize Iron-Phytosiderophore Transporter1

    PubMed Central

    Roberts, Louis A.; Pierson, Abbey J.; Panaviene, Zivile; Walker, Elsbeth L.

    2004-01-01

    Graminaceous monocots, including most of the world's staple grains (i.e. rice, corn, and wheat) use a chelation strategy (Strategy II) for primary acquisition of iron from the soil. Strategy II plants secrete phytosiderophores (PS), compounds of the mugineic acid family that form stable Fe(III) chelates in soil. Uptake of iron-PS chelates, which occurs through specific transporters at the root surface, thus represents the primary route of iron entry into Strategy II plants. The gene Yellow stripe1 (Ys1) encodes the Fe(III)-PS transporter of maize (Zea mays). Here the physiological functions performed by maize YS1 were further defined by examining the pattern of Ys1 mRNA and protein accumulation and by defining YS1 transport specificity in detail. YS1 is able to translocate iron that is bound either by PS or by the related compound, nicotianamine; thus, the role of YS1 may be to transport either of these complexes. Ys1 expression at both the mRNA and protein levels responds rapidly to changes in iron availability but is not strongly affected by limitation of copper or zinc. Our data provide no support for the idea that YS1 is a transporter of zinc-PS, based on YS1 biochemical activity and Ys1 mRNA expression patterns in response to zinc deficiency. YS1 is capable of transporting copper-PS, but expression data suggest that the copper-PS uptake has limited significance in primary uptake of copper. PMID:15107503

  8. Early senescence of the oldest leaves of Fe-deficient barley plants may contribute to phytosiderophore release from the roots.

    PubMed

    Higuchi, Kyoko; Iwase, Jun; Tsukiori, Yoshifumi; Nakura, Daiki; Kobayashi, Nahoko; Ohashi, Hidenori; Saito, Akihiro; Miwa, Eitaro

    2014-07-01

    Barley (Hordeum vulgare), which tolerates iron (Fe) deficiency, secretes a large amount of phytosiderophores from its roots. However, how barley is able to allocate resources for phytosiderophore synthesis when the carbon assimilation rate is reduced by Fe deficiency is unknown. We previously suggested that the acceleration of senescence in older leaves triggered by Fe deficiency may allow the recycling of assimilates to contribute to phytosiderophore synthesis. In this work, we show the relationship between an increase in the C/N ratio in older leaves and Fe-deficiency tolerance among three barley cultivars. The increase in the C/N ratio suggests an enhanced capacity for the retranslocation of carbohydrates or amino acids from older leaves to the sink organs. An increase in the sucrose concentration in Fe-deficient barley also suggests active redistribution of assimilates. This metabolic modulation may be supported by accelerated senescence of older leaves, as Fe deficiency increased the expression of senescence-associated genes. The older leaves of Fe-deficient barley maintained CO2 assimilation under Fe deficiency. Barley that had been Fe-deficient for 3 days preferentially allocated newly assimilated (13) C to the roots and nutrient solution. Interestingly, the oldest leaf of Fe-deficient barley released more (13) C into the nutrient solution than the second oldest leaf. Thus, the balance between anabolism and catabolism in older leaves, supported by highly regulated senescence, plays a key role in metabolic adaptation in Fe-deficient barley.

  9. Phytosiderophore Effects on Subsurface Actinide Contaminants: Potential for Phytostabilization and Phytoextraction

    SciTech Connect

    Ruggiero, Christy

    2003-06-01

    This project seeks to determine the potential of phytosiderophore-producing plants for phytostabilization and phytoextraction of actinides and some metal soil contaminants. Phytosiderophores are secreted by graminaceous plants such as barley and wheat for the solubilization, mobilization and uptake of Fe and other essential nutrients from soils. The ability for these phytosiderophores to chelate and absorb actinides using the same uptake system as for Fe is hereby investigated though characterization of actinide-phytosiderophore complexes (independently of plants), and characterization of plant uptake of such complexes.

  10. Transgenic petunia with the iron(III)-phytosiderophore transporter gene acquires tolerance to iron deficiency in alkaline environments.

    PubMed

    Murata, Yoshiko; Itoh, Yoshiyuki; Iwashita, Takashi; Namba, Kosuke

    2015-01-01

    Iron is an essential nutrient for all plants. However, terrestrial plants often suffer from iron deficiency in alkaline soil due to its extremely low solubility. Alkaline soil accounts for about 30% of all cultivated ground in the world. Plants have evolved two distinct strategies, I and II, for iron uptake from the soil. Dicots and non-graminaceous monocots use Strategy I, which is primarily based on the reduction of iron(III) to iron(II) and the uptake of iron(II) by the iron-regulated transporter, IRT1. In contrast, graminaceous plants use Strategy II to efficiently acquire insoluble iron(III). Strategy II comprises the synthesis and secretion of iron-chelating phytosiderophores, such as mugineic acids and the Yellow Stripe 1 transporter proteins of the iron(III)-phytosiderophore complex. Barley, which exhibits the highest tolerance to iron deficiency in alkaline soil among graminaceous plants, utilizes mugineic acids and the specific iron(III)-mugineic acids transporter, HvYS1. In this study, we established the transgenic plant Petunia hybrida, which originally had only Strategy I, by introducing the HvYS1 transporter gene derived from barley. When the transgenic plants were grown hydroponically in media containing the iron(III)-2'-deoxymugineic acid complex, free 2'-deoxymugineic acid and its iron(III) complex were detected in the root extract of the transgenic plant by electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry. The growth of the transgenic petunia was significantly better than that of the control host in alkaline conditions. Consequently, the transgenic plant acquired a significantly enhanced tolerance to alkaline hydroponic media in the presence of the iron(III)-2'-deoxymugineic acid complex. Furthermore, the flower color of the transgenic plant deepened. The results showed that iron-phytosiderophore complexes and their transporters can potentially be utilized to overcome the worldwide iron uptake problems to diverse

  11. Root exudation of phytosiderophores from soil-grown wheat

    PubMed Central

    Oburger, Eva; Gruber, Barbara; Schindlegger, Yvonne; Schenkeveld, Walter D C; Hann, Stephan; Kraemer, Stephan M; Wenzel, Walter W; Puschenreiter, Markus

    2014-01-01

    For the first time, phytosiderophore (PS) release of wheat (Triticum aestivum cv Tamaro) grown on a calcareous soil was repeatedly and nondestructively sampled using rhizoboxes combined with a recently developed root exudate collecting tool. As in nutrient solution culture, we observed a distinct diurnal release rhythm; however, the measured PS efflux was c. 50 times lower than PS exudation from the same cultivar grown in zero iron (Fe)-hydroponic culture. Phytosiderophore rhizosphere soil solution concentrations and PS release of the Tamaro cultivar were soil-dependent, suggesting complex interactions of soil characteristics (salinity, trace metal availability) and the physiological status of the plant and the related regulation (amount and timing) of PS release. Our results demonstrate that carbon and energy investment into Fe acquisition under natural growth conditions is significantly smaller than previously derived from zero Fe-hydroponic studies. Based on experimental data, we calculated that during the investigated period (21–47 d after germination), PS release initially exceeded Fe plant uptake 10-fold, but significantly declined after c. 5 wk after germination. Phytosiderophore exudation observed under natural growth conditions is a prerequisite for a more accurate and realistic assessment of Fe mobilization processes in the rhizosphere using both experimental and modeling approaches. PMID:24890330

  12. Rice genes involved in phytosiderophore biosynthesis are synchronously regulated during the early stages of iron deficiency in roots.

    PubMed

    Itai, Reiko Nakanishi; Ogo, Yuko; Kobayashi, Takanori; Nakanishi, Hiromi; Nishizawa, Naoko K

    2013-06-25

    The rice transcription factors IDEF1, IDEF2, and OsIRO2 have been identified as key regulators of the genes that control iron (Fe) uptake, including the biosynthesis of mugineic acid-family phytosiderophores (MAs). To clarify the onset of Fe deficiency, changes in gene expression were examined by microarray analysis using rice roots at 3, 6, 9, 12, 24, and 36 h after the onset of Fe-deficiency treatment. More than 1000 genes were found to be upregulated over a time course of 36 h. Expression of MAs-biosynthetic genes, OsIRO2, and the Fe3+-MAs complex transporter OsYSL15 was upregulated at the 24 h and 36 h time points. Moreover, these genes showed very similar patterns of expression changes, but their expression patterns were completely different from those of a metallothionein gene (OsIDS1) and the Fe2+-transporter genes OsIRT1 and OsIRT2. OsIDS1 expression was upregulated by the 6 h time point. The early induction of OsIDS1 expression was distinct from the other Fe-deficiency-inducible genes investigated and suggested a functional relationship with heavy-metal homeostasis during the early stages of Fe deficiency. We showed that many genes related to MAs biosynthesis and transports were regulated by a distinct mechanism in roots. Furthermore, differences in expression changes and timing in response to Fe deficiency implied that different combinations of gene regulation mechanisms control the initial responses to Fe deficiency.

  13. Transgenic Petunia with the Iron(III)-Phytosiderophore Transporter Gene Acquires Tolerance to Iron Deficiency in Alkaline Environments

    PubMed Central

    Murata, Yoshiko; Itoh, Yoshiyuki; Iwashita, Takashi; Namba, Kosuke

    2015-01-01

    Iron is an essential nutrient for all plants. However, terrestrial plants often suffer from iron deficiency in alkaline soil due to its extremely low solubility. Alkaline soil accounts for about 30% of all cultivated ground in the world. Plants have evolved two distinct strategies, I and II, for iron uptake from the soil. Dicots and non-graminaceous monocots use Strategy I, which is primarily based on the reduction of iron(III) to iron(II) and the uptake of iron(II) by the iron-regulated transporter, IRT1. In contrast, graminaceous plants use Strategy II to efficiently acquire insoluble iron(III). Strategy II comprises the synthesis and secretion of iron-chelating phytosiderophores, such as mugineic acids and the Yellow Stripe 1 transporter proteins of the iron(III)-phytosiderophore complex. Barley, which exhibits the highest tolerance to iron deficiency in alkaline soil among graminaceous plants, utilizes mugineic acids and the specific iron(III)-mugineic acids transporter, HvYS1. In this study, we established the transgenic plant Petunia hybrida, which originally had only Strategy I, by introducing the HvYS1 transporter gene derived from barley. When the transgenic plants were grown hydroponically in media containing the iron(III)-2′-deoxymugineic acid complex, free 2′-deoxymugineic acid and its iron(III) complex were detected in the root extract of the transgenic plant by electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry. The growth of the transgenic petunia was significantly better than that of the control host in alkaline conditions. Consequently, the transgenic plant acquired a significantly enhanced tolerance to alkaline hydroponic media in the presence of the iron(III)-2′-deoxymugineic acid complex. Furthermore, the flower color of the transgenic plant deepened. The results showed that iron-phytosiderophore complexes and their transporters can potentially be utilized to overcome the worldwide iron uptake problems to

  14. Uninhibited biosynthesis and release of phytosiderophores in the presence of heavy metal (HM) favors HM remediation.

    PubMed

    Gupta, Chandan Kumar; Singh, Bhupinder

    2017-02-23

    Production of phytosiderophore (PS) has been causally related to iron-deficiency tolerance in cereals. However, PS can also chelate heavy metal and thus may represent a viable phytoextraction strategy on contaminated soils. Two separate experiments were conducted to assess the affect of heavy metal on phytosiderophore biosynthesis and their release in the rhizosphere of wheat. Root exudates were collected from 10-day-old wheat seedlings raised on Fe-deficient nutrient solution in the presence of 2.5, 5.0, and 10 mM concentration of different heavy metals (Cd, Pb, and Ni) for 3-day period, for the phytosiderophore and the heavy metal analysis. Plant uptake of respective heavy metal was positively correlated with the heavy metal concentration of the nutrient solution. Phytosiderophore release was positively influenced in the presence of the heavy metal. Increasing concentration of Cd, Pb, and Ni showed positive correlation with the PS release until 5 mM concentration followed by a decline at 10 mM. However, a higher induction of PS release was measured in wheat seedlings treated with Cd and Pb than Ni. Further, transcript expression analysis of nicotianamine synthase (NAS) and nicotianamine amino transferase (NAAT), involved in phytosiderophore biosynthesis, was done in roots of 10-day-old Fe-deficient wheat subjected to 2.5, 5.0, and 10 mM of Cd, Pb, and Ni. Both NAS and NAAT were expressed not only under Fe deficiency but also in the presence of Cd, Pb, and Ni. Sequencing of partial cDNA of NAS revealed a nucleotide length of 998 bp, while multiple sequence alignment of NAS with HvNAS revealed 92% sequence similarity. This study irrevocably shows that phytosiderophore biosynthesis and release are not impaired in the presence of heavy metal and that phytosiderophore mediates the uptake of toxic heavy metal.

  15. The interaction of phytosiderophores with soil as a function of time

    NASA Astrophysics Data System (ADS)

    Schenkeveld, W. D. C.; Oburger, E.; Schindlegger, Y.; Regelsberger, A.; Hann, S.; Puschenreiter, M.; Kraemer, S. M.

    2012-04-01

    Graminaceous plant species (grasses) exude natural chelating agents, called phytosiderophores (PS) for the purpose of iron acquisition, in particular under conditions of iron deficiency stress. The biogeochemistry of phytosiderophores in the rhizosphere is still poorly understood. Processes like mobilization of iron or other metals by PS, and the degradation of the chelating agent were previously studied under conditions quite remote from those observed in the rhizosphere, e.g. in hydroponics systems or in soil suspensions with low soils to solution ratios. Such experimental conditions may lead to artifacts like for instance the depletion of available metal fractions. The aim of the present study is to contribute to a more accurate quantification of the source and sink terms determining PS concentrations in the rhizosphere. The mobilization of iron and other metals from two clay soils and two sandy soils by the PS deoxymugineic acid (DMA) was studied as a function of time in a batch experiment with a soil-solution ratio of 1. Both soils causing iron deficiency stress in plants and a reference soil not doing so were included. To examine the effect of ligand biodegradation on metal mobilization, treatments with and without sterilant (azide) were included. The fraction of added DMA mobilizing Fe ranged from 10 to 60% and correlates positively with Fe availability (DTPA-extractable Fe) and negatively with the clay content of the soils. In particular in soils of low Fe availability, Fe mobilization by DMA was severely compromised by mobilization of other metals including Cu, Zn, Ni and Co. The relative importance of Zn as competing cation decreases over time, while the importance of Cu increases. In the treatment without sterilant addition, metal-DMA complexes were removed from solution after 4 days in all soils; in the clay soils, Fe-DMA complexes were already removed before. The highest concentration of mobilized Fe did not depend on whether sterilant was added or not

  16. Phytosiderophore Effects on Subsurface Actinide Contaminants: Potential for Phytostabilization and Phytoextraction

    SciTech Connect

    Ruggiero, Christy

    2005-06-01

    This project seeks to understand the influence of phytosiderophore-producing plants (grasses, including crops such as wheat and barley) on the biogeochemistry of actinide and other metal contaminants in the subsurface environment, and to determine the potential of phytosiderophore-producing plants for phytostabilization and phytoextraction of actinides and some metal soil contaminants. Phytosiderophores are secreted by graminaceous plants such as barley and wheat for the solubilization, mobilization and uptake of Fe and other essential nutrients from soils. The ability for these phytosiderophores to chelate and absorb actinides using the same uptake system as for Fe is being investigated though characterization of actinide-phytosiderophore complexes (independently of plants), and characterization of plant uptake of such complexes. We may also show possible harm caused by these plants through increased chelation of actinides that increase in actinide mobilization & migration in the subsurface environment. This information can then be directly applied by either removal of harmful plants, or can be used to develop plant-based soil stabilization/remediation technologies. Such technologies could be the low-cost, low risk solution to many DOE actinide contamination problems.

  17. Effect of nitrogen on root release of phytosiderophores and root uptake of Fe(III)-phytosiderophore in Fe-deficient wheat plants.

    PubMed

    Aciksoz, Seher Bahar; Ozturk, Levent; Gokmen, Ozay Ozgur; Römheld, Volker; Cakmak, Ismail

    2011-07-01

    Root release of phytosiderophores (PSs) is an important step in iron (Fe) acquisition of grasses, and this adaptive reaction of plants is affected by various plant and environmental factors. The objectives of this study were to study the effects of varied nitrogen (N) supply on (1) root and leaf concentrations of methionine, a precursor in the PS biosynthesis, (2) PS release from roots, (3) mobilization and uptake of Fe from (59) Fe-labeled Fe(III)-hydroxide [(59) Fe(OH)(3) ] and (4) root uptake of (59) Fe-labeled Fe(III)-deoxymugineic acid (DMA) by durum wheat (Triticum durum, cv. Balcali2000) plants grown in a nutrient solution. Enhanced N supply from 0.5 to 6 mM in a nutrient solution significantly increased the root release of PS under Fe deficiency. High N supply was also highly effective in increasing mobilization and root uptake of Fe from (59) Fe-hydroxide under low Fe supply. With adequate Fe, N nutrition did not affect mobilization and uptake of Fe from (59) Fe(OH)(3) . Root uptake and shoot translocation of Fe supplied as (59) Fe(III)-DMA were also stimulated by increasing N supply. Leaf concentration of methionine was reduced by low Fe supply, and this decline was pronounced in high N plants. The results show that the root release of PS, mobilization of Fe from (59) Fe(OH)(3) and root uptake and shoot translocation of Fe(III)-PS by durum wheat are markedly affected by N nutritional status of plants. These positive N effects may have important implications for Fe nutrition of human populations and should be considered in biofortification of food crops with Fe. Copyright © Physiologia Plantarum 2011.

  18. Regulation of Phytosiderophore Release and Antioxidant Defense in Roots Driven by Shoot-Based Auxin Signaling Confers Tolerance to Excess Iron in Wheat

    PubMed Central

    Kabir, Ahmad H.; Khatun, Most A.; Hossain, Mohammad M.; Haider, Syed A.; Alam, Mohammad F.; Paul, Nishit K.

    2016-01-01

    Iron (Fe) is essential but harmful for plants at toxic level. However, how wheat plants tolerate excess Fe remains vague. This study aims at elucidating the mechanisms underlying tolerance to excess Fe in wheat. Higher Fe concentration caused morpho-physiological retardation in BR 26 (sensitive) but not in BR 27 (tolerant). Phytosiderophore and 2-deoxymugineic acid showed no changes in BR 27 but significantly increased in BR 26 due to excess Fe. Further, expression of TaSAMS. TaDMAS1, and TaYSL15 significantly downregulated in BR 27 roots, while these were upregulated in BR 26 under excess Fe. It confirms that inhibition of phytosiderophore directs less Fe accumulation in BR 27. However, phytochelatin and expression of TaPCS1 and TaMT1 showed no significant induction in response to excess Fe. Furthermore, excess Fe showed increased catalase, peroxidase, and glutathione reductase activities along with glutathione, cysteine, and proline accumulation in roots in BR 27. Interestingly, BR 27 self-grafts and plants having BR 26 rootstock attached to BR 27 scion had no Fe-toxicity induced adverse effect on morphology but showed BR 27 type expressions, confirming that shoot-derived signal triggering Fe-toxicity tolerance in roots. Finally, auxin inhibitor applied with higher Fe concentration caused a significant decline in morpho-physiological parameters along with increased TaSAMS and TaDMAS1 expression in roots of BR 27, revealing the involvement of auxin signaling in response to excess Fe. These findings propose that tolerance to excess Fe in wheat is attributed to the regulation of phytosiderophore limiting Fe acquisition along with increased antioxidant defense in roots driven by shoot-derived auxin signaling. PMID:27891139

  19. Phytosiderophore Effects on Subsurface Actinide Contaminants: Potential for Phytostabilization and Phytoextraction

    SciTech Connect

    Ruggiero, Christy

    2004-06-01

    This project seeks to understand the influence of phytosiderophore-producing plants (grasses, including crops such as wheat and barley) on the biogeochemistry of actinide and other metal contaminants in the subsurface environment, and to determine the potential of phytosiderophoreproducing plants for phytostabilization and phytoextraction of actinides and some metal soil contaminants. Phytosiderophores are secreted by graminaceous plants such as barley and wheat for the solubilization, mobilization and uptake of Fe and other essential nutrients from soils. The ability for these phytosiderophores to chelate and absorb actinides using the same uptake system, as for Fe is being investigated though characterization of actinide-phytosiderophore complexes (independently of plants), and characterization of plant uptake of such complexes. We may also show possible harm caused by increased chelation of actinides, which may increase actinide mobilization & migration in the subsurface environment. This information can then be directly applied by either removal of harmful plants, or can be used to develop plant-based soil stabilization/remediation technologies. Such technologies could be the low-cost, low risk solution to many DOE actinide contamination problems.

  20. Iron Inefficiency in Maize Mutant ys1 (Zea mays L. cv Yellow-Stripe) Is Caused by a Defect in Uptake of Iron Phytosiderophores.

    PubMed Central

    Von Wiren, N.; Mori, S.; Marschner, H.; Romheld, V.

    1994-01-01

    To determine the Fe inefficiency factors in the maize mutant ys1 (Zea mays L. cv Yellow Stripe), root exudates of Fe-inefficient ys1 and of two Fe-efficient maize cultivars (Alice, WF9) were collected in axenic nutrient solution cultures. Analysis by thin-layer chromatography and high-performance liquid chromatography revealed that under Fe deficiency ys1 released the phytosiderophore 2[prime]-deoxymugineic acid (DMA) in quantities similar to those of Alice and WF9. Under nonaxenic conditions, DMA released by plants of all three cultivars was rapidly decomposed by microorganisms in the nutrient solution. Uptake experiments with 59Fe-labeled DMA, purified from root exudates of either Fe-deficient Alice or ys1 plants, showed up to 20 times lower uptake and translocation of 59Fe in ys1 than in Alice or WF9 plants. The presence of microorganisms during preculture and short-term uptake experiments had no significant effect on uptake and translocation rates of 59Fe in Alice and ys1 plants. We conclude that Fe inefficiency in the maize mutant ys1 is the result of a defect in the uptake system for Fe-phytosiderophores. PMID:12232304

  1. Phytosiderophore release by wheat genotypes differing in zinc deficiency tolerance grown with Zn-free nutrient solution as affected by salinity.

    PubMed

    Daneshbakhsh, Bahareh; Khoshgoftarmanesh, Amir Hossein; Shariatmadari, Hossein; Cakmak, Ismail

    2013-01-01

    There is limited information concerning the effect of salinity on phytosiderophores exudation from wheat roots. The aim of this hydroponic experiment was to investigate the effect of salinity on phytosiderophore release by roots of three bread wheat genotypes differing in Zn efficiency (Triticum aestivum L. cvs. Rushan, Kavir, and Cross) under Zn deficiency conditions. Wheat seedlings were transferred to Zn-free nutrient solutions and exposed to three salinity levels (0, 60, and 120 mM NaCl). The results indicated that Cross and Rushan genotypes exuded more phytosiderophore than did the Kavir genotype. Our findings suggest that the adaptive capacity of Zn-efficient 'Cross' and 'Rushan' wheat genotypes to Zn deficiency is due partly to the higher amounts of phytosiderophore release. Only 15 days of Zn deficiency stress was sufficient to distinguish between Zn-efficient (Rushan and Cross) and Zn-inefficient (Kavir) genotypes, with the former genotypes exuding more phytosiderophore than the latter. Higher phytosiderophore exudation under Zn deficiency conditions was accompanied by greater Fe transport from root to shoot. The maximum amount of phytosiderophore was exuded at the third week in 'Cross' and at the fourth week in 'Kavir' and 'Rushan'. For all three wheat genotypes, salinity stress resulted in higher amounts of phytosiderophore exuded by the roots. In general, for 'Kavir', the largest amount of phytosiderophore was exuded from the roots at the highest salinity level (120mM NaCl), while for 'Cross' and 'Rushan', no significant difference was found in phytosiderophore exudation between the 60 and 120 mM NaCl treatments. More investigation is needed to fully understand the physiology of elevated phytosiderophore release by Zn-deficient wheat plants under salinity conditions.

  2. Phytosiderophore effects on subsurface actinide contaminants: potential for phytostabilization and phytoextraction.

    SciTech Connect

    Ruggiero, C. E.; Twary, S. N.; Deladurantaye, E.

    2003-01-01

    In recognition of the need for a safe, effective technology for long term Pu/Th/Actinide stabilization or removal from soils, we have begun an investigation of the potential for phytoremediation (phytostabilization and/or phytoextraction) of Pu and other actinide soil contaminants at DOE sites using phytosiderophore producing plants, and are investigating the contribution of phytosiderophores to actinide mobility in the subsurface environment. Phytoremediation and Phytostabilization have been proven to be a cost-effective, safe, efficient, and publicly acceptable technology for clean up and/or stabilization of contaminant metals . However, no phyto-based technologies have been developed for stabilization or removal of plutonium from soils and groundwater, and very few have been investigated for other actinides . Current metal-phytostabilization and phytoremediation techniques, predominately based around lead, nickel, and other soft-metal phytoextraction, will almost certainly be inadequate for plutonium due its distinct chemical properties . Phytosiderophore-based phytoremediation may provide technically and financially practical methods for remediation and long-term stewardship of soils that have low to moderate, near surface actinide contamination . We plan to demonstrate potential benefits of phytosiderophore-producing plants for long-term actinide contaminant stabilization by the plant's prevention of soil erosion and actinide migration through hydraulic control and/or through actinide removal through phytoextraction . We may also show possible harm caused by these plants through increased presence of actinide chelators that could increase actinide mobilization and migration in the subsurface environment. This information can then be directly applied by either removal of harmful plants, or be used to develop plant-based soil stabilization/remediation technologies .

  3. Inhibition of the in-vitro growth of Mycobacterium tuberculosis by a phytosiderophore.

    PubMed

    Rajiv, J; Dam, T; Kumar, S; Bose, M; Aggarwal, K K; Babu, C R

    2001-10-01

    Non-compliance by patients and poor clinical management due to the use of incorrect regimens are the main reasons for the development of drug resistance by mycobacterial strains. New strategies for the control of multi-drug-resistant mycobacterial strains have become a necessity for proper management of tuberculosis, which, according to the WHO report (1997), is estimated to remain among the top 10 mortality-causing diseases of the twenty-first century. One of the strategies is the use of iron-sequestering agents like siderophores as active therapeutic agents in the treatment of tuberculosis. This report describes for the first time the inhibition of the growth of Mycobacterium tuberculosis H37Ra in vitro by a phytosiderophore isolated from the root washings of Tephrosia purpurea. This finding may help in the establishment of a new drug regimen which will be more effective in the treatment of tuberculosis.

  4. Iron deficiency in barley plants: phytosiderophore release, iron translocation, and DNA methylation

    PubMed Central

    Bocchini, Marika; Bartucca, Maria Luce; Ciancaleoni, Simona; Mimmo, Tanja; Cesco, Stefano; Pii, Youry; Albertini, Emidio; Del Buono, Daniele

    2015-01-01

    All living organisms require iron (Fe) to carry out many crucial metabolic pathways. Despite its high concentrations in the geosphere, Fe bio-availability to plant roots can be very scarce. To cope with Fe shortage, plants can activate different strategies. For these reasons, we investigated Fe deficient Hordeum vulgare L. plants by monitoring growth, phytosiderophores (PS) release, iron content, and translocation, and DNA methylation, with respect to Fe sufficient ones. Reductions of plant growth, roots to shoots Fe translocation, and increases in PS release were found. Experiments on DNA methylation highlighted significant differences between fully and hemy-methylated sequences in Fe deficient plants, with respect to Fe sufficient plants. Eleven DNA bands differently methylated were found in starved plants. Of these, five sequences showed significant alignment to barley genes encoding for a glucosyltransferase, a putative acyl carrier protein, a peroxidase, a β-glucosidase and a transcription factor containing a Homeodomin. A resupply experiment was carried out on starved barley re-fed at 13 days after sowing (DAS), and it showed that plants did not recover after Fe addition. In fact, Fe absorption and root to shoot translocation capacities were impaired. In addition, resupplied barley showed DNA methylation/demethylation patterns very similar to that of barley grown in Fe deprivation. This last finding is very encouraging because it indicates as these variations/modifications could be transmitted to progenies. PMID:26217365

  5. Iron deficiency in barley plants: phytosiderophore release, iron translocation, and DNA methylation.

    PubMed

    Bocchini, Marika; Bartucca, Maria Luce; Ciancaleoni, Simona; Mimmo, Tanja; Cesco, Stefano; Pii, Youry; Albertini, Emidio; Del Buono, Daniele

    2015-01-01

    All living organisms require iron (Fe) to carry out many crucial metabolic pathways. Despite its high concentrations in the geosphere, Fe bio-availability to plant roots can be very scarce. To cope with Fe shortage, plants can activate different strategies. For these reasons, we investigated Fe deficient Hordeum vulgare L. plants by monitoring growth, phytosiderophores (PS) release, iron content, and translocation, and DNA methylation, with respect to Fe sufficient ones. Reductions of plant growth, roots to shoots Fe translocation, and increases in PS release were found. Experiments on DNA methylation highlighted significant differences between fully and hemy-methylated sequences in Fe deficient plants, with respect to Fe sufficient plants. Eleven DNA bands differently methylated were found in starved plants. Of these, five sequences showed significant alignment to barley genes encoding for a glucosyltransferase, a putative acyl carrier protein, a peroxidase, a β-glucosidase and a transcription factor containing a Homeodomin. A resupply experiment was carried out on starved barley re-fed at 13 days after sowing (DAS), and it showed that plants did not recover after Fe addition. In fact, Fe absorption and root to shoot translocation capacities were impaired. In addition, resupplied barley showed DNA methylation/demethylation patterns very similar to that of barley grown in Fe deprivation. This last finding is very encouraging because it indicates as these variations/modifications could be transmitted to progenies.

  6. Ab initio calculations of the Fe(II) and Fe(III) isotopic effects in citrates, nicotianamine, and phytosiderophore, and new Fe isotopic measurements in higher plants

    NASA Astrophysics Data System (ADS)

    Moynier, Frédéric; Fujii, Toshiyuki; Wang, Kun; Foriel, Julien

    2013-05-01

    Iron is one of the most abundant transition metal in higher plants and variations in its isotopic compositions can be used to trace its utilization. In order to better understand the effect of plant-induced isotopic fractionation on the global Fe cycling, we have estimated by quantum chemical calculations the magnitude of the isotopic fractionation between different Fe species relevant to the transport and storage of Fe in higher plants: Fe(II)-citrate, Fe(III)-citrate, Fe(II)-nicotianamine, and Fe(III)-phytosiderophore. The ab initio calculations show firstly, that Fe(II)-nicotianamine is ˜3‰ (56Fe/54Fe) isotopically lighter than Fe(III)-phytosiderophore; secondly, even in the absence of redox changes of Fe, change in the speciation alone can create up to ˜1.5‰ isotopic fractionation. For example, Fe(III)-phytosiderophore is up to 1.5‰ heavier than Fe(III)-citrate2 and Fe(II)-nicotianamine is up to 1‰ heavier than Fe(II)-citrate. In addition, in order to better understand the Fe isotopic fractionation between different plant components, we have analyzed the iron isotopic composition of different organs (roots, seeds, germinated seeds, leaves and stems) from six species of higher plants: the dicot lentil (Lens culinaris), and the graminaceous monocots Virginia wild rye (Elymus virginicus), Johnsongrass (Sorghum halepense), Kentucky bluegrass (Poa pratensis), river oat (Uniola latifolia), and Indian goosegrass (Eleusine indica). The calculations may explain that the roots of strategy-II plants (Fe(III)-phytosiderophore) are isotopically heavier (by about 1‰ for the δ56Fe) than the upper parts of the plants (Fe transported as Fe(III)-citrate in the xylem or Fe(II)-nicotianamine in the phloem). In addition, we suggest that the isotopic variations observed between younger and older leaves could be explained by mixing of Fe received from the xylem and the phloem.

  7. A New Member of the Graphene Family: Graphene Acid.

    PubMed

    Jankovský, Ondřej; Nováček, Michal; Luxa, Jan; Sedmidubský, David; Fila, Vlastimil; Pumera, Martin; Sofer, Zdeněk

    2016-11-21

    A new member of the family of graphene derivatives, namely, graphene acid with a composition close to C1 (COOH)1 , was prepared by oxidation of graphene oxide. The synthetic procedure is based on repeated oxidation of graphite with potassium permanganate in an acidic environment. The oxidation process was studied in detail after each step. The multiple oxidations led to oxidative removal of other oxygen functional groups formed in the first oxidation step. Detailed chemical analysis showed only a minor amount of other oxygen-containing functional groups such as hydroxyl and the dominant presence of carboxyl groups in a concentration of about 30 wt %. Further oxidation led to complete decomposition of graphene acid. The obtained material exhibits unique sorption capacity towards metal ions and carbon dioxide. The highly hydrophilic nature of graphene acid allowed the assembly of ultrathin free-standing membranes with high transparency.

  8. A new transgenic rice line exhibiting enhanced ferric iron reduction and phytosiderophore production confers tolerance to low iron availability in calcareous soil

    PubMed Central

    Hamada, Tatsuro; Senoura, Takeshi; Kobayashi, Takanori; Aung, May Sann; Ishimaru, Yasuhiro; Ogo, Yuko; Nakanishi, Hiromi; Nishizawa, Naoko K.

    2017-01-01

    Iron (Fe) deficiency is a critical agricultural problem, especially in calcareous soil, which is distributed worldwide. Rice plants take up Fe(II) from soil through a OsIRT1 transporter (Strategy I-related system) and also take up Fe(III) via a phytosiderophore-based system (Strategy II system). However, rice plants are susceptible to low-Fe conditions because they have low Fe(III) reduction activity and low-level phytosiderophore secretion. Previously, we produced transgenic rice plants expressing a mutationally reconstructed yeast ferric chelate reductase, refre1/372, under the control of the OsIRT1 promoter. This transgenic rice line exhibited higher Fe(III) chelate reductase activity and tolerance to Fe deficiency. In addition, we produced transgenic rice overexpressing the Fe deficiency-inducible transcription factor, OsIRO2, which regulates the expression of various genes involved in the strategy II Fe(III) uptake system, including OsNAS1, OsNAAT1, OsDMAS1, OsYSL15, and TOM1. This transgenic rice exhibited improved phytosiderophore secretion ability and tolerance to Fe deficiency. In the present research, transgenic rice plants that possess both the OsIRT1 promoter-refre1/372 and the 35S promoter-OsIRO2 (RI lines) were produced to enhance both Strategy I Fe(II) reductase ability and Strategy II phytosiderophore productivity. RI lines exhibited enhanced tolerance to Fe-deficient conditions at the early and middle-late stages of growth in calcareous soil, compared to both the non-transgenic line and lines harboring either OsIRT1 promoter-refre1/372 or 35S promoter-OsIRO2 alone. RI lines also exhibited a 9-fold higher yield than the non-transgenic line. Moreover, we successfully produced Fe-deficiency-tolerant Tachisugata rice, which is a high-biomass variety used as fodder. Collectively, our results demonstrate that combined enhancement of two Fe uptake systems in rice is highly effective in conferring tolerance to low Fe availability in calcareous soil. PMID

  9. A new transgenic rice line exhibiting enhanced ferric iron reduction and phytosiderophore production confers tolerance to low iron availability in calcareous soil.

    PubMed

    Masuda, Hiroshi; Shimochi, Erika; Hamada, Tatsuro; Senoura, Takeshi; Kobayashi, Takanori; Aung, May Sann; Ishimaru, Yasuhiro; Ogo, Yuko; Nakanishi, Hiromi; Nishizawa, Naoko K

    2017-01-01

    Iron (Fe) deficiency is a critical agricultural problem, especially in calcareous soil, which is distributed worldwide. Rice plants take up Fe(II) from soil through a OsIRT1 transporter (Strategy I-related system) and also take up Fe(III) via a phytosiderophore-based system (Strategy II system). However, rice plants are susceptible to low-Fe conditions because they have low Fe(III) reduction activity and low-level phytosiderophore secretion. Previously, we produced transgenic rice plants expressing a mutationally reconstructed yeast ferric chelate reductase, refre1/372, under the control of the OsIRT1 promoter. This transgenic rice line exhibited higher Fe(III) chelate reductase activity and tolerance to Fe deficiency. In addition, we produced transgenic rice overexpressing the Fe deficiency-inducible transcription factor, OsIRO2, which regulates the expression of various genes involved in the strategy II Fe(III) uptake system, including OsNAS1, OsNAAT1, OsDMAS1, OsYSL15, and TOM1. This transgenic rice exhibited improved phytosiderophore secretion ability and tolerance to Fe deficiency. In the present research, transgenic rice plants that possess both the OsIRT1 promoter-refre1/372 and the 35S promoter-OsIRO2 (RI lines) were produced to enhance both Strategy I Fe(II) reductase ability and Strategy II phytosiderophore productivity. RI lines exhibited enhanced tolerance to Fe-deficient conditions at the early and middle-late stages of growth in calcareous soil, compared to both the non-transgenic line and lines harboring either OsIRT1 promoter-refre1/372 or 35S promoter-OsIRO2 alone. RI lines also exhibited a 9-fold higher yield than the non-transgenic line. Moreover, we successfully produced Fe-deficiency-tolerant Tachisugata rice, which is a high-biomass variety used as fodder. Collectively, our results demonstrate that combined enhancement of two Fe uptake systems in rice is highly effective in conferring tolerance to low Fe availability in calcareous soil.

  10. Identification and molecular characterization of the nicotianamine synthase gene family in bread wheat.

    PubMed

    Bonneau, Julien; Baumann, Ute; Beasley, Jesse; Li, Yuan; Johnson, Alexander A T

    2016-12-01

    Nicotianamine (NA) is a non-protein amino acid involved in fundamental aspects of metal uptake, transport and homeostasis in all plants and constitutes the biosynthetic precursor of mugineic acid family phytosiderophores (MAs) in graminaceous plant species. Nicotianamine synthase (NAS) genes, which encode enzymes that synthesize NA from S-adenosyl-L-methionine (SAM), are differentially regulated by iron (Fe) status in most plant species and plant genomes have been found to contain anywhere from 1 to 9 NAS genes. This study describes the identification of 21 NAS genes in the hexaploid bread wheat (Triticum aestivum L.) genome and their phylogenetic classification into two distinct clades. The TaNAS genes are highly expressed during germination, seedling growth and reproductive development. Fourteen of the clade I NAS genes were up-regulated in root tissues under conditions of Fe deficiency. Protein sequence analyses revealed the presence of endocytosis motifs in all of the wheat NAS proteins as well as chloroplast, mitochondrial and secretory transit peptide signals in four proteins. These results greatly expand our knowledge of NAS gene families in graminaceous plant species as well as the genetics underlying Fe nutrition in bread wheat. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  11. Targeting Hyaluronic Acid Family for Cancer Chemoprevention and Therapy

    PubMed Central

    Lokeshwar, Vinata B.; Mirza, Summan; Jordan, Andre

    2016-01-01

    Hyaluronic acid or hyaluronan (HA) is perhaps one of the most uncomplicated large polymers that regulates several normal physiological processes and, at the same time, contributes to the manifestation of a variety of chronic and acute diseases, including cancer. Members of the HA signaling pathway (HA synthases, HA receptors, and HYAL-1 hyaluronidase) have been experimentally shown to promote tumor growth, metastasis, and angiogenesis, and hence each of them is a potential target for cancer therapy. Furthermore, as these members are also overexpressed in a variety of carcinomas, targeting of the HA family is clinically relevant. A variety of targeted approaches have been developed to target various HA family members, including small-molecule inhibitors and antibody and vaccine therapies. These treatment approaches inhibit HA-mediated intracellular signaling that promotes tumor cell proliferation, motility, and invasion, as well as induction of endothelial cell functions. Being nontoxic, nonimmunogenic, and versatile for modifications, HA has been used in nanoparticle preparations for the targeted delivery of chemotherapy drugs and other anticancer compounds to tumor cells through interaction with cell-surface HA receptors. This review discusses basic and clinical translational aspects of targeting each HA family member and respective treatment approaches that have been described in the literature. PMID:25081525

  12. Tomato ABSCISIC ACID STRESS RIPENING (ASR) gene family revisited.

    PubMed

    Golan, Ido; Dominguez, Pia Guadalupe; Konrad, Zvia; Shkolnik-Inbar, Doron; Carrari, Fernando; Bar-Zvi, Dudy

    2014-01-01

    Tomato ABSCISIC ACID RIPENING 1 (ASR1) was the first cloned plant ASR gene. ASR orthologs were then cloned from a large number of monocot, dicot and gymnosperm plants, where they are mostly involved in response to abiotic (drought and salinity) stress and fruit ripening. The tomato genome encodes five ASR genes: ASR1, 2, 3 and 5 encode low-molecular-weight proteins (ca. 110 amino acid residues each), whereas ASR4 encodes a 297-residue polypeptide. Information on the expression of the tomato ASR gene family is scarce. We used quantitative RT-PCR to assay the expression of this gene family in plant development and in response to salt and osmotic stresses. ASR1 and ASR4 were the main expressed genes in all tested organs and conditions, whereas ASR2 and ASR3/5 expression was two to three orders of magnitude lower (with the exception of cotyledons). ASR1 is expressed in all plant tissues tested whereas ASR4 expression is limited to photosynthetic organs and stamens. Essentially, ASR1 accounted for most of ASR gene expression in roots, stems and fruits at all developmental stages, whereas ASR4 was the major gene expressed in cotyledons and young and fully developed leaves. Both ASR1 and ASR4 were expressed in flower organs, with ASR1 expression dominating in stamens and pistils, ASR4 in sepals and petals. Steady-state levels of ASR1 and ASR4 were upregulated in plant vegetative organs following exposure to salt stress, osmotic stress or the plant abiotic stress hormone abscisic acid (ABA). Tomato plants overexpressing ASR1 displayed enhanced survival rates under conditions of water stress, whereas ASR1-antisense plants displayed marginal hypersensitivity to water withholding.

  13. Increased abundance of proteins involved in phytosiderophore production in boron-tolerant barley.

    PubMed

    Patterson, John; Ford, Kris; Cassin, Andrew; Natera, Siria; Bacic, Antony

    2007-07-01

    Boron (B) phytotoxicity affects cereal-growing regions worldwide. Although B-tolerant barley (Hordeum vulgare) germplasm is available, molecules responsible for this tolerance mechanism have not been defined. We describe and use a new comparative proteomic technique, iTRAQ peptide tagging (iTRAQ), to compare the abundances of proteins from B-tolerant and -intolerant barley plants from a 'Clipper' x 'Sahara' doubled-haploid population selected on the basis of a presence or absence of two B-tolerance quantitative trait loci. iTRAQ was used to identify three enzymes involved in siderophore production (Iron Deficiency Sensitive2 [IDS2], IDS3, and a methylthio-ribose kinase) as being elevated in abundance in the B-tolerant plants. Following from this result, we report a potential link between iron, B, and the siderophore hydroxymugineic acid. We believe that this study highlights the potency of the iTRAQ approach to better understand mechanisms of abiotic stress tolerance in cereals, particularly when applied in conjunction with bulked segregant analysis.

  14. Effectiveness of a free folic acid supplement program in family planning clinics.

    PubMed

    Watkins, Margaret L; Brustrom, Jennifer; Schulman, Jane

    2004-06-01

    Adequate periconceptional folic acid consumption lowers the risk for neural tube defects. We report the results of an evaluation of a folic acid intervention in Georgia family planning clinics that provided free folic acid supplements or fortified breakfast cereal. Six family planning clinics participated in the evaluation. Three clinics provided folic acid pills and educational materials to clients, two provided super-fortified cereal and educational materials, and one clinic provided educational materials only. Participants between the ages of 18 and 45 who visited the clinics in 2000 completed a brief survey and provided a blood sample. Of the 1093 women who participated, we evaluated the 165 women who had returned to the clinic at least once during the study period. We compared participants' survey and serum folate data from their first and subsequent visits. Participation in the intervention was associated with increased knowledge about folic acid, (odds ratio, 1.94; 95% confidence interval, 1.37-2.76), but was not directly associated with increased self-reported folic acid consumption or increased serum folate levels. Reported use of folic acid supplements or cereal within two days of a visit was associated with higher serum folate levels. Knowledge about folic acid was one of the best predictors of self-reported folic acid consumption. Participation in the intervention increased clients' knowledge about folic acid but did not directly increase reported folic acid consumption. Because knowledge predicted folic acid consumption, the intervention may be indirectly associated with increased consumption of folic acid.

  15. Chlorogenic acid protects MSCs against oxidative stress by altering FOXO family genes and activating intrinsic pathway.

    PubMed

    Li, Shiyong; Bian, Hetao; Liu, Zhe; Wang, Ye; Dai, Jianghua; He, Wenfeng; Liao, Xingen; Liu, Rongrong; Luo, Jun

    2012-01-15

    Chlorogenic acid as an antioxidant exists widely in edible and medicinal plants, and can protect cell against apoptosis induced by oxidative stress. However, its molecular mechanisms remain largely unknown. Here, we showed that Chlorogenic acid suppressed reactive oxygen species increase by activation of Akt phosphorylation,and increased FOXO family genes and anti-apoptotic protein Bcl-2 expression in MSCs culturing under oxidative stress. In addition, PI-3Kinase Inhibitor (2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, LY294002) could suppress the Chlorogenic acid-induced: (1) the cellular protective role, (2) the increase of the FOXO family genes expression, (3) increased expression of Bcl-2. These results suggested that Chlorogenic acid protected MSCs against apoptosis via PI3K/AKT signal and FOXO family genes. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Constitutive expression of a barley Fe phytosiderophore transporter increases alkaline soil tolerance and results in iron partitioning between vegetative and storage tissues under stress.

    PubMed

    Gómez-Galera, Sonia; Sudhakar, Duraialagaraja; Pelacho, Ana M; Capell, Teresa; Christou, Paul

    2012-04-01

    Cereals have evolved chelation systems to mobilize insoluble iron in the soil, but in rice this process is rather inefficient, making the crop highly susceptible to alkaline soils. We therefore engineered rice to express the barley iron-phytosiderophore transporter (HvYS1), which enables barley plants to take up iron from alkaline soils. A representative transgenic rice line was grown in standard (pH 5.5) or alkaline soil (pH 8.5) to evaluate alkaline tolerance and iron mobilization. Transgenic plants developed secondary tillers and set seeds when grown in standard soil although iron concentration remained similar in leaves and seeds compared to wild type. However, when grown in alkaline soil transgenic plants exhibited enhanced growth, yield and iron concentration in leaves compared to the wild type plants which were severely stunted. Transgenic plants took up iron more efficiently from alkaline soil compared to wild type, indicating an enhanced capacity to increase iron mobility ex situ. Interestingly, all the additional iron accumulated in vegetative tissues, i.e. there was no difference in iron concentration in the seeds of wild type and transgenic plants. Our data suggest that iron uptake from the rhizosphere can be enhanced through expression of HvYS1 and confirm the operation of a partitioning mechanism that diverts iron to leaves rather than seeds, under stress.

  17. Using Amino Acid Correlation and Community Detection Algorithms to Identify Functional Determinants in Protein Families

    PubMed Central

    Bleicher, Lucas; Lemke, Ney; Garratt, Richard Charles

    2011-01-01

    Correlated mutation analysis has a long history of interesting applications, mostly in the detection of contact pairs in protein structures. Based on previous observations that, if properly assessed, amino acid correlation data can also provide insights about functional sub-classes in a protein family, we provide a complete framework devoted to this purpose. An amino acid specific correlation measure is proposed, which can be used to build networks summarizing all correlation and anti-correlation patterns in a protein family. These networks can be submitted to community structure detection algorithms, resulting in subsets of correlated amino acids which can be further assessed by specific parameters and procedures that provide insight into the relationship between different communities, the individual importance of community members and the adherence of a given amino acid sequence to a given community. By applying this framework to three protein families with contrasting characteristics (the Fe/Mn-superoxide dismutases, the peroxidase-catalase family and the C-type lysozyme/α-lactalbumin family), we show how our method and the proposed parameters and procedures are related to biological characteristics observed in these protein families, highlighting their potential use in protein characterization and gene annotation. PMID:22205928

  18. Bacteriocins of lactic acid bacteria: extending the family.

    PubMed

    Alvarez-Sieiro, Patricia; Montalbán-López, Manuel; Mu, Dongdong; Kuipers, Oscar P

    2016-04-01

    Lactic acid bacteria (LAB) constitute a heterogeneous group of microorganisms that produce lactic acid as the major product during the fermentation process. LAB are Gram-positive bacteria with great biotechnological potential in the food industry. They can produce bacteriocins, which are proteinaceous antimicrobial molecules with a diverse genetic origin, posttranslationally modified or not, that can help the producer organism to outcompete other bacterial species. In this review, we focus on the various types of bacteriocins that can be found in LAB and the organization and regulation of the gene clusters responsible for their production and biosynthesis, and consider the food applications of the prototype bacteriocins from LAB. Furthermore, we propose a revised classification of bacteriocins that can accommodate the increasing number of classes reported over the last years.

  19. Bicyclic alpha,omega-dicarboxylic acid derivatives from a colonial tunicate of the family Polyclinidae.

    PubMed

    Bao, Baoquan; Dang, Hung The; Zhang, Ping; Hong, Jongki; Lee, Chong-O; Cho, Hee Young; Jung, Jee H

    2009-11-01

    In the course of our search for bioactive metabolites from a colonial tunicate of the family Polyclinidae, six new (1-6) cyclic fatty acid derivatives were isolated. Their planar structures were established on the basis of NMR and MS spectroscopic analyses. The relative configuration was determined by NOESY experiment. Compounds 1-6 represent a fused bicyclic skeleton possibly derived from alpha,omega-dicarboxylic acids such as eicosanedioic acid or docosanedioic acid via a Diels-Alder type of cyclization. Compounds 1-4 and 6 showed mild cytotoxicity against a panel of five human solid tumor cell lines.

  20. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

    PubMed Central

    Gomez-Ospina, Natalia; Potter, Carol J.; Xiao, Rui; Manickam, Kandamurugu; Kim, Mi-Sun; Kim, Kang Ho; Shneider, Benjamin L.; Picarsic, Jennifer L.; Jacobson, Theodora A.; Zhang, Jing; He, Weimin; Liu, Pengfei; Knisely, A. S.; Finegold, Milton J.; Muzny, Donna M.; Boerwinkle, Eric; Lupski, James R.; Plon, Sharon E.; Gibbs, Richard A.; Eng, Christine M.; Yang, Yaping; Washington, Gabriel C.; Porteus, Matthew H.; Berquist, William E.; Kambham, Neeraja; Singh, Ravinder J.; Xia, Fan; Enns, Gregory M.; Moore, David D.

    2016-01-01

    Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection. PMID:26888176

  1. Characterization of glucosylceramides in leaves of the grass family (Poaceae): Pooideae has unsaturated hydroxy fatty acids.

    PubMed

    Watanabe, Masayuki; Imai, Hiroyuki

    2011-01-01

    The glucosylceramide components were characterized in the 33 species of the grass family (Poaceae). Pooideae contained 4-hydroxy-8-sphingenines [i.e., t18:1(8Z) plus t18:1(8E)] as major components, the relative levels of t18:1(8Z) being higher than those of the 8-E isomers. 2-Hydroxy arachidic acid was a major component in all species other than Pooideae, whereas Pooideae had a high content of 2-hydroxytetracosenoic acid.

  2. A new family of extraterrestrial amino acids in the Murchison meteorite.

    PubMed

    Koga, Toshiki; Naraoka, Hiroshi

    2017-04-04

    The occurrence of extraterrestrial organic compounds is a key for understanding prebiotic organic synthesis in the universe. In particular, amino acids have been studied in carbonaceous meteorites for almost 50 years. Here we report ten new amino acids identified in the Murchison meteorite, including a new family of nine hydroxy amino acids. The discovery of mostly C3 and C4 structural isomers of hydroxy amino acids provides insight into the mechanisms of extraterrestrial synthesis of organic compounds. A complementary experiment suggests that these compounds could be produced from aldehydes and ammonia on the meteorite parent body. This study indicates that the meteoritic amino acids could be synthesized by mechanisms in addition to the Strecker reaction, which has been proposed to be the main synthetic pathway to produce amino acids.

  3. Common recognition principles across diverse sequence and structural families of sialic acid binding proteins.

    PubMed

    Bhagavat, Raghu; Chandra, Nagasuma

    2014-01-01

    Sialic acids form a large family of 9-carbon monosaccharides and are integral components of glycoconjugates. They are known to bind to a wide range of receptors belonging to diverse sequence families and fold classes and are key mediators in a plethora of cellular processes. Thus, it is of great interest to understand the features that give rise to such a recognition capability. Structural analyses using a non-redundant data set of known sialic acid binding proteins was carried out, which included exhaustive binding site comparisons and site alignments using in-house algorithms, followed by clustering and tree computation, which has led to derivation of sialic acid recognition principles. Although the proteins in the data set belong to several sequence and structure families, their binding sites could be grouped into only six types. Structural comparison of the binding sites indicates that all sites contain one or more different combinations of key structural features over a common scaffold. The six binding site types thus serve as structural motifs for recognizing sialic acid. Scanning the motifs against a non-redundant set of binding sites from PDB indicated the motifs to be specific for sialic acid recognition. Knowledge of determinants obtained from this study will be useful for detecting function in unknown proteins. As an example analysis, a genome-wide scan for the motifs in structures of Mycobacterium tuberculosis proteome identified 17 hits that contain combinations of the features, suggesting a possible function of sialic acid binding by these proteins.

  4. Expanding the Cyanuric Acid Hydrolase Protein Family to the Fungal Kingdom

    PubMed Central

    Dodge, Anthony G.; Preiner, Chelsea S.

    2013-01-01

    The known enzymes that open the s-triazine ring, the cyanuric acid hydrolases, have been confined almost exclusively to the kingdom Bacteria and are all homologous members of the rare cyanuric acid hydrolase/barbiturase protein family. In the present study, a filamentous fungus, Sarocladium sp. strain CA, was isolated from soil by enrichment culturing using cyanuric acid as the sole source of nitrogen. A reverse-genetic approach identified a fungal cyanuric acid hydrolase gene composed of two exons and one intron. The translated spliced sequence was 39 to 53% identical to previously characterized bacterial cyanuric acid hydrolases. The sequence was used to generate a gene optimized for expression in Escherichia coli and encoding an N-terminally histidine-tagged protein. The protein was purified by nickel affinity and anion-exchange chromatography. The purified protein was shown by 13C nuclear magnetic resonance (13C-NMR) to produce carboxybiuret as the product, which spontaneously decarboxylated to yield biuret and carbon dioxide. The protein was very narrow in substrate specificity, showing activity only with cyanuric acid and N-methyl cyanuric acid. Barbituric acid was an inhibitor of enzyme activity. Sequence analysis identified genes with introns in other fungi from the Ascomycota that, if spliced, are predicted to encode proteins with cyanuric acid hydrolase activity. The Ascomycota cyanuric acid hydrolase homologs are most closely related to cyanuric acid hydrolases from Actinobacteria. PMID:24039269

  5. Increased urinary excretion of beta-aminoisobutyric acid in a Danish family.

    PubMed

    Sjølin, K E

    1988-08-01

    During collection of a control material for determination of urinary excretion of beta-aminoisobutyric acid (beta-AIB), female high excretors were found in four generations in a Danish family. The heredity seemed to be sex related and dominant, unlike previous communications about genetically conditioned high excretors of beta-AIB.

  6. Progressive familial intrahepatic cholestasis and inborn errors of bile acid synthesis.

    PubMed

    Jankowska, Irena; Socha, Piotr

    2012-06-01

    Progressive familial intrahepatic cholestasis (PFIC), types 1, 2 and 3, are due to defects in genes involved in bile secretion (FIC1, BSEP, MDR3). PFIC and inborn errors of bile acid synthesis (IEBAS) often present in infancy with cholestasis. The distinctive feature of PFIC 1 and 2 and IEBAS is a normal level of GGT, while IEBAS are suspected in patients with low plasma bile acids concentration. Molecular testing, urinary bile acid analysis (IEBAS), liver biopsy and immuno-staining are used for the diagnosis. Some patients with PFIC can be successfully treated with ursodeoxycholic acid or partial external biliary diversion. IEBAS is treated with cholic acid. Liver transplantation is required for cirrhosis with liver failure. Hepatocarcinoma has been reported in PFIC2.

  7. The solute carrier family 10 (SLC10): beyond bile acid transport

    PubMed Central

    da Silva, Tatiana Claro; Polli, James E.; Swaan, Peter W.

    2012-01-01

    The solute carrier (SLC) family 10 (SLC10) comprises influx transporters of bile acids, steroidal hormones, various drugs, and several other substrates. Because the seminal transporters of this family, namely, sodium/taurocholate cotransporting polypeptide (NTCP; SLC10A1) and the apical sodium-dependent bile acid transporter (ASBT; SLC10A2), were primarily bile acid transporters, the term “sodium bile salt cotransporting family” was used for the SLC10 family. However, this notion became obsolete with the finding of other SLC10 members that do not transport bile acids. For example, the sodium-dependent organic anion transporter (SOAT; SLC10A6) transports primarily sulfated steroids. Moreover, NTCP was shown to also transport steroids and xenobiotics, including HMG-CoA inhibitors (statins). The SLC10 family contains four additional members, namely, P3 (SLC10A3; SLC10A3), P4 (SLC10A4; SLC10A4), P5 (SLC10A5; SLC10A5) and SLC10A7 (SLC10A7), several of which were unknown or considered hypothetical until approximately a decade ago. While their substrate specificity remains undetermined, great progress has been made towards their characterization in recent years. SLC10A4 may participate in vesicular storage or exocytosis of neurotransmitters or mastocyte mediators, whereas SLC10A5 and SLC10A7 may be involved in solute transport and SLC10A3 may have a role as a housekeeping protein. Finally, the newly found role of bile acids in glucose and energy homeostasis, via the TGR5 receptor, sheds new light on the clinical relevance of ASBT and NTCP. The present mini-review provides a brief summary of recent progress on members of the SLC10 family. PMID:23506869

  8. Characterization of an Arabidopsis enzyme family that conjugates amino acids to indole-3-acetic acid.

    PubMed

    Staswick, Paul E; Serban, Bogdan; Rowe, Martha; Tiryaki, Iskender; Maldonado, Marién T; Maldonado, Mitsa C; Suza, Walter

    2005-02-01

    Substantial evidence indicates that amino acid conjugates of indole-3-acetic acid (IAA) function in auxin homeostasis, yet the plant enzymes involved in their biosynthesis have not been identified. We tested whether several Arabidopsis thaliana enzymes that are related to the auxin-induced soybean (Glycine max) GH3 gene product synthesize IAA-amino acid conjugates. In vitro reactions with six recombinant GH3 enzymes produced IAA conjugates with several amino acids, based on thin layer chromatography. The identity of the Ala, Asp, Phe, and Trp conjugates was verified by gas chromatography-mass spectrometry. Insertional mutations in GH3.1, GH3.2, GH3.5, and GH3.17 resulted in modestly increased sensitivity to IAA in seedling root. Overexpression of GH3.6 in the activation-tagged mutant dfl1-D did not significantly alter IAA level but resulted in 3.2- and 4.5-fold more IAA-Asp than in wild-type seedlings and mature leaves, respectively. In addition to IAA, dfl1-D was less sensitive to indole-3-butyric acid and naphthaleneacetic acid, consistent with the fact that GH3.6 was active on each of these auxins. By contrast, GH3.6 and the other five enzymes tested were inactive on halogenated auxins, and dfl1-D was not resistant to these. This evidence establishes that several GH3 genes encode IAA-amido synthetases, which help to maintain auxin homeostasis by conjugating excess IAA to amino acids.

  9. The SLC3 and SLC7 families of amino acid transporters.

    PubMed

    Fotiadis, Dimitrios; Kanai, Yoshikatsu; Palacín, Manuel

    2013-01-01

    Amino acids are necessary for all living cells and organisms. Specialized transporters mediate the transfer of amino acids across plasma membranes. Malfunction of these proteins can affect whole-body homoeostasis giving raise to diverse human diseases. Here, we review the main features of the SLC3 and SLC7 families of amino acid transporters. The SLC7 family is divided into two subfamilies, the cationic amino acid transporters (CATs), and the L-type amino acid transporters (LATs). The latter are the light or catalytic subunits of the heteromeric amino acid transporters (HATs), which are associated by a disulfide bridge with the heavy subunits 4F2hc or rBAT. These two subunits are glycoproteins and form the SLC3 family. Most CAT subfamily members were functionally characterized and shown to function as facilitated diffusers mediating the entry and efflux of cationic amino acids. In certain cells, CATs play an important role in the delivery of L-arginine for the synthesis of nitric oxide. HATs are mostly exchangers with a broad spectrum of substrates and are crucial in renal and intestinal re-absorption and cell redox balance. Furthermore, the role of the HAT 4F2hc/LAT1 in tumor growth and the application of LAT1 inhibitors and PET tracers for reduction of tumor progression and imaging of tumors are discussed. Finally, we describe the link between specific mutations in HATs and the primary inherited aminoacidurias, cystinuria and lysinuric protein intolerance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Growth responses of 53 open-pollinated loblolly pine families to ozone and acid rain

    SciTech Connect

    McLaughlin, S.B.; Edwards, N.T.; Hanson, P.J.

    1994-03-01

    Field exposures of 9950 containerized 12-wk-old loblolly pine (Pinustaeda L.) seedlings representing 53 commercially important, open-pollinated families were conducted to evaluate individual and interactive effects of acid rain and O{sub 3} on growth response. A 36-plot field research facility comprised of 33 open-top chambers and three open plots was used to test effects of five O{sub 3} levels that included ambient (A) and seasonally integrated levels that were 0.53, 1.10, 1.58, or 2.15 times ambient. Individual effects of three levels of simulated acid rain (pH 3.3, 4.5, and 5.2) as well as their interaction with O{sub 3} at 0.53A, 1.58A, and 2.15A levels were also included. Exposure to ambient air reduced average growth in height (26%), diameter (5%), and volume (14%) compared with growth of seedlings exposed to a 47% lower dose in charcoal filtered (CF) air. Responses to increasing O{sub 3} above ambient levels varied widely between families, became increasingly inhibitory at the highest O{sub 3} levels, but did not significantly exceed growth reductions found in ambient air. Diameter growth was reduced in most families by all levels of O{sub 3} addition. Acid rain caused a general stimulation of height growth at ambient levels (pH 4.5), while both height and diameter growth were reduced at a mean pH of 3.3. Significant antagonism between rainfall acidity and O{sub 3} effects on height and biomass increment was detected with increasing pollutant concentrations. Ozone reduced root/shoot biomass in most families, while acid rain did not. 51 refs., 6 figs., 6 tabs.

  11. Genome-wide linkage analysis for uric acid in families enriched for hypertension

    PubMed Central

    Rule, Andrew D.; Fridley, Brooke L.; Hunt, Steven C.; Asmann, Yan; Boerwinkle, Eric; Pankow, James S.; Mosley, Thomas H.; Turner, Stephen T.

    2009-01-01

    Background. Uric acid is heritable and associated with hypertension and insulin resistance. We sought to identify genomic regions influencing serum uric acid in families in which two or more siblings had hypertension. Methods. Uric acid levels and microsatellite markers were assayed in the Genetic Epidemiology Network of Arteriopathy (GENOA) cohort (1075 whites and 1333 blacks) and the Hypertension Genetic Epidemiology Network (HyperGEN) cohort (1542 whites and 1627 blacks). Genome-wide linkage analyses of uric acid and bivariate linkage analyses of uric acid with an additional surrogate of insulin resistance were completed. Pathway analysis explored gene sets enriched at loci influencing uric acid. Results. In the GENOA white cohort, loci influencing uric acid were identified on chromosome 8 at 135 cM [multipoint logarithm of odds score (MLS) = 2.4], on chromosome 9 at 113 cM (MLS = 3.7) and on chromosome 16 at 93 cM (MLS = 2.3), but did not replicate in HyperGEN. At these loci, there was evidence of pleiotropy with other surrogates of insulin resistance and genes in the fructose and mannose metabolism pathway were enriched. In the HyperGEN-black cohort, there was some evidence of a locus for uric acid on chromosome 4 at 135 cM (MLS = 2.4) that had modest replication in GENOA (MLS = 1.2). Conclusions. Several novel loci linked to uric acid were identified but none showed clear replication. Widespread diuretic use, a medication that raises uric acid levels, was an important study limitation. Bivariate linkage analyses and pathway analysis were consistent with genes regulating insulin resistance and fructose metabolism contributing to the heritability of uric acid. PMID:19258383

  12. [Impact of family members and health care providers on the use of folic acid in pregnant women].

    PubMed

    Zheng, Shan; Wang, Minzhen; Bai, Ya'na; Hu, Xiaobin; Zhang, Rongqiang; Du, Wenqi; Li, Liansheng; Li, Jingyu; Cheng, Ning

    2011-01-01

    To investigate the impact of family members and health care providers on the use of folic acid supplements in pregnant women, and to provide basic data for improving the effectiveness of folic acid intervention. A cross-sectional study was conducted in hospitals and households from June to September in 2009. Face-to-face anonymous questionnaires were distributed to 2094 women, who were pregnant at least three months or postpartum in one year, in two counties of Gansu Province. The awareness rate of folic acid was in 62.2% of 2094 pregnant women, and 25.4% of them have taken folic acid. Higher knowledge about folic acid of family members (OR = 0.268, 95% CI 0.208 - 0.346), agreed with taking folic acid by family members (OR = 0.103, 95% CI 0.031 -0.338), and urging pregnant women to take folic acid by family members (OR = 0.147, 95% CI 0.115 - 0.190) were significant predictors for having folic acid taken by pregnant women. Propagating knowledge related to folic acid (OR = 0.252, 95% CI 0.197 - 0.323) and directing pregnant women to use folic acid (OR = 0.168, 95% CI 0.096 - 0.296) by health care providers were also the important predictors for folic acid intake. Family members and health care providers play an important role in affecting the use of folic acid among pregnant women. In order to improve the effectiveness of intervention with folic acid, family members of pregnant women and health care providers should be included into the target population to receive an intensive propaganda campaign on folic acid education to improve the use of folic acid in pregnant women extensively.

  13. Developmental changes in aspartate-family amino acid biosynthesis in pea chloroplasts

    SciTech Connect

    Mills, W.R.; Cato, L.W.; Stephens, B.W.; Reeves, M. )

    1990-05-01

    Isolated chloroplasts are known to synthesize the asp-derived amino acids (ile, hse, lys and thr) from ({sup 14}C)asp (Mills et al, 1980, Plant Physiol. 65, 1166). Now, we have studied the influence of tissue age on essential amino acid biosynthesis in pea (Pisum sativum) plastids. Chloroplasts from the younger (third and fourth) leaves of 12 day old plants, were 2-3 times more active in synthesizing lys and thr from ({sup 14}C)asp than those from older (first or second) leaves. We also examined two key pathway enzymes (aspartate kinase and homoserine dehydrogenase); with each enzyme,a activity in younger leaves was about 2 times that in plastids from older tissue. Both lys- and thr-sensitive forms of aspartate kinase are known in plants; in agreement with earlier work, we found that lys-sensitive activity was about 4 times higher in the younger tissues, while the thr-sensitive activity changed little during development (Davies and Miflin, 1977, Plant Sci. Lett. 9, 323). Recently the role of aspartate kinase and homoserine dehydrogenase in controlling asp-family amino acid synthesis has been questioned (Giovanelli et al, 1989, Plant Physiol. 90, 1584); we hope that measurements of amino acid levels in chloroplasts as well as further enzyme studies will help us to better understand the regulation of asp-family amino acid synthesis.

  14. Interaction of Dietary Fatty Acids with Tumour Necrosis Factor Family Cytokines during Colon Inflammation and Cancer

    PubMed Central

    Straková, Nicol; Vaculová, Alena Hyršlová; Tylichová, Zuzana; Šafaříková, Barbora; Kozubík, Alois

    2014-01-01

    Intestinal homeostasis is precisely regulated by a number of endogenous regulatory molecules but significantly influenced by dietary compounds. Malfunction of this system may result in chronic inflammation and cancer. Dietary essential n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acid butyrate produced from fibre display anti-inflammatory and anticancer activities. Both compounds were shown to modulate the production and activities of TNF family cytokines. Cytokines from the TNF family (TNF-α, TRAIL, and FasL) have potent inflammatory activities and can also regulate apoptosis, which plays an important role in cancer development. The results of our own research showed enhancement of apoptosis in colon cancer cells by a combination of either docosahexaenoic acid (DHA) or butyrate with TNF family cytokines, especially by promotion of the mitochondrial apoptotic pathway and modulation of NFκB activity. This review is focused mainly on the interaction of dietary PUFAs and butyrate with these cytokines during colon inflammation and cancer development. We summarised recent knowledge about the cellular and molecular mechanisms involved in such effects and outcomes for intestinal cell behaviour and pathologies. Finally, the possible application for the prevention and therapy of colon inflammation and cancer is also outlined. PMID:24876678

  15. Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer.

    PubMed

    Hofmanová, Jiřina; Straková, Nicol; Vaculová, Alena Hyršlová; Tylichová, Zuzana; Safaříková, Barbora; Skender, Belma; Kozubík, Alois

    2014-01-01

    Intestinal homeostasis is precisely regulated by a number of endogenous regulatory molecules but significantly influenced by dietary compounds. Malfunction of this system may result in chronic inflammation and cancer. Dietary essential n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acid butyrate produced from fibre display anti-inflammatory and anticancer activities. Both compounds were shown to modulate the production and activities of TNF family cytokines. Cytokines from the TNF family (TNF- α, TRAIL, and FasL) have potent inflammatory activities and can also regulate apoptosis, which plays an important role in cancer development. The results of our own research showed enhancement of apoptosis in colon cancer cells by a combination of either docosahexaenoic acid (DHA) or butyrate with TNF family cytokines, especially by promotion of the mitochondrial apoptotic pathway and modulation of NF κ B activity. This review is focused mainly on the interaction of dietary PUFAs and butyrate with these cytokines during colon inflammation and cancer development. We summarised recent knowledge about the cellular and molecular mechanisms involved in such effects and outcomes for intestinal cell behaviour and pathologies. Finally, the possible application for the prevention and therapy of colon inflammation and cancer is also outlined.

  16. Molecular basis of essential amino acid transport from studies of insect nutrient amino acid transporters of the SLC6 family (NAT-SLC6)

    PubMed Central

    Boudko, Dmitri Y.

    2012-01-01

    Two protein families that represent major components of essential amino acid transport in insects have been identified. They are annotated as the SLC6 and SLC7 families of transporters according to phylogenetic proximity to characterized amino acid transporters (HUGO nomenclature). Members of these families have been identified as important apical and basolateral parts of transepithelial essential amino acid absorption in the metazoan alimentary canal. Synergistically, they play critical physiological roles as essential substrate providers to diverse metabolic processes, including generic protein synthesis. This review briefly clarifies the requirements for amino acid transport and a variety of amino acid transport mechanisms, including the aforementioned families. Further it focuses on the large group of Nutrient Amino acid Transporters (NATs), which comprise a recently identified subfamily of the Neurotransmitter Sodium Symporter family (NSS or SLC6). The first insect NAT, cloned from the caterpillar gut, has a broad substrate spectrum similar to mammalian B0 transporters. Several new NAT-SLC6 members have been characterized in an effort to explore mechanisms for the essential amino acid absorption in model dipteran insects. The identification and functional characterization of new B0-like and narrow specificity transporters of essential amino acids in fruit fly and mosquitoes leads to a fundamentally important insight: that NATs evolved and act together as the integrated active core of a transport network that mediates active alimentary absorption and systemic distribution of essential amino acids. This role of NATs is projected from the most primitive prokaryotes to the most complex metazoan organisms, and represents an interesting platform for unraveling the molecular evolution of amino acid transport and modeling amino acid transport disorders. The comparative study of NATs elucidates important adaptive differences between essential amino acid transportomes

  17. Clustering of protein families into functional subtypes using Relative Complexity Measure with reduced amino acid alphabets

    PubMed Central

    2010-01-01

    Background Phylogenetic analysis can be used to divide a protein family into subfamilies in the absence of experimental information. Most phylogenetic analysis methods utilize multiple alignment of sequences and are based on an evolutionary model. However, multiple alignment is not an automated procedure and requires human intervention to maintain alignment integrity and to produce phylogenies consistent with the functional splits in underlying sequences. To address this problem, we propose to use the alignment-free Relative Complexity Measure (RCM) combined with reduced amino acid alphabets to cluster protein families into functional subtypes purely on sequence criteria. Comparison with an alignment-based approach was also carried out to test the quality of the clustering. Results We demonstrate the robustness of RCM with reduced alphabets in clustering of protein sequences into families in a simulated dataset and seven well-characterized protein datasets. On protein datasets, crotonases, mandelate racemases, nucleotidyl cyclases and glycoside hydrolase family 2 were clustered into subfamilies with 100% accuracy whereas acyl transferase domains, haloacid dehalogenases, and vicinal oxygen chelates could be assigned to subfamilies with 97.2%, 96.9% and 92.2% accuracies, respectively. Conclusions The overall combination of methods in this paper is useful for clustering protein families into subtypes based on solely protein sequence information. The method is also flexible and computationally fast because it does not require multiple alignment of sequences. PMID:20718947

  18. Interleukin-1 family members are enhanced in psoriasis and suppressed by vitamin D and retinoic acid.

    PubMed

    Balato, Anna; Schiattarella, Maria; Lembo, Serena; Mattii, Martina; Prevete, Nella; Balato, Nicola; Ayala, Fabio

    2013-04-01

    Interleukin (IL)-1 family comprise 11 members that play an important role in immune regulation and inflammatory process. Retinoids exert complex effects on the immune system, having anti-inflammatory effects in chronic dermatological diseases. Vitamin D (vitD) and analogs have been shown to suppress TNF-α-induced IL-1α in human keratinocytes (KCs). In the present study, we investigated IL-1 family members in psoriasis and the effects of vitD and retinoic acid (RA) on these members. We analyzed IL-1 family members gene expression in psoriatic skin and in ex vivo skin organ culture exposed to TNF-α, IL-17 or broadband UVB; afterwards, treatment with vitD or RA was performed and IL-1 family members mRNA was evaluated. Similarly, KCs were stimulated with IL-17 and subsequently treated with vitD. IL-1 family members were enhanced in psoriatic skin and in ex vivo skin organ cultures after pro-inflammatory stimuli (TNF-α, IL-17 and UVB). RA and vitD were able to suppress this enhancement.

  19. Protein sequence alignment with family-specific amino acid similarity matrices

    PubMed Central

    2011-01-01

    Background Alignment of amino acid sequences by means of dynamic programming is a cornerstone sequence comparison method. The quality of alignments produced by dynamic programming critically depends on the choice of the alignment scoring function. Therefore, for a specific alignment problem one needs a way of selecting the best performing scoring function. This work is focused on the issue of finding optimized protein family- and fold-specific scoring functions for global similarity matrix-based sequence alignment. Findings I utilize a comprehensive set of reference alignments obtained from structural superposition of homologous and analogous proteins to design a quantitative statistical framework for evaluating the performance of alignment scoring functions in global pairwise sequence alignment. This framework is applied to study how existing general-purpose amino acid similarity matrices perform on individual protein families and structural folds, and to compare them to family-specific and fold-specific matrices derived in this work. I describe an adaptive alignment procedure that automatically selects an appropriate similarity matrix and optimized gap penalties based on the properties of the sequences being aligned. Conclusions The results of this work indicate that using family-specific similarity matrices significantly improves the quality of the alignment of homologous sequences over the traditional sequence alignment based on a single general-purpose similarity matrix. However, using fold-specific similarity matrices can only marginally improve sequence alignment of proteins that share the same structural fold but do not share a common evolutionary origin. The family-specific matrices derived in this work and the optimized gap penalties are available at http://taurus.crc.albany.edu/fsm. PMID:21846354

  20. Hypertension aggregates in families of kidney stone patients with high urinary excretion of uric acid.

    PubMed

    Tisler, A; Pierratos, A; Honey, J D; Bull, S B; Logan, A G

    1999-12-01

    To determine whether kidney stone disease (KSD) and hypertension (HTN) share a common familial component that is determined by a specific urinary biochemical abnormality. Familial aggregation study. Two hundred and twelve KSD patients, aged 18-50 years, collected a 24-h urine sample to measure the urinary excretion of uric acid, calcium, oxalate, magnesium and citrate, and were interviewed about the occurrence of HTN among first-degree relatives. Positive family history (FHx) of HTN defined as two or more relatives with HTN, and HTN occurring in the fathers, mothers and siblings. Positive FHx of HTN was significantly associated with increasing urinary excretion of uric acid (P = 0.03) but not with the excretion of the other substances. When the patients were divided into those with and without hyperuricosuria, the adjusted odds ratio (OR) for positive FHx of HTN in a hyperuricosuric KSD patient was 3.8 (95% CI, 1.22-11.66). Separate analysis on the occurrence of HTN in the fathers, mothers and siblings of the probands indicated that hyperuricosuria is positively related to HTN occurring in the siblings of the patients (P < 0.001) but not in the fathers or in the mothers. The adjusted OR for HTN occurring in siblings of hyperuricosuric patients compared with siblings of non-hyperuricosuric patients was 3.8 (2.12-6.67). Siblings of KSD patients with hyperuricosuria had a significantly increased prevalence of HTN that could not be accounted for by age, family size, body-mass index and personal history of HTN of the probands. Additional studies need to be undertaken to determine whether this familial clustering has a genetic or environmental origin.

  1. Global trophic position comparison of two dominant mesopelagic fish families (Myctophidae, Stomiidae) using amino acid nitrogen isotopicanalyses

    EPA Science Inventory

    We examined the biogeochemical and ecological mechanisms responsible for variability in bulk tissue and amino acid (AA) stable nitrogen isotope compositions in two groups of important mesopelagic fish families, Myctophidae (lanternfishes) and Stomiidae (dragonfishes), from five d...

  2. Global trophic position comparison of two dominant mesopelagic fish families (Myctophidae, Stomiidae) using amino acid nitrogen isotopicanalyses

    EPA Science Inventory

    We examined the biogeochemical and ecological mechanisms responsible for variability in bulk tissue and amino acid (AA) stable nitrogen isotope compositions in two groups of important mesopelagic fish families, Myctophidae (lanternfishes) and Stomiidae (dragonfishes), from five d...

  3. Increased Abundance of Proteins Involved in Phytosiderophore Production in Boron-Tolerant Barley1[C][W

    PubMed Central

    Patterson, John; Ford, Kris; Cassin, Andrew; Natera, Siria; Bacic, Antony

    2007-01-01

    Boron (B) phytotoxicity affects cereal-growing regions worldwide. Although B-tolerant barley (Hordeum vulgare) germplasm is available, molecules responsible for this tolerance mechanism have not been defined. We describe and use a new comparative proteomic technique, iTRAQ peptide tagging (iTRAQ), to compare the abundances of proteins from B-tolerant and -intolerant barley plants from a ‘Clipper’ × ‘Sahara’ doubled-haploid population selected on the basis of a presence or absence of two B-tolerance quantitative trait loci. iTRAQ was used to identify three enzymes involved in siderophore production (Iron Deficiency Sensitive2 [IDS2], IDS3, and a methylthio-ribose kinase) as being elevated in abundance in the B-tolerant plants. Following from this result, we report a potential link between iron, B, and the siderophore hydroxymugineic acid. We believe that this study highlights the potency of the iTRAQ approach to better understand mechanisms of abiotic stress tolerance in cereals, particularly when applied in conjunction with bulked segregant analysis. PMID:17478636

  4. Novel Enzyme Family Found in Filamentous Fungi Catalyzing trans-4-Hydroxylation of l-Pipecolic Acid

    PubMed Central

    Hibi, Makoto; Mori, Ryosuke; Miyake, Ryoma; Kawabata, Hiroshi; Kozono, Shoko; Takahashi, Satomi

    2016-01-01

    Hydroxypipecolic acids are bioactive compounds widely distributed in nature and are valuable building blocks for the organic synthesis of pharmaceuticals. We have found a novel hydroxylating enzyme with activity toward l-pipecolic acid (l-Pip) in a filamentous fungus, Fusarium oxysporum c8D. The enzyme l-Pip trans-4-hydroxylase (Pip4H) of F. oxysporum (FoPip4H) belongs to the Fe(II)/α-ketoglutarate-dependent dioxygenase superfamily, catalyzes the regio- and stereoselective hydroxylation of l-Pip, and produces optically pure trans-4-hydroxy-l-pipecolic acid (trans-4-l-HyPip). Amino acid sequence analysis revealed several fungal enzymes homologous with FoPip4H, and five of these also had l-Pip trans-4-hydroxylation activity. In particular, the homologous Pip4H enzyme derived from Aspergillus nidulans FGSC A4 (AnPip4H) had a broader substrate specificity spectrum than other homologues and reacted with the l and d forms of various cyclic and aliphatic amino acids. Using FoPip4H as a biocatalyst, a system for the preparative-scale production of chiral trans-4-l-HyPip was successfully developed. Thus, we report a fungal family of l-Pip hydroxylases and the enzymatic preparation of trans-4-l-HyPip, a bioactive compound and a constituent of secondary metabolites with useful physiological activities. PMID:26801577

  5. Gambogic acid is an antagonist of anti-apoptotic Bcl-2-family proteins

    PubMed Central

    Zhai, Dayong; Jin, Chaofang; Shiau, Chung-wai; Kitada, Shinichi; Satterthwait, Arnold C; Reed, John C.

    2008-01-01

    The natural product Gambogic acid (GA) has been reported to have cytotoxic activity against tumor cells in culture, and was identified as an active compound in a cell-based high-throughput screening (HTS) assay for activators of caspases, proteases involved in apoptosis. Using the anti-apoptotic Bcl-2-family protein, Bfl-1, as a target for screening of a library of natural products, we identified GA as a competitive inhibitor that displaced BH3 peptides from Bfl-1 in a fluorescent polarization assay (FPA). Analysis of competition for BH3 peptide binding revealed that GA inhibits all 6 human Bcl-2-family proteins to various extents, with Mcl-1 and Bcl-B the most potently inhibited (concentrations required for 50% inhibition [IC50] <1 μM). Competition for BH3 peptide binding was also confirmed using a time-resolved fluorescence resonance energy transfer (TR-FRET) assay. GA functionally inhibited the anti-apoptotic Bcl-2-family proteins, as demonstrated by experiments using isolated mitochondria in which recombinant purified Bcl-2-family proteins suppress SMAC release in vitro, showing that GA neutralizes their suppressive effects on mitochondria in a concentration-dependent manner. GA killed tumor cell lines via an apoptotic mechanism, whereas analogs of GA with greatly reduced potency at BH3 peptide displacement showed little or no cytotoxic activity. However, GA retained cytotoxic activity against bax−/− bak−/− cells in which anti-apoptotic Bcl-2-family proteins lack a cytoprotective phenotype, implying that GA also has additional targets that contribute to its cytotoxic mechanism. Altogether, the findings suggest that suppression of anti-apoptotic Bcl-2-family proteins may be among the cytotoxic mechanisms by which GA kills tumor cells. PMID:18566235

  6. Defining sequence space and reaction products within the cyanuric acid hydrolase (AtzD)/barbiturase protein family.

    PubMed

    Seffernick, Jennifer L; Erickson, Jasmine S; Cameron, Stephan M; Cho, Seunghee; Dodge, Anthony G; Richman, Jack E; Sadowsky, Michael J; Wackett, Lawrence P

    2012-09-01

    Cyanuric acid hydrolases (AtzD) and barbiturases are homologous, found almost exclusively in bacteria, and comprise a rare protein family with no discernible linkage to other protein families or an X-ray structural class. There has been confusion in the literature and in genome projects regarding the reaction products, the assignment of individual sequences as either cyanuric acid hydrolases or barbiturases, and spurious connection of this family to another protein family. The present study has addressed those issues. First, the published enzyme reaction products of cyanuric acid hydrolase are incorrectly identified as biuret and carbon dioxide. The current study employed (13)C nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry to show that cyanuric acid hydrolase releases carboxybiuret, which spontaneously decarboxylates to biuret. This is significant because it revealed that homologous cyanuric acid hydrolases and barbiturases catalyze completely analogous reactions. Second, enzymes that had been annotated incorrectly in genome projects have been reassigned here by bioinformatics, gene cloning, and protein characterization studies. Third, the AtzD/barbiturase family has previously been suggested to consist of members of the amidohydrolase superfamily, a large class of metallohydrolases. Bioinformatics and the lack of bound metals both argue against a connection to the amidohydrolase superfamily. Lastly, steady-state kinetic measurements and observations of protein stability suggested that the AtzD/barbiturase family might be an undistinguished protein family that has undergone some resurgence with the recent introduction of industrial s-triazine compounds such as atrazine and melamine into the environment.

  7. Biochemical Roles for Conserved Residues in the Bacterial Fatty Acid-binding Protein Family*

    PubMed Central

    Broussard, Tyler C.; Miller, Darcie J.; Jackson, Pamela; Nourse, Amanda; White, Stephen W.; Rock, Charles O.

    2016-01-01

    Fatty acid kinase (Fak) is a ubiquitous Gram-positive bacterial enzyme consisting of an ATP-binding protein (FakA) that phosphorylates the fatty acid bound to FakB. In Staphylococcus aureus, Fak is a global regulator of virulence factor transcription and is essential for the activation of exogenous fatty acids for incorporation into phospholipids. The 1.2-Å x-ray structure of S. aureus FakB2, activity assays, solution studies, site-directed mutagenesis, and in vivo complementation were used to define the functions of the five conserved residues that define the FakB protein family (Pfam02645). The fatty acid tail is buried within the protein, and the exposed carboxyl group is bound by a Ser-93-fatty acid carboxyl-Thr-61-His-266 hydrogen bond network. The guanidinium of the invariant Arg-170 is positioned to potentially interact with a bound acylphosphate. The reduced thermal denaturation temperatures of the T61A, S93A, and H266A FakB2 mutants illustrate the importance of the hydrogen bond network in protein stability. The FakB2 T61A, S93A, and H266A mutants are 1000-fold less active in the Fak assay, and the R170A mutant is completely inactive. All FakB2 mutants form FakA(FakB2)2 complexes except FakB2(R202A), which is deficient in FakA binding. Allelic replacement shows that strains expressing FakB2 mutants are defective in fatty acid incorporation into phospholipids and virulence gene transcription. These conserved residues are likely to perform the same critical functions in all bacterial fatty acid-binding proteins. PMID:26774272

  8. An improved and general streamlined phylogenetic protocol applied to the fatty acid desaturase family.

    PubMed

    Wilding, Matthew; Nachtschatt, Matthias; Speight, Robert; Scott, Colin

    2017-10-01

    Numerous tools to generate phylogenetic estimates are available, but there is no single protocol that will produce an accurate phylogenetic tree for any dataset. Here, we investigated some of those tools, paying particular attention to different alignment algorithms, in order to produce a phylogeny for the integral membrane fatty acid desaturase (FAD) family. Herein, we report a novel streamlined protocol which utilises peptide pattern recognition (PPR). This protocol can theoretically be applied universally to generate accurate multiple sequence alignments and improve downstream phylogenetic analyses. Applied to the desaturases, the protocol generated the first detailed phylogenetic estimates for the family since 2003, which suggested they may have evolved from three functionally distinct desaturases and further, that desaturases evolved first in cyanobacteria. In addition to the phylogenetic outputs, we mapped PPR sequence motifs onto an X-ray protein structure to provide insights into biochemical function and demonstrate the complementarity of PPR and phylogenetics. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Amino acid and DNA analyses in a family with ornithine transcarbamylase deficiency.

    PubMed

    Hou, J W; Wang, T R

    1996-02-01

    Ornithine transcarbamylase (OTC) is a hepatic mitochondrial enzyme involved in the detoxification of ammonia by the urea cycle. OTC deficiency is an X-linked genetic disorder, usually causing neonatal or infantile hyperammonemia, coma and death. We attended a male newborn who had poor feeding since 30 hours of age, at which time, he then rapidly progressed to a comatose state. Hyperammonemia and liver dysfunction were noted. Analysis of plasma amino acids showed elevated levels of glutamine and alanine, but a decreased level of arginine and no citrulline. OTC deficiency was diagnosed by family history of early death of newborn males on the maternal side and characteristic biochemical findings. In addition, it was proved by Southern blot analysis of genomic DNA. Although OTC deficiency has been described as the most common inborn error of ureagenesis in humans, to our knowledge, this is the first report in a Chinese family confirmed by biochemical and DNA analyses.

  10. Familial type II hyperlipoproteinemia with coronary heart disease: effect of diet-colestipol-nicotinic acid treatment.

    PubMed

    Kuo, P T; Kostis, J B; Moreyra, A E; Hayes, J A

    1981-03-01

    Heterozygous familial type II hyperlipoproteinemia (F type II) is primarily manifested in hypercholesterolemia (due to low density lipoprotein-cholesterol [LDL-C] elevation) and premature coronary heart disease (CHD). We studied sequentially the effects of low cholesterol-low saturated fat-low simple carbohydrate diet; diet and colestipol, 30 g/day; and diet, colestipol, plus nicotinic acid (NA) 3 to 7 g/day on plasma cholesterol (Ch), LDL-C, triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and angiographically documented coronary arterial lesions of 32 F type II patients. Effective control of F type II resulted in arresting the progression of angiographically demonstrated coronary arterial lesions.

  11. Genome-wide analysis of the omega-3 fatty acid desaturase gene family in Gossypium

    DOE PAGES

    Yurchenko, Olga P.; Park, Sunjung; Ilut, Daniel C.; ...

    2014-11-18

    The majority of commercial cotton varieties planted worldwide are derived from Gossypium hirsutum, which is a naturally occurring allotetraploid produced by interspecific hybridization of A- and D-genome diploid progenitor species. While most cotton species are adapted to warm, semi-arid tropical and subtropical regions, and thus perform well in these geographical areas, cotton seedlings are sensitive to cold temperature, which can significantly reduce crop yields. One of the common biochemical responses of plants to cold temperatures is an increase in omega-3 fatty acids, which protects cellular function by maintaining membrane integrity. The purpose of our study was to identify and characterizemore » the omega-3 fatty acid desaturase (FAD) gene family in G. hirsutum, with an emphasis on identifying omega-3 FADs involved in cold temperature adaptation. Results: Eleven omega-3 FAD genes were identified in G. hirsutum, and characterization of the gene family in extant A and D diploid species (G. herbaceum and G. raimondii, respectively) allowed for unambiguous genome assignment of all homoeologs in tetraploid G. hirsutum. The omega-3 FAD family of cotton includes five distinct genes, two of which encode endoplasmic reticulum-type enzymes (FAD3-1 and FAD3-2) and three that encode chloroplast-type enzymes (FAD7/8-1, FAD7/8-2, and FAD7/8-3). The FAD3-2 gene was duplicated in the A genome progenitor species after the evolutionary split from the D progenitor, but before the interspecific hybridization event that gave rise to modern tetraploid cotton. RNA-seq analysis revealed conserved, gene-specific expression patterns in various organs and cell types and semi-quantitative RT-PCR further revealed that FAD7/8-1 was specifically induced during cold temperature treatment of G. hirsutum seedlings. Conclusions: The omega-3 FAD gene family in cotton was characterized at the genome-wide level in three species, showing relatively ancient establishment of the gene family prior

  12. Plasma homovanillic acid and family history of psychotic disorders in bipolar I patients.

    PubMed

    Zumárraga, Mercedes; Dávila, Ricardo; Basterreche, Nieves; Arrue, Aurora; Goienetxea, Biotza; González-Torres, Miguel Angel; Guimón, José

    2009-04-01

    It has been suggested that the family history of psychotic disorders is useful in defining homogeneous groups of bipolar patients. The plasma homovanillic acid (pHVA) concentrations have been related to the effect of antipsychotic treatment in psychotic patients. We have studied the influence of a positive family history of psychotic disorders both on the variation of pHVA levels and on the relation between pHVA concentrations and the clinical response to treatment. Clinical status and pHVA levels were assessed in 58 medication free patients before and after 4 weeks of treatment with olanzapine and lithium. Clinical improvement correlated positively with pHVA levels on the 28th day of treatment only in the patients having first degree relatives with psychotic disorders. The pHVA levels did not decrease after 28 days of treatment. Our results reinforce the idea that a positive family history of psychosis in psychotic bipolar disorders may constitute a good basis for sub-grouping these patients.

  13. Multiple origins of crassulacean acid metabolism and the epiphytic habit in the Neotropical family Bromeliaceae

    PubMed Central

    Crayn, Darren M.; Winter, Klaus; Smith, J. Andrew C.

    2004-01-01

    The large Neotropical family Bromeliaceae presents an outstanding example of adaptive radiation in plants, containing a wide range of terrestrial and epiphytic life-forms occupying many distinct habitats. Diversification in bromeliads has been linked to several key innovations, including water- and nutrient-impounding phytotelmata, absorptive epidermal trichomes, and the water-conserving mode of photosynthesis known as crassulacean acid metabolism (CAM). To clarify the origins of CAM and the epiphytic habit, we conducted a phylogenetic analysis of nucleotide sequences for 51 bromeliad taxa by using the plastid loci matK and the rps16 intron, combined with a survey of photosynthetic pathway determined by carbon-isotope ratios for 1,873 species representing 65% of the family. Optimization of character-states onto the strict consensus tree indicated that the last common ancestor of Bromeliaceae was a terrestrial C3 mesophyte, probably adapted to moist, exposed, nutrient-poor habitats. Both CAM photosynthesis and the epiphytic habit evolved a minimum of three times in the family, most likely in response to geological and climatic changes in the late Tertiary. The great majority of epiphytic forms are now found in two lineages: in subfamily Tillandsioideae, in which C3 photosynthesis was the ancestral state and CAM developed later in the most extreme epiphytes, and in subfamily Bromelioideae, in which CAM photosynthesis predated the appearance of epiphytism. Subsequent radiation of the bromelioid line into less xeric habitats has led to reversion to C3 photosynthesis in some taxa, showing that both gain and loss of CAM have occurred in the complex evolutionary history of this family. PMID:14982989

  14. Multiple origins of crassulacean acid metabolism and the epiphytic habit in the Neotropical family Bromeliaceae.

    PubMed

    Crayn, Darren M; Winter, Klaus; Smith, J Andrew C

    2004-03-09

    The large Neotropical family Bromeliaceae presents an outstanding example of adaptive radiation in plants, containing a wide range of terrestrial and epiphytic life-forms occupying many distinct habitats. Diversification in bromeliads has been linked to several key innovations, including water- and nutrient-impounding phytotelmata, absorptive epidermal trichomes, and the water-conserving mode of photosynthesis known as crassulacean acid metabolism (CAM). To clarify the origins of CAM and the epiphytic habit, we conducted a phylogenetic analysis of nucleotide sequences for 51 bromeliad taxa by using the plastid loci matK and the rps16 intron, combined with a survey of photosynthetic pathway determined by carbon-isotope ratios for 1,873 species representing 65% of the family. Optimization of character-states onto the strict consensus tree indicated that the last common ancestor of Bromeliaceae was a terrestrial C(3) mesophyte, probably adapted to moist, exposed, nutrient-poor habitats. Both CAM photosynthesis and the epiphytic habit evolved a minimum of three times in the family, most likely in response to geological and climatic changes in the late Tertiary. The great majority of epiphytic forms are now found in two lineages: in subfamily Tillandsioideae, in which C(3) photosynthesis was the ancestral state and CAM developed later in the most extreme epiphytes, and in subfamily Bromelioideae, in which CAM photosynthesis predated the appearance of epiphytism. Subsequent radiation of the bromelioid line into less xeric habitats has led to reversion to C(3) photosynthesis in some taxa, showing that both gain and loss of CAM have occurred in the complex evolutionary history of this family.

  15. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption

    PubMed Central

    Montagnani, Marco; Abrahamsson, Anna; Gälman, Cecilia; Eggertsen, Gösta; Marschall, Hanns-Ulrich; Ravaioli, Elisa; Einarsson, Curt; Dawson, Paul A

    2006-01-01

    The etiology of most cases of idiopathic bile acid malabsorption (IBAM) is unknown. In this study, a Swedish family with bile acid malabsorption in three consecutive generations was screened for mutations in the ileal apical sodium-bile acid cotransporter gene (ASBT; gene symbol, SLC10A2) and in the genes for several of the nuclear receptors known to be important for ASBT expression: the farnesoid X receptor (FXR) and peroxisome proliferator activated receptor alpha (PPARα). The patients presented with a clinical history of idiopathic chronic watery diarrhea, which was responsive to cholestyramine treatment and consistent with IBAM. Bile acid absorption was determined using 75Se-homocholic acid taurine (SeHCAT); bile acid synthesis was estimated by measuring the plasma levels of 7α-hydroxy-4-cholesten-3-one (C4). The ASBT, FXR, and PPARα genes in the affected and unaffected family members were analyzed using single stranded conformation polymorphism (SSCP), denaturing HPLC, and direct sequencing. No ASBT mutations were identified and the ASBT gene did not segregate with the bile acid malabsorption phenotype. Similarly, no mutations or polymorphisms were identified in the FXR or PPARα genes associated with the bile acid malabsorption phenotype. These studies indicate that the intestinal bile acid malabsorption in these patients cannot be attributed to defects in ASBT. In the absence of apparent ileal disease, alternative explanations such as accelerated transit through the small intestine may be responsible for the IBAM. PMID:17171805

  16. Effect of molecular structure of phenolic families as hydroxycinnamic acids and catechins on their antioxidant effectiveness in minced fish muscle.

    PubMed

    Medina, I; Gallardo, J M; Gonzalez, M J; Lois, S; Hedges, N

    2007-05-16

    The antioxidant effectiveness of two different families of phenolic compounds, hydroxycinnamic acids and catechins, added as a power (0.001% w/w) to chilled minced horse mackerel muscle was evaluated. Caffeic acid, chlorogenic acid, o-coumaric acid, and ferulic acid were selected as hydroxycinnamic acids with similar molecular structures. Commercial catechins with different numbers of hydroxylic groups, including catechin, gallocatechin, catechin gallate, and gallocatechin gallate, were also tested. The effectiveness found was individually discussed for each family as a function of the molecular structure. The capacity of hydroxycinnamic acids for donating electrons seems to play the most significant role for retarding the development of rancidity in fish muscle. Conversely, the properties related to the ability for chelating metals and the distribution between oily and aqueous phases were not correlated with the inhibitory activities. Among hydroxycinnamic acids, the results highlighted the potent antioxidant activity of 10 ppm caffeic acid in inhibiting lipid oxidation in fish muscle. Its antioxidant efficacy was similar to that of propyl gallate. Among catechins, catechin showed the highest antioxidant activity. There was an increment of efficacy in fish muscle using concentrations ranging between 10 and 100 ppm of both caffeic acid and catechin.

  17. Bile Acid Pool Dynamics in Progressive Familial Intrahepatic Cholestasis with Partial External Bile Diversion

    PubMed Central

    Jericho, Hilary Smith; Kaurs, Elizabeth; Boverhof, Renze; Knisely, Alex; Shneider, Benjamin L; Verkade, Henkjan J; Whitington, Peter F

    2015-01-01

    Objectives Partial external bile diversion (PEBD) is an established therapy for low-GGT Progressive Familial Intrahepatic Cholestasis (PFIC). This study sought to determine if the dynamics of the cholic acid (CA) and chenodeoxycholic acid (CDCA) pools in low-GGT-PFIC subjects with successful PEBD were equivalent to those achieved with successful liver transplantation (LTX). Methods The kinetics of CA and CDCA metabolism were measured by stable isotope dilution in plasma samples in 5 PEBD subjects all with intact canalicular BSEP expression and compared to low-GGT-PFIC subjects with successful LTX. Stomal loss of bile acids was measured in PEBD subjects. Results The fractional turnover rate for CA in the PEBD group ranged from 0.5 to 4.2 d−1 (LTX group, range 0.2 – 0.9 d−1, p = 0.076) and for CDCA from 0.7 to 4.5 d−1 (LTX group 0.3 – 0.4 d−1, p = 0.009). The CA and CDCA pool sizes were equivalent between groups; however pool composition in PEBD was somewhat more hydrophilic. The CA/CDCA ratio in PEBD ranged from 0.9 to 19.5, whereas in LTX it ranged from 0.5 to 2.6. Synthesis rates computed from isotope dilution correlated well with timed output for both CA: r2 = 0.760, p = 0.024 and CDCA: r2 = 0.690, p = 0.021. Conclusions PEBD results in bile acid fractional turnover rates greater than LTX, pool sizes equivalent to LTX and pool composition that is at least as hydrophilic as produced by LTX. PMID:25383786

  18. An Amino Acid Deletion in SZT2 in a Family with Non-Syndromic Intellectual Disability

    PubMed Central

    Falcone, Michelle; Yariz, Kemal O.; Ross, David B.; Foster, Joseph; Menendez, Ibis; Tekin, Mustafa

    2013-01-01

    Autosomal recessive intellectual disability (ID) is characterized by extensive genetic heterogeneity. Recently, three mutations in SZT2 were reported in two unrelated children with unexplained infantile epileptic encephalopathy with severe ID. Here we report a European American family with three children having non-syndromic mild or moderate ID without seizures. Whole-exome sequencing of three affected siblings revealed a three base pair deletion (c.4202_4204delTTC) located in a 19 mb autozygous region on chromosome 1, leading to an amino acid deletion (p.Phe1401del) in SZT2. All three children were homozygous for the deletion and their parents were heterozygous as expected in autosomal recessive inheritance. SZT2 is highly expressed in neuronal tissues and regulates seizure threshold and neuronal excitation in mice. We conclude that the disruption of SZT2 with some residual function might lead to mild or moderate ID without seizures. PMID:24324832

  19. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis.

    PubMed

    Jacquemin, E; Hermans, D; Myara, A; Habes, D; Debray, D; Hadchouel, M; Sokal, E M; Bernard, O

    1997-03-01

    Progressive familial intrahepatic cholestasis (PFIC) is a lethal inherited childhood cholestasis of hepatocellular origin. Different subtypes of PFIC have been described according to serum gamma-glutamyl transpeptidase (GGT) activity. There is currently no effective medical therapy available for children with PFIC. We report on 39 patients with PFIC who received ursodeoxycholic acid (UDCA) orally (20-30 mg/kg b.w./day) for a period of 2 to 4 years. Group 1 (n = 26) consisted of children with normal GGT activity, and group 2 (n = 13) of children with high GGT activity. Within group 1, liver tests normalized in 11 children, improved in 5, and stabilized or worsened in 10. Within group 2, liver tests normalized in six children, improved in four, and stabilized or worsened in three. Improvement of parameters was associated with an enrichment of the circulating pool of bile acids with UDCA. Hepatosplenomegaly and pruritus disappeared or diminished in children in whom liver tests normalized. In nine of these children, liver tests worsened and normalized again after stopping and restarting UDCA. Liver histology assessed in four children after normalization of liver tests and 2 years of treatment showed a decrease in fibrosis. We conclude that UDCA should be considered in the initial therapeutic management of children with PFIC, because it appears effective in resolving or improving the liver function and the clinical status of a fair proportion of children. Chronic UDCA therapy might thus avoid the need for liver transplantation in some children with PFIC.

  20. Phylogenetic, Molecular, and Biochemical Characterization of Caffeic Acid o-Methyltransferase Gene Family in Brachypodium distachyon

    PubMed Central

    Wu, Xianting; Wu, Jiajie; Luo, Yangfan; Bragg, Jennifer; Anderson, Olin; Vogel, John; Gu, Yong Q.

    2013-01-01

    Caffeic acid o-methyltransferase (COMT) is one of the important enzymes controlling lignin monomer production in plant cell wall synthesis. Analysis of the genome sequence of the new grass model Brachypodium distachyon identified four COMT gene homologs, designated as BdCOMT1, BdCOMT2, BdCOMT3, and BdCOMT4. Phylogenetic analysis suggested that they belong to the COMT gene family, whereas syntenic analysis through comparisons with rice and sorghum revealed that BdCOMT4 on Chromosome 3 is the orthologous copy of the COMT genes well characterized in other grass species. The other three COMT genes are unique to Brachypodium since orthologous copies are not found in the collinear regions of rice and sorghum genomes. Expression studies indicated that all four Brachypodium COMT genes are transcribed but with distinct patterns of tissue specificity. Full-length cDNAs were cloned in frame into the pQE-T7 expression vector for the purification of recombinant Brachypodium COMT proteins. Biochemical characterization of enzyme activity and substrate specificity showed that BdCOMT4 has significant effect on a broad range of substrates with the highest preference for caffeic acid. The other three COMTs had low or no effect on these substrates, suggesting that a diversified evolution occurred on these duplicate genes that not only impacted their pattern of expression, but also altered their biochemical properties. PMID:23431288

  1. ω-3 Fatty Acid Ethyl Esters Diminish Postprandial Lipemia in Familial Hypercholesterolemia.

    PubMed

    Chan, Dick C; Pang, Jing; Barrett, P Hugh R; Sullivan, David R; Burnett, John R; van Bockxmeer, Frank M; Watts, Gerald F

    2016-10-01

    Impaired postprandial chylomicron metabolism induces hypertriglyceridemia and may increase the risk of atherosclerotic cardiovascular disease. Omega-3 fatty acid ethyl ester (ω-3 FAEE) supplementation decreases plasma triglycerides. However, its effect on postprandial chylomicron metabolism in familial hypercholesterolemia (FH) has not yet been investigated. We aimed to examine the effect of ω-3 FAEE supplementation on postprandial responses in plasma triglycerides, very-low-density lipoprotein (VLDL) apolipoprotein B (apoB)-100, and apoB-48 in FH patients receiving standard cholesterol-lowering treatment. We carried out an 8-week open-label, randomized, crossover intervention trial to test the effect of oral supplementation with 4 g/d ω-3 FAEE (46% eicosapentaenoic acid and 38% docosahexaenoic acid) on postprandial triglyceride, VLDL-apoB-100, and apoB-48 responses in FH patients after ingestion of an oral fat load. Plasma total and incremental triglyceride, VLDL-apoB-100, and apoB-48 0- to 10-hour area under the curve (AUC). ω-3 FAEE supplementation significantly (P < .05 in all) reduced concentrations of fasting plasma triglyceride (-20%), apoB (-8%), VLDL-apoB-100 (-26%), and apoB-48 (-36%); as well as systolic blood pressure (-6%) and diastolic blood pressure (-6%). Postprandial triglyceride and VLDL-apoB-100 total AUCs (-19% and -26%, respectively; P < .01) and incremental AUCs (-18% and -35%, respectively; P < .05), as well as postprandial apoB-48 total AUC (-30%; P < .02) were significantly reduced by ω-3 FAEE supplementation. Supplementation with ω-3 FAEEs improves postprandial lipemia in FH patients receiving standard care; this may have implications for further reducing atherosclerotic cardiovascular disease in this high-risk patient group.

  2. Biomonitoring of 2,4-Dichlorophenoxyacetic Acid Exposure and Dose in Farm Families

    PubMed Central

    Alexander, Bruce H.; Mandel, Jack S.; Baker, Beth A.; Burns, Carol J.; Bartels, Michael J.; Acquavella, John F.; Gustin, Christophe

    2007-01-01

    Objective We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and systemic dose in farm family members following an application of 2,4-D on their farm. Methods Farm families were recruited from licensed applicators in Minnesota and South Carolina. Eligible family members collected all urine during five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D. Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which then were related to potential predictors of exposure. Systemic dose was estimated using the urine collections from the application day through the third day after application. Results Median urine 2,4-D concentrations at baseline and day after application were 2.1 and 73.1 μ g/L for applicators, below the limit of detection, and 1.2 μ g/L for spouses, and 1.5 and 2.9 μ g/L for children. The younger children (4–11 years of age) had higher median post-application concentrations than the older children (≥ 12 years of age) (6.5 vs. 1.9 μ g/L). The geometric mean systemic doses (micrograms per kilogram body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32 (children 4–11 years of age), and 0.12 (children ≥ 12 years of age). Exposure to the spouses and children was primarily determined by direct contact with the application process and the number of acres treated. Multivariate models identified glove use, repairing equipment, and number of acres treated as predictors of exposure in the applicators. Conclusions We observed considerable heterogeneity of 2,4-D exposure among farm family members, primarily attributable to level of contact with the application process. Awareness of this variability and the actual magnitude of exposures are important for developing exposure and risk characterizations in 2,4-D–exposed agricultural populations. PMID:17431485

  3. A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

    PubMed Central

    Pavlenko, Natalia V; Oos, Tatiana I; Gerus, Igor I; Doeller, Uwe; Willms, Lothar

    2014-01-01

    Summary A series of novel (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of proteinogenic and nonproteinogenic α-amino acids were prepared. The synthetic methodology was based on nucleophilic addition of (trifluoromethyl)phosphinic acid or (difluoromethyl)phosphinic acid or its ethyl ester to substrates with C=N or activated C=C double bonds. Analogues of glycine, phenylglycine, alanine, valine, proline, aminomalonic and aspartic acids were thus prepared. Three-component one-pot reactions of (trifluoromethyl)phosphinic acid and dibenzylamine with aldehydes were also tested to prepare the title compounds. PMID:24778725

  4. Comparative Studies of Mammalian Acid Lipases: Evidence for a New Gene Family in Mouse and Rat (Lipo)

    PubMed Central

    Holmes, Roger S; Cox, Laura A; VandeBerg, John L

    2010-01-01

    At least six families of mammalian acid lipases (E.C. 3.1.1.-) catalyse the hydrolysis of triglycerides in the body, designated as LIPA (lysosomal), LIPF (gastric), LIPJ (testis) and LIPK, LIPM and LIPN (epidermal), which belong to the AB hydrolase superfamily. In this study, in silico methods were used to predict the amino acid sequences, secondary and tertiary structures, and gene locations for acid lipase genes and encoded proteins using data from several mammalian genome projects. Mammalian acid lipase genes were located within a gene cluster for each of the 8 mammalian genomes examined, including human (Homo sapiens), chimpanzee (Pons troglodytes), rhesus monkey (Macacca mulatta), mouse (Mus musculus), rat (Rattus norvegicus), cow (Bos taurus), horse (Equus caballus) and dog (Canis familaris), with each containing 9 coding exons. Human and mouse acid lipases shared 44-87% sequence identity and exhibited sequence alignments and identities for key amino acid residues and conservation of predicted secondary and tertiary structures with those previously reported for human gastric lipase (LIPF) (Roussel et al., 1999). Evidence for a new family of acid lipase genes is reported for mouse and rat genomes, designated as Lipo. Mouse acid lipase genes are subject to differential mRNA tissue expression, with Lipa showing wide tissue expression, while others have a more restricted tissue expression in the digestive tract (Lipf), salivary gland (Lipo) and epidermal tissues (Lipk, Lipm and Lipn). Phylogenetic analyses of the mammalian acid lipase gene families suggested that these genes are products of gene duplication events prior to eutherian mammalian evolution and derived from an ancestral vertebrate LIPA gene, which is present in the frog, Xenopus tropicalis. PMID:20598663

  5. Kinetic basis for the conjugation of auxin by a GH3 family indole-acetic acid-amido synthetase.

    PubMed

    Chen, Qingfeng; Westfall, Corey S; Hicks, Leslie M; Wang, Shiping; Jez, Joseph M

    2010-09-24

    The GH3 family of acyl-acid-amido synthetases catalyze the ATP-dependent formation of amino acid conjugates to modulate levels of active plant hormones, including auxins and jasmonates. Initial biochemical studies of various GH3s show that these enzymes group into three families based on sequence relationships and acyl-acid substrate preference (I, jasmonate-conjugating; II, auxin- and salicylic acid-conjugating; III, benzoate-conjugating); however, little is known about the kinetic and chemical mechanisms of these enzymes. Here we use GH3-8 from Oryza sativa (rice; OsGH3-8), which functions as an indole-acetic acid (IAA)-amido synthetase, for detailed mechanistic studies. Steady-state kinetic analysis shows that the OsGH3-8 requires either Mg(2+) or Mn(2+) for maximal activity and is specific for aspartate but accepts asparagine as a substrate with a 45-fold decrease in catalytic efficiency and accepts other auxin analogs, including phenyl-acetic acid, indole butyric acid, and naphthalene-acetic acid, as acyl-acid substrates with 1.4-9-fold reductions in k(cat)/K(m) relative to IAA. Initial velocity and product inhibition studies indicate that the enzyme uses a Bi Uni Uni Bi Ping Pong reaction sequence. In the first half-reaction, ATP binds first followed by IAA. Next, formation of an adenylated IAA intermediate results in release of pyrophosphate. The second half-reaction begins with binding of aspartate, which reacts with the adenylated intermediate to release IAA-Asp and AMP. Formation of a catalytically competent adenylated-IAA reaction intermediate was confirmed by mass spectrometry. These mechanistic studies provide insight on the reaction catalyzed by the GH3 family of enzymes to modulate plant hormone action.

  6. New functions of the chloroplast Preprotein and Amino acid Transporter (PRAT) family members in protein import.

    PubMed

    Rossig, Claudia; Reinbothe, Christiane; Gray, John; Valdes, Oscar; von Wettstein, Diter; Reinbothe, Steffen

    2014-01-01

    Plant cells contain distinct compartments such as the nucleus, the endomembrane system comprising the endoplasmic reticulum and Golgi apparatus, peroxisomes, vacuoles, as well as mitochondria and chloroplasts. All of these compartments are surrounded by 1 or 2 limiting membranes and need to import proteins from the cytosol. Previous work led to the conclusion that mitochondria and chloroplasts use structurally different protein import machineries in their outer and inner membranes for the uptake of cytosolic precursor proteins. Our most recent data show that there is some unexpected overlap. Three members of the family of preprotein and amino acid transporters, PRAT, were identified in chloroplasts that mediate the uptake of transit sequence-less proteins into the inner plastid envelope membrane. By analogy, mitochondria contain with TIM22 a related PRAT protein that is involved in the import of transit sequence-less proteins into the inner mitochondrial membrane. Both mitochondria and chloroplasts thus make use of similar import mechanisms to deliver some of their proteins to their final place. Because single homologs of HP20- and HP30-like proteins are present in algae such as Chlamydomonas, Ostreococcus, and Volvox, which diverged from land plants approximately 1 billion years ago, it is likely that the discovered PRAT-mediated mechanism of protein translocation evolved concomitantly with the secondary endosymbiotic event that gave rise to green plants.

  7. Lysosomal acid lipase deficiency: A hidden disease among cohorts of familial hypercholesterolemia?

    PubMed

    Chora, Joana Rita; Alves, Ana Catarina; Medeiros, Ana Margarida; Mariano, Cibelle; Lobarinhas, Goreti; Guerra, António; Mansilha, Helena; Cortez-Pinto, Helena; Bourbon, Mafalda

    Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder and an unrecognized cause of dyslipidemia. Patients usually present with dyslipidemia and altered liver function and mutations in LIPA gene are the underlying cause of LALD. The aim of this study was to investigate LALD in individuals with severe dyslipidemia and/or liver steatosis. Coding, splice regions, and promoter region of LIPA were sequenced by Sanger sequencing in a cohort of mutation-negative familial hypercholesterolemia (FH) patients (n = 492) and in a population sample comprising individuals with several types of dyslipidemia and/or liver steatosis (n = 258). This study led to the identification of LALD in 4 children referred to the Portuguese FH Study, all with a clinical diagnosis of FH. Mild liver dysfunction was present at the age of FH diagnosis; however, a diagnosis of LALD was not considered. No adults at the time of referral have been identified with LALD. LALD is a life-threatening disorder, and early identification is crucial for the implementation of specific treatment to avoid premature mortality. FH cohorts should be investigated to identify possible LALD patients, who will need appropriate treatment. These results highlight the importance of correctly identifying the etiology of the dyslipidemia. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. GH1-family 6-P-β-glucosidases from human microbiome lactic acid bacteria

    PubMed Central

    Michalska, Karolina; Tan, Kemin; Li, Hui; Hatzos-Skintges, Catherine; Bearden, Jessica; Babnigg, Gyorgy; Joachimiak, Andrzej

    2013-01-01

    In lactic acid bacteria and other bacteria, carbohydrate uptake is mostly governed by phosphoenolpyruvate-dependent phosphotransferase systems (PTSs). PTS-dependent translocation through the cell membrane is coupled with phosphorylation of the incoming sugar. After translocation through the bacterial membrane, the β-glycosidic bond in 6′-­P-­β-glucoside is cleaved, releasing 6-P-β-glucose and the respective aglycon. This reaction is catalyzed by 6-P-β-glucosidases, which belong to two glycoside hydrolase (GH) families: GH1 and GH4. Here, the high-resolution crystal structures of GH1 6-P-β-glucosidases from Lactobacillus plantarum (LpPbg1) and Streptococcus mutans (SmBgl) and their complexes with ligands are reported. Both enzymes show hydrolytic activity towards 6′-P-β-glucosides. The LpPbg1 structure has been determined in an apo form as well as in a complex with phosphate and a glucose molecule corresponding to the aglycon molecule. The S. mutans homolog contains a sulfate ion in the phosphate-dedicated subcavity. SmBgl was also crystallized in the presence of the reaction product 6-P-β-glucose. For a mutated variant of the S. mutans enzyme (E375Q), the structure of a 6′-P-salicin complex has also been determined. The presence of natural ligands enabled the definition of the structural elements that are responsible for substrate recognition during catalysis. PMID:23519420

  9. Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members.

    PubMed

    Marcos, Enrique; Crehuet, Ramon; Bahar, Ivet

    2011-09-01

    Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions) favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities.

  10. Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids.

    PubMed

    Tvrdik, P; Westerberg, R; Silve, S; Asadi, A; Jakobsson, A; Cannon, B; Loison, G; Jacobsson, A

    2000-05-01

    Whereas the physiological significance of microsomal fatty acid elongation is generally appreciated, its molecular nature is poorly understood. Here, we describe tissue-specific regulation of a novel mouse gene family encoding components implicated in the synthesis of very long chain fatty acids. The Ssc1 gene appears to be ubiquitously expressed, whereas Ssc2 and Cig30 show a restricted expression pattern. Their translation products are all integral membrane proteins with five putative transmembrane domains. By complementing the homologous yeast mutants, we found that Ssc1 could rescue normal sphingolipid synthesis in the sur4/elo3 mutant lacking the ability to synthesize cerotic acid (C(26:0)). Similarly, Cig30 reverted the phenotype of the fen1/elo2 mutant that has reduced levels of fatty acids in the C(20)-C(24) range. Further, we show that Ssc1 mRNA levels were markedly decreased in the brains of myelin-deficient mouse mutants known to have very low fatty acid chain elongation activity. Conversely, the dramatic induction of Cig30 expression during brown fat recruitment coincided with elevated elongation activity. Our results strongly implicate this new mammalian gene family in tissue-specific synthesis of very long chain fatty acids and sphingolipids.

  11. The maize (Zea mays ssp. mays var. B73) genome encodes 33 members of the purple acid phosphatase family

    PubMed Central

    González-Muñoz, Eliécer; Avendaño-Vázquez, Aida-Odette; Montes, Ricardo A. Chávez; de Folter, Stefan; Andrés-Hernández, Liliana; Abreu-Goodger, Cei; Sawers, Ruairidh J. H.

    2015-01-01

    Purple acid phosphatases (PAPs) play an important role in plant phosphorus nutrition, both by liberating phosphorus from organic sources in the soil and by modulating distribution within the plant throughout growth and development. Furthermore, members of the PAP protein family have been implicated in a broader role in plant mineral homeostasis, stress responses and development. We have identified 33 candidate PAP encoding gene models in the maize (Zea mays ssp. mays var. B73) reference genome. The maize Pap family includes a clear single-copy ortholog of the Arabidopsis gene AtPAP26, shown previously to encode both major intracellular and secreted acid phosphatase activities. Certain groups of PAPs present in Arabidopsis, however, are absent in maize, while the maize family contains a number of expansions, including a distinct radiation not present in Arabidopsis. Analysis of RNA-sequencing based transcriptome data revealed accumulation of maize Pap transcripts in multiple plant tissues at multiple stages of development, and increased accumulation of specific transcripts under low phosphorus availability. These data suggest the maize PAP family as a whole to have broad significance throughout the plant life cycle, while highlighting potential functional specialization of individual family members. PMID:26042133

  12. Identification of GH15 Family Thermophilic Archaeal Trehalases That Function within a Narrow Acidic-pH Range

    PubMed Central

    Shimodaira, Satoru; Ishida, Shin-nosuke; Amemiya, Miko; Honda, Shotaro; Sugahara, Yasusato; Oyama, Fumitaka; Kawakita, Masao

    2015-01-01

    Two glucoamylase-like genes, TVN1315 and Ta0286, from the archaea Thermoplasma volcanium and T. acidophilum, respectively, were expressed in Escherichia coli. The gene products, TVN1315 and Ta0286, were identified as archaeal trehalases. These trehalases belong to the CAZy database family GH15, although they have putative (α/α)6 barrel catalytic domain structures similar to those of GH37 and GH65 family trehalases from other organisms. These newly identified trehalases function within a narrow range of acidic pH values (pH 3.2 to 4.0) and at high temperatures (50 to 60°C), and these enzymes display Km values for trehalose higher than those observed for typical trehalases. These enzymes were inhibited by validamycin A; however, the inhibition constants (Ki) were higher than those of other trehalases. Three TVN1315 mutants, corresponding to E408Q, E571Q, and E408Q/E571Q mutations, showed reduced activity, suggesting that these two glutamic acid residues are involved in trehalase catalysis in a manner similar to that of glucoamylase. To date, TVN1315 and Ta0286 are the first archaeal trehalases to be identified, and this is the first report of the heterologous expression of GH15 family trehalases. The identification of these trehalases could extend our understanding of the relationships between the structure and function of GH15 family enzymes as well as glycoside hydrolase family enzymes; additionally, these enzymes provide insight into archaeal trehalose metabolism. PMID:25979886

  13. The maize (Zea mays ssp. mays var. B73) genome encodes 33 members of the purple acid phosphatase family.

    PubMed

    González-Muñoz, Eliécer; Avendaño-Vázquez, Aida-Odette; Montes, Ricardo A Chávez; de Folter, Stefan; Andrés-Hernández, Liliana; Abreu-Goodger, Cei; Sawers, Ruairidh J H

    2015-01-01

    Purple acid phosphatases (PAPs) play an important role in plant phosphorus nutrition, both by liberating phosphorus from organic sources in the soil and by modulating distribution within the plant throughout growth and development. Furthermore, members of the PAP protein family have been implicated in a broader role in plant mineral homeostasis, stress responses and development. We have identified 33 candidate PAP encoding gene models in the maize (Zea mays ssp. mays var. B73) reference genome. The maize Pap family includes a clear single-copy ortholog of the Arabidopsis gene AtPAP26, shown previously to encode both major intracellular and secreted acid phosphatase activities. Certain groups of PAPs present in Arabidopsis, however, are absent in maize, while the maize family contains a number of expansions, including a distinct radiation not present in Arabidopsis. Analysis of RNA-sequencing based transcriptome data revealed accumulation of maize Pap transcripts in multiple plant tissues at multiple stages of development, and increased accumulation of specific transcripts under low phosphorus availability. These data suggest the maize PAP family as a whole to have broad significance throughout the plant life cycle, while highlighting potential functional specialization of individual family members.

  14. Global trophic position comparison of two dominant mesopelagic fish families (Myctophidae, Stomiidae) using amino acid nitrogen isotopic analyses

    USGS Publications Warehouse

    Choy, C. Anela; Davison, Peter C.; Drazen, Jeffrey C.; Flynn, Adrian; Gier, Elizabeth J.; Hoffman, Joel C.; McClain-Counts, Jennifer P.; Miller, Todd W.; Popp, Brian N.; Ross, Steve W.; Sutton, Tracey T.

    2012-01-01

    The δ15N values of organisms are commonly used across diverse ecosystems to estimate trophic position and infer trophic connectivity. We undertook a novel cross-basin comparison of trophic position in two ecologically well-characterized and different groups of dominant mid-water fish consumers using amino acid nitrogen isotope compositions. We found that trophic positions estimated from the δ15N values of individual amino acids are nearly uniform within both families of these fishes across five global regions despite great variability in bulk tissue δ15N values. Regional differences in the δ15N values of phenylalanine confirmed that bulk tissue δ15N values reflect region-specific water mass biogeochemistry controlling δ15N values at the base of the food web. Trophic positions calculated from amino acid isotopic analyses (AA-TP) for lanternfishes (family Myctophidae) (AA-TP ~2.9) largely align with expectations from stomach content studies (TP ~3.2), while AA-TPs for dragonfishes (family Stomiidae) (AA-TP ~3.2) were lower than TPs derived from stomach content studies (TP~4.1). We demonstrate that amino acid nitrogen isotope analysis can overcome shortcomings of bulk tissue isotope analysis across biogeochemically distinct systems to provide globally comparative information regarding marine food web structure.

  15. Global trophic position comparison of two dominant mesopelagic fish families (Myctophidae, Stomiidae) using amino acid nitrogen isotopic analyses.

    PubMed

    Choy, C Anela; Davison, Peter C; Drazen, Jeffrey C; Flynn, Adrian; Gier, Elizabeth J; Hoffman, Joel C; McClain-Counts, Jennifer P; Miller, Todd W; Popp, Brian N; Ross, Steve W; Sutton, Tracey T

    2012-01-01

    The δ(15)N values of organisms are commonly used across diverse ecosystems to estimate trophic position and infer trophic connectivity. We undertook a novel cross-basin comparison of trophic position in two ecologically well-characterized and different groups of dominant mid-water fish consumers using amino acid nitrogen isotope compositions. We found that trophic positions estimated from the δ(15)N values of individual amino acids are nearly uniform within both families of these fishes across five global regions despite great variability in bulk tissue δ(15)N values. Regional differences in the δ(15)N values of phenylalanine confirmed that bulk tissue δ(15)N values reflect region-specific water mass biogeochemistry controlling δ(15)N values at the base of the food web. Trophic positions calculated from amino acid isotopic analyses (AA-TP) for lanternfishes (family Myctophidae) (AA-TP ∼2.9) largely align with expectations from stomach content studies (TP ∼3.2), while AA-TPs for dragonfishes (family Stomiidae) (AA-TP ∼3.2) were lower than TPs derived from stomach content studies (TP∼4.1). We demonstrate that amino acid nitrogen isotope analysis can overcome shortcomings of bulk tissue isotope analysis across biogeochemically distinct systems to provide globally comparative information regarding marine food web structure.

  16. HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid.

    PubMed

    Roy, Ajit; Ranjan, Akash

    2016-02-23

    Members of the Multiple antibiotic resistance Regulator (MarR) family of DNA binding proteins regulate transcription of a wide array of genes required for virulence and pathogenicity of bacteria. The present study reports the molecular characterization of HosA (Homologue of SlyA), a MarR protein, with respect to its target gene, DNA recognition motif, and nature of its ligand. Through a comparative genomics approach, we demonstrate that hosA is in synteny with nonoxidative hydroxyarylic acid decarboxylase (HAD) operon and is present exclusively within the mutS-rpoS polymorphic region in nine different genera of Enterobacteriaceae family. Using molecular biology and biochemical approach, we demonstrate that HosA binds to a palindromic sequence downstream to the transcription start site of divergently transcribed nonoxidative HAD operon and represses its expression. Furthermore, in silico analysis showed that the recognition motif for HosA is highly conserved in the upstream region of divergently transcribed operon in different genera of Enterobacteriaceae family. A systematic chemical search for the physiological ligand revealed that 4-hydroxybenzoic acid (4-HBA) interacts with HosA and derepresses HosA mediated repression of the nonoxidative HAD operon. Based on our study, we propose a model for molecular mechanism underlying the regulation of nonoxidative HAD operon by HosA in Enterobacteriaceae family.

  17. A clinicobiochemical study of tryptophan and other plasma and urinary amino acids in the family with Hartnup disease.

    PubMed

    Milovanović, Dragoslav D

    2003-01-01

    Two cases of Hartnup disease were diagnosed in a five member family. A changeable polymorph and severe clinical features of a 16 year old girl was described. Total plasma amino acids value was significantly decreased in the girl compared to the sum of plasma amino acids value in the brother, mother, father and to the summed maximal values of normal range. Intermediate aminoaciduria was also found with atypical amino acids pattern. Total plasma amino acids concentration was significantly reduced (27.20%) in the mother, while no significant decrease in the son (1.83%) and father (7.51%) were found compared to the summed maximal values of normal range. In the clinicaly healthy father, 38 years of age, a gross aminoaciduria with atypical pattern of amino acids was also found. Urinary amino acids concentration in the son and his mother were rather normal, although low concentration of eight amino acids was found in the mother's urine. Cerebrospinal fluid 5-hydroxyindoleacetic acid level was reduced in the girl.

  18. The Gibberellic Acid Stimulated-Like gene family in maize and its role in lateral root development.

    PubMed

    Zimmermann, Roman; Sakai, Hajime; Hochholdinger, Frank

    2010-01-01

    In an approach to study lateral root development in monocots, genome-wide searches for homologs of the Gibberellic Acid Stimulated Transcript-like (GAST-like) gene family in rice (Oryza sativa) and maize (Zea mays) were carried out. Six novel GAST-like genes in rice and 10 members of the gene family in maize, which were designated ZmGSL (for Z. mays Gibberellic Acid Stimulated-Like), were identified. The ZmGSL family encodes small proteins of 75 to 128 amino acids, which are characterized by a conserved 59 to 64 amino acid C-terminal domain. Within this domain, 17 amino acids, including 12 cysteines, are perfectly conserved. The transcript of the ZmGSL1 gene is differentially spliced into the alternative variants ZmGSL1a and ZmGSL1b, the latter of which is translated into a premature protein that lacks the C-terminal domain. The presence of an additional N-terminal cleavable signal sequence in eight of the 10 ZmGSL proteins suggests that they are secreted into the extracellular matrix. In-depth root-specific gene expression analyses carried out in the wild type and the lateral root mutants lrt1 and rum1 suggest a role for ZmGSL genes in early lateral root development, which is likely regulated by gibberellic acid. Expression patterns of ZmGSL1a and ZmGSL1b propose antagonistic functions of these splice variants during early lateral root formation.

  19. Carbon isotopes in otolith amino acids identify residency of juvenile snapper (Family: Lutjanidae) in coastal nurseries

    NASA Astrophysics Data System (ADS)

    McMahon, K. W.; Berumen, M. L.; Mateo, I.; Elsdon, T. S.; Thorrold, S. R.

    2011-12-01

    This study explored the potential for otolith geochemistry in snapper (Family: Lutjanidae) to identify residency in juvenile nursery habitats with distinctive carbon isotope values. Conventional bulk otolith and muscle stable isotope analyses (SIA) and essential amino acid (AA) SIA were conducted on snapper collected from seagrass beds, mangroves, and coral reefs in the Red Sea, Caribbean Sea, and Pacific coast of Panama. While bulk stable isotope values in otoliths showed regional differences, they failed to distinguish nursery residence on local scales. Essential AA δ13C values in otoliths, on the other hand, varied as a function of habitat type and provided a better tracer of residence in different juvenile nursery habitats than conventional bulk otolith SIA alone. A strong linear relationship was found between paired otolith and muscle essential AA δ13C values regardless of species, geographic region, or habitat type, indicating that otolith AAs recorded the same dietary information as muscle AAs. Juvenile snapper in the Red Sea sheltered in mangroves but fed in seagrass beds, while snapper from the Caribbean Sea and Pacific coast of Panama showed greater reliance on mangrove-derived carbon. Furthermore, compound-specific SIA revealed that microbially recycled detrital carbon, not water-column-based new phytoplankton carbon, was the primary carbon source supporting snapper production on coastal reefs of the Red Sea. This study presented robust tracers of juvenile nursery residence that will be crucial for reconstructing ontogenetic migration patterns of fishes among coastal wetlands and coral reefs. This information is key to determining the importance of nursery habitats to coral reef fish populations and will provide valuable scientific support for the design of networked marine-protected areas.

  20. Family history of exceptional longevity is associated with lower serum uric acid levels in Ashkenazi Jews.

    PubMed

    Lai, Jennifer Yi-Chun; Atzmon, Gil; Melamed, Michal L; Hostetter, Thomas H; Crandall, Jill P; Barzilai, Nir; Bitzer, Markus

    2012-04-01

    To test whether lower serum uric acid (UA) levels are associated with longevity independent of renal function. Cross-sectional cohort study. Ashkenazi Jewish individuals with exceptional longevity (Longevity Genes Project at Albert Einstein College of Medicine). Long-lived individuals (LLI) of Ashkenazi Jewish ethnicity (mean age ± standard deviation 97.7 ± 2.9, n = 365), their offspring (mean age ± standard deviation 68.2 ± 8.2, n = 593) and controls (without family history of longevity, mean age ± standard deviation 72.5 ± 9.9, n = 356). Association between UA levels and estimated glomerular filtration rate (eGFR) as well as chronic kidney disease (CKD) stage, and correlation of UA levels of LLI and offspring were determined. Because LLI lack an appropriate control group, UA levels, eGFR, and prevalence of hyperuricemia and CKD stages were compared between offspring and controls. Offspring were less likely to have hyperuricemia and had lower UA levels than controls. Despite negative correlation between UA levels and eGFR and positive correlation between UA levels and CKD stages, eGFR and the prevalence of CKD stage III to V were not found to be different between offspring and controls. Furthermore, significant association between UA levels in LLI and their offspring (β estimate 0.1544, 95% confidence interval = 0.08-0.23, P < .001) has been observed. Offspring had lower UA levels than controls despite similar renal function, suggesting that other factors such as UA metabolism or renal tubular transport determine UA levels. The association between UA levels and longevity is particularly intriguing because UA levels are potentially modifiable with diet and drugs. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  1. Cloning and characterization of the NapA acid phosphatase/phosphotransferase of Morganella morganii: identification of a new family of bacterial acid-phosphatase-encoding genes.

    PubMed

    Thaller, M C; Lombardi, G; Berlutti, F; Schippa, S; Rossolini, G M

    1995-01-01

    The gene encoding a minor phosphate-irrepressible acid phosphatase (named NapA) of Morganella morganii was cloned and sequenced, and its product characterized. NapA is a secreted acid phosphatase composed of four 27 kDa polypeptide subunits. The enzyme is active on several organic phosphate monoesters but not on diesters, and is also endowed with transphosphorylating activity from organic phosphoric acid esters to nucleosides and other compounds with free hydroxyl groups. Its activity is inhibited by EDTA, inorganic phosphate, nucleosides and Ca2+, but not by fluoride or tartrate, and is enhanced by Mg2+, Co2+ and Zn2+. At the sequence level, the NapA enzyme did not show similarities to any other sequenced bacterial phosphatases. However, a search for homologous genes in sequence databases allowed identification of two open reading frames located within sequenced regions of the Escherichia coli and Proteus mirabilis genomes respectively, encoding proteins of unknown function which are highly homologous to the Morganella enzyme. Moreover, the properties of the NapA enzyme are very similar to those reported for the periplasmic nonspecific acid phosphatase II of Salmonella typhimurium (for which no sequence data are available). These data point to the existence of a new family of bacterial acid phosphatases, which we propose designating class B bacterial acid phosphatases.

  2. Principal transcriptional regulation and genome-wide system interactions of the Asp-family and aromatic amino acid networks of amino acid metabolism in plants.

    PubMed

    Less, Hadar; Angelovici, Ruthie; Tzin, Vered; Galili, Gad

    2010-10-01

    Amino acid metabolism is among the most important and best recognized networks within biological systems. In plants, amino acids serve multiple functions associated with growth. Besides their function in protein synthesis, the amino acids are also catabolized into energy-associated metabolites as well we into numerous secondary metabolites, which are essential for plant growth and response to various stresses. Despite the central importance of amino acids in plants growth, elucidation of the regulation of amino acid metabolism within the context of the entire system, particularly transcriptional regulation, is still in its infancy. The different amino acids are synthesized by a number of distinct metabolic networks, which are expected to possess regulatory cross interactions between them for proper coordination of their interactive functions, such as incorporation into proteins. Yet, individual amino acid metabolic networks are also expected to differentially cross interact with various genome-wide gene expression programs and metabolic networks, in respect to their functions as precursors for various metabolites with distinct functions. In the present review, we discuss our recent genomics, metabolic and bioinformatics studies, which were aimed at addressing these questions, focusing mainly on the Asp-family metabolic network as the main example and also comparing it to the aromatic amino acids metabolic network as a second example (Angelovici et al. in Plant Physiol 151:2058-2072, 2009; Less and Galili in BMC Syst Biol 3:14, 2009; Tzin et al. in Plant J 60:156-167, 2009). Our focus on these two networks is because of the followings: (i) both networks are central to plant metabolism and growth and are also precursors for a wide range of primary and secondary metabolites that are indispensable to plant growth; (ii) the amino acids produced by these two networks are also essential to the nutrition and health of human and farm animals; and (iii) both networks contain

  3. The aspartate-family pathway of plants: linking production of essential amino acids with energy and stress regulation.

    PubMed

    Galili, Gad

    2011-02-01

    The Asp family pathway of plants is highly important from a nutritional standpoint because it leads to the synthesis of the four essential amino acids Lys, Thr, Met and Ile. These amino acids are not synthesized by human and its monogastric livestock and should be supplemented in their diets. Among the Asp-family amino acids, Lys is considered as the nutritionally most important essential amino acid because its level is most limiting in cereal grains, representing the largest source of plant foods and feeds worldwide. Metabolic engineering approaches led to significant increase in Lys level in seeds by enhancing its synthesis and reducing its catabolism. However, results from the model plant Arabidopsis showed that this approach may retard seed germination due to a major negative effect on the levels of a number of TCA cycle metabolites that associate with cellular energy. In the present review, we discuss the regulatory metabolic link of the Asp-family pathway with the TCA cycle and its biological significance upon exposure to stress conditions that cause energy deprivation. In addition, we also discuss how deep understanding of the regulatory metabolic link of the Asp-family pathway with energy and stress regulation can be used to improve Lys level in seeds of important crop species, minimizing the interference with the cellular energy status and plant-stress interaction. This review thus provides an example showing how deep understanding the inter-regulation of metabolism with plant stress physiology can lead to successful nutritional improvements with minimal negative effect on plant growth and response to stressful environments.

  4. The Human Gene SLC25A29, of Solute Carrier Family 25, Encodes a Mitochondrial Transporter of Basic Amino Acids*

    PubMed Central

    Porcelli, Vito; Fiermonte, Giuseppe; Longo, Antonella; Palmieri, Ferdinando

    2014-01-01

    The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family, many of which have been shown to transport carboxylates, amino acids, nucleotides, and cofactors across the inner mitochondrial membrane, thereby connecting cytosolic and matrix functions. In this work, a member of this family, SLC25A29, previously reported to be a mitochondrial carnitine/acylcarnitine- or ornithine-like carrier, has been thoroughly characterized biochemically. The SLC25A29 gene was overexpressed in Escherichia coli, and the gene product was purified and reconstituted in phospholipid vesicles. Its transport properties and kinetic parameters demonstrate that SLC25A29 transports arginine, lysine, homoarginine, methylarginine and, to a much lesser extent, ornithine and histidine. Carnitine and acylcarnitines were not transported by SLC25A29. This carrier catalyzed substantial uniport besides a counter-exchange transport, exhibited a high transport affinity for arginine and lysine, and was saturable and inhibited by mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. The main physiological role of SLC25A29 is to import basic amino acids into mitochondria for mitochondrial protein synthesis and amino acid degradation. PMID:24652292

  5. The human gene SLC25A29, of solute carrier family 25, encodes a mitochondrial transporter of basic amino acids.

    PubMed

    Porcelli, Vito; Fiermonte, Giuseppe; Longo, Antonella; Palmieri, Ferdinando

    2014-05-09

    The human genome encodes 53 members of the solute carrier family 25 (SLC25), also called the mitochondrial carrier family, many of which have been shown to transport carboxylates, amino acids, nucleotides, and cofactors across the inner mitochondrial membrane, thereby connecting cytosolic and matrix functions. In this work, a member of this family, SLC25A29, previously reported to be a mitochondrial carnitine/acylcarnitine- or ornithine-like carrier, has been thoroughly characterized biochemically. The SLC25A29 gene was overexpressed in Escherichia coli, and the gene product was purified and reconstituted in phospholipid vesicles. Its transport properties and kinetic parameters demonstrate that SLC25A29 transports arginine, lysine, homoarginine, methylarginine and, to a much lesser extent, ornithine and histidine. Carnitine and acylcarnitines were not transported by SLC25A29. This carrier catalyzed substantial uniport besides a counter-exchange transport, exhibited a high transport affinity for arginine and lysine, and was saturable and inhibited by mercurial compounds and other inhibitors of mitochondrial carriers to various degrees. The main physiological role of SLC25A29 is to import basic amino acids into mitochondria for mitochondrial protein synthesis and amino acid degradation.

  6. [Effects of treating with concentrated sulfuric acid on the seed germination of ten Hibiscus hamabo provenance families].

    PubMed

    Wang, Xiao-Xue; Sun, Hai-Jing; Liu, Yun; Chen, Yi-Tai; Feng, Da-Lan; Li, Sha

    2012-11-01

    The seeds from ten Hibiscus hamabo provenance families were treated with concentrated sulfuric acid for different durations (0, 10, 15, and 20 min) , and the seed germination rate, germination energy, and germination index, as well as the seed relative water adsorption rate, soluble sugar and starch contents, and alpha-amylase activity during the germination, were determined, aimed to study the effects of treating with concentrated sulfuric acid on the seed germination of H. hamabo and the differences of the seed germination among different H. hamabo provenance families. After treated with concentrated sulfuric acid, the seed germination rate, germination energy, and germination index increased significantly, and the germination time shortened remarkably. Treating with concentrated sulfuric acid for 15 minutes had the best effect, i. e., the germination rate, germination energy, and germination index were up to 95.7%, 91.3%, and 13.28, respectively, and the germination time was the shortest. The seed germination rate, germination energy, and germination index differed significantly with different provenance families, the highest germination index (15.13) being 2.12 times of the lowest germination index (7.15), and the highest germination energy (98.0%) being 1.77 times of the lowest one (55.5%). Treating with concentrated sulfuric acid accelerated the physiological and biochemical processes of seed germination, and the relative water absorption rate, soluble sugar content, and a-amylase activity were decreased after an initial increase, with the maximum at the early stage of germination. There was a significant negative relationship between the seed starch content and the seed germination index.

  7. Elevated cholesterol and bile acid synthesis in an adult patient with homozygous familial hypercholesterolemia. Reduction by a high glucose diet.

    PubMed

    Stacpoole, P W; Grundy, S M; Swift, L L; Greene, H L; Slonim, A E; Burr, I M

    1981-11-01

    Elevated levels of cholesterol synthesis are reported for several young children with homozygous familial hypercholesterolemia (HFH) and are considered to contribute directly to their hypercholesterolemia. In contrast, increased cholesterol production has not previously been found in adult patients with HFH. Using the fecal steroid balance technique, we studied rates of cholesterol and bile acid synthesis in a 24-yr-old man who had severe hypercholesterolemia typical of HFH and who lacked skin fibroblast low density lipoprotein (LDL) receptor activity. On an average diet (45% carbohydrate, 40% fat, 15% protein) mean +/- SEM cholesterol (24.8 +/- 1.4 mg/kg per d) and bile acid (11.1 +/- 1.6 mg/kg per d) excretion were approximately threefold higher than normal. When an isocaloric high carbohydrate, low fat diet (90.5% glucose oligosaccharides, 1.3% safflower oil, 8.2% crystalline amino acids was substituted, mean cholesterol (13.0 +/- 0.5 mg/kg per d) and bile acid (8.6 +/- 0.4 mg/kg per d) fell markedly. The decline in fecal steroid excretion was accompanied by modest reductions in plasma total and LDL cholesterol concentrations and by a softening of cutaneous xanthomata. Although the patient phenotypically and biochemically resembled the HFH state, his family pedigree was not noteable for hypercholesterolemia. While the patient's father had premature cardiovascular disease, his mother had no evidence of heart disease, had normal plasma total and LDL cholesterol levels, and had normal fibroblast LDL receptor activity. Likewise, the plasma cholesterol levels of three other members of the patient's family were normal. Despite the unusual genotypic background of this individual, however, the fecal balance data shows that elevated cholesterol and bile acid synthesis may occur in adult, as well as juvenile, patients with HFH and may be responsive to dietary control.

  8. Characterization and analysis of the cotton cyclopropane fatty acid synthase family and their contribution to cyclopropane fatty acid synthesis

    SciTech Connect

    Yu X. H.; Shanklin J.; Rawat, R.

    2011-05-01

    Cyclopropane fatty acids (CPA) have been found in certain gymnosperms, Malvales, Litchi and other Sapindales. The presence of their unique strained ring structures confers physical and chemical properties characteristic of unsaturated fatty acids with the oxidative stability displayed by saturated fatty acids making them of considerable industrial interest. While cyclopropenoid fatty acids (CPE) are well-known inhibitors of fatty acid desaturation in animals, CPE can also inhibit the stearoyl-CoA desaturase and interfere with the maturation and reproduction of some insect species suggesting that in addition to their traditional role as storage lipids, CPE can contribute to the protection of plants from herbivory. Three genes encoding cyclopropane synthase homologues GhCPS1, GhCPS2 and GhCPS3 were identified in cotton. Determination of gene transcript abundance revealed differences among the expression of GhCPS1, 2 and 3 showing high, intermediate and low levels, respectively, of transcripts in roots and stems; whereas GhCPS1 and 2 are both expressed at low levels in seeds. Analyses of fatty acid composition in different tissues indicate that the expression patterns of GhCPS1 and 2 correlate with cyclic fatty acid (CFA) distribution. Deletion of the N-terminal oxidase domain lowered GhCPS's ability to produce cyclopropane fatty acid by approximately 70%. GhCPS1 and 2, but not 3 resulted in the production of cyclopropane fatty acids upon heterologous expression in yeast, tobacco BY2 cell and Arabidopsis seed. In cotton GhCPS1 and 2 gene expression correlates with the total CFA content in roots, stems and seeds. That GhCPS1 and 2 are expressed at a similar level in seed suggests both of them can be considered potential targets for gene silencing to reduce undesirable seed CPE accumulation. Because GhCPS1 is more active in yeast than the published Sterculia CPS and shows similar activity when expressed in model plant systems, it represents a strong candidate gene for

  9. Identification of a family of fatty acid-speciated Sonic Hedgehog proteins, whose members display differential biological properties

    PubMed Central

    Houel, Stephane; Rodgriguez-Blanco, Jezabel; Singh, Samer; Schilling, Neal; J.Capobianco, Anthony; Ahn, Natalie G.; Robbins, David J.

    2015-01-01

    SUMMARY Hedgehog (HH) proteins are proteolytically processed into a biologically active form, which is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is over-expressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels, and showed that it was more potent than SHH isolated from over-expressing cells. Furthermore, the SHH in our preparations were modified with a diverse spectrum of fatty acids on their amino-termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts, as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins, which might be altered in different physiological and pathological contexts to regulate distinct properties of HH proteins. PMID:25732819

  10. Identification of a family of fatty-acid-speciated sonic hedgehog proteins, whose members display differential biological properties.

    PubMed

    Long, Jun; Tokhunts, Robert; Old, William M; Houel, Stephane; Rodgriguez-Blanco, Jezabel; Singh, Samer; Schilling, Neal; J Capobianco, Anthony; Ahn, Natalie G; Robbins, David J

    2015-03-03

    Hedgehog (HH) proteins are proteolytically processed into a biologically active form that is covalently modified by cholesterol and palmitate. However, most studies of HH biogenesis have characterized protein from cells in which HH is overexpressed. We purified Sonic Hedgehog (SHH) from cells expressing physiologically relevant levels and showed that it was more potent than SHH isolated from overexpressing cells. Furthermore, the SHH in our preparations was modified with a diverse spectrum of fatty acids on its amino termini, and this spectrum of fatty acids varied dramatically depending on the growth conditions of the cells. The fatty acid composition of SHH affected its trafficking to lipid rafts as well as its potency. Our results suggest that HH proteins exist as a family of diverse lipid-speciated proteins that might be altered in different physiological and pathological contexts in order to regulate distinct properties of HH proteins. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. A family of yeast proteins mediating bidirectional vacuolar amino acid transport.

    PubMed

    Russnak, R; Konczal, D; McIntire, S L

    2001-06-29

    Seven genes in Saccharomyces cerevisiae are predicted to code for membrane-spanning proteins (designated AVT1-7) that are related to the neuronal gamma-aminobutyric acid-glycine vesicular transporters. We have now demonstrated that four of these proteins mediate amino acid transport in vacuoles. One protein, AVT1, is required for the vacuolar uptake of large neutral amino acids including tyrosine, glutamine, asparagine, isoleucine, and leucine. Three proteins, AVT3, AVT4, and AVT6, are involved in amino acid efflux from the vacuole and, as such, are the first to be shown directly to transport compounds from the lumen of an acidic intracellular organelle. This function is consistent with the role of the vacuole in protein degradation, whereby accumulated amino acids are exported to the cytosol. Protein AVT6 is responsible for the efflux of aspartate and glutamate, an activity that would account for their exclusion from vacuoles in vivo. Transport by AVT1 and AVT6 requires ATP for function and is abolished in the presence of nigericin, indicating that the same pH gradient can drive amino acid transport in opposing directions. Efflux of tyrosine and other large neutral amino acids by the two closely related proteins, AVT3 and AVT4, is similar in terms of substrate specificity to transport system h described in mammalian lysosomes and melanosomes. These findings suggest that yeast AVT transporter function has been conserved to control amino acid flux in vacuolar-like organelles.

  12. Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids.

    PubMed

    Iyer, Lakshminarayan M; Tahiliani, Mamta; Rao, Anjana; Aravind, L

    2009-06-01

    Modified bases in nucleic acids present a layer of information that directs biological function over and beyond the coding capacity of the conventional bases. While a large number of modified bases have been identified, many of the enzymes generating them still remain to be discovered. Recently, members of the 2-oxoglutarate- and iron(II)-dependent dioxygenase super-family, which modify diverse substrates from small molecules to biopolymers, were predicted and subsequently confirmed to catalyze oxidative modification of bases in nucleic acids. Of these, two distinct families, namely the AlkB and the kinetoplastid base J binding proteins (JBP) catalyze in situ hydroxylation of bases in nucleic acids. Using sensitive computational analysis of sequences, structures and contextual information from genomic structure and protein domain architectures, we report five distinct families of 2-oxoglutarate- and iron(II)-dependent dioxygenase that we predict to be involved in nucleic acid modifications. Among the DNA-modifying families, we show that the dioxygenase domains of the kinetoplastid base J-binding proteins belong to a larger family that includes the Tet proteins, prototyped by the human oncogene Tet1, and proteins from basidiomycete fungi, chlorophyte algae, heterolobosean amoeboflagellates and bacteriophages. We present evidence that some of these proteins are likely to be involved in oxidative modification of the 5-methyl group of cytosine leading to the formation of 5-hydroxymethylcytosine. The Tet/JBP homologs from basidiomycete fungi such as Laccaria and Coprinopsis show large lineage-specific expansions and a tight linkage with genes encoding a novel and distinct family of predicted transposases, and a member of the Maelstrom-like HMG family. We propose that these fungal members are part of a mobile transposon. To the best of our knowledge, this is the first report of a eukaryotic transposable element that encodes its own DNA-modification enzyme with a

  13. Inhibition of aldo-keto reductase family 1 member B10 by unsaturated fatty acids.

    PubMed

    Hara, Akira; Endo, Satoshi; Matsunaga, Toshiyuki; Soda, Midori; El-Kabbani, Ossama; Yashiro, Koji

    2016-11-01

    A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, is a cytosolic NADPH-dependent reductase toward various carbonyl compounds including reactive aldehydes, and is normally expressed in intestines. The enzyme is overexpressed in several extraintestinal cancers, and suggested as a potential target for cancer treatment. We found that saturated and cis-unsaturated fatty acids inhibit AKR1B10. Among the saturated fatty acids, myristic acid was the most potent, showing the IC50 value of 4.2 μM cis-Unsaturated fatty acids inhibited AKR1B10 more potently, and linoleic, arachidonic, and docosahexaenoic acids showed the lowest IC50 values of 1.1 μM. The inhibition by these fatty acids was reversible and kinetically competitive with respect to the substrate, showing the Ki values of 0.24-1.1 μM. These fatty acids, except for α-linoleic acid, were much less inhibitory to structurally similar aldose reductase. Site-directed mutagenesis study suggested that the fatty acids interact with several active site residues of AKR1B10, of which Gln114, Val301 and Gln303 are responsible for the inhibitory selectivity. Linoleic and arachidonic acids also effectively inhibited AKR1B10-mediated 4-oxo-2-nonenal metabolism in HCT-15 cells. Thus, the cis-unsaturated fatty acids may be used as an adjuvant therapy for treatment of cancers that up-regulate AKR1B10. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. The ETS family member ERM contains an alpha-helical acidic activation domain that contacts TAFII60.

    PubMed Central

    Defossez, P A; Baert, J L; Monnot, M; de Launoit, Y

    1997-01-01

    Transcription factors are modular entities built up of discrete domains, some devoted to DNA binding and others permitting transcriptional modulation. The structure of DNA binding domains has been thoroughly investigated and structural classes clearly defined. In sharp contrast, the structural constraints put on transactivating regions, if any, are mostly unknown. Our investigations focus on ERM, a eukaryotic transcription factor of the ETS family. We have previously shown that ERM harbours two transactivating domains (TADs) with distinct functional features: AD1 lies in the first 72 amino acids of ERM, while AD2 sits in the last 62. Here we show that AD1 is a bona fide acidic TAD, for it activated transcription in yeast cells, while AD2 did not. AD1 contains a 20 amino acid stretch predicted to form an alpha-helix that is found unchanged in the related PEA3 and ER81 transcription factors. Circular dichroism analysis revealed that a 32 amino acid peptide encompassing this region is unstructured in water but folds into a helix when the hydrophobic solvent trifluoroethanol is added. The isolated helix was sufficient to activate transcription and mutations predicted to disrupt it dramatically affected AD1-driven transactivation, whereas mutations decreasing its acidity had more gentle effects. A phenylalanine residue within the helix was particularly sensitive to mutations. Finally, we observed that ERM bound TAFII60 via AD1 and bound TBP and TAFII40, presumably via other activation domains. PMID:9358152

  15. Plasma Amino Acid Levels in Children with Autism and Their Families.

    ERIC Educational Resources Information Center

    Aldred, Sarah; Moore, Kieran M.; Fitzgerald, Michael; Waring, Rosemary H.

    2003-01-01

    Plasma amino acid levels were measured in autistic (n=12), Asperger syndrome (n=11) patients, their parents and siblings. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenyalanine, asparagine, tyrosine, alanine, and lysine levels than age-matched controls. Results suggest dysregulated amino…

  16. Plasma Amino Acid Levels in Children with Autism and Their Families.

    ERIC Educational Resources Information Center

    Aldred, Sarah; Moore, Kieran M.; Fitzgerald, Michael; Waring, Rosemary H.

    2003-01-01

    Plasma amino acid levels were measured in autistic (n=12), Asperger syndrome (n=11) patients, their parents and siblings. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenyalanine, asparagine, tyrosine, alanine, and lysine levels than age-matched controls. Results suggest dysregulated amino…

  17. Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids

    PubMed Central

    Iyer, Lakshminarayan M.; Tahiliani, Mamta; Rao, Anjana; Aravind, L.

    2010-01-01

    Modified bases in nucleic acids present a layer of information that directs biological function over and beyond the coding capacity of the conventional bases. While a large number of modified bases have been identified, many of the enzymes generating them still remain to be discovered. Recently, members of the 2-oxoglutarate- and iron(II)-dependent dioxygenase superfamily, which modify diverse substrates from small molecules to biopolymers, were predicted and subsequently confirmed to catalyze oxidative modification of bases in nucleic acids. Of these, two distinct families, namely the AlkB and the kinetoplastid base J binding proteins (JBP) catalyze in situ hydroxylation of bases in nucleic acids. Using sensitive computational analysis of sequences, structures and contextual information from genomic structure and protein domain architectures, we report five distinct families of 2-oxoglutarate- and iron(II)-dependent dioxygenase that we predict to be involved in nucleic acid modifications. Among the DNA-modifying families, we show that the dioxygenase domains of the kinetoplastid base J-binding proteins belong to a larger family that includes the Tet proteins, prototyped by the human oncogene Tet1, and proteins from basidiomycete fungi, chlorophyte algae, heterolobosean amoeboflagellates and bacteriophages. We present evidence that some of these proteins are likely to be involved in oxidative modification of the 5-methyl group of cytosine leading to the formation of 5-hydroxymethyl-cytosine. The Tet/JBP homologs from basidiomycete fungi such as Laccaria and Coprinopsis show large lineage-specific expansions and a tight linkage with genes encoding a novel and distinct family of predicted transposases, and a member of the Maelstrom-like HMG family. We propose that these fungal members are part of a mobile transposon. To the best of our knowledge, this is the first report of a eukaryotic transposable element that encodes its own DNA-modification enzyme with a

  18. The fatty acid compositions of several plant seed oils belong to Leguminosae and Umbelliferae families.

    PubMed

    Öztürk, Meryem; Geçgel, Umit; Duran, Ahmet; Uslu, Nurhan; Özcan, Mehmet Musa

    2014-05-01

    In samples with 1,009, 7,723, 7,618, 7,618, 1,004 and 1,009 number, oleic acid were found as 62.0, 77.0, 74.84, 71.55, 54.52 and 62.30 %, respectively. In other samples, oleic acid content was determined between 17.43 % (1,589) and 34.86 % (1,298). Linoleic acid content of seed oils ranged from 6.52 % (7,727) to 57.29 % (1,501). In addition, linolenic acid content was found between 0.22 % (7,618) and 46.91 % (1,589). Palmitic acid content of samples changed between 2.03 % (7,727) and 19.81 % (1,298). Capric acid was found at high level in 1,009 (8.53 %), 7,727 (37.31 %) and 1,004 (8.28 %) samples. Caproic acid was found in only 7,727 (3.38 %).

  19. The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.

    PubMed

    Touré, B Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Doré, Michael; Joud, Carol; Michael, Walter; DiPietro, Lucian; van der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael

    2013-02-14

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

  20. The Role of the Acidity of N-Heteroaryl Sulfonamides as Inhibitors of Bcl-2 Family Protein–Protein Interactions

    PubMed Central

    2013-01-01

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263. PMID:24900652

  1. The SLC36 family of proton-coupled amino acid transporters and their potential role in drug transport

    PubMed Central

    Thwaites, David T; Anderson, Catriona MH

    2011-01-01

    Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H+-coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal protein breakdown. SLC36A1 has a relatively low affinity (Km 1–10 mM) for its substrates, which include zwitterionic amino and imino acids, heterocyclic amino acids and amino acid-based drugs and derivatives used experimentally and/or clinically to treat epilepsy, schizophrenia, bacterial infections, hyperglycaemia and cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of glycine, proline and hydroxyproline. SLC36A2 also transports amino acid derivatives but has a narrower substrate selectivity and higher affinity (Km 0.1–0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the mRNA level and is a high-affinity (Km 2–3 µM) transporter for proline and tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of amino acid-based drugs by mediating transport in both the small intestine and kidney. LINKED ARTICLES This article is part of a themed section on Transporters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2011.164.issue-7 PMID:21501141

  2. Genome-wide analysis of the omega-3 fatty acid desaturase gene family in Gossypium

    SciTech Connect

    Yurchenko, Olga P.; Park, Sunjung; Ilut, Daniel C.; Inmon, Jay J.; Millhollon, Jon C.; Liechty, Zach; Page, Justin T.; Jenks, Matthew A.; Chapman, Kent D.; Udall, Joshua A.; Gore, Michael A.; Dyer, John M.

    2014-11-18

    The majority of commercial cotton varieties planted worldwide are derived from Gossypium hirsutum, which is a naturally occurring allotetraploid produced by interspecific hybridization of A- and D-genome diploid progenitor species. While most cotton species are adapted to warm, semi-arid tropical and subtropical regions, and thus perform well in these geographical areas, cotton seedlings are sensitive to cold temperature, which can significantly reduce crop yields. One of the common biochemical responses of plants to cold temperatures is an increase in omega-3 fatty acids, which protects cellular function by maintaining membrane integrity. The purpose of our study was to identify and characterize the omega-3 fatty acid desaturase (FAD) gene family in G. hirsutum, with an emphasis on identifying omega-3 FADs involved in cold temperature adaptation. Results: Eleven omega-3 FAD genes were identified in G. hirsutum, and characterization of the gene family in extant A and D diploid species (G. herbaceum and G. raimondii, respectively) allowed for unambiguous genome assignment of all homoeologs in tetraploid G. hirsutum. The omega-3 FAD family of cotton includes five distinct genes, two of which encode endoplasmic reticulum-type enzymes (FAD3-1 and FAD3-2) and three that encode chloroplast-type enzymes (FAD7/8-1, FAD7/8-2, and FAD7/8-3). The FAD3-2 gene was duplicated in the A genome progenitor species after the evolutionary split from the D progenitor, but before the interspecific hybridization event that gave rise to modern tetraploid cotton. RNA-seq analysis revealed conserved, gene-specific expression patterns in various organs and cell types and semi-quantitative RT-PCR further revealed that FAD7/8-1 was specifically induced during cold temperature treatment of G. hirsutum seedlings. Conclusions: The omega-3 FAD gene family in cotton was characterized at the genome-wide level

  3. Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry

    PubMed Central

    Greaves, Jennifer; Munro, Kevin R.; Davidson, Stuart C.; Riviere, Matthieu; Wojno, Justyna; Smith, Terry K.; Tomkinson, Nicholas C. O.; Chamberlain, Luke H.

    2017-01-01

    S-acylation is a major posttranslational modification, catalyzed by the zinc finger DHHC domain containing (zDHHC) enzyme family. S-acylated proteins can be modified by different fatty acids; however, very little is known about how zDHHC enzymes contribute to acyl chain heterogeneity. Here, we used fatty acid-azide/alkyne labeling of mammalian cells, showing their transformation into acyl-CoAs and subsequent click chemistry-based detection, to demonstrate that zDHHC enzymes have marked differences in their fatty acid selectivity. This difference in selectivity was apparent even for highly related enzymes, such as zDHHC3 and zDHHC7, which displayed a marked difference in their ability to use C18:0 acyl-CoA as a substrate. Furthermore, we identified isoleucine-182 in transmembrane domain 3 of zDHHC3 as a key determinant in limiting the use of longer chain acyl-CoAs by this enzyme. This study uncovered differences in the fatty acid selectivity profiles of cellular zDHHC enzymes and mapped molecular determinants governing this selectivity. PMID:28167757

  4. Density functional theory fragment descriptors to quantify the reactivity of a molecular family: application to amino acids.

    PubMed

    Senet, P; Aparicio, F

    2007-04-14

    By using the exact density functional theory, one demonstrates that the value of the local electronic softness of a molecular fragment is directly related to the polarization charge (Coulomb hole) induced by a test electron removed (or added) from (at) the fragment. Our finding generalizes to a chemical group a formal relation between these molecular descriptors recently obtained for an atom in a molecule using an approximate atomistic model [P. Senet and M. Yang, J. Chem. Sci. 117, 411 (2005)]. In addition, a practical ab initio computational scheme of the Coulomb hole and related local descriptors of reactivity of a molecular family having in common a similar fragment is presented. As a blind test, the method is applied to the lateral chains of the 20 isolated amino acids. One demonstrates that the local softness of the lateral chain is a quantitative measure of the similarity of the amino acids. It predicts the separation of amino acids in different biochemical groups (aliphatic, basic, acidic, sulfur contained, and aromatic). The present approach may find applications in quantitative structure activity relationship methodology.

  5. Genome-Wide Survey and Expression Analysis of Amino Acid Transporter Gene Family in Rice (Oryza sativa L.)

    PubMed Central

    Zhao, Heming; Ma, Haoli; Yu, Li; Wang, Xin; Zhao, Jie

    2012-01-01

    Background Amino acid transporters (AATs) that transport amino acids across cellular membranes are essential for plant growth and development. To date, a genome-wide overview of the AAT gene family in rice is not yet available. Methodology/Principal Findings In this study, a total of 85 AAT genes were identified in rice genome and were classified into eleven distinct subfamilies based upon their sequence composition and phylogenetic relationship. A large number of OsAAT genes were expanded via gene duplication, 23 and 24 OsAAT genes were tandemly and segmentally duplicated, respectively. Comprehensive analyses were performed to investigate the expression profiles of OsAAT genes in various stages of vegetative and reproductive development by using data from EST, Microarrays, MPSS and Real-time PCR. Many OsAAT genes exhibited abundant and tissue-specific expression patterns. Moreover, 21 OsAAT genes were found to be differentially expressed under the treatments of abiotic stresses. Comparative analysis indicates that 26 AAT genes with close evolutionary relationships between rice and Arabidopsis exhibited similar expression patterns. Conclusions/Significance This study will facilitate further studies on OsAAT family and provide useful clues for functional validation of OsAATs. PMID:23166615

  6. Effects of perfluorooctane sulfuric acid on placental PRL-family hormone production and fetal growth retardation in mice.

    PubMed

    Lee, Chae Kwan; Kang, Sung Goo; Lee, Jong Tae; Lee, Soo-Woong; Kim, Jeong Ho; Kim, Dae Hwan; Son, Byung Chul; Kim, Kun Hyung; Suh, Chun Hui; Kim, Se Yeong; Park, Yeong Beom

    2015-02-05

    Perfluorooctane sulfuric acid (PFOS) is a persistent organic pollutant, causes fetal growth retardation but the mechanism is still unclear. This study focused on PFOS-induced toxicity such as placental trophoblast cell histopathological changes, endocrine function (i.e., prolactin (PRL)-family hormone production) and subsequent fetal growth retardation in mice. Maternal body weight gain, placental and fetal weights were significantly decreased in proportion to PFOS dosage. Placental efficiency (fetal weight/placental weight) was significantly reduced dose-dependently. Necrotic changes were observed in PFOS-treated placental tissues, and the area of injury increased dose-dependently. Finally, mRNA levels and maternal serum concentrations of the PRL-family hormones (mPL-II, mPLP-Cα, mPLP-K) were significantly reduced dose-dependently. In addition, the changing pattern between PRL-family hormone concentrations and fetal body weight was positively correlated. These results suggest that gestational PFOS treatment induces placental histopathological changes and disruption of endocrine function, finally may lead to fetal growth retardation in mice.

  7. Concentrations of the urinary pyrethroid metabolite 3-phenoxybenzoic acid in farm worker families in the MICASA study.

    PubMed

    Trunnelle, Kelly J; Bennett, Deborah H; Ahn, Ki Chang; Schenker, Marc B; Tancredi, Daniel J; Gee, Shirley J; Stoecklin-Marois, Maria T; Hammock, Bruce D

    2014-05-01

    Indoor pesticide exposure is a growing concern, particularly from pyrethroids, a commonly used class of pesticides. Pyrethroid concentrations may be especially high in homes of immigrant farm worker families who often live in close proximity to agricultural fields, and are faced with poor housing conditions, causing higher pest infestation and more pesticide use. We investigate exposure of farm worker families to pyrethroids in a study of mothers and children living in Mendota, CA within the population-based Mexican Immigration to California: Agricultural Safety and Acculturation (MICASA) Study. We present pyrethroid exposure based on an ELISA analysis of urinary metabolite 3-phenoxybenzoic acid (3PBA) levels among 105 women and 103 children. The median urinary 3PBA levels (children=2.56 ug/g creatinine, mothers=1.46 ug/g creatinine) were higher than those reported in population based studies for the United States general population, but similar to or lower than studies with known high levels of pyrethroid exposure. A positive association was evident between poor housing conditions and the urinary metabolite levels, showing that poor housing conditions are a contributing factor to the higher levels of 3PBA seen in the urine of these farm worker families. Further research is warranted to fully investigate sources of exposure.

  8. On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm.

    PubMed

    Marcos, Enrique; Crehuet, Ramon; Bahar, Ivet

    2010-04-08

    N-acetyl-L-glutamate kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence-->structure-->dynamics-->function.

  9. Molecular analysis of the acid sphingomyelinase deficiency in a family with an intermediate form of Niemann-Pick disease.

    PubMed Central

    Ferlinz, K; Hurwitz, R; Weiler, M; Suzuki, K; Sandhoff, K; Vanier, M T

    1995-01-01

    A novel point mutation in the lysosomal acid sphingomyelinase gene has been identified in the recently reported Serbian family with a clinically and biochemically atypical intermediate form of Niemann-Pick disease. The mutation was a T1171-->G transversion resulting in substitution of glycine for normal tryptophan at amino acid residue 391. The coding sequence was otherwise normal. All of the five affected individuals were almost certainly homoallelic, and both of the two obligate heterozygotes studied also carried the same mutation. This mutation is therefore likely to be directly associated with the atypical phenotype of these patients. Expression in COS-1 cells suggested a higher residual activity than that in cultured fibroblasts. A recently developed high-affinity rabbit antihuman sphingomyelinase antibody allowed us to study for the first time the biosynthesis, processing, and targeting of a mutant sphingomyelinase by metabolic labeling of cultured fibroblasts. The mutant enzyme protein was normally synthesized, processed, and routed to the lysosome but was apparently unstable and degraded rapidly once it reached the lysosome. Together with the finding of the relatively high residual activity in COS-1 cells, we interpret our observations to mean that instability and rapid breakdown of the mature mutant enzyme protein, due to the mutation rather than direct inactivation of the catalytic activity, is the primary mechanism for the deficiency of sphingomyelinase activity in these patients. A high prevalence of this mutation in the Serbian population is likely, since the family pedigree indicates that members from four reportedly unrelated families must have contributed the same mutation. Images Figure 2 Figure 3 PMID:7762557

  10. The EZ:Faast family of amino acid analysis kits: application of the GC-FID kit for rapid determination of plasma tryptophan and other amino acids.

    PubMed

    Badawy, Abdulla A-B

    2012-01-01

    Plasma tryptophan (Trp) and other amino acids (AA) can be determined rapidly by gas (GC) or liquid (LC) chromatography using the Phenomenex EZ:Faast(™) family of kits. Three kits are available: (1) GC-FID or -NPD, (2) GC-MS, (3) LC-MS. The two GC kits can determine 32 AA, whereas the LC-MS can determine five additional AA. All three kits, however, share the same experimental procedure up to and including the preparation of derivatised AA. The method is based on solid-phase extraction (SPE), thus saving time on prior removal of plasma or other proteins and interfering substances, and can be applied to other body fluids and experimental media and to supernatants of extracts of solid material. Briefly, SPE is performed using a proprietary cation-exchange mechanism. The acid solution of the internal standard ensures that the free amino acids are in an anionic form suitable for cationic binding. The alkaline nature of the elution medium ensures that the AA cations are released prior to derivatisation. The latter involves production of chloroformate derivatives of both the amino and carboxylic acid groups. With experience, six plasma samples can be so processed within 12 min. The shortest analytical run is <7 min per sample using the GC-FID/NPD kit. Despite its many steps, the procedure becomes second nature and an enjoyable task. I have now used the GC-FID kit with manual injection to process >1,600 plasma and other samples. Limit of detection of AA is 1 μM or less. The procedure has been validated and optimised for Trp and its main five brain uptake competitors.

  11. Predicting G-protein-coupled receptors families using different physiochemical properties and pseudo amino acid composition.

    PubMed

    Rehman, Zia-Ur; Mirza, Muhammad Tayyeb; Khan, Asifullah; Xhaard, Henri

    2013-01-01

    G-protein-coupled receptors (GPCRs) initiate signaling pathways via trimetric guanine nucleotide-binding proteins. GPCRs are classified based on their ligand-binding properties and molecular phylogenetic analyses. Nonetheless, these later analyses are in most case dependent on multiple sequence alignments, themselves dependent on human intervention and expertise. Alignment-free classifications of GPCR sequences, in addition to being unbiased, present many applications uncovering hidden physicochemical parameters shared among specific groups of receptors, to being used in automated workflows for large-scale molecular modeling applications. Current alignment-free classification methods, however, do not reach a full accuracy. This chapter discusses how GPCRs amino acid sequences can be classified using pseudo amino acid composition and multiscale energy representation of different physiochemical properties of amino acids. A hybrid feature extraction strategy is shown to be suitable to represent GPCRs and to be able to exploit GPCR amino acid sequence discrimination capability in spatial as well as transform domain. Classification strategies such as support vector machine and probabilistic neural network are then discussed in regards to GPCRs classification. The work of GPCR-Hybrid web predictor is also discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Incorporation of alpha-Ketoglutaric Acid as a Fixed Bed Scrubber Media for the Neutralization of Hydrazine Family Hypergolic Fuels

    NASA Technical Reports Server (NTRS)

    DeVor, R. W.; Santiago-Maldonado, E.; Parkerson, J. K.

    2010-01-01

    A candidate scrubber media, alpha-ketoglutaric acid (aKGA) adsorbed onto a silica-based substrate was examined as a potential alternative to the hydrazine-family hypergolic fuel neutralization techniques currently utilized at NASA/Kennedy Space Center (KSC). Helvenson et. al. has indicated that aKGA will react with hydrazines to produce non-hazardous, possibly biodegradable products. Furthermore, the authors have previously tested and demonstrated the use of aKGA aqueous solutions as a replacement neutralizing agent for citric acid, which is currently used as a scrubbing agent in liquid scrubbers at KSC. Specific properties examined include reaction efficiency, the loading capacity of aKGA onto various silica substrates, and the comparison of aKGA media performance to that of the citric acid vapor scrubber systems at KSC and a commercial vapor scrubber media. Preliminary investigations showed hydrophobic aerogel particles to be an ideal substrate for the deposition of the aKGA. Current studies have shown that the laboratory produced aKGA-Aerogel absorbent media are more efficient and cost effective than a commercially available fixed bed scrubber media, although much less cost effective than liquid-based citric acid scrubbers (although possibly safer and less labor intensive). A comparison of all three alternative scrubber technologies (liquid aKGA, solid-phase aKGA, and commercially available sorbent materials) is given considering both hypergolic neutralization capabilities and relative costs (as compared to the current citric acid scrubbing technology in use at NASA/KSC).

  13. Concentrations of the urinary pyrethroid metabolite 3-phenoxybenzoic acid in farm worker families in the MICASA study

    SciTech Connect

    Trunnelle, Kelly J.; Bennett, Deborah H.; Ahn, Ki Chang; Schenker, Marc B.; Tancredi, Daniel J.; Gee, Shirley J.; Stoecklin-Marois, Maria T.; Hammock, Bruce D.

    2014-05-01

    Indoor pesticide exposure is a growing concern, particularly from pyrethroids, a commonly used class of pesticides. Pyrethroid concentrations may be especially high in homes of immigrant farm worker families who often live in close proximity to agricultural fields, and are faced with poor housing conditions, causing higher pest infestation and more pesticide use. We investigate exposure of farm worker families to pyrethroids in a study of mothers and children living in Mendota, CA within the population-based Mexican Immigration to California: Agricultural Safety and Acculturation (MICASA) Study. We present pyrethroid exposure based on an ELISA analysis of urinary metabolite 3-phenoxybenzoic acid (3PBA) levels among 105 women and 103 children. The median urinary 3PBA levels (children=2.56 ug/g creatinine, mothers=1.46 ug/g creatinine) were higher than those reported in population based studies for the United States general population, but similar to or lower than studies with known high levels of pyrethroid exposure. A positive association was evident between poor housing conditions and the urinary metabolite levels, showing that poor housing conditions are a contributing factor to the higher levels of 3PBA seen in the urine of these farm worker families. Further research is warranted to fully investigate sources of exposure. - Highlights: • We investigate exposure of farm worker families to pyrethroids. • We present pyrethroid exposure based on an ELISA analysis of urinary 3PBA levels. • 3PBA levels were higher than those reported for the U.S. general population. • Poor housing conditions may be associated with pyrethroid exposure.

  14. An intervention study to increase knowledge and use of folic acid among relatives in neural tube defect-affected families in Washington, D.C.

    PubMed

    Byrne, Julianne; Carolan, Susan; Arcement, Rashad; Kozlowski, Matthew; Taller, Inna; Ried, Stephanie; Keating, Robert

    2005-06-01

    Little is known about the level of knowledge and use of folic acid among near relatives in U.S. families of a child with spina bifida. We hypothesized that relatives would be more knowledgeable than the general population and more likely to take folic acid. Further, we hypothesized that relatives would be more motivated by an intervention to increase their use of folic acid. We conducted an intervention study among females in families attending a hospital spina bifida clinic in Washington, DC. The 231 subjects consisted of the affected individuals, mothers, sisters, and aunts. The average age was 34 years. At baseline, most (87.4%) reported that they had heard of folic acid; 37.6% were currently taking multivitamins with folic acid and 6.9% were taking folic acid tablets. The intervention significantly increased both knowledge (to 99%) and intake of folic acid from 41.9 to 48.5%. Folic acid intake increased significantly among African-American women and women with less education, women who were older, married, with children, and nonsmokers. This intervention was successful in increasing folic acid intake among female relatives in spina bifida-affected families. By the end of the study, almost all women had heard of folic acid and folic acid use had increased by 16%. Among these women at higher than expected risk for having an affected child, this rate of intake, while more than the general population, still falls short of optimum. Fortification of food with folic acid may be the only way to ensure increased folic acid intake. (c) 2005 Wiley-Liss, Inc.

  15. Elevated levels of perfluoroalkyl acids in family members of occupationally exposed workers: the importance of dust transfer

    NASA Astrophysics Data System (ADS)

    Fu, Jianjie; Gao, Yan; Wang, Thanh; Liang, Yong; Zhang, Aiqian; Wang, Yawei; Jiang, Guibin

    2015-03-01

    The exposure pathways of perfluoroalkyl acids (PFAAs) to humans are still not clear because of the complex living environment, and few studies have simultaneously investigated the bioaccumulative behaviour of different PFAAs in humans. In this study, serum, dust, duplicate diet, and other matrices were collected around a manufacturing plant in China, and homologous series of PFAAs were analysed. PFAA levels in dust and serum of local residents in this area were considerably higher than those in non-polluted area. Although dietary intake was the major exposure pathway in the present study, dust ingestion played an important role in this case. Serum PFAAs in local residents was significantly correlated with dust PFAAs levels in their living or working microenvironment. Serum PFAAs and dust PFAAs were significantly higher in family members of occupational workers (FM) than in ordinary residents (OR) (p < 0.01). After a careful analysis of the PFAAs exposure pathway, a potential pathway in addition to direct dust ingestion was suggested: PFAAs might transferred from occupational worker's clothes to dinners via cooking processes. The bioaccumulative potential of PFHxS and PFOS were higher than other PFAAs, which suggested a substantial difference between the bioaccumulative ability of perfluorinated sulfonic acids and perfluorinated carboxylic acids.

  16. New mono- and dimeric members of the secalonic acid family: blennolides A-G isolated from the fungus Blennoria sp.

    PubMed

    Zhang, Wen; Krohn, Karsten; Flörke, Ulrich; Pescitelli, Gennaro; Di Bari, Lorenzo; Antus, Sándor; Kurtán, Tibor; Rheinheimer, Joachim; Draeger, Siegfried; Schulz, Barbara

    2008-01-01

    Blennolides A-G (2-8), seven unusual chromanones, were isolated together with secalonic acid B (1) from Blennoria sp., an endophytic fungus from Carpobrotus edulis. This is the first reported isolation of the blennolides 2 and 3 (hemisecalonic acids B and E), the existence of which as the monomeric units of the dimeric secalonic acids had long been postulated. A compound of the proposed structure 4 (beta-diversonolic ester) will need to be revised, as its reported data do not fit those of the established structure of blennolide C (4). Other monomers, the blennolides D-F (5-7) seem to be derived from blennolides A (2) and B (3) by rearrangement of the hydroaromatic ring. The heterodimer 8, composed of the monomeric blennolide A (2) and the rearranged 11-dehydroxy derivative of blennolide E (6), extends the ergochrome family with an ergoxanthin type of skeleton. The structures of the new compounds were elucidated by detailed spectroscopic analysis and further confirmed by an X-ray diffraction study of a single crystal of 2. The absolute configurations were determined by TDDFT calculations of CD spectra, including the solid-state CD/TDDFT approach. Preliminary studies showed strong antifungal and antibacterial activities of these compounds against Microbotryum violaceum and Bacillus megaterium, respectively. They were also active against the alga Chlorella fusca and the bacterium Escherichia coli.

  17. Elevated levels of perfluoroalkyl acids in family members of occupationally exposed workers: the importance of dust transfer

    PubMed Central

    Fu, Jianjie; Gao, Yan; Wang, Thanh; Liang, Yong; Zhang, Aiqian; Wang, Yawei; Jiang, Guibin

    2015-01-01

    The exposure pathways of perfluoroalkyl acids (PFAAs) to humans are still not clear because of the complex living environment, and few studies have simultaneously investigated the bioaccumulative behaviour of different PFAAs in humans. In this study, serum, dust, duplicate diet, and other matrices were collected around a manufacturing plant in China, and homologous series of PFAAs were analysed. PFAA levels in dust and serum of local residents in this area were considerably higher than those in non-polluted area. Although dietary intake was the major exposure pathway in the present study, dust ingestion played an important role in this case. Serum PFAAs in local residents was significantly correlated with dust PFAAs levels in their living or working microenvironment. Serum PFAAs and dust PFAAs were significantly higher in family members of occupational workers (FM) than in ordinary residents (OR) (p < 0.01). After a careful analysis of the PFAAs exposure pathway, a potential pathway in addition to direct dust ingestion was suggested: PFAAs might transferred from occupational worker's clothes to dinners via cooking processes. The bioaccumulative potential of PFHxS and PFOS were higher than other PFAAs, which suggested a substantial difference between the bioaccumulative ability of perfluorinated sulfonic acids and perfluorinated carboxylic acids. PMID:25791573

  18. Fatty acid profiles of five farmed Brazilian freshwater fish species from different families.

    PubMed

    Rodrigues, Bruna Leal; Canto, Anna Carolina Vilhena da Cruz Silva; Costa, Marion Pereira da; Silva, Flávio Alves da; Mársico, Eliane Teixeira; Conte-Junior, Carlos Adam

    2017-01-01

    The proximate composition and fatty acid (FA) profiles of five Brazilian freshwater fish species, namely Brycon cephalus (BC), Cichla ocellaris (CO), Prochilodus lineatus (PL), Leporinus friderici (LF) and Pseudoplatystoma corruscans (PCO), were investigated. CO and LF exhibited the highest (p < 0.05) moisture content, as well as one of the lowest (p < 0.05) lipid values, whereas BC presented the lowest (p < 0.05) moisture and, alongside PL, the highest (p < 0.05) lipid content. The predominant FAs in the evaluated fish species were palmitic, oleic, linoleic and docosahexaenoic acids. BC and CO presented high n-3 PUFA content, especially DHA, and demonstrated superior nutritional quality indices compared to the other evaluated fish species. Furthermore, a significant relationship was observed among these species, suggesting they possess similar nutritional lipid values. Thus, BC and CO were proven to be an excellent matrix with relevant lipid quality, desirable for human health.

  19. Fatty acid profiles of five farmed Brazilian freshwater fish species from different families

    PubMed Central

    Canto, Anna Carolina Vilhena da Cruz Silva; da Costa, Marion Pereira; da Silva, Flávio Alves; Mársico, Eliane Teixeira; Conte-Junior, Carlos Adam

    2017-01-01

    The proximate composition and fatty acid (FA) profiles of five Brazilian freshwater fish species, namely Brycon cephalus (BC), Cichla ocellaris (CO), Prochilodus lineatus (PL), Leporinus friderici (LF) and Pseudoplatystoma corruscans (PCO), were investigated. CO and LF exhibited the highest (p < 0.05) moisture content, as well as one of the lowest (p < 0.05) lipid values, whereas BC presented the lowest (p < 0.05) moisture and, alongside PL, the highest (p < 0.05) lipid content. The predominant FAs in the evaluated fish species were palmitic, oleic, linoleic and docosahexaenoic acids. BC and CO presented high n-3 PUFA content, especially DHA, and demonstrated superior nutritional quality indices compared to the other evaluated fish species. Furthermore, a significant relationship was observed among these species, suggesting they possess similar nutritional lipid values. Thus, BC and CO were proven to be an excellent matrix with relevant lipid quality, desirable for human health. PMID:28614390

  20. Comparative study of rosmarinic acid content in some plants of Labiatae family.

    PubMed

    Shekarchi, Maryam; Hajimehdipoor, Homa; Saeidnia, Soodabeh; Gohari, Ahmad Reza; Hamedani, Morteza Pirali

    2012-01-01

    Plants of Labiatae are used in traditional medicine and phytotherapy. Rosmarinic acid (RA) is a phenolic compound which is found in many genus of Labiatae and exhibits important biological activities. In this investigation, RA contents of 29 species of Labiatae named Salvia officinalis, Salvia limbata, Salvia virgata, Salvia hypoleuca, Salvia macrosiphon, Salvia choloroleuca, Melissa officinalis, Origanum vulgare, Lavandula angustifolia, Rosmarinus officinalis, Thymus daenensis, Thymus citriodorous, Thymus pubescens, Thymus vulgaris, Zataria multiflora, Mentha piperita, Mentha pulegium, Mentha longifolia, Mentha spicata, Mentha aquatica, Mentha crispa, Perovskia artemisoides, Zhumeria majdae, Satureja hortensis, Satureja khuzistanica, Satureja bachtiarica, Satureja atropatana, Satureja mutica and Satureja macrantha were determined by using high-performance liquid chromatographic method. The results showed that RA content in different species of Labiatae was 0.0-58.5 mg g(-1) of dried plants. The highest amount of RA was found in Mentha species especially M. spicata. M. spicata can be considered as a new source of rosmarinic acid .

  1. Synthesis and spectroscopic studies of iron (III) complex with a quinolone family member (pipemidic acid)

    NASA Astrophysics Data System (ADS)

    Skrzypek, D.; Szymanska, B.; Kovala-Demertzi, Dimitra; Wiecek, Joanna; Talik, E.; Demertzis, Mavroudis A.

    2006-12-01

    The interaction of iron (III) with pipemidic acid, Hpipem, afforded the complex [Fe (pipem) (HO)2 (H2O)]2. The new complex has been characterised by elemental analyses, infra-red, EPR and XPS spectroscopies. The monoanion, pipem, exhibits O, O ligation through the carbonyl and carboxylato oxygen atoms. Six coordinate dimer distorted octahedral configuration has been proposed for [Fe (pipem) (HO)2 (H2O)]2.

  2. Amino acids and peptides activate at least five members of the human bitter taste receptor family.

    PubMed

    Kohl, Susann; Behrens, Maik; Dunkel, Andreas; Hofmann, Thomas; Meyerhof, Wolfgang

    2013-01-09

    Amino acids and peptides represent important flavor molecules eliciting various taste sensations. Here, we present a comprehensive assessment of the interaction of various peptides and all proteinogenic amino acids with the 25 human TAS2Rs expressed in cell lines. L-Phenylalanine and L-tryptophan activate TAS2R1 and TAS2R4, respectively, whereas TAS2R4 and TAS2R39 responded to D-tryptophan. Structure-function analysis uncovered the basis for the lack of stereoselectivity of TAS2R4. The same three TAS2Rs or subsets thereof were also sensitive to various dipeptides containing L-tryptophan, L-phenylalanine, or L-leucine and to Trp-Trp-Trp, whereas Leu-Leu-Leu specifically activated TAS2R4. Trp-Trp-Trp also activated TAS2R46 and TAS2R14. Two key bitter peptides from Gouda cheese, namely, Tyr-Pro-Phe-Pro-Gly-Pro-Ile-His-Asn-Ser and Leu-Val-Tyr-Pro-Phe-Pro-Gly-Pro-Ile-His-Asn, both activated TAS2R1 and TAS2R39. Thus, the data demonstrate that the bitterness of amino acids and peptides is not mediated by specifically tuned TAS2Rs but rather is brought about by an unexpectedly complex pattern of sensitive TAS2Rs.

  3. A New Structural Family of Gas-Sorbing Coordination Polymers Derived from Phenolic Carboxylic Acids.

    PubMed

    White, Keith F; Abrahams, Brendan F; Babarao, Ravichandar; Dharma, A David; Hudson, Timothy A; Maynard-Casely, Helen E; Robson, Richard

    2015-12-07

    The structure of Li(inox)⋅2/3 DMF (inox(-) =the N-oxide of the isonicotinate anion) consists of a 3D framework with solvent-filled, square cross-section channels of approximate dimensions 5.5×5.5 Å. Unfortunately, the Li(inox) framework is unstable upon removal of DMF from the channels. When the structurally related 4-hydroxybenzoic acid (H2 hba) was used in place of Hinox, and Zn(2+) in place of the Li(+) , a structurally similar but more robust network, Zn(hba), was obtained; the isostructural compound, Co(hba), may also be prepared. Longer ligands with phenolate and carboxylate functional groups at opposite ends, such as the dianions of 4-coumaric acid (H2 cma) and 4'-hydroxy-4-biphenylcarboxylic acid (H2 hbpc), in combination with Zn(2+) yield Zn(cma) and Zn(hbpc) frameworks, respectively, with the same PtS topology but with larger channels. The coordination polymers remain intact after desolvation and exhibit microporosity, showing the ability to sorb significant quantities of CO2 , CH4 , and H2 .

  4. Comparative study of rosmarinic acid content in some plants of Labiatae family

    PubMed Central

    Shekarchi, Maryam; Hajimehdipoor, Homa; Saeidnia, Soodabeh; Gohari, Ahmad Reza; Hamedani, Morteza Pirali

    2012-01-01

    Background: Plants of Labiatae are used in traditional medicine and phytotherapy. Rosmarinic acid (RA) is a phenolic compound which is found in many genus of Labiatae and exhibits important biological activities. Materials and Methods: In this investigation, RA contents of 29 species of Labiatae named Salvia officinalis, Salvia limbata, Salvia virgata, Salvia hypoleuca, Salvia macrosiphon, Salvia choloroleuca, Melissa officinalis, Origanum vulgare, Lavandula angustifolia, Rosmarinus officinalis, Thymus daenensis, Thymus citriodorous, Thymus pubescens, Thymus vulgaris, Zataria multiflora, Mentha piperita, Mentha pulegium, Mentha longifolia, Mentha spicata, Mentha aquatica, Mentha crispa, Perovskia artemisoides, Zhumeria majdae, Satureja hortensis, Satureja khuzistanica, Satureja bachtiarica, Satureja atropatana, Satureja mutica and Satureja macrantha were determined by using high-performance liquid chromatographic method. Results: The results showed that RA content in different species of Labiatae was 0.0-58.5 mg g-1 of dried plants. The highest amount of RA was found in Mentha species especially M. spicata. Conclusion: M. spicata can be considered as a new source of rosmarinic acid . PMID:22438661

  5. Structural and mechanistic comparison of the Cyclopropane Mycolic Acid Synthases (CMAS) protein family of Mycobacterium tuberculosis.

    PubMed

    Defelipe, Lucas A; Osman, Federico; Marti, Marcelo A; Turjanski, Adrián G

    2017-08-30

    Tuberculosis (TB) is a chronic disease caused by the bacillus Mycobacterium tuberculosis(Mtb) and remains a leading cause of mortality worldwide. The bacteria has an external wall which protects it from being killed, and the enzymes involved in the biosynthesis of the cell wall components have been proposed as promising targets for future drug development efforts. Cyclopropane Mycolic Acid Synthases (CMAS) constitute a group of ten homologous enzymes which belong to the mycolic acid biosynthesis pathway. These enzymes have S-adenosyl-l-methionine (SAM) dependent methyltransferase activity with a peculiarity, each one of them has strong substrate selectivity and reaction specificity, being able to produce among other things cyclopropanes or methyl-alcohol groups from the lipid olefin group. How each CMAS processes its substrate and how the specificity and selectivity are encoded in the protein sequence and structure, is still unclear. In this work, by using a combination of modeling tools, including comparative modeling, docking, all-atom MD and QM/MM methodologies we studied in detail the reaction mechanism of cmaA2, mmaA4, and mmaA1 CMAS and described the molecular determinants that lead to different products. We have modeled the protein-substrate complex structure and determined the free energy pathway for the reaction. The combination of modeling tools at different levels of complexity allows having a complete picture of the CMAS structure-activity relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Two Amino Acid Residues Confer Different Binding Affinities of Abelson Family Kinase Src Homology 2 Domains for Phosphorylated Cortactin*

    PubMed Central

    Gifford, Stacey M.; Liu, Weizhi; Mader, Christopher C.; Halo, Tiffany L.; Machida, Kazuya; Boggon, Titus J.; Koleske, Anthony J.

    2014-01-01

    The closely related Abl family kinases, Arg and Abl, play important non-redundant roles in the regulation of cell morphogenesis and motility. Despite similar N-terminal sequences, Arg and Abl interact with different substrates and binding partners with varying affinities. This selectivity may be due to slight differences in amino acid sequence leading to differential interactions with target proteins. We report that the Arg Src homology (SH) 2 domain binds two specific phosphotyrosines on cortactin, a known Abl/Arg substrate, with over 10-fold higher affinity than the Abl SH2 domain. We show that this significant affinity difference is due to the substitution of arginine 161 and serine 187 in Abl to leucine 207 and threonine 233 in Arg, respectively. We constructed Abl SH2 domains with R161L and S187T mutations alone and in combination and find that these substitutions are sufficient to convert the low affinity Abl SH2 domain to a higher affinity “Arg-like” SH2 domain in binding to a phospho-cortactin peptide. We crystallized the Arg SH2 domain for structural comparison to existing crystal structures of the Abl SH2 domain. We show that these two residues are important determinants of Arg and Abl SH2 domain binding specificity. Finally, we expressed Arg containing an “Abl-like” low affinity mutant Arg SH2 domain (L207R/T233S) and find that this mutant, although properly localized to the cell periphery, does not support wild type levels of cell edge protrusion. Together, these observations indicate that these two amino acid positions confer different binding affinities and cellular functions on the distinct Abl family kinases. PMID:24891505

  7. Phlebotomy Treatment for Elimination of Perfluoroalkyl Acids in a Highly Exposed Family: A Retrospective Case-Series

    PubMed Central

    Genuis, Stephen J.; Liu, Yanna; Genuis, Quentin I. T.; Martin, Jonathan W.

    2014-01-01

    Background Perfluoroalkyl acids (PFAAs) are a family of commonly used synthetic chemicals that have become widespread environmental contaminants. In human serum, perfluorohexane sulfonate (PFHxS), perflurooctane sulfonate (PFOS), and perfluorooctanoate (PFOA) are most frequently detected, in part owing to their long elimination half-lives of between 3.8 yrs (PFOA) and 8.5 yrs (PFHxS). These PFAAs also cross the placenta and have been associated with developmental toxicity, and some are considered likely human carcinogens. Interventions to eliminate PFAAs in highly contaminated individuals would reduce future health risks, but minimal research has been conducted on methods to facilitate accelerated human clearance of these persistent substances. Methods Six patients with elevated serum concentrations from a single family were treated by intermittent phlebotomy over a 4–5 year period at intervals similar to, or less frequent than what is done for routine blood donation at Canadian Blood Services. The apparent elimination half-life (HLapp) for PFHxS, PFOS, and PFOA in this treated population was calculated in each patient and compared to the intrinsic elimination half-lives (HLin) from a literature reference population of untreated fluorochemical manufacturing plant retirees (n = 26, age >55 yrs). Results For all three PFAAs monitored during phlebotomy, HLapp in each of the family members (except the mother, who had a low rate of venesection) was significantly shorter than the geometric mean HL measured in the reference population, and in some cases were even shorter compared to the fastest eliminator in the reference population. Conclusion This study suggests significantly accelerated PFAA clearance with regular phlebotomy treatment, but the small sample size and the lack of controls in this clinical intervention precludes drawing firm conclusions. Given the minimal risks of intermittent phlebotomy, this may be an effective and safe clinical intervention to

  8. Comparison of the gene encoding, and the predicted amino acid composition of, platelet membrane receptor subunit glycoprotein Ibα in members of the family Felidae.

    PubMed

    Boudreaux, Mary K; Christopherson, Pete W; Blair, Cori

    2016-03-01

    There is minimal information regarding platelet receptors in the family Felidae. Comparative studies assist with identifying amino acids critical for protein structure and function. The purpose of the study was to compare the gene encoding, and the predicted amino acid composition of, platelet membrane receptor subunit GPIbα in Felidae family members. Genomic DNA samples isolated from whole blood of 13 domestic cats and 50 big cats representing 8 different species were subjected to PCR using primers designed to flank the coding region of GPIbα in overlapping fashion. PCR products were separated via electrophoresis on agarose gels, and extracted products were submitted for sequencing. DNA sequences were used to predict the length and amino acid composition of the protein. Varying protein lengths were predicted in Felidae family members which were primarily due to polymorphisms in the variable number of tandem repeats region encoding the macroglycopeptide region of GPIbα. Other areas of the gene and predicted amino acid compositions were fairly conserved when compared to human sequences and between Felidae family members. Various polymorphisms within GPIbα, including length variants encoding the macroglycopeptide region, were identified in members of the family Felidae. More studies are needed to determine if a correlation exists between various polymorphisms and predisposition for hemorrhage or thrombosis as suggested in people. © 2016 American Society for Veterinary Clinical Pathology.

  9. Conserved amino acid motifs from the novel Piv/MooV family of transposases and site-specific recombinases are required for catalysis of DNA inversion by Piv.

    PubMed

    Tobiason, D M; Buchner, J M; Thiel, W H; Gernert, K M; Karls, A C

    2001-02-01

    Piv, a site-specific invertase from Moraxella lacunata, exhibits amino acid homology with the transposases of the IS110/IS492 family of insertion elements. The functions of conserved amino acid motifs that define this novel family of both transposases and site-specific recombinases (Piv/MooV family) were examined by mutagenesis of fully conserved amino acids within each motif in Piv. All Piv mutants altered in conserved residues were defective for in vivo inversion of the M. lacunata invertible DNA segment, but competent for in vivo binding to Piv DNA recognition sequences. Although the primary amino acid sequences of the Piv/MooV recombinases do not contain a conserved DDE motif, which defines the retroviral integrase/transposase (IN/Tnps) family, the predicted secondary structural elements of Piv align well with those of the IN/Tnps for which crystal structures have been determined. Molecular modelling of Piv based on these alignments predicts that E59, conserved as either E or D in the Piv/MooV family, forms a catalytic pocket with the conserved D9 and D101 residues. Analysis of Piv E59G confirms a role for E59 in catalysis of inversion. These results suggest that Piv and the related IS110/IS492 transposases mediate DNA recombination by a common mechanism involving a catalytic DED or DDD motif.

  10. Genome-Wide Identification, Classification, and Expression Analysis of Amino Acid Transporter Gene Family in Glycine Max.

    PubMed

    Cheng, Lin; Yuan, Hong-Yu; Ren, Ren; Zhao, Shi-Qi; Han, Ya-Peng; Zhou, Qi-Ying; Ke, Dan-Xia; Wang, Ying-Xiang; Wang, Lei

    2016-01-01

    Amino acid transporters (AATs) play important roles in transporting amino acid across cellular membranes and are essential for plant growth and development. To date, the AAT gene family in soybean (Glycine max L.) has not been characterized. In this study, we identified 189 AAT genes from the entire soybean genomic sequence, and classified them into 12 distinct subfamilies based upon their sequence composition and phylogenetic positions. To further investigate the functions of these genes, we analyzed the chromosome distributions, gene structures, duplication patterns, phylogenetic tree, tissue expression patterns of the 189 AAT genes in soybean. We found that a large number of AAT genes in soybean were expanded via gene duplication, 46 and 36 GmAAT genes were WGD/segmental and tandemly duplicated, respectively. Further comprehensive analyses of the expression profiles of GmAAT genes in various stages of vegetative and reproductive development showed that soybean AAT genes exhibited preferential or distinct expression patterns among different tissues. Overall, our study provides a framework for further analysis of the biological functions of AAT genes in either soybean or other crops.

  11. The role of interleukin family in perfluorooctanoic acid (PFOA)-induced immunotoxicity.

    PubMed

    Zhang, Hangjun; Fang, Wendi; Wang, Dandan; Gao, Nana; Ding, Ying; Chen, Chao

    2014-09-15

    Perfluorooctanoic acid (PFOA), a prominent perfluorinated compound (PFC), has been widely detected in natural water bodies worldwide. In this study, zebrafish (Danio rerio) was exposed to nominal concentrations of PFOA (0.05, 0.1, 0.5, and 1 mg/L) for 21 d. After exposure, each fish was decapitated, and the spleen was removed to detect the expression patterns of P65 transcription factor, myeloid differentiation 88, relative interleukins (ILs), and antibody genes. PFOA can stimulate pro-inflammatory cytokine at a low exposure concentration (0.05 mg/L) and can inhibit pro-inflammatory cytokine at higher exposure concentrations (≥ 0.1mg/L). The results of linear correlation analysis indicate that Myd88/NF-κB pathway is one of the important pathways to mediate inflammatory cytokine (IL-1β and IL-21) in zebrafish spleen. Additionally, the relative mRNA expression level of toll-like receptor 2 (TLR2) at 1mg/L PFOA group was decreased to 56% of its corresponding level in the control. IL secretion disorder is possibly closely related to PFOA-induced TLR2 damage in zebrafish spleen. Furthermore, data show that the trends of PFOA-induced IL secretion have a relationship with Ig-secreting trend. This study demonstrates that PFOA can affect IL expression level through NF-κB, and ILs have an important function in the mediation of Ig secretion. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Dictyostelium discoideum gene family contains a long internal amino acid repeat.

    PubMed

    Ennis, H L; Giorda, R; Ohmachi, T; Shaw, D R; Blume, J E

    1991-01-01

    Two different cDNA clones denoted pTO270-6 and pTO270-11 represent two mRNAs that are developmentally regulated during spore germination in Dictyostelium discoideum. The respective mRNAs are found only during early germination and are not present in other stages of growth or multicellular development. Four different genomic clones that hybridize to sequences that are common to both of the 270 cDNA clones were isolated from Dictyostelium libraries and sequenced. Two are the genes for the two cDNAs, and the other two represent genes that do not seem to be transcribed. All four genomic sequences possess a very unusual internal feature in the deduced protein sequences composed of a monotonous repeat of the tetrapeptide threonine-glutamic acid-threonine-proline. The other portions of the proteins have no homology among themselves. The deduced protein corresponding to the 270-6 gene is very similar to avocado (Persea americana) cellulase. Since cellulose in the spore wall has to be digested during spore germination this suggests that this protein may function as an endo-(1,4)-beta-D-glucanase during germination.

  13. Crystal Chemistry of the Potassium and Rubidium Uranyl Borate Families Derived from Boric Acid Fluxes

    SciTech Connect

    Wang, Shuao; Alekseev, Evgeny V.; Stritzinger, Jared T.; Depmeier, Wulf; Albrecht-Schmitt, Thomas E.

    2010-07-19

    The reaction of uranyl nitrate with a large excess of molten boric acid in the presence of potassium or rubidium nitrate results in the formation of three new potassium uranyl borates, K{sub 2}[(UO{sub 2}){sub 2}B{sub 12}O{sub 19}(OH){sub 4}]·0.3H{sub 2}O (KUBO-1), K[(UO{sub 2}){sub 2}B{sub 10}O{sub 15}(OH){sub 5}] (KUBO-2), and K[(UO{sub 2}){sub 2}B{sub 10}O{sub 16}(OH){sub 3}]·0.7H{sub 2}O (KUBO-3) and two new rubidium uranyl borates Rb{sub 2}[(UO{sub 2}){sub 2}B{sub 13}O{sub 20}(OH){sub 5}] (RbUBO-1) and Rb[(UO{sub 2}){sub 2}B{sub 10}O{sub 16}(OH){sub 3}]·0.7H{sub 2}O (RbUBO-2). The latter is isotypic with KUBO-3. These compounds share a common structural motif consisting of a linear uranyl, UO{sub 2}{sup 2+}, cation surrounded by BO{sub 3} triangles and BO{sub 4} tetrahedra to create an UO{sub 8} hexagonal bipyramidal environment around uranium. The borate anions bridge between uranyl units to create sheets. Additional BO{sub 3} triangles extend from the polyborate layers and are directed approximately perpendicular to the sheets. All of these compounds adopt layered structures. With the exception of KUBO-1, the structures are all centrosymmetric. All of these compounds fluoresce when irradiated with long-wavelength UV light. The fluorescence spectrum yields well-defined vibronically coupled charge-transfer features.

  14. The identification of the acid-base catalyst of alpha-arabinofuranosidase from Geobacillus stearothermophilus T-6, a family 51 glycoside hydrolase.

    PubMed

    Shallom, Dalia; Belakhov, Valery; Solomon, Dmitry; Gilead-Gropper, Sara; Baasov, Timor; Shoham, Gil; Shoham, Yuval

    2002-03-13

    The alpha-L-arabinofuranosidase from Geobacillus stearothermophilus T-6 (AbfA T-6) belongs to the retaining family 51 glycoside hydrolases. The conserved Glu175 was proposed to be the acid-base catalytic residue. AbfA T-6 exhibits residual activity towards aryl beta-D-xylopyranosides. This phenomenon was used to examine the catalytic properties of the putative acid-base mutant E175A. Data from kinetic experiments, pH profiles, azide rescue, and the identification of the xylopyranosyl azide product provide firm support to the assignment of Glu175 as the acid-base catalyst of AbfA T-6.

  15. Dietary interventions (plant sterols, stanols, omega-3 fatty acids, soy protein and dietary fibers) for familial hypercholesterolaemia.

    PubMed

    Malhotra, Anita; Shafiq, Nusrat; Arora, Anjuman; Singh, Meenu; Kumar, Rajendra; Malhotra, Samir

    2014-06-10

    A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolaemia (FH). However, a consensus has yet to be reached on the most appropriate dietary treatment. Plant sterols are commonly used in FH although patients may know them by other names like phytosterols or stanols. To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia. Further, to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids, soya proteins, plant sterols or plant stanols. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register, which is compiled from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated with each new issue of The Cochrane Library), quarterly searches of MEDLINE and the prospective handsearching of one journal - Journal of Inherited Metabolic Disease. Most recent search of the Group's Inborn Errors of Metabolism Trials Register: 22 August 2013. We also searched PubMed to 05 February 2012. Randomised controlled trials, both published and unpublished, where a cholesterol-lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention were included. Two authors independently assessed the trial eligibility and risk of bias and one extracted the data, with independent verification of data extraction by a colleague. In the 2014 update of the review, 15 trials have been included, with a total of 453 participants across seven comparison groups. The included trials had either a low or unclear risk of bias for most of the parameters used for risk

  16. [Identification of new conserved and variable regions in the 16S rRNA gene of acetic acid bacteria and acetobacteraceae family].

    PubMed

    Chakravorty, S; Sarkar, S; Gachhui, R

    2015-01-01

    The Acetobacteraceae family of the class Alpha Proteobacteria is comprised of high sugar and acid tolerant bacteria. The Acetic Acid Bacteria are the economically most significant group of this family because of its association with food products like vinegar, wine etc. Acetobacteraceae are often hard to culture in laboratory conditions and they also maintain very low abundances in their natural habitats. Thus identification of the organisms in such environments is greatly dependent on modern tools of molecular biology which require a thorough knowledge of specific conserved gene sequences that may act as primers and or probes. Moreover unconserved domains in genes also become markers for differentiating closely related genera. In bacteria, the 16S rRNA gene is an ideal candidate for such conserved and variable domains. In order to study the conserved and variable domains of the 16S rRNA gene of Acetic Acid Bacteria and the Acetobacteraceae family, sequences from publicly available databases were aligned and compared. Near complete sequences of the gene were also obtained from Kombucha tea biofilm, a known Acetobacteraceae family habitat, in order to corroborate the domains obtained from the alignment studies. The study indicated that the degree of conservation in the gene is significantly higher among the Acetic Acid Bacteria than the whole Acetobacteraceae family. Moreover it was also observed that the previously described hypervariable regions V1, V3, V5, V6 and V7 were more or less conserved in the family and the spans of the variable regions are quite distinct as well.

  17. Genome-Wide Survey and Characterization of Fatty Acid Desaturase Gene Family in Brassica napus and Its Parental Species.

    PubMed

    Xue, Yufei; Chen, Baojun; Wang, Rui; Win, Aung Naing; Li, Jiana; Chai, Yourong

    2017-08-10

    Rapeseed (Brassica napus) is an important oilseed crop worldwide, and fatty acid (FA) compositions determine the nutritional and economic value of its seed oil. Fatty acid desaturases (FADs) play a pivotal role in regulating FA compositions, but to date, no comprehensive genome-wide analysis of FAD gene family in rapeseed and its parent species has been reported. In this study, using homology searches, 84, 45, and 44 FAD genes were identified in rapeseed, Brassica rapa, and Brassica oleracea genomes, respectively. These FAD genes were unevenly located in 17 chromosomes and 2 scaffolds of rapeseed, 9 chromosomes and 1 scaffold of B. rapa, and all the chromosomes of B. oleracea. Phylogenetic analysis showed that the soluble and membrane-bound FADs in the three Brassica species were divided into four and six subfamilies, respectively. Generally, the soluble FADs contained two conserved histidine boxes, while three highly conserved histidine boxes were harbored in membrane-bound FADs. Exon-intron structure, intron phase, and motif composition and position were highly conserved in each FAD subfamily. Putative subcellular locations of FAD proteins in three Brassica species were consistent with those of corresponding known FADs. In total, 25 of simple sequence repeat (SSR) loci were found in FAD genes of the three Brassica species. Transcripts of selected FAD genes in the three species were examined in various organs/tissues or stress treatments from NCBI expressed sequence tag (EST) database. This study provides a critical molecular basis for quality improvement of rapeseed oil and facilitates our understanding of key roles of FAD genes in plant growth and development and stress response.

  18. Pentalenic acid is a shunt metabolite in the biosynthesis of the pentalenolactone family of metabolites: Hydroxylation of 1-deoxypentalenic acid mediated by CYP105D7 (SAV_7469) of Streptomyces avermitilis

    PubMed Central

    Takamatsu, Satoshi; Xu, Lian-Hua; Fushinobu, Shinya; Shoun, Hirofumi; Komatsu, Mamoru; Cane, David E.; Ikeda, Haruo

    2010-01-01

    Pentalenic acid (1) has been isolated from many Streptomyces species as a co-metabolite of with the sesquiterpenoid antibiotic pentalenolactone and related natural products. We have previously reported the identification of a 13.4-kb gene cluster in the genome of Streptomyces avermitilis implicated in the biosynthesis of the pentalenolactone family of metabolites consisting of 13 ORFs. Detailed molecular genetic and biochemical studies have revealed that at least 7 genes are involved in the biosynthesis of the newly discovered metabolites, neopentalenoketolactone, but no gene specifically dedicated to the formation of pentalenic acid (1) was evident in the same gene cluster. The wild type strain of S. avermitilis as well as its derivatives mainly produce pentalenic acid (1) together with neopentalenoketolactone (9). Disruption of the sav7469 gene encoding a cytochrome P450 (CYP105D7), members of which class are associated with the hydroxylation of many structurally different compounds, abolished production of pentalenic acid (1). The sav7469-deletion mutant derived from SUKA11 carrying pKU462::ptl-clusterΔptlH accumulated 1-deoxypentalenic acid (5), but not pentalenic acid (1). Reintroduction of an extra-copy of the sav7469 gene to SUKA11 Δsav7469 carrying pKU462::ptl-clusterΔptlH restored the production of pentalenic acid (1). Recombinant CYP105D7 prepared from Escherichia coli catalyzed the oxidative conversion of 1-deoxypentalenic acid (5) to pentalenic acid (1) in the presence of the electron-transport partners, ferredoxin and ferredoxin reductase, both in vivo and in vitro. These results unambiguously demonstrate that CYP105D7 is responsible for the conversion of 1-deoxypentalenic acid (5) to pentalenic acid (1), a shunt product in the biosynthesis of the pentalenolactone family of metabolites. PMID:21081950

  19. Phosphatidic acid phospholipase A1 mediates ER–Golgi transit of a family of G protein–coupled receptors

    PubMed Central

    Kunduri, Govind; Yuan, Changqing; Parthibane, Velayoudame; Nyswaner, Katherine M.; Kanwar, Ritu; Nagashima, Kunio; Britt, Steven G.; Mehta, Nickita; Kotu, Varshika; Porterfield, Mindy; Tiemeyer, Michael; Dolph, Patrick J.; Acharya, Usha

    2014-01-01

    The coat protein II (COPII)–coated vesicular system transports newly synthesized secretory and membrane proteins from the endoplasmic reticulum (ER) to the Golgi complex. Recruitment of cargo into COPII vesicles requires an interaction of COPII proteins either with the cargo molecules directly or with cargo receptors for anterograde trafficking. We show that cytosolic phosphatidic acid phospholipase A1 (PAPLA1) interacts with COPII protein family members and is required for the transport of Rh1 (rhodopsin 1), an N-glycosylated G protein–coupled receptor (GPCR), from the ER to the Golgi complex. In papla1 mutants, in the absence of transport to the Golgi, Rh1 is aberrantly glycosylated and is mislocalized. These defects lead to decreased levels of the protein and decreased sensitivity of the photoreceptors to light. Several GPCRs, including other rhodopsins and Bride of sevenless, are similarly affected. Our findings show that a cytosolic protein is necessary for transit of selective transmembrane receptor cargo by the COPII coat for anterograde trafficking. PMID:25002678

  20. Aspartic acid at position 57 of the HLA-DQ beta chain protects against type I diabetes: a family study.

    PubMed Central

    Morel, P A; Dorman, J S; Todd, J A; McDevitt, H O; Trucco, M

    1988-01-01

    One hundred seventy-two members from 27 randomly selected multiple case Caucasian families of patients with insulin-dependent diabetes mellitus (IDDM) were studied at the DNA level to ascertain the reliability of codon 57 of the HLA-DQ beta-chain gene as a disease protection/susceptibility marker. The analysis was carried out by polymerase chain reaction amplification of DNA encoding the first domain of the DQ beta chain and by dot blot analysis of the amplified material with allele-specific oligonucleotide probes. One hundred twenty-three randomly selected healthy Caucasian donors were also tested. The results demonstrated that haplotypes carrying an aspartic acid in position 57 (Asp-57) of their DQ beta chain were significantly increased in frequency among nondiabetic haplotypes (23/38), while non-Asp-57 haplotypes were significantly increased in frequency among diabetic haplotypes (65/69). Ninety-six percent of the diabetic probands in our study were homozygous non-Asp/non-Asp as compared to 19.5% of healthy unrelated controls. This conferred a relative risk of 107 (chi 2 = 54.97; P = 0.00003) for non-Asp-57 homozygous individuals. Even though the inheritance and genetic features of IDDM are complex and are not necessarily fully explained by DQ beta chain polymorphism, this approach is much more sensitive than HLA serolog in assessing risk for IDDM. PMID:3186714

  1. Heterologous expression of glycoside hydrolase family 2 and 42 β-galactosidases of lactic acid bacteria in Lactococcus lactis.

    PubMed

    Schwab, Clarissa; Sørensen, Kim I; Gänzle, Michael G

    2010-10-01

    This study characterized a glycoside hydrolase family 42 (GH42) β-galactosidase of Lactobacillus acidophilus (LacA) and compared lactose hydrolysis, hydrolysis of oNPG, pNPG and pNPG-analogues and galactooligosaccharides (GOSs) formation to GH2 β-galactosidases of Streptococcus thermophilus (LacZ type), Lactobacillus plantarum and Leuconostoc mesenteroides subsp. cremoris (both LacLM type). Beta-galactosidases were heterologously expressed in Lactococcus lactis using a p170 derived promoter; experiments were performed with L. lactis crude cell extract (CCE). The novel GH42 β-galactosidase of Lb. acidophilus had lower activity on lactose, oNPG and pNPG but higher relative activity on pNP analogues compared to GH2 β-galactosidases, and did not transgalactosylate at high lactose concentrations. Temperature and pH optima for lactose hydrolysis varied between GH2 β-galactosidases. oNPG and pNPG were the preferred substrates for hydrolysis; in comparison, activity on pNPG-analogues was less than 1.5%. GH2 β-galactosidases formed structurally similar GOS with varying preferences. The diversity of lactic acid bacteria β-galactosidase activity in L. lactis CCE can be exploited in future nutritional or therapeutic applications. Copyright © 2010 Elsevier GmbH. All rights reserved.

  2. A Family of Negative Regulators Targets the Committed Step of de Novo Fatty Acid Biosynthesis[OPEN

    PubMed Central

    Salie, Matthew J.; Zhang, Ning; Xu, Dong; Thelen, Jay J.

    2016-01-01

    Acetyl-CoA carboxylase (ACCase) catalyzes the committed step of de novo fatty acid biosynthesis. In prokaryotes, green algae, and most plants, this enzyme is a heteromeric complex requiring four different subunits for activity. The plant complex is recalcitrant to conventional purification schemes and hence the structure and composition of the full assembly have been unclear. In vivo coimmunoprecipitation using subunit-specific antibodies identified a novel family of proteins in Arabidopsis thaliana annotated as biotin/lipoyl attachment domain containing (BADC) proteins. Results from yeast two-hybrid and coexpression in Escherichia coli confirmed that all three BADC isoforms interact with the two biotin carboxyl carrier protein (BCCP) isoforms of Arabidopsis ACCase. These proteins resemble BCCP subunits but are not biotinylated due to a mutated biotinylation motif. We demonstrate that BADC proteins significantly inhibit ACCase activity in both E. coli and Arabidopsis. Targeted gene silencing of BADC isoform 1 in Arabidopsis significantly increased seed oil content when normalized to either mass or individual seed. We conclude the BADC proteins are ancestral BCCPs that gained a new function as negative regulators of ACCase after initial loss of the biotinylation motif. A functional model is proposed. PMID:27559025

  3. Serum Uric Acid Is Associated with Carotid Plaques: The National Heart, Lung, and Blood Institute Family Heart Study

    PubMed Central

    NEOGI, TUHINA; ELLISON, R. CURTIS; HUNT, STEVEN; TERKELTAUB, ROBERT; FELSON, DAVID T.; ZHANG, YUQING

    2009-01-01

    Objective To examine the association of serum uric acid (SUA) with a marker of preclinical cardiovascular disease (CVD), carotid atherosclerotic plaques (PLQ), where early evidence of risk may be evident, focusing on individuals without CV risk factors. Methods The National Heart, Lung, and Blood Institute Family Heart Study is a multicenter study designed to assess risk factors for heart disease. PLQ were assessed with carotid ultrasound. We conducted sex-specific logistic regression to assess the association of SUA with presence of PLQ, including analyses among persons without risk factors related to both CVD and hyperuricemia. Results In total, 4866 participants had both SUA and carotid ultrasound assessed (54% women, mean age 52 yrs, mean body mass index 27.6). The association of SUA with PLQ increased with increasing SUA levels, demonstrating a dose-response relation for men [OR 1.0, 1.29, 1.61, 1.75, for SUA categories < 5 (reference), 5 to < 6, 6 to < 6.8, ≥ 6.8 mg/dl, respectively; p = 0.002]. Similar associations were found in men without CV risk factors. We found no relation of SUA with PLQ in women. Conclusion In this large study, SUA was associated with carotid atherosclerotic plaques in men. Results were similar in the absence of CV risk factors. These results suggest that SUA may have a pathophysiologic role in atherosclerosis in men. (J Rheumatol First Release Nov 15 2008; doi:10.3899/jrheum.080646) PMID:19012359

  4. Eicosapentaenoic acid in serum phospholipids relates to a less atherogenic lipoprotein profile in subjects with familial hypercholesterolemia.

    PubMed

    Sala-Vila, Aleix; Cofán, Montserrat; Mateo-Gallego, Rocío; Cenarro, Ana; Civeira, Fernando; Ros, Emilio

    2013-09-01

    Familial hypercholesterolemia (FH) carries an increased vascular risk due to lifelong elevation of the number of circulating low-density lipoprotein (LDL) particles, but also to alterations in triglyceride and high-density lipoprotein (HDL) metabolism. Supplementation with eicosapentaenoic (EPA) or docosahexaenoic (DHA) acids reduced LDL particle number and/or increased LDL size in different populations, but studies in FH are scarce. We investigated cross-sectionally whether intake of EPA and DHA in the usual diet is associated with a less atherogenic lipoprotein profile in subjects with FH (n=215). Lipoprotein particle number and size distributions were assessed with nuclear magnetic resonance spectroscopy. EPA and DHA proportions in serum phosphatidylcholine, a biomarker of fish intake, were determined by gas chromatography. After adjusting for cardiovascular risk factors, including fasting triglycerides, serum phosphatidylcholine EPA (but not DHA) related inversely to medium VLDL, total LDL particle number and very small LDL, resulting in a net direct association with LDL size. Additionally, EPA was directly associated with concentrations of large HDL. We conclude that increased serum phosphatidylcholine EPA derived from seafood intake with the usual diet is associated with a less atherogenic lipoprotein profile in subjects with FH. Increased fish intake and/or EPA supplements might contribute to reduce the residual risk of statin-treated FH subjects. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. An OmpA Family Protein, a Target of the GinI/GinR Quorum-Sensing System in Gluconacetobacter intermedius, Controls Acetic Acid Fermentation▿ †

    PubMed Central

    Iida, Aya; Ohnishi, Yasuo; Horinouchi, Sueharu

    2008-01-01

    Via N-acylhomoserine lactones, the GinI/GinR quorum-sensing system in Gluconacetobacter intermedius NCI1051, a gram-negative acetic acid bacterium, represses acetic acid and gluconic acid fermentation. Two-dimensional polyacrylamide gel electrophoretic analysis of protein profiles of strain NCI1051 and ginI and ginR mutants identified a protein that was produced in response to the GinI/GinR regulatory system. Cloning and nucleotide sequencing of the gene encoding this protein revealed that it encoded an OmpA family protein, named GmpA. gmpA was a member of the gene cluster containing three adjacent homologous genes, gmpA to gmpC, the organization of which appeared to be unique to vinegar producers, including “Gluconacetobacter polyoxogenes.” In addition, GmpA was unique among the OmpA family proteins in that its N-terminal membrane domain forming eight antiparallel transmembrane β-strands contained an extra sequence in one of the surface-exposed loops. Transcriptional analysis showed that only gmpA of the three adjacent gmp genes was activated by the GinI/GinR quorum-sensing system. However, gmpA was not controlled directly by GinR but was controlled by an 89-amino-acid protein, GinA, a target of this quorum-sensing system. A gmpA mutant grew more rapidly in the presence of 2% (vol/vol) ethanol and accumulated acetic acid and gluconic acid in greater final yields than strain NCI1051. Thus, GmpA plays a role in repressing oxidative fermentation, including acetic acid fermentation, which is unique to acetic acid bacteria and allows ATP synthesis via ethanol oxidation. Consistent with the involvement of gmpA in oxidative fermentation, its transcription was also enhanced by ethanol and acetic acid. PMID:18487322

  6. The Multiple DSF-family QS Signals are Synthesized from Carbohydrate and Branched-chain Amino Acids via the FAS Elongation Cycle

    PubMed Central

    Zhou, Lian; Yu, Yonghong; Chen, Xiping; Diab, Abdelgader Abdeen; Ruan, Lifang; He, Jin; Wang, Haihong; He, Ya-Wen

    2015-01-01

    Members of the diffusible signal factor (DSF) family are a novel class of quorum sensing (QS) signals in diverse Gram-negative bacteria. Although previous studies have identified RpfF as a key enzyme for the biosynthesis of DSF family signals, many questions in their biosynthesis remain to be addressed. In this study with the phytopathogen Xanthomonas campestris pv. campestris (Xcc), we show that Xcc produces four DSF-family signals (DSF, BDSF, CDSF and IDSF) during cell culture, and that IDSF is a new functional signal characterized as cis-10-methyl-2-dodecenoic acid. Using a range of defined media, we further demonstrate that Xcc mainly produces BDSF in the presence of carbohydrates; leucine and valine are the primary precursor for DSF biosynthesis; isoleucine is the primary precursor for IDSF biosynthesis. Furthermore, our biochemical analyses show that the key DSF synthase RpfF has both thioesterase and dehydratase activities, and uses 3-hydroxydedecanoyl-ACP as a substrate to produce BDSF. Finally, our results show that the classic fatty acid synthesis elongation cycle is required for the biosynthesis of DSF-family signals. Taken all together, these findings establish a general biosynthetic pathway for the DSF-family quorum sensing signals. PMID:26289160

  7. The Multiple DSF-family QS Signals are Synthesized from Carbohydrate and Branched-chain Amino Acids via the FAS Elongation Cycle.

    PubMed

    Zhou, Lian; Yu, Yonghong; Chen, Xiping; Diab, Abdelgader Abdeen; Ruan, Lifang; He, Jin; Wang, Haihong; He, Ya-Wen

    2015-08-20

    Members of the diffusible signal factor (DSF) family are a novel class of quorum sensing (QS) signals in diverse Gram-negative bacteria. Although previous studies have identified RpfF as a key enzyme for the biosynthesis of DSF family signals, many questions in their biosynthesis remain to be addressed. In this study with the phytopathogen Xanthomonas campestris pv. campestris (Xcc), we show that Xcc produces four DSF-family signals (DSF, BDSF, CDSF and IDSF) during cell culture, and that IDSF is a new functional signal characterized as cis-10-methyl-2-dodecenoic acid. Using a range of defined media, we further demonstrate that Xcc mainly produces BDSF in the presence of carbohydrates; leucine and valine are the primary precursor for DSF biosynthesis; isoleucine is the primary precursor for IDSF biosynthesis. Furthermore, our biochemical analyses show that the key DSF synthase RpfF has both thioesterase and dehydratase activities, and uses 3-hydroxydedecanoyl-ACP as a substrate to produce BDSF. Finally, our results show that the classic fatty acid synthesis elongation cycle is required for the biosynthesis of DSF-family signals. Taken all together, these findings establish a general biosynthetic pathway for the DSF-family quorum sensing signals.

  8. Structure of LP2179, the first representative of Pfam family PF08866, suggests a new fold with a role in amino-acid metabolism

    SciTech Connect

    Bakolitsa, Constantina; Kumar, Abhinav; Carlton, Dennis; Miller, Mitchell D.; Krishna, S.Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Elsliger, Marc-André; Feuerhelm, Julie; Grzechnik, Slawomir K.; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; Tien, Henry J.; Trout, Christina V.; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2011-08-17

    The structure of LP2179, a member of the PF08866 (DUF1831) family, suggests a novel {alpha} + {beta} fold comprising two {beta}-sheets packed against a single helix. A remote structural similarity to two other uncharacterized protein families specific to the Bacillus genus (PF08868 and PF08968), as well as to prokaryotic S-adenosylmethionine decarboxylases, is consistent with a role in amino-acid metabolism. Genomic neighborhood analysis of LP2179 supports this functional assignment, which might also then be extended to PF08868 and PF08968.

  9. Structure of LP2179, the first representative of Pfam family PF08866, suggests a new fold with a role in amino-acid metabolism

    PubMed Central

    Bakolitsa, Constantina; Kumar, Abhinav; Carlton, Dennis; Miller, Mitchell D.; Krishna, S. Sri; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Elsliger, Marc-André; Feuerhelm, Julie; Grzechnik, Slawomir K.; Grant, Joanna C.; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; McMullan, Daniel; Morse, Andrew T.; Nigoghossian, Edward; Okach, Linda; Oommachen, Silvya; Paulsen, Jessica; Reyes, Ron; Rife, Christopher L.; Tien, Henry J.; Trout, Christina V.; van den Bedem, Henry; Weekes, Dana; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The structure of LP2179, a member of the PF08866 (DUF1831) family, suggests a novel α+β fold comprising two β-sheets packed against a single helix. A remote structural similarity to two other uncharacterized protein families specific to the Bacillus genus (PF08868 and PF08968), as well as to prokaryotic S-adenosylmethionine decarboxylases, is consistent with a role in amino-acid metabolism. Genomic neighborhood analysis of LP2179 supports this functional assignment, which might also then be extended to PF08868 and PF08968. PMID:20944212

  10. The Gibberellic Acid Stimulated-Like Gene Family in Maize and Its Role in Lateral Root Development1[C][W][OA

    PubMed Central

    Zimmermann, Roman; Sakai, Hajime; Hochholdinger, Frank

    2010-01-01

    In an approach to study lateral root development in monocots, genome-wide searches for homologs of the Gibberellic Acid Stimulated Transcript-like (GAST-like) gene family in rice (Oryza sativa) and maize (Zea mays) were carried out. Six novel GAST-like genes in rice and 10 members of the gene family in maize, which were designated ZmGSL (for Z. mays Gibberellic Acid Stimulated-Like), were identified. The ZmGSL family encodes small proteins of 75 to 128 amino acids, which are characterized by a conserved 59 to 64 amino acid C-terminal domain. Within this domain, 17 amino acids, including 12 cysteines, are perfectly conserved. The transcript of the ZmGSL1 gene is differentially spliced into the alternative variants ZmGSL1a and ZmGSL1b, the latter of which is translated into a premature protein that lacks the C-terminal domain. The presence of an additional N-terminal cleavable signal sequence in eight of the 10 ZmGSL proteins suggests that they are secreted into the extracellular matrix. In-depth root-specific gene expression analyses carried out in the wild type and the lateral root mutants lrt1 and rum1 suggest a role for ZmGSL genes in early lateral root development, which is likely regulated by gibberellic acid. Expression patterns of ZmGSL1a and ZmGSL1b propose antagonistic functions of these splice variants during early lateral root formation. PMID:19926801

  11. Rhizocola hellebori gen. nov., sp. nov., an actinomycete of the family Micromonosporaceae containing 3,4-dihydroxydiaminopimelic acid in the cell-wall peptidoglycan.

    PubMed

    Matsumoto, Atsuko; Kawaguchi, Yoko; Nakashima, Takuji; Iwatsuki, Masato; Ōmura, Satoshi; Takahashi, Yōko

    2014-08-01

    An actinomycete strain, K12-0602(T), was isolated from the root of a Helleborus orientalis plant in Japan. The 16S rRNA gene sequence of strain K12-0602(T) showed that it had a close relationship with members of the family Micromonosporaceae and the 16S rRNA gene sequence similarity values between strain K12-0602(T) and type strains of type species of 27 genera belonging to the family Micromonosporaceae were below 96.2%. MK-9 (H4) and MK-9 (H6) were detected as major menaquinones, and galactose, xylose, mannose and ribose were present in the whole-cell hydrolysate. The acyl type of the peptidoglycan was glycolyl. Major fatty acids were iso-C(15 : 0), iso-C(16 : 0), C(17 : 1)ω9c and anteiso-C(17 : 0). Phosphatidylethanolamine was detected as the phospholipid corresponding to phospholipid type II. The G+C content of the genomic DNA was 67 mol%. Analyses of the cell-wall peptidoglycan by TLC and LC/MS showed that it was composed of alanine, glycine, hydroxylglutamic acid and an unknown amino acid, which was subsequently determined to be 3,4-dihydroxydiaminopimelic acid using instrumental analyses, including NMR and mass spectrometry. On the basis of the phylogenetic analysis and chemotaxonomic characteristics, strain K12-0602(T) represents a novel species of a new genus in the family Micromonosporaceae, for which the name Rhizocola hellebori gen. nov., sp. nov. is proposed. The type strain of the type species is K12-0602(T) ( = NBRC 109834(T) = DSM 45988(T)). This is the first report, to our knowledge, of 3,4-dihydroxydiaminopimelic acid being found as a diamino acid in bacterial cell-wall peptidoglycan.

  12. Specific glycosylation of α1-acid glycoprotein characterises patients with familial Mediterranean fever and obligatory carriers of MEFV

    PubMed Central

    Poland, D; Drenth, J; Rabinovitz, E; Livneh, A; Bijzet, J; van het, Hof B; van Dijk, W

    2001-01-01

    BACKGROUND—Familial Mediterranean fever (FMF) is a periodic febrile disorder, characterised by fever and serositis. The acute phase response during attacks of FMF results from the release of cytokines, which in turn induce increased expression and changed glycosylation of acute phase proteins. A recent study indicated that attacks in FMF are accompanied by a rise of plasma concentrations of serum amyloid A (SAA) and C reactive protein (CRP), which remain significantly raised during remission relative to healthy controls. Another study suggested that obligatory heterozygotes also display an inflammatory acute phase response.
OBJECTIVE—To determine the state of inflammation in homozygotic and heterozygotic MEFV genotypes.
METHODS—CRP and SAA were studied by enzyme linked immunosorbent assay (ELISA). The glycosylation of the acute phase protein, α1-acid glycoprotein (AGP), was visualised with crossed affinoimmunoelectrophoresis with concanavalin A as diantennary glycan-specific component and Aleuria aurantia lectin as fucose-specific affinity component.
RESULTS—FMF attacks were associated with an increase (p<0.05) in the serum inflammation parameters CRP, SAA, and AGP. The glycosylation of AGP showed an increase (p<0.05) in fucosylated AGP glycoforms, whereas the branching of the glycans remained unaffected. The glycosylation of AGP in the MEFV carrier group, compared with that in a healthy control group, was characterised by a significant increase (p<0.05) in branching of the glycans, whereas the fucosylation remained unaffected.
CONCLUSION—The findings suggest an FMF-specific release of cytokines, resulting in a different glycosylation of AGP between a homozygotic and heterozygotic MEFV genotype.

 PMID:11454642

  13. Systemic Concentrations of Short Chain Fatty Acids Are Elevated in Salmonellosis and Exacerbation of Familial Mediterranean Fever

    PubMed Central

    Ktsoyan, Zhanna A.; Mkrtchyan, Mkhitar S.; Zakharyan, Magdalina K.; Mnatsakanyan, Armine A.; Arakelova, Karine A.; Gevorgyan, Zaruhi U.; Sedrakyan, Anahit M.; Hovhannisyan, Alvard I.; Arakelyan, Arsen A.; Aminov, Rustam I.

    2016-01-01

    Gut microbiota-produced short chain fatty acids (SCFAs) play an important role in the normal human metabolism and physiology. Although the gradients of SCFAs from the large intestine, where they are largely produced, to the peripheral blood as well as the main routes of SCFA metabolism by different organs are known well for the healthy state, there is a paucity of information regarding how these are affected in disease. In particular, how the inflammation caused by infection or autoinflammatory disease affect the concentration of SCFAs in the peripheral venous blood. In this work, we revealed that diseases caused either by infectious agents (two Salmonella enterica serovars, S. Enteritidis, and S. Typhimurium) or by the exacerbation of an autoinflammatory disease, familial Mediterranean fever (FMF), both result in a significantly elevated systemic concentration of SCFAs. In the case of salmonellosis the concentration of SCFAs in peripheral blood was significantly and consistently higher, from 5- to 20-fold, compared to control. In the case of FMF, however, a significant increase of SCFAs in the peripheral venous blood was detected only in the acute phase of the disease, with a lesser impact in remission. It seems counterintuitive that the dysbiotic conditions, with a reduced number of gut microorganisms, produce such an effect. This phenomenon, however, must be appraised within the context of how the inflammatory diseases affect the normal physiology. We discuss a number of factors that may contribute to the “leak” and persistence of gut-produced SCFAs into the systemic circulation in infectious and autoinflammatory diseases. PMID:27252692

  14. The AAP gene family for amino acid permeases contributes to development of the cyst nematode Heterodera schachtii in roots of Arabidopsis☆

    PubMed Central

    Elashry, Abdelnaser; Okumoto, Sakiko; Siddique, Shahid; Koch, Wolfgang; Kreil, David P.; Bohlmann, Holger

    2013-01-01

    The beet cyst nematode Heterodera schachtii is able to infect Arabidopsis plants and induce feeding sites in the root. These syncytia are the only source of nutrients for the nematodes throughout their life and are a nutrient sink for the host plant. We have studied here the role of amino acid transporters for nematode development. Arabidopsis contains a large number of different amino acid transporters in several gene families but those of the AAP family were found to be especially expressed in syncytia. Arabidopsis contains 8 AAP genes and they were all strongly expressed in syncytia with the exception of AAP5 and AAP7, which were slightly downregulated. We used promoter::GUS lines and in situ RT-PCR to confirm the expression of several AAP genes and LHT1, a lysine- and histidine-specific amino acid transporter, in syncytia. The strong expression of AAP genes in syncytia indicated that these transporters are important for the transport of amino acids into syncytia and we used T-DNA mutants for several AAP genes to test for their influence on nematode development. We found that mutants of AAP1, AAP2, and AAP8 significantly reduced the number of female nematodes developing on these plants. Our study showed that amino acid transport into syncytia is important for the development of the nematodes. PMID:23831821

  15. Identification and characterization of the abscisic acid (ABA) receptor gene family and its expression in response to hormones in the rubber tree

    PubMed Central

    Guo, Dong; Zhou, Ying; Li, Hui-Liang; Zhu, Jia-Hong; Wang, Ying; Chen, Xiong-Ting; Peng, Shi-Qing

    2017-01-01

    Abscisic acid (ABA) is an essential phytohormone involved in diverse physiological processes. Although genome-wide analyses of the ABA receptor PYR/PYL/RCAR (PYL) protein/gene family have been performed in certain plant species, little is known about the ABA receptor protein/gene family in the rubber tree (Hevea brasiliensis). In this study, we identified 14 ABA receptor PYL proteins/genes (designated HbPYL1 through HbPYL14) in the most recent rubber tree genome. A phylogenetic tree was constructed, which demonstrated that HbPYLs can be divided into three subfamilies that correlate well with the corresponding Arabidopsis subfamilies. Eight HbPYLs are highly expressed in laticifers. Five of the eight genes are simultaneously regulated by ABA, jasmonic acid (JA) and ethylene (ET). The identification and characterization of HbPYLs should enable us to further understand the role of ABA signal in the rubber tree. PMID:28332623

  16. Serum fatty acids in infants, reflecting family fish consumption, were inversely associated with allergy development but not related to farm residence.

    PubMed

    Jonsson, Karin; Barman, Malin; Moberg, Sara; Sjöberg, Agneta; Brekke, Hilde K; Hesselmar, Bill; Sandberg, Ann-Sofie; Wold, Agnes E

    2016-12-01

    In this study, differences in serum fatty acid patterns between farm and nonfarm infants were investigated and related to subsequent allergy development. We also related allergy-related serum fatty acids to maternal diet and breast milk fatty acids. The FARMFLORA birth cohort included 28 farm and 37 nonfarm infants. Serum was obtained from 21 farm infants and 29 controls at four months post-partum and analysed for phospholipid fatty acids. Allergy was diagnosed by paediatricians at three years of age. Serum fatty acid patterns were similar in farm and control infants, although farm infants had lower 18:1 omega-7 proportions. Serum proportions of eicosapentaenoic acid (EPA) were unrelated to farming status, but lower in children who subsequently developed allergy, with an odds ratio of 0.47 and 95% confidence interval of 0.27-0.83 (p = 0.01) for every 0.1% EPA increase. The infants' serum EPA proportions correlated with breast milk EPA proportions, which, in turn, correlated with maternal oily fish intake during lactation. The allergy-protective effect of farming was not linked to infant serum fatty acid composition. However, healthy infants had higher proportions of EPA in their sera, probably reflecting a family diet rich in fish, compared to subsequently allergic children. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  17. How a microbial drug transporter became essential for crop cultivation on acid soils: aluminium tolerance conferred by the multidrug and toxic compound extrusion (MATE) family

    PubMed Central

    Magalhaes, Jurandir V.

    2010-01-01

    Background Aluminium (Al) toxicity is a major agricultural constraint for crop cultivation on acid soils, which comprise a large portion of the world's arable land. One of the most widely accepted mechanisms of Al tolerance in plants is based on Al-activated organic acid release into the rhizosphere, with organic acids forming stable, non-toxic complexes with Al. This mechanism has recently been validated by the isolation of bona-fide Al-tolerance genes in crop species, which encode membrane transporters that mediate Al-activated organic acid release leading to Al exclusion from root apices. In crop species such as sorghum and barley, members in the multidrug and toxic compound extrusion (MATE) family underlie Al tolerance by a mechanism based on Al-activated citrate release. Scope and Conclusions The study of Al tolerance in plants as conferred by MATE family members is in its infancy. Therefore, much is yet to be discovered about the functional diversity and evolutionary dynamics that led MATE proteins to acquire transport properties conducive to Al tolerance in plants. In this paper we review the major characteristics of transporters in the MATE family and will relate this knowledge to Al tolerance in plants. The MATE family is clearly extremely flexible with respect to substrate specificity, which raises the possibility that Al tolerance as encoded by MATE proteins may not be restricted to Al-activated citrate release in plant species. There are also indications that regulatory loci may be of pivotal importance to fully explore the potential for Al-tolerance improvement based on MATE genes. PMID:20511585

  18. Evolution of structure and function in the o-succinylbenzoate synthase/N-acylamino acid racemase family of the enolase superfamily.

    PubMed

    Glasner, Margaret E; Fayazmanesh, Nima; Chiang, Ranyee A; Sakai, Ayano; Jacobson, Matthew P; Gerlt, John A; Babbitt, Patricia C

    2006-06-30

    Understanding how proteins evolve to provide both exquisite specificity and proficient activity is a fundamental problem in biology that has implications for protein function prediction and protein engineering. To study this problem, we analyzed the evolution of structure and function in the o-succinylbenzoate synthase/N-acylamino acid racemase (OSBS/NAAAR) family, part of the mechanistically diverse enolase superfamily. Although all characterized members of the family catalyze the OSBS reaction, this family is extraordinarily divergent, with some members sharing <15% identity. In addition, a member of this family, Amycolatopsis OSBS/NAAAR, is promiscuous, catalyzing both dehydration and racemization. Although the OSBS/NAAAR family appears to have a single evolutionary origin, no sequence or structural motifs unique to this family could be identified; all residues conserved in the family are also found in enolase superfamily members that have different functions. Based on their species distribution, several uncharacterized proteins similar to Amycolatopsis OSBS/NAAAR appear to have been transmitted by lateral gene transfer. Like Amycolatopsis OSBS/NAAAR, these might have additional or alternative functions to OSBS because many are from organisms lacking the pathway in which OSBS is an intermediate. In addition to functional differences, the OSBS/NAAAR family exhibits surprising structural variations, including large differences in orientation between the two domains. These results offer several insights into protein evolution. First, orthologous proteins can exhibit significant structural variation, and specificity can be maintained with little conservation of ligand-contacting residues. Second, the discovery of a set of proteins similar to Amycolatopsis OSBS/NAAAR supports the hypothesis that new protein functions evolve through promiscuous intermediates. Finally, a combination of evolutionary, structural, and sequence analyses identified characteristics that

  19. New zwitterionic butanesulfonic acids that extend the alkaline range of four families of Good buffers: evaluation for use in biological systems.

    PubMed

    Thiel, T; Liczkowski, L; Bissen, S T

    1998-11-18

    Four new zwitterionic butanesulfonic acid buffers that are structurally related to four families of Good buffers were evaluated for use in biological systems. These buffers, with pKa values from 7.6 to 10.7, were compared with a variety of other buffers from the same family and with unrelated buffers to determine their effect on enzyme activity and on microbial growth. The activity of four enzymes with optimum pH values in the alkaline range were tested: beta-galactosidase, esterase, phosphodiesterase and alkaline phosphatase. In general, all the Good buffers, including the new butanesulfonic acid buffers, gave good activity; however, there was variation in activity of certain enzymes with certain buffers. Tris, glycine, and phosphate buffers typically showed variation in activity compared to the family of Good buffers. beta-Galactosidase, in particular, showed greater activity with Good buffers than with phosphate or Tris buffers. Similarly, growth of seven bacterial strains was consistent, with a few exceptions, for all the Good family of buffers with Tris often inhibiting growth. Quantitation of alkaline phosphatase conjugated to antibodies is an important tool in many applications in molecular biology. Several Good buffers gave good signals when compared with Tris at pH 9.5 for detection of proteins using alkaline phosphatase-conjugated antibodies.

  20. Comparative Analysis of P450 Signature Motifs EXXR and CXG in the Large and Diverse Kingdom of Fungi: Identification of Evolutionarily Conserved Amino Acid Patterns Characteristic of P450 Family

    PubMed Central

    Syed, Khajamohiddin; Mashele, Samson Sitheni

    2014-01-01

    Cytochrome P450 monooxygenases (P450s) are heme-thiolate proteins distributed across the biological kingdoms. P450s are catalytically versatile and play key roles in organisms primary and secondary metabolism. Identification of P450s across the biological kingdoms depends largely on the identification of two P450 signature motifs, EXXR and CXG, in the protein sequence. Once a putative protein has been identified as P450, it will be assigned to a family and subfamily based on the criteria that P450s within a family share more than 40% homology and members of subfamilies share more than 55% homology. However, to date, no evidence has been presented that can distinguish members of a P450 family. Here, for the first time we report the identification of EXXR- and CXG-motifs-based amino acid patterns that are characteristic of the P450 family. Analysis of P450 signature motifs in the under-explored fungal P450s from four different phyla, ascomycota, basidiomycota, zygomycota and chytridiomycota, indicated that the EXXR motif is highly variable and the CXG motif is somewhat variable. The amino acids threonine and leucine are preferred as second and third amino acids in the EXXR motif and proline and glycine are preferred as second and third amino acids in the CXG motif in fungal P450s. Analysis of 67 P450 families from biological kingdoms such as plants, animals, bacteria and fungi showed conservation of a set of amino acid patterns characteristic of a particular P450 family in EXXR and CXG motifs. This suggests that during the divergence of P450 families from a common ancestor these amino acids patterns evolve and are retained in each P450 family as a signature of that family. The role of amino acid patterns characteristic of a P450 family in the structural and/or functional aspects of members of the P450 family is a topic for future research. PMID:24743800

  1. In vitro assessment of potential intestinal absorption of some phenolic families and carboxylic acids from commercial instant coffee samples.

    PubMed

    López-Froilán, R; Ramírez-Moreno, E; Podio, N S; Pérez-Rodríguez, M L; Cámara, M; Baroni, M V; Wunderlin, D A; Sánchez-Mata, M C

    2016-06-15

    Coffee is one of the most consumed beverages in the world, being a source of bioactive compounds as well as flavors. Hydroxycinnamic acids, flavonols, and carboxylic acids have been studied in the samples of instant coffee commercialized in Spain. The studies about contents of food components should be complemented with either in vitro or in vivo bioaccessibility studies to know the amount of food components effectively available for functions in the human body. In this sense, a widely used in vitro model has been applied to assess the potential intestinal absorption of phenolic compounds and organic acids. The contents of hydroxycinnamic acids and flavonols were higher in instant regular coffee samples than in the decaffeinated ones. Bioaccessible phenolic compounds in most analyzed samples account for 20-25% of hydroxycinnamic acids and 17-26% of flavonols. This could mean that a great part of them can remain in the gut, acting as potential in situ antioxidants. Quinic, acetic, pyroglutamic, citric and fumaric acids were identified in commercial instant coffee samples. Succinic acid was found in the coffee blend containing chicory. All carboxylic acids showed a very high bioaccessibility. Particularly, acetic acid and quinic acid were found in higher contents in the samples treated with the in vitro simulation of gastrointestinal processes, compared to the original ones, which can be explained by their cleavage from chlorogenic acid during digestion. This is considered as a positive effect, since quinic acid is considered as an antioxidant inducer.

  2. Unravelling the diversity of the cyclopiazonic acid family of mycotoxins in Aspergillus flavus by UHPLC Triple-TOF HRMS

    USDA-ARS?s Scientific Manuscript database

    Cyclopiazonic acid (a-cyclopiazonic acid, a-CPA) is an indole-hydrindane-tetramic acid neurotoxin produced by various fungal species, including the notorious food and feed contaminant Aspergillus flavus. Despite its discovery in A. flavus cultures, approximately 40 years ago, its contribution to the...

  3. Two novel PRP31 premessenger ribonucleic acid processing factor 31 homolog mutations including a complex insertion-deletion identified in Chinese families with retinitis pigmentosa.

    PubMed

    Dong, Bing; Chen, Jieqiong; Zhang, Xiaohui; Pan, Zhe; Bai, Fengge; Li, Yang

    2013-01-01

    To identify the causative mutations in two Chinese families with retinitis pigmentosa (RP), and to describe the associated phenotype. Individuals from two unrelated families underwent full ophthalmic examinations. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed on the known genetic loci for autosomal dominant retinitis pigmentosa with a panel of polymorphic markers in the two families, and then all coding exons of the PRP31 premessenger ribonucleic acid processing factor 31 homolog (PRPF31) gene were screened for mutations with direct sequencing of PCR-amplified DNA fragments. Allele-specific PCR was used to validate a substitution in all available family members and 100 normal controls. A large deletion was detected with real-time quantitative PCR (RQ-PCR) using a panel of primers from regions around the PRPF31 gene. Long-range PCR, followed by DNA sequencing, was used to define the breakpoints. Clinical examination and pedigree analysis revealed two four-generation families (RP24 and RP106) with autosomal dominant retinitis pigmentosa. A significant two-point linkage odd disequilibrium score was generated at marker D19S926 (Zmax=3.55, θ=0) for family RP24 and D19S571 (Zmax=3.21, θ=0) for family RP106, and further linkage and haplotype studies confined the disease locus to chromosome 19q13.42 where the PRPF31 gene is located. Mutation screening of the PRPF31 gene revealed a novel deletion c.1215delG (p.G405fs+7X) in family RP106. The deletion cosegregated with the family's disease phenotype, but was not found in 100 normal controls. No disease-causing mutation was detected in family RP24 with PCR-based sequencing analysis. RQ-PCR and long-range PCR analysis revealed a complex insertion-deletion (indel) in the patients of family RP24. The deletion is more than 19 kb and encompasses part of the PRPF31 gene (exons 1-3), together with three adjacent genes. Our results further

  4. Perfluorooctanoic acid-induced inhibition of placental prolactin-family hormone and fetal growth retardation in mice.

    PubMed

    Suh, Chun Hui; Cho, Nam Kyoo; Lee, Chae Kwan; Lee, Chang Hee; Kim, Dae Hwan; Kim, Jeong Ho; Son, Byung Chul; Lee, Jong Tae

    2011-04-30

    Perfluorooctanoic acid (PFOA) is a persistent pollutant worldwide and even found in human cord blood and breast milk. Some animal studies have reported that PFOA causes developmental toxicity such as fetal weight loss, but the mechanism is still unclear. This study focused on developmental toxicity of PFOA, particularly impacts of PFOA on placental endocrine function such as placental prolactin (PRL)-family hormone gene expression and fetal growth in mouse. Time-mated CD-1 mice were dosed by gavage with 0, 2, 10 and 25 mg/kg B.W/day of PFOA (n-10) dissolved with de-ionized water from gestational day (GD) 11-16. During treatment, body weight of each pregnant mouse was measured daily. On day 16, caesarean sections were performed and developmental data were observed. Three placentas from three different pregnant mice were assigned to each of the following experiments. The mRNA levels of mouse placental lactogen (mPL)-II, prolactin like protein (mPLP)-E, -F and Pit-1α and β isotype mRNAs, a transacting factor of mPLs and mPLPs genes, were analyzed using northern blot, in situ hybridization and RT-PCR, respectively. Maternal body weight gain was significantly declined from GD 13 in the PFOA treated groups compared to control. Developmental data such as fetal and placental weights were significantly decreased in accordance with PFOA dosage. Number of dead fetuses and post-implantation losses were significantly increased in the PFOA-exposed groups. In addition, placental efficiency (fetal weight/placental weight) was significantly reduced in PFOA treated groups in accordance with PFOA dosage. Histopathologic changes were observed in placenta. Dose dependent necrotic changes were observed in both 10 mg and 25 mg PFOA treated groups. Cell frequency of glycogen trophoblast cell and parietal trophoblast giant cell were decreased dose dependently in the junctional zone. In the labyrinth zone, sinusoidal trophoblast giant cell frequency was decreased in the 25 mg PFOA treated

  5. Nicotianamine synthase gene family as central components in heavy metal and phytohormone response in maize.

    PubMed

    Zhou, Mei-Liang; Qi, Lei-Peng; Pang, Jun-Feng; Zhang, Qian; Lei, Zhi; Tang, Yi-Xiong; Zhu, Xue-Mei; Shao, Ji-Rong; Wu, Yan-Min

    2013-06-01

    Nicotianamine (NA) is an important divalent metal chelator and the main precursor of phytosiderophores. NA is synthesized from S-adenosylmethionine in a process catalyzed by nicotianamine synthase (NAS). In this study, a set of structural and phylogenetic analyses have been applied to identify the maize NAS genes based on the maize genome sequence release. Ten maize NAS genes have been mapped; seven of them have not been reported to date. Phylogenetic analysis and expression pattern from microarray data led to their classification into two different orthologous groups. C-terminal fusion of ZmNAS3 with GFP was found in the cytoplasm of Arabidopsis leaf protoplast. Expression analysis by reverse transcription polymerase chain reaction revealed ZmNAS genes are responsive to heavy metal ions (Ni, Fe, Cu, Mn, Zn, and Cd), and all 10 ZmNAS genes were only observed in the root tissue except of ZmNAS6. The promoter of ZmNAS genes was analyzed for the presence of different cis-element response to all kinds of phytohormones and environment stresses. We found that the ZmNAS gene expression of maize seedlings was regulated by jasmonic acid, abscisic acid, and salicylic acid. Microarray data demonstrated that the ZmNAS genes show differential, organ-specific expression patterns in the maize developmental steps. The integrated comparative analysis can improve our current view of ZmNAS genes and facilitate the functional characterization of individual members.

  6. Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial

    PubMed Central

    2013-01-01

    Background Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. Methods Patients with FAP received celecoxib (400 mg twice daily) and UDCA (1000-2000 mg daily, ~20-30 mg/kg/day, n=19) or celecoxib and placebo (n=18) orally for 6 months. Primary outcome was drug efficacy, assessed by comparing duodenal polyp density at pre- and post-intervention by blinded review of endoscopic recordings. As secondary outcomes, cell proliferation, apoptosis, and COX-2 levels in normal duodenal mucosa were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. Results In intention-to-treat analysis, deceased polyp density was observed after celecoxib/placebo treatment (p=0.029), whereas increased polyp density was observed after celecoxib/UDCA treatment (p=0.014). The difference in change in duodenal polyp density was statistically significant between the groups (p=0.011). No changes in secondary outcomes were observed. Thirty patients (81%) reported one or more adverse events, 16 patients (84%, Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE) grade 1–3) treated with celecoxib/UDCA and 14 patients (78%, CTCAE grade 1–2) treated with celecoxib/placebo. Nine patients (24%) discontinued intervention prematurely, 5 patients (26%) treated with celecoxib/UDCA and 4 patients (22%) treated with celecoxib/placebo. Conclusions Celecoxib reduces duodenal

  7. Identification of amino acid residues critical for catalysis and stability in Aspergillus niger family 1 pectin lyase A.

    PubMed Central

    Sánchez-Torres, Paloma; Visser, Jaap; Benen, Jacques A E

    2003-01-01

    Site-directed-mutagenesis studies were performed on family 1 pectin lyase A (PL1A) from Aspergillus niger to gain insight into the reaction mechanism for the pectin lyase-catalysed beta-elimination cleavage of methylesterified polygalacturonic acid and to stabilize the enzyme at slightly basic pH. On the basis of the three-dimensional structures of PL1A [Mayans, Scott, Connerton, Gravesen, Benen, Visser, Pickersgill and Jenkins (1997) Structure 5, 677-689] and the modelled enzyme-substrate complex of PL1B [Herron, Benen, Scavetta, Visser and Jurnak (2000) Proc. Natl. Acad. Sci. U.S.A. 97, 8762-8769], Asp154, Arg176, Arg236 and Lys239 were mutagenized. Substituting Arg236 with alanine or lysine rendered the enzyme completely inactive, and mutagenesis of Arg176 and Lys239 severely affected catalysis. The Asp154-->Arg and Asp154-->Glu mutant enzymes were only moderately impaired in respect of catalysis. The results strongly indicate that Arg236, which is sandwiched between Arg176 and Lys239, would initiate the reaction upon enzyme-substrate interaction, through the abstraction of the proton at C5 of the galacturonopyranose ring. The positively charged residues Arg176 and Lys239 are responsible for lowering the p K a of Arg236. Arg176 and Lys239 are maintained in a charged state by interacting with Asp154 or bulk solvent respectively. The deprotonation of the Asp186-Asp221 pair was proposed to be responsible for a pH-driven conformational change of PL1A [Mayans, Scott, Connerton, Gravesen, Benen, Visser, Pickersgill and Jenkins (1997) Structure 5, 677-689]. Substitution of Asp186 and Asp221 by Asn186 and Asn221 was expected to stabilize the enzyme. However, the Asp186-->Asn/Asp221-->Asn enzyme appeared less stable than the wild-type enzyme, even at pH 6.0, as evidenced by fluorescence studies. This demonstrates that the pH-dependent conformational change is not driven by deprotonation of the Asp186-Asp221 pair. PMID:12418964

  8. A Randomized Controlled Trial of Individual Family Psychoeducational Psychotherapy and Omega-3 Fatty Acids in Youth with Subsyndromal Bipolar Disorder

    PubMed Central

    Young, Andrea S.; Vesco, Anthony T.; Nader, Elias S.; Healy, K. Zachary; Gardner, William; Wolfson, Hannah L.; Arnold, L. Eugene

    2015-01-01

    Abstract Objective: This pilot study evaluates efficacy of omega-3 fatty acid supplementation (Ω3), individual family psychoeducational psychotherapy (IF-PEP), and their combination in youth with subsyndromal bipolar disorders (bipolar disorder not otherwise specified [BP-NOS], cyclothymic disorder [CYC]). Methods: This study was a 12 week, randomized trial of Ω3 versus placebo and IF-PEP versus active monitoring (AM) using a 2 × 2 design (Ω3 + PEP: n = 5; Ω3 + AM: n = 5; placebo + PEP: n = 7; placebo + AM: n = 6). Twenty-three youth ages 7–14 with BP-NOS or CYC were recruited via community advertisements and clinician referrals. Participants could be taking stable medication for attention-deficit/hyperactivity disorder and sleep aids, but no other psychotropics. Independent evaluators assessed participants at screen, baseline, and 2, 4, 6, 9, and 12 weeks. Primary outcome measures were the Kiddie Schedule for Affective Disorders (K-SADS) Depression (KDRS) and Mania (KMRS) Rating Scales, Children's Depression Rating Scale-Revised (CDRS-R), and Young Mania Rating Scale (YMRS). Ω3/placebo conditions were double-blind; independent evaluators were blind to psychotherapy condition. Results: Most participants (83%) completed the 12 week trial. Side effects were uncommon and mild. Intent-to-treat analyses indicated significant improvement in depressive symptoms (KDRS) for combined treatment relative to placebo and AM (p = 0.01, d = 1.70). Across groups, manic symptoms improved over time without significant treatment effects. Effect of IF-PEP on child depression compared with AM was medium (d = 0.63, CDRS-R) to large (d = 1.24, KDRS). Effect of Ω3 on depression was medium (d = 0.48, KDRS). Conclusion: IF-PEP and Ω3 are well tolerated and associated with improved mood symptoms among youth with BP-NOS and CYC. Clinicaltrials.gov Identifier: NCT01507753 PMID:26682997

  9. Assignment of function to a domain of unknown function: DUF1537 is a new kinase family in catabolic pathways for acid sugars

    PubMed Central

    Zhang, Xinshuai; Carter, Michael S.; Vetting, Matthew W.; San Francisco, Brian; Zhao, Suwen; Al-Obaidi, Nawar F.; Solbiati, Jose O.; Thiaville, Jennifer J.; de Crécy-Lagard, Valérie; Jacobson, Matthew P.; Almo, Steven C.; Gerlt, John A.

    2016-01-01

    Using a large-scale “genomic enzymology” approach, we (i) assigned novel ATP-dependent four-carbon acid sugar kinase functions to members of the DUF1537 protein family (domain of unknown function; Pfam families PF07005 and PF17042) and (ii) discovered novel catabolic pathways for d-threonate, l-threonate, and d-erythronate. The experimentally determined ligand specificities of several solute binding proteins (SBPs) for TRAP (tripartite ATP-independent permease) transporters for four-carbon acids, including d-erythronate and l-erythronate, were used to constrain the substrates for the catabolic pathways that degrade the SBP ligands to intermediates in central carbon metabolism. Sequence similarity networks and genome neighborhood networks were used to identify the enzyme components of the pathways. Conserved genome neighborhoods encoded SBPs as well as permease components of the TRAP transporters, members of the DUF1537 family, and a member of the 4-hydroxy-l-threonine 4-phosphate dehydrogenase (PdxA) oxidative decarboxylase, class II aldolase, or ribulose 1,5-bisphosphate carboxylase/oxygenase, large subunit (RuBisCO) superfamily. Because the characterized substrates of members of the PdxA, class II aldolase, and RuBisCO superfamilies are phosphorylated, we postulated that the members of the DUF1537 family are novel ATP-dependent kinases that participate in catabolic pathways for four-carbon acid sugars. We determined that (i) the DUF1537/PdxA pair participates in a pathway for the conversion of d-threonate to dihydroxyacetone phosphate and CO2 and (ii) the DUF1537/class II aldolase pair participates in pathways for the conversion of d-erythronate and l-threonate (epimers at carbon-3) to dihydroxyacetone phosphate and CO2. The physiological importance of these pathways was demonstrated in vivo by phenotypic and genetic analyses. PMID:27402745

  10. [Amino acid and peptide derivatives of the tylosin family of macrolide antibiotics modified at the aldehyde group].

    PubMed

    Sumbatian, N V; Kuznetsova, I V; Karpenko, V V; Fedorova, N V; Chertkov, V A; Korshunova, G A; Bogdanov, A A

    2010-01-01

    Fourteen new functionally active amino acid and peptide derivatives of the antibiotics tylosin, desmycosin, and 5-O-mycaminosyltylonolide were synthesized in order to study the interaction of the growing polypeptide chain with the ribosomal tunnel. The conjugation of various amino acids and peptides with a macrolide aldehyde group was carried out by two methods: direct reductive amination with the isolation of the intermediate Schiff bases or through binding via oxime using the preliminarily obtained derivatives of 2-aminooxyacetic acid.

  11. Identification and characterization of a novel member of the heterodimeric amino acid transporter family presumed to be associated with an unknown heavy chain.

    PubMed

    Chairoungdua, A; Kanai, Y; Matsuo, H; Inatomi, J; Kim, D K; Endou, H

    2001-12-28

    We identified a novel amino acid transporter designated Asc-2 (for asc-type amino acid transporter 2). Asc-2 exhibited relatively low but significant sequence similarity to the members of the heterodimeric amino acid transporters. The cysteine residue responsible for the disulfide bond formation between transporters (light chains) and heavy chain subunits in the heterodimeric amino acid transporters is conserved for Asc-2. Asc-2 is, however, not colocalized with the already known heavy chains such as 4F2 heavy chain (4F2hc) or related to b(0,+) amino acid transporter (rBAT) in mouse kidney. Because Asc-2 solely expressed or coexpressed with 4F2hc or rBAT did not induce functional activity, we generated fusion proteins in which Asc-2 is connected with 4F2hc or rBAT. The fusion proteins were sorted to the plasma membrane and expressed the function corresponding to the Na(+)-independent small neutral amino acid transport system asc. Distinct from the already identified system asc transporter Asc-1 which is associated with 4F2hc, Asc-2-mediated transport is less stereoselective and did not accept some of the high affinity substrates of Asc-1 such as alpha-aminoisobutyric acid and beta-alanine. Asc-2 message was detected in kidney, placenta, spleen, lung, and skeletal muscle. In kidney, Asc-2 protein was present in the epithelial cells lining collecting ducts. In the Western blot analysis on mouse erythrocytes and kidney, Asc-2 was detected as multiple bands in the nonreducing condition, whereas the bands shifted to a single band at lower molecular weight, suggesting the association of Asc-2 with other protein(s) via a disulfide bond. The finding of Asc-2 would lead to the establishment of a new subgroup of heterodimeric amino acid transporter family which includes transporters associated not with 4F2hc or rBAT but with other unknown heavy chains.

  12. Amino Acid Bound Surfactants: A New Synthetic Family of Polymeric Monoliths Open Up Possibilities for Chiral Separations in Capillary Electrochromatography

    PubMed Central

    He, Jun; Wang, Xiaochun; Morrill, Mike; Shamsi, Shahab A.

    2012-01-01

    By combining a novel chiral amino-acid surfactant containing acryloyl amide tail, carbamate linker and leucine head group of different chain lengths with a conventional cross linker and a polymerization technique, a new “one-pot”, synthesis for the generation of amino-acid based polymeric monolith is realized. The method promises to open up the discovery of amino-acid based polymeric monolith for chiral separations in capillary electrochromatography (CEC). Possibility of enhanced chemoselectivity for simultaneous separation of ephedrine and pseudoephedrine containing multiple chiral centers, and the potential use of this amino-acid surfactant bound column for CEC and CEC coupled to mass spectrometric detection is demonstrated. PMID:22607448

  13. Identification of the acid/base catalyst of a glycoside hydrolase family 3 (GH3) beta-glucosidase from Aspergillus niger ASKU28.

    PubMed

    Thongpoo, Preeyanuch; McKee, Lauren S; Araújo, Ana Catarina; Kongsaeree, Prachumporn T; Brumer, Harry

    2013-03-01

    The commercially important glycoside hydrolase family 3 (GH3) beta-glucosidases from Aspergillus niger are anomeric-configuration-retaining enzymes that operate through the canonical double-displacement glycosidase mechanism. Whereas the catalytic nucleophile is readily identified across all GH3 members by sequence alignments, the acid/base catalyst in this family is phylogenetically variable and less readily divined. In this report, we employed three-dimensional structure homology modeling and detailed kinetic analysis of site-directed mutants to identify the catalytic acid/base of a GH3 beta-glucosidase from A. niger ASKU28. In comparison to the wild-type enzyme and other mutants, the E490A variant exhibited greatly reduced k(cat) and k(cat)/K(m) values toward the natural substrate cellobiose (67,000- and 61,000-fold, respectively). Correspondingly smaller kinetic effects were observed for artificial chromogenic substrates p-nitrophenyl beta-D-glucoside and 2,4-dinitrophenyl beta-D-glucoside, the aglycone leaving groups of which are less dependent on acid catalysis, although changes in the rate-determining catalytic step were revealed for both. pH-rate profile analyses also implicated E490 as the general acid/base catalyst. Addition of azide as an exogenous nucleophile partially rescued the activity of the E490A variant with the aryl beta-glucosides and yielded beta-glucosyl azide as a product. These results strongly support the assignment of E490 as the acid/base catalyst in a beta-glucosidase from A. niger ASKU28, and provide crucial experimental support for the bioinformatic identification of the homologous residue in a range of related GH3 subfamily members.

  14. Role of family support and women's knowledge on pregnancy-related risks in adherence to maternal iron-folic acid supplementation in Indonesia.

    PubMed

    Wiradnyani, Luh Ade Ari; Khusun, Helda; Achadi, Endang L; Ocviyanti, Dwiana; Shankar, Anuraj H

    2016-10-01

    To examine whether women's knowledge of pregnancy-related risks and family support received during pregnancy are associated with adherence to maternal iron-folic acid (IFA) supplementation. Secondary data analysis of the 2002-03, 2007 and 2012 Indonesia Demographic and Health Survey. Analysis of the association between factors associated with adherence (consuming ≥90 IFA tablets), including the women's knowledge and family support, was performed using multivariate logistic regression. National household survey. Women (n 19 133) who had given birth within 2 years prior to the interview date. Knowledge of pregnancy-related risks was associated with increased adherence to IFA supplementation (adjusted OR=1·8; 95 % CI 1·6, 2·0), as was full family (particularly husband's) support (adjusted OR=1·9; 95 % CI 1·6, 2·3). Adequate antenatal care (ANC) visits (i.e. four or more) was associated with increased adherence (adjusted OR=2·2; 95 % CI 2·0, 2·4). However, ANC providers missed opportunities to distribute tablets and information, as among women with adequate ANC visits, 15 % reported never having received/bought any IFA tablets and 30 % had no knowledge of pregnancy-related risks. A significant interaction was observed between family support and the women's educational level in predicting adherence. Family support significantly increased the adherence among women with <9 years of education. Improving women's knowledge of pregnancy-related risks and involving family members, particularly the husband and importantly for less-educated women, improved adherence to IFA supplementation. ANC visit opportunities must be optimized to provide women with sufficient numbers of IFA tablets along with health information (especially on pregnancy-related risks) and partner support counselling.

  15. The Clinical Spectrum of Missense Mutations of the First Aspartic Acid of cbEGF-like Domains in Fibrillin-1 Including a Recessive Family

    PubMed Central

    Hilhorst-Hofstee, Yvonne; Rijlaarsdam, Marry EB; Scholte, Arthur JHA; Swart-van den Berg, Marietta; Versteegh, Michel IM; van der Schoot-van Velzen, Iris; Schäbitz, Hans-Joachim; Bijlsma, Emilia K; Baars, Marieke J; Kerstjens-Frederikse, Wilhelmina S; Giltay, Jacques C; Hamel, Ben C; Breuning, Martijn H; Pals, Gerard

    2010-01-01

    Marfan syndrome (MFS) is a dominant disorder with a recognizable phenotype. In most patients with the classical phenotype mutations are found in the fibrillin-1 gene (FBN1) on chromosome 15q21. It is thought that most mutations act in a dominant negative way or through haploinsufficiency. In 9 index cases referred for MFS we detected heterozygous missense mutations in FBN1 predicted to substitute the first aspartic acid of different calcium-binding Epidermal Growth Factor-like (cbEGF) fibrillin-1 domains. A similar mutation was found in homozygous state in 3 cases in a large consanguineous family. Heterozygous carriers of this mutation had no major skeletal, cardiovascular or ophthalmological features of MFS. In the literature 14 other heterozygous missense mutations are described leading to the substitution of the first aspartic acid of a cbEGF domain and resulting in a Marfan phenotype. Our data show that the phenotypic effect of aspartic acid substitutions in the first position of a cbEGF domain can range from asymptomatic to a severe neonatal phenotype. The recessive nature with reduced expression of FBN1 in one of the families suggests a threshold model combined with a mild functional defect of this specific mutation. © 2010 Wiley-Liss, Inc. PMID:20886638

  16. Development of validated high-performance thin layer chromatography for quantification of aristolochic acid in different species of the Aristolochiaceae family.

    PubMed

    Agrawal, Poonam; Laddha, Kirti

    2017-04-01

    This study was undertaken to isolate and quantify aristolochic acid in Aristolochia indica stem and Apama siliquosa root. Aristolochic acid is an important biomarker component present in the Aristolochiaceae family. The isolation method involved simple solvent extraction, precipitation and further purification, using recrystallization. The structure of the compound was confirmed using infrared spectroscopy, mass spectrometry and nuclear magnetic resonance. A specific and rapid high-performance thin layer chromatography (HPTLC) method was developed for analysis of aristolochic acid. The method involved separation on the silica gel 60 F254 plates using the single solvent system of n-hexane: chloroform: methanol. The method showed good linear relationship in the range 0.4-2.0 μg/spot with r(2) = 0.998. The limit of detection and limit of quantification were 62.841 ng/spot and 209.47 ng/spot, respectively. The proposed validated HPTLC method was found to be an easy to use, accurate and convenient method that could be successfully used for standardization and quality assessment of herbal material as well as formulations containing different species of the Aristolochiaceae family. Copyright © 2016. Published by Elsevier B.V.

  17. In Vivo Evidence that S-Adenosylmethionine and Fatty Acid Synthesis Intermediates Are the Substrates for the LuxI Family of Autoinducer Synthases

    PubMed Central

    Val, Dale L.; Cronan, John E.

    1998-01-01

    Many gram-negative bacteria synthesize N-acyl homoserine lactone autoinducer molecules as quorum-sensing signals which act as cell density-dependent regulators of gene expression. We have investigated the in vivo source of the acyl chain and homoserine lactone components of the autoinducer synthesized by the LuxI homolog, TraI. In Escherichia coli, synthesis of N-(3-oxooctanoyl)homoserine lactone by TraI was unaffected in a fadD mutant blocked in β-oxidative fatty acid degradation. Also, conditions known to induce the fad regulon did not increase autoinducer synthesis. In contrast, cerulenin and diazoborine, specific inhibitors of fatty acid synthesis, both blocked autoinducer synthesis even in a strain dependent on β-oxidative fatty acid degradation for growth. These data provide the first in vivo evidence that the acyl chains in autoinducers synthesized by LuxI-family synthases are derived from acyl-acyl carrier protein substrates rather than acyl coenzyme A substrates. Also, we show that decreased levels of intracellular S-adenosylmethionine caused by expression of bacteriophage T3 S-adenosylmethionine hydrolase result in a marked reduction in autoinducer synthesis, thus providing direct in vivo evidence that the homoserine lactone ring of LuxI-family autoinducers is derived from S-adenosylmethionine. PMID:9573148

  18. Occurrence of lipid A variants with 27-hydroxyoctacosanoic acid in lipopolysaccharides from members of the family Rhizobiaceae

    SciTech Connect

    Bhat, U.R.; Carlson, R.W. ); Mayer, H. ); Yokota, A. ); Hollingsworth, R.I. )

    1991-04-01

    Lipopolysaccharides (LPSs) isolated from several strains of Rhizobium, Bradyrhizobium, Agrobacterium, and Azorhizobium were screened for the presence of 27-hydroxyoctacosanoic acid. The LPSs from all strains, with the exception of Azorhizobium caulinodans, contained various amounts of this long-chain hydroxy fatty acid in the lipid A fractions. Analysis of the lipid A sugars revealed three types of backbones: those containing glucosamine (as found in Rhizobium meliloti and Thizobium fredii), those containing glucosamine and galacturonic acid (as found in Rhizobium leguminosarum bv. phaseoli, trifolii, and viciae), and those containing clucosamine and galacturonic acid (as found in Rhizobium leguminosarum bv. phaseoli, trifolii, and viciae), and those containing 2,3-diamino-2,3-dideoxyglucose either alone or in combination with glucosamine (as found in Bradyrhizobium japonicum and Bradyrhizobium sp. (Lupinus) strain DSM 30140). The distribution of 27-hydroxyoctacosamoic acid as well as analysis of lipid A backbone sugars revealed the taxonomic relatedness of various strains of the Rhizobiaceae.

  19. Accurate Mass GC/LC-Quadrupole Time of Flight Mass Spectrometry Analysis of Fatty Acids and Triacylglycerols of Spicy Fruits from the Apiaceae Family

    PubMed Central

    Nguyen, Thao; Aparicio, Mario; Saleh, Mahmoud A.

    2016-01-01

    The triacylglycerol (TAG) structure and the regio-stereospecific distribution of fatty acids (FA) of seed oils from most of the Apiaceae family are not well documented. The TAG structure ultimately determines the final physical properties of the oils and the position of FAs in the TAG molecule affects the digestion; absorption and metabolism; and physical and technological properties of TAGs. Fixed oils from the fruits of dill (Anethum graveolens), caraway (Carum carvi), cumin (Cuminum cyminum), coriander (Coriandrum sativum), anise (Pimpinella anisum), carrot (Daucus carota), celery (Apium graveolens), fennel (Foeniculum vulgare), and Khella (Ammi visnaga), all from the Apiaceae family, were extracted at room temperature in chloroform/methanol (2:1 v/v) using percolators. Crude lipids were fractionated by solid phase extraction to separate neutral triacylglycerols (TAGs) from other lipids components. Neutral TAGs were subjected to transesterification process to convert them to their corresponding fatty acids methyl esters (FAMES) using 1% boron trifluoride (BF3) in methanol. FAMES were analyzed by gas chromatography-quadrupole time of flight (GC-QTOF) mass spectrometry. Triglycerides were analyzed using high performance liquid chromatography-quadrupole time of flight (LC-QTOF) mass spectrometry. Petroselinic acid was the major fatty acid in all samples ranging from 57% of the total fatty acids in caraway up to 82% in fennel. All samples contained palmitic (16:0), palmitoleic (C16:1n-9), stearic (C18:0), petroselinic (C18:1n-12), linoleic (C18:2n-6), linolinic (18:3n-3), and arachidic (C20:0) acids. TAG were analyzed using LC-QTOF for accurate mass identification and mass spectrometry/mass spectrometry (MS/MS) techniques for regiospesific elucidation of the identified TAGs. Five major TAGs were detected in all samples but with different relative concentrations in all of the tested samples. Several other TAGs were detected as minor components and were present in

  20. Accurate Mass GC/LC-Quadrupole Time of Flight Mass Spectrometry Analysis of Fatty Acids and Triacylglycerols of Spicy Fruits from the Apiaceae Family.

    PubMed

    Nguyen, Thao; Aparicio, Mario; Saleh, Mahmoud A

    2015-12-02

    The triacylglycerol (TAG) structure and the regio-stereospecific distribution of fatty acids (FA) of seed oils from most of the Apiaceae family are not well documented. The TAG structure ultimately determines the final physical properties of the oils and the position of FAs in the TAG molecule affects the digestion; absorption and metabolism; and physical and technological properties of TAGs. Fixed oils from the fruits of dill (Anethum graveolens), caraway (Carum carvi), cumin (Cuminum cyminum), coriander (Coriandrum sativum), anise (Pimpinella anisum), carrot (Daucus carota), celery (Apium graveolens), fennel (Foeniculum vulgare), and Khella (Ammi visnaga), all from the Apiaceae family, were extracted at room temperature in chloroform/methanol (2:1 v/v) using percolators. Crude lipids were fractionated by solid phase extraction to separate neutral triacylglycerols (TAGs) from other lipids components. Neutral TAGs were subjected to transesterification process to convert them to their corresponding fatty acids methyl esters (FAMES) using 1% boron trifluoride (BF₃) in methanol. FAMES were analyzed by gas chromatography-quadrupole time of flight (GC-QTOF) mass spectrometry. Triglycerides were analyzed using high performance liquid chromatography-quadrupole time of flight (LC-QTOF) mass spectrometry. Petroselinic acid was the major fatty acid in all samples ranging from 57% of the total fatty acids in caraway up to 82% in fennel. All samples contained palmitic (16:0), palmitoleic (C16:1n-9), stearic (C18:0), petroselinic (C18:1n-12), linoleic (C18:2n-6), linolinic (18:3n-3), and arachidic (C20:0) acids. TAG were analyzed using LC-QTOF for accurate mass identification and mass spectrometry/mass spectrometry (MS/MS) techniques for regiospesific elucidation of the identified TAGs. Five major TAGs were detected in all samples but with different relative concentrations in all of the tested samples. Several other TAGs were detected as minor components and were present in

  1. Association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families

    PubMed Central

    de Andrade, Mariza; Matsumoto, Martha; Mosley, Tom H.; Kardia, Sharon; Turner, Stephen T.

    2011-01-01

    Objectives. SLC2A9 gene variants associate with serum uric acid in white populations, but little is known about African American populations. Since SLC2A9 is a transporter, gene variants may be expected to associate more closely with the fractional excretion of urate, a measure of renal tubular transport, than with serum uric acid, which is influenced by production and extrarenal clearance. Methods. Genotypes of single nucleotide polymorphisms (SNPs) distributed across the SLC2A9 gene were obtained in the Genetic Epidemiology Network of Arteriopathy cohorts. The associations of SNPs with serum uric acid, fractional excretion of urate and urine urate-to-creatinine ratio were assessed with adjustments for age, sex, diuretic use, BMI, homocysteine and triglycerides. Results. We identified SLC2A9 gene variants that were associated with serum uric acid in 1155 African American subjects (53 SNPs) and 1132 white subjects (63 SNPs). The most statistically significant SNPs in African American subjects (rs13113918) and white subjects (rs11723439) were in the latter half of the gene and explained 2.7 and 2.8% of the variation in serum uric acid, respectively. After adjustment for this SNP in African Americans, 0.9% of the variation in serum uric acid was explained by an SNP (rs1568318) in the first half of the gene. Unexpectedly, SLC2A9 gene variants had stronger associations with serum uric acid than with fractional excretion of urate. Conclusions. These findings support two different loci by which SLC2A9 variants affect uric acid levels in African Americans and suggest SLC2A9 variants affect serum uric acid level via renal and extrarenal clearance. PMID:21186168

  2. Mutational Insights into the Roles of Amino Acid Residues in Ligand Binding for Two Closely Related Family 16 Carbohydrate Binding Modules

    SciTech Connect

    Su, Xiaoyun; Agarwal, Vinayak; Dodd, Dylan; Bae, Brian; Mackie, Roderick I.; Nair, Satish K.; Cann, Isaac K.O.

    2010-11-22

    Carbohydrate binding modules (CBMs) are specialized proteins that bind to polysaccharides and oligosaccharides. Caldanaerobius polysaccharolyticus Man5ACBM16-1/CBM16-2 bind to glucose-, mannose-, and glucose/mannose-configured substrates. The crystal structures of the two proteins represent the only examples in CBM family 16, and studies that evaluate the roles of amino acid residues in ligand binding in this family are lacking. In this study, we probed the roles of amino acids (selected based on CBM16-1/ligand co-crystal structures) on substrate binding. Two tryptophan (Trp-20 and Trp-125) and two glutamine (Gln-81 and Gln-93) residues are shown to be critical in ligand binding. Additionally, several polar residues that flank the critical residues also contribute to ligand binding. The CBM16-1 Q121E mutation increased affinity for all substrates tested, whereas the Q21G and N97R mutants exhibited decreased substrate affinity. We solved CBM/substrate co-crystal structures to elucidate the molecular basis of the increased substrate binding by CBM16-1 Q121E. The Gln-121, Gln-21, and Asn-97 residues can be manipulated to fine-tune ligand binding by the Man5A CBMs. Surprisingly, none of the eight residues investigated was absolutely conserved in CBM family 16. Thus, the critical residues in the Man5A CBMs are either not essential for substrate binding in the other members of this family or the two CBMs are evolutionarily distinct from the members available in the current protein database. Man5A is dependent on its CBMs for robust activity, and insights from this study should serve to enhance our understanding of the interdependence of its catalytic and substrate binding modules.

  3. The ALMT Family of Organic Acid Transporters in Plants and Their Involvement in Detoxification and Nutrient Security.

    PubMed

    Sharma, Tripti; Dreyer, Ingo; Kochian, Leon; Piñeros, Miguel A

    2016-01-01

    About a decade ago, members of a new protein family of anion channels were discovered on the basis of their ability to confer on plants the tolerance toward toxic aluminum ions in the soil. The efflux of Al(3+)-chelating malate anions through these channels is stimulated by external Al(3+) ions. This feature of a few proteins determined the name of the entire protein family as Aluminum-activated Malate Transporters (ALMT). Meanwhile, after several years of research, it is known that the physiological roles of ALMTs go far beyond Al-detoxification. In this review article we summarize the current knowledge on this transporter family and assess their involvement in diverse physiological processes.

  4. The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond.

    PubMed

    Fedeles, Bogdan I; Singh, Vipender; Delaney, James C; Li, Deyu; Essigmann, John M

    2015-08-21

    The AlkB family of Fe(II)- and α-ketoglutarate-dependent dioxygenases is a class of ubiquitous direct reversal DNA repair enzymes that remove alkyl adducts from nucleobases by oxidative dealkylation. The prototypical and homonymous family member is an Escherichia coli "adaptive response" protein that protects the bacterial genome against alkylation damage. AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. Nine mammalian AlkB homologs exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes. This minireview presents an overview of the AlkB proteins including recent data on homologs, structural features, substrate specificities, and experimental strategies for studying DNA repair by AlkB family proteins.

  5. The ALMT Family of Organic Acid Transporters in Plants and Their Involvement in Detoxification and Nutrient Security

    PubMed Central

    Sharma, Tripti; Dreyer, Ingo; Kochian, Leon; Piñeros, Miguel A.

    2016-01-01

    About a decade ago, members of a new protein family of anion channels were discovered on the basis of their ability to confer on plants the tolerance toward toxic aluminum ions in the soil. The efflux of Al3+-chelating malate anions through these channels is stimulated by external Al3+ ions. This feature of a few proteins determined the name of the entire protein family as Aluminum-activated Malate Transporters (ALMT). Meanwhile, after several years of research, it is known that the physiological roles of ALMTs go far beyond Al-detoxification. In this review article we summarize the current knowledge on this transporter family and assess their involvement in diverse physiological processes. PMID:27757118

  6. The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond*

    PubMed Central

    Fedeles, Bogdan I.; Singh, Vipender; Delaney, James C.; Li, Deyu; Essigmann, John M.

    2015-01-01

    The AlkB family of Fe(II)- and α-ketoglutarate-dependent dioxygenases is a class of ubiquitous direct reversal DNA repair enzymes that remove alkyl adducts from nucleobases by oxidative dealkylation. The prototypical and homonymous family member is an Escherichia coli “adaptive response” protein that protects the bacterial genome against alkylation damage. AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. Nine mammalian AlkB homologs exist (ALKBH1–8, FTO), but only a subset functions as DNA/RNA repair enzymes. This minireview presents an overview of the AlkB proteins including recent data on homologs, structural features, substrate specificities, and experimental strategies for studying DNA repair by AlkB family proteins. PMID:26152727

  7. Base non-specific acid ribonuclease from Irpex lacteus, primary structure and phylogenetic relationships in RNase T2 family enzyme.

    PubMed

    Watanabe, H; Fauzi, H; Iwama, M; Onda, T; Ohgi, K; Irie, M

    1995-11-01

    Two base non-specific acid RNases (RNase Irp1 and RNase Irp2) were purified from a commercial enzyme, "Driselase" (Irpex lacteus) in a homogenous state on SDS-PAGE by several steps of chromatographic separations. RNAse Irp2 was a simple polypeptide with 235 amino acid residues and RNase Irp1 was a glycopeptide with 248 amino acid residues. The amino acid sequences of both RNases were identified by Edman degradation of the peptides derived from these RNAses. RNase Irp1 was composed of the RNase Irp2 and extra C-terminal 13 residues of peptide. The phylogenetic relation of these RNases with the other fungal RNases already known was discussed. The sequence of RNase Irp2 was very highly homologous (67.5%) with that of RNase Le2 from Lentinus edodes.

  8. Expression patterns of Brassica napus genes implicate IPT, CKX, sucrose transporter, cell wall invertase, and amino acid permease gene family members in leaf, flower, silique, and seed development.

    PubMed

    Song, Jiancheng; Jiang, Lijun; Jameson, Paula Elizabeth

    2015-08-01

    Forage brassica (Brassica napus cv. Greenland) is bred for vegetative growth and biomass production, while its seed yield remains to be improved for seed producers without affecting forage yield and quality. Cytokinins affect seed yield by influencing flower, silique and seed number, and seed size. To identify specific cytokinin gene family members as targets for breeding, as well as genes associated with yield and/or quality, a B. napus transcriptome was obtained from a mixed sample including leaves, flower buds and siliques of various stages. Gene families for cytokinin biosynthesis (BnIPT1, 2, 3, 5, 7, 8 and 9), cytokinin degradation (BnCKX1 to BnCKX7), cell wall invertase (BnCWINV1 to BnCWINV6), sugar transporter (BnSUT1 to BnSUT6) and amino acid permease (BnAAP1 to BnAAP8) were identified. As B. napus is tetraploid, homoeologues of each gene family member were sought. Using multiple alignments and phylogenetic analysis, the parental genomes of the two B. napus homoeologues could be differentiated. RT-qPCR was then used to determine the expression of gene family members and their homoeologues in leaves, flowers, siliques and seeds of different developmental stages. The expression analysis showed both temporal and organ-specific expression profiles among members of these multi-gene families. Several pairs of homoeologues showed differential expression, both in terms of level of expression and differences in temporal or organ-specificity. BnCKX2 and 4 were identified as targets for TILLING, EcoTILLING and MAS. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  9. Expression patterns of Brassica napus genes implicate IPT, CKX, sucrose transporter, cell wall invertase, and amino acid permease gene family members in leaf, flower, silique, and seed development

    PubMed Central

    Song, Jiancheng; Jiang, Lijun; Jameson, Paula Elizabeth

    2015-01-01

    Forage brassica (Brassica napus cv. Greenland) is bred for vegetative growth and biomass production, while its seed yield remains to be improved for seed producers without affecting forage yield and quality. Cytokinins affect seed yield by influencing flower, silique and seed number, and seed size. To identify specific cytokinin gene family members as targets for breeding, as well as genes associated with yield and/or quality, a B. napus transcriptome was obtained from a mixed sample including leaves, flower buds and siliques of various stages. Gene families for cytokinin biosynthesis (BnIPT1, 2, 3, 5, 7, 8 and 9), cytokinin degradation (BnCKX1 to BnCKX7), cell wall invertase (BnCWINV1 to BnCWINV6), sugar transporter (BnSUT1 to BnSUT6) and amino acid permease (BnAAP1 to BnAAP8) were identified. As B. napus is tetraploid, homoeologues of each gene family member were sought. Using multiple alignments and phylogenetic analysis, the parental genomes of the two B. napus homoeologues could be differentiated. RT-qPCR was then used to determine the expression of gene family members and their homoeologues in leaves, flowers, siliques and seeds of different developmental stages. The expression analysis showed both temporal and organ-specific expression profiles among members of these multi-gene families. Several pairs of homoeologues showed differential expression, both in terms of level of expression and differences in temporal or organ-specificity. BnCKX2 and 4 were identified as targets for TILLING, EcoTILLING and MAS. PMID:25873685

  10. CCCH-type zinc finger family in maize: genome-wide identification, classification and expression profiling under abscisic acid and drought treatments.

    PubMed

    Peng, Xiaojian; Zhao, Yang; Cao, Jiangang; Zhang, Wei; Jiang, Haiyang; Li, Xiaoyu; Ma, Qing; Zhu, Suwen; Cheng, Beijiu

    2012-01-01

    CCCH-type zinc finger proteins comprise a large protein family. Increasing evidence suggests that members of this family are RNA-binding proteins with regulatory functions in mRNA processing. Compared with those in animals, functions of CCCH-type zinc finger proteins involved in plant growth and development are poorly understood. Here, we performed a genome-wide survey of CCCH-type zinc finger genes in maize (Zea mays L.) by describing the gene structure, phylogenetic relationships and chromosomal location of each family member. Promoter sequences and expression profiles of putative stress-responsive members were also investigated. A total of 68 CCCH genes (ZmC3H1-68) were identified in maize and divided into seven groups by phylogenetic analysis. These 68 genes were found to be unevenly distributed on 10 chromosomes with 15 segmental duplication events, suggesting that segmental duplication played a major role in expansion of the maize CCCH family. The Ka/Ks ratios suggested that the duplicated genes of the CCCH family mainly experienced purifying selection with limited functional divergence after duplication events. Twelve maize CCCH genes grouped with other known stress-responsive genes from Arabidopsis were found to contain putative stress-responsive cis-elements in their promoter regions. Seven of these genes chosen for further quantitative real-time PCR analysis showed differential expression patterns among five representative maize tissues and over time in response to abscisic acid and drought treatments. The results presented in this study provide basic information on maize CCCH proteins and form the foundation for future functional studies of these proteins, especially for those members of which may play important roles in response to abiotic stresses.

  11. A genome-wide analysis of the auxin/indole-3-acetic acid gene family in hexaploid bread wheat (Triticum aestivum L.).

    PubMed

    Qiao, Linyi; Zhang, Xiaojun; Han, Xiao; Zhang, Lei; Li, Xin; Zhan, Haixian; Ma, Jian; Luo, Peigao; Zhang, Wenping; Cui, Lei; Li, Xiaoyan; Chang, Zhijian

    2015-01-01

    The Auxin/indole-3-acetic acid (Aux/IAA) gene family plays key roles in the primary auxin-response process and controls a number of important traits in plants. However, the characteristics of the Aux/IAA gene family in hexaploid bread wheat (Triticum aestivum L.) have long been unknown. In this study, a comprehensive identification of the Aux/IAA gene family was performed using the latest draft genome sequence of the bread wheat "Chinese Spring." Thirty-four Aux/IAA genes were identified, 30 of which have duplicated genes on the A, B or D sub-genome, with a total of 84 Aux/IAA sequences. These predicted Aux/IAA genes were non-randomly distributed in all the wheat chromosomes except for chromosome 2D. The information of wheat Aux/IAA proteins is also described. Based on an analysis of phylogeny, expression and adaptive evolution, we prove that the Aux/IAA family in wheat has been replicated twice in the two allopolyploidization events of bread wheat, when the tandem duplication also occurred. The duplicated genes have undergone an evolutionary process of purifying selection, resulting in the high conservation of copy genes among sub-genomes and functional redundancy among several members of the TaIAA family. However, functional divergence probably existed in most TaIAA members due to the diversity of the functional domain and expression pattern. Our research provides useful information for further research into the function of Aux/IAA genes in wheat.

  12. The ALMT family of organic acid transporters in plants and their involvement in detoxification and nutrient security

    USDA-ARS?s Scientific Manuscript database

    About a decade ago, members of a new protein family of anion channels were discovered on the basis of their ability to confer on plants the tolerance towards toxic aluminum ions in the soil. The efflux of Al3+ chelating malate anions through these channels is stimulated by external Al3+ ions. This f...

  13. Silencing of BnTT1 family genes affects seed flavonoid biosynthesis and alters seed fatty acid composition in Brassica napus.

    PubMed

    Lian, Jianping; Lu, Xiaochun; Yin, Nengwen; Ma, Lijuan; Lu, Jing; Liu, Xue; Li, Jiana; Lu, Jun; Lei, Bo; Wang, Rui; Chai, Yourong

    2017-01-01

    TRANSPARENT TESTA1 (TT1) is a zinc finger protein that contains a WIP domain. It plays important roles in controlling differentiation and pigmentation of the seed coat endothelium, and can affect the expression of early biosynthetic genes and late biosynthetic genes of flavonoid biosynthesis in Arabidopsis thaliana. In Brassica napus (AACC, 2n=38), the functions of BnTT1 genes remain unknown and few studies have focused on their roles in fatty acid (FA) biosynthesis. In this study, BnTT1 family genes were silenced by RNA interference, which resulted in yellow rapeseed, abnormal testa development (a much thinner testa), decreased seed weight, and altered seed FA composition in B. napus. High-throughput sequencing of genes differentially expressed between developing transgenic B. napus and wild-type seeds revealed altered expression of numerous genes involved in flavonoid and FA biosynthesis. As a consequence of this altered expression, we detected a marked decrease of oleic acid (C18:1) and notable increases of linoleic acid (C18:2) and α-linolenic acid (C18:3) in mature transgenic B. napus seeds by gas chromatography and near-infrared reflectance spectroscopy. Meanwhile, liquid chromatography-mass spectrometry showed reduced accumulation of flavonoids in transgenic seeds. Therefore, we propose that BnTT1s are involved in the regulation of flavonoid biosynthesis, and may also play a role in FA biosynthesis in B. napus. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Association of dietary omega-3 fatty acids with prevalence of metabolic syndrome: the National Heart, Lung, and Blood Institute Family Heart Study.

    PubMed

    Lai, Y H Lana; Petrone, Andrew B; Pankow, James S; Arnett, Donna K; North, Kari E; Ellison, R Curtis; Hunt, Steven C; Djoussé, Luc

    2013-12-01

    Metabolic syndrome (MetS), characterized by abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, and insulin resistance is a major public health concern in the United States. Omega-3 fatty acids have been relatively well studied in relation to many individual cardiovascular risk factors; however, their effects on MetS are not well established. We conducted a cross-sectional study consisting of 4941 participants from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study to assess the relation of dietary omega-3 fatty acids with the prevalence of MetS. Omega-3 intake was assessed using a food frequency questionnaire and we used generalized estimating equations to estimate adjusted odds ratios for prevalent MetS. Our study population had a mean age (SD) of 52.1 (13.9) years and 45.9% were men. The mean (SD) of dietary omega-3 fatty acids was 0.25 g/day (0.27). From the lowest to the highest quintile of dietary omega-3 fatty acids, multivariable adjusted ORs (95% CI) for MetS were 1.00 (ref), 0.90 (0.72-1.13), 1.03 (0.82-1.28), 0.94 (0.74-1.18), and 0.99 (0.77-1.25), respectively. In a secondary analysis, neither fish consumption nor dietary alpha-linolenic acid was associated with MetS. Our findings do not support an association between dietary omega-3 fatty acids and MetS in a large US population. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. The role of trefoil factor family in apparently healthy subjects administrated gastroprotective agents for the primary prevention of gastrointestinal injuries from low-dose acetylsalicylic acid: a preliminary study.

    PubMed

    Kawai, Takashi; Takagi, Yu; Fukuzawa, Mari; Yamagishi, Tetsuya; Goto, Shinya

    2011-09-01

    It is well-known that acetylsalicylic acid induces gastrointestinal complication. Recently, trefoil factor family has been reported as a mucosal protective factor. We focused on trefoil factor family as one of defensive system for gastrointestinal injuries. The aim of this trial was to evaluate trefoil factor family levels in the serum of healthy subjects with low-dose acetylsalicylic acid. Low-dose acetylsalicylic acid with placebo or proton pump inhibitor or rebamipide were administered in 30 healthy subjects. Transnasal endoscopy was performed at 0, 24 h, 3 and 7 day. Changing of trefoil factor family (1,2,3) and numbers of gastric injuries were evaluated. The numbers of gastric injuries were significantly increased in the placebo group at 3 and 7 days. Injuries in the proton pump inhibitor group were not induced, in the rebamipide group were slightly induced. Trefoil factor family level in the placebo group were decreased in 3 and 7 days compared with prior to starting the trial. Trefoil factor family may have an important association with acetylsalicylic acid-induced gastrointestinal damage. Proton pump inhibitor and rebamipide prevented low-dose acetylsalicylic acid-induced gastrointestinal complications compared with the placebo group.

  16. Genome-wide identification and expression profiling of the fatty acid desaturase gene family in the silkworm, Bombyx mori.

    PubMed

    Chen, Q M; Cheng, D J; Liu, S P; Ma, Z G; Tan, X; Zhao, P

    2014-05-13

    Fatty acid desaturases exist in all living organisms and play important roles in many different biologic processes, such as fatty acid metabolism, lipid biosynthetic processes, and pheromone biosynthetic processes. Using the available silkworm genome sequence, we identified 14 candidate fatty acid desaturase genes. Eleven genes contain 3 conserved histidine cluster motifs and 4 transmembrane domains, but their N-terminal residues exhibit obvious diversity. Phylogenetic analysis revealed that there are 6 groups; Bmdesat1 and Bmdesat5-8 were clustered into group 2, which is involved in Δ11 desaturation activity, and Bmdesat3-4 were grouped in group 1, which is involved in Δ9 desaturation activity. Twelve of the 14 genes have expressed sequence tag evidence. Microarray data and reverse transcription polymerase chain reaction analysis demonstrated that Bmdesat3-4 and Bmdesat10 were expressed from the larval to moth stages and in multiple tissues on day 3 of 5th instar larvae. Bmdesat9, Bmdesat11, and Bmdesat14 were expressed during the pupal and late-embryonic stage, suggesting that they may take part in fatty acid metabolism to provide energy. These results provide some insights into the functions of individual fatty acid desaturases in silkworm.

  17. Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) contributes to retinoic acid-induced differentiation of leukemic cells

    SciTech Connect

    Yu, Yun; Shen, Shao-Ming; Zhang, Fei-Fei; Wu, Zhao-Xia; Han, Bin; Wang, Li-Shun

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer ANP32B was down-regulated during ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Knockdown of ANP32B enhanced ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer Ectopic expression of ANP32B inhibited ATRA-induced leukemic cell differentiation. Black-Right-Pointing-Pointer ANP32B inhibited ATRA activated transcriptional activity of RAR{alpha}. -- Abstract: The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is a member of a conserved superfamily of nuclear proteins whose functions are largely unknown. In our previous work, ANP32B was identified as a novel direct substrate for caspase-3 and acted as a negative regulator for leukemic cell apoptosis. In this work, we provided the first demonstration that ANP32B expression was down-regulated during differentiation induction of leukemic cells by all-trans retinoic acid (ATRA). Knockdown of ANP32B expression by specific shRNA enhanced ATRA-induced leukemic cell differentiation, while ectopic expression of ANP32B attenuated it, indicating an inhibitory role of ANP32B against leukemic cell differentiation. Furthermore, luciferase reporter assay revealed that ANP32B might exert this role through inhibiting the ATRA dependent transcriptional activity of retinoic acid receptor (RAR{alpha}). These data will shed new insights into understanding the biological functions of ANP32B protein.

  18. The Crystal Structure of Rv0813c from Mycobacterium tuberculosis Reveals a New Family of Fatty Acid-Binding Protein-Like Proteins in Bacteria▿

    PubMed Central

    Shepard, William; Haouz, Ahmed; Graña, Martin; Buschiazzo, Alejandro; Betton, Jean-Michel; Cole, Stewart T.; Alzari, Pedro M.

    2007-01-01

    The gene Rv0813c from Mycobacterium tuberculosis, which codes for a hypothetical protein of unknown function, is conserved within the order Actinomycetales but absent elsewhere. The crystal structure of Rv0813c reveals a new family of proteins that resemble the fatty acid-binding proteins (FABPs) found in eukaryotes. Rv0813c adopts the 10-stranded β-barrel fold typical of FABPs but lacks the double-helix insert that covers the entry to the binding site in the eukaryotic proteins. The barrel encloses a deep cavity, at the bottom of which a small cyclic ligand was found to bind to the hydroxyl group of Tyr192. This residue is part of a conserved Arg-X-Tyr motif much like the triad that binds the carboxylate group of fatty acids in FABPs. Most of the residues forming the internal surface of the cavity are conserved in homologous protein sequences found in CG-rich prokaryotes, strongly suggesting that Rv0813c is a member of a new family of bacterial FABP-like proteins that may have roles in the recognition, transport, and/or storage of small molecules in the bacterial cytosol. PMID:17172346

  19. Transcriptome atlas of aromatic amino acid family metabolism-related genes in eight liver cell types uncovers the corresponding metabolic pathways in rat liver regeneration.

    PubMed

    Chang, Cuifang; Xu, CunShuan

    2010-10-01

    To explore gene expression of aromatic amino acid family metabolism and their metabolic pathways of eight liver cell types in rat liver regeneration, eight kinds of rat regenerating liver cells were isolated by using the combination of percoll density gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2.0 Array was used to detect the expression changes of genes associated with aromatic amino acid family metabolism. The transcriptome atlas showed that the metabolic pathway of phenylalanine was mainly catalyzed into tyrosine in hepatic stellate cells in the initiation stage, tyrosine was oxidized into dopa and norepinephrine in biliary epithelia cells and dendritic cells, and norepinephrine was finally catalyzed into adrenaline in biliary epithelia cells and pit cells in the progress stage. Thyroid hormone of tyrosine catabolites was synthesized from tyrosine in almost all cells in different stage of LR, among which genes of T3 biosynthesis were increased in HCs, BECs, SECs and DCs in the progress stage. Tryptophan was decarboxylated to 5-hydroxytryptamine in dendritic cells in the progress stage. Based on the results as above, we concluded that phenylalanine is the major source of tyrosine, proliferation of biliary epithelia cells and dendritic cells maybe promote by tyrosine catabolites-dopa and norepinephrine, biliary epithelia cells and pit cells maybe promote by adrenaline. T3 maybe play a major role on proliferation of HCs, BECs, SECs and DCs in the progress stage. The proliferation of dendritic cells maybe promote by tryptophan catabolites-5-hydroxytryptamine. Copyright 2010. Published by Elsevier Ltd.

  20. The maize (Zea mays L.) AUXIN/INDOLE-3-ACETIC ACID gene family: phylogeny, synteny, and unique root-type and tissue-specific expression patterns during development.

    PubMed

    Ludwig, Yvonne; Zhang, Yanxiang; Hochholdinger, Frank

    2013-01-01

    The plant hormone auxin plays a key role in the coordination of many aspects of growth and development. AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) genes encode instable primary auxin responsive regulators of plant development that display a protein structure with four characteristic domains. In the present study, a comprehensive analysis of the 34 members of the maize Aux/IAA gene family was performed. Phylogenetic reconstructions revealed two classes of Aux/IAA proteins that can be distinguished by alterations in their domain III. Seven pairs of paralogous maize Aux/IAA proteins were discovered. Comprehensive root-type and tissue-specific expression profiling revealed unique expression patterns of the diverse members of the gene family. Remarkably, five of seven pairs of paralogous genes displayed highly correlated expression patterns in roots. All but one (ZmIAA23) tested maize Aux/IAA genes were auxin inducible, displaying two types of auxin induction within three hours of treatment. Moreover, 51 of 55 (93%) differential Aux/IAA expression patterns between different root-types followed the expression tendency: crown roots > seminal roots > primary roots > lateral roots. This pattern might imply root-type-specific regulation of Aux/IAA transcript abundance. In summary, the detailed analysis of the maize Aux/IAA gene family provides novel insights in the evolution and developmental regulation and thus the function of these genes in different root-types and tissues.

  1. Structural, Biochemical, and Phylogenetic Analyses Suggest That Indole-3-Acetic Acid Methyltransferase Is an Evolutionarily Ancient Member of the SABATH Family

    SciTech Connect

    Zhao,N.; Ferrer, J.; Ross, J.; Guan, J.; Yang, Y.; Pichersky, E.; Noel, J.; Chen, F.

    2008-01-01

    The plant SABATH protein family encompasses a group of related small-molecule methyltransferases (MTs) that catalyze the S-adenosyl-L-methionine-dependent methylation of natural chemicals encompassing widely divergent structures. Indole-3-acetic acid (IAA) methyltransferase (IAMT) is a member of the SABATH family that modulates IAA homeostasis in plant tissues through methylation of IAA's free carboxyl group. The crystal structure of Arabidopsis (Arabidopsis thaliana) IAMT (AtIAMT1) was determined and refined to 2.75 Angstroms resolution. The overall tertiary and quaternary structures closely resemble the two-domain bilobed monomer and the dimeric arrangement, respectively, previously observed for the related salicylic acid carboxyl methyltransferase from Clarkia breweri (CbSAMT). To further our understanding of the biological function and evolution of SABATHs, especially of IAMT, we analyzed the SABATH gene family in the rice (Oryza sativa) genome. Forty-one OsSABATH genes were identified. Expression analysis showed that more than one-half of the OsSABATH genes were transcribed in one or multiple organs. The OsSABATH gene most similar to AtIAMT1 is OsSABATH4. Escherichia coli-expressed OsSABATH4 protein displayed the highest level of catalytic activity toward IAA and was therefore named OsIAMT1. OsIAMT1 exhibited kinetic properties similar to AtIAMT1 and poplar IAMT (PtIAMT1). Structural modeling of OsIAMT1 and PtIAMT1 using the experimentally determined structure of AtIAMT1 reported here as a template revealed conserved structural features of IAMTs within the active-site cavity that are divergent from functionally distinct members of the SABATH family, such as CbSAMT. Phylogenetic analysis revealed that IAMTs from Arabidopsis, rice, and poplar (Populus spp.) form a monophyletic group. Thus, structural, biochemical, and phylogenetic evidence supports the hypothesis that IAMT is an evolutionarily ancient member of the SABATH family likely to play a critical role in

  2. A Novel Uncultured Bacterium of the Family Gallionellaceae: Description and Genome Reconstruction Based on the Metagenomic Analysis of Microbial Community in Acid Mine Drainage.

    PubMed

    Kadnikov, V V; Ivasenko, D A; Beletsky, A V; Mardanov, A V; Danilova, E V; Pimenov, N V; Karnachuk, O V; Ravin, N V

    2016-07-01

    Drainage waters at the metal mining areas often have low pH and high content of dissolved metals due to oxidation of sulfide minerals. Extreme conditions limit microbial diversity in- such ecosystems. A drainage water microbial community (6.5'C, pH 2.65) in an open pit at the Sherlovaya Gora polymetallic open-cast mine (Transbaikal region, Eastern Siberia, Russia) was studied using metagenomic techniques. Metagenome sequencing provided information for taxonomic and functional characterization of the micro- bial community. The majority of microorganisms belonged to a single uncultured lineage representing a new Betaproteobacteria species of the genus Gallionella. While no.acidophiles are known among the cultured members of the family Gallionellaceae, similar 16S rRNA gene sequences were detected in acid mine drain- ages. Bacteria ofthe genera Thiobacillus, Acidobacterium, Acidisphaera, and Acidithiobacillus,-which are com- mon in acid mine drainage environments, were the minor components of the community. Metagenomic data were -used to determine the almost complete (-3.4 Mb) composite genome of the new bacterial. lineage desig- nated Candidatus Gallionella acididurans ShG14-8. Genome analysis revealed that Fe(II) oxidation probably involved the cytochromes localized on the outer membrane of the cell. The electron transport chain included NADH dehydrogenase, a cytochrome bc1 complex, an alternative complex III, and cytochrome oxidases of the bd, cbb3, and bo3 types. Oxidation of reduced sulfur compounds probably involved the Sox system, sul- fide-quinone oxidoreductase, adenyl sulfate reductase, and sulfate adenyltransferase. The genes required for autotrophic carbon assimilation via the Calvin cycle were present, while no pathway for nitrogen fixation was revealed. High numbers of RND metal transporters and P type ATPases were probably responsible for resis- tance to heavy metals. The new microorganism was an aerobic chemolithoautotroph of the group of

  3. N-acetylglucosaminidases from CAZy family GH3 are really glycoside phosphorylases, thereby explaining their use of histidine as an acid/base catalyst in place of glutamic acid.

    PubMed

    Macdonald, Spencer S; Blaukopf, Markus; Withers, Stephen G

    2015-02-20

    CAZy glycoside hydrolase family GH3 consists primarily of stereochemistry-retaining β-glucosidases but also contains a subfamily of β-N-acetylglucosaminidases. Enzymes from this subfamily were recently shown to use a histidine residue within a His-Asp dyad contained in a signature sequence as their catalytic acid/base residue. Reasons for their use of His rather than the Glu or Asp found in other glycosidases were not apparent. Through studies on a representative member, the Nag3 β-N-acetylglucosaminidase from Cellulomonas fimi, we now show that these enzymes act preferentially as glycoside phosphorylases. Their need to accommodate an anionic nucleophile within the enzyme active site explains why histidine is used as an acid/base catalyst in place of the anionic glutamate seen in other GH3 family members. Kinetic and mechanistic studies reveal that these enzymes also employ a double-displacement mechanism involving a covalent glycosyl-enzyme intermediate, which was directly detected by mass spectrometry. Phosphate has no effect on the rates of formation of the glycosyl-enzyme intermediate, but it accelerates turnover of the N-acetylglucosaminyl-enzyme intermediate ∼3-fold, while accelerating turnover of the glucosyl-enzyme intermediate several hundredfold. These represent the first reported examples of retaining β-glycoside phosphorylases, and the first instance of free β-GlcNAc-1-phosphate in a biological context. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Mutational analysis of amino acid residues involved in catalytic activity of a family 18 chitinase from tulip bulbs.

    PubMed

    Suzukawa, Keisuke; Yamagami, Takeshi; Ohnuma, Takayuki; Hirakawa, Hideki; Kuhara, Satoru; Aso, Yoichi; Ishiguro, Masatsune

    2003-02-01

    We expressed chitinase-1 (TBC-1) from tulip bulbs (Tulipa bakeri) in E. coli cells and used site-directed mutagenesis to identify amino acid residues essential for catalytic activity. Mutations at Glu-125 and Trp-251 completely abolished enzyme activity, and activity decreased with mutations at Asp-123 and Trp-172 when glycolchitin was the substrate. Activity changed with the mutations of Trp-251 to one of several amino acids with side-chains of little hydrophobicity, suggesting that hydrophobic interaction of Trp-251 is important for the activity. Molecular dynamics (MD) simulation analysis with hevamine as the model compound showed that the distance between Asp-123 and Glu-125 was extended by mutation of Trp-251. Kinetic studies of Trp-251-mutated chitinases confirmed these various phenomena. The results suggested that Glu-125 and Trp-251 are essential for enzyme activity and that Trp-251 had a direct role in ligand binding.

  5. Characterization of the Branched-Chain Amino Acid Aminotransferase Enzyme Family in Tomato1[W][OA

    PubMed Central

    Maloney, Gregory S.; Kochevenko, Andrej; Tieman, Denise M.; Tohge, Takayuki; Krieger, Uri; Zamir, Dani; Taylor, Mark G.; Fernie, Alisdair R.; Klee, Harry J.

    2010-01-01

    Branched-chain amino acids (BCAAs) are synthesized in plants from branched-chain keto acids, but their metabolism is not completely understood. The interface of BCAA metabolism lies with branched-chain aminotransferases (BCAT) that catalyze both the last anabolic step and the first catabolic step. In this study, six BCAT genes from the cultivated tomato (Solanum lycopersicum) were identified and characterized. SlBCAT1, -2, -3, and -4 are expressed in multiple plant tissues, while SlBCAT5 and -6 were undetectable. SlBCAT1 and -2 are located in the mitochondria, SlBCAT3 and -4 are located in chloroplasts, while SlBCAT5 and -6 are located in the cytosol and vacuole, respectively. SlBCAT1, -2, -3, and -4 were able to restore growth of Escherichia coli BCAA auxotrophic cells, but SlBCAT1 and -2 were less effective than SlBCAT3 and -4 in growth restoration. All enzymes were active in the forward (BCAA synthesis) and reverse (branched-chain keto acid synthesis) reactions. SlBCAT3 and -4 exhibited a preference for the forward reaction, while SlBCAT1 and -2 were more active in the reverse reaction. While overexpression of SlBCAT1 or -3 in tomato fruit did not significantly alter amino acid levels, an expression quantitative trait locus on chromosome 3, associated with substantially higher expression of Solanum pennellii BCAT4, did significantly increase BCAA levels. Conversely, antisense-mediated reduction of SlBCAT1 resulted in higher levels of BCAAs. Together, these results support a model in which the mitochondrial SlBCAT1 and -2 function in BCAA catabolism while the chloroplastic SlBCAT3 and -4 function in BCAA synthesis. PMID:20435740

  6. Unravelling the Diversity of the Cyclopiazonic Acid Family of Mycotoxins in Aspergillus flavus by UHPLC Triple-TOF HRMS

    PubMed Central

    Uka, Valdet; Moore, Geromy G.; Arroyo-Manzanares, Natalia; Nebija, Dashnor; De Saeger, Sarah; Diana Di Mavungu, José

    2017-01-01

    Cyclopiazonic acid (α-cyclopiazonic acid, α-CPA) is an indole-hydrindane-tetramic acid neurotoxin produced by various fungal species, including the notorious food and feed contaminant Aspergillus flavus. Despite its discovery in A. flavus cultures approximately 40 years ago, its contribution to the A. flavus mycotoxin burden is consistently minimized by our focus on the more potent carcinogenic aflatoxins also produced by this fungus. Here, we report the screening and identification of several CPA-type alkaloids not previously found in A. flavus cultures. Our identifications of these CPA-type alkaloids are based on a dereplication strategy involving accurate mass high resolution mass spectrometry data and a careful study of the α-CPA fragmentation pattern. In total, 22 CPA-type alkaloids were identified in extracts from the A. flavus strains examined. Of these metabolites, 13 have been previously reported in other fungi, though this is the first report of their existence in A. flavus. Two of our metabolite discoveries, 11,12-dehydro α-CPA and 3-hydroxy-2-oxo CPA, have never been reported for any organism. The conspicuous presence of CPA and its numerous derivatives in A. flavus cultures raises concerns about the long-term and cumulative toxicological effects of these fungal secondary metabolites and their contributions to the entire A. flavus mycotoxin problem. PMID:28098779

  7. Random exchanges of non-conserved amino acid residues among four parental termite cellulases by family shuffling improved thermostability.

    PubMed

    Ni, Jinfeng; Takehara, Motomi; Miyazawa, Mitsuhiro; Watanabe, Hirofumi

    2007-11-01

    There have been two major problems preventing applications of termite cellulases; one was difficulty for their hetelologous overexpression, and another is their low thermostability. We previously achieved adaptation of termite cellulase genes to an overexpression system of Escherichia coli by family shuffling of four orthologous cDNAs (Biosci. Biotechnol. Biochem., 2005; 69: 1711-1720). Using the adapted mutant cDNAs as parental genes combined with native-form cDNAs, we performed further family shuffling and obtained mutant cDNAs, which gave enzymes with improved thermostability. The best-evolved clone (PA68) was improved by 10 degrees C in maximum stability (retaining 90% original activity for 30 min incubation) from the parental enzymes, and kept 54% of its original activity for 150 min at 50 degrees C, whereas the most thermostable enzyme amongst the parents (A18) retained 30% of its original activity. PA68 showed 889 (micromoles of reducing sugars/min/mg of protein) in V(max) and 560 (micromoles of reducing sugars/min/mg of protein) in the specific activity against carboxymethylcellulose, which corresponds to 9.8 and 13.1 times of those of one of the ancestral enzymes rRsEG. In summary, we improved thermostability of the termite cellulase and increased the V(max) value and specific activity by combining only cDNAs encoding enzymes adapted for normal temperatures.

  8. Proteomic Analyses Reveal an Acidic Prime Side Specificity for the Astacin Metalloprotease Family Reflected by Physiological Substrates*

    PubMed Central

    Becker-Pauly, Christoph; Barré, Olivier; Schilling, Oliver; auf dem Keller, Ulrich; Ohler, Anke; Broder, Claudia; Schütte, André; Kappelhoff, Reinhild; Stöcker, Walter; Overall, Christopher M.

    2011-01-01

    Astacins are secreted and membrane-bound metalloproteases with clear associations to many important pathological and physiological processes. Yet with only a few substrates described their biological roles are enigmatic. Moreover, the lack of knowledge of astacin cleavage site specificities hampers assay and drug development. Using PICS (proteomic identification of protease cleavage site specificity) and TAILS (terminal amine isotopic labeling of substrates) degradomics approaches >3000 cleavage sites were proteomically identified for five different astacins. Such broad coverage enables family-wide determination of specificities N- and C-terminal to the scissile peptide bond. Remarkably, meprin α, meprin β, and LAST_MAM proteases exhibit a strong preference for aspartate in the peptide (P)1′ position because of a conserved positively charged residue in the active cleft subsite (S)1′. This unparalleled specificity has not been found for other families of extracellular proteases. Interestingly, cleavage specificity is also strongly influenced by proline in P2′ or P3′ leading to a rare example of subsite cooperativity. This specificity characterizes the astacins as unique contributors to extracellular proteolysis that is corroborated by known cleavage sites in procollagen I+III, VEGF (vascular endothelial growth factor)-A, IL (interleukin)-1β, and pro-kallikrein 7. Indeed, cleavage sites in VEGF-A and pro-kallikrein 7 identified by terminal amine isotopic labeling of substrates matched those reported by Edman degradation. Moreover, the novel substrate FGF-19 was validated biochemically and shown to exhibit altered biological activity after meprin processing. PMID:21693781

  9. Functional analysis of the omega-6 fatty acid desaturase (CaFAD2) gene family of the oil seed crop Crambe abyssinica

    PubMed Central

    2013-01-01

    Background Crambe abyssinica produces high erucic acid (C22:1, 55-60%) in the seed oil, which can be further increased by reduction of polyunsaturated fatty acid (PUFA) levels. The omega-6 fatty acid desaturase enzyme (FAD2) is known to be involved in PUFA biosynthesis. In crambe, three CaFAD2 genes, CaFAD2-C1, CaFAD2-C2 and CaFAD2-C3 are expressed. Results The individual effect of each CaFAD2 gene on oil composition was investigated through studying transgenic lines (CaFAD2-RNAi) for differential expression levels in relation to the composition of seed-oil. Six first generation transgenic plants (T1) showed C18:1 increase (by 6% to 10.5%) and PUFA reduction (by 8.6% to 10.2%). The silencing effect in these T1-plants ranged from the moderate silencing (40% to 50% reduction) of all three CaFAD2 genes to strong silencing (95% reduction) of CaFAD2-C3 alone. The progeny of two T1-plants (WG4-4 and WG19-6) was further analysed. Four or five transgene insertions are characterized in the progeny (T2) of WG19-6 in contrast to a single insertion in the T2 progeny of WG4-4. For the individual T2-plants of both families (WG19-6 and WG4-4), seed-specific silencing of CaFAD2-C1 and CaFAD2-C2 was observed in several individual T2-plants but, on average in both families, the level of silencing of these genes was not significant. A significant reduction in expression level (P < 0.01) in both families was only observed for CaFAD2-C3 together with significantly different C18:1 and PUFA levels in oil. Conclusions CaFAD2-C3 expression is highly correlated to levels of C18:1 (r = -0.78) and PUFA (r = 0.75), which suggests that CaFAD2-C3 is the most important one for changing the oil composition of crambe. PMID:24083776

  10. Long chain fatty acid (Lcfa) abnormalities in hyper Igd syndrome (Hids) and Familial Mediterranean Fever (Fmf): new insight into heritable periodic fevers.

    PubMed

    Simon, Anna; Drenth, Joost P H; Matern, Dietrich; Goetzman, Eric S; Hager, Elizabeth J; Gibson, K Michael

    2013-03-01

    To examine essential fatty acids (EFAs) in hyper-IgD syndrome (HIDS) and Familial Mediterranean Fever (FMF). EFAs were determined in sera derived from an archival, cross-sectional group of HIDS/FMF patients, stratified for presence and absence of fever. Control populations included healthy afebrile adults, and individuals with non-periodic fever (septic shock). EFAs were quantified using isotope dilution gas chromatography-mass spectrometry and data analyzed employing a Kruskal-Wallis non-parametric ANOVA with Dunn's post-hoc test. Sera samples derived from HIDS patients showed significantly decreased C20, C26, phytanic and pristanic acids during febrile crises that normalized in the afebrile state, and a significantly increased afebrile C22_4ω6 level that normalized with fever. Samples derived from FMF patients revealed increased ω-oxidized LCFAs as compared to controls, and the trend was for these same species to be increased in comparison to febrile, but not afebrile, HIDS patients. Individuals with non-periodic fever demonstrated global decreases in C10-C24 fatty acids, both saturated and unsaturated, accompanied by an elevated triene/tetraene ratio. Our results suggest that different mechanisms are active in hereditary periodic fever syndromes that appear unrelated to fever, including depletion of very long chain fatty acids (VLCFAs) in febrile HIDS patients and increased ω-oxidized LCFAs in patients with FMF. These findings underscore new roles for EFAs in the potential production of inflammatory species in patients with hereditary periodic fever. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

    SciTech Connect

    Heumen, Bjorn W.H. van; Roelofs, Hennie M.J.; Morsche, Rene H.M. te; Marian, Brigitte; Nagengast, Fokko M.; Peters, Wilbert H.M.

    2012-04-15

    Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cell growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.

  12. Functional Characterization of a Novel Member of the Amidohydrolase 2 Protein Family, 2-Hydroxy-1-Naphthoic Acid Nonoxidative Decarboxylase from Burkholderia sp. Strain BC1

    PubMed Central

    Pal Chowdhury, Piyali; Basu, Soumik; Dutta, Arindam

    2016-01-01

    ABSTRACT The gene encoding a nonoxidative decarboxylase capable of catalyzing the transformation of 2-hydroxy-1-naphthoic acid (2H1NA) to 2-naphthol was identified, recombinantly expressed, and purified to homogeneity. The putative gene sequence of the decarboxylase (hndA) encodes a 316-amino-acid protein (HndA) with a predicted molecular mass of 34 kDa. HndA exhibited high identity with uncharacterized amidohydrolase 2 proteins of various Burkholderia species, whereas it showed a modest 27% identity with γ-resorcylate decarboxylase, a well-characterized nonoxidative decarboxylase belonging to the amidohydrolase superfamily. Biochemically characterized HndA demonstrated strict substrate specificity toward 2H1NA, whereas inhibition studies with HndA indicated the presence of zinc as the transition metal center, as confirmed by atomic absorption spectroscopy. A three-dimensional structural model of HndA, followed by docking analysis, identified the conserved metal-coordinating and substrate-binding residues, while their importance in catalysis was validated by site-directed mutagenesis. IMPORTANCE Microbial nonoxidative decarboxylases play a crucial role in the metabolism of a large array of carboxy aromatic chemicals released into the environment from a variety of natural and anthropogenic sources. Among these, hydroxynaphthoic acids are usually encountered as pathway intermediates in the bacterial degradation of polycyclic aromatic hydrocarbons. The present study reveals biochemical and molecular characterization of a 2-hydroxy-1-naphthoic acid nonoxidative decarboxylase involved in an alternative metabolic pathway which can be classified as a member of the small repertoire of nonoxidative decarboxylases belonging to the amidohydrolase 2 family of proteins. The strict substrate specificity and sequence uniqueness make it a novel member of the metallo-dependent hydrolase superfamily. PMID:27068590

  13. LONG CHAIN FATTY ACID (LCFA) ABNORMALITIES IN HYPER IgD SYNDROME (HIDS) AND FAMILIAL MEDITERRANEAN FEVER (FMF): NEW INSIGHT INTO HERITABLE PERIODIC FEVERSa

    PubMed Central

    Simon, Anna; Drenth, Joost PH; Matern, Dietrich; Goetzman, Eric S.; Hager, Elizabeth J.; Gibson, K Michael

    2013-01-01

    Objective To examine essential fatty acids (EFAs) in hyper-IgD syndrome (HIDS) and Familial Mediterranean Fever (FMF). Methods EFAs were determined in sera derived from an archival, cross-sectional group of HIDS/FMF patients, stratified for presence and absence of fever. Control populations included healthy afebrile adults, and individuals with non-periodic fever (septic shock). EFAs were quantified using isotope dilution gas chromatography-mass spectrometry and data analyzed employing a Kruskal-Wallis non-parametric ANOVA with Dunn's post-hoc test. Results Sera samples derived from HIDS patients showed significantly decreased C20, C26, phytanic and pristanic acids during febrile crises that normalized in the afebrile state, and a significantly increased afebrile C22_ω46 level that normalized with fever. Samples derived from FMF patients revealed increased ω-oxidized LCFAs as compared to controls, and the trend was for these same species to be increased in comparison to febrile, but not afebrile, HIDS patients. Individuals with non-periodic fever demonstrated global decreases in C10–C24 fatty acids, both saturated and unsaturated, accompanied by an elevated triene/tetraene ratio. Conclusions Our results suggest that different mechanisms are active in hereditary periodic fever syndromes that appear unrelated to fever, including depletion of very long chain fatty acids (VLCFAs) in febrile HIDS patients and increased ω-oxidized LCFAs in patients with FMF. These findings underscore new roles for EFAs in the potential production of inflammatory species in patients with hereditary periodic fever. PMID:23375471

  14. Aldo-keto reductase family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-alpha in breast cancer cells.

    PubMed

    Ma, Jun; Yan, Ruilan; Zu, Xuyu; Cheng, Ji-Ming; Rao, Krishna; Liao, Duan-Fang; Cao, Deliang

    2008-02-08

    Recent studies have demonstrated that aldo-keto reductase family 1 B10 (AKR1B10), a novel protein overexpressed in human hepatocellular carcinoma and non-small cell lung carcinoma, may facilitate cancer cell growth by detoxifying intracellular reactive carbonyls. This study presents a novel function of AKR1B10 in tumorigenic mammary epithelial cells (RAO-3), regulating fatty acid synthesis. In RAO-3 cells, Sephacryl-S 300 gel filtration and DEAE-Sepharose ion exchange chromatography demonstrated that AKR1B10 exists in two distinct forms, monomers (approximately 40 kDa) bound to DEAE-Sepharose column and protein complexes (approximately 300 kDa) remaining in flow-through. Co-immunoprecipitation with AKR1B10 antibody and protein mass spectrometry analysis identified that AKR1B10 associates with acetyl-CoA carboxylase-alpha (ACCA), a rate-limiting enzyme of de novo fatty acid synthesis. This association between AKR1B10 and ACCA proteins was further confirmed by co-immunoprecipitation with ACCA antibody and pulldown assays with recombinant AKR1B10 protein. Intracellular fluorescent studies showed that AKR1B10 and ACCA proteins co-localize in the cytoplasm of RAO-3 cells. More interestingly, small interfering RNA-mediated AKR1B10 knock down increased ACCA degradation through ubiquitination-proteasome pathway and resulted in >50% decrease of fatty acid synthesis in RAO-3 cells. These data suggest that AKR1B10 is a novel regulator of the biosynthesis of fatty acid, an essential component of the cell membrane, in breast cancer cells.

  15. Influence of maternal and socioeconomic factors on breast milk fatty acid composition in urban, low-income families.

    PubMed

    Nayak, Uma; Kanungo, Suman; Zhang, Dadong; Ross Colgate, E; Carmolli, Marya P; Dey, Ayan; Alam, Masud; Manna, Byomkesh; Nandy, Ranjan Kumar; Kim, Deok Ryun; Paul, Dilip Kumar; Choudhury, Saugato; Sahoo, Sushama; Harris, William S; Wierzba, Thomas F; Ahmed, Tahmeed; Kirkpatrick, Beth D; Haque, Rashidul; Petri, William A; Mychaleckyj, Josyf C

    2017-02-15

    The lipid composition of breast milk may have a significant impact on early infant growth and cognitive development. Comprehensive breast milk data is lacking from low-income populations in the Indian subcontinent impeding assessment of deficiencies and limiting development of maternal nutritional interventions. A single breast milk specimen was collected within 6 weeks postpartum from two low-income maternal cohorts of exclusively breastfed infants, from Dhaka, Bangladesh (n = 683) and Kolkata, India (n = 372) and assayed for percentage composition of 26 fatty acids. Mature milk (>15 days) in Dhaka (n = 99) compared to Kolkata (n = 372) was higher in total saturated fatty acid (SFA; mean 48% vs. 44%) and disproportionately lower in ω3-polyunsaturated fatty acid (PUFA), hence the ω6- and ω3-PUFA ratio in Dhaka were almost double the value in Kolkata. In both sites, after adjusting for days of lactation, increased maternal education was associated with decreased SFA and PUFA, and increasing birth order or total pregnancies was associated with decreasing ω6-PUFA or ω3-PUFA by a factor of 0.95 for each birth and pregnancy. In Dhaka, household prosperity was associated with decreased SFA and PUFA and increased ω6- and ω3-PUFA. Maternal height was associated with increased SFA and PUFA in Kolkata (1% increase per 1 cm), but body mass index showed no independent association with either ratio in either cohort. In summary, the socioeconomic factors of maternal education and household prosperity were associated with breast milk composition, although prosperity may only be important in higher cost of living communities. Associated maternal biological factors were height and infant birth order, but not adiposity. Further study is needed to elucidate the underlying mechanisms of these effects.

  16. Management of familial Mediterranean fever by colchicine does not normalize the altered profile of microbial long chain fatty acids in the human metabolome.

    PubMed

    Ktsoyan, Zhanna A; Beloborodova, Natalia V; Sedrakyan, Anahit M; Osipov, George A; Khachatryan, Zaruhi A; Manukyan, Gayane P; Arakelova, Karine A; Hovhannisyan, Alvard I; Arakelyan, Arsen A; Ghazaryan, Karine A; Zakaryan, Magdalina K; Aminov, Rustam I

    2013-01-01

    In our previous works we established that in an autoinflammatory condition, familial Mediterranean fever (FMF), the gut microbial diversity is specifically restructured, which also results in the altered profiles of microbial long chain fatty acids (LCFAs) present in the systemic metabolome. The mainstream management of the disease is based on oral administration of colchicine to suppress clinical signs and extend remission periods and our aim was to determine whether this therapy normalizes the microbial LCFA profiles in the metabolome as well. Unexpectedly, the treatment does not normalize these profiles. Moreover, it results in the formation of new distinct microbial LCFA clusters, which are well separated from the corresponding values in healthy controls and FMF patients without the therapy. We hypothesize that the therapy alters the proinflammatory network specific for the disease, with the concomitant changes in gut microbiota and the corresponding microbial LCFAs in the metabolome.

  17. Three acidic residues are at the active site of a beta-propeller architecture in glycoside hydrolase families 32, 43, 62, and 68.

    PubMed

    Pons, Tirso; Naumoff, Daniil G; Martínez-Fleites, Carlos; Hernández, Lázaro

    2004-02-15

    Multiple-sequence alignment of glycoside hydrolase (GH) families 32, 43, 62, and 68 revealed three conserved blocks, each containing an acidic residue at an equivalent position in all the enzymes. A detailed analysis of the site-directed mutations so far performed on invertases (GH32), arabinanases (GH43), and bacterial fructosyltransferases (GH68) indicated a direct implication of the conserved residues Asp/Glu (block I), Asp (block II), and Glu (block III) in substrate binding and hydrolysis. These residues are close in space in the 5-bladed beta-propeller fold determined for Cellvibrio japonicus alpha-L-arabinanase Arb43A [Nurizzo et al., Nat Struct Biol 2002;9:665-668] and Bacillus subtilis endo-1,5-alpha-L-arabinanase. A sequence-structure compatibility search using 3D-PSSM, mGenTHREADER, INBGU, and SAM-T02 programs predicted indistinctly the 5-bladed beta-propeller fold of Arb43A and the 6-bladed beta-propeller fold of sialidase/neuraminidase (GH33, GH34, and GH83) as the most reliable topologies for GH families 32, 62, and 68. We conclude that the identified acidic residues are located at the active site of a beta-propeller architecture in GH32, GH43, GH62, and GH68, operating with a canonical reaction mechanism of either inversion (GH43 and likely GH62) or retention (GH32 and GH68) of the anomeric configuration. Also, we propose that the beta-propeller architecture accommodates distinct binding sites for the acceptor saccharide in glycosyl transfer reaction. Copyright 2003 Wiley-Liss, Inc.

  18. Biliary bile acids in birds of the Cotingidae family: taurine-conjugated (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid and two epimers (25R and 25S) of 3α,7α-dihydroxy-5β-cholestan-27-oic acid.

    PubMed

    Hagey, Lee R; Iida, Takashi; Ogawa, Shoujiro; Adachi, Yuuki; Une, Mizuho; Mushiake, Kumiko; Maekawa, Masamitsu; Shimada, Miki; Mano, Nariyasu; Hofmann, Alan F

    2011-01-01

    Three C(27) bile acids were found to be major biliary bile acids in the capuchinbird (Perissocephalus tricolor) and bare-throated bellbird (Procnias nudicollis), both members of the Cotingidae family of the order Passeriformes. The individual bile acids were isolated by preparative RP-HPLC, and their structures were established by RP-HPLC, LC/ESI-MS/MS and NMR as well as by a comparison of their chromatographic properties with those of authentic reference standards of their 12α-hydroxy derivatives. The most abundant bile acid present in the capuchinbird bile was the taurine conjugate of C(27) (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid, a diastereomer not previously identified as a natural bile acid. The four diastereomers of taurine-conjugated (24ξ,25ξ)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid could be distinguished by NMR and were resolved by RP-HPLC. The RRT of the diastereomers (with taurocholic acid as 1.0) were found to be increased in the following order: (24R,25R)<(24S,25R)<(24S,25S)<(24R,25S). Two epimers (25R and 25S) of C(27) 3α,7α-dihydroxy-5β-cholestan-27-oic acid were also present (as the taurine conjugates) in both bird species. Epimers of the two compounds could be distinguished by their NMR spectra and resolved by RP-HPLC with the (25S)-epimer eluting before the (25R)-epimer. Characterization of the taurine-conjugated (24R,25R)-3α,7α,24-trihydroxy-5β-cholestan-27-oic acid and two epimers (25R and 25S) of 3α,7α-dihydroxy-5β-cholestan-27-oic acid should facilitate their detection in peroxisomal disease and inborn errors of bile acid biosynthesis.

  19. Analysis of the rice mitochondrial carrier family reveals anaerobic accumulation of a basic amino acid carrier involved in arginine metabolism during seed germination.

    PubMed

    Taylor, Nicolas L; Howell, Katharine A; Heazlewood, Joshua L; Tan, Tzu Yien W; Narsai, Reena; Huang, Shaobai; Whelan, James; Millar, A Harvey

    2010-10-01

    Given the substantial changes in mitochondrial gene expression, the mitochondrial proteome, and respiratory function during rice (Oryza sativa) germination under anaerobic and aerobic conditions, we have attempted to identify changes in mitochondrial membrane transport capacity during these processes. We have assembled a preliminary rice mitochondrial carrier gene family of 50 members, defined its orthology to carriers of known function, and observed significant changes in microarray expression data for these rice genes during germination under aerobic and anaerobic conditions and across rice development. To determine if these transcript changes reflect alteration of the carrier profile itself and to determine which members of the family encode the major mitochondrial carrier proteins, we analyzed mitochondrial integral membrane protein preparations using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and peptide mass spectrometry, identifying seven distinct carrier proteins. We have used mass spectrometry-based quantitative approaches to compare the abundance of these carriers between mitochondria from dry seeds and those from aerobic- or anaerobic-germinated seeds. We highlight an anaerobic-enhanced basic amino acid carrier and show concomitant increases in mitochondrial arginase and the abundance of arginine and ornithine in anaerobic-germinated seeds, consistent with an anaerobic role of this mitochondria carrier. The potential role of this carrier in facilitating mitochondrial involvement in arginine metabolism and the plant urea cycle during the growth of rice coleoptiles and early seed nitrate assimilation under anaerobic conditions are discussed.

  20. Analysis of the Rice Mitochondrial Carrier Family Reveals Anaerobic Accumulation of a Basic Amino Acid Carrier Involved in Arginine Metabolism during Seed Germination1[W][OA

    PubMed Central

    Taylor, Nicolas L.; Howell, Katharine A.; Heazlewood, Joshua L.; Tan, Tzu Yien W.; Narsai, Reena; Huang, Shaobai; Whelan, James; Millar, A. Harvey

    2010-01-01

    Given the substantial changes in mitochondrial gene expression, the mitochondrial proteome, and respiratory function during rice (Oryza sativa) germination under anaerobic and aerobic conditions, we have attempted to identify changes in mitochondrial membrane transport capacity during these processes. We have assembled a preliminary rice mitochondrial carrier gene family of 50 members, defined its orthology to carriers of known function, and observed significant changes in microarray expression data for these rice genes during germination under aerobic and anaerobic conditions and across rice development. To determine if these transcript changes reflect alteration of the carrier profile itself and to determine which members of the family encode the major mitochondrial carrier proteins, we analyzed mitochondrial integral membrane protein preparations using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and peptide mass spectrometry, identifying seven distinct carrier proteins. We have used mass spectrometry-based quantitative approaches to compare the abundance of these carriers between mitochondria from dry seeds and those from aerobic- or anaerobic-germinated seeds. We highlight an anaerobic-enhanced basic amino acid carrier and show concomitant increases in mitochondrial arginase and the abundance of arginine and ornithine in anaerobic-germinated seeds, consistent with an anaerobic role of this mitochondria carrier. The potential role of this carrier in facilitating mitochondrial involvement in arginine metabolism and the plant urea cycle during the growth of rice coleoptiles and early seed nitrate assimilation under anaerobic conditions are discussed. PMID:20720170

  1. A novel abscisic acid- and dehydration-responsive gene family from the resurrection plant Craterostigma plantagineum encodes a plastid-targeted protein with DNA-binding activity.

    PubMed

    Phillips, Jonathan R; Hilbricht, Tobias; Salamini, Francesco; Bartels, Dorothea

    2002-06-01

    In the desiccation-tolerant resurrection plant Craterostigma plantagineum Hochst. the chloroplasts undergo major ultrastructural changes during dehydration, which are reversible upon rehydration. Such alterations argue the need for efficient protective/stabilising mechanisms to exist. Here we describe a novel gene family that is rapidly and transiently expressed in response to both dehydration and exogenously applied abscisic acid, mostly in the chloroplast-rich palisade layer on the adaxial side of the leaf. Analysis of the putative coding region suggests that the resulting protein is plastid-targeted. This was confirmed using a chimeric green fluorescent protein (GFP) reporter construct in transgenic tobacco plants - hence the gene family is termed Plastid Targeted Protein ( CpPTP). Fluorescence microscopy also revealed that CpPTP was localised in structures similar to proplastid nucleoids in transgenic tobacco ( Nicotiana tabacum L.) BY-2 cells. The ability of CpPTP to interact with DNA was demonstrated through a DNaseI protection assay. A structure-prediction programme suggests that the mature CpPTP is composed almost entirely of a pattern of hydrophobic and hydrophilic residues that form heptad repeats, which are the hallmarks of a coiled-coil domain. Given the localisation and DNA-binding property of the protein, we propose that CpPTP plays a role during the early stages of dehydration-induced chloroplast remodelling.

  2. A shared internal threonine-glutamic acid-threonine-proline repeat defines a family of Dictyostelium discoideum spore germination specific proteins.

    PubMed

    Giorda, R; Ohmachi, T; Shaw, D R; Ennis, H L

    1990-08-07

    A cDNA denoted pRK270 hybridizes to two mRNA species in RNA blots. The mRNAs specific to this clone are not expressed during vegetative growth and multicellular development. They are, however, found predominantly during early stages of spore germination, suggesting that their synthesis is rapidly and coordinately turned on during germination. Two different cDNAs named 270-6 and 270-11 were isolated, representing the two mRNAs. DNA blot analysis shows that 270 is a multigene family. Four genes were isolated from Dictyostelium genomic libraries and sequenced. The putative proteins coded for by these genes are about 51,000, 55,000, 76,000, and 100,000 Da. Two of the genes are expressed during spore germination while transcripts for the other two are not present during spore germination, vegetative growth, or the stages of multicellular development studied. The cDNAs and genes code for deduced proteins that possess a very unusual internal amino acid repeat comprised of the tetrapeptide threonine-glutamic acid-threonine-proline. The other portions of the proteins have no homology among themselves. The 270-6 protein shows excellent identity with avocado (Persea americana) cellulase, indicating that it may function as an endo-(1,4)-beta-D-glucanase.

  3. 4-O-methylation of glucuronic acid in Arabidopsis glucuronoxylan is catalyzed by a domain of unknown function family 579 protein.

    PubMed

    Urbanowicz, Breeanna R; Peña, Maria J; Ratnaparkhe, Supriya; Avci, Utku; Backe, Jason; Steet, Heather F; Foston, Marcus; Li, Hongjia; O'Neill, Malcolm A; Ragauskas, Arthur J; Darvill, Alan G; Wyman, Charles; Gilbert, Harry J; York, William S

    2012-08-28

    The hemicellulose 4-O-methyl glucuronoxylan is one of the principle components present in the secondary cell walls of eudicotyledonous plants. However, the biochemical mechanisms leading to the formation of this polysaccharide and the effects of modulating its structure on the physical properties of the cell wall are poorly understood. We have identified and functionally characterized an Arabidopsis glucuronoxylan methyltransferase (GXMT) that catalyzes 4-O-methylation of the glucuronic acid substituents of this polysaccharide. AtGXMT1, which was previously classified as a domain of unknown function (DUF) 579 protein, specifically transfers the methyl group from S-adenosyl-L-methionine to O-4 of α-D-glucopyranosyluronic acid residues that are linked to O-2 of the xylan backbone. Biochemical characterization of the recombinant enzyme indicates that GXMT1 is localized in the Golgi apparatus and requires Co(2+) for optimal activity in vitro. Plants lacking GXMT1 synthesize glucuronoxylan in which the degree of 4-O-methylation is reduced by 75%. This result is correlated to a change in lignin monomer composition and an increase in glucuronoxylan release during hydrothermal treatment of secondary cell walls. We propose that the DUF579 proteins constitute a previously undescribed family of cation-dependent, polysaccharide-specific O-methyl-transferases. This knowledge provides new opportunities to selectively manipulate polysaccharide O-methylation and extends the portfolio of structural targets that can be modified either alone or in combination to modulate biopolymer interactions in the plant cell wall.

  4. AaCAT1 of the yellow fever mosquito, Aedes aegypti: a novel histidine-specific amino acid transporter from the SLC7 family.

    PubMed

    Hansen, Immo A; Boudko, Dmitri Y; Shiao, Shin-Hong; Voronov, Dmitri A; Meleshkevitch, Ella A; Drake, Lisa L; Aguirre, Sarah E; Fox, Jeffrey M; Attardo, Geoffrey M; Raikhel, Alexander S

    2011-03-25

    Insect yolk protein precursor gene expression is regulated by nutritional and endocrine signals. A surge of amino acids in the hemolymph of blood-fed female mosquitoes activates a nutrient signaling system in the fat bodies, which subsequently derepresses yolk protein precursor genes and makes them responsive to activation by steroid hormones. Orphan transporters of the SLC7 family were identified as essential upstream components of the nutrient signaling system in the fat body of fruit flies and the yellow fever mosquito, Aedes aegypti. However, the transport function of these proteins was unknown. We report expression and functional characterization of AaCAT1, cloned from the fat body of A. aegypti. Expression of AaCAT1 transcript and protein undergoes dynamic changes during postembryonic development of the mosquito. Transcript expression was especially high in the third and fourth larval stages; however, the AaCAT1 protein was detected only in pupa and adult stages. Functional expression and analysis of AaCAT1 in Xenopus oocytes revealed that it acts as a sodium-independent cationic amino acid transporter, with unique selectivity to L-histidine at neutral pH (K(0.5)(L-His) = 0.34 ± 0.07 mM, pH 7.2). Acidification to pH 6.2 dramatically increases AaCAT1-specific His(+)-induced current. RNAi-mediated silencing of AaCAT1 reduces egg yield of subsequent ovipositions. Our data show that AaCAT1 has notable differences in its transport mechanism when compared with related mammalian cationic amino acid transporters. It may execute histidine-specific transport and signaling in mosquito tissues.

  5. Characterization of the 9-Cis-Epoxycarotenoid Dioxygenase Gene Family and the Regulation of Abscisic Acid Biosynthesis in Avocado1

    PubMed Central

    Chernys, Jacqueline T.; Zeevaart, Jan A.D.

    2000-01-01

    Avocado (Persea americana Mill. cv Lula) is a climacteric fruit that exhibits a rise in ethylene as the fruit ripens. This rise in ethylene is followed by an increase in abscisic acid (ABA), with the highest level occurring just after the peak in ethylene production. ABA is synthesized from the cleavage of carotenoid precursors. The cleavage of carotenoid precursors produces xanthoxin, which can subsequently be converted into ABA via ABA-aldehyde. Indirect evidence indicates that the cleavage reaction, catalyzed by 9-cis-epoxycarotenoid dioxygenase (NCED), is the regulatory step in ABA synthesis. Three genes encoding NCED cleavage-like enzymes were cloned from avocado fruit. Two genes, PaNCED1 and PaNCED3, were strongly induced as the fruit ripened. The other gene, PaNCED2, was constitutively expressed during fruit ripening, as well as in leaves. This gene lacks a predicted chloroplast transit peptide. It is therefore unlikely to be involved in ABA biosynthesis. PaNCED1 was induced by water stress, but expression of PaNCED3 was not detectable in dehydrated leaves. Recombinant PaNCED1 and PaNCED3 were capable of in vitro cleavage of 9-cis-xanthophylls into xanthoxin and C25-apocarotenoids, but PaNCED2 was not. Taken together, the results indicate that ABA biosynthesis in avocado is regulated at the level of carotenoid cleavage. PMID:10982448

  6. Amino acid sequence diversity within the family of antibodies bearing the major antiarsonate cross-reactive idiotype of the A strain mouse

    PubMed Central

    1983-01-01

    VH region amino acid sequences are described for five A/J anti-p- azophenylarsonate (anti-Ars) hybridoma antibodies for which the VL region sequences have previously been determined, thus completing the V domain sequences of these molecules. These antibodies all belong to the family designated Ars-A which bears the major anti-arsonate cross- reactive idiotype (CRI) of the A strain mouse. However, they differ in the degree to which they express the CRI in standard competition radioimmunoassays. Although the sequences are closely related, all are different from each other. Replacements are distributed throughout the VH region and occur in positions of the chain encoded by all three gene segments, VH, DH, and JH. It is likely that somatic diversification processes play a dominant role in producing the sequence variability in each of these segments. The number of differences from the sequence encoded by the germline is smallest for antibodies that express the CRI most strongly, suggesting that somatic diversification is responsible for loss of the CRI in members of the Ars-A antibody family. There is an unusual degree of clustering of differences in both CDR2 and CDR3 and many of the substitutions are located in "hot spots" of variation. The large number of differences between the chains prohibits the unambiguous identification of positions at which alterations play a major role in reducing the expression of the CRI. However, the data suggest that the loss of the CRI is associated with a definable repertoire of somatic changes at a restricted number of highly variable sites. PMID:6415209

  7. Members of a Novel Protein Family Containing Microneme Adhesive Repeat Domains Act as Sialic Acid-binding Lectins during Host Cell Invasion by Apicomplexan Parasites*

    PubMed Central

    Friedrich, Nikolas; Santos, Joana M.; Liu, Yan; Palma, Angelina S.; Leon, Ester; Saouros, Savvas; Kiso, Makoto; Blackman, Michael J.; Matthews, Stephen; Feizi, Ten; Soldati-Favre, Dominique

    2010-01-01

    Numerous intracellular pathogens exploit cell surface glycoconjugates for host cell recognition and entry. Unlike bacteria and viruses, Toxoplasma gondii and other parasites of the phylum Apicomplexa actively invade host cells, and this process critically depends on adhesins (microneme proteins) released onto the parasite surface from intracellular organelles called micronemes (MIC). The microneme adhesive repeat (MAR) domain of T. gondii MIC1 (TgMIC1) recognizes sialic acid (Sia), a key determinant on the host cell surface for invasion by this pathogen. By complementation and invasion assays, we demonstrate that TgMIC1 is one important player in Sia-dependent invasion and that another novel Sia-binding lectin, designated TgMIC13, is also involved. Using BLAST searches, we identify a family of MAR-containing proteins in enteroparasitic coccidians, a subclass of apicomplexans, including T. gondii, suggesting that all these parasites exploit sialylated glycoconjugates on host cells as determinants for enteric invasion. Furthermore, this protein family might provide a basis for the broad host cell range observed for coccidians that form tissue cysts during chronic infection. Carbohydrate microarray analyses, corroborated by structural considerations, show that TgMIC13, TgMIC1, and its homologue Neospora caninum MIC1 (NcMIC1) share a preference for α2–3- over α2–6-linked sialyl-N-acetyllactosamine sequences. However, the three lectins also display differences in binding preferences. Intense binding of TgMIC13 to α2–9-linked disialyl sequence reported on embryonal cells and relatively strong binding to 4-O-acetylated-Sia found on gut epithelium and binding of NcMIC1 to 6′sulfo-sialyl Lewisx might have implications for tissue tropism. PMID:19901027

  8. Elevation of fatty acid-binding protein 4 is predisposed by family history of hypertension and contributes to blood pressure elevation.

    PubMed

    Ota, Hideki; Furuhashi, Masato; Ishimura, Shutaro; Koyama, Masayuki; Okazaki, Yusuke; Mita, Tomohiro; Fuseya, Takahiro; Yamashita, Tomohisa; Tanaka, Marenao; Yoshida, Hideaki; Shimamoto, Kazuaki; Miura, Tetsuji

    2012-10-01

    Fatty acid-binding protein 4 (FABP4/A-FABP/aP2), a lipid chaperone, is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, and atherosclerosis. However, little is known about the role of FABP4 in essential hypertension. We first examined serum FABP4 concentrations in 18 normotensives (NT) and 30 nontreated essential hypertensives (EHT). The EHT were divided into 18 insulin-sensitive EHT (EHT-S) and 12 insulin-resistant EHT (EHT-R) based on their insulin-sensitivity index, the M value, determined by the hyperinsulinemic-euglycemic clamp technique. In the second study, we determined FABP4 levels in 30 young NT men with or without a family history of hypertension (FH(+) and FH(-), respectively; n = 15 each). Serum FABP4 level was significantly higher in the EHT-R than in the NT, whereas elevation of FABP4 level in the EHT-S was not statistically significant. FABP4 level was positively correlated with age, body mass index (BMI), blood pressure, and triglycerides and negatively correlated with the M value. FABP4 level was an independent predictor of mean arterial pressure after adjustment of age, gender, and adiposity. The FH(+) group had a significantly lower level of M value and higher level of FABP4 than did the FH(-) group, and FABP4 concentration was an independent determinant of the M value. FABP4 contributes to blood pressure elevation and atherogenic metabolic phenotype in hypertensives, and the elevation of FABP4 is predisposed by a family history of hypertension.

  9. Mucilaginibacter paludis gen. nov., sp. nov. and Mucilaginibacter gracilis sp. nov., pectin-, xylan- and laminarin-degrading members of the family Sphingobacteriaceae from acidic Sphagnum peat bog.

    PubMed

    Pankratov, Timofei A; Tindall, Brian J; Liesack, Werner; Dedysh, Svetlana N

    2007-10-01

    Two facultatively aerobic, heterotrophic bacteria capable of degrading pectin, xylan, laminarin and some other polysaccharides were obtained from the acidic Sphagnum peat bog Bakchar, in western Siberia, Russia, and were designated strains TPT18(T) and TPT56(T). Cells of these isolates are Gram-negative, non-motile, long rods that are covered by large capsules. On ageing, they transform into spherical L-forms. Strains TPT18(T) and TPT56(T) are acido- and psychrotolerant organisms capable of growth at pH 4.2-8.2 (with an optimum at pH 6.0-6.5) and at 2-33 degrees C (with an optimum at 20 degrees C). The major fatty acids are iso-C(15 : 0), anteiso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c); the quinones are MK-7 and MK-6. Comparative 16S rRNA gene sequence analysis revealed that the novel strains share 97 % sequence similarity and belong to the family Sphingobacteriaceae; however, they are related only distantly to members of the genera Pedobacter (91.8-93.3 % similarity) and Sphingobacterium (89.6-91.2 % similarity). The DNA G+C content of strains TPT18(T) and TPT56(T) is 42.4 and 46.1 mol%, respectively. The low DNA-DNA hybridization value (42 %) and a number of phenotypic differences between strains TPT18(T) and TPT56(T) indicated that they represent two separate species. Since the two isolates are clearly distinct from all currently described members of the family Sphingobacteriaceae, we propose a novel genus, Mucilaginibacter gen. nov., containing two novel species, Mucilaginibacter gracilis sp. nov. and Mucilaginibacter paludis sp. nov. The type strains of Mucilaginibacter gracilis and Mucilaginibacter paludis are respectively TPT18(T) (=ATCC BAA-1391(T) =VKM B-2447(T)) and TPT56(T) (=ATCC BAA-1394(T) =VKM B-2446(T)).

  10. Fatty acid binding protein 3 (fabp3) is associated with insulin, lipids and cardiovascular phenotypes of the metabolic syndrome through epigenetic modifications in a northern european family population

    PubMed Central

    2013-01-01

    Background Fatty acid-binding proteins (FABPs) play regulatory roles at the nexus of lipid metabolism and signaling. Dyslipidemia in clinical manifestation frequently co-occurs with obesity, insulin resistance and hypertension in the Metabolic Syndrome (MetS). Animal studies have suggested FABPs play regulatory roles in expressing MetS phenotypes. In our family cohort of Northern European descent, transcript levels in peripheral white blood cells (PWBCs) of a key FABPs, FABP3, is correlated with the MetS leading components. However, evidence supporting the functions of FABPs in humans using genetic approaches has been scarce, suggesting FABPs may be under epigenetic regulation. The objective of this study was to test the hypothesis that CpG methylation status of a key regulator of lipid homeostasis, FABP3, is a quantitative trait associated with status of MetS phenotypes in humans. Methods We used a mass-spec based quantitative method, EpiTYPER®, to profile a CpG island that extends from the promoter to the first exon of the FABP3 gene in our family-based cohort of Northern European descent (n=517). We then conducted statistical analysis of the quantitative relationship of CpG methylation and MetS measures following the variance-component association model. Heritability of each methylation and the effect of age and sex on CpG methylation were also assessed in our families. Results We find that methylation levels of individual CpG units and the regional average are heritable and significantly influenced by age and sex. Regional methylation was strongly associated with plasma total cholesterol (p=0.00028) and suggestively associated with LDL-cholesterol (p=0.00495). Methylation at individual units was significantly associated with insulin sensitivity, lipid particle sizing and diastolic blood pressure (p<0.0028, corrected for multiple testing for each trait). Peripheral white blood cell (PWBC) expression of FABP3 in a separate group of subjects (n=128) negatively

  11. A putative amino acid transporter of the solute carrier 6 family is upregulated by lithium and is required for resistance to lithium toxicity in Drosophila.

    PubMed

    Kasuya, J; Kaas, G A; Kitamoto, T

    2009-10-20

    Lithium is an efficacious drug for the treatment of mood disorders, and its application is also considered a potential therapy for brain damage. However, the mechanisms underlying lithium's therapeutic action and toxic effects in the nervous system remain largely elusive. Here we report on the use of a versatile genetic model, the fruit fly Drosophila melanogaster, to discover novel molecular components involved in the lithium-responsive neurobiological process. We previously identified CG15088, which encodes a putative nutrient amino acid transporter of the solute carrier 6 (SLC6) family, as one of the genes most significantly upregulated in response to lithium treatment. This gene was the only SLC6 gene induced by lithium, and was thus designated as Lithium-inducible SLC6 transporter or List. Either RNA interference (RNAi)-mediated knockdown or complete deletion of List resulted in a remarkable increase in the susceptibility of adult flies to lithium's toxic effects, whereas transgenic expression of wild-type List significantly suppressed the lithium hypersensitive phenotype of List-deficient flies. Other ions such as sodium, potassium and chloride did not induce List upregulation, nor did they affect the viability of flies with suppressed List expression. These results indicate that lithium's biochemical or physical properties, rather than general osmotic responses, are responsible for the lithium-induced upregulation of List, as well as for the lithium-susceptible phenotype observed in List knockdown flies. Interestingly, flies became significantly more susceptible to lithium toxicity when List RNAi was specifically expressed in glia than when it was expressed in neurons or muscles, which is consistent with potential glial expression of List. These results show that the List transporter confers resistance to lithium toxicity, possibly as a consequence of its amino acid transporter activity in CNS glia. Our results have provided a new avenue of investigation

  12. The family of ferrocene-stabilized silylium ions: synthesis, 29Si NMR characterization, Lewis acidity, substituent scrambling, and quantum-chemical analyses.

    PubMed

    Müther, Kristine; Hrobárik, Peter; Hrobáriková, Veronika; Kaupp, Martin; Oestreich, Martin

    2013-12-02

    The purpose of this systematic experimental and theoretical study is to deeply understand the unique bonding situation in ferrocene-stabilized silylium ions as a function of the substituents at the silicon atom and to learn about the structure parameters that determine the (29)Si NMR chemical shift and electrophilicity of these strong Lewis acids. For this, ten new members of the family of ferrocene-stabilized silicon cations were prepared by a hydride abstraction reaction from silanes with the trityl cation and characterized by multinuclear (1)H and (29)Si NMR spectroscopy. A closer look at the NMR spectra revealed that additional minor sets of signals were not impurities but silylium ions with substitution patterns different from that of the initially formed cation. Careful assignment of these signals furnished experimental proof that sterically less hindered silylium ions are capable of exchanging substituents with unreacted silane precursors. Density functional theory calculations provided mechanistic insight into that substituent transfer in which the migrating group is exchanged between two silicon fragments in a concerted process involving a ferrocene-bridged intermediate. Moreover, the quantum-chemical analysis of the (29)Si NMR chemical shifts revealed a linear relationship between δ((29)Si) values and the Fe···Si distance for subsets of silicon cations. An electron localization function and electron localizability indicator analysis shows a three-center two-electron bonding attractor between the iron, silicon, and C'(ipso) atoms, clearly distinguishing the silicon cations from the corresponding carbenium ions and boranes. Correlations between (29)Si NMR chemical shifts and Lewis acidity, evaluated in terms of fluoride ion affinities, are seen only for subsets of silylium ions, sometimes with non-intuitive trends, indicating a complicated interplay of steric and electronic effects on the degree of the Fe···Si interaction.

  13. Biosynthesis of UDP-xylose. Cloning and characterization of a novel Arabidopsis gene family, UXS, encoding soluble and putative membrane-bound UDP-glucuronic acid decarboxylase isoforms.

    PubMed

    Harper, April D; Bar-Peled, Maor

    2002-12-01

    UDP-xylose (Xyl) is an important sugar donor for the synthesis of glycoproteins, polysaccharides, various metabolites, and oligosaccharides in animals, plants, fungi, and bacteria. UDP-Xyl also feedback inhibits upstream enzymes (UDP-glucose [Glc] dehydrogenase, UDP-Glc pyrophosphorylase, and UDP-GlcA decarboxylase) and is involved in its own synthesis and the synthesis of UDP-arabinose. In plants, biosynthesis of UDP-Xyl is catalyzed by different membrane-bound and soluble UDP-GlcA decarboxylase (UDP-GlcA-DC) isozymes, all of which convert UDP-GlcA to UDP-Xyl. Because synthesis of UDP-Xyl occurs both in the cytosol and in membranes, it is not known which source of UDP-Xyl the different Golgi-localized xylosyltransferases are utilizing. Here, we describe the identification of several distinct Arabidopsis genes (named AtUXS for UDP-Xyl synthase) that encode functional UDP-GlcA-DC isoforms. The Arabidopsis genome contains five UXS genes and their protein products can be subdivided into three isozyme classes (A-C), one soluble and two distinct putative membrane bound. AtUxs from each class, when expressed in Escherichia coli, generate active UDP-GlcA-DC that converts UDP-GlcA to UDP-Xyl. Members of this gene family have a large conserved C-terminal catalytic domain (approximately 300 amino acids long) and an N-terminal variable domain differing in sequence and size (30-120 amino acids long). Isoforms of class A and B appear to encode putative type II membrane proteins with their catalytic domains facing the lumen (like Golgi-glycosyltransferases) and their N-terminal variable domain facing the cytosol. Uxs class C is likely a cytosolic isoform. The characteristics of the plant Uxs support the hypothesis that unique UDP-GlcA-DCs with distinct subcellular localizations are required for specific xylosylation events.

  14. The Src-Family Kinase Inhibitor PP2 Rescues Inducible Differentiation Events in Emergent Retinoic Acid-Resistant Myeloblastic Leukemia Cells

    PubMed Central

    Jensen, Holly A.; Styskal, Lauren E.; Tasseff, Ryan; Bunaciu, Rodica P.; Congleton, Johanna; Varner, Jeffrey D.; Yen, Andrew

    2013-01-01

    Retinoic acid is an embryonic morphogen and dietary factor that demonstrates chemotherapeutic efficacy in inducing maturation in leukemia cells. Using HL60 model human myeloid leukemia cells, where all-trans retinoic acid (RA) induces granulocytic differentiation, we developed two emergent RA-resistant HL60 cell lines which are characterized by loss of RA-inducible G1/G0 arrest, CD11b expression, inducible oxidative metabolism and p47phox expression. However, RA-treated RA-resistant HL60 continue to exhibit sustained MEK/ERK activation, and one of the two sequentially emergent resistant lines retains RA-inducible CD38 expression. Other signaling events that define the wild-type (WT) response are compromised, including c-Raf phosphorylation and increased expression of c-Cbl, Vav1, and the Src-family kinases (SFKs) Lyn and Fgr. As shown previously in WT HL60 cells, we found that the SFK inhibitor PP2 significantly increases G1/G0 cell cycle arrest, CD38 and CD11b expression, c-Raf phosphorylation and expression of the aforementioned regulators in RA-resistant HL60. The resistant cells were potentially incapable of developing inducible oxidative metabolism. These results motivate the concept that RA resistance can occur in steps, wherein growth arrest and other differentiation events may be recovered in both emergent lines. Investigating the mechanistic anomalies in resistant cell lines is of therapeutic significance and helps to mechanistically understand the response to retinoic acid’s biological effects in WT HL60 cells. PMID:23554907

  15. Characterization of the calcineurin B-Like (CBL) gene family in maize and functional analysis of ZmCBL9 under abscisic acid and abiotic stress treatments.

    PubMed

    Zhang, Fan; Li, Li; Jiao, Zhenzhen; Chen, Yangsong; Liu, Hui; Chen, Xunji; Fu, Junjie; Wang, Guoying; Zheng, Jun

    2016-12-01

    In plants, calcineurin B-like proteins (CBLs) play crucial roles in regulating calcium-signaling in response to various abiotic stresses by interacting with specific CBL-interacting protein kinases (CIPKs). However, the identities and functions of CBL gene family members in maize are largely unknown. Here, we identified from the maize genome 12 CBL genes. All 12 CBLs have conserved EF-hand domains, and half harbor myristoylation motifs. We further characterized the function of one CBL gene, ZmCBL9, which can be induced by salt, dehydration, glucose and abscisic acid (ABA) treatments. Overexpression of ZmCBL9 enhanced resistance or tolerance to ABA, glucose, salt and osmotic stress in Arabidopsis and complemented the hypersensitive phenotype of the Arabidopsis cbl9 mutant in response to ABA and abiotic stress. The ZmCBL9 gene negatively regulates the expression of genes in the ABA signaling, biosynthesis and catabolism pathways. Moreover, the ZmCBL9 protein is found to interact with eight maize CIPKs and these ZmCIPK genes were up-regulated by different stress treatments, including salt, dehydration, glucose, low potassium and ABA. These results suggest that ZmCBL9 may interact with various ZmCIPKs to regulate the abiotic stress and ABA response signaling in plants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Desulfosporosinus acidiphilus sp. nov.: a moderately acidophilic sulfate-reducing bacterium isolated from acid mining drainage sediments : New taxa: Firmicutes (Class Clostridia, Order Clostridiales, Family Peptococcaceae).

    PubMed

    Alazard, Didier; Joseph, Manon; Battaglia-Brunet, Fabienne; Cayol, Jean-Luc; Ollivier, Bernard

    2010-05-01

    An obligately anaerobic, spore-forming, acidophilic sulfate-reducing bacterium, strain SJ4(T), was isolated from an acid mining effluent decantation pond sediment sample (pH around 3.0). Cells were Gram negative, non-motile, curved rods occurring singly. Strain SJ4(T) grew at pH 3.6-5.5 with an optimum at pH 5.2. Strain SJ4(T) utilized H(2), lactate, pyruvate, glycerol, glucose, and fructose as electron donors. Lactate and glucose were weakly used. Sulfate was used as electron acceptors, but not sulfite, elemental sulfur, arsenate (V), and fumarate. The G + C content of genomic DNA was 42.3 mol% (HPLC). 16S rRNA gene sequence analysis indicated that strain SJ4(T) belonged to the genus Desulfosporosinus within the family Peptococcaceae in the phylum Firmicutes. The level of 16S rRNA gene sequence similarity with other Desulfosporosinus species was 94.7-96.2%, D. orientis DSM 765(T) (similarity of 96.2%) and D. auripigmenti DSM 13351(T) (similarity of 95%) being its closest relatives. DNA-DNA relatedness values with D. orientis and D. auripigmenti were 16.5 and 31.8%, respectively. On the basis of phenotypic, phylogenetic, and genetic characteristics, strain SJ4(T) represents a novel species within the genus Desulfosporosinus, for which the name Desulfosporosinus acidiphilus sp. nov. is proposed. The type strain is SJ4(T) (=DSM 22704(T) = JCM 16185(T)).

  17. [Familial hypercholesterolemia].

    PubMed

    Turpin, G; Bruckert, E

    1999-12-01

    Familial hypercholesterolemia is characterized by a high plasma LDL-cholesterol level. The low-density particles are the end-product of the triglyceride-rich particles, i.e. VLDL, synthetized by the liver. These triglyceride-rich particles are subsequently transformed into intermediate density lipoprotein by the lipoprotein lipase and LDL after further triglyceride hydrolysis by the hepatic lipase. The LDL particles are taken up in all cells by the mean of the LDL receptor. A large body of evidence (including experimental, clinical, epidemiological data as well as the results of large trial with lipid lowering drugs) has accumulated to establish that these particles are one of the major causative factor of atherosclerosis and its complications. Two different mechanisms may be at work in the familial hypercholesterolemia: a mutation in the LDL receptor or a single mutation in the apolipoprotein B100. Specific therapeutic intervention should be undertaken to decrease the risk to develop cardiovascular disease, mainly coronary heart disease. The therapeutic intervention includes both a diet low in saturated fatty acids and cholesterol and statins which are now the first line therapy. Fibrates are proposed to those who do not tolerate statins and LDL-apheresis is associated to statin in the rare homozygous familial hypercholesterolemia.

  18. Family Therapy

    MedlinePlus

    ... Family therapy is a type of psychological counseling (psychotherapy) that helps family members improve communication and resolve ... organizations? Do you have specialty training in family psychotherapy? What is your experience with my family's type ...

  19. Structure, localization and transcriptional properties of two classes of retinoic acid receptor alpha fusion proteins in acute promyelocytic leukemia (APL): structural similarities with a new family of oncoproteins.

    PubMed Central

    Kastner, P; Perez, A; Lutz, Y; Rochette-Egly, C; Gaub, M P; Durand, B; Lanotte, M; Berger, R; Chambon, P

    1992-01-01

    Acute promyelocytic leukemia (APL) is due to a chromosomal t(15;17) translocation which involves a novel human gene, Myl, (also named PML) and the retinoic acid (RA) receptor alpha (RAR-alpha) gene. We report here the characterization of Myl and of the reciprocal MylRAR (PMLRAR) and RARMyl (RARPML) fusion transcripts which are found in two classes of APL patients. Myl displays similarities with a new family of proteins of which some members are fused to protooncogenes in the transforming proteins RFP-ret and T18. The speckled nuclear localization of Myl, as well as its sequence homology with the 52 kDa component of the RO/SSA ribonucleoprotein particle, suggest that Myl may be present in a ribonucleoprotein complex. In contrast to both Myl and RAR-alpha whose localization is essentially nuclear in the presence or absence of RA, MylRAR which is largely cytoplasmic in the absence of RA appears to be translocated to the nucleus in the presence of RA. Myl and MylRAR can associate in vitro and this association is mediated by a coiled coil in the Myl sequence. In vivo this association results in a colocalization of Myl and MylRAR which is identical to that of MylRAR alone. Studies of activation of transcription from the promoters of several RA target genes indicate that MylRARs have altered transcription activation properties when compared with RAR-alpha. Most notably, MylRAR represses markedly the activity of some RA target promoters in the absence of RA. Western blot analyses of patient samples show that MylRAR is expressed to a much higher level than wild type RAR-alpha originating from the normal allele. Taken together, these results suggest that MylRAR may interfere in a dominant manner with both Myl and RAR functions. Images PMID:1311253

  20. Ralstonia solanacearum Requires PopS, an Ancient AvrE-Family Effector, for Virulence and To Overcome Salicylic Acid-Mediated Defenses during Tomato Pathogenesis

    PubMed Central

    Jacobs, Jonathan M.; Milling, Annett; Mitra, Raka M.; Hogan, Clifford S.; Ailloud, Florent; Prior, Philippe; Allen, Caitilyn

    2013-01-01

    ABSTRACT During bacterial wilt of tomato, the plant pathogen Ralstonia solanacearum upregulates expression of popS, which encodes a type III-secreted effector in the AvrE family. PopS is a core effector present in all sequenced strains in the R. solanacearum species complex. The phylogeny of popS mirrors that of the species complex as a whole, suggesting that this is an ancient, vertically inherited effector needed for association with plants. A popS mutant of R. solanacearum UW551 had reduced virulence on agriculturally important Solanum spp., including potato and tomato plants. However, the popS mutant had wild-type virulence on a weed host, Solanum dulcamara, suggesting that some species can avoid the effects of PopS. The popS mutant was also significantly delayed in colonization of tomato stems compared to the wild type. Some AvrE-type effectors from gammaproteobacteria suppress salicylic acid (SA)-mediated plant defenses, suggesting that PopS, a betaproteobacterial ortholog, has a similar function. Indeed, the popS mutant induced significantly higher expression of tomato SA-triggered pathogenesis-related (PR) genes than the wild type. Further, pretreatment of roots with SA exacerbated the popS mutant virulence defect. Finally, the popS mutant had no colonization defect on SA-deficient NahG transgenic tomato plants. Together, these results indicate that this conserved effector suppresses SA-mediated defenses in tomato roots and stems, which are R. solanacearum’s natural infection sites. Interestingly, PopS did not trigger necrosis when heterologously expressed in Nicotiana leaf tissue, unlike the AvrE homolog DspEPcc from the necrotroph Pectobacterium carotovorum subsp. carotovorum. This is consistent with the differing pathogenesis modes of necrosis-causing gammaproteobacteria and biotrophic R. solanacearum. PMID:24281716

  1. Glutathione transferase supergene family in tomato: Salt stress-regulated expression of representative genes from distinct GST classes in plants primed with salicylic acid.

    PubMed

    Csiszár, Jolán; Horváth, Edit; Váry, Zsolt; Gallé, Ágnes; Bela, Krisztina; Brunner, Szilvia; Tari, Irma

    2014-05-01

    A family tree of the multifunctional proteins, glutathione transferases (GSTs, EC 2.5.1.18) was created in Solanum lycopersicum based on homology to known Arabidopsis GSTs. The involvement of selected SlGSTs was studied in salt stress response of tomato primed with salicylic acid (SA) or in un-primed plants by real-time qPCR. Selected tau GSTs (SlGSTU23, SlGSTU26) were up-regulated in the leaves, while GSTs from lambda, theta, dehydroascorbate reductase and zeta classes (SlGSTL3, SlGSTT2, SlDHAR5, SlGSTZ2) in the root tissues under salt stress. Priming with SA exhibited a concentration dependency; SA mitigated the salt stress injury and caused characteristic changes in the expression pattern of SlGSTs only at 10(-4) M concentration. SlGSTF4 displayed a significant up-regulation in the leaves, while the abundance of SlGSTL3, SlGSTT2 and SlGSTZ2 transcripts were enhanced in the roots of plants primed with high SA concentration. Unexpectedly, under high salinity the SlDHAR2 expression decreased in primed roots as compared to the salt-stressed plants, however, the up-regulation of SlDHAR5 isoenzyme contributed to the maintenance of DHAR activity in roots primed with high SA. The members of lambda, theta and zeta class GSTs have a specific role in salt stress acclimation of tomato, while SlGSTU26 and SlGSTF4, the enzymes with high glutathione conjugating activity, characterize a successful priming in both roots and leaves. In contrast to low concentration, high SA concentration induced those GSTs in primed roots, which were up-regulated under salt stress. Our data indicate that induction of GSTs provide a flexible tool in maintaining redox homeostasis during unfavourable conditions. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Structural comparison of AP endonucleases from the exonuclease III family reveals new amino acid residues in human AP endonuclease 1 that are involved in incision of damaged DNA.

    PubMed

    Redrejo-Rodríguez, Modesto; Vigouroux, Armelle; Mursalimov, Aibek; Grin, Inga; Alili, Doria; Koshenov, Zhanat; Akishev, Zhiger; Maksimenko, Andrei; Bissenbaev, Amangeldy K; Matkarimov, Bakhyt T; Saparbaev, Murat; Ishchenko, Alexander A; Moréra, Solange

    2016-01-01

    Oxidatively damaged DNA bases are substrates for two overlapping repair pathways: DNA glycosylase-initiated base excision repair (BER) and apurinic/apyrimidinic (AP) endonuclease-initiated nucleotide incision repair (NIR). In the BER pathway, an AP endonuclease cleaves DNA at AP sites and 3'-blocking moieties generated by DNA glycosylases, whereas in the NIR pathway, the same AP endonuclease incises DNA 5' to an oxidized base. The majority of characterized AP endonucleases possess classic BER activities, and approximately a half of them can also have a NIR activity. At present, the molecular mechanism underlying DNA substrate specificity of AP endonucleases remains unclear mainly due to the absence of a published structure of the enzyme in complex with a damaged base. To identify critical residues involved in the NIR function, we performed biochemical and structural characterization of Bacillus subtilis AP endonuclease ExoA and compared its crystal structure with the structures of other AP endonucleases: Escherichia coli exonuclease III (Xth), human APE1, and archaeal Mth212. We found conserved amino acid residues in the NIR-specific enzymes APE1, Mth212, and ExoA. Four of these positions were studied by means of point mutations in APE1: we applied substitution with the corresponding residue found in NIR-deficient E. coli Xth (Y128H, N174Q, G231S, and T268D). The APE1-T268D mutant showed a drastically decreased NIR activity and an inverted Mg(2+) dependence of the AP site cleavage activity, which is in line with the presence of an aspartic residue at the equivalent position among other known NIR-deficient AP endonucleases. Taken together, these data show that NIR is an evolutionarily conserved function in the Xth family of AP endonucleases.

  3. Ralstonia solanacearum requires PopS, an ancient AvrE-family effector, for virulence and To overcome salicylic acid-mediated defenses during tomato pathogenesis.

    PubMed

    Jacobs, Jonathan M; Milling, Annett; Mitra, Raka M; Hogan, Clifford S; Ailloud, Florent; Prior, Philippe; Allen, Caitilyn

    2013-11-26

    During bacterial wilt of tomato, the plant pathogen Ralstonia solanacearum upregulates expression of popS, which encodes a type III-secreted effector in the AvrE family. PopS is a core effector present in all sequenced strains in the R. solanacearum species complex. The phylogeny of popS mirrors that of the species complex as a whole, suggesting that this is an ancient, vertically inherited effector needed for association with plants. A popS mutant of R. solanacearum UW551 had reduced virulence on agriculturally important Solanum spp., including potato and tomato plants. However, the popS mutant had wild-type virulence on a weed host, Solanum dulcamara, suggesting that some species can avoid the effects of PopS. The popS mutant was also significantly delayed in colonization of tomato stems compared to the wild type. Some AvrE-type effectors from gammaproteobacteria suppress salicylic acid (SA)-mediated plant defenses, suggesting that PopS, a betaproteobacterial ortholog, has a similar function. Indeed, the popS mutant induced significantly higher expression of tomato SA-triggered pathogenesis-related (PR) genes than the wild type. Further, pretreatment of roots with SA exacerbated the popS mutant virulence defect. Finally, the popS mutant had no colonization defect on SA-deficient NahG transgenic tomato plants. Together, these results indicate that this conserved effector suppresses SA-mediated defenses in tomato roots and stems, which are R. solanacearum's natural infection sites. Interestingly, PopS did not trigger necrosis when heterologously expressed in Nicotiana leaf tissue, unlike the AvrE homolog DspEPcc from the necrotroph Pectobacterium carotovorum subsp. carotovorum. This is consistent with the differing pathogenesis modes of necrosis-causing gammaproteobacteria and biotrophic R. solanacearum. The type III-secreted AvrE effector family is widely distributed in high-impact plant-pathogenic bacteria and is known to suppress plant defenses for virulence. We

  4. Association of polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) and fatty acid-binding protein-3 and fatty acid-binding protein-4 (FABP3 and FABP4) with fatty acid composition of bovine milk.

    PubMed

    Nafikov, R A; Schoonmaker, J P; Korn, K T; Noack, K; Garrick, D J; Koehler, K J; Minick-Bormann, J; Reecy, J M; Spurlock, D E; Beitz, D C

    2013-09-01

    The main goal of this study was to develop tools for genetic selection of animals producing milk with a lower concentration of saturated fatty acids (SFA) and a higher concentration of unsaturated fatty acids (UFA). The reasons for changing milk fatty acid (FA) composition were to improve milk technological properties, such as for production of more spreadable butter, and milk nutritional value with respect to the potentially adverse effects of SFA on human health. We hypothesized that genetic polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) fatty acid transport protein gene and fatty acid binding protein (FABP)-3 and FABP-4 (FABP3 and FABP4) would affect the selectivity of FA uptake into, and FA redistribution inside, mammary epithelial cells, resulting in altered FA composition of bovine milk. The objectives of our study were to discover genetic polymorphisms in SLC27A6, FABP3, and FABP4, and to test those polymorphisms for associations with milk FA composition. The results showed that after pairwise comparisons between SLC27A6 haplotypes for significantly associated traits, haplotype H3 was significantly associated with 1.37 weight percentage (wt%) lower SFA concentration, 0.091 lower SFA:UFA ratio, and 0.17 wt% lower lauric acid (12:0) concentration, but 1.37 wt% higher UFA and 1.24 wt% higher monounsaturated fatty acid (MUFA) concentrations compared with haplotype H1 during the first 3 mo of lactation. Pairwise comparisons between FABP4 haplotypes for significantly associated traits showed that haplotype H3 was significantly associated with 1.04 wt% lower SFA concentration, 0.079 lower SFA:UFA ratio, 0.15 wt% lower lauric acid (12:0), and 0.27 wt% lower myristic acid (14:0) concentrations, but 1.04 wt% higher UFA and 0.91 wt% higher MUFA concentrations compared with haplotype H1 during the first 3 mo of lactation. Percentages of genetic variance explained by H3 versus H1 haplotype substitutions for SLC27A6 and FABP4 ranged from 2.50 to 4.86% and

  5. The use of TLC-DPPH* test with image processing to study direct antioxidant activity of phenolic acid fractions of selected Lamiaceae family species.

    PubMed

    Cieśla, Łukasz; Staszek, Dorota; Kowalska, Teresa; Waksmundzka-Hajnos, Monika

    2013-01-01

    TLC coupled with 2,2-diphenyl-1-picrylhydrazyl staining was used to analyze phenolic acid fractions of selected Salvia and Thymus species. Documented videoscans were processed by means of an image processing program. This is the first time that free phenolic acids fractions, as well as fractions containing phenolic acids derived from basic and acidic hydrolysis, have been analyzed and compared for selected sage and thyme species. The analyzed samples along with caffeic acid (CA; standard) were chromatographed on silica gel plates with toluene-ethyl acetate-formic acid (60 + 40 + 1, v/v/v) mobile phase. The extracts were investigated with respect to the activity of CA. It was found that CA was most abundant in the fractions derived from basic hydrolysis. This compound was not detected in any of the fractions obtained after acidic hydrolysis. S. officinalis and S. triloba have similar free radical scavenging activity fingerprints obtained for all the analyzed fractions.

  6. Family History

    MedlinePlus

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  7. Family Folklore

    ERIC Educational Resources Information Center

    Kotkin, Amy J.; Baker, Holly C.

    1977-01-01

    Discusses the Family Folklore Program of the Smithsonian Institution's annual Festival of American Folklife, in which the whole family can be involved in tracing family history through story telling, photographs, etc. (MS)

  8. Family History

    MedlinePlus

    ... Aneurysms » Diagnosis » Family History A- A A+ Family History Familial intracranial aneurysms are generally defined as the ... patients with an Intracranial Aneurysm (IA) have a history of smoking at some time in their life. ...

  9. Family Folklore

    ERIC Educational Resources Information Center

    Kotkin, Amy J.; Baker, Holly C.

    1977-01-01

    Discusses the Family Folklore Program of the Smithsonian Institution's annual Festival of American Folklife, in which the whole family can be involved in tracing family history through story telling, photographs, etc. (MS)

  10. Family Literacy

    ERIC Educational Resources Information Center

    Holloway, John H.

    2004-01-01

    Research indicates that family literacy programs can provide opportunities for educational success for parents and children. The benefits reaped by the children in family literacy workshops are presented.

  11. Family Privilege

    ERIC Educational Resources Information Center

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  12. Family Literacy.

    ERIC Educational Resources Information Center

    Washington, Charles W., Ed.

    1996-01-01

    This newsletter theme issue focuses on the impact of learning disabilities within families, specifically families with low literacy skills. It explores the effectiveness of family literacy programs, examines the connection between the field of family literacy and learning disabilities (LD), and offers suggestions on how to work with students with…

  13. Family Privilege

    ERIC Educational Resources Information Center

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  14. From unexpected reactions to a new family of ionic co-crystals: the case of barbituric acid with alkali bromides and caesium iodide.

    PubMed

    Braga, Dario; Grepioni, Fabrizia; Maini, Lucia; Prosperi, Susanna; Gobetto, Roberto; Chierotti, Michele R

    2010-11-07

    Pressing solid barbituric acid with KBr to prepare samples for IR spectroscopy leads to the formation of an ionic co-crystal, in which the co-former is a classical ionic salt; co-crystal formation is also obtained with the other alkali bromides (LiBr, NaBr, RbBr and CsBr) and with caesium iodide. The simultaneous presence of alkali and halide ions affects the dissolution properties of barbituric acid in water.

  15. Associations of Whole Blood n-3 and n-6 Polyunsaturated Fatty Acids with Blood Pressure in Children and Adolescents - Results from the IDEFICS/I.Family Cohort.

    PubMed

    Wolters, Maike; Pala, Valeria; Russo, Paola; Risé, Patrizia; Moreno, Luis A; De Henauw, Stefaan; Mehlig, Kirsten; Veidebaum, Toomas; Molnár, Denés; Tornaritis, Michael; Galli, Claudio; Ahrens, Wolfgang; Börnhorst, Claudia

    2016-01-01

    Polyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents. In a subsample of 1267 children aged 2-9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status. The baseline level of arachidonic acid was positively associated with subsequent systolic BP (β = 0.08, P = 0.002) and diastolic BP (β = 0.07, P<0.001). In thin/normal weight children, baseline alpha-linolenic (β = -1.13, P = 0.003) and eicosapentaenoic acid (β = -0.85, P = 0.003) levels were inversely related to baseline and also to subsequent systolic BP and alpha-linolenic acid to subsequent diastolic BP. In overweight/obese children, baseline eicosapentaenoic acid level was positively associated with baseline diastolic BP (β = 0.54, P = 0.005). Low blood arachidonic acid levels in the whole sample and high n-3 PUFA levels in thin/normal weight children are associated with lower and therefore healthier BP. The beneficial effects of high n-3 PUFA on BP were not observed in overweight/obese children, suggesting that they may have been overlaid by the unfavorable effects of excess weight.

  16. Associations of Whole Blood n-3 and n-6 Polyunsaturated Fatty Acids with Blood Pressure in Children and Adolescents – Results from the IDEFICS/I.Family Cohort

    PubMed Central

    Pala, Valeria; Russo, Paola; Risé, Patrizia; Moreno, Luis A.; De Henauw, Stefaan; Mehlig, Kirsten; Veidebaum, Toomas; Molnár, Denés; Tornaritis, Michael; Galli, Claudio; Ahrens, Wolfgang; Börnhorst, Claudia

    2016-01-01

    Background Polyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents. Methods In a subsample of 1267 children aged 2–9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status. Results The baseline level of arachidonic acid was positively associated with subsequent systolic BP (β = 0.08, P = 0.002) and diastolic BP (β = 0.07, P<0.001). In thin/normal weight children, baseline alpha-linolenic (β = -1.13, P = 0.003) and eicosapentaenoic acid (β = -0.85, P = 0.003) levels were inversely related to baseline and also to subsequent systolic BP and alpha-linolenic acid to subsequent diastolic BP. In overweight/obese children, baseline eicosapentaenoic acid level was positively associated with baseline diastolic BP (β = 0.54, P = 0.005). Conclusions Low blood arachidonic acid levels in the whole sample and high n-3 PUFA levels in thin/normal weight children are associated with lower and therefore healthier BP. The beneficial effects of high n-3 PUFA on BP were not observed in overweight/obese children, suggesting that they may have been overlaid by the unfavorable effects of excess weight. PMID:27806134

  17. Xanthomonas campestris FabH is required for branched-chain fatty acid and DSF-family quorum sensing signal biosynthesis

    PubMed Central

    Yu, Yong-Hong; Hu, Zhe; Dong, Hui-Juan; Ma, Jin-Cheng; Wang, Hai-Hong

    2016-01-01

    Xanthomonas campestris pv. campestris (Xcc), a Gram-negative phytopathogenic bacterium, causes black rot disease of cruciferous vegetables. Although Xcc has a complex fatty acid profile comprised of straight-chain fatty acids and branched-chain fatty acids (BCFAs), and encodes a complete set of genes required for fatty acid synthesis, there is still little known about the mechanism of BCFA synthesis. We reported that expression of Xcc fabH restores the growth of Ralstonia solanacearum fabH mutant, and this allows the R. solanacearum fabH mutant to produce BCFAs. Using in vitro assays, we demonstrated that Xcc FabH is able to condense branched-chain acyl-CoAs with malonyl-ACP to initiate BCFA synthesis. Moreover, although the fabH gene is essential for growth of Xcc, it can be replaced with Escherichia coli fabH, and Xcc mutants failed to produce BCFAs. These results suggest that Xcc does not have an obligatory requirement for BCFAs. Furthermore, Xcc mutants lost the ability to produce cis-11-methyl-2-dodecenoic acid, a diffusible signal factor (DSF) required for quorum sensing of Xcc, which confirms that the fatty acid synthetic pathway supplies the intermediates for DSF signal biosynthesis. Our study also showed that replacing Xcc fabH with E. coli fabH affected Xcc pathogenesis in host plants. PMID:27595587

  18. Xanthomonas campestris FabH is required for branched-chain fatty acid and DSF-family quorum sensing signal biosynthesis.

    PubMed

    Yu, Yong-Hong; Hu, Zhe; Dong, Hui-Juan; Ma, Jin-Cheng; Wang, Hai-Hong

    2016-09-06

    Xanthomonas campestris pv. campestris (Xcc), a Gram-negative phytopathogenic bacterium, causes black rot disease of cruciferous vegetables. Although Xcc has a complex fatty acid profile comprised of straight-chain fatty acids and branched-chain fatty acids (BCFAs), and encodes a complete set of genes required for fatty acid synthesis, there is still little known about the mechanism of BCFA synthesis. We reported that expression of Xcc fabH restores the growth of Ralstonia solanacearum fabH mutant, and this allows the R. solanacearum fabH mutant to produce BCFAs. Using in vitro assays, we demonstrated that Xcc FabH is able to condense branched-chain acyl-CoAs with malonyl-ACP to initiate BCFA synthesis. Moreover, although the fabH gene is essential for growth of Xcc, it can be replaced with Escherichia coli fabH, and Xcc mutants failed to produce BCFAs. These results suggest that Xcc does not have an obligatory requirement for BCFAs. Furthermore, Xcc mutants lost the ability to produce cis-11-methyl-2-dodecenoic acid, a diffusible signal factor (DSF) required for quorum sensing of Xcc, which confirms that the fatty acid synthetic pathway supplies the intermediates for DSF signal biosynthesis. Our study also showed that replacing Xcc fabH with E. coli fabH affected Xcc pathogenesis in host plants.

  19. Family Violence and Family Physicians

    PubMed Central

    Herbert, Carol P.

    1991-01-01

    The acronym IDEALS summarizes family physicians' obligations when violence is suspected: to identify family violence; document injuries; educate families and ensure safety for victims; access resources and coordinate care; co-operate in the legal process; and provide support for families. Failure to respond reflects personal and professional experience and attitudes, fear of legal involvement, and lack of knowledge. Risks of intervention include physician burnout, physician overfunctioning, escalation of violence, and family disruption. PMID:21228987

  20. Familial hyperargininaemia.

    PubMed Central

    Terheggen, H G; Lowenthal, A; Lavinha, F; Colombo, J P

    1975-01-01

    A third case of hyperargininaemia occurring in one family was studied from birth. In cord blood serum arginine concentration was only slightly raised, but arginase activity in red blood cell haemolysates was very low. In the urine on day 2 a typical cystinuria pattern was present. Arginine concentration in serum increased to 158 mumol/100 ml on the 41st day of life. Later determinations of the arginase activity in peripheral blood showed values below the sensitivity of the method. Blood ammonia was consistently high, and cystinuria was present. The enzymatic defect was further displayed by intravenous loading tests with arginine. Serum urea values were predominantly normal or near the lower limit of normal, suggesting the presence of other metabolic pathways of urea synthesis. In urine there was no excretion of guanidinosuccinic acid, while the excretion of other monosubstituted guanidine derivatives was increased, pointing to a connexion with hyperargininaemia. Owing to parental attitude, a low protein diet (1-5 g/kg) was introduced only late. The infant developed severe mental retardation, athetosis, and spasticity. PMID:1124944

  1. Family Life

    MedlinePlus

    ... Family and Friends Talking About Cancer Family Life Parenting While Living With Cancer How A Child Understands ... Learn more about how to get support for parenting while living with cancer . The importance of communication ...

  2. Family Violence

    MedlinePlus

    ... help. About Military OneSource Benefits Home and Family Finances Legal Issues Personal Financial Management and Taxes Taxes ... Surveys Site Map Categories Confidential Help Family & Relationships Finance & Legal Health & Wellness Education & Employment On & Off-Base ...

  3. Familial gigantism

    PubMed Central

    de Herder, Wouter W.

    2012-01-01

    Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas. PMID:22584702

  4. Cytochrome P450 Family Member CYP704B2 Catalyzes the ω -Hydroxylation of Fatty Acids and Is Required for Anther Cutin Biosynthesis and Pollen Exine Formation in Rice[W][OA

    PubMed Central

    Li, Hui; Pinot, Franck; Sauveplane, Vincent; Werck-Reichhart, Danièle; Diehl, Patrik; Schreiber, Lukas; Franke, Rochus; Zhang, Ping; Chen, Liang; Gao, Yawei; Liang, Wanqi; Zhang, Dabing

    2010-01-01

    The anther cuticle and microspore exine act as protective barriers for the male gametophyte and pollen grain, but relatively little is known about the mechanisms underlying the biosynthesis of the monomers of which they are composed. We report here the isolation and characterization of a rice (Oryza sativa) male sterile mutant, cyp704B2, which exhibits a swollen sporophytic tapetal layer, aborted pollen grains without detectable exine, and undeveloped anther cuticle. In addition, chemical composition analysis indicated that cutin monomers were hardly detectable in the cyp704B2 anthers. These defects are caused by a mutation in a cytochrome P450 family gene, CYP704B2. The CYP704B2 transcript is specifically detected in the tapetum and the microspore from stage 8 of anther development to stage 10. Heterologous expression of CYP704B2 in yeast demonstrated that CYP704B2 catalyzes the production of ω -hydroxylated fatty acids with 16 and 18 carbon chains. Our results provide insights into the biosynthesis of the two biopolymers sporopollenin and cutin. Specifically, our study indicates that the ω -hydroxylation pathway of fatty acids relying on this ancient CYP704B family, conserved from moss to angiosperms, is essential for the formation of both cuticle and exine during plant male reproductive and spore development. PMID:20086189

  5. Cytochrome P450 family member CYP704B2 catalyzes the {omega}-hydroxylation of fatty acids and is required for anther cutin biosynthesis and pollen exine formation in rice.

    PubMed

    Li, Hui; Pinot, Franck; Sauveplane, Vincent; Werck-Reichhart, Danièle; Diehl, Patrik; Schreiber, Lukas; Franke, Rochus; Zhang, Ping; Chen, Liang; Gao, Yawei; Liang, Wanqi; Zhang, Dabing

    2010-01-01

    The anther cuticle and microspore exine act as protective barriers for the male gametophyte and pollen grain, but relatively little is known about the mechanisms underlying the biosynthesis of the monomers of which they are composed. We report here the isolation and characterization of a rice (Oryza sativa) male sterile mutant, cyp704B2, which exhibits a swollen sporophytic tapetal layer, aborted pollen grains without detectable exine, and undeveloped anther cuticle. In addition, chemical composition analysis indicated that cutin monomers were hardly detectable in the cyp704B2 anthers. These defects are caused by a mutation in a cytochrome P450 family gene, CYP704B2. The CYP704B2 transcript is specifically detected in the tapetum and the microspore from stage 8 of anther development to stage 10. Heterologous expression of CYP704B2 in yeast demonstrated that CYP704B2 catalyzes the production of omega -hydroxylated fatty acids with 16 and 18 carbon chains. Our results provide insights into the biosynthesis of the two biopolymers sporopollenin and cutin. Specifically, our study indicates that the omega -hydroxylation pathway of fatty acids relying on this ancient CYP704B family, conserved from moss to angiosperms, is essential for the formation of both cuticle and exine during plant male reproductive and spore development.

  6. Genome-wide identification, classification and expression profiling of nicotianamine synthase (NAS) gene family in maize

    PubMed Central

    2013-01-01

    Background Nicotianamine (NA), a ubiquitous molecule in plants, is an important metal ion chelator and the main precursor for phytosiderophores biosynthesis. Considerable progress has been achieved in cloning and characterizing the functions of nicotianamine synthase (NAS) in plants including barley, Arabidopsis and rice. Maize is not only an important cereal crop, but also a model plant for genetics and evolutionary study. The genome sequencing of maize was completed, and many gene families were identified. Although three NAS genes have been characterized in maize, there is still no systematic identification of maize NAS family by genomic mining. Results In this study, nine NAS genes in maize were identified and their expression patterns in different organs including developing seeds were determined. According to the evolutionary relationship and tissue specific expression profiles of ZmNAS genes, they can be subgrouped into two classes. Moreover, the expression patterns of ZmNAS genes in response to fluctuating metal status were analysed. The class I ZmNAS genes were induced under Fe deficiency and were suppressed under Fe excessive conditions, while the expression pattern of class II genes were opposite to class I. The complementary expression patterns of class I and class II ZmNAS genes confirmed the classification of this family. Furthermore, the histochemical localization of ZmNAS1;1/1;2 and ZmNAS3 were determined using in situ hybridization. It was revealed that ZmNAS1;1/1;2, representing the class I genes, mainly expressed in cortex and stele of roots with sufficient Fe, and its expression can expanded in epidermis, as well as shoot apices under Fe deficient conditions. On the contrary, ZmNAS3, one of the class II genes, was accumulated in axillary meristems, leaf primordia and mesophyll cells. These results suggest that the two classes of ZmNAS genes may be regulated on transcriptional level when responds to various demands for iron uptake, translocation

  7. Family Support.

    ERIC Educational Resources Information Center

    Wieck, Colleen, Ed.; McBride, Marijo, Ed.

    1990-01-01

    This "Feature Issue" of the quarterly journal "Impact" presents 19 brief articles on family support systems in the United States for persons with developmental disabilities and their families. Emphasis is on provisions of Public Law 99-457. Articles include: "Family Support in the United States: Setting a Course for the…

  8. Family Matters.

    ERIC Educational Resources Information Center

    Featherstone, Joseph

    1979-01-01

    Emphasizing the family as the center of political/policy debates is the result of the tradition of romanticizing family virtues and a set of events ("the sixities"). Author sees the family emerging as a symbol in communal social policy development. Warns of dangers inherent in seeking private solutions to collective problems. (Author/CSS)

  9. Family Involvement.

    ERIC Educational Resources Information Center

    Liontos, Lynn Balster

    1992-01-01

    Family involvement in schools will work only when perceived as an enlarged concept focusing on all children, including those from at-risk families. Each publication reviewed here is specifically concerned with family involvement strategies concerned with all children or targeted at primarily high risk students. Susan McAllister Swap looks at three…

  10. A third MRX family (MRX68) is the result of mutation in the long chain fatty acid-CoA ligase 4 (FACL4) gene: proposal of a rapid enzymatic assay for screening mentally retarded patients

    PubMed Central

    Longo, I; Frints, S; Fryns, J; Meloni, I; Pescucci, C; Ariani, F; Borghgraef, M; Raynaud, M; Marynen, P; Schwartz, C; Renieri, A; Froyen, G

    2003-01-01

    Background: The gene encoding fatty acid CoA ligase 4 (FACL4) is mutated in families with non-specific X linked mental retardation (MRX) and is responsible for cognitive impairment in the contiguous gene syndrome ATS-MR (Alport syndrome and mental retardation), mapped to Xq22.3. This finding makes this gene a good candidate for other mental retardation disorders mapping in this region. Methods: We have screened the FACL4 gene in eight families, two MRX and six syndromic X linked mental retardation (MRXS), mapping in a large interval encompassing Xq22.3. Results: We have found a missense mutation in MRX68. The mutation (c.1001C>T in the brain isoform) cosegregates with the disease and changes a highly conserved proline into a leucine (p.P375L) in the first luciferase domain, which markedly reduces the enzymatic activity. Furthermore, all heterozygous females showed completely skewed X inactivation in blood leucocytes, as happens in all reported females with other FACL4 point mutations or deletions. Conclusions: Since the FACL4 gene is highly expressed in brain, where it encodes a brain specific isoform, and is located in hippocampal and cerebellar neurones, a role for this gene in cognitive processes can be expected. Here we report the third MRX family with a FACL4 mutation and describe the development of a rapid enzymatic assay on peripheral blood that we propose as a sensitive, robust, and efficient diagnostic tool in mentally retarded males. PMID:12525535

  11. Italian families and family interventions.

    PubMed

    Casacchia, Massimo; Roncone, Rita

    2014-06-01

    In Italy, as in many countries, relatives are closely involved in caring for persons with physical and mental disorders. The Italian scenario lends itself to routine involvement of family members in psychiatric treatment because, despite becoming smaller and smaller, Italian families keep close ties, and men and women do not leave the parental home until relatively late. The authors describe the impact of international family psychosocial research on the Italian mental health services (MHSs) and the main psychosocial interventions currently in use, including family psychoeducational interventions and the "Milan family therapy approach." They also highlight the contribution Italian researchers have given to the study of important variables in integrated mental disorder care, such as family burden of care, relatives' attitudes, family functioning, and satisfaction with the MHSs. Finally, they discuss the difficulties of implementing and disseminating family interventions within the Italian MHS, despite the growing evidence of their effectiveness.

  12. Characterization of the Candida albicans Amino Acid Permease Family: Gap2 Is the Only General Amino Acid Permease and Gap4 Is an S-Adenosylmethionine (SAM) Transporter Required for SAM-Induced Morphogenesis

    PubMed Central

    Kraidlova, Lucie; Schrevens, Sanne; Tournu, Hélène; Van Zeebroeck, Griet; Sychrova, Hana

    2016-01-01

    ABSTRACT Amino acids are key sources of nitrogen for growth of Candida albicans. In order to detect and take up these amino acids from a broad range of different and changing nitrogen sources inside the host, this fungus must be able to adapt via its expression of genes for amino acid uptake and further metabolism. We analyzed six C. albicans putative general amino acid permeases based on their homology to the Saccharomyces cerevisiae Gap1 general amino acid permease. We generated single- and multiple-deletion strains and found that, based on growth assays and transcriptional or posttranscriptional regulation, Gap2 is the functional orthologue to ScGap1, with broad substrate specificity. Expression analysis showed that expression of all GAP genes is under control of the Csy1 amino acid sensor, which is different from the situation in S. cerevisiae, where the expression of ScGAP1 is not regulated by Ssy1. We show that Gap4 is the functional orthologue of ScSam3, the only S-adenosylmethionine (SAM) transporter in S. cerevisiae, and we report that Gap4 is required for SAM-induced morphogenesis. IMPORTANCE Candida albicans is a commensal organism that can thrive in many niches in its human host. The environmental conditions at these different niches differ quite a bit, and this fungus must be able to sense these changes and adapt its metabolism to them. Apart from glucose and other sugars, the uptake of amino acids is very important. This is underscored by the fact that the C. albicans genome encodes 6 orthologues of the Saccharomyces. cerevisiae general amino acid permease Gap1 and many other amino acid transporters. In this work, we characterize these six permeases and we show that C. albicans Gap2 is the functional orthologue of ScGap1 and that C. albicans Gap4 is an orthologue of ScSam3, an S-adenosylmethionine (SAM) transporter. Furthermore, we show that Gap4 is required for SAM-induced morphogenesis, an important virulence factor of C. albicans. PMID

  13. Characterization of the Candida albicans Amino Acid Permease Family: Gap2 Is the Only General Amino Acid Permease and Gap4 Is an S-Adenosylmethionine (SAM) Transporter Required for SAM-Induced Morphogenesis.

    PubMed

    Kraidlova, Lucie; Schrevens, Sanne; Tournu, Hélène; Van Zeebroeck, Griet; Sychrova, Hana; Van Dijck, Patrick

    2016-01-01

    Amino acids are key sources of nitrogen for growth of Candida albicans. In order to detect and take up these amino acids from a broad range of different and changing nitrogen sources inside the host, this fungus must be able to adapt via its expression of genes for amino acid uptake and further metabolism. We analyzed six C. albicans putative general amino acid permeases based on their homology to the Saccharomyces cerevisiae Gap1 general amino acid permease. We generated single- and multiple-deletion strains and found that, based on growth assays and transcriptional or posttranscriptional regulation, Gap2 is the functional orthologue to ScGap1, with broad substrate specificity. Expression analysis showed that expression of all GAP genes is under control of the Csy1 amino acid sensor, which is different from the situation in S. cerevisiae, where the expression of ScGAP1 is not regulated by Ssy1. We show that Gap4 is the functional orthologue of ScSam3, the only S-adenosylmethionine (SAM) transporter in S. cerevisiae, and we report that Gap4 is required for SAM-induced morphogenesis. IMPORTANCECandida albicans is a commensal organism that can thrive in many niches in its human host. The environmental conditions at these different niches differ quite a bit, and this fungus must be able to sense these changes and adapt its metabolism to them. Apart from glucose and other sugars, the uptake of amino acids is very important. This is underscored by the fact that the C. albicans genome encodes 6 orthologues of the Saccharomyces. cerevisiae general amino acid permease Gap1 and many other amino acid transporters. In this work, we characterize these six permeases and we show that C. albicans Gap2 is the functional orthologue of ScGap1 and that C. albicans Gap4 is an orthologue of ScSam3, an S-adenosylmethionine (SAM) transporter. Furthermore, we show that Gap4 is required for SAM-induced morphogenesis, an important virulence factor of C. albicans.

  14. [The effect of diet ratio of polyunsaturated fatty acids of omega-3 and omega-6 families on activity of aminotransferases and gamma-glutamyltransferase in rat blood serum].

    PubMed

    Ketsa, O V; Marchenko, M M

    2014-01-01

    The effect of diet fat compositions with various ratio of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) activities in blood serum of 45 white mongrel rats weighing 90-110 g (9 animals in group) has been investigated. Fat components in the semi-synthetic diet, compiled on the basis of AIN-93 diet, and sources of omega-6 and omega-3 PUFA were presented by sunflower oil, soybean oil and fish oil. It has been shown that four-week inclusion of linoleic acid (LA) and alpha-linolenic acid (alpha-LNA) in a ratio of 7:1 into the diet (soybean oil) as well as use of only omega-6 PUFA (sunflower oil) has lead to an increase in the activity of ALT and GGT in rat blood serum compared to control animals treated with the complex of linolenic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid through the mixture of sunflower oil and fish oil (9:1) with the ratio of omega-6 and omega-3 PUFA 7:1. Along with this, the AST:ALT ratio (de Ritis ratio) was lower (p < 0.05) as compared with the control group of rat, amounting respectively 0.92 +/- 0.08 and 0.79 +/- 0.12 vs 1.26 +/- 0.10. The use of high doses of omega-3 fatty acids (600 mg EPA and 400 mg DHA per kg of animal weight per day coming through fish oil) did not affect the activity of ALT and GGT, but increased AST serum activity (0.47 +/- 0.04 micromoles/min per mg protein) and the de Ritis ratio (2.53 +/- 0.23). The diet deprived with fat increased enzyme activity of ALT, AST and GGT in rat blood serum.

  15. Self-cleaving RNA: Characterization of a family of hammerhead self-cleaving ribonucleic acids by sup 1 H NMR spectroscopy

    SciTech Connect

    Caviani, A.M.

    1990-08-01

    Nucleic acid structure can be examined on two levels; macroscopic and microscopic. Macroscopically the structure of a particular nucleic acid correlates with its function within the cell. It is also found as double stranded helices, but in addition can adopt a more globular form; short double helical domains connected by single stranded regions. However different the macroscopic structure of nucleic acids, all are assembled from essentially the same microscopic building blocks. These building blocks of nucleic acids possess properties which are useful to NMR spectroscopists. Labile protons which can be observed under the conditions of hydrogen bonding are exemplified by the imino protons of the building blocks thymidine, uracil, and guanine. These protons are involved in a hydrogen bond when G, T, and U are paired with their corresponding partners in the Watson-Crick geometry. The imino protons of single stranded regions are generally not protected from exchange, and are not observed. NMR spectroscopy of the imino protons can furnish information about the tertiary, as well as the secondary, structure of a ribonucleic acid. Certainly the availability of the tRNA crystal structure simplified the assignment task for the NMR spectroscopists studying this molecule. Armed with this information, the spectroscopists, in a sense, already knew what to look for. In the absence of a crystal structure, one must be able to assign secondary and tertiary interactions whose origins are unknown. Finally, the motivation for the work in this thesis becomes clear; to study the structure of an RNA, in the absence of crystallographic information, not only to learn about the particular species under study, but also to begin laying a foundation for the general application of NMR spectroscopy to the study of relatively large RNA molecules.

  16. Mass spectrometric amino acid sequencing of a mixture of seed storage proteins (napin) from Brassica napus, products of a multigene family.

    PubMed

    Gehrig, P M; Krzyzaniak, A; Barciszewski, J; Biemann, K

    1996-04-16

    The amino acid sequences of a number of closely related proteins ("napin") isolated from Brassica napus were determined by mass spectrometry without prior separation into individual components. Some of these proteins correspond to those previously deduced (napA, BngNAP1, and gNa), chiefly from DNA sequences. Others were found to differ to a varying extent (BngNAP1', BngNAP1A, BngNAP1B, BngNAP1C, gNa', and gNaA). The short chains of gNa and gNa' and of BngNAP1 and BngNAP1' differ by the replacement of N-terminal proline by pyroglutamic acid; the long chains of gNaA and BngNAP1B contain a six amino acid stretch, MQGQQM, which is present in gNa (according to its DNA sequence) but absent from BngNAP1 and BngNAP1C. These alternations of sequences between napin isoforms are most likely due to homologous recombination of the genetic material, but some of the changes may also be due to RNA editing. The amino acids that follow the untruncated C termini of those napin chains for which the DNA sequences are known (napA, BngNAP1, and gNa) are aromatic amino acids. This suggests that the processing of the proprotein leading to the C termini of the two chains is due to the action of a protease that specifically cleaves a G/S-F/Y/W bond.

  17. Development of potential manufacturing routes for substituted thiophenes--preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides.

    PubMed

    Hull, John W; Romer, Duane R; Podhorez, David E; Ash, Mezzie L; Brady, Christine H

    2007-09-04

    Dow AgroSciences has been investigating a new family of functionalized 2,6-dihaloaryl 1,2,4-triazole insecticides featuring specifically targeted insecticidal activities coupled with low mammalian toxicity. With broad spectrum control of both chewing and sap-feeding pests in mind, this family of compounds has been under investigation for aphid, mite, and whitefly control in food crop protection as well as ornamental applications. Two specific targets for development have been the 2,6-dihalo 1,2,4-triazoles XR-693 and XR-906, which require a supply of the halogenated 2-thiophenecarboxylic acid derivatives 1, 2, and 3 for assembly of the C-ring portion of the triazole products. Potential manufacturing routes to three halogenated 2-thiophenecarboxylic acid derivatives 4-bromo-3-methyl-2-thiophenecarbonyl chloride 1, 3,4,5-trichloro-2-thiophenecarbonyl chloride 2, and 3,4,5-trichloro-2-thiophenecarbonitrile 3 from commercially available thiophene raw materials have been developed and demonstrated on a laboratory scale. A one-pot bromination/debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of 2-thiophenecarbonitrile with chlorine gas at 500 degrees C with an average residence time of 6 seconds gave 3,4,5-trichloro-2-thiophenenitrile 3 in a 69% distilled yield, a process that was carried out on a multi-kilogram scale in the laboratory. Finally, a route for the preparation of 3,4,5-trichloro-2-thiophenecarbonyl chloride 2 was developed from tetrachlorothiophene via either a lithiation reaction with n-butyllithium in MTBE solvent, or by a previously reported Grignard method using 1,2-dibromoethane as activator, followed by carbonation of the anion with CO2 to give the trichloro-2-thiophenecarboxylic acid, which was

  18. Development of potential manufacturing routes for substituted thiophenes – Preparation of halogenated 2-thiophenecarboxylic acid derivatives as building blocks for a new family of 2,6-dihaloaryl 1,2,4-triazole insecticides

    PubMed Central

    Hull, John W; Romer, Duane R; Podhorez, David E; Ash, Mezzie L; Brady, Christine H

    2007-01-01

    Background Dow AgroSciences has been investigating a new family of functionalized 2,6-dihaloaryl 1,2,4-triazole insecticides featuring specifically targeted insecticidal activities coupled with low mammalian toxicity. With broad spectrum control of both chewing and sap-feeding pests in mind, this family of compounds has been under investigation for aphid, mite, and whitefly control in food crop protection as well as ornamental applications. Two specific targets for development have been the 2,6-dihalo 1,2,4-triazoles XR-693 and XR-906, which require a supply of the halogenated 2-thiophenecarboxylic acid derivatives 1, 2, and 3 for assembly of the C-ring portion of the triazole products. Results Potential manufacturing routes to three halogenated 2-thiophenecarboxylic acid derivatives 4-bromo-3-methyl-2-thiophenecarbonyl chloride 1, 3,4,5-trichloro-2-thiophenecarbonyl chloride 2, and 3,4,5-trichloro-2-thiophenecarbonitrile 3 from commercially available thiophene raw materials have been developed and demonstrated on a laboratory scale. A one-pot bromination/debromination procedure developed for 3-methylthiophene gave 2,4-dibromo-3-methylthiophene. Carboxylic acid functionality was then introduced either by a Grignard metallation followed by carbonation with CO2, or by a palladium catalyzed carbonylation procedure under CO pressure. The vapor phase chlorination of 2-thiophenecarbonitrile with chlorine gas at 500°C with an average residence time of 6 seconds gave 3,4,5-trichloro-2-thiophenenitrile 3 in a 69% distilled yield, a process that was carried out on a multi-kilogram scale in the laboratory. Finally, a route for the preparation of 3,4,5-trichloro-2-thiophenecarbonyl chloride 2 was developed from tetrachlorothiophene via either a lithiation reaction with n-butyllithium in MTBE solvent, or by a previously reported Grignard method using 1,2-dibromoethane as activator, followed by carbonation of the anion with CO2 to give the trichloro-2-thiophenecarboxylic acid

  19. Natural and synthetic poly(malic acid)-based derivates: a family of versatile biopolymers for the design of drug nanocarriers.

    PubMed

    Loyer, Pascal; Cammas-Marion, Sandrine

    2014-08-01

    The field of specific drug delivery is an expanding research domain. Besides the use of liposomes formed from various lipids, natural and synthetic polymers have been developed to prepare more efficient drug delivery systems either under macromolecular prodrugs or under particulate nanovectors. To ameliorate the biocompatibility of such nanocarriers, degradable natural or synthetic polymers have attracted the interest of many researchers. In this context, poly(malic acid) (PMLA) extracted from microorganisms or synthesized from malic or aspartic acid was used to prepare water-soluble drug carriers or nanoparticles. Within this review, both the preparation and the applications of PMLA derivatives are described emphasizing the in vitro and in vivo assays. The results obtained by several groups highlight the interest of such polyesters in the field of drug delivery.

  20. Role of Transmembrane Domain 8 in Substrate Selectivity and Translocation of SteT, a Member of the l-Amino Acid Transporter (LAT) Family*

    PubMed Central

    Bartoccioni, Paola; del Rio, César; Ratera, Merce; Kowalczyk, Lukasz; Baldwin, Jocelyn M.; Zorzano, Antonio; Quick, Matthias; Baldwin, Stephen A.; Vázquez-Ibar, José Luis; Palacín, Manuel

    2010-01-01

    System l-amino acid transporters (LAT) belong to the amino acid, polyamine, and organic cation superfamily of transporters and include the light subunits of heteromeric amino acid transporters and prokaryotic homologues. Cysteine reactivity of SteT (serine/threonine antiporter) has been used here to study the substrate-binding site of LAT transporters. Residue Cys-291, in transmembrane domain 8 (TM8), is inactivated by thiol reagents in a substrate protectable manner. Surprisingly, DTT activated the transporter by reducing residue Cys-291. Cysteine-scanning mutagenesis of TM8 showed DTT activation in the single-cysteine mutants S287C, G294C, and S298C, lining the same α-helical face. S-Thiolation in Escherichia coli cells resulted in complete inactivation of the single-cysteine mutant G294C. l-Serine blocked DTT activation with an EC50 similar to the apparent KM of this mutant. Thus, S-thiolation abolished substrate translocation but not substrate binding. Mutation of Lys-295, to Cys (K295C) broadened the profile of inhibitors and the spectrum of substrates with the exception of imino acids. A structural model of SteT based on the structural homologue AdiC (arginine/agmatine antiporter) positions residues Cys-291 and Lys-295 in the putative substrate binding pocket. All this suggests that Lys-295 is a main determinant in the recognition of the side chain of SteT substrates. In contrast, Gly-294 is not facing the surface, suggesting conformational changes involving TM8 during the transport cycle. Our results suggest that TM8 sculpts the substrate-binding site and undergoes conformational changes during the transport cycle of SteT. PMID:20610400

  1. Perfluorooctanoic acid and environmental risks

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids (PFAA) family of chemicals, which consist of a carbon backbone typically four to fourteen carbons in length and a charged functional moiety.

  2. Perfluorooctanoic acid and environmental risks

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids (PFAA) family of chemicals, which consist of a carbon backbone typically four to fourteen carbons in length and a charged functional moiety.

  3. Plant fatty acid hydroxylases

    DOEpatents

    Somerville, Chris; Broun, Pierre; van de Loo, Frank

    2001-01-01

    This invention relates to plant fatty acyl hydroxylases. Methods to use conserved amino acid or nucleotide sequences to obtain plant fatty acyl hydroxylases are described. Also described is the use of cDNA clones encoding a plant hydroxylase to produce a family of hydroxylated fatty acids in transgenic plants. In addition, the use of genes encoding fatty acid hydroxylases or desaturases to alter the level of lipid fatty acid unsaturation in transgenic plants is described.

  4. Inactive methyl indole-3-acetic acid ester can be hydrolyzed and activated by several esterases belonging to the AtMES esterase family of Arabidopsis.

    PubMed

    Yang, Yue; Xu, Richard; Ma, Choong-Je; Vlot, A Corina; Klessig, Daniel F; Pichersky, Eran

    2008-07-01

    The plant hormone auxin (indole-3-acetic acid [IAA]) is found both free and conjugated to a variety of carbohydrates, amino acids, and peptides. We have recently shown that IAA could be converted to its methyl ester (MeIAA) by the Arabidopsis (Arabidopsis thaliana) enzyme IAA carboxyl methyltransferase 1. However, the presence and function of MeIAA in vivo remains unclear. Recently, it has been shown that the tobacco (Nicotiana tabacum) protein SABP2 (salicylic acid binding protein 2) hydrolyzes methyl salicylate to salicylic acid. There are 20 homologs of SABP2 in the genome of Arabidopsis, which we have named AtMES (for methyl esterases). We tested 15 of the proteins encoded by these genes in biochemical assays with various substrates and identified several candidate MeIAA esterases that could hydrolyze MeIAA. MeIAA, like IAA, exerts inhibitory activity on the growth of wild-type roots when applied exogenously. However, the roots of Arabidopsis plants carrying T-DNA insertions in the putative MeIAA esterase gene AtMES17 (At3g10870) displayed significantly decreased sensitivity to MeIAA compared with wild-type roots while remaining as sensitive to free IAA as wild-type roots. Incubating seedlings in the presence of [(14)C]MeIAA for 30 min revealed that mes17 mutants hydrolyzed only 40% of the [(14)C]MeIAA taken up by plants, whereas wild-type plants hydrolyzed 100% of absorbed [(14)C]MeIAA. Roots of Arabidopsis plants overexpressing AtMES17 showed increased sensitivity to MeIAA but not to IAA. Additionally, mes17 plants have longer hypocotyls and display increased expression of the auxin-responsive DR5:beta-glucuronidase reporter gene, suggesting a perturbation in IAA homeostasis and/or transport. mes17-1/axr1-3 double mutant plants have the same phenotype as axr1-3, suggesting MES17 acts upstream of AXR1. The protein encoded by AtMES17 had a K(m) value of 13 microm and a K(cat) value of 0.18 s(-1) for MeIAA. AtMES17 was expressed at the highest levels in shoot

  5. Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism.

    PubMed

    Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K; McMullan, Daniel; Krishna, S Sri; Miller, Mitchell D; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L; Feuerhelm, Julie; Grant, Joanna C; Grzechnik, Anna; Grzechnik, Slawomir K; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A; Klock, Heath E; Knuth, Mark W; Kozbial, Piotr; Marciano, David; Morse, Andrew T; Murphy, Kevin D; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L; Sefcovic, Natasha; Tien, Henry J; Trame, Christine B; Trout, Christina V; van den Bedem, Henry; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O; Wooley, John; Elsliger, Marc Andre; Deacon, Ashley M; Godzik, Adam; Lesley, Scott A; Wilson, Ian A

    2010-10-01

    The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis.

  6. The AP-3 adaptor complex mediates sorting of yeast and mammalian PQ-loop-family basic amino acid transporters to the vacuolar/lysosomal membrane

    PubMed Central

    Llinares, Elisa; Barry, Abdoulaye Oury; André, Bruno

    2015-01-01

    The limiting membrane of lysosomes in animal cells and that of the vacuole in yeast include a wide variety of transporters, but little is known about how these proteins reach their destination membrane. The mammalian PQLC2 protein catalyzes efflux of basic amino acids from the lysosome, and the similar Ypq1, −2, and −3 proteins of yeast perform an equivalent function at the vacuole. We here show that the Ypq proteins are delivered to the vacuolar membrane via the alkaline phosphatase (ALP) trafficking pathway, which requires the AP-3 adaptor complex. When traffic via this pathway is deficient, the Ypq proteins pass through endosomes from where Ypq1 and Ypq2 properly reach the vacuolar membrane whereas Ypq3 is missorted to the vacuolar lumen via the multivesicular body pathway. When produced in yeast, PQLC2 also reaches the vacuolar membrane via the ALP pathway, but tends to sort to the vacuolar lumen if AP-3 is defective. Finally, in HeLa cells, inhibiting the synthesis of an AP-3 subunit also impairs sorting of PQLC2 to lysosomes. Our results suggest the existence of a conserved AP-3-dependent trafficking pathway for proper delivery of basic amino acid exporters to the yeast vacuole and to lysosomes of human cells. PMID:26577948

  7. The AP-3 adaptor complex mediates sorting of yeast and mammalian PQ-loop-family basic amino acid transporters to the vacuolar/lysosomal membrane.

    PubMed

    Llinares, Elisa; Barry, Abdoulaye Oury; André, Bruno

    2015-11-18

    The limiting membrane of lysosomes in animal cells and that of the vacuole in yeast include a wide variety of transporters, but little is known about how these proteins reach their destination membrane. The mammalian PQLC2 protein catalyzes efflux of basic amino acids from the lysosome, and the similar Ypq1, -2, and -3 proteins of yeast perform an equivalent function at the vacuole. We here show that the Ypq proteins are delivered to the vacuolar membrane via the alkaline phosphatase (ALP) trafficking pathway, which requires the AP-3 adaptor complex. When traffic via this pathway is deficient, the Ypq proteins pass through endosomes from where Ypq1 and Ypq2 properly reach the vacuolar membrane whereas Ypq3 is missorted to the vacuolar lumen via the multivesicular body pathway. When produced in yeast, PQLC2 also reaches the vacuolar membrane via the ALP pathway, but tends to sort to the vacuolar lumen if AP-3 is defective. Finally, in HeLa cells, inhibiting the synthesis of an AP-3 subunit also impairs sorting of PQLC2 to lysosomes. Our results suggest the existence of a conserved AP-3-dependent trafficking pathway for proper delivery of basic amino acid exporters to the yeast vacuole and to lysosomes of human cells.

  8. ATP-Dependent Binding Cassette Transporter G Family Member 16 Increases Plant Tolerance to Abscisic Acid and Assists in Basal Resistance against Pseudomonas syringae DC30001[W][OPEN

    PubMed Central

    Ji, Hao; Peng, Yanhui; Meckes, Nicole; Allen, Sara; Stewart, C. Neal; Traw, M. Brian

    2014-01-01

    Plants have been shown previously to perceive bacteria on the leaf surface and respond by closing their stomata. The virulent bacterial pathogen Pseudomonas syringae pv tomato DC3000 (PstDC3000) responds by secreting a virulence factor, coronatine, which blocks the functioning of guard cells and forces stomata to reopen. After it is inside the leaf, PstDC3000 has been shown to up-regulate abscisic acid (ABA) signaling and thereby suppress salicylic acid-dependent resistance. Some wild plants exhibit resistance to PstDC3000, but the mechanisms by which they achieve this resistance remain unknown. Here, we used genome-wide association mapping to identify an ATP-dependent binding cassette transporter gene (ATP-dependent binding cassette transporter G family member16) in Arabidopsis (Arabidopsis thaliana) that contributes to wild plant resistance to PstDC3000. Through microarray analysis and β-glucuronidase reporter lines, we showed that the gene is up-regulated by ABA, bacterial infection, and coronatine. We also used a green fluorescent protein fusion protein and found that transporter is more likely to localize on plasma membranes than in cell walls. Transferred DNA insertion lines exhibited consistent defective tolerance of exogenous ABA and reduced resistance to infection by PstDC3000. Our conclusion is that ATP-dependent binding cassette transporter G family member16 is involved in ABA tolerance and contributes to plant resistance against PstDC3000. This is one of the first examples, to our knowledge, of ATP-dependent binding cassette transporter involvement in plant resistance to infection by a bacterial pathogen. It also suggests a possible mechanism by which plants reduce the deleterious effects of ABA hijacking during pathogen attack. Collectively, these results improve our understanding of basal resistance in Arabidopsis and offer unique ABA-related targets for improving the innate resistance of plants to bacterial infection. PMID:25146567

  9. Family Empowerment.

    ERIC Educational Resources Information Center

    Sinclair, Mary F., Ed.; And Others

    1992-01-01

    This feature issue of IMPACT focuses on the empowerment of families with a member who has a developmental disability. It presents strategies and models for a collaborative, respectful approach to service provision, and presents the experiences of families in seeking support and assistance. Feature articles include "Two Generations of…

  10. Family Life.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

  11. Family Potyviridae

    USDA-ARS?s Scientific Manuscript database

    The International Committee on the Taxonomy of Viruses potyvirus study group has revised the description of the family Potyviridae for inclusion in the ICTV 9th report. Characteristic features of each genus within the family is presented. Revised criteria for demarcation and nomenclature of viral sp...

  12. Family, Extended

    ERIC Educational Resources Information Center

    Patton, Jessica Rae

    2006-01-01

    Parents are a child's first and most influential teacher. People hear this truism often, yet nowhere has the author seen it more taken to heart than at Tower Street Elementary School. The school's efforts to form a true partnership with students' families--from involving families in the first day of school, to the principal making home visits, to…

  13. Family Workshops

    ERIC Educational Resources Information Center

    Bennett, Dave; Rees-Jones, Tanny

    1978-01-01

    A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

  14. Family Workshops

    ERIC Educational Resources Information Center

    Bennett, Dave; Rees-Jones, Tanny

    1978-01-01

    A Family Workshop is an informal, multidisciplined educational program for adults and children, organized by a team of teachers. This article discusses the Lavender Hill Family Workshop, one of many, which attempts to provide education in various subject areas for adults and for children while also integrating both objectives in order to educate…

  15. Family Reunification

    ERIC Educational Resources Information Center

    Wulczyn, Fred

    2004-01-01

    Reunifying children placed in foster care with their birth parents is a primary goal of the child welfare system. Yet, relatively little is known about the reunification process. This article analyzes new data on trends in family reunification and discovers: (1) Although most children still exit foster care through family reunification, exit…

  16. Family Life.

    ERIC Educational Resources Information Center

    Naturescope, 1986

    1986-01-01

    Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

  17. GmCYP82A3, a Soybean Cytochrome P450 Family Gene Involved in the Jasmonic Acid and Ethylene Signaling Pathway, Enhances Plant Resistance to Biotic and Abiotic Stresses

    PubMed Central

    Yan, Qiang; Cui, Xiaoxia; Lin, Shuai; Gan, Shuping; Xing, Han; Dou, Daolong

    2016-01-01

    The cytochrome P450 monooxygenases (P450s) represent a large and important enzyme superfamily in plants. They catalyze numerous monooxygenation/hydroxylation reactions in biochemical pathways, P450s are involved in a variety of metabolic pathways and participate in the homeostasis of phytohormones. The CYP82 family genes specifically reside in dicots and are usually induced by distinct environmental stresses. However, their functions are largely unknown, especially in soybean (Glycine max L.). Here, we report the function of GmCYP82A3, a gene from soybean CYP82 family. Its expression was induced by Phytophthora sojae infection, salinity and drought stresses, and treatment with methyl jasmonate (MeJA) or ethephon (ETH). Its expression levels were consistently high in resistant cultivars. Transgenic Nicotiana benthamiana plants overexpressing GmCYP82A3 exhibited strong resistance to Botrytis cinerea and Phytophthora parasitica, and enhanced tolerance to salinity and drought stresses. Furthermore, transgenic plants were less sensitive to jasmonic acid (JA), and the enhanced resistance was accompanied with increased expression of the JA/ET signaling pathway-related genes. PMID:27588421

  18. Levels of free fatty acids (FFA) are associated with insulin resistance but do not explain the relationship between adiposity and insulin resistance in Hispanic Americans: the IRAS Family Study.

    PubMed

    Miller, Melissa R; Pereira, Rocio I; Langefeld, Carl D; Lorenzo, Carlos; Rotter, Jerome I; Chen, Yii-Der Ida; Bergman, Richard N; Wagenknecht, Lynne E; Norris, Jill M; Fingerlin, Tasha E

    2012-09-01

    We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study. In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S(I)); and 3) levels of adiposity and S(I), additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S(I.) After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P = 2.33 × 10(-3); SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S(I) (P = 8.10 × 10(-11)). Increasing BMI, VAT, and SAT were also associated with decreasing S(I) (BMI: P = 4.98 × 10(-71); VAT: P = 1.48 × 10(-64); SAT: P = 4.21 × 10(-62)), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S(I) (P = 0.021). Although levels of circulating FFA are associated both with increasing adiposity and decreasing S(I), they do not appear to mediate the association between levels of adiposity and S(I) in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.

  19. A family of entangled coordination polymers constructed from a flexible V-shaped long bicarboxylic acid and auxiliary N-donor ligands: Luminescent sensing

    NASA Astrophysics Data System (ADS)

    Wang, Jun; Bai, Chao; Hu, Huai-Ming; Yuan, Fei; Xue, Gang-Lin

    2017-05-01

    Eight Zn(II)-based coordination polymers, namely, [Zn2L2(2,2'-bipy)]n·nH2O (1), [Zn2L2(phen)]n·nH2O (2), [ZnL(phen)(H2O)]n (3), [Zn3L3(4,4'-bipy)]n (4), [Zn2L2(4,4'-bipy)2]n [Zn2L2(H2O)2]n·2nH2O (5), [Zn4L4(bpp)2]n (6), [ZnL(bbi)0.5]n (7), [ZnL(bpz)]n (8) (H2L=4,4'-{[1,2-phenylenebis-(methylene)]bis(oxy)}dibenzoic acid, 2,2'-bipy =2,2'-bipyridine, phen =1,10-phenanthroline, 4,4'-bpy=4,4'-bipyridine, bpp =1,3-bis(4-pyridyl)propane, bbi=1,4-bis(imidazol-1-yl)butane, bpz=3,3‧,5,5‧-tetramethyl-4,4‧-bipyrazole), have been hydrothermally synthesized and structurally characterized. 1-8 display various coordination motifs with different entangled forms and conformations due to the effect of the assistant N-donor ligands. The photoluminescent properties of compounds 1-8 in solid state were studied. Interestingly, 3 exhibits highly efficient luminescent sensing for Cu2+ cations and CrO42- anions, as well as detection ability for the different organic solvents and nitro explosives. These results indicated that it could be utilized as a multi-responsive luminescent sensor. Furthermore, compound 3 also shows good chemical resistance to both acidity and alkalinity solutions with pH ranging from 2 to 13. Thus, multi-photofunctionality and fluorescent response to pH have been combined in the 3, which is the first example in the Zn-based hybrid materials.

  20. In vitro evaluation of the genotoxicity of a family of novel MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer and PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    He, Lili; Yang, Likai; Zhang, Zhi-rong; Gong, Tao; Deng, Li; Gu, Zhongwei; Sun, Xun

    2009-11-01

    Despite the booming development of nanoparticle materials for pharmaceutical applications, studies on their genotoxicity are few. In our previous efforts to develop an intravenous nanoparticle material, a family of novel monomethoxy(polyethylene glycol)-poly(D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) polymers was synthesized. The cytotoxicity and genotoxicity of nine kinds of selected blank PELGE and PLGA (poly(D,L-lactic and glycolic acid)) nanoparticles were evaluated using methyl thiazolyl tetrazolium (MTT), micronucleus (MN) and sister chromatid exchange (SCE) assays with or without the addition of a metabolic activation system (S9 mix), using Chinese hamster ovary (CHO) cells. The cytotoxicity of nanoparticles exhibited a dose-dependent response, with a concentration of 5 mg ml-1 being the turning point. The frequencies of MN observed in samples treated with various nanoparticles were not statistically different from those seen in the negative controls in the presence or absence of the S9 mix. Also, no cell cycle delay was observed. The numbers of SCE per cell observed in samples treated with five kinds of PELGE nanoparticles were significantly greater than those found in the negative controls with or without the S9 mix. The discrepancies found in the two assays suggest that the five kinds of nanoparticles may produce only a weakly clastogenic response.

  1. Family Health and Family Planning.

    ERIC Educational Resources Information Center

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This document is made up of a selection of some of the papers distributed to participants in courses on "Family Health and Family Planning" which have been organized each year since 1973 by the International Children's Center and the World Health Organization Regional Office for Europe. Six courses, held between 1973 and 1978, brought together a…

  2. Family Health and Family Planning.

    ERIC Educational Resources Information Center

    World Health Organization, Copenhagen (Denmark). Regional Office for Europe.

    This document is made up of a selection of some of the papers distributed to participants in courses on "Family Health and Family Planning" which have been organized each year since 1973 by the International Children's Center and the World Health Organization Regional Office for Europe. Six courses, held between 1973 and 1978, brought together a…

  3. Lead discovery for mammalian elongation of long chain fatty acids family 6 using a combination of high-throughput fluorescent-based assay and RapidFire mass spectrometry assay.

    PubMed

    Takamiya, Mari; Sakurai, Masaaki; Teranishi, Fumie; Ikeda, Tomoko; Kamiyama, Tsutomu; Asai, Akira

    2016-11-25

    A high-throughput RapidFire mass spectrometry assay is described for elongation of very long-chain fatty acids family 6 (Elovl6). Elovl6 is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids. Elovl6 may be a new therapeutic target for fat metabolism disorders such as obesity, type 2 diabetes, and nonalcoholic steatohepatitis. To identify new Elovl6 inhibitors, we developed a high-throughput fluorescence screening assay in 1536-well format. However, a number of false positives caused by fluorescent interference have been identified. To pick up the real active compounds among the primary hits from the fluorescence assay, we developed a RapidFire mass spectrometry assay and a conventional radioisotope assay. These assays have the advantage of detecting the main products directly without using fluorescent-labeled substrates. As a result, 276 compounds (30%) of the primary hits (921 compounds) in a fluorescence ultra-high-throughput screening method were identified as common active compounds in these two assays. It is concluded that both methods are very effective to eliminate false positives. Compared with the radioisotope method using an expensive (14)C-labeled substrate, the RapidFire mass spectrometry method using unlabeled substrates is a high-accuracy, high-throughput method. In addition, some of the hit compounds selected from the screening inhibited cellular fatty acid elongation in HEK293 cells expressing Elovl6 transiently. This result suggests that these compounds may be promising lead candidates for therapeutic drugs. Ultra-high-throughput fluorescence screening followed by a RapidFire mass spectrometry assay was a suitable strategy for lead discovery against Elovl6.

  4. Asteroid families

    NASA Astrophysics Data System (ADS)

    Nesvorný, David; Bottke, William F.; Vokrouhlický, David; Morbidelli, Alessandro; Jedicke, Robert

    An asteroid family is a group of asteroids with similar orbits and spectra that was produced by a collisional breakup of a large parent body. To identify asteroid families, researchers look for clusters of asteroid positions in the space of proper orbital elements. These elements, being more constant over time than osculating orbital elements, provide a dynamical criterion of whether a group of bodies has a common ancestor. More than fifty asteroid families have been identified to date. Their analysis produced several important insights into the physics of large scale collisions, dynamical processes affecting small bodies in the Solar System, and surface and interior properties of asteroids.

  5. Conversion of nicotinic acid to trigonelline is catalyzed by N-methyltransferase belonged to motif B′ methyltransferase family in Coffea arabica

    SciTech Connect

    Mizuno, Kouichi; Matsuzaki, Masahiro; Kanazawa, Shiho; Tokiwano, Tetsuo; Yoshizawa, Yuko; Kato, Misako

    2014-10-03

    Graphical abstract: Trigonelline synthase catalyzes the conversion of nicotinic acid to trigonelline. We isolated and characterized trigonelline synthase gene(s) from Coffea arabica. - Highlights: • Trigonelline is a major compound in coffee been same as caffeine is. • We isolated and characterized trigonelline synthase gene. • Coffee trigonelline synthases are highly homologous with coffee caffeine synthases. • This study contributes the fully understanding of pyridine alkaloid metabolism. - Abstract: Trigonelline (N-methylnicotinate), a member of the pyridine alkaloids, accumulates in coffee beans along with caffeine. The biosynthetic pathway of trigonelline is not fully elucidated. While it is quite likely that the production of trigonelline from nicotinate is catalyzed by N-methyltransferase, as is caffeine synthase (CS), the enzyme(s) and gene(s) involved in N-methylation have not yet been characterized. It should be noted that, similar to caffeine, trigonelline accumulation is initiated during the development of coffee fruits. Interestingly, the expression profiles for two genes homologous to caffeine synthases were similar to the accumulation profile of trigonelline. We presumed that these two CS-homologous genes encoded trigonelline synthases. These genes were then expressed in Escherichiacoli, and the resulting recombinant enzymes that were obtained were characterized. Consequently, using the N-methyltransferase assay with S-adenosyl[methyl-{sup 14}C]methionine, it was confirmed that these recombinant enzymes catalyzed the conversion of nicotinate to trigonelline, coffee trigonelline synthases (termed CTgS1 and CTgS2) were highly identical (over 95% identity) to each other. The sequence homology between the CTgSs and coffee CCS1 was 82%. The pH-dependent activity curve of CTgS1 and CTgS2 revealed optimum activity at pH 7.5. Nicotinate was the specific methyl acceptor for CTgSs, and no activity was detected with any other nicotinate derivatives, or

  6. Variation of S/G Ratio and Lignin Content in a Populus Family Influences the Release of Xylose by Dilute Acid Hydrolysis.

    SciTech Connect

    Davison, Brian H; Drescher, Sadie R; Tuskan, Gerald A; Davis, Dr. Mark F.; Nghiem, Nhuan Phu

    2006-01-01

    Wood samples from second generation Populus cross were shown to have different lignin contents and S/G ratios (S: syringyl-like lignin structures; G: guaiacyl-like lignin structures). The lignin contents varied from 22.7% to 25.8% and the S/G ratio from 1.8 to 2.3. Selected samples spanning these ranges were hydrolyzed with dilute (1%) sulfuric acid to release fermentable sugars. The conditions were chosen for partial hydrolysis of the hemicellulosic fraction to maximize the expression of variation among samples. The results indicated that both lignin contents and S/G ratio significantly affected the yield of xylose. For example, the xylose yield of the 25.8% lignin and 2.3 S/G (hihg lignin, high S/G) sample produced 30% of the theoretical yield, whereas the xylose yield of the 22.7% lignin and 1.8 S/G (low lignin, low S/G) was 55% of the theoretical value. These results indicate that lignin content and composition among genetic variants within a single species can influence the hydrolyzability of the biomass.

  7. FAMILY PIOPHILIDAE.

    PubMed

    Wolff, Marta; Pérez, Sandra; Grisales, Diana

    2016-06-14

    Piophilidae is a little family poorly known in Colombia, with only Piophila casei (L.) and Stearibia nigriceps Meigen reported so far. This catalogue expands the distribution of these species to other localities in the country.

  8. Unusual families.

    PubMed

    Golombok, Susan

    2005-03-01

    The introduction of assisted reproduction has led to unusual forms of procreation. This article describes the social consequences of lesbian motherhood and of families headed by single heterosexual mothers.

  9. Family dysfunction

    PubMed Central

    Hayaki, Chie; Anno, Kozo; Shibata, Mao; Iwaki, Rie; Kawata, Hiroshi; Sudo, Nobuyuki; Hosoi, Masako

    2016-01-01

    Abstract Previous studies have shown differences in the psychosocial factors related to chronic localized pain (CLP) and chronic widespread pain (CWP). However, no studies have done an evaluation of differences between CLP and CWP from the viewpoint of family functioning. We did a cross-sectional study in a tertiary care setting to investigate possible differences in the relation of CWP and CLP to family functioning. Patients with CLP (N = 126) or CWP (N = 75) were assessed for family functioning by the Family Assessment Device (FAD) and a comparison was done. Logistic regression analysis was used to estimate associations of family functioning subscales with pain status (CWP vs CLP), controlling for demographic variables, pain variables; pain duration, pain ratings, pain disability, and psychological factors; depression, anxiety, and catastrophizing. The odds ratios (ORs) for the presence of CWP were calculated. Compared to patients with CLP, patients with CWP showed a lower functional status for Roles and Affective Involvement. The ORs for CWP were significantly higher in lower functioning Roles (OR: 2.38, 95% CI: 1.21–4.65) and Affective Involvement (OR: 2.86, 95% CI: 1.56–5.24) after adjusting for demographic variables. The significant association of CWP to Roles and Affective Involvement remained after controlling for the pain variables and psychological factors. This study shows that the families of patients with CWP have poorer family functioning than those with CLP. Our findings suggest that early identification and interventions for the family dysfunction of chronic pain patients are important to the treatment and prevention of CWP. PMID:27930535

  10. A new IS4 family insertion sequence, IS4Bsu1, responsible for genetic instability of poly-gamma-glutamic acid production in Bacillus subtilis.

    PubMed

    Nagai, T; Tran, L S; Inatsu, Y; Itoh, Y

    2000-05-01

    Certain Bacillus subtilis strains, such as B. subtilis (natto) starter strains for the manufacture of natto (fermented soybeans), produce capsular poly-gamma-glutamate (gammaPGA). In B. subtilis (natto), gammaPGA synthesis is controlled by the ComP-ComA two-component regulatory system and thereby induced at the beginning of the stationary growth phase. We have found a new insertion sequence (IS), designated IS4Bsu1, in the comP gene of a spontaneous gammaPGA-negative mutant of B. subtilis (natto) NAF4. IS4Bsu1 (1,406 bp), the first IS discovered in B. subtilis, encodes a putative transposase (Tpase) with a predicted M(r) of 34,895 (374 residues) which displays similarity to the Tpases of IS4 family members. Southern blot analyses have identified 6 to 11 copies of IS4Bsu1, among which 6 copies were at the same loci, in the chromosomes of B. subtilis (natto) strains, including NAF4, three commercial starters, and another three gammaPGA-producing B. subtilis (natto) strains. All of the eight spontaneous gammaPGA(-) mutants, which were derived from five independent NAF4 cultures, had a new additional IS4Bsu1 copy in comP at six different positions within 600 bp of the 5'-terminal region. The target sites of IS4Bsu1 were determined to be AT-rich 9-bp sequences by sequencing the flanking regions of IS4Bsu1 in mutant comP genes. These results indicate that IS4Bsu1 transposes by the replicative mechanism, in contrast to other IS4 members that use the conservative mechanism, and that most, if not all, of spontaneous gammaPGA(-) mutants appear to have resulted from the insertion of IS4Bsu1 exclusively into comP. The presence of insertion hot spots in comP, which is essential for gammaPGA synthesis, as well as high transposition activity, would account for the high frequency of spontaneous gammaPGA(-) mutation by IS4Bsu1 in B. subtilis (natto).

  11. A New IS4 Family Insertion Sequence, IS4Bsu1, Responsible for Genetic Instability of Poly-γ-Glutamic Acid Production in Bacillus subtilis

    PubMed Central

    Nagai, Toshiro; Phan Tran, Lam-Son; Inatsu, Yasuhiro; Itoh, Yoshifumi

    2000-01-01

    Certain Bacillus subtilis strains, such as B. subtilis (natto) starter strains for the manufacture of natto (fermented soybeans), produce capsular poly-γ-glutamate (γPGA). In B. subtilis (natto), γPGA synthesis is controlled by the ComP-ComA two-component regulatory system and thereby induced at the beginning of the stationary growth phase. We have found a new insertion sequence (IS), designated IS4Bsu1, in the comP gene of a spontaneous γPGA-negative mutant of B. subtilis (natto) NAF4. IS4Bsu1 (1,406 bp), the first IS discovered in B. subtilis, encodes a putative transposase (Tpase) with a predicted Mr of 34,895 (374 residues) which displays similarity to the Tpases of IS4 family members. Southern blot analyses have identified 6 to 11 copies of IS4Bsu1, among which 6 copies were at the same loci, in the chromosomes of B. subtilis (natto) strains, including NAF4, three commercial starters, and another three γPGA-producing B. subtilis (natto) strains. All of the eight spontaneous γPGA− mutants, which were derived from five independent NAF4 cultures, had a new additional IS4Bsu1 copy in comP at six different positions within 600 bp of the 5′-terminal region. The target sites of IS4Bsu1 were determined to be AT-rich 9-bp sequences by sequencing the flanking regions of IS4Bsu1 in mutant comP genes. These results indicate that IS4Bsu1 transposes by the replicative mechanism, in contrast to other IS4 members that use the conservative mechanism, and that most, if not all, of spontaneous γPGA− mutants appear to have resulted from the insertion of IS4Bsu1 exclusively into comP. The presence of insertion hot spots in comP, which is essential for γPGA synthesis, as well as high transposition activity, would account for the high frequency of spontaneous γPGA− mutation by IS4Bsu1 in B. subtilis (natto). PMID:10762236

  12. A family of silver(I) complexes built with 2-sulfoterephthalic acid monosodium salt and different aminopyridine ligands: Syntheses, structures and properties

    NASA Astrophysics Data System (ADS)

    Zhang, Jie; Tan, Gai-Xiu; Liu, Bao-Lin; Dai, Yu-Bei; Xu, Na; Wen, Wei-Fen; Cao, Chong; Xiao, Hong-Ping

    2017-05-01

    Five Ag(I) coordination complexes, namely, [Ag6(2-stp)2(3-methyl-2-apy)3·H2O]n (1), [Ag3(2-stp)(4-methyl-2-apy)3]n (2), [Na2Ag18(2-stp)4(2-Hstp)4(5-methyl-2-apy)16 (H2O)4·11H2O]n (3), Ag3(2-stp)(6-methy-2-apy)4·H2O (4), and [Ag6(2-stp)2(6-methyl-2-apy)8(H2O)2·H2O]n (5) (2-NaH2stp = 2-sulfoterephthalic acid monosodium salt, 3-methyl-2-apy = 3-methyl-2-aminopyridine, 4-methyl-2-apy = 4-methyl-2-aminopyridine, 5-methyl-2-apy = 5-methyl-2-aminopyridine, 6-methyl-2-apy = 6-methyl-2-aminopyridine), have been synthesized and structurally characterized. Complexes 1 and 2 show two-dimensional network. In complex 3, the adjacent Ag10 units are bridged by 5-methyl-2-apy ligands to form a 2D infinite undulated sheet. Adjacent 2D sheets are linked by coordinative bonds between carboxylic oxygen atoms and Na(I) ions to form a 3D coordination polymer. Complex 4 is a 0-D discrete trinuclear molecule, and the self-complementary the Osbnd H⋯O and Nsbnd H⋯O hydrogen bonds incorporating hydrogen bond motifs extend these molecules into a 2D supramolecular framework. Compound 5 exhibits 1D-chain structure. However, complex 5 shows 3D supramolecular structure results from the linkage of neighboring layers through a rich hydrogen-bonding between uncoordinated sulfonates, amino groups and coordinated carboxylates. The thermogravimetric analyses and photoluminescence of the complexes were also investigated.

  13. Cloning and Phylogenetic Analysis of Brassica napus L. Caffeic Acid O-Methyltransferase 1 Gene Family and Its Expression Pattern under Drought Stress

    PubMed Central

    Lu, Kun; Yuan, Jianglian; Huang, Jieheng; Du, Hai; Li, Jiana

    2016-01-01

    For many plants, regulating lignin content and composition to improve lodging resistance is a crucial issue. Caffeic acid O-methyltransferase (COMT) is a lignin monomer-specific enzyme that controls S subunit synthesis in plant vascular cell walls. Here, we identified 12 BnCOMT1 gene homologues, namely BnCOMT1-1 to BnCOMT1-12. Ten of 12 genes were composed of four highly conserved exons and three weakly conserved introns. The length of intron I, in particular, showed enormous diversification. Intron I of homologous BnCOMT1 genes showed high identity with counterpart genes in Brassica rapa and Brassica oleracea, and intron I from positional close genes in the same chromosome were relatively highly conserved. A phylogenetic analysis suggested that COMT genes experience considerable diversification and conservation in Brassicaceae species, and some COMT1 genes are unique in the Brassica genus. Our expression studies indicated that BnCOMT1 genes were differentially expressed in different tissues, with BnCOMT1-4, BnCOMT1-5, BnCOMT1-8, and BnCOMT1-10 exhibiting stem specificity. These four BnCOMT1 genes were expressed at all developmental periods (the bud, early flowering, late flowering and mature stages) and their expression level peaked in the early flowering stage in the stem. Drought stress augmented and accelerated lignin accumulation in high-lignin plants but delayed it in low-lignin plants. The expression levels of BnCOMT1s were generally reduced in water deficit condition. The desynchrony of the accumulation processes of total lignin and BnCOMT1s transcripts in most growth stages indicated that BnCOMT1s could be responsible for the synthesis of a specific subunit of lignin or that they participate in other pathways such as the melatonin biosynthesis pathway. PMID:27832102

  14. Staphylococcus aureus Mutants Lacking the LytR-CpsA-Psr Family of Enzymes Release Cell Wall Teichoic Acids into the Extracellular Medium

    PubMed Central

    Chan, Yvonne G. Y.; Frankel, Matthew B.; Dengler, Vanina; Schneewind, Olaf

    2013-01-01

    The LytR-CpsA-Psr (LCP) proteins are thought to transfer bactoprenol-linked biosynthetic intermediates of wall teichoic acid (WTA) to the peptidoglycan of Gram-positive bacteria. In Bacillus subtilis, mutants lacking all three LCP enzymes do not deposit WTA in the envelope, while Staphylococcus aureus Δlcp mutants display impaired growth and reduced levels of envelope phosphate. We show here that the S. aureus Δlcp mutant synthesized WTA yet released ribitol phosphate polymers into the extracellular medium. Further, Δlcp mutant staphylococci no longer restricted the deposition of LysM-type murein hydrolases to cell division sites, which was associated with defects in cell shape and increased autolysis. Mutations in S. aureus WTA synthesis genes (tagB, tarF, or tarJ2) inhibit growth, which is attributed to the depletion of bactoprenol, an essential component of peptidoglycan synthesis (lipid II). The growth defect of S. aureus tagB and tarFJ mutants was alleviated by inhibition of WTA synthesis with tunicamycin, whereas the growth defect of the Δlcp mutant was not relieved by tunicamycin treatment or by mutation of tagO, whose product catalyzes the first committed step of WTA synthesis. Further, sortase A-mediated anchoring of proteins to peptidoglycan, which also involves bactoprenol and lipid II, was not impaired in the Δlcp mutant. We propose a model whereby the S. aureus Δlcp mutant, defective in tethering WTA to the cell wall, cleaves WTA synthesis intermediates, releasing ribitol phosphate into the medium and recycling bactoprenol for peptidoglycan synthesis. PMID:23935043

  15. Importance of Family Routines

    MedlinePlus

    ... Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care Communication & Discipline Types of Families Media Work & Play Getting Involved in Your Community Healthy Children > Family Life > Family Dynamics > The Importance of Family ...

  16. Toxicology of Perfluoroalkyl Acids*

    EPA Science Inventory

    The perfluoroalkyl acids (PFAAs) are a family of organic chemicals consisting of a perfluorinated carbon backbone (4-12 in length) and an acidic functional moiety (carboxylate or sulfonate). These compounds are chemically stable, have excellent surface-tension reducing properties...

  17. Family welfare.

    PubMed

    Sinha, N K

    1992-01-01

    Between 1901-1921, India gained 12.9 million people because mortality remained high. The death rate fell between 1921-1951, but birth rates remained the same. Therefore 110 million people were added--2 times the population increase between 1891-1921. Between 1951-1981, the population increased to 324 million. Socioeconomic development was responsible for most of the downward trend in the birth rate during the 20th century. Even though large families were the norm in early India, religious leaders encouraged small family size. The 1st government family planning clinics in the world opened in Mysore and Bangalore in 1930. Right before Independence, the Bhore Committee made recommendations to reduce population growth such as increasing the age of marriage for girls. Since 1951 there has been a change in measures and policies geared towards population growth with each of the 7 5-Year Plans because policy makers applied what they learned from each previous plan. The 1st 5-Year Plan emphasized the need to understand what factors contribute to population growth. It also integrated family planning services into health services of hospitals and health centers. The government was over zealous in its implementation of the sterilization program (2nd 5-Year Plan, 1956-1961), however, which hurt family planning programs for many years. As of early 1992, sterilization, especially tubectomy, remained the most popular family planning method, however. The 7th 5-Year Plan changed its target of reaching a Net Reproductive Rate of 1 by 2001 to 2006-2011. It set a goal of 100% immunization coverage by 1990 but it did not occur. In 1986, the Ministry of Health and Family Welfare planned to make free contraceptives available in urban and rural areas and to involve voluntary organizations. The government needs to instill measures to increase women's status, women's literacy, and age of marriage as well as to eliminate poverty, ensure old age security, and ensure child survival and

  18. [Correction of polyhypovitaminosis in rats, having standard and enriched with polyunsaturated fatty acids family omega-3 diets with different doses of vitamins].

    PubMed

    Beketova, N A; Vrzhesinskaia, O A; Kodentsova, V M; Kosheleva, O V; Preverzeva, O G; Sokol'nikov, A A

    2013-01-01

    The efficiency of the correction of combined alimentary vitamin deficit in male Wistar rats (body weight 90-121 g) fed standard diet or enriched with omega-3 polyunsaturated fatty acids diet (by replacing sunflower oil (4.5% of the diet) with linseed oil) with different doses (physiological and enhanced) of vitamins has been investigated. The control group of animals (n = 12) received a complete semisynthetic diet during all experimental period (42 d). The animals of the test groups (each of 20 rats) received vitamin-deficient diet containing sunflower or linseed oil and 20% per cent of vitamin mixture amount in control diet from which vitamin E had been excluded. After 28 days of such feeding each of test groups was divided into two subgroups (6-8 rats in each), and the next 14 days the animals of subgroups received the diet with different degree of vitamin compensation (50 or 180% percent of vitamin content in the diet of the control group). The addition of both low and high vitamin dose in deficient diet based on standard fat component did not compensate the reduced liver vitamin A content, which amounted to 47.4% of the level in the liver of the control group. The lack of vitamin E in animals was eliminated only after adding of the enhanced dose of vitamin E to the ration. Recovering of decreased plasma and liver B2 level, plasma 25(OH)D and liver vitamin B1 content have been occurred after addition of the low dose of these vitamins to rat diet. Increasing of omega-3 PUFA diet level improved vitamins A and D sufficiency to some extent, but was accompanied by the significant reduction of rat liver alfa-tocopherol content both under combined vitamin deficiency (by 14%) and increased vitamins consumption (by 43%). PUFA enrichment of the diet of rats with vitamin deficiency had no impact on vitamin B1 and B2 liver level. The use of high doses of vitamins for a long time to eliminate a combined deficiency of vitamins has been proved.

  19. Cloning and characterization of phosphorus starvation inducible Brassica napus PURPLE ACID PHOSPHATASE 12 gene family, and imprinting of a recently evolved MITE-minisatellite twin structure.

    PubMed

    Lu, Kun; Chai, You-Rong; Zhang, Kai; Wang, Rui; Chen, Li; Lei, Bo; Lu, Jun; Xu, Xin-Fu; Li, Jia-Na

    2008-10-01

    Purple acid phosphatase (PAP) is important for phosphorus assimilation and in planta redistribution. In this study, seven Brassica napus PAP12 (BnPAP12) genes orthologous to Arabidopsis thaliana PAP12 (AtPAP12) are isolated and characterized. NCBI BLASTs, multi-alignments, conserved domain prediction, and featured motif/residue characterization indicate that all BnPAP12 members encode dimeric high molecular weight plant PAPs. BnPAP12-1, BnPAP12-2, BnPAP12-3 and BnPAP12-7 (Group I) have six introns and encode 469-aa polypeptides structurally comparable to AtPAP12. BnPAP12-4 and BnPAP12-6 (Group II) have seven introns and encode 526-aa PAP12s. Encoding a 475-aa polypeptide, BnPAP12-5 (Group III) is evolved from a chimera of 5' part of Group I and 3' part of Group II. Sequence characterization and Southern detection suggest that there are about five BnPAP12 alleles. Homoeologous non-allelic fragment exchanges exist among BnPAP12 genes. BnPAP12-4 and BnPAP12-6 are imprinted with a Tourist-like miniature inverted-repeat transposable element (MITE) which is tightly associated with a novel minisatellite composed of four 36-bp tandem repeats. Existing solely in B. rapa/oleracea lineage, this recently evolved MITE-minisatellite twin structure does not impair transcription and coding capacity of the imprinted genes, and could be used to identify close relatives of B. rapa/oleracea lineage within Brassica. It is also useful for studying MITE activities especially possible involvement in minisatellite formation and gene structure evolution. BnPAP12-6 is silent in transcription. All other BnPAP12 genes basically imitate AtPAP12 in tissue specificity and Pi-starvation induced expression pattern, but divergence and complementation are distinct among them. Alternative polyadenylation and intron retention also exist in BnPAP12 mRNAs.

  20. Multigene families in African swine fever virus: family 505.

    PubMed Central

    Rodriguez, J M; Yañez, R J; Pan, R; Rodriguez, J F; Salas, M L; Viñuela, E

    1994-01-01

    Sequencing of restriction fragment EcoRI A-SalI C of African swine fever virus has revealed the existence of a multigene family, designated family 505 because of the average number of amino acids in the proteins, composed of seven homologous and tandemly arranged genes. All the genes of family 505 are expressed during infection. Primer extension analysis showed that transcription is initiated a short distance (3 to 62 nucleotides) from the start codon of the corresponding open reading frame. The proteins of family 505 showed similarity to those of family 360 from African swine fever virus. In particular, a striking conservation of three regions at the amino terminus of the polypeptides was observed. Images PMID:8139051

  1. The "putative" role of transcription factors from HlWRKY family in the regulation of the final steps of prenylflavonid and bitter acids biosynthesis in hop (Humulus lupulus L.).

    PubMed

    Matoušek, Jaroslav; Kocábek, Tomáš; Patzak, Josef; Bříza, Jindřich; Siglová, Kristýna; Mishra, Ajay Kumar; Duraisamy, Ganesh Selvaraj; Týcová, Anna; Ono, Eiichiro; Krofta, Karel

    2016-10-01

    Lupulin glands localized in female hop (Humulus lupulus L.) cones are valuable source of bitter acids, essential oils and polyphenols. These compounds are used in brewing industry and are important for biomedical applications. In this study we describe the potential effect of transcription factors from WRKY family in the activation of the final steps of lupulin biosynthesis. In particular, lupulin gland-specific transcription factor HlWRKY1 that shows significant similarity to AtWRKY75, has ability to activate the set of promoters driving key genes of xanthohumol and bitter acids biosynthesis such as chalcone synthase H1, valerophenone synthase, prenyltransferase 1, 1L and 2 and O-methyltransferase-1. When combined with co-factor HlWDR1 and silencing suppressor p19, HlWRKY1 is able to enhance transient expression of gus gene driven by Omt1 and Chs_H1 promoters to significant level as compared to 35S promoter of CaMV in Nicotiana. benthamiana. Transformation of hop with dual Agrobacterium vector bearing HlWRKY1/HlWDR1 led to ectopic overexpression of these transgenes and further activation of lupulin-specific genes expression in hop leaves. It was further showed that (1) HlWRKY1 is endowed with promoter autoactivation; (2) It is regulated by post-transcriptional gene silencing (PTGS) mechanism; (3) It is stimulated by kinase co-expression. Since HlWRKY1 promotes expression of lupulin-specific HlMyb3 gene therefore it can constitute a significant component in hop lupulin regulation network. Putative involvement of HlWRKY1 in the regulation of lupulin biosynthesis may suggest the original physiological function of lupulin components in hop as flower and seed protective compounds.

  2. Characterization of the fatty acyl elongase (elovl) gene family, and hepatic elovl and delta-6 fatty acyl desaturase transcript expression and fatty acid responses to diets containing camelina oil in Atlantic cod (Gadus morhua).

    PubMed

    Xue, Xi; Feng, Charles Y; Hixson, Stefanie M; Johnstone, Kim; Anderson, Derek M; Parrish, Christopher C; Rise, Matthew L

    2014-09-01

    For aquaculture to become sustainable, there is a need to substitute fish oil [FO, rich in ω3 long chain polyunsaturated fatty acids (LC-PUFA) such as 20:5ω3 (EPA) and 22:6ω3 (DHA)] in aquafeed with plant oils such as camelina oil [CO, rich in C18 PUFA such as 18:3ω3 (ALA) and 18:2ω6 (LNA)]. The LC-PUFA are essential components in fish diets for maintaining optimal health, physiology and growth. However, most marine fish including Atlantic cod are inefficient at producing LC-PUFA from shorter chain precursors. Since elovl genes encode enzymes that play key roles in fatty acid biosynthesis, we hypothesized that they may be involved in Atlantic cod responses to diets rich in 18:3ω3 and 18:2ω6. Ten members of the cod elovl gene family were characterized at the mRNA level. RT-PCR was used to study constitutive expression of elovl transcripts in fifteen tissues. Some transcripts (e.g. elovl5) were ubiquitously expressed, while others had tissue-specific expression (e.g. elovl4a in brain and eye). Cod fed a CO-containing diet (100% CO replacement of FO and including solvent-extracted fish meal) had significantly lower weight gain, with significant up-regulation of elovl5 and fadsd6 transcripts in the liver as shown by QPCR analysis, compared with cod on a FO control diet after a 13-week trial. Multivariate statistical analyses (SIMPER and PCA) indicated that high 18:3ω3 and/or low ω3 LC-PUFA levels in the liver were associated with the up-regulation of elovl5 and fadsd6, which are involved in LC-PUFA biosynthesis in cod.

  3. Three nicotianamine synthase genes isolated from maize are differentially regulated by iron nutritional status.

    PubMed

    Mizuno, Daichi; Higuchi, Kyoko; Sakamoto, Tatsuya; Nakanishi, Hiromi; Mori, Satoshi; Nishizawa, Naoko K

    2003-08-01

    Nicotianamine synthase (NAS) is an enzyme that is critical for the biosynthesis of the mugineic acid family of phytosiderophores in graminaceous plants, and for the homeostasis of metal ions in nongraminaceous plants. We isolated one genomic NAS clone, ZmNAS3, and two cDNA NAS clones, ZmNAS1 and ZmNAS2, from maize (Zea mays cv Alice). In agreement with the increased secretion of phytosiderophores with Fe deficiency, ZmNAS1 and ZmNAS2 were positively expressed only in Fe-deficient roots. In contrast, ZmNAS3 was expressed under Fe-sufficient conditions, and was negatively regulated by Fe deficiency. This is the first report describing down-regulation of NAS gene expression in response to Fe deficiency in plants, shedding light on the role of nicotianamine in graminaceous plants, other than as a precursor in phytosiderophore production. ZmNAS1-green fluorescent protein (sGFP) and ZmNAS2-sGFP were localized at spots in the cytoplasm of onion (Allium cepa) epidermal cells, whereas ZmNAS3-sGFP was distributed throughout the cytoplasm of these cells. ZmNAS1 and ZmNAS3 showed NAS activity in vitro, whereas ZmNAS2 showed none. Due to its duplicated structure, ZmNAS2 was much larger (65.8 kD) than ZmNAS1, ZmNAS3, and previously characterized NAS proteins (30-38 kD) from other plant species. We reveal that maize has two types of NAS proteins based on their expression pattern and subcellular localization.

  4. Progressive familial intrahepatic cholestasis.

    PubMed

    Jacquemin, E

    1999-06-01

    Progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, is an inherited disorder of childhood in which cholestasis of hepatocellular origin often presents in the neonatal period and leads to death from liver failure before adolescence. The pattern of appearance of affected children within families is consistent with autosomal recessive inheritance. Several studies have provided support for the heterogeneity of this clinical entity suggesting the existence of different types due to different disorders affecting the hepatocyte and related to defects of bile acid secretion or bile acid metabolism. Recent molecular and genetic studies have identified genes responsible for three types of PFIC and have shown that PFIC was related to mutations in hepatocellular transport system genes involved in bile formation. These findings now provide specific diagnostic tools for the investigation of children with PFIC and should allow prenatal diagnosis in the future. Genotype-phenotype correlations performed in patients treated with ursodeoxycholic acid or biliary diversion should allow those PFIC patients who could benefit from these therapies to be precisely identified. In the future, other therapies, such as cell and gene therapies, might be considered and could also represent an alternative to liver transplantation.

  5. Family Hypnotherapy.

    ERIC Educational Resources Information Center

    Araoz, Daniel L.; Negley-Parker, Esther

    1985-01-01

    A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

  6. FAMILY TYMOVIRIDAE

    USDA-ARS?s Scientific Manuscript database

    This article provides a brief review of the taxonomic structure, virion properties, genome organization and replication strategy, antigenic properties, and biological properties of viruses in the family Tymoviridae. Criteria for demarcation of genus and species are provided. A brief review of each...

  7. Familial hypercholesterolemia

    MedlinePlus

    A diet low in cholesterol and saturated fat and rich in unsaturated fat may help to control your LDL level. People with a family history of this condition, particularly if both parents carry the defective gene, may want to seek genetic counseling.

  8. Family Hypnotherapy.

    ERIC Educational Resources Information Center

    Araoz, Daniel L.; Negley-Parker, Esther

    1985-01-01

    A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

  9. Family Violence.

    ERIC Educational Resources Information Center

    Sorgen, Carol, Ed.

    1979-01-01

    This quarterly publication, issued by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), contains articles dealing with family violence and alcohol abuse, children of alcoholic parents, training programs for counselors, and confidentiality of client records. The three articles on alcohol abuse suggest that: (1) there is a clear…

  10. My Family.

    ERIC Educational Resources Information Center

    Alaska State-Operated Schools, Anchorage.

    This elementary reader is designed for use in a bilingual Inupiat-English program in Buckland and Deering, Alaska. It is the story of a small boy named Paul and his family. The Inupiat text and its English equivalent are never in opposition. The Inupiat text is presented on a picture page, with the English on the back. The illustrations, by J.…

  11. FAMILY SCATHOPHAGIDAE.

    PubMed

    Wolff, Marta; Grisales, Diana; Nihei, Silvio S

    2016-06-14

    Scathophagidae (Diptera, Calyptratae) is an uncommon group of flies. In Colombia there was no scientific record of this family until now. In this paper we report for the first time the genus Scatogera and the species S. primogenita Albuquerque, collected over 3000m. and previously collected in Ecuador.

  12. FAMILY ASILIDAE.

    PubMed

    Wolff, Marta; Lamas, Carlos José Einicker

    2016-06-14

    Asilidae is one of the largest Diptera families with more than 7,000 recognized species worldwide. All their species are predators on arthropods, mainly insects. This catalogue presents 71 species distributed in 26 genera, ten tribes or generic groups and four subfamilies. For each species we present the available geographical information and relevant references.

  13. Serving Families.

    ERIC Educational Resources Information Center

    Link, Geoffrey; Beggs, Marjorie; Seiderman, Ethel

    Parent Services Project (PSP), the first comprehensive program of resources and mental health activities for parents offered at child care centers in the San Francisco Bay Area (California), has expanded to centers in six states, serving over 19,000 families. This report describes the program's history, aims, and achievements, along with specific…

  14. Serving Families.

    ERIC Educational Resources Information Center

    Link, Geoffrey; Beggs, Marjorie; Seiderman, Ethel

    Parent Services Project (PSP), the first comprehensive program of resources and mental health activities for parents offered at child care centers in the San Francisco Bay Area (California), has expanded to centers in six states, serving over 19,000 families. This report describes the program's history, aims, and achievements, along with specific…

  15. Familial dysautonomia.

    PubMed

    Slaugenhaupt, Susan A; Gusella, James F

    2002-06-01

    Familial dysautonomia is a developmental disorder of the sensory and autonomic nervous system. Recent studies have shown that two mutations in the gene IKBKAP are responsible for the disease. IKAP, the IKBKAP-encoded protein, is a member of the recently identified human Elongator complex. The major FD mutation is a splice mutation that results in aberrant tissue-specific mRNA splicing.

  16. FAMILY LAUXANIIDAE.

    PubMed

    Silva, Vera Cristina

    2016-06-14

    An updated Catalogue of the Lauxaniidae of Colombia is presented. This acalyptratae family is poorly known in Colombia, with only 36 described species in 33 genera. This paper expands the distribution of 24 species to Colombia. At total, 63 species are reported here for Colombia.

  17. A 21-amino acid peptide from the cysteine cluster II of the family D DNA polymerase from Pyrococcus horikoshii stimulates its nuclease activity which is Mre11-like and prefers manganese ion as the cofactor.

    PubMed

    Shen, Yulong; Tang, Xiao-Feng; Yokoyama, Hideshi; Matsui, Eriko; Matsui, Ikuo

    2004-01-01

    Family D DNA polymerase (PolD) is a new type of DNA polymerase possessing polymerization and 3'-5' exonuclease activities. Here we report the characterization of the nuclease activity of PolD from Pyrococcus horikoshii. By site-directed mutagenesis, we verified that the putative Mre11-like nuclease domain in the small subunit (DP1), predicted according to computer analysis and structure inference reported previously, is the catalytic domain. We show that D363, H365 and H454 are the essential residues, while D407, N453, H500, H563 and H565 are critical residues for the activity. We provide experimental evidence demonstrating that manganese, rather than magnesium, is the preferable metal ion for the nuclease activity of PolD. We also show that DP1 alone is insufficient to perform full catalysis, which additionally requires the formation of the PolD complex and manganese ion. We found that a 21 amino acid, subunit-interacting peptide of the sequence from cysteine cluster II of the large subunit (DP2) stimulates the exonuclease activity of DP1 and the internal deletion mutants of PolD lacking the 21-aa sequence. This indicates that the putative zinc finger motif of the cysteine cluster II is deeply involved in the nucleolytic catalysis.

  18. A 21-amino acid peptide from the cysteine cluster II of the family D DNA polymerase from Pyrococcus horikoshii stimulates its nuclease activity which is Mre11-like and prefers manganese ion as the cofactor

    PubMed Central

    Shen, Yulong; Tang, Xiao-Feng; Yokoyama, Hideshi; Matsui, Eriko; Matsui, Ikuo

    2004-01-01

    Family D DNA polymerase (PolD) is a new type of DNA polymerase possessing polymerization and 3′–5′ exonuclease activities. Here we report the characterization of the nuclease activity of PolD from Pyrococcus horikoshii. By site-directed mutagenesis, we verified that the putative Mre11-like nuclease domain in the small subunit (DP1), predicted according to computer analysis and structure inference reported previously, is the catalytic domain. We show that D363, H365 and H454 are the essential residues, while D407, N453, H500, H563 and H565 are critical residues for the activity. We provide experimental evidence demonstrating that manganese, rather than magnesium, is the preferable metal ion for the nuclease activity of PolD. We also show that DP1 alone is insufficient to perform full catalysis, which additionally requires the formation of the PolD complex and manganese ion. We found that a 21 amino acid, subunit-interacting peptide of the sequence from cysteine cluster II of the large subunit (DP2) stimulates the exonuclease activity of DP1 and the internal deletion mutants of PolD lacking the 21-aa sequence. This indicates that the putative zinc finger motif of the cysteine cluster II is deeply involved in the nucleolytic catalysis. PMID:14704353

  19. Structures of the first representatives of Pfam family PF06684 (DUF1185) reveal a novel variant of the Bacillus chorismate mutase fold and suggest a role in amino-acid metabolism

    PubMed Central

    Bakolitsa, Constantina; Kumar, Abhinav; Jin, Kevin K.; McMullan, Daniel; Krishna, S. Sri; Miller, Mitchell D.; Abdubek, Polat; Acosta, Claire; Astakhova, Tamara; Axelrod, Herbert L.; Burra, Prasad; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Elias, Ylva; Ellrott, Kyle; Ernst, Dustin; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Grzechnik, Slawomir K.; Han, Gye Won; Jaroszewski, Lukasz; Johnson, Hope A.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Marciano, David; Morse, Andrew T.; Murphy, Kevin D.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Paulsen, Jessica; Puckett, Christina; Reyes, Ron; Rife, Christopher L.; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Trout, Christina V.; van den Bedem, Henry; Weekes, Dana; White, Aprilfawn; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-Andre; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

    2010-01-01

    The crystal structures of BB2672 and SPO0826 were determined to resolutions of 1.7 and 2.1 Å by single-wavelength anomalous dispersion and multiple-wavelength anomalous dispersion, respectively, using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). These proteins are the first structural representatives of the PF06684 (DUF1185) Pfam family. Structural analysis revealed that both structures adopt a variant of the Bacillus chorismate mutase fold (BCM). The biological unit of both proteins is a hexamer and analysis of homologs indicates that the oligomer interface residues are highly conserved. The conformation of the critical regions for oligomerization appears to be dependent on pH or salt concentration, suggesting that this protein might be subject to environmental regulation. Structural similarities to BCM and genome-context analysis suggest a function in amino-acid synthesis. PMID:20944209

  20. Family Structure and Family Processes in Mexican American Families

    PubMed Central

    Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun

    2010-01-01

    Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct, CD/ODD and MDD symptoms, and greater parent-child conflict than their counterparts in two parent families. Single parent mothers reported greater economic hardship, depression and family stress. Family stress and parent-child conflict emerged as significant mediators of the association between family structure and early adolescent outcomes, suggesting important processes linking MA single parent families and adolescent adjustment. PMID:21361925

  1. [Family violence].

    PubMed

    Manoudi, F; Chagh, R; Es-soussi, M; Asri, F; Tazi, I

    2013-09-01

    Family violence is a serious public health problem, the scale of which is seriously increasing in Morocco. Although it has existed for a long time, we ignore the real characteristics of this plague in our country; our work consisted in an epidemiological approach of family violence in Marrakech during 2006. After elaborating a questionnaire, which allows the study of the demographic and social profile of the families, the study of violence exercised in the family and the evaluation of the depression in the women, we led an inquiry amongst 265 women. Analysis of the results obtained has allowed us to underline the following characteristics: 16.6% of the women in our sample had been physically beaten; the young age is a risk factor; the age range most affected by violence is in women between the ages of 30 and 40 and which represent 39% of the battered women; domestic violence touches all the social, economic and cultural classes: in our study, 63% of the women having undergone violence were housewives, 25% were managers and 3% senior executives; family problems were the most important cause of violence in our study, representing 32.32%. Requests for money was the cause in 11.3% of the cases, and imposed sexual relations were found in 6.8% of the cases; alcoholism is an aggravating factor of family violence; 27.3% of the spouses who assaulted their wives were drunk; 52% of the assaulted women were victims of violence in childhood and 36% had been witness to their father's violence; in 63.6% of the cases of violence, the children were witnesses, and in 25% of the cases the children were victims of violence at the same time as their mothers; 50% of the women victims of violence did not react, while 38.6% left home, and 9.1 filed for divorce. Thirty-two percent of the assaulted woman had been traumatised by the aggression; the association of depression and violence was very high, 343% of the battered women in our study suffered from severe depression. This work

  2. Family Therapy and Disturbed Families.

    ERIC Educational Resources Information Center

    Zuk, Gerald H., Ed.; Boszormenyi-Nagy, Ivan, Ed.

    Presented at a conference at which authors represented major theoretical positions in the field, most of the papers use family therapy as an important source of observations or ideas, or as a means to pinpoint methodological problems. Papers are grouped in sections as follows: four which introduce the reader to the field of specialization, provide…

  3. Family Therapy and Disturbed Families.

    ERIC Educational Resources Information Center

    Zuk, Gerald H., Ed.; Boszormenyi-Nagy, Ivan, Ed.

    Presented at a conference at which authors represented major theoretical positions in the field, most of the papers use family therapy as an important source of observations or ideas, or as a means to pinpoint methodological problems. Papers are grouped in sections as follows: four which introduce the reader to the field of specialization, provide…

  4. Family Centers

    DTIC Science & Technology

    1992-12-30

    quality service delivery to meet the needs of the DoD personnel and their families, in accordance with DoD Directive 1342.17 (reference (a)). 4...facility, and program standards. f. Develop and forward to ASD(FM&P), for review and approval, a comprehensive evaluation system to measure the...of future services and the continuation, expansion, or termination of others. (3) Service-wide measurement criteria for monitoring and evaluating the

  5. Apoptosis of HL-60 human leukemia cells induced by Asiatic acid through modulation of B-cell lymphoma 2 family proteins and the mitogen-activated protein kinase signaling pathway.

    PubMed

    Wu, Qiuling; Lv, Tingting; Chen, Yan; Wen, Lu; Zhang, Junli; Jiang, Xudong; Liu, Fang

    2015-07-01

    The toxicities of conventional chemotherapeutic agents to normal cells restrict their dosage and clinical efficacy in acute leukemia; therefore, it is important to develop novel chemotherapeutics, including natural products, which selectively target cancer-specific pathways. The present study aimed to explore the effect of the chemopreventive agent asiatic acid (AA) on the proliferation and apoptotic rate of the leukemia cell line HL-60 and investigated the mechanisms underlying its anti-tumor activity. The effect of AA on the proliferation of HL-60 cells was evaluated using the MTT assay. Annexin V-fluorescein isothiocyanate/propidium iodide double staining followed by flow cytometric analysis as well as Hoechst 33258 staining were used to analyze the apoptotic rate of the cells. Furthermore, changes of survivin, B-cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 expressions were detected by western blot analysis. AA blocked the growth of HL-60 cells in a dose- and time-dependent manner. The IC50-value of AA on HL-60 cells was 46.67 ± 5.08 µmol/l for 24 h. AA induced apoptosis in a dose-dependent manner, which was inhibited in the presence of Z-DEVD-FMK, a specific inhibitor of caspase. The anti-apoptotic proteins Bcl-2, Mcl-1 and survivin were downregulated by AA in a dose-dependent manner. Concurrently, AA inhibited ERK and p38 phosphorylation in a dose-dependent manner, while JNK phosphorylation was not affected. In conclusion, the present study indicated that the p38 and ERK pathways, as well as modulation of Bcl-2 family and survivin proteins were key regulators of apoptosis induced in HL-60 cells in response to AA.

  6. 2′-Deoxymugineic acid promotes growth of rice (Oryza sativa L.) by orchestrating iron and nitrate uptake processes under high pH conditions

    PubMed Central

    Araki, Ryoichi; Kousaka, Kayoko; Namba, Kosuke; Murata, Yoshiko; Murata, Jun

    2015-01-01

    Poaceae plants release 2′-deoxymugineic acid (DMA) and related phytosiderophores to chelate iron (Fe), which often exists as insoluble Fe(III) in the rhizosphere, especially under high pH conditions. Although the molecular mechanisms behind the biosynthesis and secretion of DMA have been studied extensively, little information is known about whether DMA has biological roles other than chelating Fe in vivo. Here, we demonstrate that hydroponic cultures of rice (Oryza sativa) seedlings show almost complete restoration in shoot height and soil-plant analysis development (SPAD) values after treatment with 3–30 μm DMA at high pH (pH 8.0), compared with untreated control seedlings at normal pH (pH 5.8). These changes were accompanied by selective accumulation of Fe over other metals. While this enhanced growth was evident under high pH conditions, DMA application also enhanced seedling growth under normal pH conditions in which Fe was fairly accessible. Microarray and qRT-PCR analyses revealed that exogenous DMA application attenuated the increased expression levels of various genes related to Fe transport and accumulation. Surprisingly, despite the preferential utilization of ammonium over nitrate as a nitrogen source by rice, DMA application also increased nitrate reductase activity and the expression of genes encoding high-affinity nitrate transporters and nitrate reductases, all of which were otherwise considerably lower under high pH conditions. These data suggest that exogenous DMA not only plays an important role in facilitating the uptake of environmental Fe, but also orchestrates Fe and nitrate assimilation for optimal growth under high pH conditions. PMID:25393516

  7. 2'-Deoxymugineic acid promotes growth of rice (Oryza sativa L.) by orchestrating iron and nitrate uptake processes under high pH conditions.

    PubMed

    Araki, Ryoichi; Kousaka, Kayoko; Namba, Kosuke; Murata, Yoshiko; Murata, Jun

    2015-01-01

    Poaceae plants release 2'-deoxymugineic acid (DMA) and related phytosiderophores to chelate iron (Fe), which often exists as insoluble Fe(III) in the rhizosphere, especially under high pH conditions. Although the molecular mechanisms behind the biosynthesis and secretion of DMA have been studied extensively, little information is known about whether DMA has biological roles other than chelating Fe in vivo. Here, we demonstrate that hydroponic cultures of rice (Oryza sativa) seedlings show almost complete restoration in shoot height and soil-plant analysis development (SPAD) values after treatment with 3-30 μm DMA at high pH (pH 8.0), compared with untreated control seedlings at normal pH (pH 5.8). These changes were accompanied by selective accumulation of Fe over other metals. While this enhanced growth was evident under high pH conditions, DMA application also enhanced seedling growth under normal pH conditions in which Fe was fairly accessible. Microarray and qRT-PCR analyses revealed that exogenous DMA application attenuated the increased expression levels of various genes related to Fe transport and accumulation. Surprisingly, despite the preferential utilization of ammonium over nitrate as a nitrogen source by rice, DMA application also increased nitrate reductase activity and the expression of genes encoding high-affinity nitrate transporters and nitrate reductases, all of which were otherwise considerably lower under high pH conditions. These data suggest that exogenous DMA not only plays an important role in facilitating the uptake of environmental Fe, but also orchestrates Fe and nitrate assimilation for optimal growth under high pH conditions. © 2014 The Authors The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.

  8. From Family Therapy to Family Intervention.

    PubMed

    Josephson, Allan M

    2015-07-01

    For many, family therapy refers to sessions in which all family members are present. Yet in contemporary psychiatry there are many ways to work with families in addition to this classic concept. This article proposes family intervention as an encompassing term for a new family paradigm in child and adolescent psychiatry. Developmental psychopathology is a guiding principle of this paradigm. A full range of ways to work with families clinically is described with clinical examples. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Family and family therapy in the Netherlands.

    PubMed

    Wagenaar, Karin; Baars, Jan

    2012-04-01

    This article describes how families are functioning in the Netherlands, and how family therapy is used in mental healthcare. In the open Dutch society, new ideas are easily incorporated, as exemplified by the rapid introduction and growth of family therapy in the 1980s. In recent decades, however, family therapy has lost ground to other treatment models that are more individually orientated, and adhere to stricter protocols. This decline of family therapy has been exacerbated by recent budget cuts in mental healthcare. In regular healthcare institutes family therapy now has a marginal position at best, although family treatment models are used in specific areas such as forensic treatments. In addition, the higher trained family therapists have found their own niches to work with couples and families. We argue that a stronger position of family therapy would be beneficial for patients and for families, in order to counteract the strong individualization of Dutch society.

  10. Developmental Toxicity of Perfluoroalkyl Acid Mixtures in CD-1 Mice

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) belong to a family of fluoro-organic compounds known as perfluoroalkyl acids (PFAAs). PFAAs have been widely used in industrial and commercial applications, and have been found to be...

  11. Developmental Toxicity of Perfluoroalkyl Acid Mixtures in CD-1 Mice

    EPA Science Inventory

    Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA) belong to a family of fluoro-organic compounds known as perfluoroalkyl acids (PFAAs). PFAAs have been widely used in industrial and commercial applications, and have been found to be...

  12. Roles within the Family

    MedlinePlus

    ... Adoption & Foster Care Communication & Discipline Types of Families Media Work & Play Getting ... Within the Family Page Content Article Body Families are not democracies. Each family has its own ways of deciding ...

  13. FAMILY DROSOPHILIDAE.

    PubMed

    Tidon, Rosana; Almeida, Jonathan Mendes De

    2016-06-14

    This catalogue presents 176 species distributed in 17 genera and four tribes of Drosophilidae in Colombia, with both subfamilies, Drosophilinae and Steganinae, represented in the Colombian territory. This is probably an underestimate of the real richness of drosophilid species in the country, for two reasons. First, there are relatively few collections of Drosophilidae in Colombia, resulting in significant spatial gaps in the sampling of these flies. Second, we have not considered here species that have already been recorded in neighbour countries but not in Colombia. Consequently, there are certainly several described species, as well as new species, that occur in this area but are not listed here. We hope that this catalogue will stimulate new inventories of drosophilids in Colombia, contributing to fill gaps in the knowledge of this family of flies in the country.

  14. Familial dysautonomia.

    PubMed

    Axelrod, Felicia B

    2004-03-01

    Familial dysautonomia (FD) is a neurodevelopmental genetic disorder within the larger classification of hereditary sensory and autonomic neuropathies, each caused by a different genetic error. The FD gene has been identified as IKBKAP. Mutations result in tissue-specific expression of mutant IkappaB kinase-associated protein (IKAP). The genetic error probably affects development, as well as maintenance, of neurons because there is neuropathological and clinical progression. Pathological alterations consist of decreased unmyelinated and small-fiber neurons. Clinical features reflect widespread involvement of sensory and autonomic neurons. Sensory loss includes impaired pain and temperature appreciation. Autonomic features include dysphagia, vomiting crises, blood pressure lability, and sudomotor dysfunction. Central dysfunction includes emotional lability and ataxia. With supportive treatment, prognosis has improved greatly. About 40% of patients are over age 20 years. The cause of death is usually pulmonary failure, unexplained sudden deaths, or renal failure. With the discovery of the genetic defect, definitive treatments are anticipated.

  15. Family Psychology and Family Therapy in Japan.

    ERIC Educational Resources Information Center

    Kameguchi, Kenji; Murphy-Shigematsu, Stephen

    2001-01-01

    Reviews the development of family psychology and family therapy in Japan, tracing the origins of these movements, explaining how these fields were activated by the problem of school refusal, and describing an approach to family therapy that has been developed to work with families confronting this problem, as well as preventive programs of family…

  16. The Family Hero in Black Alcoholism Families.

    ERIC Educational Resources Information Center

    Brisbane, Francis L.

    1989-01-01

    Uses data from 20 case studies of Black adult female children of alcoholic parents to discuss Family Hero role often assumed by oldest or only female child in Black alcoholism families. Explains how female-dominated survival role of Family Hero in Black families is significantly more related to racial and cultural factors than numbers alone may…

  17. Integrating Family Resilience and Family Stress Theory.

    ERIC Educational Resources Information Center

    Patterson, Joan M.

    2002-01-01

    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)

  18. Positive Family Functioning.

    ERIC Educational Resources Information Center

    Sussman, Marvin B.

    The persistence of the nuclear family as the primary social unit in the United States and most all other societies, especially complex ones, is a fact. Values shape the definition of family, especially the "good family," and the "great debate" of this period on family failure, family corruption and the family's near demise originates in…

  19. Family Orientation in Family Medicine Training

    PubMed Central

    Talbot, Yves R.; Tannenbaum, David

    1990-01-01

    Teaching about the family has become an important part of the family medicine curriculum. The family orientation index, a 39-item questionnaire, was designed to evaluate the family orientation of services and care provided as well as the teaching and research. The questionnaire was distributed to 55 program directors at 16 Canadian universities. The response rate was 84%. The results indicate that the family orientation of services is less than optimal. PMID:21233938

  20. Protein family classification using sparse Markov transducers.

    PubMed

    Eskin, E; Grundy, W N; Singer, Y

    2000-01-01

    In this paper we present a method for classifying proteins into families using sparse Markov transducers (SMTs). Sparse Markov transducers, similar to probabilistic suffix trees, estimate a probability distribution conditioned on an input sequence. SMTs generalize probabilistic suffix trees by allowing for wild-cards in the conditioning sequences. Because substitutions of amino acids are common in protein families, incorporating wildcards into the model significantly improves classification performance. We present two models for building protein family classifiers using SMTs. We also present efficient data structures to improve the memory usage of the models. We evaluate SMTs by building protein family classifiers using the Pfam database and compare our results to previously published results.

  1. GIPC gene family (Review).

    PubMed

    Katoh, Masaru

    2002-06-01

    GIPC1/GIPC/RGS19IP1, GIPC2, and GIPC3 genes constitute the human GIPC gene family. GIPC1 and GIPC2 show 62.0% total-amino-acid identity. GIPC1 and GIPC3 show 59.9% total-amino-acid identity. GIPC2 and GIPC3 show 55.3% total-amino-acid identity. GIPCs are proteins with central PDZ domain and GIPC homology (GH1 and GH2) domains. PDZ, GH1, and GH2 domains are conserved among human GIPCs, Xenopus GIPC/Kermit, and Drosophila GIPC/ LP09416. Bioinformatics revealed that GIPC genes are linked to prostanoid receptor genes and DNAJB genes in the human genome as follows: GIPC1 gene is linked to prostaglandin E receptor 1 (PTGER1) gene and DNAJB1 gene in human chromosome 19p13.2-p13.1 region; GIPC2 gene to prostaglandin F receptor (PTGFR) gene and DNAJB4 gene in human chromosome 1p31.1-p22.3 region; GIPC3 gene to thromboxane A2 receptor (TBXA2R) gene in human chromosome 19p13.3 region. GIPC1 and GIPC2 mRNAs are expressed together in OKAJIMA, TMK1, MKN45 and KATO-III cells derived from diffuse-type of gastric cancer, and are up-regulated in several cases of primary gastric cancer. PDZ domain of GIPC family proteins interact with Frizzled-3 (FZD3) class of WNT receptor, insulin-like growth factor-I (IGF1) receptor, receptor tyrosine kinase TrkA, TGF-beta type III receptor (TGF-beta RIII), integrin alpha6A subunit, transmembrane glycoprotein 5T4, and RGS19/RGS-GAIP. Because RGS19 is a member of the RGS family that regulate heterotrimeric G-protein signaling, GIPCs might be scaffold proteins linking heterotrimeric G-proteins to seven-transmembrane-type WNT receptor or to receptor tyrosine kinases. Therefore, GIPC1, GIPC2 and GIPC3 might play key roles in carcinogenesis and embryogenesis through modulation of growth factor signaling and cell adhesion.

  2. Family ties: constructing family time in low-income families.

    PubMed

    Tubbs, Carolyn Y; Roy, Kevin M; Burton, Linda M

    2005-03-01

    "Family time" is reflected in the process of building and fortifying family relationships. Whereas such time, free of obligatory work, school, and family maintenance activities, is purchased by many families using discretionary income, we explore how low-income mothers make time for and give meaning to focused engagement and relationship development with their children within time constraints idiosyncratic to being poor and relying on welfare. Longitudinal ethnographic data from 61 low-income African American, European American, and Latina American mothers were analyzed to understand how mothers construct family time during daily activities such as talking, play, and meals. We also identify unique cultural factors that shape family time for low-income families, such as changing temporal orientations, centrality of television time, and emotional burdens due to poverty. Implications for family therapy are also discussed.

  3. Functional neighbors: inferring relationships between nonhomologous protein families using family-specific packing motifs.

    PubMed

    Bandyopadhyay, Deepak; Huan, Jun; Liu, Jinze; Prins, Jan; Snoeyink, Jack; Wang, Wei; Tropsha, Alexander

    2010-09-01

    We describe a new approach for inferring the functional relationships between nonhomologous protein families by looking at statistical enrichment of alternative function predictions in classification hierarchies such as Gene Ontology (GO) and Structural Classification of Proteins (SCOP). Protein structures are represented by robust graph representations, and the fast frequent subgraph mining algorithm is applied to protein families to generate sets of family-specific packing motifs, i.e., amino acid residue-packing patterns shared by most family members but infrequent in other proteins. The function of a protein is inferred by identifying in it motifs characteristic of a known family. We employ these family-specific motifs to elucidate functional relationships between families in the GO and SCOP hierarchies. Specifically, we postulate that two families are functionally related if one family is statistically enriched by motifs characteristic of another family, i.e., if the number of proteins in a family containing a motif from another family is greater than expected by chance. This function-inference method can help annotate proteins of unknown function, establish functional neighbors of existing families, and help specify alternate functions for known proteins.

  4. Familial hypercholesterolaemia in Portugal.

    PubMed

    Bourbon, M; Alves, A C; Medeiros, A M; Silva, S; Soutar, A K

    2008-02-01

    Familial hypercholesterolaemia (FH) is characterised clinically by an increased level of circulating LDL cholesterol that leads to lipid accumulation in tendons and arteries, premature atherosclerosis and increased risk of coronary heart disease (CHD). Although Portugal should have about 20,000 cases, this disease is severely under-diagnosed in our country, this being the first presentation of Portuguese data on FH. A total of 602 blood samples were collected from 184 index patients and 418 relatives from several centres throughout Portugal. Fifty-three different mutations were found in 83 index patients, 79 heterozygous and 4 with two defective LDLR alleles. Additionally, 4 putative alterations were found in 8 patients but were not considered mutations causing disease, mainly because they did not co-segregate with hypercholesterolaemia in the families. Three unrelated patients were found to be heterozygous for the APOB(3500) mutation and two unrelated patients were found to be heterozygous for a novel mutation in PCSK9, predicted to cause a single amino acid substitution, D374H. Cascade screening increased the number of FH patients identified genetically to 204. The newly identified FH patients are now receiving counselling and treatment based on the genetic diagnosis. The early identification of FH patients can increase their life expectancy and quality of life by preventing the development of premature CHD if patients receive appropriate pharmacological treatment.

  5. Family and family therapy in Russia.

    PubMed

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

    2012-04-01

    This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized.

  6. Evolution of rosmarinic acid biosynthesis.

    PubMed

    Petersen, Maike; Abdullah, Yana; Benner, Johannes; Eberle, David; Gehlen, Katja; Hücherig, Stephanie; Janiak, Verena; Kim, Kyung Hee; Sander, Marion; Weitzel, Corinna; Wolters, Stefan

    2009-01-01

    Rosmarinic acid and chlorogenic acid are caffeic acid esters widely found in the plant kingdom and presumably accumulated as defense compounds. In a survey, more than 240 plant species have been screened for the presence of rosmarinic and chlorogenic acids. Several rosmarinic acid-containing species have been detected. The rosmarinic acid accumulation in species of the Marantaceae has not been known before. Rosmarinic acid is found in hornworts, in the fern family Blechnaceae and in species of several orders of mono- and dicotyledonous angiosperms. The biosyntheses of caffeoylshikimate, chlorogenic acid and rosmarinic acid use 4-coumaroyl-CoA from the general phenylpropanoid pathway as hydroxycinnamoyl donor. The hydroxycinnamoyl acceptor substrate comes from the shikimate pathway: shikimic acid, quinic acid and hydroxyphenyllactic acid derived from l-tyrosine. Similar steps are involved in the biosyntheses of rosmarinic, chlorogenic and caffeoylshikimic acids: the transfer of the 4-coumaroyl moiety to an acceptor molecule by a hydroxycinnamoyltransferase from the BAHD acyltransferase family and the meta-hydroxylation of the 4-coumaroyl moiety in the ester by a cytochrome P450 monooxygenase from the CYP98A family. The hydroxycinnamoyltransferases as well as the meta-hydroxylases show high sequence similarities and thus seem to be closely related. The hydroxycinnamoyltransferase and CYP98A14 from Coleus blumei (Lamiaceae) are nevertheless specific for substrates involved in RA biosynthesis showing an evolutionary diversification in phenolic ester metabolism. Our current view is that only a few enzymes had to be "invented" for rosmarinic acid biosynthesis probably on the basis of genes needed for the formation of chlorogenic and caffeoylshikimic acid while further biosynthetic steps might have been recruited from phenylpropanoid metabolism, tocopherol/plastoquinone biosynthesis and photorespiration.

  7. Family Reading Night

    ERIC Educational Resources Information Center

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

    2007-01-01

    This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

  8. Bequeathing Family Continuity.

    ERIC Educational Resources Information Center

    Spanier, Graham B.

    1989-01-01

    Notes that many children who experience abuse, family disruption, or poverty reach adulthood with a strong commitment to family life. Questions whether changes in American families are indicators of pathology, deterioration, and instability; and asks how dysfunctional families transmit commitment to the concept of family to succeeding generations.…

  9. Family Therapy and Ideology.

    ERIC Educational Resources Information Center

    Bernal, Guillermo; Ysern, Eduardo

    1986-01-01

    Argues that the family and the enterprise of family therapy are social systems and under the influence of the ideology particular to a given society. The strategic family therapy treatment of a family with a drug-addicted member serves as an example to clarify the ideological themes of contemporary family therapy. (Author/BL)

  10. Effects of family connection and family individuation.

    PubMed

    Bell, Linda G; Bell, David C

    2009-09-01

    This prospective longitudinal study explores the differential effects of family connection and family individuation measured during adolescence on later midlife well-being. Home interviews were held in the 1970s with 99 families of 245 adolescents. Connection and individuation in the family system were measured by self-report, a projective exercise, and coding of taped family interactions. Twenty-five years later, telephone interviews were conducted with 54 men and 120 women (representing 82 families) who had been adolescents in the 1970s interviews. Family connection (measured during adolescence) was associated with self-acceptance and positive relationships at midlife partially mediated by marriage. Family individuation (measured during adolescence) was associated with personal autonomy at midlife.

  11. Progressive familial intrahepatic cholestasis.

    PubMed

    Cavestro, Giulia Martina; Frulloni, Luca; Cerati, Elena; Ribeiro, Luciana Andrea; Corrente, Vincenzo; Sianesi, Mario; Franzè, Angelo; Di Mario, Francesco

    2002-01-01

    Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive childhood cholestasis of hepatocellular origin. PFIC 1, also known as Byler disease, was first described in Amish kindred. It is characterized by cholestasis often arising in the neonatal period and it leads to death due to liver failure. PFIC 1, like Benign Recurrent Intrahepatic Cholestasis (BRIC) which is the benign form of the same disease, recognizes mutations in the ATP8B1 gene. PFIC 2 disease is clinically similar to PFIC 1 but it has a different gene mutation causing a defect in the Bile Salt Export Pump (BSEP), exclusively expressed in the liver and involved in the canalicular secretion of bile acids. PFIC 3 usually appears later in life and it has a higher risk of portal hypertension, gastrointestinal bleeding and liver failure. This particular form of disease (the only one with high serum values of g-glutamil transpeptidase), is associated to a genetic defect in the class III multidrug resistance protein (MDR). External biliary diversion and ursodeoxycholic acid therapy, should be considered as the initial therapy in these patients, even if liver transplantation still seems to be the only solution for most patients.

  12. Family Capital: Implications for Interventions with Families

    ERIC Educational Resources Information Center

    Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

    2011-01-01

    Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

  13. Revamping Family Preservation Services for Native Families.

    ERIC Educational Resources Information Center

    Coleman, Heather; Unrau, Yvonne A.; Manyfingers, Brenda

    2001-01-01

    Examines the philosophy and program structures of family preservation services (FPS) in the context of providing services to Native American families with child welfare issues. Explores Native cultural concepts of family, child rearing, time, and spirituality. Outlines cross-cultural training needs for FPS workers related to cultural awareness,…

  14. Family Capital: Implications for Interventions with Families

    ERIC Educational Resources Information Center

    Belcher, John R.; Peckuonis, Edward V.; Deforge, Bruce R.

    2011-01-01

    Social capital has been extensively discussed in the literature as building blocks that individuals and communities utilize to leverage system resources. Similarly, some families also create capital, which can enable members of the family, such as children, to successfully negotiate the outside world. Families in poverty confront serious…

  15. General consideration on sialic acid chemistry.

    PubMed

    Cao, Hongzhi; Chen, Xi

    2012-01-01

    Sialic acids, also known as neuraminic acids, are a family of negatively charged α-keto acids with a nine-carbon backbone. These unique sugars have been found at the termini of many glycan chains of vertebrate cell surface, which play pivotal roles in mediating or modulating a variety of physiological and pathological processes. This brief review covers general approaches for synthesizing sialic acid containing structures. Recently developed synthetic methods along with structural diversities and biological functions of sialic acid are discussed.

  16. National Military Family Association

    MedlinePlus

    ... have good news and bad news for military families. MORE Military Families Brace for What’s Next In Syria President Trump ordered an airstrike in Syria leaving military families wondering what's next. More April is the Month ...

  17. Normal Functioning Family

    MedlinePlus

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Español Text Size Email Print Share Normal Functioning Family Page Content Article Body Is there any way ...

  18. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  19. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  20. Family Health History and Diabetes

    MedlinePlus

    ... Risk Test Family Health History Quiz Family Health History Quiz Family health history is an important risk ... Should Ask Your Family About Diabetes & Family Health History Knowing your family health history is important. Here ...

  1. Familial mesothelioma: a report of two families

    SciTech Connect

    Hammar, S.P.; Bockus, D.; Remington, F.; Freidman, S.; LaZerte, G.

    1989-02-01

    Five reports of familial mesothelioma in which mesotheliomas occurred in two or more family members have been recorded in the medical literature. In this report, we describe two examples of familial mesothelioma. In one family, three brothers who worked in the asbestos insulation industry developed mesothelioma. In the second family, the father, who was occupationally exposed to asbestos, died from a tubulopapillary peritoneal mesothelioma 11 years before his son died from an identical histologic type of peritoneal mesothelioma. Our report, as with those previously recorded, suggests that genetic factors may be important in the genesis of some mesotheliomas.

  2. Familial Pulmonary Fibrosis

    MedlinePlus

    ... Patients & Visitors Giving For Professionals Treatment & Programs Health Information Doctors & Departments Research & Science Education & Training Home Conditions Familial Pulmonary Fibrosis Familial ...

  3. Families and family therapy in Hong Kong.

    PubMed

    Tse, Samson; Ng, Roger M K; Tonsing, Kareen N; Ran, Maosheng

    2012-04-01

    Family therapy views humans not as separate entities, but as embedded in a network of relationships, highlighting the reciprocal influences of one's behaviours on one another. This article gives an overview of family demographics and the implementation of family therapy in Hong Kong. We start with a review of the family demographics in Hong Kong and brief notes on families in mainland China. Demographics show that the landscape has changed markedly in the past decade, with more cross-border marriages, an increased divorce rate, and an ageing overall population - all of which could mean that there is increasing demand for professional family therapy interventions. However, only a limited number of professionals are practising the systems-based approach in Hong Kong. Some possible reasons as to why family therapy is not well disseminated and practised are discussed. These reasons include a lack of mental health policy to support family therapy, a lack of systematic family therapy training, and a shortage of skilled professionals. Furthermore, challenges in applying the western model in Chinese culture are also outlined. We conclude that more future research is warranted to investigate how family therapy can be adapted for Chinese families.

  4. Family hardship, family instability, and cognitive development.

    PubMed

    Schoon, Ingrid; Jones, Elizabeth; Cheng, Helen; Maughan, Barbara

    2012-08-01

    Associations between the characteristics of the family environment, in particular poverty and family structure, and cognitive development are well established, yet little is known about the role of timing and accumulation of risk in early childhood. The aim of this paper is to assess the associations between income poverty, family instability and cognitive development in early childhood. In particular, it tests the relative role of family economic hardship compared with family instability in affecting cognitive functioning at the age of 5 years. The study draws on data from the UK Millennium Cohort, linking data collected in infancy, age 3, and age 5 years. Cognitive ability was directly assessed at age 5 years with the British Ability Scales. Using regression models we examine associations between persistent income poverty, family transitions, and children's cognitive ability, controlling for family demographics and housing conditions, as well as child characteristics. The findings suggest that the experience of persistent economic hardship as well as very early poverty undermines cognitive functioning at 5 years of age. Family instability shows no significant association with cognitive functioning after controlling for family poverty, family demographics, housing and a set of control variables indicating child characteristics. Persistent poverty is a crucial risk factor undermining children's cognitive development--more so than family instability.

  5. Strengthening Family Practices for Latino Families

    PubMed Central

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    The study examined the effectiveness of a culturally-adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9–12 year old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted with each family. Parental stress, parent-child dysfunctional relations, and child behavior problems were reduced in the families receiving the intervention; family hardiness and family attachment were improved. Findings contribute to the validation of the SFP with Latinos, and can be used to inform social work practice with Puerto Rican families. PMID:20871785

  6. Family psychology and family therapy in Japan.

    PubMed

    Kameguchi, K; Murphy-Shigematsu, S

    2001-01-01

    The development of family psychology and family therapy in Japan has occurred mostly since the 1980s. This development was originally activated by the major social issue in contemporary Japan of school refusal, in which more than 127,000 children either overtly refuse to or claim that they cannot go to school. From a family perspective, this problem is analyzed as it relates to the confusion that children experience from unbalanced and unclear boundaries in family relations or "membranes." An approach to family therapy that adapts systems theory and integrates a clay sculpting medium has been developed to work with Japanese families confronting this problem. The design and implementation of preventative family psychology programs applied at the community level are also an important part of the future development in these fields.

  7. Omega-3 Fatty Acids during Pregnancy

    MedlinePlus

    OMEGA-3 FATTY ACIDS DURING PREGNANCY S HARE W ITH W OMEN OMEGA-3 FATTY ACIDS DURING PREGNANCY During pregnancy, your baby gets most ... eat and vitamins you take. Omega-3 fatty acids (omega-3s) are an important family of building ...

  8. Bile acid transporters

    PubMed Central

    Dawson, Paul A.; Lan, Tian; Rao, Anuradha

    2009-01-01

    In liver and intestine, transporters play a critical role in maintaining the enterohepatic circulation and bile acid homeostasis. Over the past two decades, there has been significant progress toward identifying the individual membrane transporters and unraveling their complex regulation. In the liver, bile acids are efficiently transported across the sinusoidal membrane by the Na+ taurocholate cotransporting polypeptide with assistance by members of the organic anion transporting polypeptide family. The bile acids are then secreted in an ATP-dependent fashion across the canalicular membrane by the bile salt export pump. Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter. The bile acids are shuttled across the enterocyte to the basolateral membrane and effluxed into the portal circulation by the recently indentified heteromeric organic solute transporter, OSTα-OSTβ. In addition to the hepatocyte and enterocyte, subgroups of these bile acid transporters are expressed by the biliary, renal, and colonic epithelium where they contribute to maintaining bile acid homeostasis and play important cytoprotective roles. This article will review our current understanding of the physiological role and regulation of these important carriers. PMID:19498215

  9. Bile acid transporters.

    PubMed

    Dawson, Paul A; Lan, Tian; Rao, Anuradha

    2009-12-01

    In liver and intestine, transporters play a critical role in maintaining the enterohepatic circulation and bile acid homeostasis. Over the past two decades, there has been significant progress toward identifying the individual membrane transporters and unraveling their complex regulation. In the liver, bile acids are efficiently transported across the sinusoidal membrane by the Na(+) taurocholate cotransporting polypeptide with assistance by members of the organic anion transporting polypeptide family. The bile acids are then secreted in an ATP-dependent fashion across the canalicular membrane by the bile salt export pump. Following their movement with bile into the lumen of the small intestine, bile acids are almost quantitatively reclaimed in the ileum by the apical sodium-dependent bile acid transporter. The bile acids are shuttled across the enterocyte to the basolateral membrane and effluxed into the portal circulation by the recently indentified heteromeric organic solute transporter, OSTalpha-OSTbeta. In addition to the hepatocyte and enterocyte, subgroups of these bile acid transporters are expressed by the biliary, renal, and colonic epithelium where they contribute to maintaining bile acid homeostasis and play important cytoprotective roles. This article will review our current understanding of the physiological role and regulation of these important carriers.

  10. Families in Transition .

    ERIC Educational Resources Information Center

    Bundy, Michael L., Ed.; Gumaer, James, Ed.

    1984-01-01

    Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

  11. Family Participation in Policymaking.

    ERIC Educational Resources Information Center

    Caplan, Elizabeth, Ed.; Blankenship, Kelly, Ed.; McManus, Marilyn, Ed.

    1998-01-01

    This bulletin focuses on family participation in mental health policymaking and highlights state efforts to increase family involvement. Articles include: (1) "Promoting Family Member Involvement in Children's Mental Health Policy Making Bodies," which describes how different states are promoting family member involvement in various statutory and…

  12. Black Families. Third Edition.

    ERIC Educational Resources Information Center

    McAdoo, Harriette Pipes, Ed.

    The chapters of this collection explore the experiences of black families in the United States and Africa, today and in the past. They are: (1) "African American Families: A Historical Note" (John Hope Franklin); (2) "African American Families and Family Values" (Niara Sudarkasa); (3) "Old-Time Religion: Benches Can't Say…

  13. Black Families. Third Edition.

    ERIC Educational Resources Information Center

    McAdoo, Harriette Pipes, Ed.

    The chapters of this collection explore the experiences of black families in the United States and Africa, today and in the past. They are: (1) "African American Families: A Historical Note" (John Hope Franklin); (2) "African American Families and Family Values" (Niara Sudarkasa); (3) "Old-Time Religion: Benches Can't Say…

  14. The Family in Treatment.

    ERIC Educational Resources Information Center

    Dunlop, Jean D.

    This paper describes Laurelhurst Manor's family treatment program to help families affected by chemical dependency, a 7-month program which treats family members from the perspective of developmental stages and family roles. The center, located in Portland, Oregon, is a 40-bed, free-standing facility having a 20-bed adolescent unit and a 20-bed…

  15. The Changing Family Structure.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation Newsletter, 1993

    1993-01-01

    This newsletter issue contains feature articles and short reports on how and why family structures are undergoing substantial change in many parts of the world. These articles include: (1) "The Changing Family Structure," a review of how families are changing and why; (2) "Peru: Families in the Andes"; (3) "Thailand:…

  16. Folic Acid

    MedlinePlus

    Folic acid is used to treat or prevent folic acid deficiency. It is a B-complex vitamin needed by ... Folic acid comes in tablets. It usually is taken once a day. Follow the directions on your prescription label ...

  17. Aspartic acid

    MedlinePlus

    ... also called asparaginic acid. Aspartic acid helps every cell in the body work. It plays a role in: Hormone production and release Normal nervous system function Plant sources of aspartic acid include: Legumes such as ...

  18. Forcefield_NCAA: Ab Initio Charge Parameters to Aid in the Discovery and Design of Therapeutic Proteins and Peptides with Unnatural Amino Acids and Their Application to Complement Inhibitors of the Compstatin Family

    PubMed Central

    2015-01-01

    We describe the development and testing of ab initio derived, AMBER ff03 compatible charge parameters for a large library of 147 noncanonical amino acids including β- and N-methylated amino acids for use in applications such as protein structure prediction and de novo protein design. The charge parameter derivation was performed using the RESP fitting approach. Studies were performed assessing the suitability of the derived charge parameters in discriminating the activity/inactivity between 63 analogs of the complement inhibitor Compstatin on the basis of previously published experimental IC50 data and a screening procedure involving short simulations and binding free energy calculations. We found that both the approximate binding affinity (K*) and the binding free energy calculated through MM-GBSA are capable of discriminating between active and inactive Compstatin analogs, with MM-GBSA performing significantly better. Key interactions between the most potent Compstatin analog that contains a noncanonical amino acid are presented and compared to the most potent analog containing only natural amino acids and native Compstatin. We make the derived parameters and an associated web interface that is capable of performing modifications on proteins using Forcefield_NCAA and outputting AMBER-ready topology and parameter files freely available for academic use at http://selene.princeton.edu/FFNCAA. The forcefield allows one to incorporate these customized amino acids into design applications with control over size, van der Waals, and electrostatic interactions. PMID:24932669

  19. Fungal lectins: a growing family.

    PubMed

    Kobayashi, Yuka; Kawagishi, Hirokazu

    2014-01-01

    Fungi are members of a large group of eukaryotic organisms that include yeasts and molds, as well as the most familiar member, mushrooms. Fungal lectins with unique specificity and structures have been discovered. In general, fungal lectins are classified into specific families based on their amino acid sequences and three-dimensional structures. In this chapter, we provide an overview of the approximately 80 types of mushroom and fungal lectins that have been isolated and studied to date. In particular, we have focused on ten fungal lectins (Agaricus bisporus, Agrocybe cylindracea, Aleuria aurantia, Aspergillus oryzae, Clitocybe nebularis, Marasmius oreades, Psathyrella velutina, Rhizopus stolonifer, Pholiota squarrosa, Polyporus squamosus), many of which are commercially available and their properties, sugar-binding specificities, structural grouping into families, and applications for biological research being described. The sialic acid-specific lectins (Agrocybe cylindracea and Polyporus squamosus) and fucose-specific lectins (Aleuria aurantia, Aspergillus oryzae, Rhizopus stolonifer, and Pholiota squarrosa) each showed potential for use in identifying sialic acid glycoconjugates and fucose glycoconjugates. Although not much is currently known about fungal lectins compared to animal and plant lectins, the knowledge accumulated thus far shows great promise for several applications in the fields of taxonomy, biomedicine, and molecular and cellular biology.

  20. Plant ALDH10 Family

    PubMed Central

    Kopečný, David; Končitíková, Radka; Tylichová, Martina; Vigouroux, Armelle; Moskalíková, Hana; Soural, Miroslav; Šebela, Marek; Moréra, Solange

    2013-01-01

    Plant ALDH10 family members are aminoaldehyde dehydrogenases (AMADHs), which oxidize ω-aminoaldehydes to the corresponding acids. They have been linked to polyamine catabolism, osmoprotection, secondary metabolism (fragrance), and carnitine biosynthesis. Plants commonly contain two AMADH isoenzymes. We previously studied the substrate specificity of two AMADH isoforms from peas (PsAMADHs). Here, two isoenzymes from tomato (Solanum lycopersicum), SlAMADHs, and three AMADHs from maize (Zea mays), ZmAMADHs, were kinetically investigated to obtain further clues to the catalytic mechanism and the substrate specificity. We also solved the high resolution crystal structures of SlAMADH1 and ZmAMADH1a because these enzymes stand out from the others regarding their activity. From the structural and kinetic analysis, we can state that five residues at positions 163, 288, 289, 444, and 454 (PsAMADHs numbering) can, directly or not, significantly modulate AMADH substrate specificity. In the SlAMADH1 structure, a PEG aldehyde derived from the precipitant forms a thiohemiacetal intermediate, never observed so far. Its absence in the SlAMADH1-E260A structure suggests that Glu-260 can activate the catalytic cysteine as a nucleophile. We show that the five AMADHs studied here are capable of oxidizing 3-dimethylsulfoniopropionaldehyde to the cryo- and osmoprotectant 3-dimethylsulfoniopropionate. For the first time, we also show that 3-acetamidopropionaldehyde, the third aminoaldehyde besides 3-aminopropionaldehyde and 4-aminobutyraldehyde, is generally oxidized by AMADHs, meaning that these enzymes are unique in metabolizing and detoxifying aldehyde products of polyamine degradation to nontoxic amino acids. Finally, gene expression profiles in maize indicate that AMADHs might be important for controlling ω-aminoaldehyde levels during early stages of the seed development. PMID:23408433

  1. Structures of Cvnh Family Lectins

    NASA Astrophysics Data System (ADS)

    Gronenborn, Angela M.

    Members of the CVNH family are found in a restricted range of eukaryotic organisms as diverse as filamentous ascomycetes and seedless plants. All CVNH proteins so far exhibit a fold that matches the unique fold of the cyanobacterial protein. The CVNH domain is a versatile protein module, and, with some exceptions, comprises 101-150 aa with two sequential repeats of 50 amino acids. We determined high resolution structures of CVNHs from Tuber borchii, Ceratopteris richardii, Neurospora crassa, and Gibberella zeae, representing different phylogenetic groups. All proteins exhibit the same fold and the overall structures resemble that of the founding member of the family, CVN, albeit with noteworthy differences in loop conformation and detailed local structure.

  2. Acid Rain

    USGS Publications Warehouse

    Bricker, Owen P.; Rice, Karen C.

    1995-01-01

    Although acid rain is fading as a political issue in the United States and funds for research in this area have largely disappeared, the acidity of rain in the Eastern United States has not changed significantly over the last decade, and it continues to be a serious environmental problem. Acid deposition (commonly called acid rain) is a term applied to all forms of atmospheric deposition of acidic substances - rain, snow, fog, acidic dry particulates, aerosols, and acid-forming gases. Water in the atmosphere reacts with certain atmospheric gases to become acidic. For example, water reacts with carbon dioxide in the atmosphere to produce a solution with a pH of about 5.6. Gases that produce acids in the presence of water in the atmosphere include carbon dioxide (which converts to carbonic acid), oxides of sulfur and nitrogen (which convert to sulfuric and nitric acids}, and hydrogen chloride (which converts to hydrochloric acid). These acid-producing gases are released to the atmosphere through natural processes, such as volcanic emissions, lightning, forest fires, and decay of organic matter. Accordingly, precipitation is slightly acidic, with a pH of 5.0 to 5.7 even in undeveloped areas. In industrialized areas, most of the acid-producing gases are released to the atmosphere from burning fossil fuels. Major emitters of acid-producing gases include power plants, industrial operations, and motor vehicles. Acid-producing gases can be transported through the atmosphere for hundreds of miles before being converted to acids and deposited as acid rain. Because acids tend to build up in the atmosphere between storms, the most acidic rain falls at the beginning of a storm, and as the rain continues, the acids "wash out" of the atmosphere.

  3. Nontraditional family romance.

    PubMed

    Corbett, K

    2001-07-01

    Family stories lie at the heart of psychoanalytic developmental theory and psychoanalytic clinical technique, but whose family? Increasingly, lesbian and gay families, multiparent families, and single-parent families are relying on modern reproductive technologies to form families. The contemplation of these nontraditional families and the vicissitudes of contemporary reproduction lead to an unknowing of what families are, including the ways in which psychoanalysts configure the family within developmental theory. This article focuses on the stories that families tell in order to account for their formation--stories that include narratives about parental union, parental sexuality, and conception. The author addresses three constructs that inform family stories and that require rethinking in light of the category crises posed by and for the nontraditional family: (1) normative logic, (2) family reverie and the construction of a family romance, and (3) the primal scene. These constructs are examined in tandem with detailed clinical material taken from the psychotherapy of a seven-year-old boy and his two mothers.

  4. Strengthening Family Practices for Latino Families

    ERIC Educational Resources Information Center

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

  5. Strengthening Family Practices for Latino Families

    ERIC Educational Resources Information Center

    Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

    2010-01-01

    This study examined the effectiveness of a culturally adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9- to 12-year-old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted…

  6. The Family Relationships Grid: Measuring Family Structure.

    ERIC Educational Resources Information Center

    Copeland, Anne P.; And Others

    This study examined the Family Relationships Grid (FRG), a new measure of family structure that evaluates alliances, identification, isolation, and the relative strength of sibling and marital relationships. Subjects were 52 female and 35 male adolescents who were recruited through a university course and who each had at least one sibling.…

  7. Family Roles, Alcoholism, and Family Dysfunction.

    ERIC Educational Resources Information Center

    Alford, Karola M.

    1998-01-01

    Examines family roles in college undergraduates (N=748). Comparing role identification found no differences between children of alcoholics (ACOA) and non-ACOAs. Differences were found in participants from dysfunctional families. Results suggest a need for clinicians to re-think the use of role conceptualization in therapeutic work with ACOAs, with…

  8. Family Therapy for the "Truncated" Nuclear Family.

    ERIC Educational Resources Information Center

    Zuk, Gerald H.

    1980-01-01

    The truncated nuclear family consists of a two-generation group in which conflict has produced a polarization of values. The single-parent family is at special risk. Go-between process enables the therapist to depolarize sharply conflicted values and reduce pathogenic relating. (Author)

  9. Putting the "family" back into family therapy.

    PubMed

    Breunlin, Douglas C; Jacobsen, Elizabeth

    2014-09-01

    In this article, we examine the field of family therapy by drawing a distinction between two forms of practice: Whole Family Therapy (WFT), defined as treating the whole family, and Relational Family Therapy (RFT), defined as working with a subsystem of the family or an individual while retaining a systemic lens. Our thesis is that the practice of WFT has been in decline for some time and steps must be taken to keep it from becoming a defunct practice. We consider the trajectory of WFT and RFT throughout the development of family therapy through reference to the people, the literature, training, and practice patterns associated with family therapy. We remind the reader of the many benefits of WFT and suggest that today WFT is likely to be practiced in conjunction with RFT and individual therapy. Since training of family therapists today is largely located in degree-granting programs, we identify constraints to including WFT in such programs. We conclude by offering suggestions that can enhance a program's ability to train students in WFT. © 2014 FPI, Inc.

  10. Family perspective on a family care program.

    PubMed

    Shimizu, Helena Eri; Rosales, Carlos

    2008-01-01

    This study aimed at assessing the family's perspective on a family care program to better understand the challenges and potential capacities for changing the health care model. A qualitative study was carried out to assess the Family Health Program in the city of São Sebastião, Brasília, Brazil. Data was collected through direct systematic observations of the workflow developed by the program's team, and through focal groups with family members. The discourse of the collective subject was used in data analysis and showed that health prevention and promotion actions and the relationship between providers and consumers were positively evaluated while access to health services, drugs and providers was negatively evaluated. There is no assurance of comprehensive and continuous care to the family, which points to the need of reviewing the strategies of health service organization for more effective involvement of the community to meet their health needs.

  11. Acid Rain.

    ERIC Educational Resources Information Center

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  12. Acid Rain.

    ERIC Educational Resources Information Center

    Openshaw, Peter

    1987-01-01

    Provides some background information on acid deposition. Includes a historical perspective, describes some effects of acid precipitation, and discusses acid rain in the United Kingdom. Contains several experiments that deal with the effects of acid rain on water quality and soil. (TW)

  13. Developmental Toxicity of Perfluorinated Phosphonic Acids in Mice

    EPA Science Inventory

    Perfluorinated phosphonic acids (PFPAs) are a third member of the perfluoroalkyl acid (PFAA) family, and are structurally similar to the perfluoroalkyl sulfonates and perfluoroalkyl carboxylates. PFPAs are used primarily as a surfactant defoaming agent in pesticide production. Re...

  14. Developmental Toxicity of Perfluorinated Phosphonic Acids in Mice

    EPA Science Inventory

    Perfluorinated phosphonic acids (PFPAs) are a third member of the perfluoroalkyl acid (PFAA) family, and are structurally similar to the perfluoroalkyl sulfonates and perfluoroalkyl carboxylates. PFPAs are used primarily as a surfactant defoaming agent in pesticide production. Re...

  15. Invest in Family*

    PubMed Central

    Shah, Nilesh; De Sousa, Avinash

    2015-01-01

    The family is an integral part of one's life. It is very essential that every individual employed or unemployed invests time therein. The family is a source of support and growth for an individual, and the lack of family support or loneliness may be a causative factor in the genesis of psychiatric disorders, especially depression. In India, family plays a paramount role when it comes to mental health of the individual. Tips on how one should invest time in one's family along with the role of a family in one's personal and social structure are discussed. PMID:25838732

  16. Recent insights into iron homeostasis and their application in graminaceous crops

    PubMed Central

    KOBAYASHI, Takanori; NAKANISHI, Hiromi; NISHIZAWA, Naoko K.

    2010-01-01

    Higher plants utilize various mechanisms to maintain iron homeostasis. To acquire sparingly soluble iron from the rhizosphere, graminaceous plants synthesize natural iron (III) chelators known as mugineic acid family phytosiderophores (MAs). Recent research has uncovered various genes involved in iron uptake and translocation, as well as factors regulating the expression of these genes, especially in rice. Manipulation of these molecular components is used to produce transgenic crops with enhanced tolerance to iron deficiency, or with a high seed iron content. Since iron homeostasis is closely linked to that of other mineral elements, an understanding of this phenomenon will serve as the basis for the production of crops with low concentrations of toxic metals and transgenic plants for phytoremediation. PMID:21084773

  17. Chemoprevention in familial adenomatous polyposis.

    PubMed

    Kim, Brian; Giardiello, Francis M

    2011-08-01

    Familial adenomatous polyposis (FAP) predictably leads to adenomas and eventual adenocarcinomas in the lower gastrointestinal tract and less frequently, the upper gastrointestinal tract. Chemopreventive strategies have been studied in FAP patients to delay the development of adenomas in the upper and lower gastrointestinal tract, as well as to prevent recurrence of adenomas in the retained rectum of patients after prophylactic surgery with colectomy and ileorectal anastamosis (IRA). The nonsteroidal anti-inflammatory drug (NSAID) sulindac and selective cyclooxygenase-2 (COX-2) inhibitor celecoxib reduce polyposis of the retained rectum after colectomy with IRA. Reports of cardiovascular risks of some NSAIDs and selective COX-2 inhibitors have led to promising studies of lower doses in combination with ursodeoxycholic acid, statin, and difluoromethylornithine. Curcumin and eicosapentaenoic acid show efficacy in small clinical trials of FAP chemoprevention. This article will review the concept of chemoprevention and the current clinical literature in FAP chemoprevention.

  18. Chemoprevention in familial adenomatous polyposis

    PubMed Central

    Kim, Brian; Giardiello, Francis M.

    2013-01-01

    Familial adenomatous polyposis (FAP) predictably leads to adenomas and eventual adenocarcinomas in the lower gastrointestinal tract and less frequently, the upper gastrointestinal tract. Chemopreventive strategies have been studied in FAP patients to delay the development of adenomas in the upper and lower gastrointestinal tract, as well as to prevent recurrence of adenomas in the retained rectum of patients after prophylactic surgery with colectomy and ileorectal anastamosis (IRA). The nonsteroidal anti-inflammatory drug (NSAID) sulindac and selective cyclooxygenase-2 (COX-2) inhibitor celecoxib reduce polyposis of the retained rectum after colectomy with IRA. Reports of cardiovascular risks of some NSAIDs and selective COX-2 inhibitors have led to promising studies of lower doses in combination with ursodeoxycholic acid, statin, and difluoromethylornithine. Curcumin and eicosapentaenoic acid show efficacy in small clinical trials of FAP chemoprevention. This article will review the concept of chemoprevention and the current clinical literature in FAP chemoprevention. PMID:22122775

  19. Government and the Family

    ERIC Educational Resources Information Center

    Mondale, Walter F.

    1975-01-01

    In order to deal successfully with the changes and pressures placed upon families, article considered the extent government policies are helping or hurting families, and what kind of support services are available. (Author/RK)

  20. Unique Family Living Situations

    MedlinePlus

    ... if the family home changes for reasons of divorce, death, or economics? Factors, such as shifting between ... blending families when a parent remarries after a divorce or death of a spouse, or moving in ...

  1. Choosing a Family Doctor

    MedlinePlus

    ... Mental Health Sex and Birth Control Sex and Sexuality Birth Control Family HealthInfants and Toddlers Kids and ... Mental Health Sex and Birth Control Sex and Sexuality Birth Control Family HealthInfants and Toddlers Kids and ...

  2. Assessing Postpartum Family Functioning

    PubMed Central

    Midmer, Deana; Talbot, Yves

    1988-01-01

    The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals. PMID:21253238

  3. Family Caregiver Alliance

    MedlinePlus

    ... on your schedule. Look for our launch soon! FAMILY CARE NAVIGATOR ─ Click on Your State AL AK ... County Smart Patients Caregivers Community In partnership with Family Caregiver Alliance Learn more Caregiver Research Veterans suffer ...

  4. Folded and unfolded conformations of the omega-3 polyunsaturated fatty acid family: ch(3)ch(2)[ch=chch(2)](b)[ch(2)](m)cooh: first principles study.

    PubMed

    Law, Jacqueline M S; Szori, Milan; Izsak, Robert; Penke, Botond; Csizmadia, Imre G; Viskolcz, Bela

    2006-05-11

    Polyunsaturated fatty acids (PUFA) like stearidonic acid (SDA;18:4 n-3) eicosapentaenoic acid (EPA; 20:5 n-3), and docosahexaenoic acid (DHA; 22:6 n-3) and its chain fragment models were studied at B3LYP/6-31G(d) levels of theory. Significant conformations for the cis and trans isomers were selected to obtained the thermodynamic functions (DeltaH, DeltaS, DeltaG) for the cis-trans isomerization and for folding using the B3LYP/6-311+G(2d,p)//B3LYP/6-31G(d) level of theory. The structural analysis shows that there are significant differences in thermodynamic function of the trans- and cis-PUFAs. The trans-cis isomerization energy values reinforce the consistency and the relative accuracy of theoretical model calculations. The observed flexibility of naturally cis PUFAs could be explained by a very special "smooth basin" PES of the motif of sp(2)-sp(3)-sp(2) hybrid states as reported previously (J. Phys. Chem. A 2005, 109, 520-533). We assumed that intrinsic thermodynamic functions may describe this flexible folding process. The folding enthalpy as well as the folding entropy suggests that there is a new role of the cis-PUFAs in membranes: these cis isomers may have a strong influence on membrane stability and permeability. The average length of the cis helix and beta PUFA was approximated. The difference between the lengths of these two structures is approximately 10 A.

  5. Sodium-coupled and electrogenic transport of B-complex vitamin nicotinic acid by slc5a8, a member of the Na/glucose co-transporter gene family

    PubMed Central

    Gopal, Elangovan; Fei, You-Jun; Miyauchi, Seiji; Zhuang, Lina; Prasad, Puttur D.; Ganapathy, Vadivel

    2005-01-01

    SMCT (sodium-coupled monocarboxylate transporter; slc5a8) is a Na+-coupled transporter for lactate, pyruvate and short-chain fatty acids. Similar to these already known substrates of SMCT, the water-soluble B-complex vitamin nicotinic acid also exists as a monocarboxylate anion (nicotinate) under physiological conditions. Therefore we evaluated the ability of SMCT to mediate the uptake of nicotinate. In mammalian cells, the cloned mouse SMCT (slc5a8) induced the uptake of nicotinate. The SMCT-induced uptake was Na+-dependent. The Michaelis constant for the uptake process was 296±88 μM. The Na+-activation kinetics indicated that at least two Na+ ions are involved in the process. Among the various structural analogues tested, nicotinate was the most effective substrate. Nicotinamide and methylnicotinate were not recognized by the transporter. 2-Pyrazine carboxylate and isonicotinate interacted with the transporter to a moderate extent. SMCT-mediated uptake of nicotinate was inhibited by lactate and pyruvate. In the Xenopus laevis oocyte expression system, SMCT-mediated nicotinate transport was electrogenic, as evident from the nicotinate-induced inward currents under voltage-clamp conditions. Substrate-induced currents in this expression system corroborated the substrate specificity determined in the mammalian cell expression system. The kinetic parameters with regard to the affinity of the transporter for nicotinate and the Hill coefficient for Na+ activation, determined by using the oocyte expression system, were also similar to those obtained from the mammalian cell expression system. We conclude that SMCT functions not only as a Na+-coupled transporter for short-chain fatty acids and lactate but also as a Na+-coupled transporter for the water-soluble vitamin nicotinic acid. PMID:15651982

  6. Electrophilic nitro-fatty acids prevent astrocyte-mediated toxicity to motor neurons in a cell model of familial amyotrophic lateral sclerosis via nuclear factor erythroid 2-related factor activation.

    PubMed

    Diaz-Amarilla, Pablo; Miquel, Ernesto; Trostchansky, Andrés; Trias, Emiliano; Ferreira, Ana M; Freeman, Bruce A; Cassina, Patricia; Barbeito, Luis; Vargas, Marcelo R; Rubbo, Homero

    2016-06-01

    Nitro-fatty acids (NO2-FA) are electrophilic signaling mediators formed in tissues during inflammation, which are able to induce pleiotropic cytoprotective and antioxidant pathways including up regulation of Nuclear factor erythroid 2-related factor 2 (Nrf2) responsive genes. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons associated to an inflammatory process that usually aggravates the disease progression. In ALS animal models, the activation of the transcription factor Nrf2 in astrocytes confers protection to neighboring neurons. It is currently unknown whether NO2-FA can exert protective activity in ALS through Nrf2 activation. Herein we demonstrate that nitro-arachidonic acid (NO2-AA) or nitro-oleic acid (NO2-OA) administrated to astrocytes expressing the ALS-linked hSOD1(G93A) induce antioxidant phase II enzyme expression through Nrf2 activation concomitant with increasing intracellular glutathione levels. Furthermore, treatment of hSOD1(G93A)-expressing astrocytes with NO2-FA prevented their toxicity to motor neurons. Transfection of siRNA targeted to Nrf2 mRNA supported the involvement of Nrf2 activation in NO2-FA-mediated protective effects. Our results show for the first time that NO2-FA induce a potent Nrf2-dependent antioxidant response in astrocytes capable of preventing motor neurons death in a culture model of ALS.

  7. The aconitate hydratase family from Citrus

    PubMed Central

    2010-01-01

    Background Research on citrus fruit ripening has received considerable attention because of the importance of citrus fruits for the human diet. Organic acids are among the main determinants of taste and organoleptic quality of fruits and hence the control of fruit acidity loss has a strong economical relevance. In citrus, organic acids accumulate in the juice sac cells of developing fruits and are catabolized thereafter during ripening. Aconitase, that transforms citrate to isocitrate, is the first step of citric acid catabolism and a major component of the citrate utilization machinery. In this work, the citrus aconitase gene family was first characterized and a phylogenetic analysis was then carried out in order to understand the evolutionary history of this family in plants. Gene expression analyses of the citrus aconitase family were subsequently performed in several acidic and acidless genotypes to elucidate their involvement in acid homeostasis. Results Analysis of 460,000 citrus ESTs, followed by sequencing of complete cDNA clones, identified in citrus 3 transcription units coding for putatively active aconitate hydratase proteins, named as CcAco1, CcAco2 and CcAco3. A phylogenetic study carried on the Aco family in 14 plant species, shows the presence of 5 Aco subfamilies, and that the ancestor of monocot and dicot species shared at least one Aco gene. Real-time RT-PCR expression analyses of the three aconitase citrus genes were performed in pulp tissues along fruit development in acidic and acidless citrus varieties such as mandarins, oranges and lemons. While CcAco3 expression was always low, CcAco1 and CcAco2 genes were generally induced during the rapid phase of fruit growth along with the maximum in acidity and the beginning of the acid reduction. Two exceptions to this general pattern were found: 1) Clemenules mandarin failed inducing CcAco2 although acid levels were rapidly reduced; and 2) the acidless "Sucreña" orange showed unusually high levels

  8. The aconitate hydratase family from Citrus.

    PubMed

    Terol, Javier; Soler, Guillermo; Talon, Manuel; Cercos, Manuel

    2010-10-19

    Research on citrus fruit ripening has received considerable attention because of the importance of citrus fruits for the human diet. Organic acids are among the main determinants of taste and organoleptic quality of fruits and hence the control of fruit acidity loss has a strong economical relevance. In citrus, organic acids accumulate in the juice sac cells of developing fruits and are catabolized thereafter during ripening. Aconitase, that transforms citrate to isocitrate, is the first step of citric acid catabolism and a major component of the citrate utilization machinery. In this work, the citrus aconitase gene family was first characterized and a phylogenetic analysis was then carried out in order to understand the evolutionary history of this family in plants. Gene expression analyses of the citrus aconitase family were subsequently performed in several acidic and acidless genotypes to elucidate their involvement in acid homeostasis. Analysis of 460,000 citrus ESTs, followed by sequencing of complete cDNA clones, identified in citrus 3 transcription units coding for putatively active aconitate hydratase proteins, named as CcAco1, CcAco2 and CcAco3. A phylogenetic study carried on the Aco family in 14 plant species, shows the presence of 5 Aco subfamilies, and that the ancestor of monocot and dicot species shared at least one Aco gene. Real-time RT-PCR expression analyses of the three aconitase citrus genes were performed in pulp tissues along fruit development in acidic and acidless citrus varieties such as mandarins, oranges and lemons. While CcAco3 expression was always low, CcAco1 and CcAco2 genes were generally induced during the rapid phase of fruit growth along with the maximum in acidity and the beginning of the acid reduction. Two exceptions to this general pattern were found: 1) Clemenules mandarin failed inducing CcAco2 although acid levels were rapidly reduced; and 2) the acidless "Sucreña" orange showed unusually high levels of expression of

  9. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  10. Families in Multicultural Perspective.

    ERIC Educational Resources Information Center

    Ingoldsby, Bron B., Ed.; Smith, Suzanna, Ed.

    Covering contemporary Third World as well as Western families, this teaching text addresses topics essential for developing a multicultural perspective on the family. It is an ideal text for comparative family courses and includes exercises (as well as exercise guidelines for instructors) developed to challenge students' existing viewpoints and…

  11. Treatment of violent families.

    PubMed Central

    Bell, C. C.; Chance-Hill, G.

    1991-01-01

    Family violence is responsible for a significant proportion of homicides, a major cause of premature deaths in African-Americans. This article reviews the prevalence of family violence and explores associated risk factors. Principles and tips of treatment, along with a cognitive framework to guide the actual therapy, are outlined. Finally, issues of preventing family violence are discussed. PMID:2038079

  12. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  13. Families in Transition.

    ERIC Educational Resources Information Center

    Britton, Patti O., Ed.; McGee, Michael, Ed.

    1987-01-01

    This issue of "Emphasis" deals with families in transition, providing some model programs for the new family and some historical perspectives on how families have developed over time. Articles include: (1) "Nostalgia on the Right" (Nancy Theriot); (2) "Heart to Heart" (Nancy Harrington-MacLennan); (3) "The Media Get the Message" (Janet Alyn); (4)…

  14. Rape: A Family Crisis.

    ERIC Educational Resources Information Center

    White, Priscilla N.; Rollins, Judith C.

    1981-01-01

    Rape is a crisis shared by the victim and her family. The family's reaction is influenced by cultural views such as viewing rape as sex rather than violence. Adaptive responses can be supported by open expression, education, and family, as well as individual counseling. (JAC)

  15. Books in the Family.

    ERIC Educational Resources Information Center

    Swinger, Alice K.

    1989-01-01

    Opportunities for parents to encourage reading in the family are noted and ways to enhance the reading experience are discussed, including writing letters to book characters, singing combined with reading aloud, supplementing school subjects with enjoyable reading, sharing books at family gatherings, and using family experiences for book…

  16. Year of the Family.

    ERIC Educational Resources Information Center

    California Agriculture, 1994

    1994-01-01

    This special issue focuses on problems and challenges confronting the California family and on research and extension efforts to provide at least partial answers. Research briefs by staff include "Challenges Confront the California Family" (state trends in poverty, divorce, single-parent families, child abuse, delinquency, teen births,…

  17. Family Violence: An Overview.

    ERIC Educational Resources Information Center

    National Center on Child Abuse and Neglect (DHHS/OHDS), Washington, DC.

    Family violence is a widespread problem; research has shown multiple factors are associated with family violence. Types of family violence include spouse abuse; elder abuse and neglect; child abuse and neglect; parent abuse; and sibling abuse. There are three types of spouse abuse: physical abuse, sexual violence, and psychological/emotional…

  18. Family Customs and Traditions.

    ERIC Educational Resources Information Center

    MacGregor, Cynthia

    Recognizing the importance of maintaining open communication with immediate and extended family members, this book provides a compilation of ideas for family traditions and customs that are grounded in compassion and human kindness. The traditions were gathered from families in the United States and Canada who responded to advertisements in…

  19. Single Mothers "Do" Family

    ERIC Educational Resources Information Center

    Nelson, Margaret K.

    2006-01-01

    This paper explores how single mothers both incorporate others into family life (e.g., when they ask others to care for their children) and simultaneously "do families" in a manner that holds out a vision of a "traditional" family structure. Drawing on research with White, rural single mothers, the author explores the manner in which these women…

  20. Changing Family Forms.

    ERIC Educational Resources Information Center

    Seibert, M. Therese; Willetts, Marion C.

    2000-01-01

    Explores the definition of family. Considers three facets of the contemporary family measured by U.S. Census statistics: (1) marriage and divorce trends; (2) declining fertility; and (3) the rise in single-headed families. Addresses the societal changes (economic, cultural, legal, and technological) that have influenced the changes in family…

  1. Family Customs and Traditions.

    ERIC Educational Resources Information Center

    MacGregor, Cynthia

    Recognizing the importance of maintaining open communication with immediate and extended family members, this book provides a compilation of ideas for family traditions and customs that are grounded in compassion and human kindness. The traditions were gathered from families in the United States and Canada who responded to advertisements in…

  2. Launching Family Message Journals.

    ERIC Educational Resources Information Center

    Wollman-Bonilla, Julie

    This lesson introduces Family Message Journals, a tool for encouraging family involvement and supporting writing to reflect and learn. First and second graders are led into composing through demonstration, guided writing, and finally independent writing of messages that they will bring home for family to read and write a reply. During the three…

  3. Fatherhood and Family Support.

    ERIC Educational Resources Information Center

    Goetz, Kathy, Ed.

    1996-01-01

    On the assumption that fathers have been relatively absent from family support programs, this publication of the Family Resource Coalition addresses the role of fathers in family support programs, examines the impact of fathers on their children, and describes programs involving fathers successfully. Articles include: (1) "What's Behind the…

  4. Family Planning & Literacy.

    ERIC Educational Resources Information Center

    International Planned Parenthood Federation, London (England).

    This publication is an International Planned Parenthood Federation (IPPF) annotated bibliography of books and articles concerned with family planning and literacy. The subject is divided into four major listings: (1) Literacy; (2) Education; (3) Literacy and Family Planning; and (4) Functional Literacy/Family Planning Projects and Programs.…

  5. Family Support Evaluation.

    ERIC Educational Resources Information Center

    Lalley, Jacqueline, Ed.; Ahsan, Nilofer, Ed.

    1998-01-01

    The Family Resource Coalition of America (FRCA) and the National Resource Center for Family Centered Practice convened a meeting of evaluators, policymakers, and program practitioners to discuss the issue of evaluation in the field of family support. The goal was to bring together those who were implementing programs, evaluating programs, and…

  6. Families in Multicultural Perspective.

    ERIC Educational Resources Information Center

    Ingoldsby, Bron B., Ed.; Smith, Suzanna, Ed.

    Covering contemporary Third World as well as Western families, this teaching text addresses topics essential for developing a multicultural perspective on the family. It is an ideal text for comparative family courses and includes exercises (as well as exercise guidelines for instructors) developed to challenge students' existing viewpoints and…

  7. Toward the Postmodern Family

    ERIC Educational Resources Information Center

    Shorter, Edward

    1976-01-01

    Examines three aspects of family life that are evolving in directions that have no historical precedent--adolescent indifference to the family's identity that shows up in the discontinuity of values from parents to children, instability in the life of the couple, and systematic demolition of the nuclear family. (Author/IRT)

  8. The Resiliency of Families.

    ERIC Educational Resources Information Center

    Morrison, T. R.

    According to researchers, the family may be changing but it is still one of the central institutions in society. Studies report a shift in more than 20 attitudes and values, most of which relate to the context of family life. Specifically, these include attitudes toward marriage, divorce, childbearing, childrearing, working women, family violence,…

  9. Strengthening America's Families.

    ERIC Educational Resources Information Center

    Alvarado, Rose; Kumpfer, Karol

    2000-01-01

    Improving parenting practices and the family environment is the most effective, enduring strategy for combating juvenile delinquency. Describes the Office of Juvenile Justice and Delinquency Prevention's Strengthening America's Families Initiative. Highlights several family-focused prevention programs identified as exemplary, explaining how they…

  10. Doing Better for Families

    ERIC Educational Resources Information Center

    OECD Publishing (NJ3), 2011

    2011-01-01

    All OECD governments want to give parents more choice in their work and family decisions. This book looks at the different ways in which governments support families. It seeks to provide answers to questions like: Is spending on family benefits going up, and how does it vary by the age of the child? Has the crisis affected public support for…

  11. A story of family.

    PubMed

    Condon, Barbara Backer

    2010-07-01

    The author of this column gives a vivid description of Parse's humanbecoming family model as lived in community. The story of M'Barek (Mark), who was imprisoned for 18 years, draws readers to a new understanding of family and community. Through the process of storytelling, Parse's essences of family are discussed.

  12. Family II. Leptospiraceae Hovind-Hougen 1979, 245AL

    USDA-ARS?s Scientific Manuscript database

    Bacteria within the Family Leptospiraceae comprise a diverse group of three bacterial genera, Leptospira, Leptonema, and Turneriella. These bacteria are aerobes that consume long-chain fatty acids and alcohols as carbon and energy sources. Some members of this Family cause serious infections in ani...

  13. The Arabidopsis thaliana At4g13040 gene, a unique member of the AP2/EREBP family, is a positive regulator for salicylic acid accumulation and basal defense against bacterial pathogens.

    PubMed

    Giri, Mrunmay Kumar; Swain, Swadhin; Gautam, Janesh Kumar; Singh, Subaran; Singh, Nidhi; Bhattacharjee, Lipika; Nandi, Ashis Kumar

    2014-06-15

    The Arabidopsis genome contains a large number of putative transcription factors, containing a DNA binding domain similar to APETALA2/ethylene response element binding protein (AP2/EREBP), for most of which a function is not known. Phylogenetic analysis divides the Apetala 2 (AP2) super-family into 5 major groups: AP2, RAV, ethylene response factor (ERF), dehydration response element binding protein (DREB) and At4g13040. Similar to ERF and DREB, the At4g13040 protein contains only one AP2 domain; however, its structural uniqueness places it into a distinct group. In this article, we report that At4g13040 (referred herein as Apetala 2 family protein involved in SA mediated disease defense 1 - APD1) is an important regulator for SA mediated plant defense. The APD1 gene is upregulated upon pathogen inoculation, exogenous SA application and in the mutant that constitutively activates SA signaling. The T-DNA insertion lines (inserted in the APD1 promoter), which fail to induce expression upon pathogen inoculation, are compromised for resistance against virulent bacterial pathogens and show reduced induction of pathogenesis related 1 gene. Our results suggest that APD1 functions downstream of PAD4 in Arabidopsis and promotes pathogen-induced SA accumulation. Exogenous SA application completely restores the loss-of-resistance phenotype of the apd1 mutant. Thus, APD1 is a positive regulator of disease defense that functions upstream of SA accumulation.

  14. [Aristolochic acid nephropathy].

    PubMed

    Witkowicz, Joanna

    2009-01-01

    Aristolochic acid nephropathy is a chronic, fibrosing, interstitial nephritis caused by aristolochic acid (AA), which is a component of the plants of Aristolochiacae family. It was first reported in 1993, in Belgium as a Chinese herb nephropathy, in patients who received a slimming regimen containing AA. The term aristolochic acid nephropathy also includes Balcan endemic nephropathy and other endemic tubulointerstitial fibrosis. Moreover, AA is a human carcinogen which induces urothelial cancer. The AA-containing herbs are banned in many countries and FDA published the warnings concerning the safety of AA-containing botanical remedies in 2000. Regarding the increasing interest in herbal medicines, uncontrolled access to botanical remedies and replacement of one herb by another AA-containing compounds makes thousands of people all around the world at risk of this grave disease.

  15. The solute carrier 6 family of transporters

    PubMed Central

    Bröer, Stefan; Gether, Ulrik

    2012-01-01

    The solute carrier 6 (SLC6) family of the human genome comprises transporters for neurotransmitters, amino acids, osmolytes and energy metabolites. Members of this family play critical roles in neurotransmission, cellular and whole body homeostasis. Malfunction or altered expression of these transporters is associated with a variety of diseases. Pharmacological inhibition of the neurotransmitter transporters in this family is an important strategy in the management of neurological and psychiatric disorders. This review provides an overview of the biochemical and pharmacological properties of the SLC6 family transporters. LINKED ARTICLES BJP published a themed section on Transporters in 2011. To view articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2011.164.issue-7/issuetoc PMID:22519513

  16. Progressive familial intrahepatic cholestasis.

    PubMed

    Jacquemin, Emmanuel

    2012-09-01

    Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal-recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and associated with mutations in hepatocellular transport-system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may arise later in infancy, in childhood or even during young adulthood. The main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT) activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due to defects in ATP8B1 encoding the FIC1 protein and in ABCB11 encoding bile salt export pump (BSEP) protein, respectively. Defects in ABCB4, encoding multidrug resistance 3 protein (MDR3), impair biliary phospholipid secretion, resulting in PFIC3. Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests to exclude other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates for whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis may be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA) therapy should be initiated in all patients to prevent liver damage. In some PFIC1 and PFIC2 patients, biliary diversion may also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation. Monitoring of liver tumors

  17. Progressive familial intrahepatic cholestasis.

    PubMed

    Davit-Spraul, Anne; Gonzales, Emmanuel; Baussan, Christiane; Jacquemin, Emmanuel

    2009-01-08

    Progressive familial intrahepatic cholestasis (PFIC) refers to heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin. The exact prevalence remains unknown, but the estimated incidence varies between 1/50,000 and 1/100,000 births. Three types of PFIC have been identified and related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 usually appear in the first months of life, whereas onset of PFIC3 may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. PFIC patients usually develop fibrosis and end-stage liver disease before adulthood. Serum gamma-glutamyltransferase (GGT) activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP). Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3), impair biliary phospholipid secretion resulting in PFIC3. Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis. Antenatal diagnosis can be proposed for affected families in which a mutation has been identified. Ursodeoxycholic acid (UDCA) therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation. Monitoring of

  18. Consolidation of glycosyl hydrolase family 30 : a dual domain 4/7 hydrolase family consisting of two structurally distinct groups

    Treesearch

    Franz J. St John; Javier M. Gonzalez; Edwin Pozharski

    2010-01-01

    In this work glycosyl hydrolase (GH) family 30 (GH30) is analyzed and shown to consist of its currently classified member sequences as well as several homologous sequence groups currently assigned within family GH5. A large scale amino acid sequence alignment and a phylogenetic tree were generated and GH30 groups and subgroups were designated. A partial rearrangement...

  19. Management of Melanoma Families

    PubMed Central

    Bergman, Wilma; Gruis, Nelleke A.

    2010-01-01

    In this review we have aimed to focus on the clinical management of familial melanoma patients and their relatives. Along this line three major topics will be discussed: (1) management/screening of familial melanoma families: what is advised and what is the evidence thereof; (2) variability of families worldwide with regard to clinical phenotype, including cancer spectrum and likelihood of finding germline mutations and (3) background information for clinicians on the molecular biology of familial melanoma and recent developments in this field. PMID:24281082

  20. Family traditions and generations.

    PubMed

    Schneiderman, Gerald; Barrera, Maru

    2009-01-01

    Currently, traditional family values that have been passed down through generations appear to be at risk. This has significant implications for the stability and health of individuals, families, and communities. This article explores selected issues related to intergenerational transmission of family values and cultural beliefs, with particular reference to Western culture and values that are rooted in Jewish and Christian traditions. It also examines family values and parenting styles as they influence the developing perspective of children and the family's adaptation to a changing world.

  1. Familial colorectal cancer.

    PubMed

    Lung, M S; Trainer, A H; Campbell, I; Lipton, L

    2015-05-01

    Identifying individuals with a genetic predisposition to developing familial colorectal cancer (CRC) is crucial to the management of the affected individual and their family. In order to do so, the physician requires an understanding of the different gene mutations and clinical manifestations of familial CRC. This review summarises the genetics, clinical manifestations and management of the known familial CRC syndromes, specifically Lynch syndrome, familial adenomatous polyposis, MUTYH-associated neoplasia, juvenile polyposis syndrome and Peutz-Jeghers syndrome. An individual suspected of having a familial CRC with an underlying genetic predisposition should be referred to a familial cancer centre to enable pre-test counselling and appropriate follow up. © 2015 Royal Australasian College of Physicians.

  2. Family practice in Turkey.

    PubMed

    Ozsahin, Akatli Kursad

    2014-03-01

    The national project 'Transformation in Health' was started in 2005 to provide expert primary care by family physicians, and decrease expenses in Turkey. The number of family physicians was far below the need, so public physicians were promoted to family physician status after a 10-day intensive course. The government declared some satisfactory results, but privately paid family physicians were not accepted into the system. Furthermore, the government stopped paying for their services from private settings. Some family physicians became unemployed as the major payer for all forms of medical care in Turkey denied their services. The process showed it's value in time. Nevertheless, family physicians should be the core of this transformation as family medicine is an academic and a scientific discipline and a primary care-oriented specialty with its own specific educational content, research and base of evidence, which cannot be achieved through standard medical education.

  3. Acid rain

    SciTech Connect

    Stensland, G.J.

    1983-11-01

    A series of definitions for the field of acid rain studies are presented. Protocols for acid rain sampling and monitoring are also presented. A procedure for calculatory precipitation pH is discussed. 11 references, 1 table.

  4. Folic acid

    MedlinePlus

    ... of childhood cancer of the white blood cells. Iron deficiency. Taking folic acid with iron supplements is not ... supplements without folic acid for treating and preventing iron deficiency and anemia caused by too little iron in ...

  5. Aminocaproic Acid

    MedlinePlus

    Aminocaproic acid is used to control bleeding that occurs when blood clots are broken down too quickly. This type ... the baby is ready to be born). Aminocaproic acid is also used to control bleeding in the ...

  6. Obeticholic Acid

    MedlinePlus

    Obeticholic acid is used alone or in combination with ursodiol (Actigall, Urso) to treat primary biliary cholangitis (PBC; a ... were not treated successfully with ursodiol alone. Obeticholic acid is in a class of medications called farnesoid ...

  7. Acid mucopolysaccharides

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003368.htm Acid mucopolysaccharides To use the sharing features on this page, please enable JavaScript. Acid mucopolysaccharides is a test that measures the amount ...

  8. Ethacrynic Acid

    MedlinePlus

    Ethacrynic acid, a 'water pill,' is used to treat swelling and fluid retention caused by various medical problems. It ... Ethacrynic acid comes as a tablet to take by mouth. It is usually taken once or twice a day ...

  9. Ascorbic Acid

    MedlinePlus

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C in ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops to ...

  10. Aristolochic Acids

    MedlinePlus

    ... Sciences NIH-HHS www.niehs.nih.gov Aristolochic Acids Key Points Report on Carcinogens Status Known to be human carcinogens Aristolochia Clematitis Aristolochic Acids n Known human carcinogens n Found in certain ...

  11. Amino acids

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002222.htm Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  12. Mefenamic Acid

    MedlinePlus

    Mefenamic acid is used to relieve mild to moderate pain, including menstrual pain (pain that happens before or during a menstrual period). Mefenamic acid is in a class of medications called NSAIDs. ...

  13. Multiplex families with epilepsy

    PubMed Central

    Afawi, Zaid; Oliver, Karen L.; Kivity, Sara; Mazarib, Aziz; Blatt, Ilan; Neufeld, Miriam Y.; Helbig, Katherine L.; Goldberg-Stern, Hadassa; Misk, Adel J.; Straussberg, Rachel; Walid, Simri; Mahajnah, Muhammad; Lerman-Sagie, Tally; Ben-Zeev, Bruria; Kahana, Esther; Masalha, Rafik; Kramer, Uri; Ekstein, Dana; Shorer, Zamir; Wallace, Robyn H.; Mangelsdorf, Marie; MacPherson, James N.; Carvill, Gemma L.; Mefford, Heather C.; Jackson, Graeme D.; Scheffer, Ingrid E.; Bahlo, Melanie; Gecz, Jozef; Heron, Sarah E.; Corbett, Mark; Mulley, John C.; Dibbens, Leanne M.; Korczyn, Amos D.

    2016-01-01

    Objective: To analyze the clinical syndromes and inheritance patterns of multiplex families with epilepsy toward the ultimate aim of uncovering the underlying molecular genetic basis. Methods: Following the referral of families with 2 or more relatives with epilepsy, individuals were classified into epilepsy syndromes. Families were classified into syndromes where at least 2 family members had a specific diagnosis. Pedigrees were analyzed and molecular genetic studies were performed as appropriate. Results: A total of 211 families were ascertained over an 11-year period in Israel. A total of 169 were classified into broad familial epilepsy syndrome groups: 61 generalized, 22 focal, 24 febrile seizure syndromes, 33 special syndromes, and 29 mixed. A total of 42 families remained unclassified. Pathogenic variants were identified in 49/211 families (23%). The majority were found in established epilepsy genes (e.g., SCN1A, KCNQ2, CSTB), but in 11 families, this cohort contributed to the initial discovery (e.g., KCNT1, PCDH19, TBC1D24). We expand the phenotypic spectrum of established epilepsy genes by reporting a familial LAMC3 homozygous variant, where the predominant phenotype was epilepsy with myoclonic-atonic seizures, and a pathogenic SCN1A variant in a family where in 5 siblings the phenotype was broadly consistent with Dravet syndrome, a disorder that usually occurs sporadically. Conclusion: A total of 80% of families were successfully classified, with pathogenic variants identified in 23%. The successful characterization of familial electroclinical and inheritance patterns has highlighted the value of studying multiplex families and their contribution towards uncovering the genetic basis of the epilepsies. PMID:26802095

  14. Valproic Acid

    MedlinePlus

    Valproic acid is used alone or with other medications to treat certain types of seizures. Valproic acid is also used to treat mania (episodes of ... to relieve headaches that have already begun. Valproic acid is in a class of medications called anticonvulsants. ...

  15. Protein family classification using sparse markov transducers.

    PubMed

    Eskin, Eleazar; Noble, William Stafford; Singer, Yoram

    2003-01-01

    We present a method for classifying proteins into families based on short subsequences of amino acids using a new probabilistic model called sparse Markov transducers (SMT). We classify a protein by estimating probability distributions over subsequences of amino acids from the protein. Sparse Markov transducers, similar to probabilistic suffix trees, estimate a probability distribution conditioned on an input sequence. SMTs generalize probabilistic suffix trees by allowing for wild-cards in the conditioning sequences. Since substitutions of amino acids are common in protein families, incorporating wild-cards into the model significantly improves classification performance. We present two models for building protein family classifiers using SMTs. As protein databases become larger, data driven learning algorithms for probabilistic models such as SMTs will require vast amounts of memory. We therefore describe and use efficient data structures to improve the memory usage of SMTs. We evaluate SMTs by building protein family classifiers using the Pfam and SCOP databases and compare our results to previously published results and state-of-the-art protein homology detection methods. SMTs outperform previous probabilistic suffix tree methods and under certain conditions perform comparably to state-of-the-art protein homology methods.

  16. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner...

  17. Opening Doors: Understanding School and Family Influences on Family Involvement

    ERIC Educational Resources Information Center

    Carlisle, Erin; Stanley, Lindsey; Kemple, Kristen Mary

    2005-01-01

    Family involvement in schooling can benefit young children, teachers, and families. Family involvement in schools can be influenced by both school-related and family-related factors. School-related factors include teachers' attitudes toward families, and school and teacher expectations. Family-related factors include ethnicity, prior school…

  18. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner is...

  19. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 4 2011-04-01 2011-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner is...

  20. 24 CFR 982.515 - Family share: Family responsibility.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Family share: Family responsibility... Assistance Payment § 982.515 Family share: Family responsibility. (a) The family share is calculated by subtracting the amount of the housing assistance payment from the gross rent. (b) The family rent to owner is...