Defining mixed-use: which land uses promote walking?

A growing body of literature finds that mixed-use development can affect trip frequency, trip length and mode choice. Though researchers have explored the general impacts of this type of development on travel, few have examined which specific land uses should be mixed to achieve transportation-related goals. This Master's Project addresses this gap in the literature, focusing on the influence of mixed land uses on utilitarian walking. Built environment data was related to utilitarian walking and total walking for individuals (n=251) in Montgomery County, Maryland. For a variety of land uses, exposure measures included the distance from participants' homes to the closest instance of each land use (presence), the number of instances of each land use within ½ and ¼ mile buffers of homes (intensity), and the number of different land uses present within ½ and ¼ mile buffers of homes (diversity). Distances to bus stops, fast food restaurants, grocery stores, Metro stations, offices, physical activity uses, recreational facilities, restaurants, social uses and sports facilities were negatively associated with transportation walking (OR .01- .90). The intensities of bus stops, grocery stores, offices, and retail stores were positively correlated with utilitarian walking (OR 1.04-5.51). Furthermore, a dose-response relationship between land use diversity and walking for transport was detected. Results suggest that planners, policymakers and developers can encourage physical activity and promote walking as a travel mode choice through the careful design of mixed-use developments.Master of City and Regional Plannin

Interview with Norman Krumholz

Norman Krumholz is a towering figure in the eyes of many planners. A proponent of equity planning—the term Paul Davidoff coined in 1965 to refer to planning for the whole city and prioritizing the needs of populations habitually excluded from the process—he pioneered approaches to improve the quality of life in disadvantaged communities. During Krumholz’s groundbreaking ten years as Cleveland’s planning director from 1969-1979, he put this theory into practice, later describing his experiences in a book entitled Making Equity Planning Work. Krumholz visited UNC-Chapel Hill on Oct. 9, 2008, to deliver a public lecture titled “New Roles and New Status for Planners.” In the talk, co-sponsored by the Department of City of Regional Planning and the Center for Urban and Regional Studies, Krumholz described how the changing shape of cities poses new challenges for today’s planners. He dispelled several myths about industrial cities, including the belief that “the decline can be reversed and the cities restored to their former glory.” Instead of emphasizing greening efforts, New Urbanism, and blockbuster stadium projects, he said planners should focus on the basics: fixing cities’ schools, services, and safety. In an exclusive Carolina Planning interview, editors Wendy Baucom and Heather Schroeder sat down with Krumholz before his public lecture to speak about the biggest issues facing today’s planners. Given his track record, it may be no surprise that Krumholz encourages planners to continue breaking the mold

Mitochondrial metabolism of sexual and asexual blood stages of the malaria parasite Plasmodium falciparum

BACKGROUND: The carbon metabolism of the blood stages of Plasmodium falciparum, comprising rapidly dividing asexual stages and non-dividing gametocytes, is thought to be highly streamlined, with glycolysis providing most of the cellular ATP. However, these parasitic stages express all the enzymes needed for a canonical mitochondrial tricarboxylic acid (TCA) cycle, and it was recently proposed that they may catabolize glutamine via an atypical branched TCA cycle. Whether these stages catabolize glucose in the TCA cycle and what is the functional significance of mitochondrial metabolism remains unresolved. RESULTS: We reassessed the central carbon metabolism of P. falciparum asexual and sexual blood stages, by metabolically labeling each stage with (13)C-glucose and (13)C-glutamine, and analyzing isotopic enrichment in key pathways using mass spectrometry. In contrast to previous findings, we found that carbon skeletons derived from both glucose and glutamine are catabolized in a canonical oxidative TCA cycle in both the asexual and sexual blood stages. Flux of glucose carbon skeletons into the TCA cycle is low in the asexual blood stages, with glutamine providing most of the carbon skeletons, but increases dramatically in the gametocyte stages. Increased glucose catabolism in the gametocyte TCA cycle was associated with increased glucose uptake, suggesting that the energy requirements of this stage are high. Significantly, whereas chemical inhibition of the TCA cycle had little effect on the growth or viability of asexual stages, inhibition of the gametocyte TCA cycle led to arrested development and death. CONCLUSIONS: Our metabolomics approach has allowed us to revise current models of P. falciparum carbon metabolism. In particular, we found that both asexual and sexual blood stages utilize a conventional TCA cycle to catabolize glucose and glutamine. Gametocyte differentiation is associated with a programmed remodeling of central carbon metabolism that may be required for parasite survival either before or after uptake by the mosquito vector. The increased sensitivity of gametocyte stages to TCA-cycle inhibitors provides a potential target for transmission-blocking drugs

The key glycolytic enzyme phosphofructokinase is involved in resistance to antiplasmodial glycosides

ABSTRACT Plasmodium parasites rely heavily on glycolysis for ATP production and for precursors for essential anabolic pathways, such as the methylerythritol phosphate (MEP) pathway. Here, we show that mutations in the Plasmodium falciparum glycolytic enzyme, phosphofructokinase (PfPFK9), are associated with in vitro resistance to a primary sulfonamide glycoside (PS-3). Flux through the upper glycolysis pathway was significantly reduced in PS-3-resistant parasites, which was associated with reduced ATP levels but increased flux into the pentose phosphate pathway. PS-3 may directly or indirectly target enzymes in these pathways, as PS-3-treated parasites had elevated levels of glycolytic and tricarboxylic acid (TCA) cycle intermediates. PS-3 resistance also led to reduced MEP pathway intermediates, and PS-3-resistant parasites were hypersensitive to the MEP pathway inhibitor, fosmidomycin. Overall, this study suggests that PS-3 disrupts core pathways in central carbon metabolism, which is compensated for by mutations in PfPFK9, highlighting a novel metabolic drug resistance mechanism in P. falciparum. IMPORTANCE Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue, causing 405,000 deaths and 228 million cases in 2018. Understanding key metabolic processes in malaria parasites is critical to the development of new drugs to combat this major infectious disease. The Plasmodium glycolytic pathway is essential to the malaria parasite, providing energy for growth and replication and supplying important biomolecules for other essential Plasmodium anabolic pathways. Despite this overreliance on glycolysis, no current drugs target glycolysis, and there is a paucity of information on critical glycolysis targets. Our work addresses this unmet need, providing new mechanistic insights into this key pathway

Invasion of the Red Seaweed \u3cem\u3eHeterosiphonia japonica\u3c/em\u3e Spans Biogeographic Provinces in the Western North Atlantic Ocean

The recent invasion of the red alga Heterosiphonia japonica in the western North Atlantic Ocean has provided a unique opportunity to study invasion dynamics across a biogeographical barrier. Native to the western North Pacific Ocean, initial collections in 2007 and 2009 restricted the western North Atlantic range of this invader to Rhode Island, USA. However, through subtidal community surveys, we document the presence of Heterosiphonia in coastal waters from Maine to New York, USA, a distance of more than 700 km. This geographical distribution spans a well-known biogeographical barrier at Cape Cod, Massachusetts. Despite significant differences in subtidal community structure north and south of Cape Cod, Heterosiphonia was found at all but two sites surveyed in both biogeographic provinces, suggesting that this invader is capable of rapid expansion over broad geographic ranges. Across all sites surveyed, Heterosiphonia comprised 14% of the subtidal benthic community. However, average abundances of nearly 80% were found at some locations. As a drifting macrophyte, Heterosiphonia was found as intertidal wrack in abundances of up to 65% of the biomass washed up along beaches surveyed. Our surveys suggest that the high abundance of Heterosiphonia has already led to marked changes in subtidal community structure; we found significantly lower species richness in recipient communities with higher Heterosiphona abundances. Based on temperature and salinity tolerances of the European populations, we believe Heterosiphonia has the potential to invade and alter subtidal communities from Florida to Newfoundland in the western North Atlantic

Global Analysis of Protein N-Myristoylation and Exploration of N-Myristoyltransferase as a Drug Target in the Neglected Human Pathogen Leishmania donovani

N-Myristoyltransferase (NMT) modulates protein function through the attachment of the lipid myristate to the N terminus of target proteins, and is a promising drug target in eukaryotic parasites such as Leishmania donovani. Only a small number of NMT substrates have been characterized in Leishmania, and a global picture of N-myristoylation is lacking. Here, we use metabolic tagging with an alkyne-functionalized myristic acid mimetic in live parasites followed by downstream click chemistry and analysis to identify lipidated proteins in both the promastigote (extracellular) and amastigote (intracellular) life stages. Quantitative chemical proteomics is used to profile target engagement by NMT inhibitors, and to define the complement of N-myristoylated proteins. Our results provide new insight into the multiple pathways modulated by NMT and the pleiotropic effects of NMT inhibition. This work constitutes the first global experimental analysis of protein lipidation in Leishmania, and reveals the extent of NMT-related biology yet to be explored for this neglected human pathogen

Organic carbon dataset of paper submitted to Journal of Geophysical Research: Biogeosciences entitled "Seasonal and Spatial Variability of Dissolved Carbon Concentration and Composition in Lake Michigan Tributaries"

Dissolved organic matter (DOM) is a complex mixture of many compounds, and its composition dictates numerous reactions in the environment. Large lakes and marine coastlines receive DOM from watersheds that differ widely in their land cover, with potential implications for both the quantity and composition of carbon inputs. Seasonal variation in DOM quantity and composition may also differ among tributaries and be mediated by land cover. Here, we quantify spatial (i.e., among tributary) and seasonal variation in DOM concentration, DOM composition based on ultraviolet-visible spectroscopy, and alkalinity across 101 tributaries of Lake Michigan, one of the world’s largest lakes, using a synoptic sampling approach. Wetland land cover has the largest effect on DOM, producing high concentrations of DOM that is more aromatic and larger in apparent molecular weight. Seasonal variation is also pronounced, with concentrations and aromaticity of DOM peaking in fall across most tributaries. Watershed lithology and land cover both affect alkalinity, with higher values associated with the geography of carbonate bedrock and in urbanized watersheds. Watershed land cover has a larger affect than season on all organic carbon parameters. However, seasonal variation is especially important for DOM composition. This disparity suggests that environmental processing of DOM within river channels mediates its composition more than its concentrations. Considering the wide range of land cover and lithology around Lake Michigan and other large water bodies, accounting for both spatial and seasonal dynamics is essential for understanding controls on DOM delivery.SMB was supported by NSF CBET (1802388). Additional funding for this work was provided by a Department of Interior Northeast Climate Adaptation Science Center graduate fellowship to RJM. Additional funds were provided to RJM through a UW-Madison Department of Zoology Graduate Fellowship

Invasion of the red seaweed Heterosiphonia japonica spans biogeographic provinces in the Western North Atlantic Ocean.

The recent invasion of the red alga Heterosiphonia japonica in the western North Atlantic Ocean has provided a unique opportunity to study invasion dynamics across a biogeographical barrier. Native to the western North Pacific Ocean, initial collections in 2007 and 2009 restricted the western North Atlantic range of this invader to Rhode Island, USA. However, through subtidal community surveys, we document the presence of Heterosiphonia in coastal waters from Maine to New York, USA, a distance of more than 700 km. This geographical distribution spans a well-known biogeographical barrier at Cape Cod, Massachusetts. Despite significant differences in subtidal community structure north and south of Cape Cod, Heterosiphonia was found at all but two sites surveyed in both biogeographic provinces, suggesting that this invader is capable of rapid expansion over broad geographic ranges. Across all sites surveyed, Heterosiphonia comprised 14% of the subtidal benthic community. However, average abundances of nearly 80% were found at some locations. As a drifting macrophyte, Heterosiphonia was found as intertidal wrack in abundances of up to 65% of the biomass washed up along beaches surveyed. Our surveys suggest that the high abundance of Heterosiphonia has already led to marked changes in subtidal community structure; we found significantly lower species richness in recipient communities with higher Heterosiphona abundances. Based on temperature and salinity tolerances of the European populations, we believe Heterosiphonia has the potential to invade and alter subtidal communities from Florida to Newfoundland in the western North Atlantic

Disaggregate Land Uses and Walking

Background: Although researchers have explored associations between mixed-use development and physical activity, few have examined the influence of specific land uses. Purpose: This study analyzes how the accessibility, intensity, and diversity of nonresidential land uses are related to walking for transportation. Methods: Multinomial logistic regression was used to investigate associations between walking for transportation and neighborhood land uses in a choice-based sample of individuals (n=260) in Montgomery County MD. Land uses examined included banks, bus stops, fast-food restaurants, grocery stores, libraries, rail stations, offices, parks, recreation centers, nonfast-food restaurants, retail, schools, sports facilities, night uses, physical activity uses, and social uses. Exposure to these uses was measured as the street distance from participants' homes to the closest instance of each land use (accessibility); the number of instances of each land use (intensity); and the number of different land uses (diversity). Data were collected from 2004-2006 and analyzed in 2009-2010. Results: After adjusting for individual-level characteristics, the distances to banks, bus stops, fast-food restaurants, grocery stores, rail stations, physical activity uses, recreational facilities, restaurants, social uses and sports facilities were associated negatively with transportation walking (ORs [95% CI] range from 0.01 [0.001, 0.11] to 0.91 [0.85, 0.97]). The intensities of bus stops, grocery stores, offices, and retail stores in participants' neighborhoods were associated positively with transportation walking (ORs [95% CI] range from 1.05 [1.01, 1.08] to 5.42 [1.73, 17.01]). Land-use diversity also was associated positively with walking for transportation (ORs [95% CI] range from 1.39 [1.20, 1.59] to 1.69 [1.30, 2.20]). Conclusions: The accessibility and intensity of certain nonresidential land uses, along with land-use diversity, are positively associated with walking for transportation. A careful mix of land uses in a neighborhood can encourage physical activity.close18232