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Role of milk and dairy intake in cognitive function in older adults: a systematic review and meta-analysis.
No full textBackground: As aging populations increase across the globe, research on lifestyle factors that prevent cognitive decline and dementia is urgently needed. Therefore, a systematic review was conducted to examine the effects of varying levels of milk intake alone or in combination with other dairy products on the outcomes of cognitive function and disorders in adults.Keywords: Milk, Cognitive decline, Alzheimer's disease, Meta-analysis, Systematic review.Springer Open
Fishing for answers: Investigating Fibrodysplasia Ossificans Progressiva using a novel adult zebrafish model
No full textAbstract: Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant genetic disorder in humans characterized by the gradual ossification of fibrous tissues, including skeletal muscle, tendons, and ligaments. In humans, activating mutations in the Type I BMP/TGFβ family member receptor, ACVR1, are associated with FOP. Zebrafish acvr1l, previously known as alk8, is the functional ortholog of human ACVR1. The objective of this work is to create and characterize the first adult zebrafish model for FOP, providing a useful tool to study the development and progression of FOP-like symptoms. Constitutively active mutations in zebrafish acvr1l cause early lethal defects. Therefore, to study roles for activating acvr1l mutations in adult zebrafish, gateway cloning was used to create a vector containing the hsp70l heat shock promoter driving the expression of mCherry-tagged constitutively active Acvr1l (Q204D). Constructs were injected into single cell stage BMP response element reporter (Bre:GFP) zebrafish to create stable Tg(Bre:GFP); Tg(hsp70l:acvr1l_Q204D-mCherry) lines. Beginning at 2 weeks post fertilization, developmentally staged transgenic animals were subjected to daily one-hour heat shock treatments (3 weeks to 12 months) to induce Acvr1lQ204D expression. Micro-CT was used on whole animals to confirm FOP-like skeletal defects. Acvr1lQ204D-expressing animals displayed HO formation, abnormal spinal curvature, vertebral fusions, and malformation of pelvic fins, as compared to heat shocked Tg(Bre:GFP) animals and non-heat shocked controls. Histological stains (Safranin O and Hall and Brunt's Quadruple Stain) were used to confirm the presence of cartilaginous proteoglycans and mineralized tissue formation in the HO lesions. As injury is a known trigger for HO development in human FOP patients, several injury models were tested on Acvr1lQ204D-expressing animals to induce the formation of reliable, replicable HO. Activin A injection, cardiotoxin injection, and caudal fin clip injuries were all developed. None of these methods resulted in HO formation at the site of injury. However, cardiotoxin injected and caudal fin clipped animals did develop HO at distant sties, including the body cavity and along the spine. In summary, these results suggest that heat-shocked Acvr1lQ204D-expressing adult zebrafish provide an informative model for human FOP, but further work is needed to identify an effective method for inducing reliable site-directed HO.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Cell, Molecular & Developmental Biology.Advisor: Pamela Yelick.Committee: Leif Oxburgh, Clifford Rosen, Laura Liscum, and Aris Economides.Keywords: Biology, Molecular biology, and Genetics
GLAST regulates glutamate dynamics and interneuron maturation in the developing cortex
No full textAbstract: The astrocytic glutamate transporters GLAST and GLT-1 are highly expressed in the neocortex and are critical for regulation of extracellular glutamate concentrations. Glutamate, in turn, regulates many aspects of postnatal cortical development. However, the relative contributions and functional roles of GLAST and GLT-1 in the developing postnatal cortex are not well understood. The main goal of this dissertation is to test the hypothesis that astrocytic glutamate transporters contribute to postnatal cortical circuit development. To test this hypothesis, I used heterozygous mouse models where there is 50% reduction of GLAST or GLT-1 protein levels. Using astrocyte glutamate transporter recordings, I show that GLAST is the predominant astrocytic transporter during postnatal cortical development, while GLT-1 becomes dominant in the mature cortex. This functional finding confirms previous studies characterizing GLAST and GLT-1 expression and suggests that GLAST might be critical for the development of cortical circuits. By recording tonic NMDA currents, we show that decreased GLAST function leads to increased ambient glutamate in the developing cortex. Previous work done in the lab had shown that fast-spiking interneurons in the cortex are particularly susceptible to tonic NMDA activation due to their NMDAR subunit composition. Therefore, I tested whether the effects of altered tonic glutamate signaling had cell-type specific effects. Fast-spiking interneurons in the GLAST+/- cortex, but not excitatory pyramidal cells, have altered action potential firing and intrinsic membrane properties during development and altered morphology in the mature somatosensory cortex. Additionally, inhibitory synapse number and interneuron distribution in the cortical layers are altered in the mature GLAST+/- cortex. Finally, I found that the broad deficits in inhibitory circuits correlate with altered slice hyperexcitability in the mature GLAST+/- cortex, suggesting that loss of GLAST function during development leads to loss of inhibitory control of cortical networks. Since the GLT-1+/- cortex was not hyperexcitable at this mature stage, the results suggest that the aberrant cortical network activity observed results from disruptions during development that persist in the GLAST+/- cortex, rather than from deficits in acute glutamate uptake capacity. Taken together, the results from my thesis project indicate that GLAST, specifically, regulates glutamate in the developing neocortex and that its function is critical for the maturation of inhibitory function in cortical circuits. This main finding is in contrast with earlier work done in the thesis highlighting a role for GLT-1 in the acute response to kainic acid-induced seizures.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Neuroscience.Advisor: Chris Dulla.Committee: Michele Jacob, Yongjie Yang, and Janice Naegele.Keyword: Neurosciences
Relative Sea Level, Tides, and Extreme Water Levels in Boston Harbor From 1825 to 2018.
No full textUsing newly‐discovered archival measurements, we construct an instrumental record of water levels and storm tides in Boston (MA) since 1825. After ascertaining the 19th century datum and correcting for a 0-0.03 m bias in the modern tide‐gauge record, we show that local, decadally‐averaged relative sea level (RSL) rose by 0.28 ± 0.05 m since 1826, with an acceleration of 0.023 ± 0.009 mm/yr2. Tide range decreased by 5.5% between 1830 and 1910, due in large part to dredging and filling of Boston Harbor, and trended slightly upward thereafter. An evaluation of storm events since 1825 suggests that trends in flood risk are driven by RSL rise, with a small contribution by tidal trends. Sea‐level rise also interacts with the 18.6 year nodal cycle in tide amplitudes to produce decadal fluctuations in hazard. Conditional sampling of the 1825-2018 record shows that storm tides with a 0.01-0.5 annual probability (100 and 2 year events) are 0.1-0.2 m larger during periods with above‐average tidal amplitudes. Similarly, the once‐in‐25 year event during elevated tidal forcing becomes a once‐in‐100 year event during periods of reduced tides. A plurality of historic flood events—including floods in 1851, 1978, and 2018—occurred near the peak of the tidal nodal cycle. Projections to the year 2100 suggest that decadal fluctuations in tide characteristics will interact with relative sea‐level rise to produce a fluctuating hazard over time, with periods of relative stationarity (e.g., the 2020s) bracketed by relatively abrupt increases in flood hazard (the early 2030s
Capacity to Participate: A Case Study of Resident Participation in Somerville, MA
No full textAbstract: This thesis aims to better understand residents' capacity to engage in participatory planning processes through a nuanced look at the specific activities residents use and challenges they experience once they are already engaged in participatory processes. This thesis also aims to elaborate the role community groups play in supporting residents' engagement in participatory processes. I explore these challenges in the context of six organized resident groups that have been engaged in decision-making processes in Union Square, Somerville, MA, during the last five years. This thesis finds that residents experienced numerous challenges when participating in decision-making opportunities, pursued a variety of tasks aimed at contending with these challenges, and gained substantial support for their participation from community groups. However, community groups appeared to experience participation differently whether they were legitimized by the City or by the community. Receiving just a little recognition from the City may be worse than receiving none.Thesis (M.A.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Laurie Goldman.Committee: Penn Loh.Keyword: Urban planning
The role of deficits in KCC2-mediated ion transport in the development and severity of temporal lobe epilepsy
No full textAbstract: Temporal lobe epilepsy is the most common form of human epilepsy, believed to arise in part from compromised GABAergic inhibition. GABAA receptors permit an inward chloride flux to mediate membrane hyperpolarization and restrict neuronal firing. In most adult brain neurons, the activity of the membrane expressed type 2 K+-Cl- cotransporter (KCC2) maintains the low intracellular chloride necessary for inward chloride flux through GABAA receptors. Deficits in KCC2 are observed in brain tissue surgically removed from refractory temporal lobe epilepsy patients and in animal models of epileptogenesis. How these deficits affect the development and severity of temporal lobe epilepsy is unknown. To test this, I first performed local field potential recordings in ex vivo brain slices of the mouse temporal lobe to understand the role of KCC2 transport on network dynamics. Using multiple in vitro models of epileptiform activity, I show that deficits in KCC2 transport increase the severity of seizure events through prolonging the clonic phase of after-discharges. These results indicated that KCC2 mediated ion transport plays a critical role in the mechanisms of seizure termination. Next, I sought to understand the effects of KCC2 deficits in the pathophysiology of temporal lobe epilepsy. To test this, I locally ablated KCC2 in subsets of CAMKII positive neurons in the adult mouse hippocampus. The removal of KCC2 compromised GABAergic inhibitory signaling, confirming the role of KCC2 in setting and maintaining the reversal potential of GABAAR mediated anion flux (EGABA). Reducing KCC2 in the hippocampus in vivo resulted in spontaneous, recurring generalized seizures. Furthermore, these mice developed hippocampal sclerosis, characterized by reactive astrogliosis and neuronal loss. My results suggest KCC2 plays a key role in hippocampal network function and the development and severity of temporal lobe epilepsy.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Neuroscience.Advisor: Stephen Moss.Committee: Jamie Maguire, Chris Dulla, Michele Jacobs, and Shilpa Kadam.Keywords: Neurosciences, Biology, and Medicine
A Micromolding-based Evaporation-Polymerization Technique for Rapid and Tunable Fabrication of Hydrogel Films Containing Micropatterned Opal Structures
No full textAbstract: Opal-structured thin-film hydrogel materials hold great potential for utility in a wide range of sensing applications. However, it remains significantly challenging to synthesize these films in a rapid, inexpensive and reliable manner. Prevailing techniques especially suffer from long opal deposition times, and often tend to involve complex and relatively expensive steps. In this thesis, I examined a reliable, rapid and inexpensive micromolding-based evaporation-polymerization method for fabricating poly (ethylene glycol)-based opal-structured thin films. Specifically, intense, highly uniform opalescent colors were achieved by filling microwells in a PDMS mold with Polystyrene (PS) bead solution and allowing the liquid in the bead solution to evaporate in a controlled manner so that the PS beads were arranged into a Face-centered cubic (FCC) structure. Then, upon drying, the interstitial spaces of the packed structure were filled with a UV-curable poly(ethylene glycol) diacrylate (PEGDA) prepolymer solution. The prepolymer solution was polymerized under UV light and the opal-containing PEG films recovered by peeling them off from the mold. Opal deposition using my evaporation-aided technique reduces deposition time to 30-45 minutes only. In addition, the as-prepared films show high tunability of opal color by simply changing PEGDA content in the prepolymer solution. Swelling and de-swelling studies show highly reversible and tunable responsiveness of the films to wetness, pointing to potential applications in humidity sensing. Finally, SEM images confirm the preservation of the FCC structure of the opals in these films.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Chemical and Biological Engineering.Advisor: Hyunmin Yi.Committee: Ayse Asatekin, and Qiaobing Xu.Keywords: Nanotechnology, Materials Science, and Chemical engineering
Trip Duration and Mode Choice Analysis: A study of Below Median Income Households in the Boston Metropolitan Region
No full textAbstract: Many factors of the built and the non-built environment can significantly influence travel behavior. This thesis will assess how the built environment can influence the time that an individual spends traveling while controlling for their socio-economic characteristics. Additionally, the study will look at how the built environment influences the choice of non-automobile modes of transportation: walk, bike and transit. The focus of the study is on trips made by individuals in below median income households in the Boston Metropolitan Region using the Massachusetts Travel Survey of 2010 in combination with build environment data developed by the Environment Protection Agency. This study confirms previous research suggesting that density, diversity and design variables of the built environment have a significant influence on daily mobility decisions on both travel duration and mode choice. Specifically, accessibility of jobs by the working age population at the origin was found to significantly influence trip durations as well as mode choice. The results suggest the continued role of jobs-housing balance to improve accessibility for low-income households in the region. The thesis ends by highlighting the factors that need to be considered by planners and policy makers to positively influence the use of non- automobile mode choices in the Boston Metropolitan Region as it plans for a sustainable future.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisor: Sumeeta Srinivasan.Committee: Mary Davis.Keywords: Transportation, and Urban planning
Expanding the green network on rooftops: A Study of integrating green roofs as a part of urban green space planning
No full textAbstract: This thesis explores the concept of green roofs and urban green space planning. Through a quantitative GIS analysis and various qualitative content analysis on most recent open space plans in Boston, this thesis aims to look at whether existing open space plans have considered applying spatial planning elements for green roofs, a prominent type of green infrastructure. Various green roofs programs and ordinances in the US recognized the multifunctionality of green roofs. But in the aspect of spatial planning, green roofs have not been integrated as a part of open space management. However, in the most recent Open Space and Recreation Plan 2015 - 2021, some green roofs key words could be found in the plan that indicates that the city is open to extend the functions of green roofs and explore ways to enhance urban green space network that includes green infrastructure.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Urban and Environmental Policy and Planning.Advisors: Justin Hollander, and Sumeeta Srinivasan.Keyword: Urban planning
Impacts of Salinity and Polymer Coating on the Mobility of Iron Oxide Nanoparticles in Porous Media
No full textAbstract: Iron Oxide Nanoparticles represent a technology useful for more efficiently locating oil in reservoirs. This research analyzes the effects of Ionic strength, electrolyte species, and porous media on polymer coated, iron oxide nanoparticle transport. Berea and Bentheimer intact sandstone cores were chosen as porous media for their compositional differences and because, they represent reservoirs in which the majority of oil is found.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Civil Engineering.Advisor: Kurt Pennell.Committee: John Germaine, and Natalie Capiro.Keyword: Environmental engineering