Surface and lightning sources of nitrogen oxides over the United States: Magnitudes, chemical evolution, and outflow

We use observations from two aircraft during the ICARTT campaign over the eastern United States and North Atlantic during summer 2004, interpreted with a global 3-D model of tropospheric chemistry (GEOS-Chem) to test current understanding of regional sources, chemical evolution, and export of NOx. The boundary layer NOx data provide top-down verification of a 50% decrease in power plant and industry NOx emissions over the eastern United States between 1999 and 2004. Observed NOx concentrations at 8–12 km altitude were 0.55 ± 0.36 ppbv, much larger than in previous U.S. aircraft campaigns (ELCHEM, SUCCESS, SONEX) though consistent with data from the NOXAR program aboard commercial aircraft. We show that regional lightning is the dominant source of this upper tropospheric NOx and increases upper tropospheric ozone by 10 ppbv. Simulating ICARTT upper tropospheric NOx observations with GEOS-Chem requires a factor of 4 increase in modeled NOx yield per flash (to 500 mol/ flash). Observed OH concentrations were a factor of 2 lower than can be explained from current photochemical models, for reasons that are unclear. A NOy-CO correlation analysis of the fraction f of North American NOx emissions vented to the free troposphere as NOy (sum of NOx and its oxidation products) shows observed f = 16 ± 10% and modeled f = 14 ± 9%, consistent with previous studies. Export to the lower free troposphere is mostly HNO3 but at higher altitudes is mostly PAN. The model successfully simulates NOy export efficiency and speciation, supporting previous model estimates of a large U.S. anthropogenic contribution to global tropospheric ozone through PAN export

Diverse examples from managing invasive vertebrate species on inhabited islands of the United States

A wide array of sizes, ecosystems, cultures, and invasive wildlife are represented among inhabited islands. Here, six cases from the United States of America (US) are selected to illustrate the high diversity of invasive animal management issues and objectives. We outline the background, define the problems and management objectives. We identify the management approaches and discuss the results and influences as they specifically relate to inhabited islands. The examples are: (1) Gambian giant pouched rats on Grassy Key, Florida; (2) coqui frogs on Kaua’i, Hawai’i; (3) feral swine on Cayo Costa Island, Florida; (4) rodents and monitor lizards on Cocos Island, Guam; (5) black spiny-tailed iguanas (ctenosaurs) on Gasparilla Island, Florida; and (6) mongooses on Puerto Rico. The outcomes of the programs are discussed, particularly in relation to the impact of human habitation on success

IL-33 potentiates histaminergic itch

BACKGROUND: Itch is a common symptom that can greatly diminish quality of life. Histamine is a potent endogenous pruritogen, and while antihistamines are often the first-line treatment for itch, in conditions like chronic spontaneous urticaria (CSU), many patients remain symptomatic while receiving maximal doses. Mechanisms that drive resistance to antihistamines are poorly defined. OBJECTIVES: Signaling of the alarmin cytokine IL-33 in sensory neurons is postulated to drive chronic itch by inducing neuronal sensitization to pruritogens. Thus, we sought to determine if IL-33 can augment histamine-induced (histaminergic) itch. METHODS: Itch behavior was assessed in response to histamine after IL-33 or saline administration. Various stimuli and conditional and global knockout mice were utilized to dissect cellular mechanisms. Multiple existing transcriptomic data sets were evaluated, including single-cell RNA sequencing of human and mouse skin, microarrays of isolated mouse mast cells at steady state and after stimulation with IL-33, and microarrays of skin biopsy samples from subjects with CSU and healthy controls. RESULTS: IL-33 amplifies histaminergic itch independent of IL-33 signaling in sensory neurons. Mast cells are the top expressors of the IL-33 receptor in both human and mouse skin. When stimulated by IL-33, mouse mast cells significantly increase IL-13 levels. Enhancement of histaminergic itch by IL-33 relies on a mast cell- and IL-13-dependent mechanism. IL-33 receptor expression is increased in lesional skin of subjects with CSU compared to healthy controls. CONCLUSIONS: Our findings suggest that IL-33 signaling may be a key driver of histaminergic itch in mast cell-associated pruritic conditions such as CSU

Decreased function of survival motor neuron protein impairs endocytic pathways

This document is the Accepted Manuscript version. The final, definitive version is available online at https://doi.org/10.1073/pnas.1600015113.Spinal muscular atrophy (SMA) is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein, with 1 in 40 Caucasians being heterozygous for a disease allele. SMN is critical for the assembly of numerous ribonucleoprotein complexes, yet it is still unclear how reduced SMN levels affect motor neuron function. Here, we examined the impact of SMN depletion in Caenorhabditis elegans and found that decreased function of the SMN ortholog SMN-1 perturbed endocytic pathways at motor neuron synapses and in other tissues. Diminished SMN-1 levels caused defects in C. elegans neuromuscular function, and smn-1 genetic interactions were consistent with an endocytic defect. Changes were observed in synaptic endocytic proteins when SMN-1 levels decreased. At the ultrastructural level, defects were observed in endosomal compartments, including significantly fewer docked synaptic vesicles. Finally, endocytosis-dependent infection by JC polyomavirus (JCPyV) was reduced in human cells with decreased SMN levels. Collectively, these results demonstrate for the first time, to our knowledge, that SMN depletion causes defects in endosomal trafficking that impair synaptic function, even in the absence of motor neuron cell death.Peer reviewedFinal Accepted Versio

Inferring marine distribution of Canadian and Irish Atlantic salmon (Salmo salar L.) in the North Atlantic from tissue concentrations of bio-accumulated Caesium 137

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in ICES Journal of Marine Science following peer review. The definitive publisher-authenticated version “Spares A.D., Reader J.M., Stokesbury M.J.W., McDermott T., Zikovsky L., Avery T.S., Dadswell M.J. Inferring marine distribution of Canadian and Irish Atlantic salmon (Salmo salar L.) in the North Atlantic from tissue concentrations of bio-accumulated caesium 137. (2007) ICES Journal of Marine Science, 64 (2), pp. 394–404” is available online at: http://icesjms.oxfordjournals.org/content/64/2/394peer-reviewedAtlantic salmon returning from marine migrations to eastern Canada and western Ireland during 2002 and 2003 were analysed for tissue concentrations of bio-accumulated caesium 137 (137Cs). Salmon from Canadian and Irish waters demonstrated concentrations (0.20 ± 0.14 Bq kg-1 and 0.19 ± 0.09 Bq kg-1, mean ± s.d., respectively) suggesting similar oceanic feeding distributions during migration. Canadian aquaculture escapees had a similar mean tissue concentration (0.28 ± 0.22 Bq kg-1), suggesting migration with wild salmon. However, significantly higher concentrations in 1-sea-winter (1SW) escapees (0.43 ± 0.25 Bq kg-1) may alternatively suggest feeding within local estuaries. High concentrations in some Canadian 1SW salmon indicated trans-Atlantic migration. Low concentrations of Canadian multi-sea-winter (MSW) salmon suggested a feeding distribution in the Labrador and Irminger Seas before homeward migration, because those regions have the lowest surface water 137Cs levels. Estimates of wild Canadian and Irish salmon feeding east of the Faroes (~8oW) were 14.2% and 10.0% (1SW, 24.7% and 11.5%; MSW, 2.9% and 0.0%), respectively. We propose that most anadromous North Atlantic salmon utilize the North Atlantic Gyre for marine migration and should be classified as a single trans-Atlantic straddling stock

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Reducing the Blood Pressure–Related Burden of Cardiovascular Disease: Impact of Achievable Improvements in Blood Pressure Prevention and Control

BACKGROUND: US blood pressure reduction policies are largely restricted to hypertensive populations and associated benefits are often estimated based on unrealistic interventions. METHODS AND RESULTS: We used multivariable linear regression to estimate incidence rate differences contrasting the impact of 2 pragmatic hypothetical interventions to reduce coronary heart disease, stroke, and heart failure (HF) incidence: (1) a population-wide intervention that reduced systolic blood pressure by 1 mm Hg and (2) targeted interventions that reduced the prevalence of unaware, untreated, or uncontrolled blood pressure above goal (per Eighth Joint National Committee treatment thresholds) by 10%. In the Atherosclerosis Risk in Communities Study (n=15 744; 45 to 64 years at baseline, 1987-1989), incident coronary heart disease and stroke were adjudicated by physician panels. Incident HF was defined as the first hospitalization with discharge diagnosis code of "428." A 10% proportional reduction in unaware, untreated, or uncontrolled blood pressure above goal resulted in ≈4.61, 3.55, and 11.01 fewer HF events per 100,000 person-years in African Americans, and 3.77, 1.63, and 4.44 fewer HF events per 100 000 person-years, respectively, in whites. In contrast, a 1 mm Hg population-wide systolic blood pressure reduction was associated with 20.3 and 13.3 fewer HF events per 100 000 person-years in African Americans and whites, respectively. Estimated event reductions for coronary heart disease and stroke were smaller than for HF, but followed a similar pattern for both population-wide and targeted interventions. CONCLUSIONS: Modest population-wide shifts in systolic blood pressure could have a substantial impact on cardiovascular disease incidence and should be developed in parallel with interventions targeting populations with blood pressure above goal