Nucleophilic substitution by amide nitrogen in the aromatic rings of [zn − H]˙+ ions; the structures of the [b2 − H − 17]˙+ and [c1 − 17]+ ions

Peptide radical cations that contain an aromatic amino acid residue cleave to give [zn − H]˙+ ions with [b2 − H − 17]˙+ and [c1 − 17]+ ions, the dominant products in the dissociation of [zn − H]˙+, also present in lower abundance in the CID spectra. Isotopic labeling in the aromatic ring of [Yπ˙GG]+ establishes that in the formation of [b2 − H − 17]˙+ ions a hydrogen from the δ-position of the Y residue is lost, indicating that nucleophilic substitution on the aromatic ring has occurred. A preliminary DFT investigation of nine plausible structures for the [c1 − 17]+ ion derived from [Yπ˙GG]+ shows that two structures resulting from attack on the aromatic ring by oxygen and nitrogen atoms from the peptide backbone have significantly better energies than other isomers. A detailed study of [Yπ˙GG]+ using two density functionals, B3LYP and M06-2X, with a 6-31++G(d,p) basis set gives a higher barrier for attack on the aromatic ring of the [zn − H]˙+ ion by nitrogen than by the carbonyl oxygen. However, subsequent rearrangements involving proton transfers are much higher in energy for the oxygen-substituted isomer leading to the conclusion that the [c1 − 17]+ ions are the products of nucleophilic attack by nitrogen, protonated 2,7-dihydroxyquinoline ions. The [b2 − H − 17]˙+ ions are formed by loss of glycine from the same intermediates involved in the formation of the [c1 − 17]+ ions.postprin

Formation, isomerization and dissociation of ε- and α-carbon-centered tyrosylglycylglycine radical cations

postprin

Novel Cβ–Cγ Bond Cleavages of Tryptophan-Containing Peptide Radical Cations

In this study, we observed unprecedented cleavages of the Cβ–Cγ bonds of tryptophan residue side chains in a series of hydrogen-deficient tryptophan-containing peptide radical cations (M•+) during low-energy collision-induced dissociation (CID). We used CID experiments and theoretical density functional theory (DFT) calculations to study the mechanism of this bond cleavage, which forms [M – 116]+ ions. The formation of an α-carbon radical intermediate at the tryptophan residue for the subsequent Cβ–Cγ bond cleavage is analogous to that occurring at leucine residues, producing the same product ions; this hypothesis was supported by the identical product ion spectra of [LGGGH – 43]+ and [WGGGH – 116]+, obtained from the CID of [LGGGH]•+ and [WGGGH]•+, respectively. Elimination of the neutral 116-Da radical requires inevitable dehydrogenation of the indole nitrogen atom, leaving the radical centered formally on the indole nitrogen atom ([Ind]•-2), in agreement with the CID data for [WGGGH]•+ and [W1-CH3GGGH]•+; replacing the tryptophan residue with a 1-methyltryptophan residue results in a change of the base peak from that arising from a neutral radical loss (116 Da) to that arising from a molecule loss (131 Da), both originating from Cβ–Cγ bond cleavage. Hydrogen atom transfer or proton transfer to the γ-carbon atom of the tryptophan residue weakens the Cβ–Cγ bond and, therefore, decreases the dissociation energy barrier dramatically

Microbial community composition in sediments resists perturbation by nutrient enrichment

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 5 (2011): 1540–1548, doi:10.1038/ismej.2011.22.Functional redundancy in bacterial communities is expected to allow microbial assemblages to survive perturbation by allowing continuity in function despite compositional changes in communities. Recent evidence suggests, however, that microbial communities change both composition and function as a result of disturbance. We present evidence for a third response: resistance. We examined microbial community response to perturbation caused by nutrient enrichment in salt marsh sediments using deep pyrosequencing of 16S rRNA and functional gene microarrays targeting the nirS gene. Composition of the microbial community, as demonstrated by both genes, was unaffected by significant variations in external nutrient supply, despite demonstrable and diverse nutrient–induced changes in many aspects of marsh ecology. The lack of response to external forcing demonstrates a remarkable uncoupling between microbial composition and ecosystem-level biogeochemical processes and suggests that sediment microbial communities are able to resist some forms of perturbation.Funding for this research came from NSF(DEB-0717155 to JEH, DBI-0400819 to JLB). Support for the sequencing facility came from NIH and NSF (NIH/NIEHS-P50-ES012742-01 and NSF/OCE 0430724-J Stegeman PI to HGM and MLS, and WM Keck Foundation to MLS). Salary support provided from Princeton University Council on Science and Technology to JLB. Support for development of the functional gene microarray provided by NSF/OCE99-081482 to BBW. The Plum Island fertilization experiment was funded by NSF (DEB 0213767 and DEB 0816963)

Biotic and abiotic retention, recycling and remineralization of metals in the ocean

Trace metals shape both the biogeochemical functioning and biological structure of oceanic provinces. Trace metal biogeochemistry has primarily focused on modes of external supply of metals from aeolian, hydrothermal, sedimentary and other sources. However, metals also undergo internal transformations such as abiotic and biotic retention, recycling and remineralization. The role of these internal transformations in metal biogeochemical cycling is now coming into focus. First, the retention of metals by biota in the surface ocean for days, weeks or months depends on taxon-specific metal requirements of phytoplankton, and on their ultimate fate: that is, viral lysis, senescence, grazing and/or export to depth. Rapid recycling of metals in the surface ocean can extend seasonal productivity by maintaining higher levels of metal bioavailability compared to the influence of external metal input alone. As metal-containing organic particles are exported from the surface ocean, different metals exhibit distinct patterns of remineralization with depth. These patterns are mediated by a wide range of physicochemical and microbial processes such as the ability of particles to sorb metals, and are influenced by the mineral and organic characteristics of sinking particles. We conclude that internal metal transformations play an essential role in controlling metal bioavailability, phytoplankton distributions and the subsurface resupply of metals

Abdominal muscle fatigue following exercise in chronic obstructive pulmonary disease

<p>Abstract</p> <p>Background</p> <p>In patients with chronic obstructive pulmonary disease, a restriction on maximum ventilatory capacity contributes to exercise limitation. It has been demonstrated that the diaphragm in COPD is relatively protected from fatigue during exercise. Because of expiratory flow limitation the abdominal muscles are activated early during exercise in COPD. This adds significantly to the work of breathing and may therefore contribute to exercise limitation. In healthy subjects, prior expiratory muscle fatigue has been shown itself to contribute to the development of quadriceps fatigue. It is not known whether fatigue of the abdominal muscles occurs during exercise in COPD.</p> <p>Methods</p> <p>Twitch gastric pressure (TwT10Pga), elicited by magnetic stimulation over the 10^ththoracic vertebra and twitch transdiaphragmatic pressure (TwPdi), elicited by bilateral anterolateral magnetic phrenic nerve stimulation were measured before and after symptom-limited, incremental cycle ergometry in patients with COPD.</p> <p>Results</p> <p>Twenty-three COPD patients, with a mean (SD) FEV₁40.8(23.1)% predicted, achieved a mean peak workload of 53.5(15.9) W. Following exercise, TwT₁₀Pga fell from 51.3(27.1) cmH₂O to 47.4(25.2) cmH₂O (p = 0.011). TwPdi did not change significantly; pre 17.0(6.4) cmH₂O post 17.5(5.9) cmH₂O (p = 0.7). Fatiguers, defined as having a fall TwT10Pga ≥ 10% had significantly worse lung gas transfer, but did not differ in other exercise parameters.</p> <p>Conclusions</p> <p>In patients with COPD, abdominal muscle but not diaphragm fatigue develops following symptom limited incremental cycle ergometry. Further work is needed to establish whether abdominal muscle fatigue is relevant to exercise limitation in COPD, perhaps indirectly through an effect on quadriceps fatigability.</p

Nutrient Enrichment and Food Web Composition Affect Ecosystem Metabolism in an Experimental Seagrass Habitat

Food web composition and resource levels can influence ecosystem properties such as productivity and elemental cycles. In particular, herbivores occupy a central place in food webs as the species richness and composition of this trophic level may simultaneously influence the transmission of resource and predator effects to higher and lower trophic levels, respectively. Yet, these interactions are poorly understood.Using an experimental seagrass mesocosm system, we factorially manipulated water column nutrient concentrations, food chain length, and diversity of crustacean grazers to address two questions: (1) Does food web composition modulate the effects of nutrient enrichment on plant and grazer biomasses and stoichiometry? (2) Do ecosystem fluxes of dissolved oxygen and nutrients more closely reflect above-ground biomass and community structure or sediment processes? Nutrient enrichment and grazer presence generally had strong effects on biomass accumulation, stoichiometry, and ecosystem fluxes, whereas predator effects were weaker or absent. Nutrient enrichment had little effect on producer biomass or net ecosystem production but strongly increased seagrass nutrient content, ecosystem flux rates, and grazer secondary production, suggesting that enhanced production was efficiently transferred from producers to herbivores. Gross ecosystem production (oxygen evolution) correlated positively with above-ground plant biomass, whereas inorganic nutrient fluxes were unrelated to plant or grazer biomasses, suggesting dominance by sediment microbial processes. Finally, grazer richness significantly stabilized ecosystem processes, as predators decreased ecosystem production and respiration only in the zero- and one- species grazer treatments.Overall, our results indicate that consumer presence and species composition strongly influence ecosystem responses to nutrient enrichment, and that increasing herbivore diversity can stabilize ecosystem flux rates in the face of perturbations

Estimates of new and total productivity in central Long Island Sound from in situ measurements of nitrate and dissolved oxygen

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 36 (2013): 74-97, doi:10.1007/s12237-012-9560-5.Biogeochemical cycles in estuaries are regulated by a diverse set of physical and biological variables that operate over a variety of time scales. Using in situ optical sensors, we conducted a high-frequency time-series study of several biogeochemical parameters at a mooring in central Long Island Sound from May to August 2010. During this period, we documented well-defined diel cycles in nitrate concentration that were correlated to dissolved oxygen, wind stress, tidal mixing, and irradiance. By filtering the data to separate the nitrate time series into various signal components, we estimated the amount of variation that could be ascribed to each process. Primary production and surface wind stress explained 59% and 19%, respectively, of the variation in nitrate concentrations. Less frequent physical forcings, including large-magnitude wind events and spring tides, served to decouple the relationship between oxygen, nitrate, and sunlight on about one-quarter of study days. Daytime nitrate minima and dissolved oxygen maxima occurred nearly simultaneously on the majority (> 80%) of days during the study period; both were strongly correlated with the daily peak in irradiance. Nighttime nitrate maxima reflected a pattern in which surface-layer stocks were depleted each afternoon and recharged the following night. Changes in nitrate concentrations were used to generate daily estimates of new primary production (182 ± 37 mg C m-2 d-1) and the f-ratio (0.25), i.e., the ratio of production based on nitrate to total production. These estimates, the first of their kind in Long Island Sound, were compared to values of community respiration, primary productivity, and net ecosystem metabolism, which were derived from in situ measurements of oxygen concentration. Daily averages of the three metabolic parameters were 1660 ± 431, 2080 ± 419, and 429 ± 203 mg C m-2 d-1, respectively. While the system remained weakly autotrophic over the duration of the study period, we observed very large day-to-day differences in the f-ratio and in the various metabolic parameters.This work was supported by the Yale Institute for Biospheric Studies, the Sounds Conservancy of the Quebec-Labrador Foundation, and the Yale School of Forestry and Environmental Studies Carpenter-Sperry Fund.2014-01-0

Addison's disease symptoms - a cross sectional study in urban South Africa

BACKGROUND: Addison's disease is a potentially life-threatening disorder, and prompt diagnosis, and introduction of steroid replacement has resulted in near normal life-expectancy. There are limited data describing the clinical presentation of Addison's disease in South Africa. It is hypothesised that patients may present in advanced state of ill-health, compared to Western countries. Patients A national database of patients was compiled from primary care, referral centres and private practices. 148 patients were enrolled (97 white, 34 mixed ancestry, 5 Asian and 12 black). METHODS: Demographic and clinical data were elicited using questionnaires. Biochemical data were obtained from folder reviews and laboratory archived results. RESULTS: The majority of the cohort was women (62%). The median and inter-quartile age range (IQR) of patients at enrolment was 46.0 (32.0-61.0) years, with a wide range from 2.8-88.0 years. The median and IQR age at initial diagnosis was 34.0 (20.0-45.0) years (range 0.02-77.0) years, indicating that at the time of enrolment, the patients, on average, were diagnosed with Addison's disease 12 years previously. Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%. Loss of consciousness as a presenting feature was recorded in 20 %. with a 95% confidence interval [CI] of (14-28%) and shock occurred in 5% CI (1.5-8.5%). Case-finding was recorded at 3.1 per million. CONCLUSIONS: The usual constellation of hyperpigmentation, nausea, vomiting and weight loss suggests Addison's disease, but a significant proportion present with an advanced state of ill-health and Addisonian crises. A lower prevalence rate, compared to Western countries is suggested

Perspectives and Integration in SOLAS Science

Why a chapter on Perspectives and Integration in SOLAS Science in this book? SOLAS science by its nature deals with interactions that occur: across a wide spectrum of time and space scales, involve gases and particles, between the ocean and the atmosphere, across many disciplines including chemistry, biology, optics, physics, mathematics, computing, socio-economics and consequently interactions between many different scientists and across scientific generations. This chapter provides a guide through the remarkable diversity of cross-cutting approaches and tools in the gigantic puzzle of the SOLAS realm. Here we overview the existing prime components of atmospheric and oceanic observing systems, with the acquisition of ocean–atmosphere observables either from in situ or from satellites, the rich hierarchy of models to test our knowledge of Earth System functioning, and the tremendous efforts accomplished over the last decade within the COST Action 735 and SOLAS Integration project frameworks to understand, as best we can, the current physical and biogeochemical state of the atmosphere and ocean commons. A few SOLAS integrative studies illustrate the full meaning of interactions, paving the way for even tighter connections between thematic fields. Ultimately, SOLAS research will also develop with an enhanced consideration of societal demand while preserving fundamental research coherency. The exchange of energy, gases and particles across the air-sea interface is controlled by a variety of biological, chemical and physical processes that operate across broad spatial and temporal scales. These processes influence the composition, biogeochemical and chemical properties of both the oceanic and atmospheric boundary layers and ultimately shape the Earth system response to climate and environmental change, as detailed in the previous four chapters. In this cross-cutting chapter we present some of the SOLAS achievements over the last decade in terms of integration, upscaling observational information from process-oriented studies and expeditionary research with key tools such as remote sensing and modelling. Here we do not pretend to encompass the entire legacy of SOLAS efforts but rather offer a selective view of some of the major integrative SOLAS studies that combined available pieces of the immense jigsaw puzzle. These include, for instance, COST efforts to build up global climatologies of SOLAS relevant parameters such as dimethyl sulphide, interconnection between volcanic ash and ecosystem response in the eastern subarctic North Pacific, optimal strategy to derive basin-scale CO2 uptake with good precision, or significant reduction of the uncertainties in sea-salt aerosol source functions. Predicting the future trajectory of Earth’s climate and habitability is the main task ahead. Some possible routes for the SOLAS scientific community to reach this overarching goal conclude the chapter