Comparison of CLEC-2 and GPVI signaling in platelets: the role of adaptor proteins

GPVI activates platelets through an ITAM pathway by activation of Src and Syk kinases leading to activation of PLCy2. CLEC-2 has been shown to activate platelets using an ITAM-like sequence in its cytoplasmic tail that is also dependent on Src and Syk kinases, but shows a partial rather than an absolute dependence on adapter SLP-76 for activation of PLCy2. The aim of this thesis is to understand some of the key differences in these signalling pathways. GPVI is in complex with FcRwhich contains the ITAM sequence (Yxx(L/I)x6−12Yxx(L/I)). These two tyrosines provide a docking site for the tandem-SH2 domains of Syk. In this thesis I show that CLEC-2 signalling through Syk is mediated by phosphorylation of the CLEC-2 YxxL sequence, receptor dimerisation and cross-linking by the Syk SH2 domains. I also show that the differential requirement for SLP-76 is not mediated by Gads. Both signalling pathways also show partial dependency for LAT. I also show that a novel protein, G6f, is not able to substitute for LAT in this signalling pathway and also exclude the LAT-family proteins PAG, LIME, LAX and NTAL as potential LAT replacements in platelet activation by GPVI. These results extend our understanding of platelet activation by CLEC-2.

Understanding the link between single cell and population scale responses of Escherichia coli in differing ligand gradients

We formulate an agent-based population model of Escherichia coli cells which incorporates a description of the chemotaxis signalling cascade at the single cell scale. The model is used to gain insight into the link between the signalling cascade dynamics and the overall population response to differing chemoattractant gradients. Firstly, we consider how the observed variation in total (phosphorylated and unphosphorylated) signalling protein concentration affects the ability of cells to accumulate in differing chemoattractant gradients. Results reveal that a variation in total cell protein concentration between cells may be a mechanism for the survival of cell colonies across a wide range of differing environments. We then study the response of cells in the presence of two different chemoattractants.In doing so we demonstrate that the population scale response depends not on the absolute concentration of each chemoattractant but on the sensitivity of the chemoreceptors to their respective concentrations. Our results show the clear link between single cell features and the overall environment in which cells reside.

Methane cross-validation between three Fourier Transform Spectrometers: SCISAT ACE-FTS, GOSAT TANSO-FTS, and ground-based FTS measurements in the Canadian high Arctic

We present cross-validation of remote sensing measurements of methane profiles in the Canadian high Arctic. Accurate and precise measurements of methane are essential to understand quantitatively its role in the climate system and in global change. Here, we show a cross-validation between three datasets: two from spaceborne instruments and one from a ground-based instrument. All are Fourier Transform Spectrometers (FTSs). We consider the Canadian SCISAT Atmospheric Chemistry Experiment (ACE)-FTS, a solar occultation infrared spectrometer operating since 2004, and the thermal infrared band of the Japanese Greenhouse Gases Observing Satellite (GOSAT) Thermal And Near infrared Sensor for carbon Observation (TANSO)-FTS, a nadir/off-nadir scanning FTS instrument operating at solar and terrestrial infrared wavelengths, since 2009. The ground-based instrument is a Bruker 125HR Fourier Transform Infrared (FTIR) spectrometer, measuring mid-infrared solar absorption spectra at the Polar Environment Atmospheric Research Laboratory (PEARL) Ridge Lab at Eureka, Nunavut (80° N, 86° W) since 2006. For each pair of instruments, measurements are collocated within 500 km and 24 h. An additional criterion based on potential vorticity values was found not to significantly affect differences between measurements. Profiles are regridded to a common vertical grid for each comparison set. To account for differing vertical resolutions, ACE-FTS measurements are smoothed to the resolution of either PEARL-FTS or TANSO-FTS, and PEARL-FTS measurements are smoothed to the TANSO-FTS resolution. Differences for each pair are examined in terms of profile and partial columns. During the period considered, the number of collocations for each pair is large enough to obtain a good sample size (from several hundred to tens of thousands depending on pair and configuration). Considering full profiles, the degrees of freedom for signal (DOFS) are between 0.2 and 0.7 for TANSO-FTS and between 1.5 and 3 for PEARL-FTS, while ACE-FTS has considerably more information (roughly 1° of freedom per altitude level). We take partial columns between roughly 5 and 30 km for the ACE-FTS–PEARL-FTS comparison, and between 5 and 10 km for the other pairs. The DOFS for the partial columns are between 1.2 and 2 for PEARL-FTS collocated with ACE-FTS, between 0.1 and 0.5 for PEARL-FTS collocated with TANSO-FTS or for TANSO-FTS collocated with either other instrument, while ACE-FTS has much higher information content. For all pairs, the partial column differences are within ± 3 × 1022 molecules cm−2. Expressed as median ± median absolute deviation (expressed in absolute or relative terms), these differences are 0.11 ± 9.60 × 10^20 molecules cm−2 (0.012 ± 1.018 %) for TANSO-FTS–PEARL-FTS, −2.6 ± 2.6 × 10^21 molecules cm−2 (−1.6 ± 1.6 %) for ACE-FTS–PEARL-FTS, and 7.4 ± 6.0 × 10^20 molecules cm−2 (0.78 ± 0.64 %) for TANSO-FTS–ACE-FTS. The differences for ACE-FTS–PEARL-FTS and TANSO-FTS–PEARL-FTS partial columns decrease significantly as a function of PEARL partial columns, whereas the range of partial column values for TANSO-FTS–ACE-FTS collocations is too small to draw any conclusion on its dependence on ACE-FTS partial columns.

Regional projections of extreme apparent temperature days in Africa and the related potential risk to human health

Regional climate modelling was used to produce high resolution climate projections for Africa, under a “business as usual scenario”, that were translated into potential health impacts utilizing a heat index that relates apparent temperature to health impacts. The continent is projected to see increases in the number of days when health may be adversely affected by increasing maximum apparent temperatures (AT) due to climate change. Additionally, climate projections indicate that the increases in AT results in a moving of days from the less severe to the more severe Symptom Bands. The analysis of the rate of increasing temperatures assisted in identifying areas, such as the East African highlands, where health may be at increasing risk due to both large increases in the absolute number of hot days, and due to the high rate of increase. The projections described here can be used by health stakeholders in Africa to assist in the development of appropriate public health interventions to mitigate the potential health impacts from climate change.

Re-examining the U.K.'s greatest tornado outbreak: forecasting the limited extent of tornadoes along a cold front

On 23 November 1981, a strong cold front swept across the U.K., producing tornadoes from the west to the east coasts. An extensive campaign to collect tornado reports by the Tornado and Storm Research Organisation (TORRO) resulted in 104 reports, the largest U.K. outbreak. The front was simulated with a convection-permitting numerical model down to 200-m horizontal grid spacing to better understand its evolution and meteorological environment. The event was typical of tornadoes in the U.K., with convective available potential energy (CAPE) less than 150 J kg-1, 0-1-km wind shear of 10-20 m s-1, and a narrow cold-frontal rainband forming precipitation cores and gaps. A line of cyclonic absolute vorticity existed along the front, with maxima as large as 0.04 s-1. Some hook-shaped misovortices bore kinematic similarity to supercells. The narrow swath along which the line was tornadic was bounded on the equatorward side by weak vorticity along the line and on the poleward side by zero CAPE, enclosing a region where the environment was otherwise favorable for tornadogenesis. To determine if the 104 tornado reports were plausible, first possible duplicate reports were eliminated, resulting in as few as 58 tornadoes to as many as 90. Second, the number of possible parent misovortices that may have spawned tornadoes is estimated from model output. The number of plausible tornado reports in the 200-m grid-spacing domain was 22 and as many as 44, whereas the model simulation was used to estimate 30 possible parent misovortices within this domain. These results suggest that 90 reports was plausible.

Predictability of the Arctic sea ice edge

Skillful sea ice forecasts from days to years ahead are becoming increasingly important for the operation and planning of human activities in the Arctic. Here we analyze the potential predictability of the Arctic sea ice edge in six climate models. We introduce the integrated ice-edge error (IIEE), a user-relevant verification metric defined as the area where the forecast and the “truth” disagree on the ice concentration being above or below 15%. The IIEE lends itself to decomposition into an absolute extent error, corresponding to the common sea ice extent error, and a misplacement error. We find that the often-neglected misplacement error makes up more than half of the climatological IIEE. In idealized forecast ensembles initialized on 1 July, the IIEE grows faster than the absolute extent error. This means that the Arctic sea ice edge is less predictable than sea ice extent, particularly in September, with implications for the potential skill of end-user relevant forecasts.

The Impact of Vitamin A Supplementation on the Immune System of Vitamin A-deficient Children

Background & Aims: To investigate the effect of vitamin A supplementation on parameters of the immune system of vitamin A-deficient children. Methods: The study was carried out in four phases: 1) determination of serum retinol in 631 children from 36 to 83 months of age; 2) assessment of immunological markers [immunoglobulins and complement fractions, immunophenotyping of T and B lymphocytes, and natural killer (NK) cells], blood count, and serum ferritin of 52 vitamin A-deficient children (serum retinol <0.70 mu mol/L); 3) supplementation of the 52 deficient children with 200,000 IU of vitamin A; 4) determination of serum retinol and the immunological parameters 2 months after vitamin A supplementation. Results: Before vitamin A supplementation, 24.0% of the children were anemic and 4.3 %had reduced ferritin concentrations. There was no significant difference between mean values of retinol according to the presence/absence of anemia. The mean values of the humoral and cellular immunological parameters did not show a statistically significant difference before and after supplementation with vitamin A. Children with concomitant hypovitaminosis A and anemia presented a significant increase in absolute CD4 and CD8 T-cell counts after vitamin A supplementation (p < 0.05). Conclusion: Vitamin A had an effect on the recruitment of T and B lymphocytes to the circulation of children with hypovitaminosis A and anemia.

Narrowing socioeconomic inequality in child stunting: the Brazilian experience, 1974-2007

Objective To assess trends in the prevalence and social distribution of child stunting in Brazil to evaluate the effect of income and basic service redistribution policies implemented in that country in the recent past. Methods The prevalence of stunting (height-for-age z score below 2 using the Child Growth Standards of the World Health Organization) among children aged less than 5 years was estimated from data collected during national household surveys carried out in Brazil in 1974-75 (n = 34 409), 1989 (n = 7374), 1996 (n = 4149) and 2006-07 (n = 4414). Absolute and relative socioeconomic inequality in stunting was measured by means of the slope index and the concentration index of inequality, respectively. Findings Over a 33-year period, we documented a steady decline in the national prevalence of stunting from 37.1% to 7.1%. Prevalence dropped from 59.0% to 11.2% in the poorest quintile and from 12.1% to 3.3% among the wealthiest quintile. The decline was particularly steep in the last 10 years of the period (1996 to 2007), when the gaps between poor and wealthy families with children under 5 were also reduced in terms of purchasing power; access to education, health care and water and sanitation services; and reproductive health indicators. Conclusion In Brazil, socioeconomic development coupled with equity-oriented public policies have been accompanied by marked improvements in living conditions and a substantial decline in child undernutrition, as well as a reduction of the gap in nutritional status between children in the highest and lowest socioeconomic quintiles. Future studies will show whether these gains will be maintained under the current global economic crisis.

Resonant Wave Interactions in the Equatorial Waveguide

Weakly nonlinear interactions among equatorial waves have been explored in this paper using the adiabatic version of the equatorial beta-plane primitive equations in isobaric coordinates. Assuming rigid lid vertical boundary conditions, the conditions imposed at the surface and at the top of the troposphere were expanded in a Taylor series around two isobaric surfaces in an approach similar to that used in the theory of surface-gravity waves in deep water and capillary-gravity waves. By adopting the asymptotic method of multiple time scales, the equatorial Rossby, mixed Rossby-gravity, inertio-gravity, and Kelvin waves, as well as their vertical structures, were obtained as leading-order solutions. These waves were shown to interact resonantly in a triad configuration at the O(epsilon) approximation. The resonant triads whose wave components satisfy a resonance condition for their vertical structures were found to have the most significant interactions, although this condition is not excluding, unlike the resonant conditions for the zonal wavenumbers and meridional modes. Thus, the analysis has focused on such resonant triads. In general, it was found that for these resonant triads satisfying the resonance condition in the vertical direction, the wave with the highest absolute frequency always acts as an energy source (or sink) for the remaining triad components, as usually occurs in several other physical problems in fluid dynamics. In addition, the zonally symmetric geostrophic modes act as catalyst modes for the energy exchanges between two dispersive waves in a resonant triad. The integration of the reduced asymptotic equations for a single resonant triad shows that, for the initial mode amplitudes characterizing realistic magnitudes of atmospheric flow perturbations, the modes in general exchange energy on low-frequency (intraseasonal and/or even longer) time scales, with the interaction period being dependent upon the initial mode amplitudes. Potential future applications of the present theory to the real atmosphere with the inclusion of diabatic forcing, dissipation, and a more realistic background state are also discussed.

THE GEMINI NICI PLANET-FINDING CAMPAIGN: DISCOVERY OF A SUBSTELLAR L DWARF COMPANION TO THE NEARBY YOUNG M DWARF CD-35 2722

We present the discovery of a wide (67 AU) substellar companion to the nearby (21 pc) young solar-metallicity M1 dwarf CD-35 2722, a member of the approximate to 100 Myr AB Doradus association. Two epochs of astrometry from the NICI Planet-Finding Campaign confirm that CD-35 2722 B is physically associated with the primary star. Near-IR spectra indicate a spectral type of L4 +/- 1 with a moderately low surface gravity, making it one of the coolest young companions found to date. The absorption lines and near-IR continuum shape of CD-35 2722 B agree especially well the dusty field L4.5 dwarf 2MASS J22244381-0158521, while the near-IR colors and absolute magnitudes match those of the 5 Myr old L4 planetary-mass companion, 1RXS J160929.1-210524 b. Overall, CD-35 2722 B appears to be an intermediate-age benchmark for L dwarfs, with a less peaked H-band continuum than the youngest objects and near-IR absorption lines comparable to field objects. We fit Ames-Dusty model atmospheres to the near-IR spectra and find T(eff) = 1700-1900 K and log(g) = 4.5 +/- 0.5. The spectra also show that the radial velocities of components A and B agree to within +/- 10 km s(-1), further confirming their physical association. Using the age and bolometric luminosity of CD-35 2722 B, we derive a mass of 31 +/- 8 M(Jup) from the Lyon/Dusty evolutionary models. Altogether, young late-M to mid-L type companions appear to be overluminous for their near-IR spectral type compared with field objects, in contrast to the underluminosity of young late-L and early-T dwarfs.

Open cluster survival within the solar circle: Teutsch 145 and Teutsch 146 star

Teutsch 145 and Teutsch 146 are shown to be open clusters (OCs) orbiting well inside the solar circle, a region where several dynamical processes combine to disrupt most OCs on a time-scale of a few 108 yr. BVI photometry from the GALILEO telescope is used to investigate the nature and derive the fundamental and structural parameters of the optically faint and poorly known OCs Teutsch 145 and 146. These parameters are computed by means of field-star-decontaminated colour-magnitude diagrams and stellar radial density profiles (RDPs). Cluster mass estimates are made based on the intrinsic mass functions (MFs). We derive the ages 200+100(-50) and 400 +/- 100 Myr, and the distances from the Sun d(circle dot) = 2.7 +/- 0.3 and 3.8 +/- 0.2 kpc, respectively, for Teutsch 145 and 146. Their integrated apparent and absolute magnitudes are m(V) approximate to 12.4 and 13.3 and M(V) approximate to -5.6 and -5.3. The MFs (detected for stars with m greater than or similar to 1 M(circle dot)) have slopes similar to Salpeter`s initial mass function. Extrapolated to the H-burning limit, the MFs would produce total stellar masses of similar to 1400 M(circle dot), typical of relatively massive OCs. Both OCs are located deep into the inner Galaxy and close to the Crux-Scutum arm. Since cluster-disruption processes are important, their primordial masses must have been higher than the present-day values. The conspicuous stellar density excess observed in the innermost bin of both RDPs might reflect the dynamical effects induced by a few 108 yr of external tidal stress.

The intracratonic Caraibas-Itacarambi earthquake of December 09, 2007 (4.9 m(b)), Minas Gerais State, Brazil

On December 9, 2007, a 4.9 m(b) earthquake occurred in the middle of the Sao Francisco Craton, in a region with no known previous activity larger than 4 m(b). This event reached intensity VII MM (Modified Mercalli) causing the first fatal victim in Brazil. The activity had started in May 25, 2007 with a 3.5 magnitude event and continued for several months, motivating the deployment of a local 6-station network. A three week seismic quiescence was observed before the mainshock. Initial absolute hypocenters were calculated with best fitting velocity models and then relative locations were determined with hypoDD. The aftershock distribution indicates a 3 km long rupture for the mainshock. The fault plane solution, based on P-wave polarities and hypocentral trend, indicates a reverse faulting mechanism on a N30 degrees E striking plane dipping about 40 degrees to the SE. The rupture depth extends from about 0.3 to 1.2 km only. Despite the shallow depth of the mainshock, no surface feature could be correlated with the fault plane. Aeromagnetic data in the epicentral area show short-wavelength lineaments trending NNE-SSW to NE-SW which we interpret as faults and fractures in the craton basement beneath the surface limestone layer. We propose that the Caraibas-Itacarambi seismicity is probably associated with reactivation of these basement fractures and faults under the present E-W compressional stress field in this region of the South American Plate. (c) 2009 Elsevier B.V. All rights reserved.

Palaeomagnetism, rock magnetism and AMS of the Cabo Magmatic Province, NE Brazil, and the opening of South Atlantic

P>Reconstruction of the South Atlantic opening has long been a matter of debate and several models have been proposed. One problem in tracing properly the Atlantic history arises from the existence of a long interval without geomagnetic reversals, the Cretaceous Normal Superchron, for which ages are difficult to assign. Palaeomagnetism may help in addressing this issue if high-quality palaeomagnetic poles are available for the two drifting continental blocks, and if precise absolute ages are available. In this work we have investigated the Cabo Magmatic Province, northeastern Brazil, recently dated at 102 +/- 1 Ma (zircon fission tracks, Ar39/Ar40). All volcanic and plutonic rocks showed stable thermal and AF demagnetization patterns, and exhibit primary magnetic signatures. AMS data also support a primary origin for the magnetic fabric and is interpreted to be contemporaneous of the rock formation. The obtained pole is located at 335.9 degrees E/87.9 degrees S (N = 24; A(95) = 2.5; K = 138) and satisfies modern quality criteria, resulting in a reference pole for South America at similar to 100 Ma. This new pole also gives an insight to test and discuss the kinematic models currently proposed for the South Atlantic opening during mid-Cretaceous.

Upper-mantle seismic anisotropy from SKS splitting in the South American stable platform: A test of asthenospheric flow models beneath the lithosphere

Upper-mantle seismic anisotropy has been extensively used to infer both present and past deformation processes at lithospheric and asthenospheric depths. Analysis of shear-wave splitting (mainly from core-refracted SKS phases) provides information regarding upper-mantle anisotropy. We present average measurements of fast-polarization directions at 21 new sites in poorly sampled regions of intra-plate South America, such as northern and northeastern Brazil. Despite sparse data coverage for the South American stable platform, consistent orientations are observed over hundreds of kilometers. Over most of the continent, the fast-polarization direction tends to be close to the absolute plate motion direction given by the hotspot reference model HS3-NUVEL-1A. A previous global comparison of the SKS fast-polarization directions with flow models of the upper mantle showed relatively poor correlation on the continents, which was interpreted as evidence for a large contribution of ""frozen"" anisotropy in the lithosphere. For the South American plate, our data indicate that one of the reasons for the poor correlation may have been the relatively coarse model of lithospheric thicknesses. We suggest that improved models of upper-mantle flow that are based on more detailed lithospheric thicknesses in South America may help to explain most of the observed anisotropy patterns.

Morphology, molecular phylogeny, and taxonomic inconsistencies in the study of Bradypus sloths (Pilosa: Bradypodidae)

This study focuses on morphological and molecular data analyses, misidentifications, and phylogenetic inconsistencies regarding Bradypus variegatus (the brown-throated sloth) and B. tridactylus (the pale-throated sloth). Misidentifications were recorded on 75 of 313 museum specimens of Bradypus. Almost 90% of the misidentified specimens were B. variegatus from north-central Brazil, erroneously attributed to B. tridactylus. These misidentified specimens are reported in taxonomic reviews as the southernmost records of B. tridactylus. A history of confusing nomenclature regarding sloth species exists, and these particular misidentifications could be attributable to the similarity in face and throat color between B. variegatus from north-central Brazil and B. tridactylus. The molecular phylogeny of morphologically confirmed sloth specimens exhibits 2 monophyletic lineages representing B. variegatus and B. tridactylus. The split time between these 2 lineages was estimated at 6 million years ago (mya), contradicting previous studies that estimated this divergence to be 0.4 mya. Taxonomic inconsistencies were detected when comparing the molecular phylogeny to previously published DNA sequences ascribed to B. tridactylus. Misidentification or introgression could underlie such phylogenetic incongruities. Regardless of their causes, these discrepancies lead to misstatements regarding geographic distribution, phylogeny, and taxonomy of B. variegatus and B. tridactylus.