Characterizing the Adsorption-Bioavailability Relationship of PAHs Adsorbed to Carbon Nanomaterials in the Aquatic Environment

Concurrent with the high applicability of carbon nanomaterials (CNM) in a variety of fields and the potential use for pollution remediation, there is the inevitable release of CNMs into the environment. As a consequence of their unique physicochemical properties, CNMs entering the environment will interact with both abiotic and biotic factors. With CNM concentrations estimated to range from parts per billion to low parts per million and their high adsorption affinity for organic contaminants, there is significant concern that CNMs will act as œcontaminant transporters . Even though adsorption and desorption of contaminants from CNMs play a significant role in the ultimate fate of adsorbed compounds, currently there is little conclusive information characterizing the relationship between adsorption behavior and bioavailability of CNM-adsorbed contaminants. The goal of the present research was to establish a comprehensive understanding of the key mechanisms influencing bioavailability of CNM-adsorbed organic contaminants. To accomplish this, I utilized a systematic approach to characterize the influence of CNM morphology, contaminant physicochemical properties, and contaminant mixtures on the resulting bioavailability of the adsorbed compounds, where polycyclic aromatic hydrocarbons (PAHs) were selected as a model class of organic contaminants. Adsorption behavior of a suite of PAHs by suspended multi-walled carbon nanotubes (MWCNTs) and exfoliated graphene (GN) was characterized using batch adsorption isotherm techniques and fitting experimental data with established adsorption models. Bioavailability of CNM-adsorbed PAHs to Pimephales promelas (fathead minnow) was quantified using bile analysis via fluorescence spectroscopy. Multiple linear regression techniques were used to assess the influence of CNM type, PAH physicochemical characteristics, and concentration effects on adsorption of PAHs by MWCNTs as well as to model the relationship between adsorption behavior and the resulting bioavailability of MWCNT-adsorbed PAHs. While CNM structure and surface area differed, adsorption affinity was more influenced by PAH physicochemical characteristics. In particular, differences in adsorption of PAHs between MWCNT and GN became insignificant as hydrophobic and Ï€-Ï€ interactions with the particular PAHs increased. Similarly, bioavailability of CNM-adsorbed PAHs was less influenced by the type of CNM and more influenced by the PAHs physicochemical properties, particularly the size and morphology of the PAH molecules. A further investigation with a greater range of PAHs, showed that molecular morphology of small less hydrophobic PAHs was particularly influential on bioavailability when adsorbed to MWCNTs. Though adsorption of chemically similar PAHs was nearly identical in single-solute solutions, the resulting bioavailability was not the same and was attributed to differences in the PAH\u27s Ï€ electron system as a function of structure and aromatic makeup. Additionally, modeling the relationship between adsorption affinity (i.e. Log Kd) and resulting bioavailability of MWCNT-adsorbed PAHs, showed a direct correlation when Log Kd was greater than 2.5, where only the aqueous concentration of PAH remained bioavailable. However, lower adsorption affinity resulted in a variable amount of the MWCNT-adsorbed PAH remaining bioavailable in an unpredictable manner. The results of this work also indicated that there was a concentration effect influencing adsorption affinity and bioavailability. This was determined to largely be a function of molecular surface area coverage of MWCNT resulting in a change of the adsorption process from more heterogenous to more homogenous. Finally, adsorption of two pairs of chemically similar PAHs, (1) phenanthrene and anthracene and (2) fluoranthene and pyrene, in bi-solute mixtures confirmed that structural makeup of the molecule is signficantly influential on the adsorption-bioavailability relationship. PAHs that have increased contact with the surface of MWCNT, such as anthracene being linear to align with the curved surface of the tube or fluoranthene being more flexible to bend with the curved surface of the tube, outcompeted their chemically similar isoforms. Competitive interactions between PAHs at the surface of MWCNT decreased adsorption affinity of both PAHs within the bi-solute system thus increased bioavailability of the adsorbed PAHs. However, the effect of competition on PAH bioavailability appeared to be greater for less hydrophobic PAHs (i.e. phenanthrene and anthracene) compared with the more hydrophobic PAH pair (i.e. fluoranthene and pyrene). This was attributed to adsorption affinity of phenanthrene and anthracene dipping below Log Kd = 2.5 due to competitive interactions in a bi-solute system. Similar to the single solute studies, only when Log Kd \u3e 2.5 was bioavailability of adsorbed PAHs largely associated with just the aqueous concentration of PAH left in the system. Overall, the results of this work indicate that there is a correlation between bioavailability of CNM-adsorbed PAHs and observed adsorption behavior in aqueous systems, which is largely driven by the adsorbate\u27s physicochemical characteristics. Factors influencing CNM adsorption affinity of PAHs prior to organismal ingestion, such as concentration and competition, also influence bioavailability of the CNM-adsorbed PAHs in a similar manner. However, adsorption behavior of PAHs by CNMs in aqueous solution is not a perfect prediction of the resulting uptake of PAH into P. promelas bile, though my data does indicate an adsorption affinity threshold at which MWCNTs can significantly reduce bioavailability of the adsorbed PAHs. This work furthered our understanding in the factors that may predominantly influence the bioavailability of CNM-adsorbed organic contaminants and provided initial insight into the complex interactions that may occur after consumption on CNM-contaminant complexes that should be focused on in the future

Characterizing the Effect of Suspended Carbon Nanotubes on the Bioavailablility of Adsorbed Fluoranthene to P. Promelas

The introduction of carbon nanomaterials into the environment has increased exponentially in the last decade, causing environmental as well as health concerns. One concern is the interaction that such nanomaterials have with the biota in the aquatic ecosystem and the direct and indirect toxic effects that may result. Previous research has documented a positive influence of natural organic matter (NOM) on the stability of carbon nanotube (CNTs) suspensions in surface waters. Further, research has quantified the ability of these carbon nanomaterials to adsorb aquatic contaminants such as polycyclic aromatic hydrocarbons (PAHs). Though both CNTs and PAHs can co-occur in wastewater treatment effluents few studies have investigated the bioavailability of these adsorbed PAHs to fish. The goal of this research was to characterize the bioavailability of fluoranthene (FLU) adsorbed to suspended muliwalled-carbon nanotubes (MWNTs) in a solution containing NOM. Results indicated that while NOM was critical for producing stable MWNT suspensions, it did not influence the bioavailability of FLU to P. promelas in the absence of MWNTs. Adsorption isotherms indicated that NOM significantly influenced the adsorption of FLU to MWNTs. P. promelas were exposed for 16 hrs in moderately hard water (MHW) containing only FLU, FLU in the presence of different concentrations of NOM, and FLU adsorbed to MWNTs in the presence of NOM. Bioavailable FLU was quantified in each exposure through bile analysis using a fluorescence microplate reader. Results indicated that 2 mg/L NOM as dissolved organic carbon (DOC) were sufficient to produce a stable MWNT suspension. The bioavailability of FLU was significantly reduced in the presence of this suspension. Through comparing the concentration of FLU metabolites in the bile to the concentration of FLU added to MWNT and DOC solutions we were able to quantify the relative bioavailability of FLU adsorbed to MWNTs. Results indicate that approximately 60-90% of the FLU was adsorbed to the MWNTs and that adsorbed FLU was not bioavailable to P. promelas

Can we use local climate zones for predicting malaria prevalence across sub-Saharan African cities?

Malaria burden is increasing in sub-Saharan cities because of rapid and uncontrolled urbanization. Yet very few studies have studied the interactions between urban environments and malaria. Additionally, no standardized urban land-use/land-cover has been defined for urban malaria studies. Here, we demonstrate the potential of local climate zones (LCZs) for modeling malaria prevalence rate (PfPR2-10) and studying malaria prevalence in urban settings across nine sub-Saharan African cities. Using a random forest classification algorithm over a set of 365 malaria surveys we: (i) identify a suitable set of covariates derived from open-source earth observations; and (ii) depict the best buffer size at which to aggregate them for modeling PfPR2-10. Our results demonstrate that geographical models can learn from LCZ over a set of cities and be transferred over a city of choice that has few or no malaria surveys. In particular, we find that urban areas systematically have lower PfPR2-10 (5%-30%) than rural areas (15%-40%). The PfPR2-10 urban-to-rural gradient is dependent on the climatic environment in which the city is located. Further, LCZs show that more open urban environments located close to wetlands have higher PfPR2-10. Informal settlements - represented by the LCZ 7 (lightweight lowrise) - have higher malaria prevalence than other densely built-up residential areas with a mean prevalence of 11.11%. Overall, we suggest the applicability of LCZs for more exploratory modeling in urban malaria studies. © 2020 The Author(s). Published by IOP Publishing Ltd.info:eu-repo/semantics/publishe

Motion-Aware Mosaicing for Confocal Laser Endomicroscopy

Probe-based Confocal Laser Endomicroscopy (pCLE) pro- vides physicians with real-time access to histological information during standard endoscopy procedures, through high-resolution cellular imaging of internal tissues. Earlier work on mosaicing has enhanced the potential of this imaging modality by meeting the need to get a complete representation of the imaged region. However, with approaches, the dynamic information, which may be of clinical interest, is lost. In this study, we propose a new mosaic construction algorithm for pCLE sequences based on a min-cut optimization and gradient-domain composition. Its main advantage is that the motion of some structures within the tissue such as blood cells in capillaries, is taken into account. This allows physicians to get both a sharper static representation and a dynamic representation of the imaged tissue. Results on 16 sequences acquired in vivo on six different organs demonstrate the clinical relevance of our approach

Population Distribution, Settlement Patterns and Accessibility across Africa in 2010

The spatial distribution of populations and settlements across a country and their interconnectivity and accessibility from urban areas are important for delivering healthcare, distributing resources and economic development. However, existing spatially explicit population data across Africa are generally based on outdated, low resolution input demographic data, and provide insufficient detail to quantify rural settlement patterns and, thus, accurately measure population concentration and accessibility. Here we outline approaches to developing a new high resolution population distribution dataset for Africa and analyse rural accessibility to population centers. Contemporary population count data were combined with detailed satellite-derived settlement extents to map population distributions across Africa at a finer spatial resolution than ever before. Substantial heterogeneity in settlement patterns, population concentration and spatial accessibility to major population centres is exhibited across the continent. In Africa, 90% of the population is concentrated in less than 21% of the land surface and the average per-person travel time to settlements of more than 50,000 inhabitants is around 3.5 hours, with Central and East Africa displaying the longest average travel times. The analyses highlight large inequities in access, the isolation of many rural populations and the challenges that exist between countries and regions in providing access to services. The datasets presented are freely available as part of the AfriPop project, providing an evidence base for guiding strategic decisions

Diffusion of Subsidized ACTs in Accredited Drug Shops in Tanzania: Determinants of Stocking and Characteristics of Early and Late Adopters.

Many households in sub-Saharan Africa utilize the private sector as a primary source of treatment for malaria episodes. Expanding access to effective treatment in private drug shops may help reduce incidence of severe disease and mortality. This research leveraged a longitudinal survey of stocking of subsidized artemisinin combination therapies (ACTs), an effective anti-malarial, in Accredited Drug Dispensing Outlets (ADDOs) in two regions of Tanzania. This provided a unique opportunity to explore shop and market level determinants of product diffusion in a developing country retail market. 356 ADDOs in the Rukwa and Mtwara regions of Tanzania were surveyed at seven points between Feb 2011 and May 2012. Shop level audits were used to measure the availability of subsidized ACTs at each shop. Data on market and shop level factors were collected during the survey and also extracted from GIS layers. Regression and network based methodologies were used. Shops classified as early and late adopters, following Rogers' model of product diffusion, were compared. The Bass model of product diffusion was applied to determine whether shops stocked ACTs out of a need to imitate market competitors or a desire to satisfy customer needs. Following the introduction of a subsidy for ACTs, stocking increased from 12% to nearly 80% over the seven survey rounds. Stocking was influenced by higher numbers of proximal shops and clinics, larger customer traffic and the presence of a licensed pharmacist. Early adopters were characterized by a larger percentage of customers seeking care for malaria, a larger catchment and sourcing from specific wholesalers/suppliers. The Bass model of product diffusion indicated that shops were adopting products in response to competitor behavior, rather than customer demand. Decisions to stock new pharmaceutical products in Tanzanian ADDOs are influenced by a combination of factors related to both market competition and customer demand, but are particularly influenced by the behavior of competing shops. Efforts to expand access to new pharmaceutical products in developing country markets could benefit from initial targeting of high profile shops in competitive markets and wholesale suppliers to encourage faster product diffusion across all drug retailers

Binding adaptation of GS 441524 diversifies macro domains and downregulate SARS CoV 2 de MARylation capacity

Viral infection in cells triggers a cascade of molecular defense mechanisms to maintain host cell homoeostasis. One of these mechanisms is ADP ribosylation, a fundamental post translational modification PTM characterized by the addition of ADP ribose ADPr on substrates. Poly ADP ribose polymerases PARPs are implicated in this process and they perform ADP ribosylation on host and pathogen proteins. Some viral families contain structural motifs that can reverse this PTM. These motifs known as macro domains MDs are evolutionarily conserved protein domains found in all kingdoms of life. They are divided in different classes with the viral belonging to Macro D type class because of their properties to recognize and revert the ADP ribosylation. Viral MDs are potential pharmaceutical targets, capable to counteract host immune response. Sequence and structural homology between viral and human MDs are an impediment for the development of new active compounds against their function. Remdesivir, is a drug administrated in viral infections inhibiting viral replication through RNA dependent RNA polymerase RdRp . Herein, GS 441524, the active metabolite of the remdesivir, is tested as a hydrolase inhibitor for several viral MDs and for its binding to human homologs found in PARPs. This study presents biochemical and biophysical studies, which indicate that GS 441524 selectively modifies SARS CoV 2 MD de MARylation activity, while it does not interact with hPARP14 MD2 and hPARP15 MD2. The structural investigation of MD GS 441524 complexes, using solution NMR and X ray crystallography, discloses the impact of certain amino acids in ADPr binding cavity suggesting that F360 and its adjacent residues tune the selective binding of the inhibitor to SARS CoV 2 M

Caffeic acid phenethyl ester decreases acute pneumonitis after irradiation in vitro and in vivo

BACKGROUND: Lung cancer is relatively resistant to radiation treatment and radiation pneumonitis is a major obstacle to increasing the radiation dose. We previously showed that Caffeic acid phenethyl ester (CAPE) induces apoptosis and increases radiosensitivity in lung cancer. To determine whether CAPE, an antioxidant and an inhibitor of NF-kappa B, could be a useful adjuvant agent for lung cancer treatment, we examine the effects of CAPE on irradiated normal lung tissue in this study. METHODS: We compared the effects of CAPE on cytotoxicity and intracellular oxidative stress in normal lung fibroblast and a lung cancer cell line. For in vivo analysis, whole thorax radiation (single dose 10 Gy and 20 Gy) was delivered to BALB/c male mice with or without CAPE pretreatment. NF- kappaB activation and the expression levels of acute inflammatory cytokines were evaluated in mice after irradiation. RESULTS: The in vitro studies showed that CAPE cause no significant cytotoxicity in normal lung as compared to lung cancer cells. This is probably due to the differential effect on the expression of NF-kappa B between normal and malignant lung cells. The results from in vivo study showed that CAPE treatment decreased the expression of inflammatory cytokines including IL-1 alpha and beta, IL-6, TNF-alpha and TGF- beta, after irradiation. Moreover, histological and immunochemical data revealed that CAPE decreased radiation- induced interstitial pneumonitis and TGF-beta expression. CONCLUSION: This study suggests that CAPE decreases the cascade of inflammatory responses induced by thoracic irradiation without causing toxicity in normal lung tissue. This provides a rationale for combining CAPE and thoracic radiotherapy for lung cancer treatment in further clinical studies