Facilitated Release of Doxorubicin from Biodegradable Mesoporous Silica Nanoparticles

Cervical cancer is one of the most common causes of cancer death for women in the United States. The current treatment with chemotherapy drugs has significant side effects and may cause harm to healthy cells rather than cancer cells. In order to combat the potential side effects, nanoparticles composed of mesoporous silica were created to house the chemotherapy drug doxorubicin (DOX). The silica network contains the drug, and a pH study was conducted to determine the conditions for the nanoparticle to disperse the drug. The introduction of disulfide bonds within the nanoparticle created a framework to efficiently release 97% of DOX in acidic environments and 40% release in neutral environments. The denotation of acidic versus neutral environments was important as cancer cells are typically acidic. The chemistry was proved with the incubation of the loaded nanoparticle into HeLa cells for a cytotoxicity report and confocal imaging. The use of the framework for the anticancer drug was shown to be effective for the killing of cancerous cells

City-As-School: Internship-based Learning in New York City Public Schools

Paints a portrait of a high school with experiential learning at its core; at City-As-School in New York City, internships take the place of many classroom-based courses

Lake Whatcom Watershed Land Acquisition Project: environmental impact assessment

The purpose of this report is to reexamine and reevaluate the environmental impacts of the Lake Whatcom Watershed Land Acquisition Ordinance, (Ordinance 2000-09-058) which was passed by the City of Bellingham in the fall of 2000. The ordinance placed a $6.00 fee on the monthly drinking water bill of customers

Analyzing pathogenic (double-stranded (ds) DNA-specific) plasma cells via immunofluorescence microscopy

Introduction While protective plasma cells (PCs) are an important part of the individual’s immune defense, autoreactive plasma cells such as dsDNA-specific plasma cells contribute to the pathogenesis of autoimmune diseases like systemic lupus erythematosus (SLE). However, the research on dsDNA-specific plasma cells was restricted to the ELISpot technique, with its limitations, as no other attempt for identification of dsDNA-reactive plasma cells had been successful. Methods With improved fluorochrome labeling of dsDNA, removal of DNA aggregates, and enhanced blocking of unspecific binding, we were able to specifically detect dsDNA-reactive plasma cells by immunofluorescence microscopy. Results Via this novel technique we were able to distinguish short-lived (SLPCs) and long-lived (LLPCs) autoreactive plasma cells, discriminate dsDNA-specific plasma cells according to their immunoglobulin class (IgG, IgM, and IgA) and investigate autoreactive (dsDNA) and vaccine- induced ovalbumin (Ova) plasma cells in parallel. Conclusions The detection of autoreactive dsDNA-specific plasma cells via immunofluorescence microscopy allows specific studies on pathogenic and protective plasma cell subsets and their niches, detailed evaluation of therapeutic treatments and therefore offers new possibilities for basic and clinical research

Children’s use of reasoning by exclusion to track identities of occluded objects

Reasoning by exclusion allows us to infer properties of unobserved objects from currently observed objects, formalized by P or Q, not P, therefore Q. Previous work suggested that, by age 3, children can use this kind of reasoning to infer the location of a hidden object after learning that another location is empty (e.g. Mody & Carey, 2016). In the current study, we asked whether children could use reasoning by exclusion to infer the identities of previously unobserved occluded objects in a task that required them to track the locations of multiple occluded objects. Forty-nine 4-7-yearolds viewed animated arrays of virtual “cards” depicting images which were then hidden by occluders. The occluders then swapped locations during the maintenance period. Children were asked to select which card was hidden in a probed location. During the encoding period, we manipulated whether children saw all the card faces (Face-up block) or all but one of the card faces (Exclusion block), for which children had to reason by exclusion to infer the target in half of the trials. We found that all children succeeded in the Face-up block, but only 6-year-olds succeed in the Exclusion block when they had to deploy logical reasoning to identify a previously-unseen hidden target. Our results suggest that children’s ability to reason by exclusion to infer the identity of a hidden target while tracking multiple objects and locations may undergo protracted development.Published versio

Soil bacterial diversity is associated with human population density in urban greenspaces

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of American Chemical Society for personal use, not for redistribution. The definitive version was published in Environmental Science and Technology 52 (2018): 5115–5124, doi:10.1021/acs.est.7b06417.Urban greenspaces provide extensive ecosystem services, including pollutant remediation, water management, carbon maintenance, and nutrient cycling. However, while the urban soil microbiota underpin these services, we still have limited understanding of the factors that influence their distribution. We characterized soil bacterial communities from turf-grasses associated with urban parks, streets and residential sites across a major urban environment, including a gradient of human population density. Bacterial diversity was significantly positively correlated with the population density; and species diversity was greater in park and street soils, compared to residential soils. Population density and greenspace type also led to significant differences in the microbial community composition that was also significantly correlated with soil pH, moisture and texture. Co-occurrence network analysis revealed that microbial guilds in urban soils were well correlated. Abundant soil microbes in high density population areas had fewer interactions, while abundant bacteria in high moisture soils had more interactions. These results indicate the significant influence of changes in urban demographics and land-use on soil microbial communities. As urbanization is rapidly growing across the planet, it is important to improve our understanding of the consequences of urban zoning on the soil microbiota.This study is supported by the Earth Microbiome Project (http://www.earthmicrobiome.org/) and the China Scholarship Council (http://en.csc.edu.cn/).2019-04-0

Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1

Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI-tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr83 and Glu73, respectively. When Glu73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu73 residue