Exposure To Atmospheric Metals Using Moss Bio-Indicators And Neonatal Health Outcomes In Portland, Oregon

Background: Exposures to certain metals are associated with adverse birth outcomes, including inhibited fetal growth and congenital defects. Previous studies focused on metals such as lead and arsenic, and primarily assessed exposure using biological monitoring, which does not provide insights into sources. Examining exposure to metals via atmospheric pathways is challenging due to a lack of high-resolution air-pollution data. We applied a unique map of atmospheric metal pollution, derived from bio-indicator moss samples, as a screening tool to study neonatal health risks of atmospheric metal pollution in Portland, Oregon, a city of 640,000 people with several metal-emitting industrial sources. Methods: We used previously collected data of metal concentrations measured in 346 moss samples in December 2013, to which an inverse-distance weighting scheme was applied to map ambient/environmental metal concentrations. Birth records for Portland live births (2008-2014) were obtained from the Oregon Health Authority. Exposure to atmospheric metals was assigned based on mother’s residential address. Metal exposure was evaluated continuously and by quartile. Associations were evaluated for six metals previously identified as metalloestrogens toxic to plant and animal life (arsenic, cadmium, chromium, cobalt, nickel, lead) and two birth outcomes (preterm (weeks), very preterm (weeks)) using logistic regression models with adjustment for birth characteristics and demographic variables. Results: Results indicate statistically significant associations between chromium exposure and preterm birth (OR=1.10, 95% CI: 1.02, 1.19) and very preterm birth (OR=1.10, 95% CI: 1.01, 1.19). Stratifying metal exposure by quartiles found some evidence of a dose-response effect for arsenic, cobalt and lead, but not for other metals. Stratified analysis by mother’s race (white / non-white) finds that cadmium, chromium and lead are significant risk factors for very preterm birth among non-white women, but not among white women. Conclusions: Results suggest that atmospheric metal exposure to chromium, measured via bio-indicator moss samples, is associated with an increased risk of preterm and very preterm birth. Exposure to cadmium, chromium and lead is a significant risk factor for very preterm birth among non-white women, indicating an effect due to race; this is an important result that requires further investigation. This novel exposure metric may be useful when bio-monitoring and more invasive/expensive exposure metrics are not feasible

Investigation of EMIC wave scattering as the cause for the BARREL 17 January 2013 relativistic electron precipitation event: A quantitative comparison of simulation with observations

Abstract Electromagnetic ion cyclotron (EMIC) waves were observed at multiple observatory locations for several hours on 17 January 2013. During the wave activity period, a duskside relativistic electron precipitation (REP) event was observed by one of the Balloon Array for Radiation belt Relativistic Electron Losses (BARREL) balloons and was magnetically mapped close to Geostationary Operational Environmental Satellite (GOES) 13. We simulate the relativistic electron pitch angle diffusion caused by gyroresonant interactions with EMIC waves using wave and particle data measured by multiple instruments on board GOES 13 and the Van Allen Probes. We show that the count rate, the energy distribution, and the time variation of the simulated precipitation all agree very well with the balloon observations, suggesting that EMIC wave scattering was likely the cause for the precipitation event. The event reported here is the first balloon REP event with closely conjugate EMIC wave observations, and our study employs the most detailed quantitative analysis on the link of EMIC waves with observed REP to date. Key PointsQuantitative analysis of the first balloon REP with closely conjugate EMIC wavesOur simulation suggests EMIC waves to be a viable cause for the REP eventThe adopted model is proved to be applicable to simulating the REP event

Observations of coincident EMIC wave activity and dusk-side energetic electron precipitation on 18-19 January 2013

Electromagnetic ion cyclotron (EMIC) waves have been suggested to be a cause of radiation belt electron loss to the atmosphere. Here simultaneous, magnetically conjugate measurements are presented of EMIC wave activity, measured at geosynchronous orbit and on the ground, and energetic electron precipitation, seen by the BARREL balloon campaign, on two consecutive days in January 2013. Multiple bursts of precipitation were observed on the dusk-side of the magnetosphere at the end of 18 Jan and again late on 19 Jan, concurrent with particle injections, substorm activity, and enhanced magnetospheric convection. The structure, timing, and spatial extent of the waves are compared to those of the precipitation during both days to determine when and where EMIC waves cause radiation belt electron precipitation. The conjugate measurements presented here provide observational support of the theoretical picture of dusk-side interaction of EMIC waves and MeV electrons leading to radiation belt loss

Observations of Radiation Belt Losses Due to Cyclotron Wave-Particle Interactions

Electron loss to the atmosphere plays a critical role in driving dynamics of the Earths Van Allen radiation belts and slot region. This is a review of atmospheric loss of radiation belt electrons caused by plasma wave scattering via Doppler-shifted cyclotron resonance. In particular, the focus is on observational signatures of electron loss, which include direct measurements of precipitating electrons, measured properties of waves that drive precipitation, and variations in the trapped population resulting from loss. We discuss wave and precipitation measurements from recent missions, including simultaneous multi-payload observations, which have provided new insight into the dynamic nature of the radiation belts

Participatory Mapping to Address Neighborhood Level Data Deficiencies for food Security Assessment in Southeastern Virginia, USA

Background: Food is not equitably available. Deficiencies and generalizations limit national datasets, food security assessments, and interventions. Additional neighborhood level studies are needed to develop a scalable and transferable process to complement national and internationally comparative data sets with timely, granular, nuanced data. Participatory geographic information systems (PGIS) offer a means to address these issues by digitizing local knowledge. Methods: The objectives of this study were two-fold: (i) identify granular locations missing from food source and risk datasets and (ii) examine the relation between the spatial, socio-economic, and agency contributors to food security. Twenty-nine subject matter experts from three cities in Southeastern Virginia with backgrounds in food distribution, nutrition management, human services, and associated research engaged in a participatory mapping process. Results: Results show that publicly available and other national datasets are not inclusive of non-traditional food sources or updated frequently enough to reflect changes associated with closures, expansion, or new programs. Almost 6 percent of food sources were missing from publicly available and national datasets. Food pantries, community gardens and fridges, farmers markets, child and adult care programs, and meals served in community centers and homeless shelters were not well represented. Over 24 km2 of participant identified need was outside United States Department of Agriculture low income, low access areas. Economic, physical, and social barriers to food security were interconnected with transportation limitations. Recommendations address an international call from development agencies, countries, and world regions for intervention methods that include systemic and generational issues with poverty, incorporate non-traditional spaces into food distribution systems, incentivize or regulate healthy food options in stores, improve educational opportunities, increase data sharing. Conclusions: Leveraging city and regional agency as appropriate to capitalize upon synergistic activities was seen as critical to achieve these goals, particularly for non-traditional partnership building. To address neighborhood scale food security needs in Southeastern Virginia, data collection and assessment should address both environment and utilization issues from consumer and producer perspectives including availability, proximity, accessibility, awareness, affordability, cooking capacity, and preference. The PGIS process utilized to facilitate information sharing about neighborhood level contributors to food insecurity and translate those contributors to intervention strategies through discussion with local subject matter experts and contextualization within larger scale food systems dynamics is transferable

Mechanism of the formation of DNA–protein cross-links by antitumor cisplatin

DNA–protein cross-links are formed by various DNA-damaging agents including antitumor platinum drugs. The natures of these ternary DNA–Pt–protein complexes (DPCLs) can be inferred, yet much remains to be learned about their structures and mechanisms of formation. We investigated the origin of these DPCLs and their cellular processing on molecular level using gel electrophoresis shift assay. We show that in cell-free media cisplatin [cis-diamminedichloridoplatinum(II)] forms DPCLs more effectively than ineffective transplatin [trans-diamminedichloridoplatinum(II)]. Mechanisms of transformation of individual types of plain DNA adducts of the platinum complexes into the DPCLs in the presence of several DNA-binding proteins have been also investigated. The DPCLs are formed by the transformation of DNA monofunctional and intrastrand cross-links of cisplatin. In contrast, interstrand cross-links of cisplatin and monofunctional adducts of transplatin are stable in presence of the proteins. The DPCLs formed by cisplatin inhibit DNA polymerization or removal of these ternary lesions from DNA by nucleotide excision repair system more effectively than plain DNA intrastrand or monofunctional adducts. Thus, the bulky DNA–protein cross-links formed by cisplatin represent a more distinct and persisting structural motif recognized by the components of downstream cellular systems processing DNA damage considerably differently than the plain DNA adducts of this metallodrug

Walking of antitumor bifunctional trinuclear PtII complex on double-helical DNA

The trinuclear BBR3464 ([{trans-PtCl(NH3)2}2µ-(trans-Pt(NH3)2(H2N(CH2)6NH2)2)]4+) belongs to the polynuclear class of platinum-based anticancer agents. DNA adducts of this complex differ significantly in structure and type from those of clinically used mononuclear platinum complexes, especially, long-range (Pt, Pt) intrastrand and interstrand cross-links are formed in both 5′–5′ and 3′–3′ orientations. We show employing short oligonucleotide duplexes containing single, site-specific cross-links of BBR3464 and gel electrophoresis that in contrast to major DNA adducts of clinically used platinum complexes, under physiological conditions the coordination bonds between platinum and N7 of G residues involved in the cross-links of BBR3464 can be cleaved. This cleavage may lead to the linkage isomerization reactions between this metallodrug and double-helical DNA. Differential scanning calorimetry of duplexes containing single, site-specific cross-links of BBR3464 reveals that one of the driving forces that leads to the lability of DNA cross-links of this metallodrug is a difference between the thermodynamic destabilization induced by the cross-link and by the adduct into which it could isomerize. The rearrangements may proceed in the way that cross-links originally formed in one strand of DNA can spontaneously translocate from one DNA strand to its complementary counterpart, which may evoke walking of the platinum complex on DNA molecule

Mechanism of double-base lesion bypass catalyzed by a Y-family DNA polymerase

As a widely used anticancer drug, cis-diamminedichloroplatinum(II) (cisplatin) reacts with adjacent purine bases in DNA to form predominantly cis-[Pt(NH3)2{d(GpG)-N7(1),-N7(2)}] intrastrand cross-links. Drug resistance, one of the major limitations of cisplatin therapy, is partially due to the inherent ability of human Y-family DNA polymerases to perform translesion synthesis in the presence of DNA-distorting damage such as cisplatin–DNA adducts. To better understand the mechanistic basis of translesion synthesis contributing to cisplatin resistance, this study investigated the bypass of a single, site-specifically placed cisplatin-d(GpG) adduct by a model Y-family DNA polymerase, Sulfolobus solfataricus DNA polymerase IV (Dpo4). Dpo4 was able to bypass this double-base lesion, although, the incorporation efficiency of dCTP opposite the first and second cross-linked guanine bases was decreased by 72- and 860-fold, respectively. Moreover, the fidelity at the lesion decreased up to two orders of magnitude. The cisplatin-d(GpG) adduct affected six downstream nucleotide incorporations, but interestingly the fidelity was essentially unaltered. Biphasic kinetic analysis supported a universal kinetic mechanism for the bypass of DNA lesions catalyzed by various translesion DNA polymerases. In conclusion, if human Y-family DNA polymerases adhere to this bypass mechanism, then translesion synthesis by these error-prone enzymes is likely accountable for cisplatin resistance observed in cancer patients

Fluorophore Labeled Kinase Detects Ligands That Bind within the MAPK Insert of p38α Kinase

The vast majority of small molecules known to modulate kinase activity, target the highly conserved ATP-pocket. Consequently, such ligands are often less specific and in case of inhibitors, this leads to the inhibition of multiple kinases. Thus, selective modulation of kinase function remains a major hurdle. One of the next great challenges in kinase research is the identification of ligands which bind to less conserved sites and target the non-catalytic functions of protein kinases. However, approaches that allow for the unambiguous identification of molecules that bind to these less conserved sites are few in number. We have previously reported the use of fluorescent labels in kinases (FLiK) to develop direct kinase binding assays that exclusively detect ligands which stabilize inactive (DFG-out) kinase conformations. Here, we present the successful application of the FLiK approach to develop a high-throughput binding assay capable of directly monitoring ligand binding to a remote site within the MAPK insert of p38α mitogen-activated protein kinase (MAPK). Guided by the crystal structure of an initially identified hit molecule in complex with p38α, we developed a tight binding ligand which may serve as an ideal starting point for further investigations of the biological function of the MAPK insert in regulating the p38α signaling pathway