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Urban estuaries receive large volumes of effluents from municipal wastewater treatment facilities containing numerous contaminants, such as pharmaceuticals residues. Water was sampled for 16 highly prescribed pharmaceuticals at 17 sites along the Long Island Sound (LIS) estuary located in the Northeastern U.S. Pharmaceutical concentrations were highest in western LIS, ranging from non-detect to 71 ng L−1 and declining steadily eastward, while river samples from four major tributaries ranged from non-detect to 83 ng L−1. Two tracers, sucralose and caffeine, accurately predicted pharmaceutical behavior in LIS while only sucralose was effective at the river sites. Sucralose also tracked well with the salinity gradient in LIS, exhibiting conservative behavior along the transect. Attenuation factors were determined for measurable pharmaceuticals and compared against sucralose to estimate the magnitude of decline in concentrations that may be attributable to in situ degradation and partitioning. The results demonstrate sucralose's effectiveness as a tracer of wastewater-borne contaminants under estuarine conditions.

Medical academics welcomed publication of the government’s vision for the future of clinical research delivery.123 For the vision to succeed, however, there needs to be a concerted effort to foster a research friendly environment at every level of medicine. Throughout their careers, doctors must be able seamlessly to integrate clinical and academic activities. There should be clear and …

The deployment of aqueous film forming foams (AFFF) used for firefighting during emergencies and training often releases per- and polyfluoroalkyl substances (PFAS) into the environment. In October 2018, first responders in Providence, RI, USA applied an AFFF during a fuel spill. Due to the proximity of the incident to the upper reaches of Narragansett Bay (NB), an unknown quantity of gasoline and AFFF entered the estuary via surface runoff and stormwater drains. Water samples near the spill were collected approximately 15 hours after the incident and analyzed for 24 PFAS. Minor increases in measured PFAS concentrations were observed relative to pre- and post-spill samples at monitoring sites near the incident, except 6:2-fluorotelomer sulfonate (6:2-FTS) that peaked post-spill (max 311 ng/L). After performing the total oxidizable precursor (TOP) assay on water samples and the AFFF concentrate, significant increases in perfluorocarboxylic acids (PFCAs) were observed. One compound, 6:2 fluorotelomer mercaptoalkylamido sulfonate (6:2-FTSAS), was identified as a major component of the AFFF used. Peak areas of 6:2-FTSAS and the degradation product 6:2-FTSAS-sulfoxide corresponded to observed increases in the TOP assay results and were useful as tracers of AFFF in surrounding waters. Elevated levels of PFAS at the time of sampling were limited to a confined area of the Providence River due to river flow and tidal action. Observed concentrations were also compared to hydrodynamic model results, and results confirmed rapid dissipation of AFFF components with distance from the spill. However, modeled results did not capture possible secondary releases of AFFF from local municipal stormwater and sewer infrastructure, as observational data suggest. The multiple lines of evidence of PFAS present in surface waters permitted a better assessment of the potential environmental impacts from products such as AFFF for which the chemical composition is largely unknown.

Per- and polyfluoroalkyl substances (PFAS) are anthropogenic, globally distributed chemicals. Legacy PFAS, including perfluorooctane sulfonate (PFOS), have been regularly detected in marine fauna but little is known about their current levels or the presence of novel PFAS in seabirds. We measured 36 emerging and legacy PFAS in livers from 31 juvenile seabirds from Massachusetts Bay, Narragansett Bay, and the Cape Fear River Estuary (CFRE), USA. PFOS was the major legacy perfluoroalkyl acid present, making up 58% of concentrations observed across all habitats (range: 11 – 280 ng/g). Novel PFAS were confirmed in chicks hatched downstream of a fluoropolymer production site in the CFRE - a perfluorinated ether sulfonic acid (Nafion byproduct-2; range: 1 – 110 ng/g) and two perfluorinated ether carboxylic acids (PFO(4)DA and PFO(5)DoDA; PFO(5)DoDA range: 5 – 30 ng/g). PFOS was inversely associated with phospholipid content in livers from CFRE and Massachusetts Bay individuals, while δ(13)C, an indicator of marine vs. terrestrial foraging, was positively correlated with some long-chain PFAS in CFRE chick livers. These results detail concentrations of legacy and novel PFAS across different marine ecosystems along the US Atlantic East Coast. There is also an indication that seabird phospholipid dynamics are negatively impacted by PFAS, which should be further explored given the importance of lipids for seabirds.

Increased consumption and improper disposal of prescription medication, such as beta (β)-blockers, contribute to their introduction into waterways and may pose threats to non-target aquatic organisms. There has been rising concern about the impacts of these prescription drugs on coastal ecosystems, especially because wastewater treatment plants are not designed to eliminate them from the discharge. Few studies have characterized the sublethal effects of β-blocker exposures in marine invertebrates. The overall aim of our research is to identify cellular responses of two commercially important filter-feeding marine bivalves, hard clams (Mercenaria mercenaria) and Eastern oysters (Crassostrea virginica), upon exposures to two β-blocker drugs, propranolol and metoprolol. In vitro exposures with bivalve digestive gland and gill tissues were conducted where tissues were separately exposed to each drug for 24 h. Tissue samples were analyzed for cellular damage (lysosomal membrane destabilization and lipid peroxidation), total antioxidant capacity, and glutathione-s-transferase activity. Elevated damage and changes in enzyme activities were noted in the exposed tissues at environmentally relevant concentrations. Differences in species and tissue sensitivities and responses to exposures were also observed. These studies enhance our understanding of the potential impacts of prescription medication on coastal organisms. Additionally, this work demonstrates that filter-feeders may serve as good model organisms to examine the effects of unintended environmental exposures to β-blockers. These studies are part of our ongoing work aimed at evaluation of sublethal biomarkers of pharmaceutical exposures and identification of key events that can contribute to the development of adverse outcome pathways (AOPs).

It is well known that copper (Cu) is toxic to marine organisms. We measured and compared the acute toxicity of several forms of Cu (including nanoCu) amended into a marine sediment with mysids and amphipods. For all the forms of Cu tested, toxicity, measured as the median lethal concentration, ranged from 708 to > 2400 mg Cu/kg (dry sediment) for mysids and 258 to 1070 mg Cu/kg (dry sediment) for amphipods. Environ Toxicol Chem 2018;37:2677-2681. © 2018 SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

The widespread use of pharmaceuticals by human populations results in their sustained discharge to surface waters via wastewater treatment plants (WWTPs). In this study, 16 highly prescribed pharmaceuticals were quantified along a 250 km transect of the Hudson River Estuary and New York Harbor to describe their sources and spatial patterns. Sampling was conducted over two dry weather periods in May and July 2016, at 72 sites which included mid-channel and nearshore sites, as well as locations influenced by tributaries and WWTP outfalls. The detection frequency of the study pharmaceuticals was almost identical between the May and July sampling periods at 55% and 52%, respectively. Six pharmaceuticals were measurable at 92% or more of the sites during both sampling periods, illustrating their ubiquitous presence throughout the study area. Individual pharmaceutical concentrations were highly variable spatially, ranging from non-detect to 3810 ng/L during the study. Major factors controlling concentrations were proximity and magnitude of WWTP discharges, inputs from tributaries and tidal mixing. Two compounds, sucralose and caffeine, were evaluated as tracers to identify wastewater sources and assess pharmaceutical behavior. Sucralose was useful in identifying wastewater inputs to the river and concentrations showed excellent correlations with numerous pharmaceuticals in the study. Caffeine-sucralose ratios showed potential in identifying discharges of untreated wastewater occurring during a combined sewage overflow event. Many of the study pharmaceuticals were present throughout the Hudson River Estuary as a consequence of sustained wastewater discharge. Whereas some concentrations were above published effects levels, a more complete risk assessment is needed to understand the potential for ecological impacts due to pharmaceuticals in the Hudson River Estuary.

The widespread use of copper nanomaterials (CuNMs) as antibacterial and antifouling agents in consumer products increases the risk for metal contamination and adverse effects in aquatic environments. Information gaps exist on the potential toxicity of CuNMs in marine environments. We exposed field-collected marine meio- and macrobenthic communities to sediments spiked with micronized copper azole (MCA) using a novel method that brings intact benthic cores into the laboratory and exposes the organisms via surface application of sediments. Treatments included field and laboratory controls, 3 spiked sediments: low-MCA (51.9 mg/kg sediment), high-MCA (519 mg/kg sediment), and CuSO4 (519 mg/kg sediment). In addition, single-species acute testing was performed with both MCA and CuSO4. Our results indicate that meio- and macrofaunal assemblages exposed to High-MCA and CuSO4 treatments differed significantly from both the laboratory control and the low-MCA treatments. Differences in macrofauna were driven by decreases in 3 Podocopa ostracod species, the bivalve Gemma gemma, and the polychaetes Exogone verugera and Prionospio heterobranchia relative to the laboratory control. Differences in the meiofaunal community are largely driven by nematodes. The benthic community test results were more sensitive than the single-species test results. Findings of this investigation indicate that CuNMs represent a source of risk to marine benthic communities comparable to that of dissolved Cu. Environ Toxicol Chem 2017;9999:1–14. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

The behavior and fate of pharmaceutical ingredients in coastal marine ecosystems are not well understood. To address this, the spatial and temporal distribution of 15 high-volume pharmaceuticals were measured over a 1-yr period in Narragansett Bay (RI, USA) to elucidate factors and processes regulating their concentration and distribution. Dissolved concentrations ranged from below detection to 313 ng/L, with 4 pharmaceuticals present at all sites and sampling periods. Eight pharmaceuticals were present in suspended particulate material, ranging in concentration from below detection to 44 ng/g. Partitioning coefficients were determined for some pharmaceuticals, with their range and variability remaining relatively constant throughout the study. Normalization to organic carbon content provided no benefit, indicating other factors played a greater role in regulating partitioning behavior. Within the upper bay, the continuous influx of wastewater treatment plant effluents resulted in sustained, elevated levels of pharmaceuticals. A pharmaceutical concentration gradient was apparent from this zone to the mouth of the bay. For most of the pharmaceuticals, there was a strong relationship with salinity, indicating conservative behavior within the estuary. Short flushing times in Narragansett Bay coupled with pharmaceuticals' presence overwhelmingly in the dissolved phase indicate that most pharmaceuticals will be diluted and transported out of the estuary, with only trace amounts of several compounds sequestered in sediments. The present study identifies factors controlling the temporal and spatial dynamics of dissolved and particulate pharmaceuticals; their partitioning behavior provides an increased understanding of their fate, including bioavailability in an urban estuary. Environ Toxicol Chem 2017;36:1846-1855. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Narragansett Bay is an urban estuary that historically has been impacted by long-term discharge of sanitary wastewater (WW) effluents. High-density water sampling was conducted in Narragansett Bay, RI, USA, in an effort to understand the distribution and behavior of sucralose, an artificial sweetener that has shown utility as a sanitary wastewater tracer. Water samples were collected at sixty-seven sites and analyzed for sucralose, whose performance was compared to other tracers present in wastewater effluents. Concentrations of sucralose were much higher than the other tracers measured, carbamazepine and caffeine, ranging from 18 to 3180 ng/L and corresponded well with salinity (r2 = 0.88), demonstrating conservative behavior throughout the Bay. Mapped interpolation data using an empirical bayesian kriging model clearly show the spatial trends of WW and how estuarine processes influence dilution and dispersion throughout the Bay. These findings provide further evidence of the efficacy of sucralose as a wastewater tracer in large urban estuaries where continuous high-volume discharge of WW occur.

Emerging per- and polyfluorinated compounds (PFAS) compounds are of increasing interest for environmental monitoring, one being hexafluoropropylene oxide-dimer acid (HFPO-DA), commonly referred to as GenX. The following review describes existing liquid chromatography-mass spectrometry (LC-MS) methods used to analyze HFPO-DA, including sample preparation and method sensitivity relative to other PFAS. Analytical challenges are also described, in particular the significant formation of in-source fragmentation, dimer and dimer adducts which detract from [M−H](−) signal. Lastly, detected levels of HFPO-DA in environmental and biological samples are compared across the limited number of available field exposure studies, which found several μg/L concentrations in water samples taken near fluorochemical plant discharges.

The Pawtuxet River in Rhode Island, USA has a long history of industrial activity and pollutant discharges. Metal contamination of the river sediments are well documented and historically exceeded toxicity thresholds for a variety of organisms. The Pawtuxet River dam, a low-head dam at the mouth of the river, was removed in August 2011. The removal of the dam was part of an effort to restore the riverine ecosystem after centuries of anthropogenic impact. Sediment traps were deployed below the dam to assess changes in metal concentrations and fluxes (Ag, Cd, Cr, Cu, Ni, Pb, & Zn) from the river system into Pawtuxet Cove. Sediment traps were deployed for an average duration of 24 days each, and deployments continued for 15 months after the dam was removed. Metal concentrations in the trapped suspended particulate matter (SPM) dropped following dam removal (e.g. 460 mg/kg to 276 mg/kg for Zn) and remained below pre-removal levels for most of the study. However, particle bound metal fluxes rose immediately following dam removal (e.g. 1206 g/d to 4248 g/d for Zn). Changes in flux rates during the study period indicated that river volumetric flow rates acted as the primary mechanism controlling the flux of metals into Pawtuxet Cove and ultimately upper Narragansett Bay. While SPM metal concentrations initially dropped after removal of the dam, no discernable effect on the concentration or flux of the study metals exiting the river could be associated with removal of the Pawtuxet River dam. This article is protected by copyright. All rights reserved

It is well known that copper (Cu) is toxic to marine organisms. We measured and compared the acute toxicity of several forms of Cu (including nanoCu) amended into a marine sediment with mysids and amphipods. For all the forms of Cu tested, toxicity, measured as the median lethal concentration, ranged from 708 to2400 mg Cu/kg (dry sediment) for mysids and 258 to 1070 mg Cu/kg (dry sediment) for amphipods. Environ Toxicol Chem 2018;37:2677-2681. © 2018 SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Benzotriazoles (BZTs) are used in a broad range of commercial and industrial products, particularly as metal corrosion inhibitors and as ultraviolet (UV) light stabilizer additives in plastics and polymers. In this study, dated sediment cores from two east coast estuaries were analyzed for commonly used BZTs. In Narragansett Bay, UV stabilizing BZTs (UV-BZTs) were present at high levels from 1961 on, reflecting their patent date, local production and long-term preservation in sediment. In Salem Sound, UV-BZTs were present at concentrations consistent with other coastal marine locations not influenced by BZT production. Anticorrosive BZTs (AC-BZTs) were found in both cores, with the highest levels reported to date present in Narragansett Bay, indicating sorption to, and preservation in, sediments. This study revealed that both classes of BZTs have remained structurally intact over time in coastal sediment cores, demonstrating their resistance to degradation and persistence in environmental compartments.

One application of nanocopper is as a wood-preserving pesticide in pressure-treated lumber. Recent research has shown that pressure-treated lumber amended with micronized copper azole (MCA), which contains nanosized copper, releases copper under estuarine and marine conditions. The form of copper released (i.e., ionic, nanocopper [1-100 nm in size]) is not fully understood but will affect the bioavailability and toxicity of the metal. In the present study, multiple lines of evidence, including size fractionation, ion-selective electrode electrochemistry, comparative toxicity, and copper speciation were used to determine the form of copper released from lumber blocks and sawdust. The results of all lines of evidence supported the hypothesis that ionic copper was released from MCA lumber and sawdust, with little evidence that nanocopper was released. For example, copper concentrations in size fractionations of lumber block aqueous leachates including unfiltered, 0.1 μm, and 3 kDa were not significantly different, suggesting that the form of copper released was in the size range operationally defined as dissolved. These results correlated with the ion-selective electrode data which detects only ionic copper. In addition, comparative toxicity testing resulted in a narrow range of median lethal concentrations (221-257 μg/L) for MCA lumber blocks and CuSO4 . We conclude that ionic copper was released from the nanocopper pressure-treated lumber under estuarine and marine conditions. Environ Toxicol Chem 2018;37:1969-1979. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Little is known about the release of metal engineered nanomaterials (ENMs) from consumer goods, including lumber treated with micronized copper. Micronized copper is a recent form of antifouling wood preservative containing nanosized copper particles for use in pressure-treated lumber. The present study investigated the concentrations released and the release rate of total copper over the course of 133 d under freshwater, estuarine, and marine salinity conditions (0, 1, 10, and 30‰) for several commercially available pressure-treated lumbers: micronized copper azole (MCA) at 0.96 and 2.4 kg/m3 , alkaline copper quaternary (ACQ) at 0.30 and 9.6 kg/m3 , and chromated copper arsenate (CCA) at 40 kg/m3 . Lumber was tested as blocks and as sawdust. Overall, copper was released from all treated lumber samples. Under leaching conditions, total release ranged from 2 to 55% of the measured copper originally in the lumber, with release rate constants from the blocks of 0.03 to 2.71 (units per day). Generally, measured release and modeled equilibrium concentrations were significantly higher in the estuarine conditions compared with freshwater or marine salinities, whereas rate constants showed very limited differences between salinities. Furthermore, organic carbon was released during the leaching and demonstrated a significant relationship with released copper concentrations as a function of salinity. The results indicate that copper is released into estuarine/marine waters from multiple wood treatments including lumber amended with nanoparticle-sized copper. Environ Toxicol Chem 2018;37:1956-1968. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

In this study, methods and approaches were developed and tested to assess changes in contaminant fluxes resulting from dam removal in a riverine system. Sediment traps and passive samplers were deployed to measure particulate and dissolved polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the water column prior to and following removal of a small, low-head dam in the Pawtuxet River, an urbanized river located in Cranston, RI, USA. During the study, concentrations of particulate and dissolved PAHs ranged from 21.5 to 103 μg/g and from 68 to 164 ng/L, respectively. Overall, temporal trends of PAHs showed no increases in either dissolved or particulate phases following removal of the dam. Dissolved concentrations of PCBs were very low, remaining below 1.72 ng/L at all sites. Particulate PCB concentrations across sites and time showed slightly greater variability, ranging from 80 to 469 ng/g, but with no indication that dam removal influenced any increases. Particulate PAHs and PCBs were sampled continuously at the site located below the dam and did not show sustained increases in concentration resulting from dam removal. The employment of passive sampling technology and sediment traps was highly effective in monitoring the concentrations and flux of contaminants moving through the river system. Variations in river flow had no effect on the concentration of contaminants in the dissolved or particulate phases, but did influence the flux rate of contaminants exiting the river. Overall, dam removal did not cause measurable sediment disturbance or increase the concentration or fluxes of dissolved or particulate PAHs and PCBs. This is due in large part to low volumes of impounded sediment residing above the dam and highly armored sediments in the river channel, which limited erosion. Results from this study will be used to improve methods and approaches that assess the short- and long-term impacts ecological restoration activities such as dam removal have on the release and transport of sediment-bound contaminants.

Medical education is a dynamic and continually evolving process, some of which is style, and some of which is linked to changing perspectives in medical practice. A paper by Reis et al., taken in conjunction with the recent paper from an ad hoc International Review Committee (Schoenbaum et al.), provides a reflective view of where Israeli medical education stood in 2014 and places it in an international perspective. Reis at al also take this further, showing that in Israel change is occurring as a result of this review and comment on a number of important issues where further reflection, discussion, and work is required.

In many coastal watersheds and ecosystems, rivers discharging to estuaries receive waters from domestic wastewater-treatment plants resulting in the release and distribution of pharmaceuticals to the marine environment. In the present study, 15 active pharmaceutical ingredients were measured regularly over 1 yr in the dissolved and particulate phases as they entered Narragansett Bay from the Pawtuxet River in Cranston (Rhode Island, USA). Of the active pharmaceutical ingredients measured, 14 were consistently present in the dissolved phase, with concentrations ranging from below detection to310 ng/L, whereas 8 were present in the particulate phase (0.2-18 ng/g). Partition coefficients (K

Sites throughout Boston Harbor were analyzed for caffeine to assess its utility as a tracer in identifying sources of sanitary wastewater. Caffeine ranged from 15ng/L in the outer harbor to a high of 185ng/L in the inner harbor. Inner harbor concentrations were a result of combined sewage overflow (CSO) events as well as illicit discharge of sanitary sewage into municipal storm drains. Comparing current results to data from 1998 to 1999 shows reductions in caffeine levels. Reductions are attributed to termination of effluent discharge to the harbor, declines in the number of CSOs and discharge volume along with efforts to eliminate illicit discharges. Spatial distributions of caffeine identified CSOs as major contemporary sources to the inner harbor. The findings further establish the utility of caffeine as a tracer for sanitary wastewater contamination in urban estuaries and demonstrate the efficacy of pollution reduction strategies undertaken in recent decades in Boston Harbor.

Triclosan (5-chloro-2-[2,4-dichlorophenoxy]phenol) is a relatively new, commonly used antimicrobial compound found in many personal care products. Triclosan is toxic to marine organisms at the micrograms per liter level, can photodegrade to a dioxin, can accumulate in humans, and has been found to be stable in marine sediments for over 30 years. To determine the effects of triclosan on marine benthic communities, intact sediment cores were brought into the laboratory and held under flowing seawater conditions. A 2-cm layer of triclosan-spiked sediment was applied to the surface, and after a two-week exposure the meio- and macrofaunal communities were assessed for differences in composition relative to nonspiked cores. A high triclosan treatment (180 mg/kg dry wt) affected both the meio- and the macrobenthic communities. There were no discernible differences with a low-triclosan treatment (14 mg/kg dry wt). This exposure method is effective for testing the benthic community response to sediment contaminants, but improvements should be made with regard to the amount and method of applying the overlying sediment to prevent smothering of fragile benthic organisms. Environ. Toxicol. Chem. 2013;32:384–392. © 2012 SETAC

Myeloperoxidase (MPO) is a major protein constituent of the primary granules of vertebrate neutrophils. It catalyses the hydrogen peroxide-mediated oxidation of halide ions to hypohalous acids, especially HOCl. These reactive oxygen species can participate in a variety of secondary reactions, leading to modifications of amino acids and many types of biological macromolecules. The classic paradigm views MPO as a component of the phagocyte oxygen-dependent intracellular microbicidal system, and thus an important arm of the effector phase of innate immune responses. However, the limited immunodeficiency associated with lack of MPO in mouse and human models has challenged this paradigm. In this review we examine more recent information on the interaction between MPO, its bioreactive reaction products, and targets within the inflammatory microenvironment. We propose that two assumptions of the current model may require revisiting. First, many important targets of MPO modification are extracellular, rather than present only within the phagolysosome, such as various components of neutrophil extracellular traps. Second, we suggest that the pro-inflammatory pathological role of MPO may be a particular feature of chronic inflammation. In the physiological setting of acute neutrophil-mediated inflammation MPO may also form part of a negative feedback loop which down-regulates inflammation, limits tissue damage, and facilitates the switch from innate to adaptive immunity. This different perspective on this well-studied enzyme may usefully inform further research into its function in health and disease.

The tuberculin skin test (TST) is a model of integrated innate and adaptive human immune responses to Mycobacterium tuberculosis, but the component processes that are involved in this model have not previously been defined in vivo. We used transcriptional profiling to study these responses within the TST at molecular and system levels. Skin biopsies from TST injection sites were examined in subjects classified as TST(+) or TST(-) by clinical and histological criteria. Genome-wide expression arrays showed evolution of immune responses reflecting T-cell activation and recruitment with uniquely Th1-polarized responses and cytotoxic T cells (CTLs). In addition, distinct innate immune and IFN-γ-stimulated gene expression signatures were identified, under the regulation of NF-κB and STAT1 transcriptional control. These were highly enriched for chemokines and MHC class II molecules providing a potential mechanism for paracrine amplification of inflammatory responses in the TST, by supporting cellular recruitment and enhancing antigen presentation. The same repertoire of innate and adaptive immune responses was evident in TST(+) and TST(-) subjects alike, clinically positive TSTs being distinguished only by quantitatively greater differences. These data provide new insights into complex multifaceted responses within the TST, with much greater sensitivity than previous clinical or histological assessments.

We studied the microbial food web in the upper 100 m of the water column in iron-limited sub-Antarctic HNLC waters south-east of New Zealand in the SAGE experiment in 2004, with focus on bacterioplankton. Samples were collected daily from inside and outside the iron enriched patch. Short term enrichment experiments were conducted on board in 4 L polycarbonate bottles with water outside the iron enriched patch to study single and combined effects of micronutrient additions on microbial food web. Low bacterial growth was recorded in the study area with community turnover times of 50 h or more during the study period. Measurements of bacterial standing stocks and production rates in the study show minor responses to the large scale iron enrichment, with increase in rates and stocks after the first enrichment and at the end of the study period after the third iron enrichment when solar radiation increased and wind mixing decreased. The average daily bacterial production rates were 31.5 and 33.7 mgCm −2 d −1 for the OUT and IN stations, respectively; thus overall there was not a significant difference between the control and the iron-enriched patch. In the bottle experiments bacterial thymidine incorporation showed responses to single iron and silicic acid enrichments and a major growth response to the combined iron and sucrose enrichments. Phytoplankton chlorophyll- a showed clear stimulation by single additions of iron and silicic acid and silicic acid enhanced the iron impact. Cobalt additions had no effect on bacteria growth and a negative effect on phytoplankton growth. Low bacterial in situ growth rates and the enrichment experiments suggest that bacteria are co-limited by iron and carbon, and that bacterial iron uptake is dependent on carbon supply by the food web. With the high iron quota (μmol Fe mol C −1 ) bacteria may scavenge considerable amounts of the excess iron, and thus influence the relative importance of the microbial food web as a carbon sink.

CD98, a heterodimeric type II transmembrane protein, is involved in many different cellular events, ranging from amino acid transport to cell-cell adhesion. Little is known about the positive and negative signalling pathways involved in these responses. Therefore, we examined the role of conventional protein kinase C (PKC) isoforms during CD98-induced intracellular signalling and homotypic aggregation of U937 cells. The CD98-induced aggregation was enhanced by the general protein kinase inhibitors GF109203X and staurosporin, and by specific PKC-alpha/-beta peptide inhibitor 19-27, but inhibited by PKC activators such as phorbol 12-myristate 13-acetate (PMA). PMA-inhibition was reversed by PKC inhibitors recognising the ATP-binding site in PKC (e.g. staurosporin, GF109203X and Go6983). Inhibitors which bind to diacylglycerol (DAG) or Ca(2+)-binding sites of PKC (calphostin C and Go6967) had no effect. PMA-induced translocation of conventional PKC (cPKC) isozymes (alpha, beta and gamma), but decreased the expression of PKC-delta, which plays an important role in CD98-induced homotypic aggregation. PMA treatment also suppressed the surface level of CD98 but not CD29, CD18 and CD147, dose- and time-dependently. These data provide evidence that PMA-responsive cPKC isoforms (alpha, beta and gamma) play a key role in negative regulation of CD98 signalling and homotypic aggregation.

Objective: The cellular innate immune response to HIV-1 is poorly characterized. In view of HIV-1 tropism for macrophages, which can be activated via pattern recognition receptorstotriggerantimicrobialdefences,weinvestigatedinnateimmuneresponsesto HIV-1 by monocyte-derived macrophages. Design: In a model of productive HIV-1 infection, cellular innate immune responses to HIV-1 were investigated, at the level of transcription factor activation, specific gene expression and genome-wide transcriptional profiling. In addition, the viral determinants of macrophage responses and the physiological effect of innate immune cellular activation on HIV-1 replication were assessed. Results: Productive HIV-1 infection did not activate nuclear factor-kB and interferon regulatory factor 3 transcription factors or interferon gene expression (IFN) and caused remarkably small changes to the host-cell transcriptome, with no evidence of inflammatory or IFN signatures. Evasion of IFN induction was not dependent on HIV-1 envelope-mediated cellular entry, inhibition by accessory proteins or reverse transcription of ssRNA that may reduce innate immune cellular activation by viral RNA. Furthermore, IFNb priming did not sensitize responses to HIV-1. Importantly, exogenous IFNb or stimulation with the RNA analogue poly I:C to simulate innate immune activation invoked HIV-1 restriction. Conclusion: We conclude that macrophageslack functional pattern recognition receptorsforthisvirusandthatHIV-1tropismformacrophageshelpstoestablishafootholdin the host without triggering innate immune cellular activation, which would otherwise block viral infection effectively. ! 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2009, 23:2255‐2263

Macrophages contribute to HIV-1 infection at many levels. They provide permissive cells at the site of inoculation, augment virus transfer to T cells, generate long-lived viral reservoirs, and cause bystander cell apoptosis. A body of evidence suggests that the role of macrophages in cellular host defense is also compromised by HIV-1 infection. In this respect, macrophages are potent cells of the innate immune system that initiate and regulate wide-ranging immunological responses. This study focuses on the effect of HIV-1 infection on innate immune responses by macrophages at the level of signal transduction, whole genome transcriptional profiling, and cytokine secretion. We show that in an ex vivo model, M-CSF-differentiated monocyte-derived macrophages uniformly infected with replicating CCR5-tropic HIV-1, without cytopathic effect, exhibit selective attenuation of the NF-κB activation pathway in response to TLR4 and TLR2 stimulation. However, functional annotation clustering analysis of genome-wide transcriptional responses to LPS stimulation suggests substantial preservation of gene expression changes at the systems level, with modest attenuation of a subset of up-regulated LPS-responsive genes, and no effect on a selection of inflammatory cytokine responses at the protein level. These results extend existing reports of inhibitory interactions between HIV-1 accessory proteins and NF-κB signaling pathways, and whole genome expression profiling provides comprehensive assessment of the consequent effects on immune response gene expression. Unexpectedly, our data suggest innate immune responses are broadly preserved with limited exceptions, and pave the way for further study of the complex relationship between HIV-1 and immunological pathways within macrophages.

Purpose: Hypochlorous acid, a product of neutrophil myeloperoxidase, is a powerful enhancer of antigen processing and presentation. In this study, we examine whether ovarian epithelial cells (SK-OV-3) exposed to hypochlorous acid can stimulate T cells from patients with ovarian epithelial cancer that recognize common tumor antigens as well as autologous tumor.Experimental Design: T cells from human leukocyte antigen (HLA)-A2+ and HLA-A2− patients or healthy controls were stimulated with autologous dendritic cells cocultured with the generic ovarian tumor line SK-OV-3, previously exposed to hypochlorous acid.Results: Hypochlorous acid–treated SK-OV-3 cells drove expansion of CD8+ T cells from HLA-A2+ individuals, which recognized the HLA-A2–restricted tumor antigen epitopes of HER-2/neu (E75 and GP2) and MUC1 (M1.1 and M1.2). Up to 4.1% of the T cells were positive for the HER-2/neu KIFGSLAFL epitope using pentamer staining. Dendritic cells loaded with oxidized SK-OV-3 cells and further matured with CD40 agonistic antibody or monophosphoryl lipid A additionally induced CD4+ class II–restricted responses. Critically, T cells stimulated with mature oxidized SK-OV-3 (but not a control oxidized melanoma cell line) directly recognized autologous tumor cells isolated from patient ascites.Conclusions: Immunization with mature dendritic cells loaded with a generic oxidized tumor cell line stimulates a polyclonal antitumor response that recognizes autologous tumor. These findings suggest a new immunotherapeutic strategy to extend remission in ovarian cancer.

Dendritic cells (DCs) sense the presence of conserved microbial structures in their local microenvironment via specific pattern recognition receptors (PRRs). This leads to a programme of changes, which include migration and activation, and enables them to induce adaptive T cell immunity. Mitogen-activated protein kinases (MAPKs) are implicated in this response, but the pathways leading from PRR ligation to MAPK activation, and hence DC activation, are not fully understood. Recent studies in the nervous system have suggested that the mixed lineage kinase (MLK) family of MAPK kinase kinase proteins may be involved as an intermediary step between PRRs and MAPKs. Therefore, in this study, we have used a well-established DC model to explore the role of MLKs in these cells. Messenger RNA for MLKs 2, 3, 4 and DLK and protein for MLKs 2, 3 and DLK are found in DC. DC activation in response to model PRR ligands, such as LPS or poly (I:C), is accompanied by phosphorylation of MLK3. In contrast, another known PRR ligand, zymosan, induces little MLK3 phosphorylation. Inhibition of MLK activity using a pharmacological inhibitor, CEP11004, blocks p38 and Jun N-terminal kinase (JNK) MAPK activation in response to LPS and poly (I:C), but not zymosan. The inhibition is associated with a block in DC activation as measured by cell-surface marker expression and cytokine secretion. Thus, MLKs are expressed in DC, and are implicated in DC activation, and the involvement of MLKs appears to be selective, depending on the nature of the DC stimulus.

This review summarizes current knowledge about the mixed lineage kinases (MLKs) and explores their potential role in inflammation and immunity. MLKs were identified initially as signalling molecules in the nervous system. They were also shown to play a role in the cell cycle. Further studies documented three groups of MLKs, and showed that they may be activated via the c-Jun NH2 terminal kinase (JNK) pathway, and by Rho GTPases. The biochemistry of the MLKs has been investigated in considerable detail. Homodimerization and heterodimerization can occur, and both autophosphorylation and autoinhibition are seen. The interaction between MLKs and JNK interacting protein (JIP) scaffolds, and the resultant effects on mitogen activated protein kinases, have been identified. Clearly, there is some redundancy within the MLK pathway(s), since mice which lack the MLK3 molecule are not abnormal. However, using a combination of biochemical analysis and pharmacological inhibitors, several recent studies in vitro have suggested that MLKs are not only expressed in cells of the immune system (as well as in the nervous system), but also may be implicated selectively in the signalling pathway that follows on toll-like receptor ligation in innate sentinel cells, such as the dendritic cell.

A 2014 external review of medical schools in Israel identified several issues of importance to the nation's health. This paper focuses on three inter-related policy-relevant topics: planning the physician and healthcare workforce to meet the needs of Israel's population in the 21(st) century; enhancing the coordination and efficiency of medical education across the continuum of education and training; and the financing of medical education. All three involve both education and health care delivery. The physician workforce is aging and will need to be replenished. Several physician specialties have been in short supply, and some are being addressed through incentive programs. Israel's needs for primary care clinicians are increasing due to growth and aging of the population and to the increasing prevalence of chronic conditions at all ages. Attention to the structure and content of both undergraduate and graduate medical education and to aligning incentives will be required to address current and projected workforce shortage areas. Effective workforce planning depends upon data that can inform the development of appropriate policies and on recognition of the time lag between developing such policies and seeing the results of their implementation. The preclinical and clinical phases of Israeli undergraduate medical education (medical school), the mandatory rotating internship (stáge), and graduate medical education (residency) are conducted as separate "silos" and not well coordinated. The content of basic science education should be relevant to clinical medicine and research. It should stimulate inquiry, scholarship, and lifelong learning. Clinical exposures should begin early and be as hands-on as possible. Medical students and residents should acquire specific competencies. With an increasing shift of medical care from hospitals to ambulatory settings, development of ambulatory teachers and learning environments is increasingly important. Objectives such as these will require development of new policies. Undergraduate medical education (UME) in Israel is financed primarily through universities, and they receive funds through VATAT, an education-related entity. The integration of basic science and clinical education, development of earlier, more hands-on clinical experiences, and increased ambulatory and community-based medical education will demand new funding and operating partnerships between the universities and the health care delivery system. Additional financing policies will be needed to ensure the appropriate infrastructure and support for both educators and learners. If Israel develops collaborations between various government agencies such as the Ministries of Education, Health, and Finance, the universities, hospitals, and the sick funds (HMOs), it should be able to address successfully the challenges of the 21st century for the health professions and meet its population's needs.

The morphology of antigen-presenting dendritic cells (DCs) is characterized by the presence of numerous long dendrites. The formation of these processes is shown to require the interaction between the beta1-integrin (CD29) on the surface of the DCs and fibronectin in the extracellular matrix. This interaction occurs at focal contacts formed at the tips of dendrites, which contain high concentrations of the beta1-integrins, actin and the cytoskeletal proteins vinculin, paxillin and talin. Dendrites contain an extensive microtubule (MT) network, and are retracted in the presence of the MT inhibitor colchicine, suggesting that MTs are essential for dendrite stability. The dendritic morphology is shown to contribute directly to an enhanced ability to capture dendritic cell specific ICAM-3 grabbing nonintegrin (DC-SIGN)-coated beads. Time-lapse photography demonstrates that dendrites are highly dynamic structures, with cells extending and retracting multiple dendrites in different directions over a 3-h period. This motility increases the area scanned by an individual DC by over 2-fold. The unusual combination of a dendritic morphology and high motility is likely to play a major role in the efficient function of DCs as sentinels of the immune system.

The central role of dendritic cells (DC) in the initiation of immune responses requires these cells to be able to determine the degree of danger in their microenvironment. Abrogating the activity of type I interferon (IFN) secreted after lipopolysaccharide (LPS) stimulation of DC inhibits CD86 and human leucocyte antigen-DR (HLA-DR) upregulation at a low LPS concentration. At a higher concentration of LPS, while changes in surface phenotype are not dependent on type I IFN, this cytokine is required for maximal secretion of interleukin-12 (IL-12) and tumour necrosis factor-alpha (TNFalpha) by DC. Thus, the secretion and autocrine activity of type I IFN after Toll-like receptor stimulation enables DC to orchestrate a hierarchical maturation response with regard to changes in surface phenotype and secretion of cytokines. In addition, the activation of nuclear factor-kappaB and p38 pathways in DC can occur either in an additive fashion when DC are exposed to dual stimulation or can be activated in discrete phases over time when DC are exposed to LPS alone. The differential activation of these pathways provides a mechanism for DC to integrate the activation by multiple stimuli and thus amplify responses to pathogen infection.

A novel shipboard gas tension device (GTD) that measures total dissolved air pressure in ocean surface waters is described and demonstrated. In addition, an improved method to estimate dissolved N 2 levels from simultaneous measurements of gas tension, dissolved O 2 , water temperature, and salinity is described. Other than a flow-through plenum, the shipboard GTD is similar to the previously described moored-mode GTD (McNeil et al., 1995, Deep-Sea Research I 42, 819–826). The plenum has an integrated water-side screen to protect the membrane, and prevent the membrane from flexing in super-saturated near surface waters. The sampling scheme uses a well mixed and thermally insulated 15 L container that is flushed by the ship's seawater intake at a rate of 3–15 L min −1 . Dissolved gas sensors are placed inside this container and flushed with a small recirculation pump. Laboratory data that characterize the response of the modified GTD are presented. The modified GTD has a constant, isothermal, characteristic (e-folding) response time of typically 11±2 min at 20 °C. The response time decreases with increasing temperature and varies by ±35% over a temperature range of 5–35 °C. Results of field measurements, collected on the R.V. Brown between New York and Puerto Rico during September 2002, are presented, and provide the first look at co-variability in surface ocean N 2 , O 2 , and CO 2 levels over horizontal length scales of several kilometers. Dissolved N 2 concentrations decreased by approximately 16% as the ship sailed from the colder northern continental shelf waters, across the Gulf Stream, and into the warmer northwestern Atlantic Ocean. Historical database measurements, buoy time series, and satellite imagery, are used to aid interpretation of the dissolved gas levels.

Regulated migration and spatial localization of dendritic cells (DCs) are critical events during the initiation of physiologic immune responses and maintenance of tolerance. Here we have used cells deficient in the Wiskott-Aldrich syndrome protein (WASp) to demonstrate the importance of dynamic remodeling of the actin cytoskeleton for these trafficking processes to occur in vitro and in vivo. On fibronectin-coated surfaces, WASp-null immature murine DCs exhibited defects both of attachment and detachment, resulting in impaired net translocation compared with normal cells. The chemokinetic response to CCL21, which is critical for normal lymphatic trafficking, was also abrogated in the absence of WASp. In vivo in both fluorescein isothiocyanate (FITC) and oxazolone contact hypersensitivity models, WASp-null Langerhans cell (LC) migration was compromised, as judged by exit from the skin as well as by homing to the draining lymph node (LN). Furthermore, following systemic challenge with lipopolysaccharide (LPS) or toxoplasma-derived antigen, WASp-null DCs showed incomplete redistribution to T-cell areas in the spleen. Instead, they were retained ectopically in the marginal zone. DC trafficking in vivo is therefore dependent on a normally regulated actin cytoskeleton, which performs an essential function during maintenance of physiologic immunity and when disturbed may contribute significantly to the immunopathology of Wiskott-Aldrich Syndrome.

A recent online article in the Journal of Medical Ethics, which received wide media coverage, raised the possibility that children are being ‘subjected to torture’ due to the ‘fervent or fundamentalist views’ of their parents. However, the quality of argument in that article was inadequate to sustain such a radical thesis. There was no engagement with the perspectives of different religious traditions about end-of-life care. Instead the authors invoked practices such as male infant circumcision which are wholly irrelevant to the end-of-life theme. There were serious failings in relation to core principles of social and epide-miological research practice: the study based its conclusion on a sample of only six cases and failed to consider even the more obvious confounding features. Rather than demonizing the religious beliefs of parents there should be recognition of the need for mutual respect, dialogue based on an ‘expert-expert relationship’ and collaboration based on ‘shared understanding’.

Purpose of reviewInfection with herpes simplex virus remains a significant cause of disease. The host immune system plays an important role in containing viral replication, and there has been considerable progress in defining which components of immunity are key to the resolution of infection. Nevertheless, effective immunoprophylaxis or immunotherapy has not yet been achieved.Recent findingsRecent work has focused on understanding the early events leading to the herpes simplex virus-specific immune response, in particular on the role of antigen-presenting dendritic cells. Herpes simplex virus has evolved a number of ways of interfering with antigen presentation by dendritic cells, thus presumably impeding or delaying the host immune response. Nevertheless, herpes simplex virus triggers strong cellular and humoral immunity. The ability of dendritic cells to take up dead or dying infected cells and cross-present them to cognate T cells may be the key to resolving this apparent paradox. Interaction between dendritic cell subsets, and particularly the virus-induced release of type I interferons may be essential to drive efficient antigen cross-presentation and subsequent T-cell activation.SummaryA greater understanding of the importance of dendritic cells in driving viral immunity, and of the ligands that activate these cells and the cytokines they secrete, has provided novel vaccination strategies. The delivery of immunomodulatory genes together with viral antigens, for example by DNA vaccination, may harness the full potential of dendritic cells, and achieve the goal of effective immunological control of herpes simplex virus.

CD43 (leukosialin, sialophorin), a prominent component of the hemopoietic cell surface, has an enigmatic role in cell–cell interaction. The observation that CD43 ligation triggers homotypic aggregation of monoblastoid U937 cells has permitted analysis of this: CD43-induced aggregation was distinguishable from CD29- (also known as β1 integrin) or CD98- (also known as 4F2, or fusion-related protein 1) induced aggregation, with different energy requirements and with partial dependence on β2 integrins. Previous studies have focused on the role of CD43 ligation in tyrosine phosphorylation. However, in the homotypic adhesion assay, although there is initial tyrosine phosphorylation, protein tyrosine kinase inhibitors did not block aggregation. Therefore, other signaling pathways were examined. CD43 ligation induced protein tyrosine dephosphorylation, and protein tyrosine phosphatase inhibitors blocked aggregation. Activation of MAP kinases was not necessary. Cytoskeletal inhibitors amplified aggregation. Protein kinase C (PKC) inhibitors amplified aggregation, implicating PKC as a negative regulator. CD43 ligation up-regulated surface adhesion molecules and enhanced CD29- and CD98-induced aggregation. Thus, CD43 participation in cell–cell adhesion is under stringent control, involving both surface events and several different intracellular signaling pathways, acting together to regulate the process. These mechanisms add a further dimension to the potential role of CD43 in tissue immune responses.

1. Staurosporine is a broad-specificity kinase inhibitor, which has acted as lead compound for the development of some novel cytotoxic compounds for treatment of cancer. This study investigates the unexpected observation that staurosporine can also induce homotypic cellular aggregation. 2. In this study, staurosporine is shown to activate rapid homotypic aggregation of U937 cells, at concentrations below those required to induce cell death. This activity is a particular feature of staurosporine, and is not shared by a number of other kinase inhibitors. The proaggregating activity of staurosporine is inhibited by deoxyglucose, cytochalasin B and colchicine. Staurosporine-induced aggregation can be distinguished from that induced by the phorbol 12-myristate 13-acetate by faster kinetics and insensitivity to cycloheximide. Staurosporine induces translocation of conventional and novel, but not atypical isoforms of protein kinase C (PKC). Aggregation induced by staurosporine is inhibited by a number of inhibitors of PKC isoforms, and by inhibitors of protein tyrosine kinases. Staurosporine also induces rapid phosphorylation of ERK and p38, and inhibitors of both these enzymes block aggregation. 3. Staurosporine induces dysregulated activation of multiple kinase signaling pathways in U937 cells, and the combined activity of several of these pathways is essential for the induction of aggregation.

SUMMARYDendritic cells (DCs) play an important role in determining immunogenicity and the subsequent immune response. They may also have a role in maintaining peripheral tolerance to self-antigens by initiating an immune response only in the context of danger signals released from cells during stress, damage or death. These signals may originate from surrounding T cells as well as from other cells. Therefore, in this study the effect of autologous T cell injury on DC morphology and function has been investigated. Co-incubation of apoptotic or necrotic T cells with immature DCs altered their morphology towards a more mature appearance, with more cells showing activation as judged by spreading and formation of arborizing long processes. The apoptotic autologous T cells were rarely phagocytosed by immature DCs, compared to macrophages. The DC surface phenotype was not affected by the co-incubation with autologous injured T cells. The ability of DCs to elicit a secondary immune response was not altered by exposure to autologous injured T cells. These findings suggest that DC can continue to function in T cell activation, rather than in tolerogenic mode, even in the presence of large numbers of dying autologous T cells, such as may be present in the aftermath of an acute antiviral response.

CD98 is a protein found on the surface of many activated cell types, and is implicated in the regulation of cellular differentiation, adhesion, growth, and apoptosis. Despite many studies addressing CD98 function, there is little information on the intracellular signalling pathways that mediate its activity. In this study, we examine protein kinase pathways that are activated following ligation by the CD98 antibody AHN-18, an antibody that induces U937 homotypic aggregation and inhibits antigen presenting activity and T-cell activation. Ligation by CD98 antibody AHN-18 induces tyrosine kinase activity, but inhibition of this activity does not affect U937 aggregation. Ligation also induces membrane translocation of the serine/threonine kinase novel PKCdelta, but not other members of the PKC family. Translocation is blocked by rottlerin, and this inhibitor also blocks aggregation. PKCdelta activation in turn mediates activation of ERK1/2 and p38, as well as tyrosine phosphorylation of multiple proteins, and MAPK activation is essential for cellular aggregation. One of the targets of CD98-induced tyrosine phosphorylation is itself PKCdelta, suggesting that this phosphorylation may act as a negative feedback to limit the overall activation of the CD98 pathway.

Initiation of adaptive immunity requires activation of dendritic cells (DC) by "danger" signals. This study examines the functional consequences of activating a cellular stress response in human DC. Anisomycin, a potent inducer of this "stress" response, selectively activates p38 kinase in DC at low concentrations, and both p38 kinases and JNKs at higher concentrations. Activation of p38, was accompanied by an increase in the potency of dendritic cells to activate T cells. In contrast to LPS, anisomycin had no effect on the expression of several DC activation markers. Anisomycin synergised with LPS in driving release of IL-12 and TNF-alpha. Anisomycin also enhanced the formation of clusters between DC and T cells. Enhanced cytokine release and clustering were both inhibited by the selective p38 alpha and p38 beta inhibitor SB203580. This study demonstrates that the cellular stress response, mediated via p38 kinases, plays an important role in the regulation of several aspects of DC function.

Several lines of evidence suggest that dendritic cells (DCs), the most potent antigen-presenting cells known, play a role in the immunological control of herpes simplex virus (HSV) infections. HSV infection of DCs induced submaximal maturation, but DCs failed to mature further in response to lipopolysaccharide (LPS). LPS induced interleukin (IL)-12 secretion, and the induction of primary and secondary T cell responses were impaired by infection. Ultimately, DC infection resulted in delayed, asynchronous apoptotic cell death. However, infected DCs induced HSV recall responses in some individuals. Furthermore, soluble factors secreted by DCs after infection induced DC maturation and primed for IL-12 secretion after LPS stimulation. These data support a pathogenetic model of HSV infection, in which initial delay in the generation of immune responses to HSV at peripheral sites is mediated by disruption of DC function but is overcome by bystander DC maturation and cross-presentation of HSV antigens.

The toxicity, bioaccumulation, and biotransformation of citrate and polyvinylpyrrolidone (PVP) coated silver nanoparticles (NPs) (AgNP-citrate and AgNP-PVP) in marine organisms via marine sediment exposure was investigated. Results from 7-d sediment toxicity tests indicate that AgNP-citrate and AgNP-PVP did not exhibit toxicity to the amphipod (Ampelisca abdita) and mysid (Americamysis bahia) at ≤75 mg/kg dry wt. A 28-d bioaccumulation study showed that Ag was significantly accumulated in the marine polychaete Nereis virens (N. virens) in the AgNP-citrate, AgNP-PVP and a conventional salt (AgNO3) treatments. Synchrotron X-ray absorption spectroscopy (XAS) results showed the distribution of Ag species in marine sediments amended with AgNP-citrate, AgNP-PVP, and AgNO3 was AgCl (50–65%) > Ag2S (32–42%) > Ag metal (Ag0) (3–11%). In N virens, AgCl (25–59%) and Ag2S (10–31%) generally decreased and, Ag metal (32–44%) increased, relative to the sediments. The patterns of speciation in the worm were different depending upon the coating of the AgNP and both types of AgNPs were different than the AgNO3 salt. These results show that the AgNP surface capping agents influenced Ag uptake, biotransformation, and/or excretion. To our knowledge, this is the first demonstration of the bioaccumulation and speciation of AgNPs in a marine organism (N. virens).

Kinetic studies of the reactions of 3-pentoxy with NO and O2 have been performed using laser-induced fluorescence detection of 3-pentoxy radicals. Experiments were carried out at a total pressure of 50 Torr at subambient temperatures. Arrhenius expressions are obtained for the reactions of 3-pentoxy with NO (kNO) and O2 (kO2): kNO = (5.6 ± 1.6) × 10-13 exp[(7.8 ± 0.6) kJ mol-1/RT] cm3 molecule-1 s-1 (216−276 K), and kO2 = (4.1 ± 1.2) × 10-15 exp[(2.6 ± 0.6) kJ mol-1/RT] cm3 molecule-1 s-1 (220−285 K). No pressure dependence was observed for either rate constant at 243 K between 50 and 150 Torr. The negative temperature dependence of kNO is significantly larger than that of other alkoxy radicals, and this suggests a 298 K rate constant that is only one-third to half those measured for other alkoxy radicals. The small negative temperature dependence of kO2 is different from the small positive temperature dependence observed for ethoxy and propoxy radicals but is comparable to that previously observed for 2...

This Letter reports the first kinetic study of 2-butoxy radicals to employ direct monitoring of the radical. The reactions of 2-butoxy with O2 and NO are investigated using laser-induced fluorescence (LIF). The Arrhenius expressions for the reactions of 2-butoxy with NO (k 1 ) and O 2 (k 2 ) in the temperature range 223–311 K have been determined to be k 1 =(7.50±1.69)×10 −12 × exp ((2.98±0.47) kJ mol −1 / RT ) cm 3 molecule −1 s −1 and k 2 =(1.33±0.43)×10 −15 × exp ((5.48±0.69) kJ mol −1 / RT ) cm 3 molecule −1 s −1 . No pressure dependence was found for the rate constants of the reaction of 2-butoxy with NO at 223 K between 50 and 175 Torr.

Purpose: To identify mutations in families with acute intermittent porphyria, an autosomal dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase. Methods: Mutations were identified by direct solid phase sequencing. Results: Two novel missense mutations E80G and T78P and three previously reported mutations, R173W, G111R, and the splice site lesion, IVS1+1, were detected, each in an unrelated proband. The causality of the novel missense mutations was demonstrated by expression studies. Conclusion: These findings provide for the precise diagnosis of carriers in these families and further expand the molecular heterogeneity of AIP.

A murine model that closely resembles human cerebral malaria is presented, in which characteristic features of parasite sequestration and inflammation in the brain are clearly demonstrable. “Young” (BALB/c × C57BL/6)F1mice infected withPlasmodium berghei(ANKA) developed typical neurological symptoms 7 to 8 days later and then died, although their parasitemias were below 20%. Older animals were less susceptible. Immunohistopathology and ultrastructure demonstrated that neurological symptoms were associated with sequestration of both parasitized erythrocytes and leukocytes and with clogging and rupture of vessels in both cerebral and cerebellar regions. Increases in tumor necrosis factor alpha and CD54 expression were also present. Similar phenomena were absent or substantially reduced in older infected but asymptomatic animals. These findings suggest that this murine model is suitable both for determining precise pathogenetic features of the cerebral form of the disease and for evaluating circumventive interventions.