Diatom Proteomics Reveals Unique Acclimation Strategies to Mitigate Fe Limitation

Phytoplankton growth rates are limited by the supply of iron (Fe) in approximately one third of the open ocean, with major implications for carbon dioxide sequestration and carbon (C) biogeochemistry. To date, understanding how alteration of Fe supply changes phytoplankton physiology has focused on traditional metrics such as growth rate, elemental composition, and biophysical measurements such as photosynthetic competence (Fv/Fm). Researchers have subsequently employed transcriptomics to probe relationships between changes in Fe supply and phytoplankton physiology. Recently, studies have investigated longer-term (i.e. following acclimation) responses of phytoplankton to various Fe conditions. In the present study, the coastal diatom, Thalassiosira pseudonana, was acclimated (10 generations) to either low or high Fe conditions, i.e. Fe-limiting and Fe-replete. Quantitative proteomics and a newly developed proteomic profiling technique that identifies low abundance proteins were employed to examine the full complement of expressed proteins and consequently the metabolic pathways utilized by the diatom under the two Fe conditions. A total of 1850 proteins were confidently identified, nearly tripling previous identifications made from differential expression in diatoms. Given sufficient time to acclimate to Fe limitation, T. pseudonana up-regulates proteins involved in pathways associated with intracellular protein recycling, thereby decreasing dependence on extracellular nitrogen (N), C and Fe. The relative increase in the abundance of photorespiration and pentose phosphate pathway proteins reveal novel metabolic shifts, which create substrates that could support other well-established physiological responses, such as heavily silicified frustules observed for Fe-limited diatoms. Here, we discovered that proteins and hence pathways observed to be down-regulated in short-term Fe starvation studies are constitutively expressed when T. pseudonana is acclimated (i.e., nitrate and nitrite transporters, Photosystem II and Photosystem I complexes). Acclimation of the diatom to the desired Fe conditions and the comprehensive proteomic approach provides a more robust interpretation of this dynamic proteome than previous studies.This work was supported by National Science Foundation grants OCE1233014 (BLN) and the Office of Polar Programs Postdoctoral Fellowship grant 0444148 (BLN). DRG was supported by National Institutes of Health 5P30ES007033-10. AH and MTM were supported by Natural Sciences and Engineering Research Council of Canada. RFS and PWB were supported by the New Zealand Royal Society Marsden Fund and the Ministry of Science. This work is supported in part by the University of Washington's Proteomics Computer Resource Centre (UWPR95794). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Elastic constants of nematic liquid crystals of uniaxial symmetry

We study in detail the influence of molecular interactions on the Frank elastic constants of uniaxial nematic liquid crystals composed of molecules of cylindrical symmetry. A brief summary of the status of theoretical development for the elastic constants of nematics is presented. Considering a pair potential having both repulsive and attractive parts numerical calculations are reported for three systems MBBA, PAA and 8OCB. For these systems the length-to-width ratio ${x_0}$ is estimated from the experimentally proposed structure of the molecules. The repulsive interaction is represented by a repulsion between hard ellipsoids of revolution (HER) and the attractive potential is represented by the quadrupole and dispersion interactions. From the numerical results we observe that in the density range of nematics the contribution of the quadrupole and dispersion interactions are small as compared to the repulsive HER interaction. The inclusion of attractive interaction reduces the values of elastic constants ratios. The temperature variation of elastic constants ratios are reported and compared with the experimental values. A reasonably good agreement between theory and experiment is observed

Appropriateness of Upper Gastrointestinal Endoscopy: Comparison of American and Swiss Criteria

Objective: Examine the reproducibility of the RAND method for developing criteria for the appropriateness of medical procedures. Design: Comparison of two sets of explicit criteria for appropriateness of upper gastrointestinal (UGI) endoscopy, developed by separate expert panels from two countries.Setting: United States, Switzerland. Study participants: National experts from different medical specialties involved in the referral or application of UGI endoscopy.Interventions: Each panel was presented with about 500clinical scenarios (indications)that were rated on a nine-point scale as to the appropriateness of performing UGI endoscopy for a patient with that clinical presentation. Main outcome measurer: (1) distribution of appropriateness ratings and intrapanel agreement categories between the two panels, (2)between-panel agreement of assigning appropriateness for comparable indications and, (3) percentage of indications with major between-panel differences. Results: Ratings for 2/3 of indications could be compared. The Swiss panel showed higher intrapanel agreement (54.6% versus 46.2% p=0.002). Seventy-eight percent of comparable Indications were assigned to indentical categories of appropriateness by both panels (kappa=0.76,P <0.001). For 93% of the 376 comparable indications, there were no major interpanel differences. Conclusion: Separate expert panels in different countries, using a standardized methodology, produce criteria for appropriatenesof medical procedures that are similar. Given the resources being invested throught the world in devilping criteria and guidelines, international collaboration in seeking optimal use of limited health care resources should be intensifled. © 1997 Elsevier Science Ltd. All rights reserve

Predictors of contraction and expansion of area of occupancy for British birds

Copyright © 2014 The Author(s) Published by the Royal SocietyGeographical range dynamics are driven by the joint effects of abiotic factors, human ecosystem modifications, biotic interactions and the intrinsic organismal responses to these. However, the relative contribution of each component remains largely unknown. Here, we compare the contribution of life-history attributes, broad-scale gradients in climate and geographical context of species’ historical ranges, as predictors of recent changes in area of occupancy for 116 terrestrial British breeding birds (74 contractors, 42 expanders) between the early 1970s and late 1990s. Regional threat classifications demonstrated that the species of highest conservation concern showed both the largest contractions and the smallest expansions. Species responded differently to climate depending on geographical distribution—northern species changed their area of occupancy (expansion or contraction) more in warmer and drier regions, whereas southern species changed more in colder and wetter environments. Species with slow life history (larger body size) tended to have a lower probability of changing their area of occupancy than species with faster life history, whereas species with greater natal dispersal capacity resisted contraction and, counterintuitively, expansion. Higher geographical fragmentation of species' range also increased expansion probability, possibly indicating a release from a previously limiting condition, for example through agricultural abandonment since the 1970s. After accounting statistically for the complexity and nonlinearity of the data, our results demonstrate two key aspects of changing area of occupancy for British birds: (i) climate is the dominant driver of change, but direction of effect depends on geographical context, and (ii) all of our predictors generally had a similar effect regardless of the direction of the change (contraction versus expansion). Although we caution applying results from Britain's highly modified and well-studied bird community to other biogeographic regions, our results do indicate that a species' propensity to change area of occupancy over decadal scales can be explained partially by a combination of simple allometric predictors of life-history pace, average climate conditions and geographical context.Australian Research CouncilIntegrated Program of IC&DTFCT (Fundação para a Ciência e a Tecnologia

Obesity: A Biobehavioral Point of View

Excerpt: If you ask an overweight person, “Why are you fat?’, you will, almost invariably, get the answer, “Because 1 eat too much.” You will get this answer in spite of the fact that of thirteen studies, six find no significant differences in the caloric intake of obese versus nonobese subjects, five report that the obese eat significantly less than the nonobese, and only two report that they eat significantly more

Mass tracking for chemical analysis: the causes of ozone formation in southern Ontario during BAQS-Met 2007

A three-level nested regional air pollution model has been used to study the processes leading to high ozone concentrations in the southern Great Lakes region of North America. The highest resolution simulations show that complex interactions between the lake-breeze circulation and the synoptic flow lead to significant enhancements in the photochemical production and transport of ozone at the local scale. Mass tracking of individual model processes show that Lakes Erie and St. Clair frequently act as photochemical ozone production regions, with average mid-day production rates of up to 3 ppbv per hour. Enhanced ozone levels are evident over these two lakes in 23-day-average surface ozone fields. Analysis of other model fields and aircraft measurements suggests that vertical circulation enhances ozone levels at altitudes up to 1500 m over Lake St. Clair, whereas subsidence enhances ozone over Lake Erie in a shallow layer only 250 m deep. Mass tracking of model transport shows that lake-breeze surface convergence zones combined with the synoptic flow can then carry ozone and its precursors hundreds of kilometers from these source areas, in narrow, elongated features. Comparison with surface mesonet ozone observations confirm the presence, magnitude, and timing of these features, which can create local ozone enhancements on the order of 30 ppbv above the regional ozone levels. Sensitivity analyses of model-predicted ozone and HO&lt;sub&gt;x&lt;/sub&gt; concentrations show that most of the region is VOC-limited, and that the secondary oxidation pathways of aromatic hydrocarbons have a key role in setting the region&apos;s ozone and HO&lt;sub&gt;x&lt;/sub&gt; levels

Diatom Proteomics Reveals Unique Acclimation Strategies to Mitigate Fe Limitation

Phytoplankton growth rates are limited by the supply of iron (Fe) in approximately one third of the open ocean, with major implications for carbon dioxide sequestration and carbon (C) biogeochemistry. To date, understanding how alteration of Fe supply changes phytoplankton physiology has focused on traditional metrics such as growth rate, elemental composition, and biophysical measurements such as photosynthetic competence (Fv/Fm). Researchers have subsequently employed transcriptomics to probe relationships between changes in Fe supply and phytoplankton physiology. Recently, studies have investigated longer-term (i.e. following acclimation) responses of phytoplankton to various Fe conditions. In the present study, the coastal diatom, Thalassiosira pseudonana, was acclimated (10 generations) to either low or high Fe conditions, i.e. Fe-limiting and Fe-replete. Quantitative proteomics and a newly developed proteomic profiling technique that identifies low abundance proteins were employed to examine the full complement of expressed proteins and consequently the metabolic pathways utilized by the diatom under the two Fe conditions. A total of 1850 proteins were confidently identified, nearly tripling previous identifications made from differential expression in diatoms. Given sufficient time to acclimate to Fe limitation, T. pseudonana up-regulates proteins involved in pathways associated with intracellular protein recycling, thereby decreasing dependence on extracellular nitrogen (N), C and Fe. The relative increase in the abundance of photorespiration and pentose phosphate pathway proteins reveal novel metabolic shifts, which create substrates that could support other well-established physiological responses, such as heavily silicified frustules observed for Fe-limited diatoms. Here, we discovered that proteins and hence pathways observed to be down-regulated in short-term Fe starvation studies are constitutively expressed when T. pseudonana is acclimated (i.e., nitrate and nitrite transporters, Photosystem II and Photosystem I complexes). Acclimation of the diatom to the desired Fe conditions and the comprehensive proteomic approach provides a more robust interpretation of this dynamic proteome than previous studies

Long-term exposure to outdoor air pollution and the incidence of chronic obstructive pulmonary disease in a national English cohort.

OBJECTIVES: The role of outdoor air pollution in the incidence of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated this question using a large, nationally representative cohort based on primary care records linked to hospital admissions. METHODS: A cohort of 812 063 patients aged 40-89 years registered with 205 English general practices in 2002 without a COPD diagnosis was followed from 2003 to 2007. First COPD diagnoses recorded either by a general practitioner (GP) or on admission to hospital were identified. Annual average concentrations in 2002 for particulate matter with an aerodynamic diameter <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), ozone and sulfur dioxide (SO2) at 1 km(2) resolution were estimated from emission-based dispersion models. Hazard ratios (HRs) per interquartile range change were estimated from Cox models adjusting for age, sex, smoking, body mass index and area-level deprivation. RESULTS: 16 034 participants (1.92%) received a COPD diagnosis from their GP and 2910 participants (0.35%) were admitted to hospital for COPD. After adjustment, HRs for GP recorded COPD and PM10, PM2.5 and NO2 were close to unity, positive for SO2 (HR=1.07 (95% CI 1.03 to 1.11) per 2.2 µg/m(3)) and negative for ozone (HR=0.94 (0.89 to 1.00) per 3 µg/m(3)). For admissions HRs for PM2.5 and NO2 remained positive (HRs=1.05 (0.98 to 1.13) and 1.06 (0.98 to 1.15) per 1.9 µg/m(3) and 10.7 µg/m(3), respectively). CONCLUSIONS: This large population-based cohort study found limited, inconclusive evidence for associations between air pollution and COPD incidence. Further work, utilising improved estimates of air pollution over time and enhanced socioeconomic indicators, is required to clarify the association between air pollution and COPD incidence

Deconfinement Transition and Bound States in Frustrated Heisenberg Chains: Regimes of Forced and Spontaneous Dimerization

We use recently developed strong-coupling expansion methods to study the two-particle spectra for the frustrated alternating Heisenberg model, consisting of an alternating nearest neighbor antiferromagnetic exchange and a uniform second neighbor antiferromagnetic exchange. Starting from the limit of weakly coupled dimers, we develop high order series expansions for the effective Hamiltonian in the two-particle subspace. In the limit of a strong applied dimerization, we calculate accurately various properties of singlet and triplet bound states and quintet antibound states. We also develop series expansions for bound state energies in various sectors, which can be extrapolated using standard methods to cases where the external bond-alternation goes to zero. We study the properties of singlet and triplet bound states in the latter limit and suggest a crucial role for the bound states in the unbinding of triplets and deconfinement of spin-half excitations.Comment: 17 figures, revte

The antisense oligonucleotide nusinersen for treatment of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular degenerative disease characterized by loss of spinal cord motor neurons leading to progressive muscle wasting. The most common pathology results from a homozygous disruption in the survival motor neuron 1 (SMN1) gene on chromosome 5q13 via deletion, conversion, or mutation. SMN2 is a near duplicate of SMN1 that can produce full-length SMN mRNA transcripts, but its overall production capability of these mRNA transcripts is lower than that seen in SMN1. This leads to lower levels of functional SMN protein within motor neurons. The FDA approved nusinersen in December 2016 to treat SMA associated with SMN1 gene mutation. It is administered directly to the central nervous system by intrathecal injection. An antisense oligonucleotide (ASO) drug, nusinersen, provides an upcoming and promising treatment option for SMA and represents a novel pharmacological approach with a mechanism of action relevant for other neurodegenerative disorders. Nusinersen begins with four initial loading doses that are followed by three maintenance doses per year. Three major studies (CHERISH, ENDEAR, and NURTURE) have shown to improve motor function in early and late-onset individuals and reduce the chances of ventilator requirements in pre-symptomatic infants. Studies investigating the timing of drug delivery in mouse models of SMA report the best outcomes when drugs are delivered early before any significant motor function is lost. Nusinersen is a novel therapeutic approach with consistent results in all three studies and is proof of the novel concept for treating SMA and other neurodegenerative disorders in the future