Sinhala Buddhist Nationalism and Islamophobia in Contemporary Sri Lanka

In recent years, Sri Lanka’s small Muslim minority has become the target of hatred and violence from right-wing organizations such as the Bodu Bala Sena (BBS), who claim to be protecting the country’s Sinhala Buddhist majority from an emerging Islamic threat. In this thesis, I consider the sudden upsurge of anti-Muslim sentiment in Sri Lanka in the context of fears about global political Islam and minority persecution in Muslim-majority states. Drawing on fieldwork conducted in Sri Lanka with Buddhist monks and laypeople associated with the BBS and other nationalist groups, I consider the linkages between geographical politics, gendered bodies, and food consumption in Sinhala Buddhist Islamophobic discourse. I argue that globalization, which makes the politically weak Sri Lankan Muslim minority appear connected to powerful foreign forces, is deeply implicated in the BBS’s fear of a Muslim takeover, particularly due to Buddhist nationalist concerns about the Sinhala majority’s own lack of global influence. This work contributes to theorizations of majority-minority relations by suggesting that globally disconnected majorities who fear the possibility of “trading places” with globally connected minorities will justify violence and repression against the latter on supposedly defensive grounds

Comment on Martinez-Garcia et al. 'Heavy metals in human bones in different historical epochs'.

Martínez-García et al. (Sci. Tot Env. 348:51–72) have examined heavy metal exposure of humans in the Cartagena region using analysis of archaeological bones. An analysis of the lead and iron levels they report shows that they are physiologically implausible and must therefore result from diagenesis. This, and analogy with the known diagenetic origin of certain other elements, suggests that the other metal analyses they report are also unlikely to be in vivo concentrations. Lifetime heavy metal exposure cannot be deduced from diagenetically altered concentrations

STUDY OF LOW PHYTIC ACID 1 LOCUS IN MAIZE

Phytic acid (myo-inositol-1,2,3,4,5,6-hexakisphosphate; InsP6) is ubiquitous in eukaryotic cells and constitutes the major storage form of phosphate in plant seeds (from 60% to 80%). During maturation it is accumulated in the protein storage vacuole in inclusions called globoids; the phosphate groups present in phytic acid (PA) are able to form phytate salts (phytin) binding important mineral cations. In mature maize kernels, 80% of PA is localized in the scutellum and the remaining 20% in the aleurone layer. The phosphorus stored as PA is remobilized during germination by phytase enzymes: these are also found in many microorganisms. Regarding the involvement of P in agricultural production and its sustainability, it has been estimated that nearly 50% of elemental P used yearly in global agricultural activities is accumulated in the PA. PA forming mixed salts with mineral cations is mainly excreted by monogastric animals and humans because they do not have phytase activity in their digestive systems. Considering that seeds are an important component of animal feed and human food, the limitations of phosphorus and micronutrients bioavailability imply a decrease in their nutritional value. Furthermore the undigested phosphorous contained in excreted phytin can contribute to water pollution (eutrophication). These negative effects have led to breeding programmes which have the aim of reducing the PA content in the seeds of several cultivated plants. The main way to reach this result by conventional breeding is the isolation of low phytic acid (lpa) mutations, capable of restraining the biosynthesis or the storage of PA in the seed; the increased P and mineral cation bioavailability in lpa seeds is confirmed by nutritional trials. In maize three low phytic acid mutants have been isolated: lpa1 and lpa2 by chemical mutagenesis, lpa3 by transposon tagging. Compared to the other mutations in maize, lpa1 exhibited the major reduction of PA in the seed, this comes with a proportional increase of free P without changing the total P content. Taking advantage of this property, lpa mutants can be recognized by the HIP (high inorganic phosphate) phenotype of the seeds. The Lpa1 gene encodes for ZmMRP4 (accession number EF586878) a multidrug-associated-protein (MRP) belonging to the subfamily of ATP-binding cassette (ABC) transmembrane transporters. MRP proteins are implicated in different roles like the transport of organic ions and anthocyanins, detoxification of xenobiotic compounds, transpiration control, and tolerance to oxidative stress. The role of this MRP protein is not completely understood but it is fundamental for phytic acid accumulation and viability of seeds. low phytic acid mutants isolated in rice and soybean are related to defects in homologues of the maize ABC transporter. It was observed that lpa mutations found in several crops usually bring pleiotropic effects on plant and seed performance, such as reduced germination and emergence rate, lower seed filling, weakening in stress resistance. The presence of pleiotropic effects shows that lpa mutations influence not only the seed but also the whole plant and its production. This can reflect the relevance of inositol phosphates as multifunctioning molecules, and their involvement in fundamental signaling and developmental pathways, like DNA repair, RNA editing, chromatin remodeling and control of gene expression. Furthermore phytic acid exhibits, by its ability to chelate iron, a potent antioxidant activity, avoiding the formation of reactive oxygen species. With the aim to isolate new maize low phytic acid mutants mutagenesis treatment were performed with EMS (ethyl-methanesulfonate). Since wild type mature maize seeds contain high amount of phytic phosphate and low free phosphate content, we screened the mutagenized population looking for seeds containing high levels of free phosphate (HIP phenotype), a typical feature of lpa. In previous studies a single recessive lpa mutation (originally named lpa241 and obtained by EMS pollen-tratment mutagenesis) was isolated and described, it was allelic to the lpa1-1 mutant, and was consequently renamed lpa1-241. A first evidence of non-Mendelian inheritance of lpa1 trait came from the appearance of unexpected free phosphate phenotypes in Lpa1/lpa1-241. When heterozygous families were selfed, we observed an overall increase of the mutant phenotype ratio due to the appearance of weak and intermediate phenotype, not consistent with a monogenic recessive mutation. This phenomenon can be explained with a partial Lpa1 allele silencing caused by trans interaction with the paramutagenic lpa1-241 allele. We performed genetic and molecular analyses of the lpa1-241 mutation that indicate an epigenetic origin of this trait, that is, a paramutagenic interaction that results in meiotically heritable changes in ZmMRP4 gene expression, causing a strong pleiotropic effect on the whole plant. To our knowledge, this is the first report of a paramutagenic activity not involving flavonoid biosynthesis in maize, but regarding a key enzyme of an important metabolic pathway in plants. We isolate a new maize (Zea mays L.) low phytic acid 1 mutant allele obtained by chemical EMS seed mutagenesis. We performed the allelism test with two other lpa1 mutants: lpa1-1 and lpa1-241, our mutant failed to complement these mutants. This mutant, named lpa1-7, exhibits a monogenic recessive inheritance and lethality as homozygous. We demonstrate that in vitro cultivation can overcome lethality allowing the growth of adult plants and we report data regarding embryo and leaf abnormalities and other defects caused by negative pleiotropic effects of this mutation. We conducted two experiments to ascertain the nature of lpa1-7 and. we also performed physiological analysis, histological observations and considerations regarding the effects of the lpa1 mutations on the plant. Pigmented maize contains anthocyanins and phenolic compounds which are phytochemicals synthesized in the plant by secondary metabolism; although these compounds are considered as non-nutritive, in these years the interest in antioxidant and bioactive properties has increased due to their health benefits. Anthocyanins are water soluble secondary metabolites belonging to the class of flavonoids and they play important roles in several aspect of plant biology. The anthocyanins are present in the vacuole in a glycosilated form and their colour is influenced in part by the pH of this compart. In maize they are synthesized by a complex pathway made up of more than 20 genes, and regulated by two classes of transcription factors: r1/b1 bHLH genes and c1/pl1/p1 MYB gene families. Our aim is the constitution of maize inbred lines carrying low phytic acid mutations together with regulatory genes pushing the anthocyanin accumulation in the kernels and seedlings, so they can compensate the leak in antioxidant activity induced by the low phytic acid mutation. We found that the lpa1-241 line is able to alter the accumulation of anthocyanin in kernel tissues. The anthocyanins, are present in the vacuole where their colour is dependent on the pH. In maize the anthocyanins are cytoplasmically synthesized molecules probably transported in the vacuole by ZmMRP3 gene activity. We observed an interaction between the accumulation of anthocyanin pigments in the kernel and the lpa mutations. In fact the lpa1-241 mutant accumulates a higher level of anthocyanins as compared to wild type either in the embryo or in the aleurone layer in a genotype able to accumulate anthocyanin. Furthermore, we demonstrate that these pigments are mislocalised in the cytoplasm, conferring a blue pigmentation of the scutellum, because of the neutral/basic pH of this cellular compartment; expression analysis showed a reduction of ZmMRP3 anthocyanins\u2019 transporter gene expression. On the whole, these data strongly suggest a possible interaction between the lpa mutation and anthocyanin accumulation and compartmentalization in the kernel

NOS1AP polymorphisms reduce NOS1 activity and interact with prolonged repolarization in arrhythmogenesis

Aims  NOS1AP single-nucleotide polymorphisms (SNPs) correlate with QT prolongation and cardiac sudden death in patients affected by long QT syndrome type 1 (LQT1). NOS1AP targets NOS1 to intracellular effectors. We hypothesize that NOS1AP SNPs cause NOS1 dysfunction and this may converge with prolonged action-potential duration (APD) to facilitate arrhythmias. Here we test (i) the effects of NOS1 inhibition and their interaction with prolonged APD in a guinea pig cardiomyocyte (GP-CMs) LQT1 model; (ii) whether pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from LQT1 patients differing for NOS1AP variants and mutation penetrance display a phenotype compatible with NOS1 deficiency. Methods and results  In GP-CMs, NOS1 was inhibited by S-Methyl-L-thiocitrulline acetate (SMTC) or Vinyl-L-NIO hydrochloride (L-VNIO); LQT1 was mimicked by IKs blockade (JNJ303) and β-adrenergic stimulation (isoproterenol). hiPSC-CMs were obtained from symptomatic (S) and asymptomatic (AS) KCNQ1-A341V carriers, harbouring the minor and major alleles of NOS1AP SNPs (rs16847548 and rs4657139), respectively. In GP-CMs, NOS1 inhibition prolonged APD, enhanced ICaL and INaL, slowed Ca2+ decay, and induced delayed afterdepolarizations. Under action-potential clamp, switching to shorter APD suppressed ‘transient inward current’ events induced by NOS1 inhibition and reduced cytosolic Ca2+. In S (vs. AS) hiPSC-CMs, APD was longer and ICaL larger; NOS1AP and NOS1 expression and co-localization were decreased. Conclusion  The minor NOS1AP alleles are associated with NOS1 loss of function. The latter likely contributes to APD prolongation in LQT1 and converges with it to perturb Ca2+ handling. This establishes a mechanistic link between NOS1AP SNPs and aggravation of the arrhythmia phenotype in prolonged repolarization syndromes

Insulin and serine metabolism as sex-specific hallmarks of Alzheimer's disease in the human hippocampus

Healthy aging is an ambitious aspiration for humans, but neurodegenerative disorders, such as Alzheimer's disease (AD), strongly affect quality of life. Using an integrated omics approach, we investigate alterations in the molecular composition of postmortem hippocampus samples of healthy persons and individuals with AD. Profound differences are apparent between control and AD male and female cohorts in terms of up- and downregulated metabolic pathways. A decrease in the insulin response is evident in AD when comparing the female with the male group. The serine metabolism (linked to the glycolytic pathway and generating the N-methyl-D-aspartate [NMDA] receptor coagonist D-serine) is also significantly modulated: the D-Ser/total serine ratio represents a way to counteract age-related cognitive decline in healthy men and during AD onset in women. These results show how AD changes and, in certain respects, almost reverses sex-specific proteomic and metabolomic profiles, highlighting how different pathophysiological mechanisms are active in men and women

Serine metabolism during differentiation of human iPSC-derived astrocytes

: Astrocytes are essential players in development and functions, being particularly relevant as regulators of brain energy metabolism, ionic homeostasis and synaptic transmission. They are also the major source of l-serine in the brain, which is synthesized from the glycolytic intermediate 3-phosphoglycerate through the phosphorylated pathway. l-Serine is the precursor of the two main co-agonists of the N-methyl-d-aspartate receptor, glycine and d-serine. Strikingly, dysfunctions in both l- and d-serine metabolism are associated with neurological and psychiatric disorders. Here, we exploited a differentiation protocol, based on the generation of human mature astrocytes from neural stem cells, and investigated the modification of the proteomic and metabolomic profile during the differentiation process. We show that differentiated astrocytes are more similar to mature rather than to reactive ones, and that axogenesis and pyrimidine metabolism increase up to 30 days along with the folate cycle and sphingolipid metabolism. Consistent with the proliferation and cellular maturation processes that are taking place, also the intracellular levels of l-serine, glycine, threonine, l- and d-aspartate (which level is unexpectedly higher than that of d-serine) show the same biosynthetic time course. A significant utilization of l-serine from the medium is apparent while glycine is first consumed and then released with a peak at 30 days, parallel to its intracellular level. These results underline how metabolism changes during astrocyte differentiation, highlight that d-serine synthesis is restricted in differentiated astrocytes and provide a valuable model for developing potential novel therapeutic approaches to address brain diseases, especially the ones related to serine metabolism alterations

Calmodulinopathy: Functional Effects of CALM Mutations and Their Relationship With Clinical Phenotypes

In spite of the widespread role of calmodulin (CaM) in cellular signaling, CaM mutations lead specifically to cardiac manifestations, characterized by remarkable electrical instability and a high incidence of sudden death at young age. Penetrance of the mutations is surprisingly high, thus postulating a high degree of functional dominance. According to the clinical patterns, arrhythmogenesis in CaM mutations can be attributed, in the majority of cases, to either prolonged repolarization (as in long-QT syndrome, LQTS phenotype), or to instability of the intracellular Ca2+ store (as in catecholamine-induced tachycardias, CPVT phenotype). This review discusses how mutations affect CaM signaling function and how this may relate to the distinct arrhythmia phenotypes/mechanisms observed in patients; this involves mechanistic interpretation of negative dominance and mutation-specific CaM-target interactions. Knowledge of the mechanisms involved may allow critical approach to clinical manifestations and aid in the development of therapeutic strategies for “calmodulinopathies,” a recently identified nosological entity

Religiousness as tourist performances: a case study of Greek Orthodox pilgrimage

The aim of this paper is to decipher ways of experiencing religiousness through tourist performances, intersecting textual approaches with the essential embodiment and materiality of the tourist world. Exploring the diversity of religious tourists’ practices within the Greek Orthodox context, two dimensions underpinning religious tourist experience are highlighted: institutional performances and unconventional performances. Focussing on the embodied experience and drawing upon theories of performance, the paper critiques the interplays of body and place to re-conceptualise current understanding of the pilgrimage/tourism relationship. In doing so, the paper proposes that tourism and religion are not separate entities but linked through embodied notions of godliness sensed through touristic performances