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"Taylor, Sarah"
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High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis
2023
Single-cell and spatial technologies that profile gene expression across a whole tissue are revolutionizing the resolution of molecular states in clinical samples. Current commercially available technologies provide whole transcriptome single-cell, whole transcriptome spatial, or targeted in situ gene expression analysis. Here, we combine these technologies to explore tissue heterogeneity in large, FFPE human breast cancer sections. This integrative approach allowed us to explore molecular differences that exist between distinct tumor regions and to identify biomarkers involved in the progression towards invasive carcinoma. Further, we study cell neighborhoods and identify rare boundary cells that sit at the critical myoepithelial border confining the spread of malignant cells. Here, we demonstrate that each technology alone provides information about molecular signatures relevant to understanding cancer heterogeneity; however, it is the integration of these technologies that leads to deeper insights, ushering in discoveries that will progress oncology research and the development of diagnostics and therapeutics.
The integration of single-cell and spatial data can provide a more comprehensive picture of the network of cells within the tumour microenvironment. Here the authors use a combination of single-cell and spatial technologies including 10x Xenium to characterise serial formalin-fixed, paraffin-embedded human breast cancer sections.
Journal Article
Spatial transcriptomics at subspot resolution with BayesSpace
by
Smythe, Kimberly S.
,
Guenthoer, Jamie
,
Uytingco, Cedric R.
in
631/114/2415
,
631/208/199
,
631/250/2503
2021
Recent spatial gene expression technologies enable comprehensive measurement of transcriptomic profiles while retaining spatial context. However, existing analysis methods do not address the limited resolution of the technology or use the spatial information efficiently. Here, we introduce BayesSpace, a fully Bayesian statistical method that uses the information from spatial neighborhoods for resolution enhancement of spatial transcriptomic data and for clustering analysis. We benchmark BayesSpace against current methods for spatial and non-spatial clustering and show that it improves identification of distinct intra-tissue transcriptional profiles from samples of the brain, melanoma, invasive ductal carcinoma and ovarian adenocarcinoma. Using immunohistochemistry and an in silico dataset constructed from scRNA-seq data, we show that BayesSpace resolves tissue structure that is not detectable at the original resolution and identifies transcriptional heterogeneity inaccessible to histological analysis. Our results illustrate BayesSpace’s utility in facilitating the discovery of biological insights from spatial transcriptomic datasets.
BayesSpace increases the resolution of spatial transcriptomics by using neighborhood information.
Journal Article
From subjects to citizens : society and the everyday state in India and Pakistan, 1947-1970
\"Offers a fresh and timely perspective on the broader field of early postcolonial South Asian history\"-- Provided by publisher.
Vitamin D in Toddlers, Preschool Children, and Adolescents
2020
Background: Vitamin D supplementation is known to both prevent and treat rickets, a disease of hypomineralized bone. Childhood is a period of great bone development and, therefore, attention to the vitamin D needed to optimize bone health in childhood is imperative. Summary: Observational studies have pointed to a vitamin D status, as indicated by a 25-hydroxyvitamin D concentration, of 50 nmol/L to ensure avoidance of rickets and of 75 nmol/L to optimize health. However, the benefits of achieving these levels of vitamin D status are less evident when pediatric randomized, controlled trials are performed. In fact, no specific pediatric vitamin D supplementation has been established by the existing evidence. Yet, study of vitamin D physiology continues to uncover further potential benefits to vitamin D sufficiency. This disconnection between vitamin D function and trials of supplementation has led to new paths of investigation, including establishment of the best method to measure vitamin D status, examination of genetic variation in vitamin D metabolism, and consideration that vitamin D status is a marker of another variable, such as physical activity, and its association with bone health. Nevertheless, vitamin D supplementation in the range of 10–50 μg/day appears to be safe for children and remains a promising intervention that may yet be supported by clinical trials as a method to optimize pediatric health. Key Message: Pediatric vitamin D status is associated with avoidance of rickets. Randomized, controlled trials of vitamin D supplementation for pediatric bone health are limited and equivocal in their results. Beyond bone, decreased risk for autoimmune, infectious, and allergic diseases has been associated with higher vitamin D status. The specific vitamin D supplementation to optimize toddler, child, and adolescent outcomes is unknown, but doses 10–50 μg/day are safe and may be beneficial.
Journal Article
Supplying urban ecosystem services through multifunctional green infrastructure in the United States
by
Lovell, Sarah Taylor
,
Taylor, John R.
in
Adaptations
,
Animal, plant and microbial ecology
,
Applied ecology
2013
This paper summarizes a strategy for supplying ecosystem services in urban areas through a participatory planning process targeting multifunctional green infrastructure. We draw from the literature on landscape multifunctionality, which has primarily been applied to agricultural settings, and propose opportunities to develop urban green infrastructure that could contribute to the sustainable social and ecological health of the city. Thinking in terms of system resilience, strategies might focus on the potential for green infrastructure to allow for adaptation and even transformation in the face of future challenges such as climate change, food insecurity, and limited resources. Because planning for multiple functions can be difficult when many diverse stakeholders are involved, we explored decision support tools that could be applied to green infrastructure planning in the early stages, to engage the public and encourage action toward implementing a preferred solution. Several specific ecosystem services that could be relevant for evaluating current and future urban green spaces include: plant biodiversity, food production, microclimate control, soil infiltration, carbon sequestration, visual quality, recreation, and social capital. Integrating such ecosystem services into small-scale greening projects could allow for creativity and local empowerment that would inspire broader transformation of green infrastructure at the city level. Those cities committing to such an approach by supporting greening projects are likely to benefit in the long run through the value of ecosystem services for urban residents and the broader public.
Journal Article
Vitamin D for very preterm infants—determining the how, when, and why
2024
A recent survey study found that 400 IU/day vitamin D is the most common dose in United States neonatal intensive care units. Results of clinical trials are inconsistent, and, therefore, have not determined the optimal vitamin D dose for efficacy and safety in the neonatal intensive care unit. Future studies must consider the unique attributes of perinatal vitamin D metabolism and the potential role of vitamin D in immune function and organ development. IMPACT: Preterm infant vitamin D metabolism is a complex yet important area of research.
Journal Article
Interannual monsoon wind variability as a key driver of East African small pelagic fisheries
by
Kelly, Stephen
,
Roberts, Michael J.
,
Scott, Lucy
in
704/106/829/2737
,
704/106/829/826
,
Annual variations
2020
Small pelagic fisheries provide food security, livelihood support and economic stability for East African coastal communities—a region of least developed countries. Using remotely- sensed and field observations together with modelling, we address the biophysical drivers of this important resource. We show that annual variations of fisheries yield parallel those of chlorophyll-a (an index of phytoplankton biomass). While enhanced phytoplankton biomass during the Northeast monsoon is triggered by wind-driven upwelling, during the Southeast monsoon, it is driven by two current induced mechanisms: coastal “dynamic uplift” upwelling; and westward advection of nutrients. This biological response to the Southeast monsoon is greater than that to the Northeast monsoon. For years unaffected by strong
El-Niño
/
La-Niña
events, the Southeast monsoon wind strength over the south tropical Indian Ocean is the main driver of year-to-year variability. This has important implications for the predictability of fisheries yield, its response to climate change, policy and resource management.
Journal Article