74201 research outputs found
Sort by
Anthocyanin and phenolic derivatives in blueberry juice produce CYP3A inhibition in vitro, and identification of these compounds and related derivatives in human plasma
No full textAbstract: Interactions of natural products with prescription drugs have become an issue of medical and public health concern. Blueberry juice at low concentrations produces inhibition of cytochrome P450 (CYP) 3A activity in vitro1. As the pharmacologically active constituents in blueberry juice, anthocyanin and phenolic reveal inhibit effect on CYP3A. Of 4 anthocyanin derivatives and 3 phenolic compounds were measured as potential inhibitor in screen inhibition test, result showed that Malvidin-3-glucoside, Peonidin-3-glucoside, Delphinidin-3-glucoside, Cyanidin-3-glucoside and Quercetin inhibited examined human microsome in a concentration-dependent manner featuring IC50 values from 8.8uM up to 89.2uM. To better understand the absorption and pharmacokinetic profile of blueberry anthocyanin and phenolic after consumed by human, a clinical study was involved. In human study, 12 healthy volunteers were required to take either water (300ml) or 50:50 mixture of lowbush and highbush blueberry juice (300ml) twice a day, and the blood samples were drawing during 12h after index substrate administration. Here, proteins remove, liquid-liquid extraction, high-performance liquid chromatography and mass spectrometry techniques are described for isolation, separation and identification of anthocyanin and phenolic in human plasma.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Pharmacology and Drug Development.Advisor: David Greenblatt.Keyword: Pharmacology
GLIAL REGULATION OF CIRCADIAN BEHAVIOR
No full textAbstract: Circadian rhythms are ubiquitous throughout nature. The molecular oscillators that generate these rhythms are components of nearly every part of biological life. While neuronal circadian circuitry is well studied, knowledge about the contribution of glial cells is currently limited. Recent studies in Drosophila and rodents have identified astrocytes as particularly important components of circadian rhythms. Manipulations of clock genes, calcium signaling, glutamate signaling, and vesicle secretion in astrocytes resulted in abnormal circadian behavior. While we now know that astrocytes are important for maintaining circadian rhythms, many questions remain about how these cells interact with circadian circuitry. Given that we know astrocytes communicate with neurons to regulate behavior, I focused my studies on identifying the signals used by these cells. My thesis describes two approaches towards identifying glial components important for behavioral rhythmicity. First, I describe a genome-wide microRNA (miRNA)-based screen to identify brain glial cell processes required for circadian behavior. To identify glial miRNAs that regulate circadian rhythmicity, I employed a collection of "miR-sponges" to inhibit miRNA function in a glia-specific manner. My initial screen identified 20 glial miRNAs that regulate circadian behavior. I studied two miRNAs - miR-263b and miR-274 - in detail and found that both function in adult astrocytes to regulate behavior. Astrocyte-specific inhibition of miR-263b or miR-274 in adults acutely impairs circadian locomotor activity rhythms with no apparent effect on glial or clock cell viability. To identify potential RNA targets of miR-263b and miR-274, I screened 35 predicted miRNA targets, employing RNAi directed against each target. I found that glial knockdown of two putative miR-274 targets - CG4328 and MESK2 - resulted in significantly decreased rhythmicity. Homology of the miR-274 targets to mammalian counterparts suggests mechanisms that might be relevant for the glial regulation of rhythmicity. A second approach to understanding glial functions utilized cell type-specific profiling of fly astrocytes to identify RNAs showing circadian changes in abundance. I used a tagged ribosomal subunit to affinity purify RNA collected from astrocytes across two days for RNA-sequencing. Dr. Amy Yu performed the initial processing of the sequencing data. I then performed qualitative analysis of the results. 724 RNAs were found to exhibit circadian changes in abundance. Of those cycling genes, 576 were determined to be high-confidence astrocyte genes. I confirmed the list included cycling of core clock genes and known astrocyte genes. I performed gene ontology analysis to identify overrepresented categories of biological processes and molecular functions. Among the overrepresented biological processes were multiple development related processes along with the category of circadian rhythm. Using the FlyBase annotations, I identified a number of genes with circadian or transmitter-related signaling functions. The largest categories of molecular functions were ATP binding and structural components of ribosomes. In looking at the overall landscape of astrocyte protein synthesis, I observed two major phases of translation throughout the day, similar to a previous gene profiling study on clock cells. Together, these studies add to our knowledge of glial functions in regulating circadian behavior. Insights into how glial cells interact with neurons to modulate behavior advance our understanding of pathologies that may result from glial dysfunction.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Neuroscience.Advisor: Rob Jackson.Committee: Michele Jacob, Leon Reijmers, Chris Dulla, and David Van Vactor.Keyword: Neurosciences
Gulf Migration and Cross-Nationality Relationships: A Network Case Study from Kuwait's Private Sector.
No full textSubmitted in partial fulfillment of the degree Master of Arts in Law and Diplomacy at the Fletcher School of Law and Diplomacy. Abstract: Media, human rights, and even scholarly discourses about the experiences of noncitizens living and working in the GCC rely overwhelmingly on narratives of socio-political exclusion and economic exploitation. The central emphasis on ethnocracy and the kafala sponsorship system often obscures the multifaceted nature of Gulf residents’ everyday interactions with one another, interactions which go beyond the segmenting effects of ethnically-motivated citizenship and migration policies. Building off of existing Gulf migration literature and through a network analysis of formal and informal relations among employees at a Kuwaiti construction company, this paper paints a richer picture of how residents with different ethnic and class backgrounds relate to one another. The case demonstrates the utility of network analysis in augmenting ethnographic studies of Gulf societies, laying the groundwork for more extensive future research
Modeling Damage Scenarios: An Analysis of How Damage Function Specification Affects the Optimal Carbon Price.
No full textMy project is an analysis of the ways in which modifying damage function specification affects integrated assessment model output. My main concern is the effect on the carbon price, an estimate of the marginal social cost of carbon, which measures the sum of the market and externality costs associated with carbon usage. The level of the carbon price has important implications for policy makers focused on minimizing the economic damages caused by climate change. Using a popular integrated assessment model, DICE 2016R, I model one scenario in which damages from climate change are applied to the growth of output, and a second in which they become catastrophic after a temperature based tipping point is crossed. After modeling each scenario I undertake a sensitivity analysis and model decomposition to consider how changes to key characteristics of the damage function affect carbon price estimates.I find that applying damages to growth consistently causes carbon price projections to increase dramatically. Across a range of empirically based parameterizations, growth effects damages result in carbon prices that are between four and ten times as high as those projected by the DICE 2016R model. While catastrophic damage scenarios lead to a wider range of outcomes, they too lead to carbon price estimates that can be as high as four times the DICE 2016R carbon price. These findings suggest that the standard DICE 2016R results may be dramatically underestimating damages from climate change, and that if recent empirical estimates are accurate, policy makers must curb emissions much more swiftly than previously thought
Evaluating the Relationship Between Habitat Interspersion and Abundance of the Hawaiian Gallinule.
No full textHabitat selection is a crucial behavioral process that affects fitness and reproductive success in animal species. Understanding habitat selection also has strong implications for the success of habitat management plans and the conservation of endangered species. The endangered Hawaiian Gallinule (Gallinula galeata sandvicensis) is a wetland specialist endemic to two islands in Hawaii. It has suffered extensive habitat loss, particularly through conversion for agriculture and by extensive urbanization; the remaining habitat has a fragmented distribution. This loss is severe on the island of Oahu, where 75% of its wetlands have been lost since human arrival to the island. Despite its importance, little research has been published for this species and little is known about the details of Hawaiian gallinule habitat requirements beyond basic associations, mostly garnered from studies of other subspecies. My research focuses on understanding the effect of interspersion, defined as the intermixing of water, emergent vegetation, floating vegetation, and bare ground, on the abundance of the Hawaiian gallinule. We gathered abundance and interspersion data at freshwater coastal wetlands along the coast of the island of Oahu between the months of May and August 2015-2017.We determined the relationship between five interspersion metrics (Contagion, Edge Density, Edge Length, Edge Index, and Simpson’s Diversity Index) and gallinule abundance using general linear models. Our analyses revealed that, among the interspersion metrics we evaluated, edge length is the best predictor of gallinule abundance in ponds on the island of Oahu. We therefore believe that the direct creation of interspersion with an emphasis on maximizing emergent/water edges could be an indispensable management tactic at increasing gallinule numbers
Chemicalized America.
No full textSince growing up in the Mount Washington Valley of New Hampshire, Mabel has always been fascinated by nature and the environment. She focuses her work around the ongoing conversation between humans and the earth. She utilizes the idea of a self-reflective experience, combined with the notion that humanity has, over time, begun to destroy the earth. Working primarily with oils to portray fragmented paintings, Mabel also adds sculptural elements into her works. She portrays an experience through her paintings that aims to make the audience feel emotional responsibility.Keywords: Painting, oil paint, mirror, environment, human development, climate change, destruction, wildlife, reflection, self-reflection
Nucleophilic Probes to Enrich the Phosphoserine and Phosphothreonine Proteomes.
No full textPhosphorylation is an important posttranslational modification to proteins that enables regulation of protein activity as well as signaling via cascades of kinases. Phosphoproteomic studies have been difficult given the suppression of ionization by the negative charges on phosphate and the non-stoichiometric nature of phosphorylation. Phosphotyrosine has been able to be studied on a proteomic scale since there are effective antibodies against it, but all antibodies that have been developed against phosphoserine and phosphothreonine have been sequence specific. To mitigate these problems, we propose eliminating phosphate from proteins using phospholyase enzymes (resulting in dehydroalanine and dehydrobutyrine) followed by the addition of immunogenic probes to allow for separation of previously phosphorylated proteins from cell lysates. In addition to enrichment, this will also increase ionization. A nucleophilic probe to enrich previously phosphorylated serine residues has been developed containing a biotin functionality, and an iodo-functionalized biotin derivative has been developed to target dehydrobutyrine using radical chemistry. Kinetics studies have been performed with the nucleophilic probe and it has been shown to be selective for dehydroalanine. The radical reaction has been shown to successfully label both dehydroalanine and dehydrobutyrine. With both of these probes in hand, phosphoproteomic analysis will be improved by enrichment using the immunogenic handles on the probes and ionization will also be improved since the previously phosphorylated site will no longer contain negative charges. To this end, preliminary lysate experiments have been performed that show that phospholyase enzymes can successfully eliminate phosphate in cell lysates and future experiments will show that the synthesized probes can label the eliminated sites in lysates
The Upstream Transcriptional Regulation of the COPD-linked DSP Gene.
No full textChronic obstructive pulmonary disorder (COPD) is a disease that affects millions of people around the world. There are many factors that can lead to the development of the disease, including certain genetic risk factors. In this study, the upstream regulation of the COPD-linked gene DSP is investigated in an attempt to understand how the gene feeds into the pathology of the disease. A possible association with the Yap1 transcription factor induced by changes in the stiffness of the matrix was explored. 16HBE cells were grown on plastic and collagen-coated plates that mimicked the extracellular matrix, and no increase in YAP1 expression was observed. Further knockdown experiments with YAP1 did not reveal a strong relationship to DSP expression. The rs2076295 SNP was also investigated, having been linked to lower expression of DSP. A reporter plasmid containing the SNP region upstream of the DSP promoter controlling expression of luciferase was constructed and used to confirm that the risk allele of the SNP region resulted in lower expression levels of DSP in 16HBE cells. The metagenomics tool DeepSEA was used to explore and screen new transcription factor candidates for further experimentation
Measuring the Affordability of Nutritious Diets in Africa: Price Indexes for Diet Diversity and the Cost of Nutrient Adequacy.
No full textPolicies and programs often aim to improve the affordability of nutritious diets, but existing food price indexes are based on observed quantities that may not meet nutritional goals. To measure changes in the cost of reaching international standards of diet quality, we introduce a new cost of diet diversity index based on the lowest-cost way to include at least five different food groups as defined by the widely used minimum dietary diversity for women (MDD-W) indicator and compare that to a Cost of Nutrient Adequacy indicator for the lowest-cost way to meet estimated average requirements of essential nutrients and dietary energy
Factors associated with wasting among children under five years old in South Asia: Implications for action.
No full textSouth Asia continues to carry the greatest share and number of wasted children worldwide. Understanding the determinants of wasting is important as policymakers renew efforts to tackle this persistent public health and development problem. Using data from national surveys in Bangladesh, India, the Maldives, Nepal, Pakistan and Afghanistan, this analysis explores factors associated with wasting among children aged 0 to 59 month