Non-invasive evaluation of ventricular refractoriness and its dispersion during ventricular fibrillation in patients with implantable cardioverter defibrillator

BACKGROUND: Local ventricular refractoriness and its dispersion during ventricular fibrillation (VF) have not been well evaluated, due to methodological difficulties. METHODS: In this study, a non-invasive method was used in evaluation of local ventricular refractoriness and its dispersion during induced VF in 11 patients with VF and/or polymorphic ventricular tachycardia (VT) who have implanted an implantable cardioverter defibrillator (ICD). Bipolar electrograms were simultaneously recorded from the lower oesophagus behind the posterior left ventricle (LV) via an oesophageal electrode and from the right ventricular (RV) apex via telemetry from the implanted ICD. VF intervals were used as an estimate of the ventricular effective refractory period (VERP). In 6 patients, VERP was also measured during sinus rhythm at the RV apex and outflow tract (RVOT) using conventional extra stimulus technique. RESULTS: Electrograms recorded from the RV apex and the lower esophagus behind the posterior LV manifested distinct differences of the local ventricular activities. The estimated VERPs during induced VF in the RV apex were significantly shorter than that measured during sinus rhythm using extra stimulus technique. The maximal dispersion of the estimated VERPs during induced VF between the RV apex and posterior LV was that of 10 percentile VF interval (40 ± 27 ms), that is markedly greater than the previously reported dispersion of ventricular repolarization without malignant ventricular arrhythmias (30–36 ms). CONCLUSIONS: This study verified the feasibility of recording local ventricular activities via oesophageal electrode and via telemetry from an implanted ICD and the usefulness of VF intervals obtained using this non-invasive technique in evaluation of the dispersion of refractoriness in patients with ICD implantation

Chinese and Korean Characters Engage the Same Visual Word Form Area in Proficient Early Chinese-Korean Bilinguals

A number of recent studies consistently show an area, known as the visual word form area (VWFA), in the left fusiform gyrus that is selectively responsive for visual words in alphabetic scripts as well as in logographic scripts, such as Chinese characters. However, given the large difference between Chinese characters and alphabetic scripts in terms of their orthographic rules, it is not clear at a fine spatial scale, whether Chinese characters engage the same VWFA in the occipito-temporal cortex as alphabetic scripts. We specifically compared Chinese with Korean script, with Korean script serving as a good example of alphabetic writing system, but matched to Chinese in the overall square shape. Sixteen proficient early Chinese-Korean bilinguals took part in the fMRI experiment. Four types of stimuli (Chinese characters, Korean characters, line drawings and unfamiliar Chinese faces) were presented in a block-design paradigm. By contrasting characters (Chinese or Korean) to faces, presumed VWFAs could be identified for both Chinese and Korean characters in the left occipito-temporal sulcus in each subject. The location of peak response point in these two VWFAs were essentially the same. Further analysis revealed a substantial overlap between the VWFA identified for Chinese and that for Korean. At the group level, there was no significant difference in amplitude of response to Chinese and Korean characters. Spatial patterns of response to Chinese and Korean are similar. In addition to confirming that there is an area in the left occipito-temporal cortex that selectively responds to scripts in both Korean and Chinese in early Chinese-Korean bilinguals, our results show that these two scripts engage essentially the same VWFA, even at the level of fine spatial patterns of activation across voxels. These results suggest that similar populations of neurons are engaged in processing the different scripts within the same VWFA in early bilinguals

The elementary events underlying force generation in neuronal lamellipodia

We have used optical tweezers to identify the elementary events underlying force generation in neuronal lamellipodia. When an optically trapped bead seals on the lamellipodium membrane, Brownian fluctuations decrease revealing the underlying elementary events. The distribution of bead velocities has long tails with frequent large positive and negative values associated to forward and backward jumps occurring in 0.1–0.2 ms with varying amplitudes up to 20 nm. Jump frequency and amplitude are reduced when actin turnover is slowed down by the addition of 25 nM Jasplakinolide. When myosin II is inhibited by the addition of 20 μM Blebbistatin, jump frequency is reduced but to a lesser extent than by Jasplainolide. These jumps constitute the elementary events underlying force generation

Lovastatin Modulates Glycogen Synthase Kinase-3β Pathway and Inhibits Mossy Fiber Sprouting after Pilocarpine-Induced Status Epilepticus

This study was undertaken to assay the effect of lovastatin on the glycogen synthase kinase-3 beta (GSK-3β) and collapsin responsive mediator protein-2 (CRMP-2) signaling pathway and mossy fiber sprouting (MFS) in epileptic rats. MFS in the dentate gyrus (DG) is an important feature of temporal lobe epilepsy (TLE) and is highly related to the severity and the frequency of spontaneous recurrent seizures. However, the molecular mechanism of MFS is mostly unknown. GSK-3β and CRMP-2 are the genes responsible for axonal growth and neuronal polarity in the hippocampus, therefore this pathway is a potential target to investigate MFS. Pilocarpine-induced status epilepticus animal model was taken as our researching material. Western blot, histological and electrophysiological techniques were used as the studying tools. The results showed that the expression level of GSK-3β and CRMP-2 were elevated after seizure induction, and the administration of lovastatin reversed this effect and significantly reduced the extent of MFS in both DG and CA3 region in the hippocampus. The alteration of expression level of GSK-3β and CRMP-2 after seizure induction proposes that GSK-3β and CRMP-2 are crucial for MFS and epiletogenesis. The fact that lovastatin reversed the expression level of GSK-3β and CRMP-2 indicated that GSK-3β and CRMP-2 are possible to be a novel mechanism of lovatstain to suppress MFS and revealed a new therapeutic target and researching direction for studying the mechanism of MFS and epileptogenesis

Sensitivity of the Himalayan orography representation in simulation of winter precipitation using Regional Climate Model (RegCM) nested in a GCM

This document is the Accepted Manuscript version of the following article: Tiwari, P.R., Kar, S.C., Mohanty, U.C., Climate Dynamics (2017). The final publication is available at Springer via https://link.springer.com/article/10.1007%2Fs00382-017-3567-3. The Accepted Manuscript is under embargo. Embargo end date: 24 February 2018.The role of the Himalayan orography representationin a Regional Climate Model (RegCM4) nested inNCMRWF global spectral model is examined in simulatingthe winter circulation and associated precipitation over theNorthwest India (NWI; 23°–37.5°N and 69°–85°E) region.For this purpose, nine different set of orography representationsfor nine distinct precipitation years (three years eachfor wet, normal and dry) have been considered by increasing(decreasing) 5, 10, 15, and 20% from the mean height(CNTRL) of the Himalaya in RegCM4 model. Validationwith various observations revealed a good improvementin reproducing the precipitation intensity and distributionwith increased model height compared to the resultsobtained from CNTRL and reduced orography experiments.Further it has been found that, increase in heightby 10% (P10) increases seasonal precipitation about 20%,while decrease in height by 10% (M10) results around 28%reduction in seasonal precipitation as compared to CNTRLexperiment over NWI region. This improvement in precipitationsimulation comes due to better representation ofvertical pressure velocity and moisture transport as thesefactors play an important role in wintertime precipitationprocesses over NWI region. Furthermore, a comparison of model-simulated precipitation with observed precipitationat 17 station locations has been also carried out. Overall,the results suggest that when the orographic increment of10% (P10) is applied on RegCM4 model, it has better skillin simulating the precipitation over the NWI region andthis model is a useful tool for further regional downscalingstudies.Peer reviewe

Disruption of a GATA4/Ankrd1 Signaling Axis in Cardiomyocytes Leads to Sarcomere Disarray: Implications for Anthracycline Cardiomyopathy

Doxorubicin (Adriamycin) is an effective anti-cancer drug, but its clinical usage is limited by a dose-dependent cardiotoxicity characterized by widespread sarcomere disarray and loss of myofilaments. Cardiac ankyrin repeat protein (CARP, ANKRD1) is a transcriptional regulatory protein that is extremely susceptible to doxorubicin; however, the mechanism(s) of doxorubicin-induced CARP depletion and its specific role in cardiomyocytes have not been completely defined. We report that doxorubicin treatment in cardiomyocytes resulted in inhibition of CARP transcription, depletion of CARP protein levels, inhibition of myofilament gene transcription, and marked sarcomere disarray. Knockdown of CARP with small interfering RNA (siRNA) similarly inhibited myofilament gene transcription and disrupted cardiomyocyte sarcomere structure. Adenoviral overexpression of CARP, however, was unable to rescue the doxorubicin-induced sarcomere disarray phenotype. Doxorubicin also induced depletion of the cardiac transcription factor GATA4 in cardiomyocytes. CARP expression is regulated in part by GATA4, prompting us to examine the relationship between GATA4 and CARP in cardiomyocytes. We show in co-transfection experiments that GATA4 operates upstream of CARP by activating the proximal CARP promoter. GATA4-siRNA knockdown in cardiomyocytes inhibited CARP expression and myofilament gene transcription, and induced extensive sarcomere disarray. Adenoviral overexpression of GATA4 (AdV-GATA4) in cardiomyocytes prior to doxorubicin exposure maintained GATA4 levels, modestly restored CARP levels, and attenuated sarcomere disarray. Interestingly, siRNA-mediated depletion of CARP completely abolished the Adv-GATA4 rescue of the doxorubicin-induced sarcomere phenotype. These data demonstrate co-dependent roles for GATA4 and CARP in regulating sarcomere gene expression and maintaining sarcomeric organization in cardiomyocytes in culture. The data further suggests that concurrent depletion of GATA4 and CARP in cardiomyocytes by doxorubicin contributes in large part to myofibrillar disarray and the overall pathophysiology of anthracycline cardiomyopathy

Acadesine Kills Chronic Myelogenous Leukemia (CML) Cells through PKC-Dependent Induction of Autophagic Cell Death

CML is an hematopoietic stem cell disease characterized by the t(9;22) (q34;q11) translocation encoding the oncoprotein p210BCR-ABL. The effect of acadesine (AICAR, 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) a compound with known antileukemic effect on B cell chronic lymphoblastic leukemia (B-CLL) was investigated in different CML cell lines. Acadesine triggered loss of cell metabolism in K562, LAMA-84 and JURL-MK1 and was also effective in killing imatinib-resistant K562 cells and Ba/F3 cells carrying the T315I-BCR-ABL mutation. The anti-leukemic effect of acadesine did not involve apoptosis but required rather induction of autophagic cell death. AMPK knock-down by Sh-RNA failed to prevent the effect of acadesine, indicating an AMPK-independent mechanism. The effect of acadesine was abrogated by GF109203X and Ro-32-0432, both inhibitor of classical and new PKCs and accordingly, acadesine triggered relocation and activation of several PKC isoforms in K562 cells. In addition, this compound exhibited a potent anti-leukemic effect in clonogenic assays of CML cells in methyl cellulose and in a xenograft model of K562 cells in nude mice. In conclusion, our work identifies an original and unexpected mechanism by which acadesine triggers autophagic cell death through PKC activation. Therefore, in addition to its promising effects in B-CLL, acadesine might also be beneficial for Imatinib-resistant CML patients

High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×10(6) Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8-8×10(5) Da).In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation.We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13

Lower Respiratory Tract Infection Induced by a Genetically Modified Picornavirus in Its Natural Murine Host

Infections with the picornavirus, human rhinovirus (HRV), are a major cause of wheezing illnesses and asthma exacerbations. In developing a murine model of picornaviral airway infection, we noted the absence of murine rhinoviruses and that mice are not natural hosts for HRV. The picornavirus, mengovirus, induces lethal systemic infections in its natural murine hosts, but small genetic differences can profoundly affect picornaviral tropism and virulence. We demonstrate that inhalation of a genetically attenuated mengovirus, vMC0, induces lower respiratory tract infections in mice. After intranasal vMC0 inoculation, lung viral titers increased, peaking at 24 h postinoculation with viral shedding persisting for 5 days, whereas HRV-A01a lung viral titers decreased and were undetectable 24 h after intranasal inoculation. Inhalation of vMC0, but not vehicle or UV-inactivated vMC0, induced an acute respiratory illness, with body weight loss and lower airway inflammation, characterized by increased numbers of airway neutrophils and lymphocytes and elevated pulmonary expression of neutrophil chemoattractant CXCR2 ligands (CXCL1, CXCL2, CXCL5) and interleukin-17A. Mice inoculated with vMC0, compared with those inoculated with vehicle or UV-inactivated vMC0, exhibited increased pulmonary expression of interferon (IFN-α, IFN-β, IFN-λ), viral RNA sensors [toll-like receptor (TLR)3, TLR7, nucleotide-binding oligomerization domain containing 2 (NOD2)], and chemokines associated with HRV infection in humans (CXCL10, CCL2). Inhalation of vMC0, but not vehicle or UV-inactivated vMC0, was accompanied by increased airway fluid myeloperoxidase levels, an indicator of neutrophil activation, increased MUC5B gene expression, and lung edema, a sign of infection-related lung injury. Consistent with experimental HRV inoculations of nonallergic, nonasthmatic human subjects, there were no effects on airway hyperresponsiveness after inhalation of vMC0 by healthy mice. This novel murine model of picornaviral airway infection and inflammation should be useful for defining mechanisms of HRV pathogenesis in humans

Environmentally induced changes in antioxidant phenolic compounds levels in wild plants

[EN] Different adverse environmental conditions cause oxidative stress in plants by generation of reactive oxygen species (ROS). Accordingly, a general response to abiotic stress is the activation of enzymatic and non-enzymatic antioxidant systems. Many phenolic compounds, especially flavonoids, are known antioxidants and efficient ROS scavengers in vitro, but their exact role in plant stress responses in nature is still under debate. The aim of our work is to investigate this role by correlating the degree of environmental stress with phenolic and flavonoid levels in stress-tolerant plants. Total phenolic and antioxidant flavonoid contents were determined in 19 wild species. Meteorological data and plant and soil samples were collected in three successive seasons from four Mediterranean ecosystems: salt marsh, dune, semiarid and gypsum habitats. Changes in phenolic and flavonoid levels were correlated with the environmental conditions of the plants and were found to depend on both the taxonomy and ecology of the investigated species. Despite species-specific differences, principal component analyses of the results established a positive correlation between plant phenolics and several environmental parameters, such as altitude, and those related to water stress: temperature, evapotranspiration, and soil water deficit. The correlation with salt stress was, however, very weak. The joint analysis of all the species showed the lowest phenolic and flavonoid levels in the halophytes from the salt marsh. This finding supports previous data indicating that the halophytes analysed here do not undergo oxidative stress in their natural habitat and therefore do not need to activate antioxidant systems as a defence against salinity.This work has been funded by the Spanish Ministry of Science and Innovation (Project CGL2008-00438/BOS), with contribution from the European Regional Development Fund. Thanks to Dr. Rafael Herrera for critical reading of the manuscript.Bautista, I.; Boscaiu, M.; Lidón, A.; Llinares Palacios, JV.; Lull, C.; Donat-Torres, MP.; Mayoral García-Berlanga, O.... (2016). Environmentally induced changes in antioxidant phenolic compounds levels in wild plants. Acta Physiologiae Plantarum. 38(1):1-15. https://doi.org/10.1007/s11738-015-2025-2S115381Agati G, Biricolti S, Guidi L, Ferrini F, Fini A, Tattini M (2011) The biosynthesis of flavonoids is enhanced similarly by UV radiation and root zone salinity in L. vulgare leaves. J Plant Physiol 168:204–212Agati G, Brunetti C, Di Ferdinando M, Ferrini F, Pollastri S, Tattini M (2013) Functional roles of flavonoids in photoprotection: new evidence, lessons from the past. Plant Physiol Biochem 72:35–45Albert A, Sareedenchai V, Heller W, Seidlitz HK, Zidorn C (2009) Temperature is the key to altitudinal variation of phenolics in Arnica montana L. cv. ARBO. Oecologia 160:1–8Appel K, Hirt H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55:373–399Bachereau F, Marigo G, Asta J (1998) Effect of solar radiation (UV and visible) at high altitude on CAM-cycling and phenolic compounds biosynthesis in Sedum album. Physiol Plant 104:203–210Ballizany WL, Hofmann RV, Jahufer MZZ, Barrett BB (2012) Multivariate associations of flavonoid and biomass accumulation in white clover (Trifolium repens) under drought. Funct Plant Biol 39:167–177Bieza K, Lois R (2001) An Arabidopsis mutant tolerant to lethal ultraviolet-B levels shows constitutively elevated accumulation of flavonoids and other phenolics. Plant Physiol 126:1105–1115Bilger W, Rolland M, Nybakken L (2007) UV screening in higher plants induced by low temperature in the absence of UV-B radiation. Photochem Photobiol Sci 6:190–195Blumthaler M, Ambach M, Ellinger R (1997) Increase in solar UV radiation with altitude. J Photochem Photobiol B 39:130–134Boscaiu M, Lull C, Llinares J, Vicente O, Boira H (2013) Proline as a biochemical marker in relation to the ecology of two halophytic Juncus species. J Plant Ecol 6:177–186Bose J, Rodrigo-Moreno A, Shabala S (2013) ROS homeostasis in halophytes in the context of salinity stress tolerance. J Exp Bot 65:1241–1257Brown DE, Rashotte AM, Murphy AS, Normanly J, Tague BW, Peer WA, Taiz L, Muday GK (2001) Flavonoids act as a negative regulators of auxin transport in vivo in Arabidopsis. Plant Physiol 126:524–535Burchard P, Bilger W, Weissenböck G (2000) Contribution of hydroxycinnamates and flavonoids to epidermal shielding of UV-A and UV-B radiation in developing rye primary leaves as assessed by ultraviolet-induced chlorophyll fluorescence measurements. Plant Cell Environ 23:1373–1380Burriel F, Hernando V (1947) Nuevo método para determinar el fósforo asimilable en los suelos. Anales de Edafología Fisiología Vegetal 9:611–622Cheynier V, Comte G, Davies KM, Lattanzio V, Martens S (2013) Plant phenolics: recent advances on their biosynthesis, genetics, and ecophysiology. Plant Physiol Biochem 72:1–20Coman C, Rugina OD, Socaciu C (2012) Plants and natural compounds with antidiabetic action. Not Bot Horti Agrobo 40:314–325Di Ferdinando M, Brunetti C, Fini A, Tattini M (2012) Flavonoids as antioxidants in plants under abiotic stresses. In: Ahmad P, Prasad MNV (eds) Abiotic stress responses in plants: metabolism, productivity and sustainability. Springer, New York, pp 159–179Di Ferdinando M, Brunetti C, Agati G, Tattini M (2014) Multiple functions of polyphenols in plants inhabiting unfavourable Mediterranean areas. Environ Exper Bot 103:107–116FAO (1990) Management of gypsiferous soils. FAO Soils Bull, p 62Fini A, Brunetti C, Di Ferdinando M, Ferrini F, Tattini M (2011) Stress-induced flavonoid biosynthesis and the antioxidant machinery of plants. Plant Signal Behav 6:709–711Gil R, Lull C, Boscaiu M, Bautista I, Lidón A, Vicente O (2011) Soluble carbohydrates as osmolytes in several halophytes from a Mediterranean salt marsh. Not Bot Horti Agrobo 39:9–17Gil R, Bautista I, Boscaiu M, Lidón A, Wankhade S, Sánchez H, Llinares J, Vicente O (2014) Responses of five Mediterranean halophytes to seasonal changes in environmental conditions. AoB Plants 6: plu049Gould KS, Lister C (2006) Flavonoid function in plants. In: Andersen ØM, Marham KR (eds) Flavonoids, chemistry, biochemistry and application. CRC Press, Boca Raton, pp 397–442Hajimahmoodi M, Moghaddam G, Ranjbar AM, Khazani H, Sadeghi N, Oveisi MR, Jannat B (2013) Total phenolic, flavonoids, tannin content and antioxidant power of some Iranian pomegranate flower cultivars (Punica granatum L.). Am J Plant Sci 4:1815–1820Halliwell B (2006) Reactive species and antioxidants. Redox biology is a fundamental theme of aerobic life. Plant Physiol 141:312–322Harborne JB, Williams C (2000) Advances in flavonoid research since 1992. Phytochemistry 55:481–504Hernández I, Alegre L, Munné-Bosch S (2004) Drought-induced changes in flavonoids and other low molecular weight antioxidants in Cistus clusii grown under Mediterranean field conditions. Tree Physiol 24:1303–1311Hernández I, Alegre L, Van Breusegem F, Munné-Bosch S (2008) How relevant are flavonoids as antioxidants in plants? Trends Plant Sci 14:125–132Iwashina T (2000) The structure and distribution of the flavonoids in plants. J Plant Res 113:287–299Jaakola L, Määttä-Riihinen K, Kärenlampi S, Hohtola A (2004) Activation of flavonoid biosynthesis by solar radiation in bilberry (Vaccinium myrtillus L.) leaves. Planta 218:721–728Jenkins GI (2009) Signal transduction in responses to UB-B radiation. Annu Rev Plant Biol 60:407–431Jenkins GI, Long JC, Wade HK, Shenton MR, Bibikova TN (2001) UV and blue light signalling: pathways regulating chalcone synthase gene expression in Arabidopsis. New Phytol 151:121–131Kaulen H, Schell J, Kreuzaler F (1986) Light-induced expression of the chimeric chalcone synthase-NPTII gene in tobacco cells. EMBO J 5:1–8Kim DO, Jeong SW, Lee CY (2003) Antioxidant capacity of phenolic phytochemicals from various cultivars of plums. Food Chem 81:321–326Kirakosyan A, Seymour E, Kaufman PB, Warber S, Bolling S, Chang SC (2003) Antioxidant capacity of polyphenolic extracts from leaves of Crataegus laevigata and Crataegus monogyna (Hawthorn) subjected to drought and cold stress. J Agr Food Chem 51:3973–3976Knudssen D, Peterson GA, Pratt PF (1982) Lithium, Sodium and Potassium. In: Page AL et al (eds) Methods of soil analysis, chemical and microbiological properties. American Society of Agronomy, Madison, pp 225–246Koes RE, Spelt CE, Mol JNM (1989) The chalcone synthase multigene family of Petunia hybrida (V30): differential, light-regulated expression during flower development and UV light induction. Plant Mol Biol 12:213–225Körner C (1999) Alpine plant life. Functional plant ecology of high mountain ecosytems, BerlinKumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J 2013:1–16Kuo S (1996) Phosphorus. In: Spark D (ed) Methods of soil analysis: chemical methods, part 3. American Society of Agronomy, Madison, pp 869–919Lavola A (1998) Accumulation of flavonoids and related compounds in birch induced by UV-B irradiance. Tree Physiol 18:53–58Li J, Ou-Lee TM, Raba R, Amundson RG, Last RL (1993) Arabidopsis flavonoid mutants are hypersensitive to UV-B radiation. Plant Cell 5:171–179Llinares JV, Bautista I, Donat MP, Lidón A, Lull C, Mayoral O, Wankhade S, Boscaiu M, Vicente O (2015) Responses to environmental stress in plants adapted to Mediterranean gypsum habitats. Not Sci Biol 7:34–44Marinova D, Ribarova F, Atanassova M (2005) Total phenolics and total flavonoids in Bulgarian fruits and vegetables. J Univ Chem Technol Metall 40:255–260Martens H, Naes T (1989) Multivariate calibration. Wiley, New YorkMurai Y, Takemura S, Takeda K, Kitajima K, Iwashina T (2009) Altitudinal variation of UV-absorbing compounds in Plantago asiatica. Biochem Syst Ecol 37:78–384Nakabayashi R, Yonekura-Sakakibara K, Urano K, Suzuki M, Yamada Y, Nishizawa T, Matsuda F, Kojima M, Sakakibara H, Shinozaki K, Michael AJ, Tohge T, Yamazaki M, Saito K (2014) Enhancement of oxidative and drought tolerance in Arabidopsis by overaccumulation of antioxidant flavonoids. Plant J 77:367–379Napoli CA, Fahy D, Wang HY, Taylor LP (1999) white anther: a petunia mutant that abolishes pollen flavonoid accumulation, induces male sterility, and is complemented by a chalcone synthase transgene. Plant Physiol 120:615–622Nechita A, Cotea VV, Nechita CB, Pincu RR, Mihai CT, Colibaba CL (2012) Study of cytostatic and cytotoxic activity of several polyphenolic extracts obtained from Vitis vinifera. Not Bot Horti Agrobo 40:216–221Nelson DW, Sommers LE (1982) Total carbon, organic carbon, and organic matter. In: Page AL et al (eds) Methods of soil analysis, chemical and microbiological properties. Soil Science Society of America, Madison, pp 539–577Nelson RE, Klameth LC, Nettleton WD (1978) Determining soil gypsum content and expressing properties of gypsiferous soils. Soil Sci Soc Am J 42:659–661Nile SH, Khobragade CN (2010) Antioxidant activity and flavonoid derivatives of Plumbago zeylanica. J Nat Prod 3:130–133Park HL, Lee SW, Jung KH, Hahn TR, Cho MH (2013) Transcriptomic analysis of UV-treated rice leaves reveals UV-induced phytoalexin biosynthetic pathways and their regulatory networks in rice. Phytochemistry 96:57–71Pękal A, Pyrzynska K (2014) Evaluation of aluminium complexation reaction for flavonoid content assay. Food Anal Method 7:1776–1782Pollastri S, Tattini M (2011) Flavonols: old compounds for old roles. Ann Bot 108:1225–1233Ravishankar D, Rajora AK, Greco F, Osborn HM (2013) Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell B 45:2821–2831Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Bio Med 20:933–956Rieger G, Müller M, Guttenberger H, Bucar F (2008) Influence of altitudinal variation on the content of phenolic compounds in wild populations of Calluna vulgaris, Sambucus nigra, and Vaccinium myrtillus. J Agric Food Chem 58:9080–9086Rivas-Martínez S, Rivas-Saenz S (1996–2009) Worldwide bioclimatic classification system. Phytosociological Research Center, Spain. http://www.globalbioclimatics.org . Accessed 1 July 2013Rohman A, Riyanto S, Yuniarti N, Saputra WR, Utami R, Mulatsih W (2010) Antioxidant activity, total phenolic, and total flavonoid of extracts and fractions of red fruit (Pandanus conoideus Lam). Int Food Res J 17:97–106Romano B, Pagano E, Montanaro V, Fortunato AL, Milic N, Borrelli F (2013) Novel insights into the pharmacology of flavonoids. Phytother Res 27:1588–1596Rozema J, van de Staaij J, Björn LO, Caldwell MM (1997) UV-B as an environmental factor in plant life: stress and regulation. Trends Ecol Evol 12:22–28Rozema J, Bjorn LO, Bornman JF, Gaberščik A, Häder DP, Trošt T, Germ M, Klisch M, Gröniger A, Sinha RP, Lebert M, He YY, Buffoni-Hall R, de Bakker NVJ, van de Staaij J, Meijkamp BB (2002) The role of UV-B radiation in aquatic and terrestrial ecosystems—an experimental and functional analysis of the evolution of UV-absorbing compounds. Photochem Photobiol B Biol 66:2–12Schulze-Lefert P, Dangl JL, Becker-André M, Hahlbrock K, Schulz W (1989) Inducible in vivo DNA footprints define sequences necessary for UV light activation of the parsley chalcone synthase gene. EMBO J 8:651–656Sena MM, Frighetto RTS, Valarini PJ, Tokeshi H, Poppi RJ (2002) Discrimination of management effects on soil parameters by using principal component analysis: a multivariate analysis case study. Soil Till Res 67:171–181Shulaev V, Oliver DJ (2006) Metabolic and proteomic markers for oxidative stress. New tools for reactive oxygen species research. Plant Physiol 141:367–372Singleton VL, Rossi JA Jr (1965) Colorimetry of total phenolics with phosphomolybdic phosphotungstic acid reagents. Am J EnolVitic 16:144–158Spitaler R, Winkler A, Lins I, Yanar S, Stuppner H, Zidorn C (2008) Altitudinal variation of phenolic contents in flowering heads of Arnica montana cv. ARBO: a 3-year comparison. J Chem Ecol 34:369–375Stapleton AE, Walbot V (1994) Flavonoids can protect maize DNA from the induction of UV radiation damage. Plant Physiol 105:881–889Takahashi M, Asada K (1988) Superoxide production in aprotic interior of chloroplast thylakoids. Arch Biochem Biophys 267:714–722Tattini M, Gravano E, Pinelli P, Mulinacci N, Romani A (2000) Flavonoids accumulate in leaves and glandular trichomes of Phillyrea latifolia exposed to excess solar radiation. New Phytol 148:69–77Tattini M, Galardi C, Pinelli P, Massai R, Remorini D, Agati G (2004) Differential accumulation of flavonoids and hydroxycinnamates in leaves of Ligustrum vulgare under excess light and drought stress. New Phytol 163:547–561Treutter D (2005) Significance of flavonoids in plant resistance and enhancement of their biosynthesis. Plant Biol 7:581–591Treutter D (2006) Significance of flavonoids in plant resistance: a review. Environ Chem Lett 4:147–157Van Breusegem F, Dat JF (2006) Reactive oxygen species in plant cell death. Plant Physiol 141:384–390Williams CA, Grayer RJ (2004) Anthocyanins and other flavonoids. Nat Prod Rep 21:539–573Winkel-Shirley B (2002) Biosynthesis of flavonoids and effect of stress. Curr Opin Plant Biol 5:218–223Ylstra B, Touraev A, Benito Moreno RM, Stöger E, van Tunen AA, Vicente O, Mol JNM, Heberle-Bors E (1992) Flavonols stimulate development, germination and tube growth of tobacco pollen. Plant Physiol 100:902–907Zhishen J, Mengcheng T, Jianming W (1999) The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chem 64:555–559Zidorn C, Schubert B, Stuppner H (2005) Altitudinal differences in the contents of phenolics in flowering heads of three members of the tribe Lactuceae (Asteraceae) occurring as introduced species in New Zealand. Biochem Syst Ecol 33:855–87