Interrogating the Light Bugs

My paintings engage with ideas of time, memory and displacement. Intricately painted works appear to cover other layers of information hidden underneath through the act of rubbing, masking and erasing with unconventional tools such as scour pads, toilet brushes and rags, creating a surface that resembles a complex topographical map. But unlike a traditional cartographer, I seek to map my inner world

Transient Cenozoic tectonic stages in the southern margin of the Caribbean plate : U-Th/He thermochronological constraints from Eocene plutonic rocks in the Santa Marta massif and Serranía de Jarara, northern Colombia

We use U-Th/(He) zircon and apatite thermochronology and Al in hornblende geobarometry from Eocene granitoids of the Sierra Nevada de Santa Marta and Guajira uplifted massifs in northern Colombia to elucidate the exhumation history of the northern South America continental margin and its bearing to Cenozoic Caribbean- South American plate interactions. Aluminium in hornblende geobarometry from the Eocene Santa Marta batholith yields pressures between 4.9±0.6kbar and 6.4±0.6kbar, which indicate that at least, 14.7-19.2km of unroofing took place since 56-50Ma in the northwestern Sierra Nevada de Santa Marta. In the Guajira Peninsula, calculated pressures for the Eocene Parashi stock are 2.3±0.6kbar and 3±0.6kbar. Stratigraphic considerations pertaining to Oligocene conglomerates from the Guajira area suggest that 6.9-9km of crust was lost between 50Ma and ca. 26Ma. U-Th/He zircon and apatite thermochronology from granitoids in the Sierra Nevada de Santa Marta shows the existence of major exhumation events in the Late Eocene (ca. 45-40Ma), Late Oligocene (ca. 25Ma) and Miocene (ca. 15Ma). The Guajira region records the Late Eocene to Early Oligocene (35-25Ma) event, but it lacks evidence for the Miocene exhumation phase. These differences reflect isolation of the Guajira region from the Sierra Nevada de Santa Marta and the Andean chain due to extensive block rotation and transtensional tectonics that affected the region during post-Eocene times. The post-Eocene events correlate in time with an increased convergence rate and the frontal approach of North and South America. It is suggested that the two major tectonic mechanisms that govern exhumation in these Caribbean massifs are: 1) subduction of the Caribbean plate, and 2) post Eocene changes in plate convergence obliquity and rates that caused the South American continental margin blocks to override the Caribbean plate. Temporal correlation with other Caribbean and Northern Andean events allows to resolve the regional Cenozoic plate tectonic reorganizations experienced by the South American, Caribbean and Pacific plates at a regional scale

Multiple Anticancer Effects of Damsin and Coronopilin Isolated from Ambrosia arborescens on Cell Cultures

Terpenoids in plants are important sources for drug discovery. In this study, we extracted damsin and coronopilin, two sesquiterpene lactones, from Ambrosia arborescens and examined their anticancer effects on cell cultures. Damsin and coronopilin inhibited cell proliferation, DNA biosynthesis and formation of cytoplasmic DNA histone complexes in Caco-2 cells, with damsin being more potent than coronopilin. Further studies using the luciferase reporter system showed that damsin and coronopilin also inhibited expressions of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT3), indicating that these sesquiterpenes can interfere with NF- κB and STAT3 pathways. Finally, we examined the effects of two synthetic dibrominated derivatives of damsin, 11α,13- dibromodamsin and 11β,13-dibromodamsin. While bromination appeared to weaken the antiproliferative effects of damsin, the β epimer had strong inhibitory effects on STAT3 activation. In conclusion, the sesquiterpene lactones damsin and coronopilin have inhibitory effects on cell proliferation, DNA biosynthesis and NF-κB and STAT3 pathways, thus being potentially important for discovery of drugs against cancer

Validation of the diabetes, hypertension and hyperlipidemia (DHL) knowledge instrument in Malaysia

BACKGROUND: Patient's knowledge on diabetes, hypertension and hyperlipidaemia and its medications can be used as one of the outcome measures to assess the effectiveness of educational intervention. To date, no such instrument has been validated in Malaysia. Therefore, the aim of this study was to evaluate the validity and reliability of the Diabetes, Hypertension and Hyperlipidemia (DHL) knowledge instrument for assessing the knowledge of patients with type 2 diabetes in Malaysia. METHODS: A 28-item instrument which comprised of 5 domains: diabetes, hypertension, hyperlipidemia, medications and general issues was designed and tested. One point was given for every correct answer, whilst zero was given for incorrect answers. Scores ranged from 0 to 28, which were then converted into percentage. This was administered to 77 patients with type 2 diabetes in a tertiary hospital, who were on medication(s) for diabetes and who could understand English (patient group), and to 40 pharmacists (professional group). The DHL knowledge instrument was administered again to the patient group after one month. Excluded were patients less than 18 years old. RESULTS: Flesch reading ease was 60, which is satisfactory, while the mean difficulty factor(SD) was 0.74(0.21), indicating that DHL knowledge instrument was moderately easy. Internal consistency of the instrument was good, with Cronbach's alpha = 0.791. The test-retest scores showed no significant difference for 26 out of the 28 items, indicating that the questionnaire has achieved stable reliability. The overall mean(SD) knowledge scores was significantly different between the patient and professional groups 74.35(14.88) versus 93.84(6.47), p < 0.001. This means that the DHL knowledge instrument could differentiate the knowledge levels of participants. The DHL knowledge instrument shows similar psychometric properties as other validated questionnaires. CONCLUSIONS: The DHL knowledge instrument shows good promise to be adopted as an instrument for assessing diabetic patients' knowledge concerning their disease conditions and medications in Malaysia

Dietary L-Tryptophan Consumption Determines the Number of Colonic Regulatory T cells and Susceptibility to Colitis via GPR15

Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3+ regulatory T (Treg) cells and local immune homeostasis. Ingested L-Trp is converted by host IDO1/2 enzymes, but not by gut microbiota, to compounds that induce GPR15 transcription preferentially in Treg cells via the aryl hydrocarbon receptor. Consequently, two weeks of dietary L-Trp supplementation nearly double the colonic GPR15+ Treg cells via GPR15-mediated homing and substantially reduce the future risk of colitis. In addition, humans consume 3–4 times less L-Trp per kilogram of body weight and have fewer colonic GPR15+ Treg cells than mice. Thus, we uncover a microbiota-independent mechanism linking dietary L-Trp and colonic Treg cells, that may have therapeutic potential

Regulatory T Cell Induction during Plasmodium chabaudi Infection Modifies the Clinical Course of Experimental Autoimmune Encephalomyelitis

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is used as an animal model for human multiple sclerosis (MS), which is an inflammatory demyelinating autoimmune disease of the central nervous system characterized by activation of Th1 and/or Th17 cells. Human autoimmune diseases can be either exacerbated or suppressed by infectious agents. Recent studies have shown that regulatory T cells play a crucial role in the escape mechanism of Plasmodium spp. both in humans and in experimental models. These cells suppress the Th1 response against the parasite and prevent its elimination. Regulatory T cells have been largely associated with protection or amelioration in several autoimmune diseases, mainly by their capacity to suppress proinflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we verified that CD4(+)CD25(+) regulatory T cells (T regs) generated during malaria infection (6 days after EAE induction) interfere with the evolution of EAE. We observed a positive correlation between the reduction of EAE clinical symptoms and an increase of parasitemia levels. Suppression of the disease was also accompanied by a decrease in the expression of IL-17 and IFN-γ and increases in the expression of IL-10 and TGF-β1 relative to EAE control mice. The adoptive transfer of CD4(+)CD25(+) cells from P. chabaudi-infected mice reduced the clinical evolution of EAE, confirming the role of these T regs. CONCLUSIONS/SIGNIFICANCE: These data corroborate previous findings showing that infections interfere with the prevalence and evolution of autoimmune diseases by inducing regulatory T cells, which regulate EAE in an apparently non-specific manner

Tuftsin Promotes an Anti-Inflammatory Switch and Attenuates Symptoms in Experimental Autoimmune Encephalomyelitis

Multiple sclerosis (MS) is a demyelinating autoimmune disease mediated by infiltration of T cells into the central nervous system after compromise of the blood-brain barrier. We have previously shown that administration of tuftsin, a macrophage/microglial activator, dramatically improves the clinical course of experimental autoimmune encephalomyelitis (EAE), a well-established animal model for MS. Tuftsin administration correlates with upregulation of the immunosuppressive Helper-2 Tcell (Th2) cytokine transcription factor GATA-3. We now show that tuftsin-mediated microglial activation results in shifting microglia to an anti-inflammatory phenotype. Moreover, the T cell phenotype is shifted towards immunoprotection after exposure to tuftsin-treated activated microglia; specifically, downregulation of pro-inflammatory Th1 responses is triggered in conjunction with upregulation of Th2-specific responses and expansion of immunosuppressive regulatory T cells (Tregs). Finally, tuftsin-shifted T cells, delivered into animals via adoptive transfer, reverse the pathology observed in mice with established EAE. Taken together, our findings demonstrate that tuftsin decreases the proinflammatory environment of EAE and may represent a therapeutic opportunity for treatment of MS