Phylogenetic and ontogenetic influences on the distribution of anthocyanins and betacyanins in leaves of tropical plants

We examined the anatomy of expanding, mature, and senescing leaves of tropical plants for the presence of red pigments: anthocyanins and betacyanins. We studied 463 species in total, 370 genera, belonging to 94 families. This included 21 species from five families in the Caryophyllales, where betacyanins are the basis for red color. We also included 14 species of ferns and gymnosperms in seven families and 29 species with undersurface coloration at maturity. We analyzed 399 angiosperm species (74 families) for factors (especially developmental and evolutionary) influencing anthocyanin production during expansion and senescence. During expansion, 44.9% produced anthocyanins and only 13.5% during senescence. At both stages, relatively few patterns of tissue distributions developed, primarily in the mesophyll, and very few taxa produced anthocyanins in dermal and ground tissue simultaneously. Of the 35 species producing anthocyanins both in development and senescence, most had similar cellular distributions. Anthocyanin distributions were identical in different developing leaves of three heteroblastic taxa. Phylogeny has influenced the distribution of anthocyanins in the epidermis and mesophyll of expanding leaves and the palisade parenchyma during senescence, although these influences are not strong. Betacyanins appear to have similar distributions in leaves of taxa within the Caryophyllales and, perhaps, similar functions. The presence of anthocyanins in the mesophyll of so many species is inconsistent with the hypothesis of protection against UV damage or fungal pathogens, and the differing tissue distributions indicate that the pigments may function in different ways, as in photoprotection and freeradical scavenging.

Pigment dynamics and autumn leaf senescence in a New England deciduous forest, eastern USA

The leaves of woody plants at Harvard Forest in Central Massachusetts, USA, changed color during senescence; 70% (62/89) of the woody species examined anatomically contained anthocyanins during senescence. Anthocyanins were not present in summer green leaves, and appeared primarily in the vacuoles of palisade parenchyma cells. Yellow coloration was a result of the unmasking of xanthophyll pigments in senescing chloroplasts. In nine red-senescing species, anthocyanins were not detectable in mature leaves, and were synthesized de novo in senescence, with less than 20 m g cm - 2 of chlorophyll remaining. Xanthophyll concentrations declined in relation to chlorophyll to the same extent in both yellow- and red-leaved taxa. Declines in the maximum photosystem II quantum yield of leaves collected prior to dawn were only slightly less in the red-senescing species, indicating no long-term protective activity. Red-leaved species had significantly greater mass/area and lower chlorophyll a / b ratios during senescence. Nitrogen tissue concentrations in mature and senescent leaves negatively correlated to anthocyanin concentrations in senescent leaves, weak evidence for more efficient nitrogen resorption in anthocyanic species. Shading retarded both chlorophyll loss and anthocyanin production in Cornus alternifolia , Acer rubrum , Acer saccharum , Quercus rubra and Viburnum alnifolium . It promoted chlorophyll loss in yellow-senescing Fagus grandifolia . A reduced red : far-red ratio did not affect this process. Anthocyanins did not increase leaf temperatures in Q. rubra and Vaccinium corymbosum on cold and sunny days. The timing of leaf-fall was remarkably constant from year to year, and the order of senescence of individual species was consistent.

Anthocyanins in Autumn Leaf Senescence

Anthocyanins are synthesized during leaf senescence in certain plants across virtually all biomes, but are most spectacular in the autumn foliage of temperate deciduous forests. The patterns of color production in senescing foliage depend at least partly upon species composition and their phenology. Both ecological and physiological explanations have been raised to explain why plants produce this pigment just before leaf fall. Physiological explanations, as photoprotection, predict that cyanic leaves would be better able to resorb nitrogen during the process of chlorophyll degradation. Ecological explanations predict better dispersal of propagules advertised by association with the brilliantly colored leaves (plausible for only a minority of species), or warning against egg-laying activity of herbivorous insects, as aphids. These hypotheses make predictions that we now can test, to help us understand this old mystery - and majestic phenomenon.

Tests of the Intersensory Redundancy Hypothesis across early postnatal development

The Intersensory Redundancy Hypothesis (IRH; Bahrick & Lickliter, 2000, 2002, 2012) predicts that early in development information presented to a single sense modality will selectively recruit attention to modality-specific properties of stimulation and facilitate learning of those properties at the expense of amodal properties (unimodal facilitation). Vaillant (2010) demonstrated that bobwhite quail chicks prenatally exposed to a maternal call alone (unimodal stimulation) are able to detect a pitch change, a modality-specific property, in subsequent postnatal testing between the familiarized call and the same call with altered pitch. In contrast, chicks prenatally exposed to a maternal call paired with a temporally synchronous light (redundant audiovisual stimulation) were unable to detect a pitch change. According to the IRH (Bahrick & Lickliter, 2012), as development proceeds and the individual's perceptual abilities increase, the individual should detect modality-specific properties in both nonredundant, unimodal and redundant, bimodal conditions. However, when the perceiver is presented with a difficult task, relative to their level of expertise, unimodal facilitation should become evident. The first experiment of the present study exposed bobwhite quail chicks 24 hr after hatching to unimodal auditory, nonredundant audiovisual, or redundant audiovisual presentations of a maternal call for 10min/hr for 24 hours. All chicks were subsequently tested 24 hr after the completion of the stimulation (72 hr following hatching) between the familiarized maternal call and the same call with altered pitch. Chicks from all experimental groups (unimodal, nonredundant audiovisual, and redundant audiovisual exposure) significantly preferred the familiarized call over the pitch-modified call. The second experiment exposed chicks to the same exposure conditions, but created a more difficult task by narrowing the pitch range between the two maternal calls with which they were tested. Chicks in the unimodal and nonredundant audiovisual conditions demonstrated detection of the pitch change, whereas the redundant audiovisual exposure group did not show detection of the pitch change, providing evidence of unimodal facilitation. These results are consistent with predictions of the IRH and provide further support for the effects of unimodal facilitation and the role of task difficulty across early development.

The Sesquiterpene Lactone Dehydroleucodine Triggers Senescence and Apoptosis in Association with Accumulation of DNA Damage Markers

Sesquiterpene lactones (SLs) are plant-derived compounds that display anti-cancer effects. Some SLs derivatives have a marked killing effect on cancer cells and have therefore reached clinical trials. Little is known regarding the mechanism of action of SLs. We studied the responses of human cancer cells exposed to various concentrations of dehydroleucodine (DhL), a SL of the guaianolide group isolated and purified from Artemisia douglasiana (Besser), a medicinal herb that is commonly used in Argentina. We demonstrate for the first time that treatment of cancer cells with DhL, promotes the accumulation of DNA damage markers such as phosphorylation of ATM and focal organization of γH2AX and 53BP1. This accumulation triggers cell senescence or apoptosis depending on the concentration of the DhL delivered to cells. Transient DhL treatment also induces marked accumulation of senescent cells. Our findings help elucidate the mechanism whereby DhL triggers cell cycle arrest and cell death and provide a basis for further exploration of the effects of DhL in in vivo cancer treatment models.

Evidence of the heterogeneous market hypothesis using wavelet multi -resolution analysis

In finance literature many economic theories and models have been proposed to explain and estimate the relationship between risk and return. Assuming risk averseness and rational behavior on part of the investor, the models are developed which are supposed to help in forming efficient portfolios that either maximize (minimize) the expected rate of return (risk) for a given level of risk (rates of return). One of the most used models to form these efficient portfolios is the Sharpe's Capital Asset Pricing Model (CAPM). In the development of this model it is assumed that the investors have homogeneous expectations about the future probability distribution of the rates of return. That is, every investor assumes the same values of the parameters of the probability distribution. Likewise financial volatility homogeneity is commonly assumed, where volatility is taken as investment risk which is usually measured by the variance of the rates of return. Typically the square root of the variance is used to define financial volatility, furthermore it is also often assumed that the data generating process is made of independent and identically distributed random variables. This again implies that financial volatility is measured from homogeneous time series with stationary parameters. In this dissertation, we investigate the assumptions of homogeneity of market agents and provide evidence for the case of heterogeneity in market participants' information, objectives, and expectations about the parameters of the probability distribution of prices as given by the differences in the empirical distributions corresponding to different time scales, which in this study are associated with different classes of investors, as well as demonstrate that statistical properties of the underlying data generating processes including the volatility in the rates of return are quite heterogeneous. In other words, we provide empirical evidence against the traditional views about homogeneity using non-parametric wavelet analysis on trading data, The results show heterogeneity of financial volatility at different time scales, and time-scale is one of the most important aspects in which trading behavior differs. In fact we conclude that heterogeneity as posited by the Heterogeneous Markets Hypothesis is the norm and not the exception.

Development of the Sphere Overlap Scale (SOS) : compartmentalization and the spillover hypothesis

The purpose of this study was to create a scale that could measure compartmentalization. In the first of two studies 311 working undergraduates were asked to indicate agreement with 119 items that measured compartmentalization. The resulting scale's reliability and validity were evaluated by having a second sample of 312 working students complete the items that comprise a sphere overlap scale, two measures of spillover, and a measure of personality, coping, and demoralization. Although the study's original goal was not realized, its procedures were successful in developing a short (10-item) measure of work-to-home spillover whose items loaded on a single factor. Structural equation modeling indicated that SOS items were correlated with existing measures of spillover and could be discriminated from related concepts of personality and coping. The SOS was also more highly correlated with demoralization than existing measures of spillover in hierarchical analyses that controlled for demographic factors, personality characteristics, and coping style. It is concluded that the SOS shows enough promise to warrant the cost of its appraisal as an alternative measure of spillover in a longitudinal study.

Joint hypothesis tests for multidimensional inequality indices

Acknowledgments This work has been undertaken with the support of the A*MIDEX project (n ∘ ANR-11-IDEX-0001-02) funded by the “Investissements d’Avenir” French Government program, managed by the French National Research Agency (ANR). We are grateful to Julian Williams, Editor Badi H. Baltagi and an anonymous referee for helpful comments. We are responsible for any errors.

The effect of the senescence-associated secretory phenotype (SASP) on glucose homeostasis in metabolic cells

Aim: Dysregulated glucose homeostasis is a hallmark of Type 2diabetes. A distinctive feature of ageing is the accumulation ofsenescent cells, defined as cells that have undergone irreversible lossof proliferative capacity. Characteristic of senescent cells is thesenescence-associated secretory phenotype (SASP) involving theproduction of factors which reinforce senescence arrest in neigh-bouring tissue environments. We hypothesise that SASP inducesmetabolic dysfunction in non-senescent cells, impairing glucosemetabolism and propagating insulin resistance. We sought todetermine the effect of SASP on glucose homeostasis in hepatic,adipose and skeletal muscle cell lines. Methods: Human dermal fibroblasts were subjected to a geno-toxic dose of doxorubicin to induce senescence, confirmed using ab-galactosidase assay. Conditioned media containing SASP werecollected post 24h and 48h of inducing senescence and used at20% and 40% concentrations to treat AML-12 hepatocytes, 3T3-L1 adipocytes and C2C12 myocytes for 24h and 48h. Cells andmedia were collected and glucose and lipid concentrations weremeasured before and after the respective incubation periods. Results: Cell media obtained from C2C12 myocytes exposed to40% SASP for 24h and 48h and AML-12 hepatocytes after 48hexhibited significantly higher concentrations of glucose in com-parison to control media (p < 0.0001, p < 0.05) suggesting areduced glucose uptake. Glucose utilisation remained unchanged in3T3-L1 cells. Conclusion: Our data suggest an important role for SASP inaltering glucose homeostasis and identify SASP as a potentialmediator between ageing and the increase in age-related insulinresistance.

Methods for Hypothesis Testing in Animal Carcinogenicity Experiments

Thesis (Ph.D.)--University of Washington, 2016-08

Regulators of cellular senescence and tumorigenesis

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Avaliação do potencial cancerigénico de microcistinas (cianotoxinas)

Tese de doutoramento em Farmácia (Toxicologia), apresentada à Faculdade de Farmácia da Universidade de Lisboa, 2009.

Investigation of the role of long non-coding RNAs in oncogene induced cellular senescence

Cellular senescence is a stable arrest of cell proliferation induced by several factors such as activated oncogenes, oxidative stress and shortening of telomeres. Senescence acts as a tumour suppression mechanism to halt the progression of cancer. However, senescence may also impact negatively upon tissue regeneration, thus contributing to the effects of ageing. The eukaryotic genome is controlled by various modes of transcriptional and translational regulation. Focus has therefore centred on the role of long non- coding RNAs (lncRNAs) in regulating the genome. Accordingly, understanding how lncRNAs function to regulate the senescent genome is integral to improving our knowledge and understanding of tumour suppression and ageing. Within this study, I set out to investigate the expression of lncRNAs’ expression within models of senescence. Through a custom expression array, I have shown that expression of multiple different lncRNAs is up-regulated and down regulated in IMR90 replicative senescent fibroblasts and oncogene-induced senescent melanocytes. LncRNA expression was determined to be specific to stable senescence-associated cell arrest and predominantly within the nucleus of senescent cells. In order to examine the function of lncRNA expression in senescence, I selected lncRNA transcript ENST0000430998 (lncRNA_98) to focus my investigations upon. LncRNA_98 was robustly upregulated within multiple models of senescence and efficiently depleted using anti-sense oligonucleotide technology. Characterisation and unbiased RNA-sequencing of lncRNA_98 deficient senescent cells highlighted a list of genes that are regulated by lncRNA_98 expression in senescent cells and may regulate aspects of the senescence program. Specifically, the formation of SAHF was impeded upon depletion of lncRNA_98 expression and levels of total pRB protein expression severely decreased. Validation and recapitulation of consequences of pRB depletion was confirmed through lncRNA_98 knock-out cells generated using CRISPR technology. Surprisingly, inhibition of ATM kinase functions permitted the restoration of pRB protein levels within lncRNA_98 deficient cells. I propose that lncRNA_98 antagonizes the ability of ATM kinase to downregulate pRB expression at a post-transcriptional level, thereby potentiating senescence. Furthermore, lncRNA expression was detected within fibroblasts of old individuals and visualised within senescent melanocytes in human benign nevi, a barrier to melanoma progression. Conversely, mining of 337 TCGA primary melanoma data sets highlighted that the lncRNA_98 gene and its expression was lost from a significant proportion of melanoma samples, consistent with lncRNA_98 having a tumour suppressor functions. The data presented in this study illustrates that lncRNA_98 expression has a regulatory role over pRB expression in senescence and may regulate aspects of tumourigenesis and ageing.

Expression of tumor-related Rac1b antagonizes B-Raf-induced senescence in colorectal cells

Mutations in the BRAF oncogene have been identified as a tumor-initiating genetic event in mainly melanoma, thyroid and colon cancer, resulting in an initial proliferative stimulus that is followed by a growth arrest period known as oncogene-induced senescence (OIS). It remains unknown what triggers subsequent escape from OIS to allow further tumor progression. A previous analysis revealed that overexpression of splice variant Rac1b occurs in around 80% of colorectal tumors carrying a mutation in BRAF. Using both BRaf-V600E-directed RNAi and overexpression we demonstrate that this mutation does not directly lead to Rac1b overexpression, indicating the latter as an independent event during tumor progression. Nonetheless, we observed that expression of oncogenic BRaf-V600E in non-transformed colonocytes (NCM460 cell line) increased both the transcript and protein levels of p14ARF, p15INK4b and p21CIP1 and led to increased expression of β-galactosidase, all indicators of OIS induction. Interestingly, whereas the protein levels of these markers were reduced upon Rac1b overexpression, the levels of their respective transcripts remained unchanged. Importantly, the co-expression of Rac1b with B-Raf-V600E reverted the OIS phenotype, reducing the expression levels of the cell-cycle inhibitors and β-galactosidase to those of control cells. These data identify increased Rac1b expression as one potential mechanism by which colorectal tumor cells can escape from B-Raf-induced OIS.