Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

Cluster Lenses

Clusters of galaxies are the most recently assembled, massive, bound structures in the Universe. As predicted by General Relativity, given their masses, clusters strongly deform space-time in their vicinity. Clusters act as some of the most powerful gravitational lenses in the Universe. Light rays traversing through clusters from distant sources are hence deflected, and the resulting images of these distant objects therefore appear distorted and magnified. Lensing by clusters occurs in two regimes, each with unique observational signatures. The strong lensing regime is characterized by effects readily seen by eye, namely, the production of giant arcs, multiple-images, and arclets. The weak lensing regime is characterized by small deformations in the shapes of background galaxies only detectable statistically. Cluster lenses have been exploited successfully to address several important current questions in cosmology: (i) the study of the lens(es) - understanding cluster mass distributions and issues pertaining to cluster formation and evolution, as well as constraining the nature of dark matter; (ii) the study of the lensed objects - probing the properties of the background lensed galaxy population - which is statistically at higher redshifts and of lower intrinsic luminosity thus enabling the probing of galaxy formation at the earliest times right up to the Dark Ages; and (iii) the study of the geometry of the Universe - as the strength of lensing depends on the ratios of angular diameter distances between the lens, source and observer, lens deflections are sensitive to the value of cosmological parameters and offer a powerful geometric tool to probe Dark Energy. In this review, we present the basics of cluster lensing and provide a current status report of the field.Comment: About 120 pages - Published in Open Access at: http://www.springerlink.com/content/j183018170485723/ . arXiv admin note: text overlap with arXiv:astro-ph/0504478 and arXiv:1003.3674 by other author

What "best practice" could be in Palliative Care: an analysis of statements on practice and ethics expressed by the main Health Organizations

<p>Abstract</p> <p>Background</p> <p>In palliative care it would be necessary to refer to a model. Nevertheless it seems that there are no official statements which state and describe that model. We carried out an analysis of the statements on practice and ethics of palliative care expressed by the main health organizations to show which dimensions of end-of-life care are taken into consideration.</p> <p>Methods</p> <p>The official documents by the most representative health organisations committed to the definition of policies and guidelines for palliative and end-of-life care had been considered. The documents were analysed through a framework of the components of end-of-life care derived from literature, which was composed of 4 main "areas" and of 12 "sub-areas".</p> <p>Results</p> <p>Overall, 34 organizations were identified, 7 international organisations, and 27 organisations operating on the national level in four different countries (Australia, Canada, UK and United States). Up to 56 documents were selected and analysed. Most of them (38) are position statements. Relevant quotations from the documents were presented by "areas" and "sub-areas". In general, the "sub-areas" of symptoms control as well as those referring to relational and social issues are more widely covered by the documents than the "sub-areas" related to "preparation" and to "existential condition". Indeed, the consistency of end-of-life choices with the patient's wishes, as well as completion and meaningfulness at the end of life is given only a minor relevance.</p> <p>Conclusions</p> <p>An integrated model of the best palliative care practice is generally lacking in the documents. It might be argued that the lack of a fixed and coherent model is due to the relevance of unavoidable context issues in palliative care, such as specific cultural settings, patient-centred variables, and family specificity. The implication is that palliative care staff have continuously to adapt their model of caring to the specific needs and values of each patient, more than applying a fixed, although maybe comprehensive, care model.</p

Spatial Analyses of Benthic Habitats to Define Coral Reef Ecosystem Regions and Potential Biogeographic Boundaries along a Latitudinal Gradient

Marine organism diversity typically attenuates latitudinally from tropical to colder climate regimes. Since the distribution of many marine species relates to certain habitats and depth regimes, mapping data provide valuable information in the absence of detailed ecological data that can be used to identify and spatially quantify smaller scale (10 s km) coral reef ecosystem regions and potential physical biogeographic barriers. This study focused on the southeast Florida coast due to a recognized, but understudied, tropical to subtropical biogeographic gradient. GIS spatial analyses were conducted on recent, accurate, shallow-water (0–30 m) benthic habitat maps to identify and quantify specific regions along the coast that were statistically distinct in the number and amount of major benthic habitat types. Habitat type and width were measured for 209 evenly-spaced cross-shelf transects. Evaluation of groupings from a cluster analysis at 75% similarity yielded five distinct regions. The number of benthic habitats and their area, width, distance from shore, distance from each other, and LIDAR depths were calculated in GIS and examined to determine regional statistical differences. The number of benthic habitats decreased with increasing latitude from 9 in the south to 4 in the north and many of the habitat metrics statistically differed between regions. Three potential biogeographic barriers were found at the Boca, Hillsboro, and Biscayne boundaries, where specific shallow-water habitats were absent further north; Middle Reef, Inner Reef, and oceanic seagrass beds respectively. The Bahamas Fault Zone boundary was also noted where changes in coastal morphologies occurred that could relate to subtle ecological changes. The analyses defined regions on a smaller scale more appropriate to regional management decisions, hence strengthening marine conservation planning with an objective, scientific foundation for decision making. They provide a framework for similar regional analyses elsewhere

Digalactosyl-diacylglycerol-deficiency lowers the thermal stability of thylakoid membranes

We investigated the effects of digalactosyl-diacylglycerol (DGDG) on the organization and thermal stability of thylakoid membranes, using wild-type Arabidopsis thaliana and the DGDG-deficient mutant, dgd1. Circular-dichroism measurements reveal that DGDG-deficiency hampers the formation of the chirally organized macrodomains containing the main chlorophyll a/b light-harvesting complexes. The mutation also brings about changes in the overall chlorophyll fluorescence lifetimes, measured in whole leaves as well as in isolated thylakoids. As shown by time-resolved measurements, using the lipophylic fluorescence probe Merocyanine 540 (MC540), the altered lipid composition affects the packing of lipids in the thylakoid membranes but, as revealed by flash-induced electrochromic absorbance changes, the membranes retain their ability for energization. Thermal stability measurements revealed more significant differences. The disassembly of the chiral macrodomains around 55°C, the thermal destabilization of photosystem I complex at 61°C as detected by green gel electrophoresis, as well as the sharp drop in the overall chlorophyll fluorescence lifetime above 45°C (values for the wild type—WT) occur at 4–7°C lower temperatures in dgd1. Similar differences are revealed in the temperature dependence of the lipid packing and the membrane permeability: at elevated temperatures MC540 appears to be extruded from the dgd1 membrane bilayer around 35°C, whereas in WT, it remains lipid-bound up to 45°C and dgd1 and WT membranes become leaky around 35 and 45°C, respectively. It is concluded that DGDG plays important roles in the overall organization of thylakoid membranes especially at elevated temperatures

Frequently asked questions about chlorophyll fluorescence, the sequel

[EN] Using chlorophyll (Chl) a fluorescence many aspects of the photosynthetic apparatus can be studied, both in vitro and, noninvasively, in vivo. Complementary techniques can help to interpret changes in the Chl a fluorescence kinetics. Kalaji et al. (Photosynth Res 122: 121-158, 2014a) addressed several questions about instruments, methods and applications based on Chl a fluorescence. Here, additionalChl a fluorescence-related topics are discussed again in a question and answer format. Examples are the effect of connectivity on photochemical quenching, the correction of F-V/F-M values for PSI fluorescence, the energy partitioning concept, the interpretation of the complementary area, probing the donor side of PSII, the assignment of bands of 77 K fluorescence emission spectra to fluorescence emitters, the relationship between prompt and delayed fluorescence, potential problems when sampling tree canopies, the use of fluorescence parameters in QTL studies, the use of Chl a fluorescence in biosensor applications and the application of neural network approaches for the analysis of fluorescence measurements. The answers draw on knowledge fromdifferent Chl a fluorescence analysis domains, yielding in several cases new insights.Kalaji, H.; Schansker, G.; Brestic, M.; Bussotti, F.; Calatayud, A.; Ferroni, L.; Goltsev, V.... (2017). Frequently asked questions about chlorophyll fluorescence, the sequel. Photosynthesis Research. 132(1):13-66. https://doi.org/10.1007/s11120-016-0318-yS13661321Adams WW III, Demmig-Adams B (1992) Operation of the xanthophyll cycle in higher plants in response to diurnal changes in incident sunlight. Plant 186:390–398Adams WW III, Demmig-Adams B (2004) Chlorophyll fluorescence as a tool to monitor plant response to the environment. In: Papageorgiou GC, Govindjee (eds) Advances in photosynthesis and respiration series chlorophyll fluorescence: a signature of photosynthesis, vol 19. Springer, Dordrecht, pp 583–604Adams WW III, Demmig-Adams B, Winter K, Schreiber U (1990a) The ratio of variable to maximum chlorophyll fluorescence from photosystem II, measured in leaves at ambient temperature and at 77 K, as an indicator of the photon yield of photosynthesis. Planta 180:166–174Adams WW III, Winter K, Schreiber U, Schramel P (1990b) Photosynthesis and chlorophyll fluorescence characteristics in relationship to changes in pigment and element composition of leaves of Platanus occidentalis L. during autumnal senescence. Plant Physiol 93:1184–1190Alfonso M, Montoya G, Cases R, Rodriguez R, Picorel R (1994) Core antenna complexes, CP43 and CP47, of higher plant photosystem II. Spectral properties, pigment stoichiometry, and amino acid composition. Biochemistry 33:10494–10500Allakhverdiev SI (2011) Recent progress in the studies of structure and function of photosystem II. J Photochem Photobiol B Biol 104:1–8Allakhverdiev SI, Klimov VV, Carpentier R (1994) Variable thermal emission and chlorophyll fluorescence in photosystem II particles. Proc Natl Acad Sci USA 491:281–285Allakhverdiev SI, Los DA, Mohanty P, Nishiyama Y, Murata N (2007) Glycinebetaine alleviates the inhibitory effect of moderate heat stress on the repair of photosystem II during photoinhibition. Biochim Biophys Acta 1767:1363–1371Allen JF (1992) Protein phosphorylation in regulation of photosynthesis. Biochim Biophys Acta 1098:275–335Allen JF, Bennett J, Steinback KE, Arntzen CJ (1981) Chloroplast protein phosphorylation couples platoquinone redox state to distribution of excitation energy between photosystems. Nature 291:21–25Amesz J, van Gorkom HJ (1978) Delayed fluorescence in photosynthesis. Annu Rev Plant Physiol 29:47–66Ananyev GM, Dismukes GC (1996) Assembly of the tetra-Mn site of photosynthetic water oxidation by photoactivation: Mn stoichiometry and detection of a new intermediate. Biochemistry 35:4102–4109Anderson JM, Chow WS, Goodchild DJ (1988) Thylakoid membrane organization in sun/shade acclimation. Aust J Plant Physiol 15:11–26Andrizhiyevskaya EG, Chojnicka A, Bautista JA, Diner BA, van Grondelle R, Dekker JP (2005) Origin of the F685 and F695 fluorescence in photosystem II. Photosynth Res 84:173–180Anithakumari AM, Nataraja KN, Visser RGF, van der Linden G (2012) Genetic dissection of drought tolerance and recovery potential by quantitative trait locus mapping of a diploid potato population. Mol Breed 30:1413–1429Antal TK, Krendeleva TE, Rubin AB (2007) Study of photosystem 2 heterogeneity in the sulfur-deficient green alga Chlamydomonas reinhardtii. Photosynth Res 94:13–22Antal TK, Matorin DN, Ilyash LV, Volgusheva AA, Osipov A, Konyuhow IV, Krendeleva TE, Rubin AB (2009) Probing of photosynthetic reactions in four phytoplanktonic algae with a PEA fluorometer. Photosynth Res 102:67–76Araus JL, Amaro T, Voltas J, Nakkoul H, Nachit MM (1998) Chlorophyll fluorescence as a selection criterion for grain yield in durum wheat under Mediterranean conditions. Field Crops Res 55:209–223Argyroudi-Akoyunoglou J (1984) The 77 K fluorescence spectrum of the Photosystem I pigment-protein complex CPIa. FEBS Lett 171:47–53Arnold WA (1991) Experiments. Photosynth Res 27:73–82Arnold WA, Thompson J (1956) Delayed light production by blue-green algae, red algae and purple bacteria. J Gen Physiol 39:311–318Aro EM, Hundal T, Carlberg I, Andersson B (1990) In vitro studies on light-induced inhibition of PSII and D1-protein degradation at low temperatures. Biochim Biophys Acta 1019:269–275Aro EM, Virgin I, Andersson B (1993) Photoinhibition of photosystem II. Inactivation protein damage and turnover. Biochim Biophys Acta 1143:113–134Arsalane W, Parésys G, Duval JC, Wilhelm C, Conrad R, Büchel C (1993) A new fluorometric device to measure the in vivo chlorophyll a fluorescence yield in microalgae and its use as a herbicide monitor. Eur J Phycol 28:247–252Asada K (1999) The water-water cycle in chloroplasts: scavenging of active oxygens and dissipation of excess photons. Annu Rev Plant Physiol Plant Mol Biol 50:601–639Ashraf M, Harris PJC (2004) Potential biochemical indicators of salinity tolerance in plants. Plant Sci 166:3–16Bailey S, Walters RG, Jansson S, Horton P (2001) Acclimation of Arabidopsis thaliana to the light environment: the existence of separate low light and high light responses. Planta 213:794–801Baker NR (2008) Chlorophyll fluorescence: a probe of photosynthesis in vivo. Annu Rev Plant Biol 59:659–668Baker NR, Rosenqvist E (2004) Applications of chlorophyll fluorescence can improve crop production strategies: an examination of future possibilities. J Exp Bot 55:1607–1621Ballottari M, Dall’Osto L, Morosinotto T, Bassi R (2007) Contrasting behavior of higher plant photosystem I and II antenna systems during acclimation. J Biol Chem 282:8947–8958Barbagallo RP, Oxborough K, Pallett KE, Baker NR (2003) Rapid, noninvasive screening for perturbations of metabolism and plant growth using chlorophyll fluorescence imaging. Plant Physiol 132:485–493Barber J, Malkin S, Telfer A (1989) The origin of chlorophyll fluorescence in vivo and its quenching by the photosystem II reaction centre. Philos Trans R Soc Lond B 323:227–239Barra M, Haumann M, Loja P, Krivanek R, Grundmeier A, Dau H (2006) Intermediates in assembly by photoactivation after thermally accelerated disassembly of the manganese complex of photosynthetic water oxidation. Biochemistry 45:14523–14532Baumann HA, Morrison L, Stengel DB (2009) Metal accumulation and toxicity measured by PAM-chlorophyll fluorescence in seven species of marine macroalgae. Ecotoxicol Environ Safe 72:1063–1075Bauwe H, Hagemann M, Fernie A (2010) Photorespiration: players, partners and origin. Trends Plant Sci 15:330–336Beck WF, Brudvig GW (1987) Reactions of hydroxylamine with the electron-donor side of photosystem II. Biochemistry 26:8285–8295Belgio E, Kapitonova E, Chmeliov J, Duffy CDP, Ungerer P, Valkunas L, Ruban AV (2014) Economic photoprotection in photosystem II that retains a complete light-harvesting system with slow energy traps. Nat Commun 5:4433. doi: 10.1038/ncomms5433Bell DH, Hipkins MF (1985) Analysis of fluorescence induction curves from pea chloroplasts: photosystem II reaction centre heterogeneity. Biochim Biophys Acta 807:255–262Bellafiore S, Barneche F, Peltier G, Rochaix J-D (2005) State transitions and light adaptation require chloroplast thylakoid protein kinase STN7. Nature 433:892–895Belyaeva NE, Schmitt F-J, Paschenko VZ, Riznichenko GY, Rubin AB (2015) Modeling of the redox state dynamics in photosystem II of Chlorella pyrenoidosa Chick cells and leaves of spinach and Arabidopsis thaliana from single flash-induced fluorescence quantum yield changes on the 100 ns–10 s time scale. Photosynth Res 125:123–140Bennett J (1977) Phosphorylation of chloroplast membrane polypeptides. Nature 269:344–346Bennett J (1983) Regulation of photosynthesis by reversible phosphorylation of the light-harvesting chlorophyll a/b protein. Biochem J 212:1–13Bennett J, Shaw EK, Michel H (1988) Cytochrome b6f complex is required for phosphorylation of light-harvesting chlorophyll a/b complex II in chloroplast photosynthetic membranes. Eur J Biochem 171:95–100Bennoun P (2002) The present model for chlororespiration. Photosynth Res 73:273–277Bennoun P, Li Y-S (1973) New results on the mode of action of 3,-(3,4-dichlorophenyl)-1,1-dimethylurea in spinach chloroplasts. Biochim Biophys Acta 292:162–168Berden-Zrimec M, Drinovec L, Zrimec A (2011) Delayed fluorescence. In: Suggett DJ, Borowitzka M, Prášil O (eds) Chlorophyll a fluorescence in aquatic sciences: methods and applications, developments in applied phycology, vol 4. Springer, The Netherlands, pp 293–309Berger S, Sinha AK, Roitsch T (2007) Plant physiology meets phytopathology: plant primary metabolism and plant-pathogen interactions. J Exp Bot 58:4019–4026Bernacchi CJ, Leakey ADB, Heady LE, Morgan PB, Dohleman FG, McGrath JM, Gillespie GM, Wittig VE, Rogers A, Long SP, Ort DR (2006) Hourly and seasonal variation in photosynthesis and stomatal conductance of soybean grown at future CO2 and ozone concentrations for 3 years under fully open-air field conditions. Plant Cell Environ 29:2077–2090Betterle N, Ballotari M, Zorzan S, de Bianchi S, Cazzaniga S, Dall’Osto L, Morosinotto T, Bassi R (2009) Light-induced dissociation of an antenna hetero-oligomer is needed for non-photochemical quenching induction. J Biol Chem 284:15255–15266Bielczynski LW, Schansker G, Croce R (2016) Effect of light acclimation on the organization of photosystem II super and sub-complexes in Arabidopsis thaliana. Front Plant Sci. doi: 10.3389/fpls.2016.00105Björkman O, Demmig-Adams B (1995) Regulation of photosynthetic light energy capture, conversion, and dissipation in leaves of higher plants. In: Schulze ED, Caldwell MM (eds) Ecophysiology of photosynthesis. Springer, Berlin, pp 17–47Blubaugh DJ, Cheniae GM (1990) Kinetics of photoinhibition in hydroxylamine-extracted photosystem II membranes: relevance to photoactivation and site of electron donation. Biochemistry 29:5109–5118Bock A, Krieger-Liszkay A, Ortiz de Zarate IB, Schönknecht G (2001) Cl—channel inhibitors of the arylaminobenzoate type act as photosystem II herbicides: a functional and structural study. Biochemistry 40:3273–3281Bode S, Quentmeier CC, Liao P-N, Hafi N, Barros T, Wilk L, Bittner F, Walla PJ (2009) On the regulation of photosynthesis by excitonic interactions between carotenoids and chlorophylls. Proc Natl Acad Sci USA 106:12311–12316Boekema EJ, Van Roon H, Van Breemen JFL, Dekker JP (1999) Supramolecular organization of photosystem II and its light-harvesting antenna in partially solubilized photosystem II membranes. Eur J Biochem 266:444–452Bolhar-Nordenkampf HR, Long SP, Baker NR, Öquist G, Schreiber U, Lechner EG (1989) Chlorophyll fluorescence as a probe of the photosynthetic competence of leaves in the field: a review of current Instrumentation. Funct Ecol 3:497–514Bonaventura C, Myers J (1969) Fluorescence and oxygen evolution from Chlorella pyrenoidosa. Biochim Biophys Acta 189:366–383Bonfig KB, Schreiber U, Gabler A, Roitsch T, Berger S (2006) Infection with virulent and avirulent P. syringae strains differentially affects photosynthesis and sink metabolism in Arabidopsis leaves. Planta 225:1–12Bouges-Bocquet B (1980) Kinetic models for the electron donors of photosystem II of photosynthesis. Biochim Biophys Acta 594:85–103Bradbury M, Baker NR (1981) Analysis of the slow phases of the in vivo chlorophyll fluorescence induction curve; changes in the redox state of photosystem II electron acceptors and fluorescence emission from photosystem I and II. Biochim Biophys Acta 635:542–551Brestič M, Živčák M (2013) PSII fluorescence techniques for measurement of drought and high temperature stress signal in crop plants: protocols and applications. In: Das AB, Rout GR (eds) Molecular stress physiology of plants. Springer, New Dehli, pp 87–131Brestič M, Cornic G, Fryer MJ, Baker NR (1995) Does photorespiration protect the photosynthetic apparatus in French bean leaves from photoinhibition during drought stress? Planta 196:450–457Brestič M, Živčák M, Kalaji HM, Allakhverdiev SI, Carpentier R (2012) Photosystem II thermo-stability in situ: environmentally induced acclimation and genotype-specific reactions in Triticum aestivum L. Plant Physiol Biochem 57:93–105Brody SS, Rabinowitch E (1957) Excitation lifetime of photosynthetic pigments in vitro and in vivo. Science 125:555–563Brudvig GW, Casey JL, Sauer K (1983) The effect of temperature on the formation and decay of the multiline EPR signal species associated with photosynthetic oxygen evolution. Biochim Biophys Acta 723:366–371Bukhov NG, Boucher N, Carpentier R (1997) The correlation between the induction kinetics of the photoacoustic signal and chlorophyll fluorescence in barley leaves is governed by changes in the redox state of the photosystem II acceptor side; a study under atmospheric and high CO2 concentrations. Can J Bot 75:1399–1406Bukhov N, Egorova E, Krendeleva T, Rubin A, Wiese C, Heber U (2001) Relaxation of variable chlorophyll fluorescence after illumination of dark-adapted barley leaves as influenced by the redox states of electron carriers. Photosynth Res 70:155–166Buschmann C, Koscányi L (1989) Light-induced heat production correlated with chlorophyll fluorescence and its quenching. Photosynth Res 21:129–136Bussotti F (2004) Assessment of stress conditions in Quercus ilex L. leaves by O-J-I-P chlorophyll a fluorescence analysis. Plant Biosystems 13:101–109Bussotti F, Agati G, Desotgiu R, Matteini P, Tani C (2005) Ozone foliar symptoms in woody plants assessed with ultrastructural and fluorescence analysis. New Phytol 166:941–955Bussotti F, Desotgiu R, Cascio C, Pollastrini M, Gravano E, Gerosa G, Marzuoli R, Nali C, Lorenzini G, Salvatori E, Manes F, Schaub M, Strasser RJ (2011a) Ozone stress in woody plants assessed with chlorophyll a fluorescence. A critical reassessment of existing data. Environ Exp Bot 73:19–30Bussotti F, Pollastrini M, Cascio C, Desotgiu R, Gerosa G, Marzuoli R, Nali C, Lorenzini G, Pellegrini E, Carucci MG, Salvatori E, Fusaro L, Piccotto M, Malaspina P, Manfredi A, Roccotello E, Toscano S, Gottardini E, Cristofori A, Fini A, Weber D, Baldassarre V, Barbanti L, Monti A, Strasser RJ (2011b) Conclusive remarks. Reliability and comparability of chlorophyll fluorescence data from several field teams. Environ Exp Bot 73:116–119Butler WL (1978) Energy distribution in the photochemical apparatus of photosynthesis. Annu Rev Plant Physiol 29:345–378Byrdin M, Rimke I, Schlodder E, Stehlik D, Roelofs TA (2000) Decay kinetics and quantum yields of fluorescence in photosystem I from Synechococcus elongatus with P700 in the reduced and oxidized state: Are the kinetics of excited state decay trap-limited or transfer-limited? Biophys J 79:992–1007Caffarri S, Croce R, Cattivelli L, Bassi R (2004) A look within LHCII: differential analysis of the Lhcb1-3 complexes building the major trimeric antenna complex of higher-plant photosynthesis. Biochemistry 43:9467–9476Calatayud A, Ramirez JW, Iglesias DJ, Barreno E (2002) Effects of ozone on photosynthetic CO2 exchange, chlorophyll a fluorescence and antioxidant systems in lettuce leaves. Physiol Plant 116:308–316Cascio C, Schaub M, Novak K, Desotgiu R, Bussotti F, Strasser RJ (2010) Foliar responses to ozone of Fagus sylvatica L. seedlings grown in shaded and in full sunlight conditions. Environ Exp Bot 68:188–197Cazzaniga S, Dall’Osto L, Kong S-G, Wada M, Bassi R (2013) Interaction between avoidance of photon absorption, excess energy dissipation and zeaxanthin synthesis against photooxidative stress in Arabidopsis. Plant J 76:568–579Ceppi MG, Oukarroum A, Çiçek N, Strasser RJ, Schansker G (2012) The IP amplitude of the fluorescence rise OJIP is sensitive to changes in the photosystem I content of leaves: a study on plants exposed to magnesium and sulfate deficiencies, drought stress and salt stress. Physiol Plant 144:277–288Chaudhary N, Singh S, Agrawal SB, Agrawal M (2013) Assessment of six Indian cultivars of mung bean against ozone by using foliar injury index and changes in carbon assimilation, gas exchange, chlorophyll fluorescence and photosynthetic pigments. Environ Monit Assess 185:7793–7807Chen J, Kell A, Acharya K, Kupitz C, Fromme P, Jankowiak R (2015) Critical assessment of the emission spectra of various photosystem II core complexes. Photosynth Res 124:253–265Cheng L, Fuchigami LH, Breen PJ (2000) Light absorption and partitioning in relation to nitrogen content ‘Fuji’ apple leaves. J Am Soc Hortic Sci 125:581–587Choi CJ, Berges JA, Young EB (2012) Rapid effects of diverse toxic water pollutants on chlorophyll a fluorescence: variable responses among freshwater microalgae. Water Res 46:2615–2626Chow WS, Aro EM (2005) Photoinactivation and mechanisms of recovery. In: Wydrzynski T, Satoh K (eds) Photosystem II: the light-driven water: plastoquinone oxidoreductase, advances in photosynthesis and respiration, vol 22. Springer, Dordrecht, pp 627–648Chow WS, Fan DY, Oguchi R, Jia H, Losciale P, Youn-Il P, He J, Öquist G, Shen YG, Anderson JM (2012) Quantifying and monitoring functional photosystem II and the stoichiometry of the two photosystems in leaf segments: approaches and approximations. Photosynth Res 113:63–74Christensen MG, Teicher HB, Streibig JC (2003) Linking fluorescence induction curve and biomass in herbicide screening. Pest Manag Sci 59:1303–1310Codrea CM, Aittokallio T, Keränen M, Tyystjärvi E, Nevalainen OS (2003) Feature learning with a genetic algorithm for fluorescence fingerprinting of plant species. Pattern Recognit Lett 24:2663–2673Conjeaud H, Mathis P (1980) The effect of pH on the reduction kinetics of P-680 in tris-treated chloroplasts. Biochim Biophys Acta 590:353–359Conrad R, Büchel C, Wilhelm C, Arsalane W, Berkaloff C, Duval JC (1993) Changes in yield of in-vivo fluorescence of chlorophyll a as a tool for selective herbicide monitoring. J Appl Phycol 5:505–516Cornic G, Massacci A (1996) Leaf photosynthesis under drought stress. In: Baker NR (ed) Photosynthesis and the environment. Kluwer Academic Publisher, Dordrecht, pp 347–366Cornic G, Fresneau C (2002) Photosynthetic carbon reduction and carbon oxidation cycles are the main electron sinks for photosystems II during a mild drought. Ann Bot 89:887–894Correia MJ, Chaves MMC, Pereira JS (1990) Afternoon depression in photosynthesis in grapevine leaves—evidence for a high light stress effect. J Exp Bot 41:417–426Cotrozzi L, Remorini D, Pellegrini E, Landi M, Massai R, Nali C, Guidi L, Lorenzini G (2016) Variations in physiological and biochemical traits of oak seedlings grown under drought and ozone stress. Physiol Plant 157:69–84Croce R, Zucchelli G, Garlaschi FM, Bassi R, Jennings RC (1997) Excited state equilibration in the photosystem I-light-harvesting I complex: P700 is almost isoenergetic with its antenna. Biochemistry 35:8572–8579Cser K, Vass I (2007) Radiative and non-radiative charge recombination pathways in photosystem II studied by thermoluminescence and chlorophyll fluorescence in the cyanobacterium Synechocystis 6308. Biochim Biophys Acta 1767:233–243Czyczyło-Mysza I, Tyrka M, Marcińska Skrzypek E, Karbarz M, Dziurka M, Hura T, Dziurka K, Quarrie SA (2013) Quantitative trait loci for leaf chlorophyll fluorescence parameters, chlorophyll and carotenoid contents in relation to biomass and yield in bread wheat and their chromosome deletion bin assignments. Mol Breed 32:189–210D’Haene SE, Sobotka R, Bučinská L, Dekker JP, Komenda J (2015) Interaction of the PsbH subunit with a chlorophyll bound to histidine 114 of CP47 is responsible for the red 77 K fluorescence of Photosystem II. Biochim Biophys Acta 1847:1327–1334Dang NC, Zazubovich V, Reppert M, Neupane B, Picorel R, Seibert M, Jankowiak R (2008) The CP43 proximal antenna complex of higher plant photosystem II revisited: modeling and hole burning study. J Phys Chem B 112:9921–9933Dau H (1994) Molecular mechanisms and quantitative models of variable Photosystem II fluorescence. Photochem Photobiol 60:1–23Dau H, Sauer K (1992) Electric field effect on the picosecond fluorescence of photosystem II and its relation to the energetics and kinetics of primary charge separation. Biochim Biophys Acta 1102:91–106Dau H, Zaharieva I, Haumann M (2012) Recent developments in research on water oxidation by photosystem II. Curr Opin Chem Biol 16:3–10de Wijn R, van Gorkom HJ (2001) Kinetics of electron transfer from QA to QB in photosystem II. Biochemistry 40:11912–11922de Wijn R, van Gorkom HJ (2002) The rate of charge recombination in photosystem II. Biochim Biophys Acta 1553:302–308Debus RJ (1992) The manganese and calcium ions of photosynthetic oxygen evolution. Biochim Biophys Acta 1102:269–352Degl’Innocenti E, Guidi L, Soldatini GF (2002) Characteriz

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases