01852nas a2200241 4500008004100000022001400041245012100055210006900176260016500245300001200410490000700422520084600429653001601275653003601291653002001327653001501347653001001362100002401372700002501396700003701421700002501458856012701483 2011 eng d a0388-135000aComparative and chemical proteomic approaches reveal gatifloxacin deregulates enzymes involved in glucose metabolism0 aComparative and chemical proteomic approaches reveal gatifloxaci aINTERNATIONAL MEDICAL INFORMATION CENTER, SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI, SHINJUKU-KU, TOKYO, 160-0016, JAPANbJAPANESE SOC TOXICOLOGICAL SCIENCEScDEC a787-7960 v363 a

Gatifloxacin has been associated with increased risks of hypoglycemic and hyperglycemic side effects. In order to understand the molecular mechanism of gatifloxacin induced deregulation of glucose metabolism, a Combination of comparative and chemical proteomic approaches were employed using yeast as a model system. Differential protein expression studies using two dimensional electrophoresis and mass spectrometry reveal that gatifloxacin deregulates the expression of key enzymes involved in glucose metabolism. Furthermore, affinity chromatography and LC-MSE analysis led to identification of enolase, as one of the key gatifloxacin binding proteins. Fluorescence spectrometric studies confirmed that the gatifloxacin indeed binds to enolase. Role of enolase in regulation of gatifloxacin induced dysglycemic effect is discussed.

10aantibiotics10aDifferential protein expression10aFluoroquinolone10aGlycolysis10aYeast1 aSuresh, Kesavan, K.1 aBhosale, Santosh, D.1 aThulasiram, Hirekodathakallu, V.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/comparative-and-chemical-proteomic-approaches-reveal-gatifloxacin-deregulates-enzymes-003069nas a2200289 4500008004100000022001400041245020400055210006900259260010300328300001600431490000800447520193000455100001602385700001902401700003702420700001702457700001802474700002502492700001702517700001702534700001702551700001902568700001502587700002102602700002402623856013202647 2012 eng d a0021-925800aNovel anti-inflammatory activity of epoxyazadiradione against macrophage migration inhibitory factor inhibition of tautomerase and proinflammatory activities of macrophage migration inhibitory factor0 aNovel antiinflammatory activity of epoxyazadiradione against mac a9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USAbAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INCcJUL a24844-248610 v2873 a

Macrophage migration inhibitory factor (MIF) is responsible for proinflammatory reactions in various infectious and noninfectious diseases. We have investigated the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid purified from neem (Azadirachta indica) fruits, against MIF. Epoxyazadiradione inhibited the tautomerase activity of MIF of both human (huMIF) and malaria parasites (Plasmodium falciparum (PfMIF) and Plasmodium yoelii (PyMIF)) non-competitively in a reversible fashion (K-i, 2.11-5.23 mu M). Epoxyazadiradione also significantly inhibited MIF (huMIF, PyMIF, and PfMIF)-mediated proinflammatory activities in RAW 264.7 cells. It prevented MIF-induced macrophage chemotactic migration, NF-kappa B translocation to the nucleus, up-regulation of inducible nitric-oxide synthase, and nitric oxide production in RAW 264.7 cells. Epoxyazadiradione not only exhibited anti-inflammatory activity in vitro but also in vivo. We tested the anti-inflammatory activity of epoxyazadiradione in vivo after co-administering LPS and MIF in mice to mimic the disease state of sepsis or bacterial infection. Epoxyazadiradione prevented the release of proinflammatory cytokines such as IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha when LPS and PyMIF were co-administered to BALB/c mice. The molecular basis of interaction of epoxyazadiradione with MIFs was explored with the help of computational chemistry tools and a biological knowledge base. Docking simulation indicated that the binding was highly specific and allosteric in nature. The well known MIF inhibitor (S, R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) inhibited huMIF but not MIF of parasitic origin. In contrast, epoxyazadiradione inhibited both huMIF and plasmodial MIF, thus bearing an immense therapeutic potential against proinflammatory reactions induced by MIF of both malaria parasites and human.

1 aAlam, Athar1 aHaldar, Saikat1 aThulasiram, Hirekodathakallu, V.1 aKumar, Rahul1 aGoyal, Manish1 aIqbal, Mohd, Shameel1 aPal, Chinmay1 aDey, Sumanta1 aBindu, Samik1 aSarkar, Souvik1 aPal, Uttam1 aMaiti, Nakul, C.1 aBandyopadhyay, Uday uhttps://library.ncl.res.in/content/novel-anti-inflammatory-activity-epoxyazadiradione-against-macrophage-migration-inhibitory-002209nas a2200181 4500008004100000022001400041245020800055210006900263260011000332300001400442490000800456520131200464100002501776700003101801700002901832700003701861856012901898 2012 eng d a0003-265400aPreparative separation of alpha- and beta-santalenes and (Z)-alpha- and (Z)-beta-santalols using silver nitrate-impregnated silica gel medium pressure liquid chromatography and analysis of sandalwood oil0 aPreparative separation of alpha and betasantalenes and Zalpha an aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAY a4564-45700 v1373 a

The major sesquiterpene constituents of East-Indian sandalwood oil (Z)-alpha- and (Z)-beta-santalols have shown to be responsible for most of the biological activities and organoleptic properties of sandalwood oil. The work reported here describes the strategic use of medium pressure liquid chromatography (MPLC) for the separation of both alpha- and beta-santalenes and (Z)-alpha- and (Z)-beta-santalols. Silver nitrate impregnated silica gel was used as the stationary phase in MPLC for quantitative separation of alpha- and beta-santalenes and (Z)-alpha- and (Z)-beta-santalols with mobile phases hexane and dichloromethane, respectively. The purities of alpha-santalene and (Z)-alpha-santalol obtained were >96%; however, beta-santalene and (Z)-beta-santalol were obtained with their respective inseparable epi-isomers. Limits of quantification (LoQ) relative to the FID detector were measured for important sesquiterpene alcohols of heartwood oil of S. album using serial dilutions of the standard stock solutions and demonstrated that the quality of the commercial sandalwood oil can be assessed for the content of individual sesquiterpene alcohols regulated by Australian Standard (AS2112-2003), International Organization for Standardization ISO 3518: 2002 (E) and European Union (E. U.).

1 aDaramwar, Pankaj, P.1 aSrivastava, Prabhakar, Lal1 aPriyadarshini, Balaraman1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/preparative-separation-alpha-and-beta-santalenes-and-z-alpha-and-z-beta-santalols-using-002357nas a2200289 4500008004100000022001400041245010500055210006900160260009900229300001000328490000800338520132000346653002201666653001101688653001501699653002001714653002501734100002501759700001601784700002701800700002701827700001901854700001601873700001901889700003701908856012201945 2012 eng d a0960-852400aTransformation of (+/-)-lavandulol and (+/-)-tetrahydrolavandulol by a fungal strain Rhizopus oryzae0 aTransformation of lavandulol and tetrahydrolavandulol by a funga aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLANDbELSEVIER SCI LTDcJUL a70-740 v1153 a

Biotransformation of an irregular monoterpene alcohol, (+/-)-lavandulol [(+/-)-5-methyl-2-(1-methylethenyl)-4-hexen-1-ol] (I) and its tetrahydro derivative, (+/-)-tetrahydrolavandulol [(+/-)-2-isopropyl-5-methylhexan-1-ol] (II) were studied using a soil isolated fungal strain Rhizopus oryzae. Five metabolites, 2-((3,3-dimethyloxiran-2-yl)methyl)-3-methylbut-3-en-1-ol (Ia), 2-methyl-5-(prop-1-en-2-yl)hex-2ene-1,6-diol (Ib), 2-methyl-5-(prop-1-en-2-yl)hexane-1,6-diol (Ic), 2-(3-methylbut-2-enyl)-3-methylenebutane-1,4-diol (Id), 5-methyl-2-(2-methyloxiran-2-yl)hex-4-en-1-01 (Ie) have been isolated from the fermentation medium and characterized with lavandulol as a substrate. When tetrahydrolavandulol used as a substrate, two metabolites 2-isopropyl-5-methylhexane-1,5-diol (IIa) and 2-isopentyl-3-methylbutane-1,3-diol (lib) have been isolated from the fermentation medium. Biotransformation studies with R. oryzae clearly indicate that the organism initiates the transformation either by hydroxylation at allylic methyl groups or epoxidation of double bond. GC and GCMS analyses indicated that both (R)and (S)-enantiomers of I and II have been transformed into corresponding hydroxylated or epoxy derivatives, when racemic I and II were used as substrates. (C) 2011 Elsevier Ltd. All rights reserved.

10aBiotransformation10aFungus10aLavandulol10aRhizopus oryzae10aTetrahydrolavandulol1 aDaramwar, Pankaj, P.1 aRincy, Raju1 aNiloferjahan, Siddiqui1 aKrithika, Ramakrishnan1 aGulati, Arvind1 aYadav, Amit1 aSharma, Rakesh1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/transformation-lavandulol-and-tetrahydrolavandulol-fungal-strain-rhizopus-oryzae-001812nas a2200169 4500008004100000022001400041245011800055210006900173260011000242300001400352490000700366520106400373100001901437700002101456700003701477856012801514 2013 eng d a1463-926200aBiocatalysis: fungi mediated novel and selective 12 beta- or 17 beta-hydroxylation on the basic limonoid skeleton0 aBiocatalysis fungi mediated novel and selective 12 beta or 17 be aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAR a1311-13170 v153 a

Basic limonoids carrying a 4,4,8-trimethyl-17-furanylsteroid skeleton are a class of triterpenoids and well-known for their insecticidal as well as a vast array of pharmacological activities. Rare and synthetically challenging 12 beta- and 17 beta-hydroxylation was achieved on the basic limonoid skeleton to produce a novel series of hydroxylated limonoids using fungi-mediated biocatalysis. The fungal system belonging to the genera of Mucor efficiently converted azadiradione, epoxyazadiradione, gedunin and their derivatives into corresponding 12 beta- and/or 17 beta-hydroxy derivatives. The position and stereochemistry of hydroxylation was determined by rigorous spectroscopic and crystallographic studies. This fungi-mediated stereo- and regio-selective hydroxylation process was highly efficient and mild enough to sustain chemically sensitive functional groups around the basic limonoid skeleton. Modifications of specific functional groups and variation in biocatalyst were shown to bring selectivity among 12 beta- or 17 beta-hydroxylation.

1 aHaldar, Saikat1 aKolet, Swati, P.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/biocatalysis-fungi-mediated-novel-and-selective-12-beta-or-17-beta-hydroxylation-basic-001870nas a2200229 4500008004100000022001400041245010100055210006900156260007900225300001400304490000700318520099500325653002501320653002201345653001401367100002101381700002701402700001901429700002401448700003701472856013101509 2013 eng d a0039-128X00aBiocatalyst mediated production of 6 beta,11 alpha-dihydroxy derivatives of 4-ene-3-one steroids0 aBiocatalyst mediated production of 6 beta11 alphadihydroxy deriv a360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USAbELSEVIER SCIENCE INCcNOV a1152-11580 v783 a

Biotransformation of steroids with 4-ene-3-one functionality such as progesterone (I), testosterone (II), 17 alpha-methyltestosterone (III), 4-androstene-3,17-dione (IV) and 19-nortestosterone (V) were studied by using a fungal system belonging to the genera of Mucor (M881). The fungal system efficiently and quantitatively converted these steroids in regio- and stereo-selective manner into corresponding 6 beta,11 alpha-dihydroxy compounds. Time course experiments suggested that the transformation was initiated by hydroxylation at 6 beta- or 11 alpha-(10 beta-hydroxy in case of V) to form monohydroxy derivatives which upon prolonged incubation were converted into corresponding 613,11oc-dihydroxy derivatives. The fermentation studies carried out using 5 L table-top fermentor with substrates (I and II) clearly indicates that 6 beta,11 alpha-dihydroxy derivatives of steroids with 4-ene-3-one functionality can be produced in large scale by using M881. (C) 2013 Elsevier Ltd.

10a4-Ene-3-one steroids10aBiotransformation10aMucor sp.1 aKolet, Swati, P.1 aNiloferjahan, Siddiqui1 aHaldar, Saikat1 aGonnade, Rajesh, G.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/biocatalyst-mediated-production-6-beta11-alpha-dihydroxy-derivatives-4-ene-3-one-steroids-001193nas a2200181 4500008004100000022001400041245010300055210006900158260011000227300001400337490000600351520042200357100001900779700002400798700002100822700003700843856013100880 2013 eng d a1759-966000aExpedient preparative isolation, quantification and characterization of limonoids from neem fruits0 aExpedient preparative isolation quantification and characterizat aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcAUG a5386-53910 v53 a

Major basic limonoids from Neem fruits such as azadirone, epoxyazadiradione and azadiradione were isolated in preparative scale using an automated and rapid medium pressure liquid chromatography (MPLC)-based protocol. They were individually quantified using HPLC. An LC-ESI-MS/MS-based rapid identification technique was developed for the high-throughput screening of these limonoids in phytochemical extracts.

1 aHaldar, Saikat1 aPhapale, Prasad, B.1 aKolet, Swati, P.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/expedient-preparative-isolation-quantification-and-characterization-limonoids-neem-fruits-001600nas a2200217 4500008004100000022001400041245009400055210006900149260007100218300001600289490000700305520078500312100001901097700001901116700002101135700002301156700001801179700002101197700003701218856012701255 2013 eng d a0022-326300aOne-pot fluorescent labeling protocol for complex hydroxylated bioactive natural products0 aOnepot fluorescent labeling protocol for complex hydroxylated bi a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcOCT a10192-102020 v783 a

Tagging of small bioactive molecules with a fluorophore is a highly sensitive method to trace their cellular activities through real-time visual information. Here we disclose a 7-nitrobenzo-2-oxa-1,3-diazole (NBD)-based, high-yielding, one-pot labeling protocol for hydroxylated molecules using Yamaguchi coupling as the key reaction. This methodology was successfully applied on several sensitive and complex hydroxylated bioactive compounds including 7-deacetylazadiradione, simvastatin, camptothecin, andrographolide, cinchonine, beta-dihydroartemisinin, and azadirachtin A. Further, utility of this protocol was illustrated on the cytotoxic activity of azadiradione derivatives against several cancer cell lines through cell imaging of two qualified fluorescent probes.

1 aHaldar, Saikat1 aKumar, Santosh1 aKolet, Swati, P.1 aPatil, Harshal, S.1 aKumar, Dhiraj1 aKundu, Gopal, C.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/one-pot-fluorescent-labeling-protocol-complex-hydroxylated-bioactive-natural-products-001910nas a2200265 4500008004100000022001400041245012700055210006900182260009000251300000900341490000600350520086400356100002401220700001701244700002901261700003901290700002401329700002301353700002501376700002401401700003701425700002601462700002501488856013101513 2013 eng d a2045-232200aProteome wide reduction in AGE modification in streptozotocin induced diabetic mice by hydralazine mediated transglycation0 aProteome wide reduction in AGE modification in streptozotocin in aMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDbNATURE PUBLISHING GROUPcOCT a29410 v33 a

The non-enzymatic reaction between glucose and protein can be chemically reversed by transglycation. Here we report the transglycation activity of hydralazine using a newly developed MALDI-TOF-MS based assay. Hydralazine mediated transglycation of HbA1c, plasma proteins and kidney proteins was demonstrated in streptozotocin (STZ) induced diabetic mice, as evidenced by decrease in protein glycation, as well as presence of hydralazine-glucose conjugate in urine of diabetic mice treated with hydralazine. Hydralazine down regulated the expression of Receptor for Advanced Glycation End products (RAGE), NADPH oxidase (NOX), and super oxide dismutase (SOD). These findings will provide a new dimension for developing intervention strategies for the treatment of glycation associated diseases such as diabetes complications, atherosclerosis, and aging.

1 aKesavan, Suresh, K.1 aBhat, Shweta1 aGolegaonkar, Sandeep, B.1 aJagadeeshaprasad, Mashanipalya, G.1 aDeshmukh, Arati, B.1 aPatil, Harshal, S.1 aBhosale, Santosh, D.1 aShaikh, Mahemud, L.1 aThulasiram, Hirekodathakallu, V.1 aBoppana, Ramanamurthy1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/proteome-wide-reduction-age-modification-streptozotocin-induced-diabetic-mice-hydralazine-001595nas a2200193 4500008004100000245013500041210006900176260000800245300001400253490000700267520084500274100001901119700002201138700002001160700003101180700003701211700002401248856012901272 2013 eng d00aSelf-assembly to function: design, synthesis and broad spectrum antimicrobial properties of short hybrid E-vinylogous lipopeptides0 aSelfassembly to function design synthesis and broad spectrum ant cNOV a8468-84740 v563 aNonribosomal E-vinylogous gamma-amino acids are widely present in many peptide natural products and have been exploited as inhibitors for serine and cysteine proteases. Here, we are reporting the broad spectrum antimicrobial properties and self-assembled nanostructures of various hybrid lipopeptides composed of 1:1 alternating alpha-and E-vinylogous residues. Analysis of the results revealed that self-assembled nanostructures also play a significant role in the antimicrobial and hemolytic activities. In contrast to the alpha-peptide counterparts, vinylogous hybrid peptides displayed excellent antimicrobial properties against various bacterial and fungal strains. Peptides that adopted nanofiber structures displayed less hemolytic activity, while peptides that adopted nanoneedle structures displayed the highest hemolytic activity.1 aShankar, Shiva1 aBenke, Sushil, N.1 aNagendra, Narem1 aSrivastava, Prabhakar, Lal1 aThulasiram, Hirekodathakallu, V.1 aGopi, Hosahudya, N. uhttps://library.ncl.res.in/content/self-assembly-function-design-synthesis-and-broad-spectrum-antimicrobial-properties-short01282nas a2200205 4500008004100000022001400041245008100055210006900136260011000205300001600315490000600331520047900337100001900816700002100835700002700856700002100883700002400904700003700928856011100965 2014 eng d a2046-206900aBiocatalyst mediated functionalization of salannin, an insecticidal limonoid0 aBiocatalyst mediated functionalization of salannin an insecticid aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJUN a27661-276640 v43 a

Transformation of salannin, an insecticidal C-seco limonoid was investigated using a fungal system, Cunninghamella echinulata. Salannin was efficiently converted into two metabolites, where the C-17 furan moiety was transformed into gamma-hydroxybutenolide (salanninolide) and N-(2-hydroxyethyl)-alpha,beta-unsaturated-gamma-lactam (salanninactam) analogues. Present studies have indicated salanninolide to be a metabolite in the C-seco limonoid biosynthetic pathway.

1 aHaldar, Saikat1 aKolet, Swati, P.1 aDandekar, Devdutta, S.1 aKale, Balaji, S.1 aGonnade, Rajesh, G.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/biocatalyst-mediated-functionalization-salannin-insecticidal-limonoid-001309nas a2200181 4500008004100000022001400041245010500055210006900160260011000229300001400339490000700353520052600360100002500886700003100911700002100942700003700963856012701000 2014 eng d a1477-052000aBiocatalyst mediated regio- and stereo-selective hydroxylation and epoxidation of (Z)-alpha-santalol0 aBiocatalyst mediated regio and stereoselective hydroxylation and aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcJAN a1048-10510 v123 a

Biocatalyst mediated regio- and stereo-selective hydroxylation and epoxidation on (Z)-alpha-santalol were achieved for the first time, using a fungal strain Mucor piriformis. Four novel metabolites were characterized as 10,11-cis-beta-epoxy-alpha-santalol, 5 alpha-hydroxy-(Z)-alpha-santalol, 10,11-dihydroxy-alpha-santalol and 5 alpha-hydroxy-10,11-cis-beta-epoxy-alpha-santalol. Using Amano PS lipase from Burkholderia cepacia, alpha- and beta-isomers of 10,11-cis-epoxy-alpha-santalol were resolved efficiently.

1 aDaramwar, Pankaj, P.1 aSrivastava, Prabhakar, Lal1 aKolet, Swati, P.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/biocatalyst-mediated-regio-and-stereo-selective-hydroxylation-and-epoxidation-z-alpha-002288nas a2200265 4500008004100000022001400041245012100055210006900176260007300245300000900318490000900327520130900336653003701645653000901682653001301691653002601704653001301730653001801743100001901761700002201780700002901802700002701831700003701858856012701895 2014 eng d a0021-967300aExpedient preparative isolation and tandem mass spectrometric characterization of C-seco triterpenoids from neem oil0 aExpedient preparative isolation and tandem mass spectrometric ch aPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDSbELSEVIER SCIENCE BVcOCT a1-140 v13663 a

C-seco triterpenoids are widely bioactive class of natural products with high structural complexity and diversity. The preparative isolation of these molecules with high purity is greatly desirable, although restricted due to the complexity of natural extracts. In this article we have demonstrated a Medium Pressure Liquid Chromatography (MPLC) based protocol for the isolation of eight major C-seco triterpenoids of salannin skeleton from Neem (Azadirachta indica) oil. Successive application of normal phase pre-packed silica-gel columns for the fractionation followed by reverse phase in automated MPLC system expedited the process and furnished highly pure metabolites. Furthermore, eight isolated triterpenoids along with five semi-synthesized derivatives were characterized using ultra performance liquid chromatography-electrospray ionization-quadrupole/orbitrap-MS/MS spectrometry as a rapid and sensitive identification technique. The structure-fragment relationships were established on the basis of plausible mechanistic pathway for the generation of daughter ions. The MS/MS spectral information of the triterpenoids was further utilized for the identification of studied molecules in the complex extract of stem and bark tissues from Neem. (C) 2014 Elsevier B.V. All rights reserved.

10aESI(+)-quadrupole/orbitrap-MS/MS10aMPLC10aNeem oil10aPreparative isolation10aSalannin10aTriterpenoids1 aHaldar, Saikat1 aMulani, Fayaj, A.1 aAarthy, Thiagarayaselvam1 aDandekar, Devdutta, S.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/expedient-preparative-isolation-and-tandem-mass-spectrometric-characterization-c-seco-001490nas a2200253 4500008004100000022001400041245008400055210006900139260010600208300001400314490000700328520053700335653002800872653002100900653002200921653002300943653002000966100002100986700002301007700002901030700002801059700003701087856011201124 2014 eng d a0040-403900aFungi mediated production and practical purification of (R)-(-)-3-quinuclidinol0 aFungi mediated production and practical purification of R3quinuc aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcOCT a5911-59140 v553 a

A fungal system belonging to Mucoraceae family (Mucor piriformis) was explored for the asymmetric reduction of a prochiral ketone, 3-quinuclidinone (I) in an efficient manner to produce an important pharmaceutical precursor (R)-(-)-3-quinuclidinol (II) with similar to 96% enantiomeric excess. The efficiency of the process was improved by developing a cation exchange resin (Amberlite IR-120) which assisted the purification of water soluble metabolite II from fermentation media. (C) 2014 Elsevier Ltd. All rights reserved.

10a(R)-(-)-3-Quinuclidinol10aAmberlite IR-12010aBiotransformation10aIon exchange resin10aMucor pinformis1 aKolet, Swati, P.1 aJadhav, Dipesh, D.1 aPriyadarshini, Balaraman1 aSwarge, Bhagyashree, N.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/fungi-mediated-production-and-practical-purification-r-3-quinuclidinol-002477nas a2200205 4500008004100000022001400041245010900055210006900164260009100233300001200324490000600336520165100342100002001993700002902013700001802042700003702060700002502097700002002122856012902142 2014 eng d a1932-620300aInsecticidal potential of defense metabolites from ocimum kilimandscharicum against helicoverpa armigera0 aInsecticidal potential of defense metabolites from ocimum kilima a1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USAbPUBLIC LIBRARY SCIENCEcAUG ae1043770 v93 a

Genus Ocimum contains a reservoir of diverse secondary metabolites, which are known for their defense and medicinal value. However, the defense-related metabolites from this genus have not been studied in depth. To gain deeper insight into inducible defense metabolites, we examined the overall biochemical and metabolic changes in Ocimum kilimandscharicum that occurred in response to the feeding of Helicoverpa armigera larvae. Metabolic analysis revealed that the primary and secondary metabolism of local and systemic tissues in O. kilimandscharicum was severely affected following larval infestation. Moreover, levels of specific secondary metabolites like camphor, limonene and beta-caryophyllene (known to be involved in defense) significantly increased in leaves upon insect attack. Choice assays conducted by exposing H. armigera larvae on O. kilimandscharicum and tomato leaves, demonstrated that O. kilimandscharicum significantly deters larval feeding. Further, when larvae were fed on O. kilimandscharicum leaves, average body weight decreased and mortality the larvae increased. Larvae fed on artificial diet supplemented with O. kilimandscharicum leaf extract, camphor, limonene and beta-caryophyllene showed growth retardation, increased mortality rates and pupal deformities. Digestive enzymes of H. armigera - namely, amylase, protease and lipase- showed variable patterns after feeding on O. kilimandscharicum, which implies striving of the larvae to attain required nutrition for growth, development and metamorphosis. Evidently, selected metabolites from O. kilimandscharicum possess significant insecticidal activity.

1 aSingh, Priyanka1 aJayaramaiah, Ramesha, H.1 aSarate, Priya1 aThulasiram, Hirekodathakallu, V.1 aKulkarni, Mahesh, J.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/insecticidal-potential-defense-metabolites-ocimum-kilimandscharicum-against-helicoverpa-001705nas a2200241 4500008004100000022001400041245008800055210006900143260010600212300001400318490000700332520081800339653001101157653001901168653002301187653001101210653002201221100001901243700002101262700002301283700003701306856012001343 2014 eng d a0040-403900aLipase mediated separation of triterpene structural isomers, alpha- and beta-amyrin0 aLipase mediated separation of triterpene structural isomers alph aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcMAY a3122-31250 v553 a

Pentacyclic triterpenoids alpha- and beta-amyrin possess a wide range of biological and pharmacological activities. High structural similarity between these two structural isomers makes their chromatographic separation an ineffective and tedious choice. In this study, Candida rugosa lipase catalyzed separation protocol for the isolation of individual isomers has been developed. In the presence of vinyl acetate as the acyl donor, Candida rugosa lipase carried out acetylation of beta-amyrin more efficiently as compared to alpha-amyrin leading to a kinetic separation. The conditions of transesterification reaction were optimized systematically, which was utilized to separate alpha- and beta-amyrin from a mixture obtained from the latex of Plumeria obtusa. (C) 2014 Elsevier Ltd. All rights reserved.

10aAmyrin10aCandida rugosa10aKinetic separation10aLipase10aStructural isomer1 aHaldar, Saikat1 aKale, Balaji, S.1 aJadhav, Dipesh, D.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/lipase-mediated-separation-triterpene-structural-isomers-alpha-and-beta-amyrin-002601nas a2200205 4500008004100000022001400041245014300055210006900198260008000267300001400347490000800361520175500369100001902124700002302143700002302166700002002189700003702209700002402246856012502270 2014 eng d a0032-088900aMicroRNA156: a potential graft-transmissible microrna that modulates plant architecture and tuberization in solanum tuberosum ssp andigena0 aMicroRNA156 a potential grafttransmissible microrna that modulat a15501 MONONA DRIVE, ROCKVILLE, MD 20855 USAbAMER SOC PLANT BIOLOGISTScFEB a1011-10270 v1643 a

MicroRNA156 (miR156) functions in maintaining the juvenile phase in plants. However, the mobility of this microRNA has not been demonstrated. So far, only three microRNAs, miR399, miR395, and miR172, have been shown to be mobile. We demonstrate here that miR156 is a potential graft-transmissible signal that affects plant architecture and tuberization in potato (Solanum tuberosum). Under tuber-noninductive (long-day) conditions, miR156 shows higher abundance in leaves and stems, whereas an increase in abundance of miR156 has been observed in stolons under tuber-inductive (short-day) conditions, indicative of a photoperiodic control. Detection of miR156 in phloem cells of wild-type plants and mobility assays in heterografts suggest that miR156 is a graft-transmissible signal. This movement was correlated with changes in leaf morphology and longer trichomes in leaves. Overexpression of miR156 in potato caused a drastic phenotype resulting in altered plant architecture and reduced tuber yield. miR156 overexpression plants also exhibited altered levels of cytokinin and strigolactone along with increased levels of LONELY GUY1 and StCyclin D3.1 transcripts as compared with wild-type plants. RNA ligase-mediated rapid amplification of complementary DNA ends analysis validated SQUAMOSA PROMOTER BINDING-LIKE3 (StSPL3), StSPL6, StSPL9, StSPL13, and StLIGULELESS1 as targets of miR156. Gel-shift assays indicate the regulation of miR172 by miR156 through StSPL9. miR156-resistant SPL9 overexpression lines exhibited increased miR172 levels under a short-day photoperiod, supporting miR172 regulation via the miR156-SPL9 module. Overall, our results strongly suggest that miR156 is a phloem-mobile signal regulating potato development.

1 aBhogale, Sneha1 aMahajan, Ameya, S.1 aNatarajan, Bhavani1 aRajabhoj, Mohit1 aThulasiram, Hirekodathakallu, V.1 aBanerjee, Anjan, K. uhttps://library.ncl.res.in/content/microrna156-potential-graft-transmissible-microrna-modulates-plant-architecture-and-001674nas a2200241 4500008004100000022001400041245013300055210006900188260007900257300000900336490000700345520074600352653002501098653002201123653001901145653001701164653001701181100002101198700001901219700002701238700003701265856013001302 2014 eng d a0039-128X00aMucor hiemalis mediated 14 alpha-hydroxylation on steroids: In vivo and in vitro investigations of 14 alpha-hydroxylase activity0 aMucor hiemalis mediated 14 alphahydroxylation on steroids In viv a360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USAbELSEVIER SCIENCE INCcJUL a6-120 v853 a

Transformation of testosterone and progesterone into synthetically challenging 14 alpha-hydroxy derivatives was achieved by using fungal strain Mucor hiemalis. Prolonged incubation led to the formation of corresponding 6 beta/7 alpha,14 alpha-dihydroxy metabolites. The position and stereochemistry of newly introduced hydroxyl group was determined by detailed spectroscopic analyses. The time course experiment indicated that fungal strain initiated transformation by hydroxylation at 14 alpha-position followed by at 6 beta- or 7 alpha-positions. Studies using cell-free extracts suggest that the 14 alpha-hydroxylase activity is NADPH dependent and belongs to the cytochrome P450 family. (C) 2014 Elsevier Inc. All rights reserved.

10a14 alpha-Hydroxylase10aBiotransformation10aMucor hiemalis10aProgesterone10aTestosterone1 aKolet, Swati, P.1 aHaldar, Saikat1 aNiloferjahan, Siddiqui1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/mucor-hiemalis-mediated-14-alpha-hydroxylation-steroids-vivo-and-vitro-investigations-14-002215nas a2200265 4500008004100000022001400041245011000055210006900165260010600234300001100340490000700351520121700358653001001575653002501585653002701610653002601637653002401663653001201687653002401699100002001723700002001743700003701763700002101800856012801821 2014 eng d a0031-942200aPolyketide synthesis in tobacco plants transformed with a plumbago zeylanica type III hexaketide synthase0 aPolyketide synthesis in tobacco plants transformed with a plumba aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcFEB a92-1000 v983 a

A type III polyketide synthase from Plumbago zeylanica (PzPKS) was cloned and expressed in tobacco plants to study whether the transgenic tobacco plants expressing PzPKS synthesize the pharmacologically important polyketide, plumbagin. High resolution mass spectrometry based metabolite profiling of two transgenic events and wild type tobacco plants was carried out to investigate changes in polyketides, including plumbagin. Ten polyketides, which included six pyrones and four naphthalene derivatives, were identified in PzPKS transgenic plants. While one pyrone, styry1-2-pyranone, was detected in both, wild type and transgenic tobacco plants, three pyrones were expressed only in the leaves of transgenic tobacco plants. The transgenic tobacco plants did not accumulate plumbagin, but showed accumulation of isoshinanolone in the roots, which is postulated to be the reduction product of plumbagin. In addition, leaves of transgenic tobacco plants accumulated 3-methyl-1,8-naphthalenediol, a postulated precursor of plumbagin. The results indicated the requirement of additional Plumbago-specific components in the biosynthetic pathway of this polyketide. (C) 2013 Elsevier Ltd. All rights reserved.

10aHR-MS10aMetabolite profiling10aNapthalene derivatives10aPlumbago zeylanica L.10aPolyketide synthase10aPyrones10aTobacco transgenics1 aJadhav, Supriya1 aPhapale, Prasad1 aThulasiram, Hirekodathakallu, V.1 aBhargava, Sujata uhttps://library.ncl.res.in/content/polyketide-synthesis-tobacco-plants-transformed-plumbago-zeylanica-type-iii-hexaketide-001477nas a2200205 4500008004100000022001400041245011000055210006900165260011000234300001600344490000700360520061100367100003200978700002701010700003401037700001501071700003701086700002501123856012301148 2015 eng d a1359-734500aAssessing the effect of different shapes of glyco-gold nanoparticles on bacterial adhesion and infections0 aAssessing the effect of different shapes of glycogold nanopartic aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcAUG a15669-156720 v513 a

Achieving selective and sensitive carbohydrate-protein interactions (CPIs) using nanotechnology is an intriguing area of research. Here we demonstrate that the different shapes of gold nanoparticles (AuNPs) functionalized with monosaccharides tune the bacterial aggregations. The mechanism of aggregation revealed that the large number of surface interactions of rod shaped mannose-AuNPs with E. coli ORN 178 compared with spherical and star-shaped AuNPs exhibited higher avidity and sensitivity. Moreover, such sensitive binding can be used for effective inhibition of bacterial infection of cells.

1 aChaudhary, Preeti, Madhukar1 aSangabathuni, Sivakoti1 aMurthy, Raghavendra, Vasudeva1 aPaul, Ajay1 aThulasiram, Hirekodathakallu, V.1 aKikkeri, Raghavendra uhttps://library.ncl.res.in/content/assessing-effect-different-shapes-glyco-gold-nanoparticles-bacterial-adhesion-and-002317nas a2200217 4500008004100000022001400041245014200055210006900197260009000266300002500356490000600381520140900387100002701796700003101823700001601854700002101870700002401891700001901915700003701934856012801971 2015 eng d a2045-232200aCharacterization of 10-hydroxygeraniol dehydrogenase from catharanthus roseus reveals cascaded enzymatic activity in iridoid biosynthesis0 aCharacterization of 10hydroxygeraniol dehydrogenase from cathara aMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDbNATURE PUBLISHING GROUPcFEB aArticle Number: 82580 v53 a

Catharanthus roseus [L.] is a major source of the monoterpene indole alkaloids (MIAs), which are of significant interest due to their therapeutic value. These molecules are formed through an intermediate, cis-trans-nepetalactol, a cyclized product of 10-oxogeranial. One of the key enzymes involved in the biosynthesis of MIAs is an NAD(P)(+) dependent oxidoreductase system, 10-hydroxygeraniol dehydrogenase (Cr10HGO), which catalyses the formation of 10-oxogeranial from 10-hydroxygeraniol via 10-oxogeraniol or 10-hydroxygeranial. This work describes the cloning and functional characterization of Cr10HGO from C. roseus and its role in the iridoid biosynthesis. Substrate specificity studies indicated that, Cr10HGO has good activity on substrates such as 10-hydroxygeraniol, 10-oxogeraniol or 10-hydroxygeranial over monohydroxy linear terpene derivatives. Further it was observed that incubation of 10-hydroxygeraniol with Cr10HGO and iridoid synthase (CrIDS) in the presence of NADP(+) yielded a major metabolite, which was characterized as (1R, 4aS, 7S, 7aR)-nepetalactol by comparing its retention time, mass fragmentation pattern, and co-injection studies with that of the synthesized compound. These results indicate that there is concerted activity of Cr10HGO with iridoid synthase in the formation of (1R, 4aS, 7S, 7aR)-nepetalactol, an important intermediate in iridoid biosynthesis.

1 aKrithika, Ramakrishnan1 aSrivastava, Prabhakar, Lal1 aRani, Bajaj1 aKolet, Swati, P.1 aChopade, Manojkumar1 aSoniya, Mantri1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/characterization-10-hydroxygeraniol-dehydrogenase-catharanthus-roseus-reveals-cascaded-102340nas a2200205 4500008004100000022001400041245010400055210006900159260009000228300002600318490000600344520149100350100003101841700002501872700002701897700002201924700001901946700003701965856013202002 2015 eng d a2045-232200aFunctional characterization of novel sesquiterpene synthases from Indian sandalwood, santalum album0 aFunctional characterization of novel sesquiterpene synthases fro aMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDbNATURE PUBLISHING GROUPcMAY aArticle Number: 100950 v53 a

Indian Sandalwood, Santalum album L. is highly valued for its fragrant heartwood oil and is dominated by a blend of sesquiterpenes. Sesquiterpenes are formed through cyclization of farnesyl diphosphate (FPP), catalyzed by metal dependent terpene cyclases. This report describes the cloning and functional characterization of five genes, which encode two sesquisabinene synthases (SaSQS1, SaSQS2), bisabolene synthase (SaBS), santalene synthase (SaSS) and farnesyl diphosphate synthase (SaFDS) using the transcriptome sequencing of S. album. Using Illumina next generation sequencing, 33.32 million high quality raw reads were generated, which were assembled into 84,094 unigenes with an average length of 494.17 bp. Based on the transcriptome sequencing, five sesquiterpene synthases SaFDS, SaSQS1, SaSQS2, SaBS and SaSS involved in the biosynthesis of FPP, sesquisabinene, beta-bisabolene and santalenes, respectively, were cloned and functionally characterized. Novel sesquiterpene synthases (SaSQS1 and SaSQS2) were characterized as isoforms of sesquisabinene synthase with varying kinetic parameters and expression levels. Furthermore, the feasibility of microbial production of sesquisabinene from both the unigenes, SaSQS1 and SaSQS2 in non-optimized bacterial cell for the preparative scale production of sesquisabinene has been demonstrated. These results may pave the way for in vivo production of sandalwood sesquiterpenes in genetically tractable heterologous systems.

1 aSrivastava, Prabhakar, Lal1 aDaramwar, Pankaj, P.1 aKrithika, Ramakrishnan1 aPandreka, Avinash1 aShankar, Shiva1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/functional-characterization-novel-sesquiterpene-synthases-indian-sandalwood-santalum-album-101713nas a2200205 4500008004100000022001400041245006000055210006000115260011000175300001600285490000600301520095000307100002401257700002901281700002301310700002101333700003701354700002501391856009101416 2015 eng d a2046-206900aInvestigation of antiglycation activity of isoprenaline0 aInvestigation of antiglycation activity of isoprenaline aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAR a25051-250580 v53 a

Advanced glycation end products (AGEs) are implicated in pathogenesis of diabetes and its complications. In this study, we report the ability of isoprenaline to inhibit the AGE modification of protein by fluorescence spectroscopy and western blotting. Isoprenaline was more effective in inhibiting AGE modification than aminoguanidine, a well known glycation inhibitor. Further, we show that isoprenaline inhibits at Amadori product formation during glycation reaction by various techniques such as MALDI-TOF-MS, LC-MS/MS, and fructosamine assay. Mass spectrometric analysis of the glycation reaction mixture incubated with isoprenaline suggested that it forms adducts with glucose and thus inhibits glycation. The finding of the additional property of isoprenaline of inhibiting glycation suggests that it is a potential candidate for drug repositioning for the treatment of diabetes and its complications, as it is an FDA approved drug.

1 aKolekar, Yogesh, M.1 aVannuruswamy, Garikapati1 aBansode, Sneha, B.1 aSanthakumari, B.1 aThulasiram, Hirekodathakallu, V.1 aKulkarni, Mahesh, J. uhttps://library.ncl.res.in/content/investigation-antiglycation-activity-isoprenaline-002312nas a2200253 4500008004100000022001400041245010500055210006900160260007400229300001200303490000800315520137900323653003001702653001501732653002201747653002301769653001701792100001601809700001701825700003201842700003701874700002701911856012001938 2015 eng d a0167-685700aOverexpression of squalene synthase in withania somnifera leads to enhanced withanolide biosynthesis0 aOverexpression of squalene synthase in withania somnifera leads  aVAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDSbSPRINGERcAUG a409-4200 v1223 a

Genetic engineering of secondary metabolic pathways is an emerging area of research for production and improvement of natural products in plant biotechnology. Here, we describe a systematic approach to manipulate a key regulatory step of isoprenoid biosynthetic pathway in Withania somnifera to study its effect on withanolide production. We generated T-0 W. somnifera plants overexpressing squalene synthase (WsSQS) by Agrobacterium tumefaciens mediated transformation, which were analyzed by Gus biochemical assay and PCR of hygromycin phosphotransferase (hptII) and WsSQS. qRT-PCR analyses of various transformed tissues indicated 2-5 fold increase in WsSQS transcripts in both T-0 and T-1 generations. The tissue specific protein expression studies revealed 2-3 fold increase in WsSQS, which was further confirmed by enzyme activity. These observations were corroborated with the 1.5-2 fold increase in total withanolide content of the transformed tissues. However, in leaf tissue, the levels of Withaferin A and Withanolide A increased significantly up to 4-4.5 fold. These findings demonstrate genetic engineering of isoprenoid pathway in W. somnifera resulting in enhanced production of withanolides, and also provide insights into such metabolic pathways for their manipulation to improve the pharmacological content of different medicinally important plants.

10aAgrobacterium tumefaciens10aSolanaceae10aSqualene synthase10aWithania somnifera10aWithanolides1 aPatel, Neha1 aPatel, Parth1 aKendurkar, Shuchishweta, V.1 aThulasiram, Hirekodathakallu, V.1 aKhan, Bashir, Mohammad uhttps://library.ncl.res.in/content/overexpression-squalene-synthase-withania-somnifera-leads-enhanced-withanolide-001417nas a2200181 4500008004100000022001400041245013900055210006900194260011000263300001600373490000600389520061400395100002301009700002001032700003701052700002301089856012301112 2015 eng d a2046-206900aRecyclable ionic liquid iodinating reagent for solvent free, regioselective iodination of activated aromatic and heteroaromatic amines0 aRecyclable ionic liquid iodinating reagent for solvent free regi aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcOCT a88311-883150 v53 a

This article describes a simple, efficient method for iodination of activated aromatic and heteroaromatic amines using recyclable 1-butyl-3-methylpyridinium dichloroiodate (BMPDCI) as an ionic liquid iodinating reagent, in the absence of any solvent. The main advantages are a simple efficient procedure, good yields and no need for any base/toxic heavy metals, or oxidizing agents. The ionic liquid was recovered and recycled in five subsequent reactions, without much loss of activity. This method was applied for the synthesis of the antiprotozoal drug iodoquinol and the antifungal drug clioquinol.

1 aDeshmukh, Amarsinh1 aGore, Babasaheb1 aThulasiram, Hirekodathakallu, V.1 aSwamy, Vincent, P. uhttps://library.ncl.res.in/content/recyclable-ionic-liquid-iodinating-reagent-solvent-free-regioselective-iodination-002869nas a2200253 4500008004100000022001400041245012500055210006900180260009000249300001200339490000700351520190100358653001802259653002402277653002102301653003402322653001902356653001102375100001802386700002102404700003702425700002102462856013202483 2015 eng d a0885-576500aRole of methyl jasmonate in the expression of mycorrhizal induced resistance against Fusarium oxysporum in tomato plants0 aRole of methyl jasmonate in the expression of mycorrhizal induce a24-28 OVAL RD, LONDON NW1 7DX, ENGLANDbACADEMIC PRESS LTD- ELSEVIER SCIENCE LTDcOCT a139-1450 v923 a

Arbuscular mycorrhiza (AM) colonization led to a decrease in the severity of fusarium wilt disease caused by Fusarium oxysporum f. sp. lycopersici in tomato plants. The involvement of two plant defense hormones, namely methyl jasmonate (MeJA) and salicylic acid (SA), in the expression of mycorrhiza induced resistance (MIR) against this vascular pathogen was studied in the AM colonized and non-colonized (controls) plants. Activity of lipoxygenase (LOX), which plays a role in jasmonic acid (JA) biosynthesis, as well as levels of methyl jasmonate (MeJA) increased in AM colonized plants as compared to controls, but did not show any further changes in response to F. oxysporum inoculation. On the other hand, activity of phenylalanine ammonia lyase (PAL), which is an enzyme from salicylic acid (SA) biosynthetic pathway, as well as SA levels, increased in both controls and AM colonized plants in response to application of F. oxysporum spores. Hence the JA and not the SA signalling pathway appeared to play a role in the expression of MIR against this vascular pathogen. The resistance observed in AM colonized plants was completely compromised when plants were treated with the JA biosynthesis inhibitor salicylhydroxamic acid (SHAM). This confirmed that the AM-induced increase in JA levels was involved in the expression of resistance toward F. oxysporum. The SA response gene pathogenesis-related 1 (PR1) showed an increased expression in response to F. oxysporum infection in SHAM treated AM colonized plants as compared to plants that were not treated with this JA inhibitor. This suggested the possibility that JA inhibited SA responses, at least in the roots. AM colonization therefore appeared to prime plants for improved tolerance against the vascular pathogen F. oxysporum, which was mediated through the JA signalling pathway. (C) 2015 Elsevier Ltd. All rights reserved.

10aFusarium wilt10aGlomus fasciculatum10aMethyl jasmonate10aMycorrhiza induced resistance10aSalicylic acid10aTomato1 aNair, Aswathy1 aKolet, Swati, P.1 aThulasiram, Hirekodathakallu, V.1 aBhargava, Sujata uhttps://library.ncl.res.in/content/role-methyl-jasmonate-expression-mycorrhizal-induced-resistance-against-fusarium-oxysporum-001137nas a2200205 4500008004100000022001400041245009200055210006900147260011000216300001400326490000700340520032800347100001800675700001500693700002000708700002200728700003700750700002500787856011900812 2015 eng d a1359-734500aSupramolecular scaffolds on glass slides as sugar based rewritable sensors for bacteria0 aSupramolecular scaffolds on glass slides as sugar based rewritab aTHOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLANDbROYAL SOC CHEMISTRYcMAR a6346-63490 v513 a

We describe here the sugar functionalized beta-cyclodextrin-ferrocene glass slides as fully reversible bacterial biosensors under the influence of external adamantane carboxylic acid. The prototype D-mannose - E. coli ORN 178 and L-fucose - P. aeruginosa interactions serve as a model to illustrate the new approach.

1 aGade, Madhuri1 aPaul, Ajay1 aAlex, Catherine1 aChoudhury, Devika1 aThulasiram, Hirekodathakallu, V.1 aKikkeri, Raghavendra uhttps://library.ncl.res.in/content/supramolecular-scaffolds-glass-slides-sugar-based-rewritable-sensors-bacteria-003334nas a2200277 4500008004100000022001400041245014500055210006900200260008100269300002400350490000700374520225400381653002302635653002702658653001802685653001802703100002202721700002702743700001902770700002202789700002702811700002202838700002902860700003702889856013002926 2015 eng d a1471-222900aTriterpenoid profiling and functional characterization of the initial genes involved in isoprenoid biosynthesis in neem (Azadirachta indica)0 aTriterpenoid profiling and functional characterization of the in a236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLANDbBIOMED CENTRAL LTDcSEP aArticle Number: 2140 v153 a

Background: Neem tree (Azadirachta indica) is one of the richest sources of skeletally diverse triterpenoids and they are well-known for their broad-spectrum pharmacological and insecticidal properties. However, the abundance of Neem triterpenoids varies among the tissues. Here, we delineate quantitative profiling of fifteen major triterpenoids across various tissues including developmental stages of kernel and pericarp, flower, leaf, stem and bark using UPLC-ESI (+)-HRMS based profiling. Transcriptome analysis was used to identify the initial genes involved in isoprenoid biosynthesis. Based on transcriptome analysis, two short-chain prenyltransferases and squalene synthase (AiSQS) were cloned and functionally characterized. Results: Quantitative profiling revealed differential abundance of both total and individual triterpenoid content across various tissues. RNA from tissues with high triterpenoid content (fruit, flower and leaf) were pooled to generate 79.08 million paired-end reads using Illumina GA.. platform. 41,140 transcripts were generated by d e novo assembly. Transcriptome annotation led to the identification of the putative genes involved in isoprenoid biosynthesis. Two short-chain prenyltransferases, geranyl diphosphate synthase (AiGDS) and farnesyl diphosphate synthase (AiFDS) and squalene synthase (AiSQS) were cloned and functionally characterized using transcriptome data. RT-PCR studies indicated five-fold and ten-fold higher relative expression level of AiSQS in fruits as compared to leaves and flowers, respectively. Conclusions: Triterpenoid profiling indicated that there is tissue specific variation in their abundance. The mature seed kernel and initial stages of pericarp were found to contain the highest amount of limonoids. Furthermore, a wide diversity of triterpenoids, especially C-seco triterpenoids were observed in kernel as compared to the other tissues. Pericarp, flower and leaf contained mainly ring-intact triterpenoids. The initial genes such as AiGDS, AiFDS and AiSQS involved in the isoprenoids biosynthesis have been functionally characterized. The expression levels of AiFDS and AiSQS were found to be in correlation with the total triterpenoid content in individual tissues.

10aAzadirachta indica10aQuantitative profiling10aTranscriptome10aTriterpenoids1 aPandreka, Avinash1 aDandekar, Devdutta, S.1 aHaldar, Saikat1 aUttara, Vairagkar1 aVijayshree, Shinde, G.1 aMulani, Fayaj, A.1 aAarthy, Thiagarayaselvam1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/triterpenoid-profiling-and-functional-characterization-initial-genes-involved-isoprenoid-101423nas a2200181 4500008004100000022001400041245010600055210006900161260007100230300001400301490000700315520069000322100001901012700002201031700002901053700003701082856012201119 2015 eng d a0022-326300aWhole-cell mediated 11 beta-hydroxylation on the basic limonoid skeleton by cunninghamella echinulata0 aWholecell mediated 11 betahydroxylation on the basic limonoid sk a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcJUN a6490-64950 v803 a

Regio- and stereoselective 11 beta-hydroxylation was achieved on the basic limonoid skeleton through microbial transformation. Whole cells of Cunninghamella echinulata efficiently converted basic limonoids such as epoxyazadiradione, azadiradione, and gedunin to their 11 beta-hydroxy analogues as the sole metabolite. Fermentation conditions affecting the efficiency (96%) of biotransformation including substrate concentration, incubation period, pH, and temperature were optimized. The position and stereochemistry of hydroxyl functionality on the isolated metabolites were established through extensive spectroscopic and spectrometric studies (1D, 2D NMR, ESI-MS, and MS/MS).

1 aHaldar, Saikat1 aMulani, Fayaj, A.1 aAarthy, Thiagarayaselvam1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/whole-cell-mediated-11-beta-hydroxylation-basic-limonoid-skeleton-cunninghamella-002044nas a2200265 4500008004100000022001400041245011200055210006900167260010600236300001400342490000700356520101800363653003301381653002101414653003101435653002101466100002301487700002201510700001901532700001801551700002201569700003701591700001801628856013201646 2016 eng d a0960-894X00aAzadirachta indica triterpenoids promote osteoblast differentiation and mineralization in vitro and in vivo0 aAzadirachta indica triterpenoids promote osteoblast differentiat aTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLANDbPERGAMON-ELSEVIER SCIENCE LTDcAUG a3719-37240 v263 a

Terpenoids were isolated using chromatographic purification through solvent purification technique and identified as Azadirone (1), Epoxyazadiradione (2) Azadiradione (3) Gedunin (4) Nimbin (5) Salannin (6) Azadirachtin A (7) and Azadirachtin B (8) from Azadirachta indica. Out of eight compounds, only three compounds had osteogenic activity and enhanced osteoblast proliferation, differentiation and mineralization in osteoblast cells. Active compounds stimulated osteogenic genes ALP, RunX-2 and OCN expressions in vitro, but Azadirachtin A had a maximum ability to stimulate osteoblast differentiation and mineralization compared to other two active compounds. For in vivo study, Azadirachtin A injected subcutaneously in pups, which enhanced osteogenic gene expressions and promoted bone formation rate significantly. Here, we conclude that active compounds of Azadirachta indica have osteogenic activity and Azadirachtin A has a beneficial effects on bone. (C) 2016 Elsevier Ltd. All rights reserved.

10aALP and mineralization assay10aBalb/c mice pups10aCalvarial osteoblast cells10aGene expressions1 aKushwaha, Priyanka1 aKhedgikar, Vikram1 aHaldar, Saikat1 aGautam, Jyoti1 aMulani, Fayaj, A.1 aThulasiram, Hirekodathakallu, V.1 aTrivedi, Ritu uhttps://library.ncl.res.in/content/azadirachta-indica-triterpenoids-promote-osteoblast-differentiation-and-mineralization-vitro00687nas a2200205 4500008004100000245007900041210006900120260000800189300001400197490000700211100001700218700001800235700001500253700001400268700003700282700001900319700002000338700001600358856010700374 2016 eng d00aAzadirachtin a interacts with er alpha domain and regulates bone formation0 aAzadirachtin a interacts with er alpha domain and regulates bone cNOV aS778-S7780 v271 aKushwaha, P.1 aKhedgikar, V.1 aGautam, J.1 aKumar, A.1 aThulasiram, Hirekodathakallu, V.1 aMishra, P., R.1 aTrivedi, P., K.1 aTrivedi, R. uhttps://library.ncl.res.in/content/azadirachtin-interacts-er-alpha-domain-and-regulates-bone-formation02690nas a2200253 4500008004100000245013700041210006900178260000800247300001400255490000900269520176500278100001602043700002902059700002502088700002402113700002202137700002202159700002602181700002402207700002202231700003702253700002002290856012602310 2016 eng d00aComparative functional characterization of eugenol synthase from four different ocimum species: implications on eugenol accumulation0 aComparative functional characterization of eugenol synthase from cNOV a1539-15470 v18643 a

Isoprenoids and phenylpropanoids are the major secondary metabolite constituents in Ocimum genus. Though enzymes from phenylpropanoid pathway have been characterized from few plants, limited information exists on how they modulate levels of secondary metabolites. Here, we performed phenylpropanoid profiling in different tissues from five Ocimum species, which revealed significant variations in secondary metabolites including eugenol, eugenol methyl ether, estragole and methyl cinnamate levels. Expression analysis of eugenol synthase (EGS) gene showed higher transcript levels especially in young leaves and inflorescence; and were positively correlated with eugenol contents. Additionally, transcript levels of coniferyl alcohol acyl transferase, a key enzyme diverting pool of substrate to phenylpropanoids, were in accordance with their abundance in respective species. In particular, eugenol methyl transferase expression positively correlated with higher levels of eugenol methyl ether in Ocimum tenuiflorum. Further, EGSs were functionally characterized from four Ocimum species varying in their eugenol contents. Kinetic and expression analyses indicated, higher enzyme turnover and transcripts levels, in species accumulating more eugenol. Moreover, biochemical and bioinformatics studies demonstrated that coniferyl acetate was the preferred substrate over coumaryl acetate when used, individually or together, in the enzyme assay. Overall, this study revealed the preliminary evidence for varied accumulation of eugenol and its abundance over chavicol in these Ocimum species. Current findings could potentially provide novel insights for metabolic modulations in medicinal and aromatic plants. (C) 2016 Elsevier B.V. All rights reserved.

1 aAnand, Atul1 aJayaramaiah, Ramesha, H.1 aBeedkar, Supriya, D.1 aSingh, Priyanka, A.1 aJoshi, Rakesh, S.1 aMulani, Fayaj, A.1 aDholakia, Bhushan, B.1 aPunekar, Sachin, A.1 aGade, Wasudeo, N.1 aThulasiram, Hirekodathakallu, V.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/comparative-functional-characterization-eugenol-synthase-four-different-ocimum-species02545nas a2200301 4500008004100000022001400041245015600055210006900211260009500280300001200375490000800387520137900395653002301774653003301797653001101830653002101841653002501862100002901887700001601916700002501932700002601957700002401983700002502007700002202032700003702054700002002091856013202111 2016 eng d a0006-291X00aFunctional characterization and transient expression manipulation of a new sesquiterpene synthase involved in beta-caryophyllene accumulation in Ocimum0 aFunctional characterization and transient expression manipulatio a525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USAbACADEMIC PRESS INC ELSEVIER SCIENCEcAPR a265-2710 v4733 a

The genus Ocimum has a unique blend of diverse secondary metabolites, with major proportion of terpenoids including mono- and sesquiterpenes. Although, beta-Caryophyllene, bicyclic sesquiterpene, is one of the major terpene found in Ocimum species and known to possess several biological activities, not much is known about its biosynthesis in Ocimum. Here, we describe isolation and characterization of beta-caryophyllene synthase gene from Ocimum kilimandscharicum Gurke (OkBCS- GenBank accession no. KP226502). The open reading frame of 1629 bp encoded a protein of 542 amino acids with molecular mass of 63.6 kDa and pl value of 5.66. The deduced amino acid sequence revealed 50-70% similarity with known sesquiterpene synthases from angiosperms. Recombinant OkBCS converted farnesyl diphosphate to beta-caryophyllene as a major product (94%) and 6% alpha-humulene. Expression variation of OkBCS well corroborated with beta-caryophyllene levels in different tissues from five Ocimum species. OkBCS transcript revealed higher expression in leaves and flowers. Further, agro-infiltration based transient expression manipulation with OkBCS over-expression and silencing confirmed its role in beta-caryophyllene biosynthesis. These findings may potentially be further utilized to improve plant defense against insect pests. (C) 2016 Elsevier Inc. All rights reserved.

10abeta-Caryophyllene10aNatural product biosynthesis10aOcimum10aTerpene synthase10aTransient expression1 aJayaramaiah, Ramesha, H.1 aAnand, Atul1 aBeedkar, Supriya, D.1 aDholakia, Shushan, B.1 aPunekar, Sachin, A.1 aKalunke, Raviraj, M.1 aGade, Wasudeo, N.1 aThulasiram, Hirekodathakallu, V.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/functional-characterization-and-transient-expression-manipulation-new-sesquiterpene-synthase01187nas a2200169 4500008004100000245010300041210006900144260000800213300001400221490000700235520054100242100002300783700002300806700002100829700003700850856013000887 2016 eng d00aFungal mediated kinetic resolution of racemic acetates to (R)-alcohols using fusarium proliferatum0 aFungal mediated kinetic resolution of racemic acetates to Ralcoh cOCT a4563-45670 v573 a

Fungal mediated kinetic resolution of seven acyclic/aromatic acetates was achieved using Fusarium proliferatum to furnish (R)-alcohols in high enantiomeric excess (>95%). The kinetic resolution was established as one-pot two-step de-esterification/oxidation biocatalytic process. Further, the preparative scale synthesis of (R)-(+)-1-phenylethanol was accomplished through de-esterification/oxidation of (+/-)-1-phenylethyl acetate using the whole cell of F. proliferatum NCIM 1105. (C) 2016 Elsevier Ltd. All rights reserved.

1 aJadhav, Dipesh, D.1 aPatil, Harshal, S.1 aChaya, Patil, S.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/fungal-mediated-kinetic-resolution-racemic-acetates-r-alcohols-using-fusarium-proliferatum02732nas a2200241 4500008004100000245010700041210006900148260000800217300001400225490000800239520187700247100001802124700001902142700002002161700001802181700002302199700003302222700002702255700002202282700003702304700002102341856012802362 2016 eng d00aNotch1-MAPK signaling axis regulates CD133+ cancer stem cell-mediated melanoma growth and angiogenesis0 aNotch1MAPK signaling axis regulates CD133 cancer stem cellmediat cDEC a2462-24740 v1363 a

Functional characterization and understanding of the intricate signaling mechanisms in stem-like cells is crucial for the development of effective therapies in melanoma. We have studied whether melanoma cells are phenotypically distinct and hierarchically organized according to their tumorigenic nature. We report that melanoma-specific CD133(+) cancer stem cells exhibit increased tumor-initiating potential, tumor-endothelial cell interaction, and lung metastasis. These cells are able to transdifferentiate into an endothelial-like phenotype when cultured under endothelial differentiation-promoting conditions. Mechanistically, Notch1 upregulates mitogen-activated protein kinase activation through CD133, which ultimately controls vascular endothelial growth factor and matrix metalloproteinase expression in CD133(+) stem cells leading to melanoma growth, angiogenesis, and lung metastasis. Blockade or genetic ablation of Notch1 and mitogen-activated protein kinase pathways abolishes melanoma cell migration and angiogenesis. Chromatin immunoprecipitation and reporter assays revealed that Notch1 intracellular domain regulates CD133 expression at the transcriptional level. Andrographolide inhibits Notch1 intracellular domain expression, Notch1 intracellular domaindependent CD133-mediated mitogen-activated protein kinase and activator protein-1 activation, and epithelial to mesenchymal-specific gene expression, ultimately attenuating melanoma growth and lung metastasis. Human malignant melanoma specimen analyses revealed a strong correlation between Notch1 intracellular domain, CD133, and p-p38 mitogen-activated protein kinase expression and malignant melanoma progression. Thus, targeting Notch1 and its regulated signaling network may have potential therapeutic implications for the management of cancer stem cell-mediated melanoma progression.

1 aKumar, Dhiraj1 aKumar, Santosh1 aGorain, Mahadeo1 aTomar, Deepti1 aPatil, Harshal, S.1 aRadharani, Nalukurthi, N. V.1 aKumar, Totakura, V. S.1 aPatil, Tushar, V.1 aThulasiram, Hirekodathakallu, V.1 aKundu, Gopal, C. uhttps://library.ncl.res.in/content/notch1-mapk-signaling-axis-regulates-cd133-cancer-stem-cell-mediated-melanoma-growth-and02556nas a2200277 4500008004100000022001400041245012900055210006900184260009000253490000600343520147700349100002001826700002901846700002401875700002901899700002301928700001601951700002601967700002401993700002202017700002602039700002502065700003702090700002002127856013102147 2016 eng d a2045-232200aPotential dual role of eugenol in inhibiting advanced glycation end products in diabetes: proteomic and mechanistic insights0 aPotential dual role of eugenol in inhibiting advanced glycation  aMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDbNATURE PUBLISHING GROUPcJAN0 v63 a

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of alpha-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting a-glucosidase and prevents AGE formation by binding to epsilon-amine group on lysine, protecting it from glycation, offering potential use in diabetic management.

1 aSingh, Priyanka1 aJayaramaiah, Ramesha, H.1 aAgawane, Sachin, B.1 aVannuruswamy, Garikapati1 aKorwar, Arvind, M.1 aAnand, Atul1 aDhaygude, Vitthal, S.1 aShaikh, Mahemud, L.1 aJoshi, Rakesh, S.1 aBoppana, Ramanamurthy1 aKulkarni, Mahesh, J.1 aThulasiram, Hirekodathakallu, V.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/potential-dual-role-eugenol-inhibiting-advanced-glycation-end-products-diabetes-proteomic-001165nas a2200169 4500008004100000245007800041210006900119260000800188300001400196490000700210520056400217100002300781700002400804700002300828700003700851856010700888 2016 eng d00aStereoselective quenching of cedryl carbocation in epicedrol biosynthesis0 aStereoselective quenching of cedryl carbocation in epicedrol bio cMAR a1161-11640 v573 a

Epicedrol synthase catalyzes the cyclization of achiral diphosphate substrate, (E,E)-farnesyldiphosphate (FPP) into epicedrol. GC-MS analysis of assay extracts obtained by incubating FPP with epicedrol synthase in 21.6 at % H2(18)O buffer showed the molecular ion of 224 for epicedrol. The labeled oxygen study presented here unambiguously demonstrates that the hydroxyl group of the epicedrol synthase enzymatic product, epicedrol, is derived from a water molecule, not from the phosphate moiety of the FPP. (C) 2016 Elsevier Ltd. All rights reserved.

1 aShinde, Sandip, S.1 aNavale, Govinda, R.1 aSaid, Madhukar, S.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/stereoselective-quenching-cedryl-carbocation-epicedrol-biosynthesis01209nas a2200241 4500008004100000022001400041245010700055210006900162260000800231300001400239490000600253520036900259653002700628653001700655653001200672653001500684653003100699100001800730700003200748700003700780700002500817856012500842 2017 eng d a2365-654900aEngineering cell surface glycans with carbohydrate enantiomers to alter bacterial binding and adhesion0 aEngineering cell surface glycans with carbohydrate enantiomers t cSEP a8865-88690 v23 a

Chirality of carbohydrate has critical functions in many biological processes. Changes in the configuration of even one sugar molecules may cause abnormal behavior or even inhibit specific processes. Herein, we have shown bioorthogonal conjugation of mannose enantiomers on HeLa cell surfaces induced a different rate of bacterial binding and cell adhesion.

10aBioorthogonal reaction10aCarbohydrate10aE. coli10aEnantiomer10aSurfaces functionalization1 aGade, Madhuri1 aChaudhary, Preeti, Madhukar1 aThulasiram, Hirekodathakallu, V.1 aKikkeri, Raghavendra uhttps://library.ncl.res.in/content/engineering-cell-surface-glycans-carbohydrate-enantiomers-alter-bacterial-binding-and01489nas a2200181 4500008004100000245013100041210006900172260000800241300001400249490000700263520078300270100002001053700001801073700002701091700003701118700002501155856012701180 2017 eng d00aExploring the influence of shapes and heterogeneity of glyco-gold nanoparticles on bacterial binding for preventing infections0 aExploring the influence of shapes and heterogeneity of glycogold cJUL a1116-11240 v123 aTo investigate the effects of the heterogeneity and shape of glyco-nanoprobes on carbohydrate-protein interactions (CPIs), alpha-d-mannose-and beta-d-galactose-linked homo-and heterogeneous glycodendrons were synthesized and immobilized on spherical and rod-shaped gold nanoparticles (AuNPs). Lectin and bacterial binding studies of these glyco-AuNPs clearly illustrate that multivalency and shape of AuNPs contribute significantly to CPIs than the heterogeneity of glycodendrons. Finally, bacterial infection of HeLa cells was effectively inhibited by the homogeneous glycodendron-conjugated rod-shaped AuNPs relative to their heterogeneous counterparts. Overall, these results provide insight into the role of AuNP shape and multivalency as potential factors to regulate CPIs.1 aToraskar, Suraj1 aGade, Madhuri1 aSangabathuni, Sivakoti1 aThulasiram, Hirekodathakallu, V.1 aKikkeri, Raghavendra uhttps://library.ncl.res.in/content/exploring-influence-shapes-and-heterogeneity-glyco-gold-nanoparticles-bacterial-binding03063nas a2200361 4500008004100000245013600041210006900177260000800246490000700254520182400261653003802085653001502123653002002138653002202158653001802180653003602198653001602234653002602250653003202276653002102308653002102329653001702350653002002367653002802387653001902415100001902434700001902453700002302472700003702495700002102532700001902553856012902572 2017 eng d00aOral feeding with polyunsaturated fatty acids fosters hematopoiesis and thrombopoiesis in healthy and bone marrow-transplanted mice0 aOral feeding with polyunsaturated fatty acids fosters hematopoie csep0 v473 a

Hematopoietic stem cells play the vital role of maintaining appropriate levels of cells in blood. Therefore, regulation of their fate is essential for their effective therapeutic use. Here we report the role of polyunsaturated fatty acids (PUFAs) in regulating hematopoiesis which has not been explored well so far. Mice were fed daily for 10 days with n-6/n-3 PUFAs, viz. linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid and docosahexanoic acid (DHA) in four separate test groups with phosphate-buffered saline fed mice as control set. The bone marrow cells of PUFA-fed mice showed a significantly higher hematopoiesis as assessed using side population, Lin-Sca-1(+)ckit+, colony-forming unit (CFU), long-term culture, CFU-spleen assay and engraftment potential as compared to the control set. Thrombopoiesis was also stimulated in PUFA-fed mice. A combination of DHA and AA was found to be more effective than when either was fed individually. Higher incorporation of PUFAs as well as products of their metabolism was observed in the bone marrow cells of PUFA-fed mice. A stimulation of the Wnt, CXCR4 and Notch1 pathways was observed in PUFA-fed mice. The clinical relevance of this study was evident when bone marrow-transplanted recipient mice, which were fed with PUFAs, showed higher engraftment of donor cells, suggesting that the bone marrow microenvironment may also be stimulated by feeding with PUFAs. These data indicate that oral administration of PUFAs in mice stimulates hematopoiesis and thrombopoiesis and could serve as a valuable supplemental therapy in situations of hematopoietic failure. (C) 2017 Elsevier Inc. All rights reserved.

10aBone Marrow Transplantation (Bmt)10aCord Blood10aDown-regulation10aEx-vivo Expansion10aHematopoiesis10aHematopoietic Stem Cells (Hscs)10aLipid rafts10aMyocardial-infarction10aPolyunsaturated Fatty Acids10aProgenitor Cells10aProstaglandin-e210aSelf-renewal10aSpleen Colonies10aStem-cell Proliferation10aThrombopoiesis1 aLimbkar, Kedar1 aDhenge, Ankita1 aJadhav, Dipesh, D.1 aThulasiram, Hirekodathakallu, V.1 aKale, Vaijayanti1 aLimaye, Lalita uhttps://library.ncl.res.in/content/oral-feeding-polyunsaturated-fatty-acids-fosters-hematopoiesis-and-thrombopoiesis-healthy01387nas a2200157 4500008004100000245008100041210006900122260000800191300001400199490000700213520081400220100002201034700003701056700002401093856011201117 2017 eng d00aPotent antimicrobial activity of lipidated short alpha,gamma-hybrid peptides0 aPotent antimicrobial activity of lipidated short alphagammahybri cOCT a1610-16150 v123 aHerein we report the potent antimicrobial activity of alpha,gamma-hybrid lipopeptides composed of 1:1 alternating - and gamma-amino acids. Along with their potent antimicrobial activity against various Gram-positive and Gram-negative bacteria, these hybrid lipopeptides were found to be less hemolytic. Studies into the mechanism of action revealed that these short cationic lipopeptides bind and disrupt the bacterial cell membrane. Time-kill kinetics analyses revealed that the potent alpha,gamma-hybrid lipopeptides completely inhibit bacterial growth in less than 20 minutes. Overall, the promising antimicrobial activity along with lower hemolytic activity displayed by these alpha,gamma-hybrid lipopeptides make them well suited for further exploration into the design of potent lipopeptide antibiotics.1 aBenke, Sushil, N.1 aThulasiram, Hirekodathakallu, V.1 aGopi, Hosahudya, N. uhttps://library.ncl.res.in/content/potent-antimicrobial-activity-lipidated-short-alphagamma-hybrid-peptides01813nas a2200265 4500008004100000022001400041245010000055210006900155260000800224300001400232490000800246520090300254653002101157653001301178653003501191653003401226653002601260100002401286700002001310700002201330700003701352700002001389700002001409856011801429 2018 eng d a1873-346800aDynamics of loops at the substrate entry channel determine the specificity of iridoid synthases0 aDynamics of loops at the substrate entry channel determine the s cAUG a2624-26350 v5923 a

Iridoid synthases belong to the family of short-chain dehydrogenase reductase involved in the biosynthesis of iridoids. Despite having high sequence and structural homology with progesterone 5 beta- reductase, these enzymes exhibit differential substrate specificities. Previously, two loops. L1 and L2 at substrate-binding pocket, were suggested to be involved in generating substrate specificity. However, the structural basis of specificity determinants was elusive. Here, combining sequence and structural analysis, site-directed mutagenesis, and molecular dynamics simulations, we have shown that iridoid synthase contains two channels for substrate entry whose geometries are altered by L1-L2 dynamics, primarily orchestrated by interactions of residues Glu161 and Gly162 of L1 and Asn358 of L2. A complex interplay of these interactions confer the substrate specificity to the enzyme.

10airidoid synthase10airidoids10aMolecular dynamics simulations10aprogesterone 5 beta-reductase10aSubstrate specificity1 aSandholu, Anand, S.1 aMohole, Madhura1 aDuax, William, L.1 aThulasiram, Hirekodathakallu, V.1 aSengupta, Durba1 aKulkarni, Kiran uhttps://library.ncl.res.in/content/dynamics-loops-substrate-entry-channel-determine-specificity-iridoid-synthases02898nas a2200313 4500008004100000022001400041245015200055210006900207260000800276300000700284490000700291520187700298653001702175653001402192653001802206653001402224653001502238653000902253100001802262700001902280700002002299700001902319700002202338700002002360700001702380700003702397700002102434856012902455 2018 eng d a1471-240700aEpoxyazadiradione suppresses breast tumor growth through mitochondrial depolarization and caspase-dependent apoptosis by targeting PI3K/Akt pathway0 aEpoxyazadiradione suppresses breast tumor growth through mitocho cJAN a520 v183 a

Background: Breast cancer is one of the most commonly diagnosed invasive cancers among women around the world. Among several subtypes, triple negative breast cancer (TNBC) is highly aggressive and chemoresistant. Treatment of TNBC patients has been challenging due to heterogeneity and devoid of well-defined molecular targets. Thus, identification of novel effective and selective agents against TNBC is essential. Methods: We used epoxyazadiradione to assess the cell viability, mitochondrial potential, ROS level, cell migration, apoptosis and protein expression in cell culture models of TNBC MDA-MB-231 and ER+MCF-7 breast cancer cells. The molecular mechanism was examined in two different type of breast cancer cells in response to epoxyazadiradione. We have also analyzed the effect of epoxyazadiradione on breast tumor growth using in vivo mice model. Results: In this study, we for the first time investigated that out of 10 major limonoids isolated from Azadirachta indica, epoxyazadiradione exhibits most potent anti-cancer activity in both TNBC and ER+breast cancer cells. Epoxyazadiradione induces apoptosis and inhibits PI3K/Akt-mediated mitochondrial potential, cell viability, migration and angiogenesis. It also inhibits the expression of pro-angiogenic and pro-metastatic genes such as Cox2, OPN, VEGF and MMP-9 in these cells. Furthermore, epoxyazadiradione attenuates PI3K/Akt- mediated AP-1 activation. Our in vivo data revealed that epoxyazadiradione suppresses breast tumor growth and angiogenesis in orthotopic NOD/SCID mice model. Conclusion: Our findings demonstrate that epoxyazadiradione inhibits PI3K/Akt-dependent mitochondrial depolarisation, induces apoptosis and attenuates cell migration, angiogenesis and breast tumor growth suggesting that this compound may act as a potent therapeutic agent for the management of breast cancer.

10aAngiogenesis10aApoptosis10aBreast cancer10aLimonoids10aMetastasis10aPI3K1 aKumar, Dhiraj1 aHaldar, Saikat1 aGorain, Mahadeo1 aKumar, Santosh1 aMulani, Fayaj, A.1 aYadav, Amit, S.1 aMiele, Lucio1 aThulasiram, Hirekodathakallu, V.1 aKundu, Gopal, C. uhttps://library.ncl.res.in/content/epoxyazadiradione-suppresses-breast-tumor-growth-through-mitochondrial-depolarization-and02348nas a2200169 4500008004100000245010600041210006900147260000800216300001600224490000700240520170100247100002301948700003701971700002402008700002102032856012502053 2018 eng d00aIon pairing in 1-butyl-3-methylpyridinium halide ionic liquids studied using NMR and DFT calculations0 aIon pairing in 1butyl3methylpyridinium halide ionic liquids stud cAPR a11470-114800 v203 aWe present the H-1, C-13 and N-15 NMR chemical shifts of bulk ionic liquids based on 1-butyl-3-methylimidazolium (the cation also known as 1-butyl-3-picolinium) halides (Cl-, Br- and I-) and tribromide (Br-3(-)) salts. A characterization in solution of the analogous ICl2- and I-3(-) salts is also reported. A series of DFT calculations has been run to predict the features of the NMR spectra of the pure ILs based on a few selected supramolecular ionic aggregates. To test the effect of temperature, and vibrational and conformational motions, only for the chloride salt, we also run first-principles molecular dynamics simulations of the ion pair in the gas phase, using the ADMP scheme (Atom Centered Density Matrix Propagation molecular dynamics model). The aim of our investigation is to test whether a simple DFT based approach of ion-pairing in ionic liquids is capable of providing reliable results and under which conditions the protocol is robust. We obtained a very good agreement between the calculated and experimental spectra for the three halides, where the bulk structure of the ILs is dominated by H-bond interactions between the X- anion (X = Cl, Br and I) and the ortho protons of the pyridinium ring (a structural arrangement not too different from the solid-state structure of pyridinium halides). In contrast, when the H-bond is weak, as in the Br-3(-) case, a number of supramolecular arrangements exist in solution and the simple DFT calculations of a few selected cases cannot exhaustively explore the complete energy landscape. Moreover, the dynamic effects due to thermal motion, evaluated by ADMP MD simulations of the chloride salt, appear to be not very significant.1 aSwamy, Vincent, P.1 aThulasiram, Hirekodathakallu, V.1 aRastrelli, Federico1 aSaielli, Giacomo uhttps://library.ncl.res.in/content/ion-pairing-1-butyl-3-methylpyridinium-halide-ionic-liquids-studied-using-nmr-and-dft01162nas a2200193 4500008004100000245007600041210006900117260000800186300001400194490000700208520049700215100002300712700001900735700001500754700002400769700003000793700003700823856010800860 2018 eng d00aLipase catalyzed synthesis of antimicrobial andrographolide derivatives0 aLipase catalyzed synthesis of antimicrobial andrographolide deri cJUN a1134-11410 v183 aIn this data article we describe screening of various lipases for the regioselective acylation of Andrographolide. Each lipase was screened with seven acyl donors. Amano lipase AK from Pseudomonas fluorescens was used for the synthesis of two new acylated andrographolide derivatives. Two new compounds, andrographolide-14-propionate and andrographolide-14-caproate were characterized by various spectral studies. These two derivatives showed more antimicrobial activity than andrographolide.1 aPatil, Harshal, S.1 aJadhav, Dipesh1 aPaul, Ajay1 aMulani, Fayaj, Alam1 aKaregaonkar, Shrikant, J.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/lipase-catalyzed-synthesis-antimicrobial-andrographolide-derivatives02679nas a2200325 4500008004100000022001400041245013000055210006900185260000900254300001400263490000700277520154600284653003601830653001301866653001101879653002701890653002201917653002201939653003301961100002301994700002402017700002202041700002002063700002902083700002502112700003702137700002802174700002402202856012702226 2018 eng d a0022-095700aMiRNA160 is associated with local defense and systemic acquired resistance against Phytophthora infestans infection in potato0 aMiRNA160 is associated with local defense and systemic acquired  cAPR  a2023-20360 v693 a

To combat pathogen infection, plants employ local defenses in infected sites and elicit systemic acquired resistance (SAR) in distant tissues. MicroRNAs have been shown to play a significant role in local defense, but their association with SAR is unknown. In addition, no such studies of the interaction between potato and Phytophthora infestans have been reported. We investigated the role of miR160 in local and SAR responses to P. infestans infection in potato. Expression analysis revealed induced levels of miR160 in both local and systemic leaves of infected wild-type plants. miR160 overexpression and knockdown plants exhibited increased susceptibility to infection, suggesting that miR160 levels equivalent to those of wild-type plants may be necessary for mounting local defense responses. Additionally, miR160 knockdown lines failed to elicit SAR, and grafting assays indicated that miR160 is required in both local and systemic leaves to trigger SAR. Consistently, SAR-associated signals and genes were dysregulated in miR160 knockdown lines. Furthermore, analysis of the expression of defense and auxin pathway genes and direct regulation of StGH3.6, a mediator of salicylic acid-auxin cross-talk, by the miR160 target StARF10 revealed the involvement of miR160 in antagonistic cross-talk between salicylic acid-mediated defense and auxin-mediated growth pathways. Overall, our study demonstrates that miR160 plays a crucial role in local defense and SAR responses during the interaction between potato and P. infestans.

10aAuxin-salicylic acid antagonism10amicroRNA10amiR16010aPhytophthora infestans10aSolanum chacoense10aSolanum tuberosum10asystemic acquired resistance1 aNatarajan, Bhavani1 aKalsi, Harpreet, S.1 aGodbole, Prajakta1 aMalankar, Nilam1 aThiagarayaselvam, Aarthy1 aSiddappa, Sundaresha1 aThulasiram, Hirekodathakallu, V.1 aChakrabarti, Swarup, K.1 aBanerjee, Anjan, K. uhttps://library.ncl.res.in/content/mirna160-associated-local-defense-and-systemic-acquired-resistance-against-phytophthora01927nas a2200289 4500008004100000022001400041245009800055210006900153260000900222300001400231490000700245520098200252653001401234653002001248653002701268653001701295653001401312653001101326653002001337100002301357700002301380700001501403700002201418700003001440700003701470856013001507 2018 eng d a0960-894X00aRegioselective and efficient enzymatic synthesis of antimicrobial andrographolide derivatives0 aRegioselective and efficient enzymatic synthesis of antimicrobia cAPR  a1132-11370 v283 a

Labdane diterpene andrographolide (1) is a major constituent of Andrographis paniculata and known to exhibit wide spectrum of biological activities. In this study, regioselective monoesters of (1) have been synthesized by using Amano lipase AK (Pseudomonas fluorescens) as a biocatalyst. Amano lipase AK was able to execute highly efficient esterification of hydroxyl group attached to C-14 carbon of (1) in presence of acyl donors. Among the various synthesized derivatives including two novel compounds such as andrographolide-14-propionate (3) and andrographolide-14-caproate (5) displayed antimicrobial activity against Staphylococcus aureus with low minimal inhibitory concentration (MIC) 4 mu g/mL and 16 mu g/mL respectively. Furthermore, they have shown low hemolysis activity at their respective MIC and increase in the permeability of the bacterial cell membrane as delineated by FITC uptake and SEM imaging studies. (C) 2018 Elsevier Ltd. All rights reserved.

10aAcylation10aAndrographolide10aAntimicrobial activity10abiocatalysis10aHemolysis10aLipase10aNatural product1 aPatil, Harshal, S.1 aJadhav, Dipesh, D.1 aPaul, Ajay1 aMulani, Fayaj, A.1 aKaregaonkar, Shrikant, J.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/regioselective-and-efficient-enzymatic-synthesis-antimicrobial-andrographolide-derivatives03475nas a2200205 4500008004100000020001400041245017500055210006900230260000800299490000700307520265300314100002902967700002202996700002203018700001803040700002703058700001903085700003703104856012803141 2018 eng d a1471-222900a Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension0 aTracing the biosynthetic origin of limonoids and their functiona cOCT0 v183 aBackground Neem tree serves as a cornucopia for triterpenoids called limonoids that are of profound interest to humans due to their diverse biological activities. However, the biosynthetic pathway that plant employs for the production of limonoids remains unexplored for this wonder tree. Results Herein, we report the tracing of limonoid biosynthetic pathway through feeding experiments using C-13 isotopologues of glucose in neem cell suspension. Growth and development specific limonoid spectrum of neem seedling and time dependent limonoid biosynthetic characteristics of cell lines were established. Further to understand the role of mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways in limonoid biosynthesis, Ultra Performance Liquid Chromatography (UPLC)- tandem mass spectrometry based structure-fragment relationship developed for limonoids and their isotopologues have been utilized. Analyses of labeled limonoid extract lead to the identification of signature isoprenoid units involved in azadirachtin and other limonoid biosynthesis, which are found to be formed through mevalonate pathway. This was further confirmed by treatment of cell suspension with mevinolin, a specific inhibitor for MVA pathway, which resulted in drastic decrease in limonoid levels whereas their biosynthesis was unaffected with fosmidomycin mediated plastidial methylerythritol 4-phosphate (MEP) pathway inhibition. This was also conspicuous, as the expression level of genes encoding for the rate-limiting enzyme of MVA pathway, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) was comparatively higher to that of deoxyxylulose-phosphate synthase (DXS) of MEP pathway in different tissues and also in the in vitro grown cells. Thus, this study will give a comprehensive understanding of limonoid biosynthetic pathway with differential contribution of MVA and MEP pathways. Conclusions Limonoid biosynthesis of neem tree and cell lines have been unraveled through comparative quantification of limonoids with that of neem tree and through C-13 limonoid isotopologues analysis. The undifferentiated cell lines of neem suspension produced a spectrum of C-seco limonoids, similar to parental tissue, kernel. Azadirachtin, a C-seco limonoid is produced in young tender leaves of plant whereas in the hard mature leaves of tree, ring intact limonoid nimocinol accumulates in high level. Furthermore, mevalonate pathway exclusively contributes for isoprene units of limonoids as evidenced through stable isotope labeling and no complementation of MEP pathway was observed with mevalonate pathway dysfunction, using chemical inhibitors.1 aAarthy, Thiagarayaselvam1 aMulani, Fayaj, A.1 aPandreka, Avinash1 aKumar, Ashish1 aNandikol, Sharvani, S.1 aHaldar, Saikat1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/tracing-biosynthetic-origin-limonoids-and-their-functional-groups-through-stable-isotope03076nas a2200265 4500008004100000022001400041245011900055210006900174260000800243300001400251490000600265520217000271100002302441700002202464700002402486700002002510700002002530700001902550700002202569700002102591700003702612700001802649700002002667856012302687 2019 eng d a2470-134300aAzadirachtin-A from azadirachta indica impacts multiple biological targets in cotton bollworm helicoverpa armigera0 aAzadirachtinA from azadirachta indica impacts multiple biologica cMAY a9531-95410 v43 a

Azadirachtin-A (AzaA) from the Indian neem tree (Azadirachta indica) has insecticidal properties; however, its molecular mechanism remains elusive. The ``targeted and nontargeted proteomic profiling'', metabolomics, matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) imaging, gene expression, and in silico analysis provided clues about its action on Helicoverpa armigera. Fourth instar H. armigera larvae fed on AzaA-based diet (AzaD) suffered from significant mortality, growth retardation, reduced larval mass, complications in molting, and prolonged development. Furthermore, death of AzaD-fed larvae was observed with various phenotypes like bursting, blackening, and half-molting. Liquid chromatography-mass spectrometry (LC-MS) data showed limited catabolic processing of ingested AzaA and dramatic alternations of primary metabolism in H. armigera. MALDI-TOF imaging indicated the presence of AzaA in midgut of H. armigera. In the gut, out of 79 proteins identified, 34 were upregulated, which were related to digestion, immunity, energy production, and apoptosis mechanism. On the other hand, 45 proteins were downregulated, including those from carbohydrate metabolism, lipid metabolism, and energy transfer. In the hemolymph, 21 upregulated proteins were reported to be involved in immunity, RNA processing, and mRNA-directed protein synthesis, while 7 downregulated proteins were implicated in energy transfer, hydrolysis, lipid metabolism, defense mechanisms, and amino acid storage-related functions. Subsequently, six target proteins were identified using labeled AzaA that interacted with whole insect proteins. In silico analysis suggests that AzaA could be efficiently accommodated in the hydrophobic pocket of juvenile hormone esterase and showed strong interaction with active site residues, indicating plausible targets of AzaA in H. armigera. Quantitative polymerase chain reaction analysis suggested differential gene expression patterns and partly corroborated the proteomic results. Overall, data suggest that AzaA generally targets more than one protein in H. armigera and hence could be a potent biopesticide.

1 aDawkar, Vishal, V.1 aBarage, Sagar, H.1 aBarbole, Ranjit, S.1 aFatangare, Amol1 aGrimalt, Susana1 aHaldar, Saikat1 aHeckel, David, G.1 aGupta, Vidya, S.1 aThulasiram, Hirekodathakallu, V.1 aSvatos, Ales.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/azadirachtin-azadirachta-indica-impacts-multiple-biological-targets-cotton-bollworm02608nas a2200313 4500008004100000022001400041245010700055210006900162260000800231300001000239490000700249520155900256653002801815653002501843653001101868653002101879653001301900653001801913100001601931700002901947700002501976700002602001700002502027700002402052700002202076700003702098700002002135856013902155 2019 eng d a0971-589400aTerpene profiling, transcriptome analysis and characterization of cis–terpineol synthase from Ocimum0 aTerpene profiling transcriptome analysis and characterization of cJAN a47-570 v253 a

Ocimum species produces a varied mix of different metabolites that imparts immense medicinal properties. To explore this chemo-diversity, we initially carried out metabolite profiling of different tissues of five Ocimum species and identified the major terpenes. This analysis broadly classified these five Ocimum species into two distinct chemotypes namely, phenylpropanoid-rich and terpene-rich. In particular, -caryophyllene, myrcene, limonene, camphor, borneol and selinene were major terpenes present in these Ocimum species. Subsequently, transcriptomic analysis of pooled RNA samples from different tissues of Ocimum gratissimum, O. tenuiflorum and O. kilimandscharicum identified 38 unique transcripts of terpene synthase (TPS) gene family. Full-length gene cloning, followed by sequencing and phylogenetic analysis of three TPS transcripts were carried out along with their expression in various tissues. Terpenoid metabolite and expression profiling of candidate TPS genes in various tissues of Ocimum species revealed spatial variances. Further, putative TPS contig 19414 (TPS1) was selected to corroborate its role in terpene biosynthesis. Agrobacterium-mediated transient over-expression assay of TPS1 in the leaves of O. kilimandscharicum and subsequent metabolic and gene expression analyses indicated it as a cis–terpineol synthase. Overall, present study provided deeper understanding of terpene diversity in Ocimum species and might help in the enhancement of their terpene content through advanced biotechnological approaches.

10aAgro-infiltration assay10aMetabolite profiling10aOcimum10aTerpene synthase10aTerpenes10aTranscriptome1 aAnand, Atul1 aJayaramaiah, Ramesha, H.1 aBeedkar, Supriya, D.1 aDholakia, Bhushan, B.1 aLavhale, Santosh, G.1 aPunekar, Sachin, A.1 aGade, Wasudeo, N.1 aThulasiram, Hirekodathakallu, V.1 aGiri, Ashok, P. uhttps://library.ncl.res.in/content/terpene-profiling-transcriptome-analysis-and-characterization-cis%E2%80%93terpineol-synthase-ocimum02023nas a2200265 4500008004100000022001400041245013300055210006900188260000800257300001400265490000700279520104800286653003701334653002501371653003101396653003301427653001401460653002601474100002401500700002601524700002701550700003701577700002001614856012301634 2020 eng d a0887-358500aStructural studies on 10-hydroxygeraniol dehydrogenase: a novel linear substrate-specific dehydrogenase from Catharanthus roseus0 aStructural studies on 10hydroxygeraniol dehydrogenase a novel li cSEP a1197-12060 v883 a

Conversion of 10-hydroxygeraniol to 10-oxogeranial is a crucial step in iridoid biosynthesis. This reaction is catalyzed by a zinc-dependent alcohol dehydrogenase, 10-hydroxygeraniol dehydrogenase, belonging to the family of medium-chain dehydrogenase/reductase (MDR). Here, we report the crystal structures of a novel 10-hydroxygeraniol dehydrogenase from Catharanthus roseus in its apo and nicotinamide adenine dinucleotide phosphate (NADP(+)) bound forms. Structural analysis and docking studies reveal how subtle conformational differences of loops L1, L2, L3, and helix alpha 9' at the orifice of the catalytic site confer differential activity of the enzyme toward various substrates, by modulating the binding pocket shape and volume. The present study, first of its kind, provides insights into the structural basis of substrate specificity of MDRs specific to linear substrates. Furthermore, comparison of apo and NADP(+) bound structures suggests that the enzyme adopts open and closed states to facilitate cofactor binding.

10a10-hydroxygeraniol dehydrogenase10airidoid biosynthesis10amedium-chain dehydrogenase10amonoterpene indole alkaloids10areductase10aX-ray crystallography1 aSandholu, Anand, S.1 aMujawar, Sharmila, P.1 aRamakrishnan, Krithika1 aThulasiram, Hirekodathakallu, V.1 aKulkarni, Kiran uhttps://library.ncl.res.in/content/structural-studies-10-hydroxygeraniol-dehydrogenase-novel-linear-substrate-specific00940nas a2200253 4500008004100000022001400041245013700055210006900192260000800261300001100269490000800280100002200288700002100310700001800331700002900349700002200378700002600400700002400426700002600450700002100476700002200497700003700519856013000556 2021 eng d a0031-942200aLimonoid biosynthesis 3: functional characterization of crucial genes involved in neem limonoid biosynthesis (vol 184, 112669, 2021)0 aLimonoid biosynthesis 3 functional characterization of crucial g cJUL a1127510 v1871 aPandreka, Avinash1 aChaya, Patil, S.1 aKumar, Ashish1 aAarthy, Thiagarayaselvam1 aMulani, Fayaj, A.1 aBhagyashree, Date, D.1 aShilpashree, H., B.1 aJennifer, Cheruvathur1 aPonnusamy, Sudha1 aNagegowda, Dinesh1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/limonoid-biosynthesis-3-functional-characterization-crucial-genes-involved-neem-limonoid-001797nas a2200181 4500008004100000245004600041210004600087260000800133300001200141490000600153520123400159100002801393700001601421700002401437700003701461700003601498856008101534 2021 eng d00aNeem derivatives inhibits tau aggregation0 aNeem derivatives inhibits tau aggregation cJAN a169-1780 v33 aTau is a phosphoprotein with natively unfolded conformation that functions to stabilize microtubules in axons. Alzheimer's disease pathology triggers several modifications in tau, which causes it to lose its affinity towards microtubule, thus, leading to microtubule disassembly and loss of axonal integrity. This elicit accumulation of tau as paired helical filaments is followed by stable neurofibrillary tangles formation. A large number of small molecules have been isolated from Azadirachta indica with varied medicinal applications. The intermediate and final limonoids, nimbin and salannin respectively, isolated from Azadirachta indica, were screened against tau aggregation. ThS and ANS fluorescence assay showed the role of intermediate and final limonoids in preventing heparin induced cross-β sheet formation and also decreased hydrophobicity, which are characteristic nature of tau aggregation. Transmission electron microscopy studies revealed that limonoids restricted the aggregation of tau to fibrils; in turn, limonoids led to the formation of short and fragile aggregates. Both the limonoids were non-toxic to HEK293T cells thus, substantiating limonoids as a potential lead in overcoming Alzheimer's disease.1 aNalini, Gorantla, Vijay1 aDas, Rashmi1 aMulani, Fayaj, Alam1 aThulasiram, Hirekodathakallu, V.1 aChinnathambi, Subashchandrabose uhttps://library.ncl.res.in/content/neem-derivatives-inhibits-tau-aggregation02479nas a2200253 4500008004100000022001400041245015000055210006900205260000800274300001100282490000800293520150200301100002201803700002901825700002901854700003201883700002401915700003001939700003801969700002502007700003702032700002902069856012702098 2023 eng d a0031-931700aComprehensive analysis of physiological and metabolomic responses to drought reveals specific modulation of acquired tolerance mechanisms in rice0 aComprehensive analysis of physiological and metabolomic response cMAY ae139170 v1753 a

Mild stresses induce ``acquired tolerance traits'' (ATTs) that provide tolerance when stress becomes severe. Here, we identified the genetic variability in ATTs among a panel of rice germplasm accessions and demonstrated their relevance in protecting growth and productivity under water-limited conditions. Diverse approaches, including physiological screens, association mapping and metabolomics, were adopted and revealed 43 significant marker-trait associations. Nontargeted metabolomic profiling of contrasting genotypes revealed 26 ``tolerance-related-induced'' primary and secondary metabolites in the tolerant genotypes (AC-39000 and AC-39020) compared to the susceptible one (BPT-5204) under water-limited condition. Metabolites that help maintain cellular functions, especially Calvin cycle processes, significantly accumulated more in tolerant genotypes, which resulted in superior photosynthetic capacity and hence water use efficiency. Upregulation of the glutathione cycle intermediates explains the ROS homeostasis among the tolerant genotypes, maintaining spikelet fertility, and grain yield under stress. Bioinformatic dissection of a major effect quantitative trait locus on chromosome 8 revealed genes controlling metabolic pathways leading to the production of osmolites and antioxidants, such as GABA and raffinose. The study also led to the identification of specific trait donor genotypes that can be effectively used in translational crop improvement activities.

1 aDoddaraju, Pushpa1 aDharmappa, Prathibha, M.1 aThiagarayaselvam, Aarthy1 aVijayaraghavareddy, Preethi1 aBheemanahalli, Raju1 aBasavaraddi, Priyanka, A.1 aMalagondanahalli, Mohan, Kumar V.1 aKambalimath, Sumanth1 aThulasiram, Hirekodathakallu, V.1 aSreeman, Sheshshayee, M. uhttps://library.ncl.res.in/content/comprehensive-analysis-physiological-and-metabolomic-responses-drought-reveals-specific02505nas a2200265 4500008004100000022001400041245016800055210006900223260000800292300001200300490000700312520152900319653003101848653001101879653002501890653002201915653002001937100003701957700003801994700002202032700001802054700002002072700002202092856012502114 2023 eng d a1479-262100aTargeted metabolite profiling and de novo transcriptome sequencing reveal the key terpene synthase genes in medicinally important plant, Couroupita guianensis Aubl0 aTargeted metabolite profiling and de novo transcriptome sequenci cDEC a558-5700 v213 a

The Lecythidaceae family tree, Couroupita guianensis Aubl, popularly known as Nagpushpa, is a widely cultivated ornamental tree with several uses in traditional medicine. The tree is revered as highly sacred in Indian traditional culture due to its uniquely shaped, fragrant flowers. Considering the significance, we were prompted to carry out the metabolite and transcriptome analysis of Nagapushpa. The flower, petals, stamen, stem and leaf of C. guianensis were metabolically profiled, and it was discovered that the flower tissue contained the highest terpenoid reservoir. A number of terpenoid pathway transcripts were also found in the flower tissue after transcriptome profiling. KEGG pathway mapping was carried out to correlate transcript sequences with the biosynthesis of different types of terpenes. We were able to clone three full-length terpene synthase gene candidates, i.e. monoterpene ocimene synthase, diterpene ent-kaurene synthase and sesquiterpene farnesene synthase. The transcript expression of selected terpene synthase genes was also verified in flower tissue. These cloned sequences were used for in silico structural investigations and protein function prediction at the level of 3D structure. The data presented in this study provide a comprehensive resource for the metabolic and transcriptomic profiles of C. guianensis. The study paves the way towards the elucidation of terpene biosynthetic pathway in C. guianensis and heterologous production of useful terpenoids in the future.

10aCouroupita guianensis Aubl10aflower10aMetabolite profiling10aterpene synthases10aTranscriptomics1 aThulasiram, Hirekodathakallu, V.1 aKaregaonkar, Shrikant, Jagannathr1 aSharma, Poojadevi1 aKumar, Ashish1 aRamkumar, Sudha1 aPandreka, Avinash uhttps://library.ncl.res.in/content/targeted-metabolite-profiling-and-de-novo-transcriptome-sequencing-reveal-key-terpene02157nas a2200265 4500008004100000022001400041245010100055210006900156260000900225300001100234490000700245520126900252653002601521653001601547653001901563653001801582653001801600100002301618700002201641700002101663700001901684700002601703700003701729856012501766 2025 eng d a2365-654900aSupramolecular self-assembly of glochidonol: a renewable triterpenoid from glochidion tomentosum0 aSupramolecular selfassembly of glochidonol a renewable triterpen cAUG  ae012070 v103 a

Glochidonol a lupane pentacyclic (6-6-6-6-5) triterpenoid isolated from Glochidion tomentosum, exhibited exceptional gelation ability compared to the screened lupane- and oleanane-type triterpenoids. This study represents the first report on the self-assembly behavior of glochidonol in various liquids. The molecule self-assembled to form gels in all tested aromatic solvents, whereas no gelation was observed in water or phosphate buffer. The structural and physical properties of the self-assembled glochidonol were characterized using optical microscopy, scanning electron microscopy, atomic force microscopy, and Fourier-transform infrared spectroscopy. Additionally, the glochidonol-based self-assembled fibrillar network was utilized for the encapsulation of fluorescein isothiocyanate as a model drug, highlighting its potential for biomedical applications. A glochidonol-based gel loaded with doxorubicin exhibited sustained, diffusion-mediated drug release into PBS, accompanied by partial gel degradation. Fluorescence analysis confirmed release suggesting drug-gel interactions and diffusion. The glochidonol-based gel demonstrated sustained, diffusion-controlled doxorubicin release with partial degradation under physiological conditions.

10aGlochidion tomentosum10aGlochidonol10aOrgano gelator10aSelf-assembly10aTriterpenoids1 aPatil, Harshal, S.1 aJagadeesh, K., S.1 aDinore, Jaysingh1 aSharanappa, P.1 aBaviskar, Ashwini, S.1 aThulasiram, Hirekodathakallu, V. uhttps://library.ncl.res.in/content/supramolecular-self-assembly-glochidonol-renewable-triterpenoid-glochidion-tomentosum