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Extracellular vesicles are increased in the serum of children with autism spectrum disorder, contain mitochondrial DNA, and stimulate human microglia to secrete IL-1β.
No full textBackground: Autism spectrum disorder (ASD) has been associated with brain inflammation as indicated by the activation of microglia, but the triggers are not known. Extracellular vesicles (EVs) are secreted from many cells in the blood and other biological fluids and carry molecules that could influence the function of target cells. EVs have been recently implicated in several diseases, but their presence or function in ASD has not been studied.Keywords: Autism spectrum disorder, Brain, Exosomes, Extracellular vesicles, Inflammation, IL-1β, Microglia, Mitochondrial DNA.Springer Open
Investigating cis and trans factors involved in common fragile site breakage and healing using Flex1, a subregion of FRA16D
No full textAbstract: Common Fragile Sites (CFSs) are regions of DNA that display gaps and breaks in metaphase chromosomes under replication stress. While CFSs are not normally expressed, or broken, in individuals, conditions of replication stress result in their breakage. Evidence of such sites has been found in organisms ranging from yeast to humans. Further, CFSs are often sites of rearrangement in cancer cell lines, therefore understanding their expression is very relevant to human disease. CFSs are late replicating, and conditions of replication stress result in their under-replication at the point of chromatin condensation in the cell cycle. CFSs are enriched in DNA sequences that can form abnormal, or secondary, structures, which could also play a role in their breakage. There are several theories for the cause of CFS breakage, each with varying levels of support, and this is largely due to the difficulty of studying complicated DNA sequences in mammalian cells. Here, we studied Flex1, a roughly 300 bp subregion of CFS FRA16D in S. cerevisiae that has a perfect AT repeat that is highly polymorphic in humans and predicted to form stable secondary structures in vivo. Flex1 also stalls replication in an AT repeat length-dependent manner. Working in yeast allows precise genetic control of DNA sequences, making it an excellent model system to investigate current theories for CFS breakage. We have found that breakage at Flex1 is dependent on structure-specific endonuclease (SSE) complexes Mus81-Mms4, Slx1-Slx4, and Rad1-Rad10, similar to what has been found for human SSEs at FRA16D. Thus, Flex1 serves as a model system for studying breakage and healing at a CFS sequence. The cleavage of Flex1 by Mus81 is dependent on the formation of a secondary structure by the AT repeats. By comparing the effects of different Flex1 sequences on breakage and healing, we have evidence to propose a new theory for CFS expression: CFSs are not only prone to breakage but also impaired in their ability to heal following fragility. We propose that breakage in FRA16D is initiated by SSE cleavage at Flex1, followed by difficulty healing after fragility due to the propensity of adjacent sequences to form hairpins. We also discovered a role for the fork stabilization function of the Mrc1 (hClaspin protein) in protecting against fragility at Flex1, supporting an important link between fork stalling and fragility.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Biology.Advisor: Catherine Freudenreich.Committee: Mitch McVey, Sergei Mirkin, and Sharon Cantor.Keywords: Genetics, Molecular biology, and Biology
Assessing Conservation Easements and Their Adaptability to Change in Strafford County, New Hampshire
No full textAbstract: Conservation easements have many positive benefits to society which include land preservation and protection of natural resources. Often, they are designated in perpetuity, which makes them difficult to modify and presents challenges in the face of a changing climate, landscape, and ecosystem (Owley, 2011). This content analysis assessed the conservation easements located in Strafford County, New Hampshire, in order to understand their preparedness to handle land use modifications and the amendment process. A majority of the easements in Strafford County can be characterized as encouraging open space, natural resource and habitat protection. Most do not have an amendment provision, making them less prepared to adapt to future land use needs. Amendment provisions should be included in future agreements to facilitate the modification process. It appeared that easement holders are working in close collaboration with the Charitable Trusts Unit during the amendment process which should continue to occur.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Jon Witten.Committee: Mary Davis.Keyword: Land use planning
Agriculture and Solar Energy Development in Massachusetts: Potential Conflicts and Synergies
No full textAbstract: This research explores conflicts and synergies between preserving farmland and scaling up solar development in Massachusetts. As solar technology and farming require similar inputs, it is prudent to consider ways that solar can aid farms' success. This work strives to understand whether agriculture and solar are compatible; to identify potential conflicts; and to develop a model for quantifying land available for solar development. Using snowball sampling to select sixteen experts—farmers, solar developers, and other stakeholders—I conducted semi-structured interviews from which several themes emerged: solar is a means of farm diversification; many farmers feel favorably about solar on farmland; the lack of rural electrical infrastructure and the seasonal constraints unique to farming are primary obstacles to expanding solar to farms; and solar companies exhibit varying capacities to work with farms. This study begins to fill the gaps in knowledge surrounding the intersection of Massachusetts' agricultural and solar energy sectors.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Barbara Parmenter.Committee: Timothy Griffin.Keywords: Land use planning, Agriculture economics, and Energy
The role of the tissue microenvironment in resistance and susceptibility of the rat mammary gland to carcinogenesis
No full textAbstract: ABSTRACT N-nitrosomethylurea (NMU) administration to rats of several susceptible strains leads to rapid, reproducible, tumor production. The Copenhagen (COP) rat strain, however, is completely resistant to NMU carcinogenesis. The cause of this resistance is yet unknown. Using tissue recombination experiments, our lab has shown that the mammary gland stroma is the "gatekeeper" for tumorigenesis; also, NMU-exposed stroma transformed non-exposed mammary epithelial cells (MECs) while non-exposed stroma combined with exposed MECs produced normal ductal structures. Here, I hypothesize that the tumor-resistant phenotype of COP rats is due to stromal-mediated stabilization of tissue-wide disruptions in the mammary gland that develop following carcinogenic exposure. In order to generate a surrogate model for tissue recombinations, I proposed a three-dimensional (3D) culture model that recapitulates the biochemical and biophysical forces required for the formation of normal structures found in the mammary gland. I detail the characterization of an epithelial cell line for use in hormone-responsive 3D culture. Co-culture of human MECs with rat fibroblasts in floating collagen gels results in the formation of multicellular structures. NMU treated fibroblasts from susceptible Wistar-Firth (WF) animals are involved in the formation of highly variable structures with low biological quality. Expression data derived from COP and WF cleared fat pads following NMU exposure is analyzed. I propose to study stromal factors involved in COP resistance and further, to compare stromal-epithelial interactions between resistant COP rats and Wistar-Furth rats, an NMU-susceptible rat strain. This work will give new insights into the understanding of COP resistance and broaden our understanding of stromal contributions to induction or inhibition of carcinogenesis in both of these rat strains. Those insights, in turn, will better inform us about carcinogenesis in humans. Theoretical challenges to the current prevailing theory of carcinogenesis are given and used to explain the thesis findings as well as put into context how altered development influences tumor susceptibility. The outcomes of the experiments detailed here are important for furthering our understanding of the process of tumorigenesis, provide a possible explanation for autonomous tumor remission and, more broadly, aim to widen the focus of treatment beyond the breast epithelial compartment.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Genetics.Advisors: Ana Soto, and Carlos Sonnenschein.Committee: Philip Hinds, Pamela Yelick, and Al Gustafson.Keyword: Biology
Impacts of Land Use Change on Guatemalan Food Sovereignty
No full textAbstract: In 2014 the World Food Programme estimated that 130,000 smallholder farmers in Guatemala lost crops due to a drought . That same year Guatemala also enjoyed 5-year highs in the production of water-intensive large-scale export crops: banana and sugar cane . This is one example of a series of food price and climate shocks that have caused many to question the impact of the global food system on the world's poor. Guatemala is a particularly pointed example of the issues many countries face. Its fertile soil and varied climatic regions make it a productive place to grow food. This has led to it becoming an important producer of specific agricultural goods such as coffee, sugar, bananas, and oilseed palm, yet it struggles with one of the highest rates of malnutrition in the Western Hemisphere as well as pervasive food insecurity. Some have argued that this trend is due to the allocation of prime agricultural resources to export agriculture and the forcing of non-export agriculture onto marginal lands with high climate vulnerability. This research quantifies the geographic changes in Guatemalan export and non-export agriculture over the period of 2003-2010 and relates those changes to the vulnerability of the domestic food supply to climate change and international food price spikes. I find that non-export agriculture is moving onto more marginal land at higher elevations which both reduces expected yields and increases the likelihood of crop failure.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Sumeeta Srinivasan.Committee: Timothy Griffin.Keywords: Agriculture, and Nutrition
Identifying Keys for Successful Development and their Implications for Greenhouse Gas Emissions
No full textAbstract: In recent decades, international environmental policy and development scholars argue that (i) countries act by following their near-term national interests in this physically limited earth, (ii) population and stresses on environment accompanying development are increasing globally, (iii) development is the most prioritized issue over environmental problem mitigations for both developed and developing countries, and (iv) development and environment need to both be sustainable for developing countries to succeed. Those arguments became the motivation of this dissertation, which is "To learn from successful developing countries that achieved both lower GHG emissions per capita (GHGpc) and improved development 1990-2010." Therefore this dissertation asks "What factors determine whether developing countries achieve lower GHG emissions while meeting their development goals?" Hypotheses that were tested were (i) National policy initiatives, strategies and changes in practices were effective in the successful countries; (ii) Responses to external factors were effective in the successful countries; (iii) Financing by development agencies was effective in the successful countries; and (iv) The mix of economic activities at different stages of development lead to success in the successful countries. Development was measured by the three components of the Human Development Index (HDI). GHG emissions were analyzed using a modified Kaya identity. The findings were compared with insights from 83 in-country development experts. The quantitative data analysis found that many poor countries in the world were successful in increasing their HDI and decreasing GHGpc during 1990-2010. Among them in Asia, Myanmar and Nepal were recognized as very successful countries, and Mongolia and Bangladesh as successful countries. From the qualitative data analysis, this dissertation finds that Myanmar was very successful because of its effective forestry policy regulations that reduced GHGs from land use, change and forestry (LUCF), and its shift away from agriculture and forestry into other natural resources and tertiary industries. Nepal was very successful because its policy regulations effectively improved HDI health and income parameters and reduced GHGs from LUCF, while it transitioned out of forestry and gained remittances from overseas workers and the service sector. The dissertation also finds that Mongolia was a successful country because donors' support during the economic crisis had the positive consequence of reducing GHG emissions through technical modernization, and that Bangladesh was successful because its policy regulations effectively improved its HDI parameters while domestic natural gas replaced higher emitting coal. The findings suggest a positive possibility that if a developing country can find alternative ways to generate income, it can encourage a shift out of agriculture and forestry sectors, from which many developing countries release the majority of GHGs. There is also a negative outcome if their reliance on exports of natural resources or their reliance on remittances from overseas workers increase, then GHGs in other countries may increase where those natural resources are consumed, or in the countries where the overseas workers work. It is also demonstrated that development of the four successful countries were consistent with many of the Sustainable Development Goals (SDGs) even though they were created five years after the study period. The following countries, however, did not move forward on (i) GHG related goals for Bangladesh, (ii) health and education related goals for Myanmar, and (iii) health and education related goals for Mongolia. Nepal was the only country to meet all those goals in Asia. Therefore, to achieve SDGs it is recommended that Bangladesh should improve GHG emission reduction, Myanmar should improve health and education, Mongolia should improve health, and Nepal should continue its current practices in the upcoming decade.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Diplomacy, History, and Politics.Advisor: William Moomaw.Committee: Ann Rappaport, and Shinsuke Tanaka.Keywords: Climate change, Environmental studies, and International relations
Amygdala and behavioral responses to ambiguous emotional stimuli in posttraumatic stress disorder.
No full textFunctional magnetic neuroimaging (fMRI) study comparing amygdala activation in response to surprised facial expressions with valence ratings and emotional categorization of surprised facial expressions in Vietnam veterans with and without posttraumatic stress disorder (PTSD). Submitted in partial fulfillment of the grant requirement of the Tufts Summer Scholars Program
Generalizing remotely supervised transcranial direct current stimulation (tDCS): feasibility and benefit in Parkinson's disease.
No full textBackground: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that has been shown to improve common symptoms of neurological disorders like depressed mood, fatigue, motor deficits and cognitive dysfunction. tDCS requires daily treatment sessions in order to be effective. We developed a remotely supervised tDCS (RS-tDCS) protocol for participants with multiple sclerosis (MS) to increase accessibility of tDCS, reducing clinician, patient, and caregiver burden. The goal of this protocol is to facilitate home use for larger trials with extended treatment periods. In this study we determine the generalizability of RS-tDCS paired with cognitive training (CT) by testing its feasibility in participants with Parkinson's disease (PD).Keywords: Transcranial direct current stimulation, tDCS, Telerehabilitation, Parkinson's disease, Multiple sclerosis.Springer Open
Impact of Pilot School garden project on children's food knowledge, preference and behavior in Nepal.
No full textThis presentation was from 6th Annual scientific Symposium in Nepal