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Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues: implications for epigenetic reprogramming.
Morgan HD, Dean W, Coker HA, Reik W, Petersen-Mahrt SK
DNA deaminases of the Aid/Apobec family convert cytosine into uracil and play key roles in acquired and innate immunity. The epigenetic modification by methylation of cytosine in CpG dinucleotides is also mutagenic, but this is thought to occur by spontaneous deamination. Here we show that Aid and Apobec1 are 5-methylcytosine deaminases resulting in a thymine base opposite a guanine. Their action can thus lead to C --> T transition mutations in methylated DNA, or in conjunction with repair of the T:G mismatch, to demethylation. The Aid and Apobec1 genes are located in a cluster of pluripotency genes including Nanog and Stella and are co-expressed with these genes in oocytes, embryonic germ cells, and embryonic stem cells. These results suggest that Aid and perhaps some of its family members may have roles in epigenetic reprogramming and cell plasticity. Transition in CpG dinucleotides is the most frequent mutation in human genetic diseases, and sequence context analysis of CpG transitions in the APC tumor suppressor gene suggests that DNA deaminases may play a significant role in tumor etiology.
Active genes dynamically colocalize to shared sites of ongoing transcription.
CS Osborne, L Chakalova, KE Brown, D Carter, A Horton, E Debrand, B Goyenechea, JA Mitchell, S Lopes, W Reik, P Fraser
The intranuclear position of many genes has been correlated with their activity state, suggesting that migration to functional subcompartments may influence gene expression. Indeed, nascent RNA production and RNA polymerase II seem to be localized into discrete foci or 'transcription factories'. Current estimates from cultured cells indicate that multiple genes could occupy the same factory, although this has not yet been observed. Here we show that, during transcription in vivo, distal genes colocalize to the same transcription factory at high frequencies. Active genes are dynamically organized into shared nuclear subcompartments, and movement into or out of these factories results in activation or abatement of transcription. Thus, rather than recruiting and assembling transcription complexes, active genes migrate to preassembled transcription sites.
Early intermediates of mariner transposition: catalysis without synapsis of the transposon ends suggests a novel architecture of the synaptic complex.
K Lipkow, N Buisine, DJ Lampe, R Chalmers
The mariner family is probably the most widely distributed family of transposons in nature. Although these transposons are related to the well-studied bacterial insertion elements, there is evidence for major differences in their reaction mechanisms. We report the identification and characterization of complexes that contain the Himar1 transposase bound to a single transposon end. Titrations and mixing experiments with the native transposase and transposase fusions suggested that they contain different numbers of transposase monomers. However, the DNA protection footprints of the two most abundant single-end complexes are identical. This indicates that some transposase monomers may be bound to the transposon end solely by protein-protein interactions. This would mean that the Himar1 transposase can dimerize independently of the second transposon end and that the architecture of the synaptic complex has more in common with V(D)J recombination than with bacterial insertion elements. Like V(D)J recombination and in contrast to the case for bacterial elements, Himar1 catalysis does not appear to depend on synapsis of the transposon ends, and the single-end complexes are active for nicking and probably for cleavage. We discuss the role of this single-end activity in generating the mutations that inactivate the vast majority of mariner elements in eukaryotes.
Promiscuous target interactions in the mariner transposon Himar1.
K Lipkow, N Buisine, R Chalmers
We have previously characterized the early intermediates of mariner transposition. Here we characterize the target interactions that occur later in the reaction. We find that, in contrast to the early transposition intermediates, the strand transfer complex is extremely stable and difficult to disassemble. Transposase is tightly bound to the transposon ends constraining rotation of the DNA at the single strand gaps in the target site flanking the element on either side. We also find that although the cleavage step requires Mg2+ or Mn2+ as cofactor, the strand transfer step is also supported by Ca2+, suggesting that the structure of the active site changes between cleavage and insertion. Finally, we show that, in contrast to the bacterial cut and paste transposons, mariner target interactions are promiscuous and can take place either before or after cleavage of the flanking DNA. This is similar to the behavior of the V(D)J system, which is believed to be derived from an ancestral eukaryotic transposon. We discuss the implications of promiscuous target interactions for promoting local transposition and whether this is an adaptation to facilitate the invasion of a genome following horizontal transfer to a new host species.
Vav-dependent and vav-independent phosphatidylinositol 3-kinase activation in murine B cells determined by the nature of the stimulus.
Vigorito E, Bardi G, Glassford J, Lam EW, Clayton E, Turner M
We show in this study that B cell activation following high avidity ligation of IgM or coligation of membrane Ig with CD19 elicits similar levels of Ca(2+) flux using different mechanisms. Each form of activation requires the function of Vav and PI3K. However, Vav regulates Ca(2+) flux independently of PI3K following anti-IgM cross-linking. By contrast, Vav function is essential for PI3K activation following membrane Ig (mIg)/CD19 coligation. Inhibition of PI3K revealed anti-IgM-stimulated Ca(2+) flux has a PI3K-independent component, while Ca(2+) flux following mIg/CD19 coligation is totally PI3K dependent. The p85alpha and p110delta subunits of PI3K both participate in anti-IgM and mIg/CD19 coligation-induced Ca(2+) flux, although the defects are not as severe as observed after pharmacological inhibition. This may reflect the recruitment of additional PI3K subunits, as we found that p110alpha becomes associated with CD19 upon B cell activation. These data show that the nature of the Ag encountered by B cells determines the contribution of Vav proteins to PI3K activation. Our results indicate that the strong signals delivered by multivalent cross-linking agents activate B cells in a qualitatively different manner from those triggered by coreceptor recruitment.
Sphingosine kinase 1 is an intracellular effector of phosphatidic acid.
C Delon, M Manifava, E Wood, D Thompson, S Krugmann, S Pyne, NT Ktistakis
Sphingosine kinase 1 (SK1) phosphorylates sphingosine to generate sphingosine 1-phosphate (S1P). Because both substrate and product of the enzyme are potentially important signaling molecules, the regulation of SK1 is of considerable interest. We report that SK1, which is ordinarily a cytosolic enzyme, translocates in vivo and in vitro to membrane compartments enriched in phosphatidic acid (PA), the lipid product of phospholipase D. This translocation depends on direct interaction of SK1 with PA, because recombinant purified enzyme shows strong affinity for pure PA coupled to Affi-Gel. The SK1-PA interaction maps to the C terminus of SK1 and is independent of catalytic activity or of the diacylglycerol kinase-like domain of the enzyme. Thus SK1 constitutes a novel, physiologically relevant PA effector.
Radiation-induced malignancies following radiotherapy for breast cancer.
Roychoudhuri R,Evans H,Robinson D,Moller H
With advances in diagnosis and treatment, breast cancer is becoming an increasingly survivable disease resulting in a large population of long-term survivors. Factors affecting the quality of life of such patients include the consequences of breast cancer treatment, which may have involved radiotherapy. In this study, we compare the incidence of second primary cancers in women who received breast radiotherapy with that in those who did not (non-radiotherapy). All women studied received surgery for their first breast cancer. Second cancers of the lung, colon, oesophagus and thyroid gland, malignant melanomas, myeloid leukaemias and second primary breast cancers were studied. Comparing radiotherapy and non-radiotherapy cohorts, elevated relative risks (RR) were observed for lung cancer at 10-14 years and 15 or more (15+) years after initial breast cancer diagnosis (RR 1.62, 95% confidence interval [CI] 1.05-2.54 and RR 1.49, 95% CI 1.05-2.14, respectively), and for myeloid leukaemia at 1-5 years (RR 2.99, 95% CI 1.13-9.33), for second breast cancer at 5-10 years (RR 1.34, 95% CI 1.10-1.63) and 15+ years (RR 1.26, 95% CI 1.00-1.59) and oesophageal cancer at 15+ years (RR 2.19, 95% CI 1.10-4.62).
British journal of cancer , 2004
Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM.
Ma D, Shield JP, Dean W, Leclerc I, Knauf C, Burcelin R Ré, Rutter GA, Kelsey G
Transient neonatal diabetes mellitus (TNDM) is a rare inherited diabetic syndrome apparent in the first weeks of life and again during early adulthood. The relative contributions of reduced islet beta cell number and impaired beta cell function to the observed hypoinsulinemia are unclear. The inheritance pattern of this imprinted disorder implicates overexpression of one or both genes within the TNDM locus: ZAC, which encodes a proapoptotic zinc finger protein, and HYMAI, which encodes an untranslated mRNA. To investigate the consequences for pancreatic function, we have developed a high-copy transgenic mouse line, TNDM29, carrying the human TNDM locus. TNDM29 neonates display hyperglycemia, and older adults, impaired glucose tolerance. Neonatal hyperglycemia occurs only on paternal transmission, analogous to paternal dependence of TNDM in humans. Embryonic pancreata of TNDM29 mice showed reductions in expression of endocrine differentiation factors and numbers of insulin-staining structures. By contrast, beta cell mass was normal or elevated at all postnatal stages, whereas pancreatic insulin content in neonates and peak serum insulin levels after glucose infusion in adults were reduced. Expression of human ZAC and HYMAI in these transgenic mice thus recapitulates key features of TNDM and implicates impaired development of the endocrine pancreas and beta cell function in disease pathogenesis.
The Journal of clinical investigation , 2004
Interaction between differentially methylated regions partitions the imprinted genes Igf2 and H19 into parent-specific chromatin loops.
Murrell A, Heeson S, Reik W
Imprinted genes are expressed from only one of the parental alleles and are marked epigenetically by DNA methylation and histone modifications. The paternally expressed gene insulin-like growth-factor 2 (Igf2) is separated by approximately 100 kb from the maternally expressed noncoding gene H19 on mouse distal chromosome 7. Differentially methylated regions in Igf2 and H19 contain chromatin boundaries, silencers and activators and regulate the reciprocal expression of the two genes in a methylation-sensitive manner by allowing them exclusive access to a shared set of enhancers. Various chromatin models have been proposed that separate Igf2 and H19 into active and silent domains. Here we used a GAL4 knock-in approach as well as the chromosome conformation capture technique to show that the differentially methylated regions in the imprinted genes Igf2 and H19 interact in mice. These interactions are epigenetically regulated and partition maternal and paternal chromatin into distinct loops. This generates a simple epigenetic switch for Igf2 through which it moves between an active and a silent chromatin domain.
The imprinted signaling protein XL alpha s is required for postnatal adaptation to feeding.
Plagge A, Gordon E, Dean W, Boiani R, Cinti S, Peters J, Kelsey G
Genomic imprinting, by which maternal and paternal alleles of some genes have different levels of activity, has profound effects on growth and development of the mammalian fetus. The action of imprinted genes after birth, in particular while the infant is dependent on maternal provision of nutrients, is far less well understood. We disrupted a paternally expressed transcript at the Gnas locus, Gnasxl, which encodes the unusual Gs alpha isoform XL alpha s. Mice with mutations in Gnasxl have poor postnatal growth and survival and a spectrum of phenotypic effects that indicate that XL alpha s controls a number of key postnatal physiological adaptations, including suckling, blood glucose and energy homeostasis. Increased cAMP levels in brown adipose tissue of Gnasxl mutants and phenotypic comparison with Gnas mutants suggest that XL alpha s can antagonize Gs alpha-dependent signaling pathways. The opposing effects of maternally and paternally expressed products of the Gnas locus provide tangible molecular support for the parental-conflict hypothesis of imprinting.
PLCgamma2 regulates Bcl-2 levels and is required for survival rather than differentiation of marginal zone and follicular B cells.
Bell SE, Vigorito E, McAdam S, Reynolds HM, Caraux A, Colucci F, Turner M
B cells from phospholipase C (PLC)gamma2-deficient mice express reduced levels of the pro-survival protein Bcl-2 and show a defect in the development of transitional T3 and marginal zone (MZ) B cells that reflects reduced B cell survival. Introduction of a bcl-2 transgene restored the numbers of MZ, T3 and follicular B cells in PLCgamma2(-/-) mice. Restricting the B cell repertoire in PLCgamma2-deficient mice by the introduction of a BCR transgene resulted in a striking reduction in the number of IgM-positive B cells and a paucity of IgD-expressing cells in the spleen which was also rescued by the bcl-2 transgene. BCR-stimulated ERK and IkappaBalpha phosphorylation were PLCgamma2 dependent, while calcium flux was reduced, but not abrogated, in the absence of PLCgamma2, suggesting an ancillary role for PLCgamma1. The bcl-2 transgene rescued development of PLCgamma2(-/-) B cells and serum IgM levels but did not restore BCR-mediated signaling, proliferation or serum IgG3 levels. These data suggest that PLCgamma2 performs a critical role in B cell development through regulation of survival rather than differentiation.
Macrophage release of transforming growth factor beta1 during resolution of monosodium urate monohydrate crystal-induced inflammation.
DR Yagnik, BJ Evans, O Florey, JC Mason, RC Landis, DO Haskard
It has previously been shown that as monocytes differentiate into macrophages, they lose the ability to secrete proinflammatory cytokines in response to monosodium urate monohydrate (MSU) crystals. The purpose of this study was to investigate whether MSU crystals induce macrophages to secrete antiinflammatory factor instead.
Arthritis and rheumatism , 2004
Identification and properties of imprinted genes and their control elements.
Smith RJ, Arnaud P, Kelsey G
Imprinted genes have the unusual characteristic that the copy from one parent is destined to remain inactive. Though few in number they nonetheless constitute a functionally important part of the mammalian genome. With their memory of parental origin, imprinted genes represent an important model for the epigenetic regulation of gene function and will provide invaluable paradigms to test whether we can predict epigenetic state from DNA sequence. Since their first discovery, systematic screens and some good fortune have led to identification of over seventy imprinted genes in the mouse and human: recent microarray analysis may reveal many more. With a significant number of imprinted genes now identified and completion of key mammalian genome sequences, we are able systematically to examine the organization of imprinted loci, properties of their control elements and begin to recognize common themes in imprinted gene regulation.
Cytogenetic and genome research , 2004
Genetic and genomic approaches to study placental development.
Hemberger M, Zechner U
Recent technological advances in genetic manipulation and expression profiling offer excellent opportunities to elucidate the molecular mechanisms controlling developmental processes during embryogenesis. Thus, this revolution also strongly benefits studies of the molecular genetics of placental development. Here we review the findings of several expression profiling analyses in extraembryonic tissues and assess how this work can contribute to the identification of essential components governing placental development. We further discuss the relevance of these components in the context of genetic manipulation experiments. In conclusion, the intelligent combination of genetic and genomic approaches will substantially accelerate the progress in identifying the key molecular pathways of placental development.
Trophoblast stem cells differentiate in vitro into invasive trophoblast giant cells.
Hemberger M, Hughes M, Cross JC
Trophoblast cells are characterized by an invasive behavior into the surrounding uterine tissue. In rodents, an early peri-/endovascular type of invasion exerted by trophoblast giant cells can be distinguished from a late interstitial type carried out by glycogen trophoblast cells. Analysis of the molecular mechanisms of trophoblast invasion has been hampered, however, by the complex temporal and spatial patterns of invasion. We utilized trophoblast stem (TS) cell lines to study trophoblast invasion in vitro and to establish a model that facilitates investigation of this process on the molecular level. Our results showed that trophoblast giant cells that differentiate from TS cells in vitro are capable of penetrating a reconstituted basement membrane matrix. Consequently, invasion rates were increased in various giant cell differentiation-promoting conditions. We also derived TS cell lines that are homozygous for a mutation of the Hand1 transcription factor. The Hand1-/- TS cells showed reduced levels of giant cell differentiation and exhibited an approximately 50% decrease in invasion rates. In summary, trophoblast giant cells that differentiate from TS cells in vitro recapitulate the invasive capacity of normal trophoblast cells in vivo. The TS cell system is a valuable tool to identify and quantitatively study regulators of trophoblast invasion.
Tandem repeat hypothesis in imprinting: deletion of a conserved direct repeat element upstream of H19 has no effect on imprinting in the Igf2-H19 region.
Lewis A, Mitsuya K, Constancia M, Reik W
Igf2 and H19 are reciprocally imprinted genes on mouse distal chromosome 7. They share several regulatory elements, including a differentially methylated region (DMR) upstream of H19 that is paternally methylated throughout development. The cis-acting sequence requirements for targeting DNA methylation to the DMR remain unknown; however, it has been suggested that direct tandem repeats near DMRs could be involved. Previous studies of the imprinted Rasgrf1 locus demonstrate indeed that a direct repeat element adjacent to a DMR is responsible for establishing paternal allele-specific methylation at the DMR and therefore allelic expression of the Rasgrf1 transcript. We identified a prominent and conserved direct tandem repeat 1 kb upstream of the H19 DMR and proposed that it played a similar role in imprinted regulation of H19. To test our hypothesis, we generated mice harboring a 1.7-kb targeted deletion of the direct repeat element and analyzed fetal growth, allelic expression, and methylation within the Igf2-H19 region. Surprisingly the deletion had no effect on imprinting. These results together with deletions of other repeats close to imprinted genes suggest that direct repeats may not be important for the targeting of methylation at the majority of imprinted loci and that the Rasgrf1 locus may be an exception to this rule.
Mutagenesis of the ezrin-radixin-moesin binding domain of L-selectin tail affects shedding, microvillar positioning, and leukocyte tethering.
A Ivetic, O Florey, J Deka, DO Haskard, A Ager, AJ Ridley
L-selectin is a cell adhesion molecule that mediates the initial capture (tethering) and subsequent rolling of leukocytes along ligands expressed on endothelial cells. We have previously identified ezrin and moesin as novel binding partners of the 17-amino acid L-selectin tail, but the biological role of this interaction is not known. Here we identify two basic amino acid residues within the L-selectin tail that are required for binding to ezrin-radixinmoesin (ERM) proteins: arginine 357 and lysine 362. L-selectin mutants defective for ERM binding show reduced localization to microvilli and decreased phorbol 12-myristate 13-acetate-induced shedding of the L-selectin ectodomain. Cells expressing these L-selectin mutants have reduced tethering to the L-selectin ligand P-selectin glycoprotein ligand-1, but rolling velocity on P-selectin glycoprotein ligand-1 is not affected. These results suggest that ERM proteins are required for microvillar positioning of L-selectin and that this is important both for leukocyte tethering and L-selectin shedding.
Placental-specific insulin-like growth factor 2 (Igf2) regulates the diffusional exchange characteristics of the mouse placenta.
Sibley CP, Coan PM, Ferguson-Smith AC, Dean W, Hughes J, Smith P, Reik W, Burton GJ, Fowden AL, Constância M
Restricted fetal growth is associated with postnatal mortality and morbidity and may be directly related to alterations in the capacity of the placenta to supply nutrients. We proposed previously that imprinted genes can regulate nutrient supply by the placenta. Here, we tested the hypothesis that the insulin-like growth factor 2 gene (Igf2) transcribed from the placental-specific promoter (P0) regulates the development of the diffusional permeability properties of the mouse placenta. Using mice in which placental-specific Igf2 had been deleted (P0), we measured the transfer in vivo of three inert hydrophilic solutes of increasing size (14C-mannitol, 51CrEDTA, and 14C-inulin). At embryonic day 19, placental and fetal weights in P0 conceptuses were reduced to 66% and 76%, respectively, of wild type. In P0 mutants, the permeability.surface area product for the tracers at this stage of development was 68% of that of controls; this effect was independent of tracer size. Stereological analysis of histological sections revealed the surface area of the exchange barrier in the labyrinth of the mouse placenta to be reduced and thickness increased in P0 fetuses compared to wild type. As a result, the average theoretical diffusing capacity in P0 knockout placentas was dramatically reduced to 40% of that of wild-type placentas. These data show that placental Igf2 regulates the development of the diffusional exchange characteristics of the mouse placenta. This provides a mechanism for the role of imprinted genes in controlling placental nutrient supply and fetal growth. Altered placental Igf2 could be a cause of idiopathic intrauterine growth restriction in the human.
Proceedings of the National Academy of Sciences of the United States of America , 2004
Antisense intergenic transcription in V(D)J recombination.
DJ Bolland, AL Wood, CM Johnston, SF Bunting, G Morgan, L Chakalova, PJ Fraser, AE Corcoran
Antigen receptor genes undergo variable, diversity and joining (V(D)J) recombination, which requires ordered large-scale chromatin remodeling. Here we show that antisense transcription, both genic and intergenic, occurs extensively in the V region of the immunoglobulin heavy chain locus. RNA fluorescence in situ hybridization demonstrates antisense transcription is strictly developmentally regulated and is initiated during the transition from DJ(H) to VDJ(H) recombination and terminates concomitantly with VDJ(H) recombination. Our data show antisense transcription is specific to the V region and suggest transcripts extend across several genes. We propose that antisense transcription remodels the V region to facilitate V(H)-to-DJ(H) recombination. These findings have wider implications for V(D)J recombination of other antigen receptor loci and developmental regulation of multigene loci.
Nature immunology , 2004
Germline stem cell number in the Drosophila ovary is regulated by redundant mechanisms that control Dpp signaling.
MO Casanueva, EL Ferguson
The available experimental data support the hypothesis that the cap cells (CpCs) at the anterior tip of the germarium form an environmental niche for germline stem cells (GSCs) of the Drosophila ovary. Each GSC undergoes an asymmetric self-renewal division that gives rise to both a GSC, which remains associated with the CpCs, and a more posterior located cystoblast (CB). The CB upregulates expression of the novel gene, bag of marbles (bam), which is necessary for germline differentiation. Decapentaplegic (Dpp), a BMP2/4 homologue, has been postulated to act as a highly localized niche signal that maintains a GSC fate solely by repressing bam transcription. Here, we further examine the role of Dpp in GSC maintenance. In contrast to the above model, we find that an enhancer trap inserted near the Dpp target gene, Daughters against Dpp (Dad), is expressed in additional somatic cells within the germarium, suggesting that Dpp protein may be distributed throughout the anterior germarium. However, Dad-lacZ expression within the germline is present only in GSCs and to a lower level in CBs, suggesting there are mechanisms that actively restrict Dpp signaling in germ cells. We demonstrate that one function of Bam is to block Dpp signaling downstream of Dpp receptor activation, thus establishing the existence of a negative feedback loop between the action of the two genes. Moreover, in females doubly mutant for bam and the ubiquitin protein ligase Smurf, the number of germ cells responsive to Dpp is greatly increased relative to the number observed in either single mutant. These data indicate that there are multiple, genetically redundant mechanisms that act within the germline to downregulate Dpp signaling in the Cb and its descendants, and raise the possibility that a Cb and its descendants must become refractory to Dpp signaling in order for germline differentiation to occur.
Development (Cambridge, England) , 2004
Phospholipase D.
McDermott M, Wakelam MJ, Morris AJ
Phospholipase D catalyses the hydrolysis of the phosphodiester bond of glycerophospholipids to generate phosphatidic acid and a free headgroup. Phospholipase D activities have been detected in simple to complex organisms from viruses and bacteria to yeast, plants, and mammals. Although enzymes with broader selectivity are found in some of the lower organisms, the plant, yeast, and mammalian enzymes are selective for phosphatidylcholine. The two mammalian phospholipase D isoforms are regulated by protein kinases and GTP binding proteins of the ADP-ribosylation and Rho families. Mammalian and yeast phospholipases D are also potently stimulated by phosphatidylinositol 4,5-bisphosphate. This review discusses the identification, characterization, structure, and regulation of phospholipase D. Genetic and pharmacological approaches implicate phospholipase D in a diverse range of cellular processes that include receptor signaling, control of intracellular membrane transport, and reorganization of the actin cytoskeleton. Most ideas about phospholipase D function consider that the phosphatidic acid product is an intracellular lipid messenger. Candidate targets for phospholipase-D-generated phosphatidic acid include phosphatidylinositol 4-phosphate 5-kinases and the raf protein kinase. Phosphatidic acid can also be converted to two other lipid mediators, diacylglycerol and lyso phosphatidic acid. Coordinated activation of these phospholipase-D-dependent pathways likely accounts for the pleitropic roles for these enzymes in many aspects of cell regulation.
Biochemistry and cell biology = Biochimie et biologie cellulaire , 2004
The tyrosine kinase Syk is required for light chain isotype exclusion but dispensable for the negative selection of B cells.
Meade J, Tybulewicz VL, Turner M
In this study we set out to test whether Syk was required for negative selection of immature B cells. B cells expressing a B cell antigen receptor (BCR) transgene (3-83, anti-H-2K(k)) underwent negative selection independently of Syk in both fetal liver organ culture and radiation chimera models. Furthermore, Syk-independent negative selection was not reversed by transgenic overexpression of Bcl-2. Receptor editing was not apparent in Syk-deficient B cells, presumably as a consequence of the failure of mature edited B cells to develop in the absence of Syk. Interestingly, light chain isotype exclusion by the BCR transgene failed in the absence of Syk. We observed a dramatic reduction in the overall BCR-mediated tyrosine phosphorylation of cellular proteins in Syk-deficient immature B cells. However, the tyrosine phosphorylation of a number of substrates including phospholipase C gamma 2, although reduced, was not completely abrogated. BCR ligation triggered an increase in calcium flux in the absence of Syk. Thus signaling events that mediate negative selection can still occur in the absence of Syk. This may be due to redundancy with zeta-associated protein 70 (ZAP-70), which we demonstrate to be expressed in immature B cells.
Divergent genetic and epigenetic post-zygotic isolation mechanisms in Mus and Peromyscus.
Zechner U, Shi W, Hemberger M, Himmelbauer H, Otto S, Orth A, Kalscheuer V, Fischer U, Elango R, Reis A, Vogel W, Ropers H, Rüschendorf F, Fundele R
Interspecific hybridization in the rodent genera Peromyscus and Mus results in abnormal placentation. In the Peromyscus interspecies hybrids, abnormal allelic interaction between an X-linked locus and the imprinted paternally expressed Peg3 locus was shown to cause the placental defects. In addition, loss-of-imprinting (LOI) of Peg3 was positively correlated with increased placental size. As in extreme cases this placental dysplasia constitutes a post-zygotic barrier against interspecies hybridization, this finding was the first direct proof that imprinted genes may be important in speciation and thus in evolution. In the Mus interspecies hybrids, a strong role of an X-linked locus in placental dysplasia has also been detected. However, here we show by backcross and allele specific expression analyses that neither LOI of Peg3 nor abnormal interactions between Peg3 and an X-linked locus are involved in generating placental dysplasia in Mus hybrids, although the placental phenotypes observed in the two genera seem to be identical. In contrast to this, another dysgenesis effect common to Peromyscus and Mus hybrids, altered foetal growth, is caused at least in part by the same X-chromosomal regions in both genera. These findings first underline the strong involvement of the X-chromosome in the genetics of speciation. Secondly, they indicate that disruption of epigenetic states, such as LOI, at specific loci may be involved in hybrid dysgenesis effects in one group, but not in another. Thus, we conclude that even in closely related groups divergent molecular mechanisms may be involved in the production of phenotypically similar post-zygotic barriers against hybridization.
Journal of evolutionary biology , 2004
The activation of G-protein gated inwardly rectifying K+ channels by a cloned Drosophila melanogaster neuropeptide F-like receptor.
V Reale, HM Chatwin, PD Evans
A Drosophila melanogaster G-protein-coupled receptor (NPFR76F) that is activated by neuropeptide F-like peptides has been expressed in Xenopus oocytes to determine its ability to regulate heterologously expressed G-protein-coupled inwardly rectifying potassium channels. The activated receptor produced inwardly rectifying potassium currents by a pertussis toxin-sensitive G-protein-mediated pathway and the effects were reduced in the presence of proteins, such as the betaARK 1 carboxy-tail fragment and alpha-transducin, which bind G-protein betagamma-subunits. Short Drosophila NPF-like peptides were more potent than long NPF-like peptides at coupling the receptor to the activation of inwardly rectifying potassium channels. The putative endogenous short Drosophila NPF-like peptides showed agonist-specific coupling depending on whether their actions were assessed as the activation of the inwardly rectifying potassium channels or as the activation of endogenous inward chloride channels through a co-expressed promiscuous G-protein, Galpha16. As inwardly rectifying potassium channels are known to be encoded in the Drosophila genome and the NPFR76F receptor is widely expressed in the Drosophila nervous system, the receptor could function to control neuronal excitability or slow wave potential generation in the Drosophila nervous system.


The National Union of Metalworkers of South Africa (Numsa) will no longer be embarking on a planned national strike against Comair after the parties held talks at dispute resolution body, the Commission for Conciliation, Mediation and Arbitration.
Numsa, in a statement, said the two sides would continue talks in early January over wages and shift patterns.
Comair said it was "delighted to confirm" that the potential strike by Numsa-affiliated ground staff had been averted.
"While Comair respects the right of employees to strike, we are pleased that we have made sufficient progress on outstanding matters. We look forward to the next meeting with the CCMA scheduled for the Friday, 11 January 2019, where salary increases will be discussed.


Alchemize Limited operates nationwide providing hazardous waste management and environmental services to a variety of sectors in industry (cosmetics, chemical and pharmaceutical manufacturers, transport and distribution), as well as local authorities and schools.
The safe disposal of hazardous waste and compliance with environmental regulations represent an onerous task for any organisation. At Alchemize, we have 30 years of industry experience and the necessary resources to ensure environmental and legislative obligations are met, delivering excellence as standard throughout the process. Consequently, Alchemize enjoys a high NPS rating, most of our customers have been with us since the beginning, in 2002.
Founded in 2002, Alchemize aims to deliver an efficient, rapid response to clients' needs, striving at the same time to contribute to a greener environment. Alchemize is committed to sustainability, and is a member of the UKBCSD, and an investor in the Essex Wildlife Trust.


2011-2012 Did Economic Reforms Cause China's Rapid Economic Growth and Increase Inequity?
2007-2008 Insurgencies, Counterinsurgencies, and Civil Military Relations: When, How, and Why Do Civilians Prevail?
Roberto Exequie Nunez Rivera, Rev.


Isabella Oliver launched in 2003 and will be celebrating their 10 year anniversary this October 2013. Baukjen de Swaan Arons is the Co-Founder and Creative Director of Isabella Oliver. The company originally started with three co-founders, but in the past years, it has been Baukjen and her husband, Geoff. Offering maternity styles best described as modern, chic and effortless, Isabella Oliver has forever redefined the term "maternity wear." Freeing pregnant women from frumpy, outdated and oversized maternity clothes, their tagline of "Same Woman-New Curves" is really their design and brand philosophy. The collections keep pregnancy styles simple and sleek as their designs are flattering and contemporary with pieces that will last throughout every stage of pregnancy and beyond. Isabella Oliver is unique from other lines because of their branded look using their signature techniques of wrap, ruche and drape detailing to create iconic pieces that are instantly recognizable. These clever techniques combined with excellent quality means that their designs offer a flattering fit at every stage and even look great post pregnancy.
Baukjen was inspired to launch Isabella Oliver when she was pregnant with her first child and found it difficult to find maternity wear that reflected her style and flattered her pregnancy curves. "I was inspired to change this and offer a solution for women who wanted to look and feel good about themselves at this special time. "So in 2003, we launched our first maternity collection and haven't looked back since," she shares. Creativity runs in her blood as Baukjen grew up in a family packed with stylists, fashion photographers and more. She was surrounded by lots of creative people right from the start and has always loved the energy of the creative industries. Baukjen adds, "Working in the fashion industry is really just a home away from home." She graduated from the University in Holland with a BA and MBA in Business Economics. Her father was a professor in Holland at the time and she wanted to enjoy a few years there. Baukjen also met her husband and co-founder, Geoff, in Holland.
One of their signature designs and most popular items is the Ruched Maternity Wrap Top, which looks fabulous on anyone before, during and after pregnancy. This top is crafted with the company's technique of wrapping and ruching, perfect with jeans and heels or a skirt. Easy to wear as you just wrap the long waist ties around the tee and tie at the hip for an effortlessly stylish look. What we love about this fashionable top is that it grows with you, making it a sophisticated option at every stage as it works particularly well during pregnancy, nursing and post pregnancy. Isabella Oliver is a staple among pregnant celebrities, including Natalie Portman, Angelina Jolie, Gwen Stefani, Jennifer Garner, Jennifer Lopez to mention a few. As for designs, Isabella Oliver has core styles which they carry forward through seasons because they are loved staples of customers. The company introduces and adds new colors to these styles each season while adding new styles through its continuing need for creativity. The demand from their customers varies each season and the brand strives to accommodate every need from season to season.
Baukjen says, "It is important that our customers see us as a resource, where they can be inspired or pick up styling advice, which is why we created Isabella Oliver World." Isabella Oliver World offers a unique online destination where pregnant women can read about features, watch videos and learn how to create a pregnancy wardrobe that they will love to wear. Baukjen's own personal favorites from the Isabella Oliver collection are pieces from the dress department. For everyday casual chic, she enjoys the Betty Loose Stripe Dress, which can be worn with or without a belt or over leggings. If you are looking for color and something that pops, Baukejn likes how the Vivien Print T Shirt Dress fits and its fun graphic print. Special occasions call for something a bit more extravagant and since the options for formal maternity wear are slim, every woman should consider the Marie Sequin Dress. Chic, modern and easy to wear, this take on sequins in a rich luxe hue of bronzed khaki is perfect for summer days and nights.
The company starts sourcing fabrics from around the world 14 months before a collection launches. Baukjen shares, "How a garment feels in your hand is very important, as are the colors they come in. But the deciding factor is the quality to ensure they last under intensive wear." Fabric is of utmost importance since they look at how it will feel on the skin, how it fits on the body and how it wears and washes over time. If the fabric does not tick all the boxes, they do not work with it. "For pregnant women, luxe jersey is a wonderful fabric as it grows with you and flatters your curves," Baukjen adds. Using their signature techniques of wrap, ruche, drape and tie detailing, Isabella Oliver creates pieces that perfectly fit around a woman's new curves. Their collections feature lots of different jerseys – there's something for everyone as they want women to feel like themselves – Same woman. New curves.
Another staple we want to highlight is the Maternity Wrap Dress, an iconic adjustable maternity wrap dress designed in Isabella Oliver easy care signature jersey for chic style, day or night. This fitted dress is flattering and an essential as it skims curves, offering comfort and style at every stage, during pregnancy, nursing and post pregnancy. Baukjen and her co-founders named the line Isabella Oliver after the first born children of the original founders. Her firstborn is Oliver. When it comes to ideas for their designs and collections, London is their runway of inspiration, not just for fashion but exhibitions as well. There is always so much going on in the city that they are never short of inspiration. Bauken has been inspired by fashion designers such as Celine, Chloe, Stella McCartney and others. They begin with sketching up many design ideas from their inspirations and then put them through a rigorous edit where they select the styles that will look great at 4 months and also 9 months at pregnancy. "Our main objective is to create styles that are both contemporary as well as flattering to your new curves," Baukjen says.
Baukjen has traveled far, but she loves her birthplace, Amsterdam. She enjoys cycling from one place to the next there for the beauty of it as well as the food and her endless cousins that hold a special place in her heart. She also likes New York and Paris. In her spare time, Baukjen enjoys travelling, evenings with friends, and spending time with her kids. Their collection has grown a lot over the years and they still continue to develop it by adding more product groups, such as loungewear, footwear and jewelry. In doing this, women can create their whole look as Isabella Oliver also offers styling advice. Baukjen cares about what her customers want and says, "We ask our customers for feedback on a regular basis and I love to hear what they say as it helps steer our direction." Her hope for the future is to dress more and more women around the world in Isabella Oliver. Isabella Oliver is sold at Pea in a Pod and will soon be available on ASOS, Galeries Lafayette and Fenwicks.


All Lads and Lasses of TRUE WELSH BLOOD willing to show their loyally and spirit may repair to CAERNARFON CASTLE on 20th and 21st April, 2019 where they will receive soldier-like entertainment at the ROYAL WELCH FUSILIERS MUSEUM.
The Museum is housed in two towers of Caernarfon Castle. In it you will find a wealth of original exhibits, supported by film, sound and models, which tell the story of over 300 years of service by Wales' oldest infantry regiment, in peacetime and in war, all around the world.
You can learn how the Regiment won 14 Victoria Crosses and hear the words of the famous writers who served with the Royal Welch during the First World War - Siegfried Sassoon, Robert Graves, 'Hedd Wyn', David Jones and Frank Richards. You will see what life was like for the ordinary soldier and his family and discover the Regiment's unique traditions.
Royal Welch history begins with the campaigns of William III, and includes Marlborough's wars, the American War of Independence, the wars with Revolutionary and Napoleonic France, the Crimean War, the Boer War and China. Many battalions of the Regiment saw action in the First and Second World Wars. In peacetime the Royal Welch has provided garrison troops in Canada, India, Hong Kong and the West Indies.
On the 1st March 2006 the two line Welsh Infantry regiments combined to form a new regiment - The Royal Welsh. Between 2006 and 2014 the title of the Royal Welch Fusiliers was retained as 1st Battalion Royal Welsh (The Royal Welch Fusiliers). With further defence cuts in 2014 the 1st and 2nd Battalions were combined to form the 1st Battalion, The Royal Welsh (23rd/24th/41st of Foot). The values, traditions and heritage of the Royal Welch Fusiliers are now preserved in the regular 1st Battalion, The Royal Welsh and the Reserve 3rd Battalion, The Royal Welsh.
The RWF Museum Trust has a long-term partnership with Wrexham County Borough Council. They manage on our behalf the extensive RWF Archive & RWF Museum Reserve Collection at Wrexham Museum & Archives, Regent St, Wrexham LL111RB. Any family research queries should be initially directed to their RWF Enquiries Service at: localstudies@wrexham.gov.uk or Tel: 01978 297480 (A small fee may be incurred).
Please consider a donation to enable The Museum to continue honouring the soldiers of the Royal Welch Fusiliers.


Getting more bookings and increasing RevPAR (Revenue Per Available Room) is the real big deal for hotel owners. However, mproving your hotel's average occupancy is not a simple matter as several factors affect numbers and results.
A common misbelief is that one can sell more hotel rooms by just lowering their price . This is a big blunder that must be avoided at all costs. A full hotel doesn't necessarily mean more profits. By comparing the RevPAR, the ADR ( Average Daily Room Rate) and the Occupancy Rate is it possible to have an idea of what is really convenient for a hotel or a B&B owner or manager. For example, compromising for a 100% occupancy with a low ADR could bring down the revenues if compared to a lower occupancy with higher rates. So how can a hotel owner or manager improve effectively his/her hotel's occupancy and revenue?
Your guest history is precious. That's why you should use a reliable property management system (PMS) allowing you to collect data about your guests' habits and preferences.
This data is a precious resource allowing you to discover many key facts about your business like for example your average occupancy time by time throughout the year, the average length of stay of your guests, the type of travelers staying in your hotel etc. Thanks to this data you can understand when it's best to advertise your hotel, when special offers might be useful, what services you should offer to your guests and how your hotel's occupancy is affected by special events like conventions and business meetings.
Why should a traveler choose your hotel and not a hotel just a block away? This is a question you can answer only if you know very well what your competitive lanscape is and how you are positioned in it. This competitive landscape knowledge is crucial for you business' success because it allows you to understand how you can build a competitive advantage inside your market.
The term "competitive advantage" probably makes you think of downward pricing but in reality successful competitive advantages are built more on diversification and uniqueness of your business than on offering the lowest price on the market. In fact, lowering excessively your prices may harm your business so the most important thing to aim at for your business' success is giving your guests a clear and strong reason to choose you instead of the competition. This way you not only get more clients but you also get clients who care more about buying the stay experience you can offer them than about its price.
Nowadays more than 50% of travelers use reviews to choose their hotel. This is why you must focus on getting positive reviews from your hotel's guests.
To do so you must make sure that your staff is friendly and professional, that your hotel is clean and neat and that you underpromise and overdeliver with your guests. Moreover you must find ingenious ways to remind your guests of reviewing your hotel if they are happy of your services or of letting you know privately what they didn't like about the stay experience you offered them.
In case you get some negative reviews don't worry. It's something that no business can avoid but make sure you reply in a way that highlights your professionalism and show the world how much you care about constantly improving your business.
However, reviews are not more important than storytelling on social media about your business.
Building all the necessary social media profiles, keeping them active, interacting with your followers, replying promptly to private messages and publishing often nice videos and pictures are all important actions you can take to attract people's attention to your hotel.
Every day millions of users around the world use the internet to find and book their next hotel stay.
These users use mainly two channels to search for the hotel that best satisfies their accommodation needs: Online Travel Agencies (OTA's), like booking.com and expedia.com, and search engines, like Google and Bing. Each one of these channels have pros and cons.
OTA's on the one hand are very effective in marketing your hotel and bringing you new customers but on the other they will charge you lots of fees for this.
Search engines (SE's) on the one hand help you give visibility to your business' digital footprint for free but on the other require a lot of time and efforts spent on Search Engine Optimization (SEO) if your goal is ranking high on search engine result pages (SERP's).
The best thing to do if you want to maximize web bookings for your hotel is use OTA's and at the same time work steadily and consistently on your hotel's digital footprint's SEO.
Once you start ranking high and therefore attracting direct bookings on your hotel's website you can gradually decrease the number of rooms sold on OTA's.
Promoting your hotel's brand and experience is not an easy thing to do if you do it just by yourself.
The hospitality market's competition is stiff so it's a good idea to team up with other players offering services that are complementary to the ones offered by your business, build a solid and complete stay experience and cross-promote all the services of your alliance with them.
Just to mention some, good partners include airport transfer providers, sightseeing tour organizers, sports experiences providers etc. You will be surprised by the benefits you can get in terms of increased occupancy from a solid and efficient partner network.
Summing up what we wrote in this article, if you want to improve your hotel's occupancy and RevPAR you should learn as much as you can about your clients and your competitors, build a unique competitive advantage, make sure you build a good web reputation, build an active and attractive social media universe around your business, develop a strong presence on OTA's and SE's and, last but not least, develop a strong partner network.
The results you're dreaming for your business can become a reality if you work smart and hard so start setting goals and taking action now!


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Norzagaray è una municipalità di prima classe delle Filippine, situata nella Provincia di Bulacan, nella Regione del Luzon Centrale.

Norzagaray è formata da 13 baranggay:

Bangkal
Baraka
Bigte
Bitungol
Friendship Village Resources
Matictic
Minuyan
Partida
Pinagtulayan
Poblacion
San Lorenzo
San Mateo
Tigbe

Note

Altri progetti

Collegamenti esterni

Comuni della provincia di Bulacan

redpajama_set_name: RedPajamaWikipedia


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A New Mural in Trivandrum by Dr.Ajitkumar
(Dr.Ajitkumar and his mural in Trivandrum - all mural photo credit: Jayachandran Kadambanad)
If someone thinks that Thrissur is the heartland of 'Pulikali' (A hunting game enacted by people with their bodies painted like leopards and tigers, and are pursued by actors dressed up as hunters, accompanied by the drum beats), Thiruvananthapuram (Trivandrum), the capital city of Kerala now has got something to challenge such a notion, not in real terms but conceptually. A conceptual mural painted by Dr.Ajitkumar on the hundred feet long wall of the G.V.Raja Stadium (also known as the University Stadium) facing the Kerala's massive legislative assembly building is one of the new visual attractions in the city. The four lane road laid in two tiers creates a wide corridor between the G.V.Raja stadium on the one side and the Chandrasekharan Nair Stadium, Assembly building and the famous Hanuman Temple on the other side, leaving a capacious viewing space for the new mural.
(a view of the mural)
Dr.Ajitkumar, an artist, environmentalist, a champion of Euthanasia and an urban space specialist, with this yet to be titled mural adds one more feather to his artistic cap (Now I am informed that the mural is finally christened as 'LIBERTY BODICE'). During the last few years Ajitkumar has been involved in converting the city walls into large scale murals done by many well known artists in Kerala under a project called 'Arteria', an initiative by the Kerala Tourism Development Corporation. With artists like N.N.Rimzon, B.D.Dethan, late Asanthan, Sree Lal, Kanai Kunchiraman, Pradeep Puthoor and so on painting the walls with large scale works in their hallmark styles and images, the graffiti friendly city of Trivandrum has now achieved a different look. Though there are murals at the key walls in the city (including a thirty feet mural by K.G.Subramanyan), one cannot say that the residents of the city have really got the 'kick' of these mural for a major part of the viewers are constituted by a floating population that visits the city for some work or just passes through it. However, the curiosity in the eyes of the people as they pass by these murals gives some kind of an assurance that sooner than later the city will be wake up to its transforming skin features.
(detail of Ajitkumar's mural and Delacroix' Liberty Leading the People)
The latest mural of Ajitkumar has a strategic location and it comes as a part of the 'Clean City' program of Trivandrum Corporation, which in turn is a part of the Swatch Sarveshan Abhiyan of the Government of India. The mural has a hunting scene which emulates the famous 19th century French painting 'Liberty Leading the People' by Eugene Delacorix. In the Delacoix painting one could see a bare breasted Goddess of Liberty leading its people towards victory and liberty treading over a heap of dead bodies of the vanquished. The concept of Liberty as a woman slowly takes shape into the concept of nation as a woman/mother who could suckle her children in many a country including India. Ajitkumar adopts notion into his mural but gives it a different thrust.
(detail of the mural by Ajitkumar)
Here in this mural the protagonists are two people, a huge woman and a smaller man (which formally has a concurrence with the Delacroix painting though devoid of other accompanying figures) and she is about to vanquish a leopard that lies on its back with its four legs up in the air. The leopard's elongated shapely and stretched body covers almost the whole length of the wall, which should be seen as a very effective strong strategy. The sleek body of the animal with its dots almost splits into pixels reminding one of the large scale works of the Japanese artist Takashi Murakami. But the glee that one experiences in the works of Murakami is absent in Ajitkumar's mural altogether and in its place what we see a sense of grimness, tension and controlled aggression. The bodies of the black human beings (somehow they are painted as primitive/subhuman beings) resonate with the ferociousness of the leopard not only in design but also in their tension and aggression.
(a view)
The symbolic overload is suitable for the times that the artist has chosen to paint the mural. When the times are oppressive and the commissioning establishment cannot just go against the diktats of the central governing body, the artist has to find an allegorical way to state the fact and also the 'state of affairs.' This work of art definitely does not have any overt critique on the totalitarian regimes that are around (both the homegrown and the imported varieties) but the mural says the unutterable in a different way. There is a victor and the vanquished in the work. The victors are black people. Why they are black and in a way have subhuman traits as their painted bodies have the leopard faces on? Their blackness shows the people who are to be liberated or rather seeking liberation are still black and live in subhuman conditions. They are a sort of primitives and are in fierce fight with the aggressive forces. What one notices is the political correctness that the 19th century painter had brought in his work and how Ajitkumar picks it up as a usable visual quote in disguise. The correctness lies in the dominant part/action attributed to the woman protagonist and reifying her to certain extent and also the attribution of a secondary position to the visibly male character. Does Ajitkumar want to say that in the beginning of revolution (war) the rules of political correctness are observed only to be toppled at a later stage where the man would take a dominant position? One could read so, if one thinks it should be read it in that way.
The whole action, stretched out to the hundred feet length of the stadium wall takes place against a sylvan backdrop where there are lush greenery and beautiful pink flowers. Good that the artist in a possible urgency has not tried to incorporate some familiar flora and fauna just for the heck of 'touristic' purpose. Ajitkumar as a discerning artist transposes the whole scene to a different space, a mythical space which could easily be turned/read as a historical space (as in our country often they interchange their given locations for political convenience) and spells out the eventual victory of the oppressed over the bestial forces. The color scheme has to be layered out/laid out vis-à-vis the social meanings of such colors in order to understand the picture. One could also read the scene in terms of taming the nature by people who would eventually evolve as beings with a scientific bent. A dotted big cat could be seen as nature that resists culture. Similarly it could be a totem figure that stands for earth and sky and the scene in this sense is a overcoming of the elements by human beings for 'liberating' themselves from natural 'subjugations'. In the colonial visual discourse, a tamed tiger/leopard is always seen as a domination of the colonizer over the subjects, their lands and their resources. Hunting game had become a site of male domination as well as colonial domination not only over the people but also over their 'nature'. This becomes all the more important when we see innumerable sculptures and toys where the colonial ruler is killed by a tiger (Tipu Sultan) reversing the symbolic order.
(Kings hunting scene, Colonizer attached by the Mysore Tiger)
Any work of art introduced to a city's public spaces initially redefines the space to a greater extent. It is never seen from a frontal position, the way we see a work of art in a museum or a gallery or even a film poster. This is always seen from various planes, distances, times and climatic conditions. Each time the work would create a different response in a viewer unlike a work of art would in the case of its display on a neutral gallery or museum wall. In this sense, a work of art in a public space remains impressionistic throughout its existence. Each viewer takes a different mural in his/her mind depending on the time of the day and climatic condition under which he/she has seen the work. As it is the case, it is not necessary that the authorial intent is to be discerned each time; for someone sees the tail of the leopard first and the rest later and someone sees the attacking figures first and the tiger later. Some could even miss the leopard while seeing the flowery forest behind. I sincerely hope people 'see' the mural in whatever they like and take an impression of it in their cultural consciousness. That's the way a work of art grows into the city's psyche and body as well.
Ratheesh T's 'Smell of Pepper and Jasmine', an Evidence to Political Art
(Smell of Pepper and Jasmine by Ratheesh T, oil on canvas 7x8')
Are you on a look out for some 'political art' in India? Then go to Galerie Mirchandani+Steinruecke in Mumbai where a show titled 'Nine Painters from Kerala' is currently on. I may not qualify the show as a 'political' one just because it comprises of nine artists from Kerala, a state which is hailed to be a politically charged one. Each state in India is political and each artist has turned out to be political as the time demands such politicization of artists and their art. Did I say art? Hmm…I have to make a clarification here; most of the artists who are already politicized for right or wrong reasons, to me, are not making 'political art' in a strict sense. In a politically charged atmosphere any utterance cannot go free of political under or overtones. In that sense many artists do what could be called political art but the story ends there. Some are overtly political that often become sloganeering in a sophisticated way to which one would find a befitting example in an exhibition recently concluded in Delhi's Vadehra Gallery. Titled 'Holy Shiver' this exhibition had images of Dr.B.R.Ambedkar both in painted and sculpted forms. But if you just take a metro from the Lajpat Nagar Station and get down at the Central Secretariat, just out there you could see the recently inaugurated Dr.Ambedkar Museum and Research centre and right in front of that massive building the same images of Dr.Ambedkar and the Ashokan Pillar. You may decide, which one is effective as 'art' in the eyes of the public that include public intellectuals, just intellectuals and those intelligent people who survive with their intelligence in an urban space.
(Artist Ratheesh T)
Here in this small article what I would like to articulate is the political intensity of a single work from this 'Nine Painters from Kerala' exhibition (Do not mistake that the gallery is overtly interested in the aesthetics produced in Kerala. The simple reason for this show is this that all these nine artists have been promoted by this gallery for over a decade). The work is titled 'Smell of Pepper and Jasmine' a 7x8 feet oil on canvas work by the Trivandrum based artist Ratheesh T. This artist has been doing some wonderful paintings with the images that he has sensitively as well as cynically culled from the immediate surroundings of his life. At times they become caricatures of a life that has lost its regular reality and could exist only in a caricature form in order to find relevance even in their marginalized lives. Ratheesh no longer lives a marginalized life for the riches that the art boom had brought to him have elevated his socio-economic position. But the fact of marginalization is such that even the socio-economic sublimation through education and money often does not erase the stains that a caste society has smeared on the faces of the people who survived the fringe lives. Caste is such a powerful social classification in India and only the articulation of it could remove the stigma attached to it. What Ratheesh does as an artist is this articulation with a humorous vengeance, the way Kunchan Nambiar used to do in the 18th century. There is a tremendous amount of self loathing in it but that aspect is covered with a sense of celebration which a so called 'sophisticated society' would abhor to do.
(Mill Call by Ram Kinkar Baij)
In 'Smell of Pepper and Jasmine' Ratheesh while subverting the beauty concept that is prevalent in Kerala, very strategically problematizes the notions of purity, work, social surveillance and (sexual) desire. The social relationships between castes and sub-castes have always been a problematic in Kerala. The present upper caste, Nairs, was 'Sudra' in the caste hierarchy. But with certain socio-political maneuvers Nairs reached the upper echelons of the society, establishing anything 'Nair' as the desirable position. Hence, today we see the Nairs still involved in Brahminizing itself and all the other lower castes, which were out of the four tier system of caste, by emulating the Nair codes of life create further caste divisions. Hence, even some Dalit communities find it natural to emulate what the Nair does and perpetuate the caste divisions and discriminations within their societies. The Hinduisation of Kerala society using many a religious platform tries to force out caste categories in order to homogenize them as 'Hindus' and in this attempt establishes the 'Nair' habits as the standard habits of living therefore desirable by all the lower castes. The Nairisation of Kerala society has been happening for several decades and it has reached its pinnacle in the recent years especially through the mainstream media and films. The homogenized Hindu however has not yet become 'Nair' in Kerala in terms of social relevance but has accumulated the burden of caste-ism perpetuated by the Nair caste. The white Sari with a golden border and the participation in temple rituals by the Dalits are the results of such Nairisation of the Kerala society, which in fact has become so gullible before the intoxicating power of Hindutva.
(Mullappoo Choodiya Nair Vanitha by Raja Ravi Varma)
In Ratheesh's work we see the protagonist is a dark (Dalit) woman and it is clear that she is on the way back home after a temple visit. There is something very comical about her that constantly makes her 'non-belongingness' obvious. Her body is dark but he wears a white sari with a golden border (a must for religious occasions). She is happily oblivious about her surroundings though her 'body' and the paraphernalia that embellish that body correspond to the surroundings. She is as animated and happy as the women who are running to the mills in Ram Kinkar Baij's 'Mill Call.' The strain of her vigorous walk is palpable in her tense thigh muscles of the left leg which is pushed forward. The drapery is painted in such an animated order that they not only capture the force of her bodily movement but also the wind that blows against her that billows the pallu of her sari that conceals a ghostly presence who is walking with her. I will come to this ghostly figure in a while. Before that let me see the surroundings; it has pepper plants and jasmine plant on the other side. The pepper smell could be the smell of a dark and sexually powerful body of the young woman whose rawness is temporarily covered by the 'Nair' attire. But her raw sexual appeal is as strong as the pepper and the jasmine that she wears on her hair is once again a Nair attribute (about this later). The jasmine flowers show the pure nature of her 'self' (which is often denied to a Dalit body) and also the subtle ways of love she is capable of. Ratheesh gives iconic status to a girl who is otherwise seen as a 'thozhilurappu jolikkari' or 'Kudumbashree amgam' (two government schemes that assure job to women; though it is generally for women only Dalit and OBC women go for it as these groups are seen as group of women who are uneducated and good for no other jobs than menial work).
(work by Ratheesh T)
Who/What is that ghostly presence behind her bellowing sari pallu? Clearly that is a man and is obvious from the muscled legs and a vascular palm tensed in an act of grabbing. In that moment of pure oblivion, this unidentified presence is crossing that girl and he looks back at her. We do not see his face as the whole of his upper body is covered by the edge of her sari. A very superficial reading could lead us to believe that this presence is that of any man who is about to molest a poor girl going back home alone. But thinking of it in a more 'religious or rather theological' sense we could see Ratheesh suggesting the presence of an evil angel titillating her into some sin. Or could it be a suggestion that the girl is already sinned and the sin is constantly crossing her looking back in absolute glee? What is that sin that the girl has committed? In my view, the sin could be the voluntary submission of her body to the forces of the upper caste ideology/aesthetics. She in her utter innocence has de-politicized her otherwise political body. She has just become an instrument of perpetuation. While she remains apolitical, for the viewer her body becomes the contesting field of various socio-political and aesthetical demands that subject her dark/Dalit body for their ends. Hence, Ratheesh's painting is to be seen more as a warning to the marginalized women rather than a celebration of their newly assumed 'upper caste' identity.
(JohnyML in front of Smell of Pepper and Jasmine by Ratheesh T)
The presence of Jasmine is pivotal in this work for various reasons; first of all jasmine flowers symbolize erotic passion and sexual desire. This could make our protagonist lady into a desiring and desirous subject. She is like a bomb/vedi, in the common parlance, a qualification which is never given to a Nair woman under the same circumstances but is definitely attributed to a dark/Dalit girl in whatever good dress. But the presence of Jasmine is more than that. This painting as a whole is a great critique of Raja Ravi Varma. Interestingly Ratheesh also hails from Kilimanoor, the birth place of Raja Ravi Varma. And more ironically, despite the presence of so many Dalit families around Ravi Varma's palace, who were the workers in the sprawling paddy fields just in front of them, not in a single occasion Ravi Varma had felt the compulsion to paint a working class/Dark/Dalit woman. He painted only fair skinned Nair women and the only exception was when he painted his mother in law in dark complexion. He achieved some major award from national and international exhibitions for his work titled 'Mullappoo Choodiya Nair Vanitha' (Nair Lady with Jasmine Flowers in her Hair). Here Ratheesh introduces a Dalit woman with Jasmine flowers in her hair. By doing this he indirectly asks why the body of a Nair woman doesn't become sexually desirable/available and it is so when a dark complexioned girl wears flowers in her head? When we see the whole painting in these terms, the White Sari with golden borders becomes an aesthetic reclamation of such rights from Raja Ravi Varma by a contemporary painter who happens to hail from a marginalized caste. The Jasmine flower gets a different value and the painting of drapery adds to the strength of that reclamation. Ratheesh subverts all the existing aesthetical norms created out of Ravi Varma's paintings, using the very same techniques (oil on canvas) and does it quite effectively. Political art is not painting Ambedkar's portrait and exhibiting in A-class galleries.
Posted by JohnyML at 11:13 AM No comments:
Ratheesh T's 'Smell of Pepper and Jasmine', an Evi...

redpajama_set_name: RedPajamaCommonCrawl


Minroc is a specialist in the provision of products and services to the quarry and mining industries. In-depth of knowledge in running large mining and process operations ensure that Minroc can provide a strong emphasis on project management and operations of mining, quarrying, process applications and landfill projects.
Couple with extensive mining and quarry industry know-how, Minroc has experience in all forms of Waste management, recycling to mine tailings, water management and harvesting of water.


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© 2017 Swanland Lawn Tennis Club
Swanland Village Website
Welcome to the Swanland Lawn Tennis Club website.
The club is located in the heart of the East Yorkshire village of Swanland. The club has five all-weather, flood-lit tennis courts which are open to members all year round.
The clubhouse has male and female facilities, a comfortable seating area and a kitchen which members can make full use of.
Swanland Lawn Tennis Club offers Tennis for adults and children. For adults, we have club nights and mornings throughout the week as well as a range of ladies, mixed and men's teams, competing in the local league. Regular club tournaments are hosted during the year.
Teo Arkut, the club coach, is on hand to deliver private lessons for adults and children - he also runs junior training sessions after school and at weekends during term time.
Swanland Lawn Tennis Club is a friendly and welcoming sports club and we encourage people of all standards to contact us to arrange a visit.
Get Active... Get Fit... Play Tennis @ Swanland Tennis Club
Click on the images above to find out more
WELCOME TO SWANLAND LAWN TENNIS CLUB!


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Home › Racing News › Aston Martin
Intermittent power issues and an untimely yellow sidetrack the day in the Michelin Pilot Challenge.
For Stoner Car Care Racing fielded by Automatic Racing's Rob Ecklin, Jr., the chance to race at Watkins Glen is a return to the very beginnings of his racing interests and career.
Stoner Car Care Racing Continues to Improve at Mid-Ohio
The Stoner Car Care Racing fielded by Automatic Racing team continued to make forward progress during Saturday's Mid-Ohio 120, returning to the famed Mid-Ohio Sports Car Course for the first time since 2019 to contest race four of the IMSA Michelin Pilot Challenge season.
Stoner Car Care Racing Aiming for Good Result in the Third of Three Straight Race Weekends
The Stoner Car Care Racing fielded by Automatic Racing team heads to the Mid-Ohio Sports Car Course for the Mid-Ohio 120, race four of the 2022 Michelin Pilot Challenge season.


If you are looking for a fixed dome camera – sometimes referred to as "mini-dome" – you will find it at here. You will even find some of the most compact and discreet fixed dome cameras on the market, measuring only 10 cm in diameter and 4 cm high.
Special features for buses and trains.
Our EX-SDI Dome Cameras have an active tampering alarm feature to help protect cameras against vandalism. It can detect if a camera has been redirected, obscured or tampered with, and can send alarms to operators. This is especially useful in installations with hundreds of cameras in demanding environments where keeping track of the proper functioning of all cctv cameras is difficult.
It is also useful in situations where no live viewing takes place and operators can be notified when cameras have been tampered with.
In some surveillance applications, cameras are at risk of hostile and violent attacks. While a camera or housing can never guarantee 100% protection from destructive behavior in every situation, vandalism can be mitigated by considering various aspects: camera/housing design, mounting, placement and use of intelligent video alarms.
Casings and related components that are made of metal provide better vandal protection than ones made of plastic. The shape of the housing or camera is another factor. A housing or a traditional fixed camera that protrudes from a wall or ceiling is more vulnerable to attacks (e.g., kicking or hitting) than more discretely designed housings or casings for a fixed dome or PTZ dome camera.
The smooth, rounded covering of a fixed dome or PTZ dome makes it more difficult, for example, to block the camera's view by trying to hang a piece of clothing over the camera. The more a housing or camera blends into an environment or is disguised as something other than a camera - for example, an outdoor light - the better the protection against vandalism.
The way cameras and housings are mounted is also important. A traditional fixed network camera and a PTZ dome camera that is mounted on the surface of a ceiling are more vulnerable to attacks than a fixed dome or PTZ dome camera that is mounted flush to a ceiling or wall, where only the transparent part of the camera or housing is visible.
Another important consideration is how the cabling to a camera is mounted. Maximum protection is provided when the cable is pulled directly through the wall or ceiling behind the camera. In this way, there are no visible cables to tamper with. If this is not possible, a metal conduit tube should be used to protect cables from attacks.