CLEC-2 is not required for platelet aggregation at arteriolar shear

The C-type lectin receptor CLEC-2 is expressed primarily on the surface of platelets, where it is present as a dimer, and is found at low level on a subpopulation of other hematopoietic cells, including mouse neutrophils [1–4] Clustering of CLEC-2 by the snake venom toxin rhodocytin, specific antibodies or its endogenous ligand, podoplanin, elicits powerful activation of platelets through a pathway that is similar to that used by the collagen receptor glycoprotein VI (GPVI) [4–6]. The cytosolic tail of CLEC-2 contains a conserved YxxL sequence preceded by three upstream acidic amino acid residues, which together form a novel motif known as a hemITAM. Ligand engagement induces tyrosine phosphorylation of the hemITAM sequence providing docking sites for the tandem-SH2 domains of the tyrosine kinase Syk across a CLEC-2 receptor dimer [3]. Tyrosine phosphorylation of Syk by Src family kinases and through autophosphorylation leads to stimulation of a downstream signaling cascade that culminates in activation of phospholipase C γ2 (PLCγ2) [4,6]. Recently, CLEC-2 has been proposed to play a major role in supporting activation of platelets at arteriolar rates of flow [1]. Injection of a CLEC-2 antibody into mice causes a sustained depletion of the C-type lectin receptor from the platelet surface [1]. The CLEC-2-depleted platelets were unresponsive to rhodocytin but underwent normal aggregation and secretion responses after stimulation of other platelet receptors, including GPVI [1]. In contrast, there was a marked decrease in aggregate formation relative to controls when CLEC-2-depleted blood was flowed at arteriolar rates of shear over collagen (1000 s−1 and 1700 s−1) [1]. Furthermore, antibody treatment significantly increased tail bleeding times and mice were unable to occlude their vessels after ferric chloride injury [1]. These data provide evidence for a critical role for CLEC-2 in supporting platelet aggregation at arteriolar rates of flow. The underlying mechanism is unclear as platelets do not express podoplanin, the only known endogenous ligand of CLEC-2. In the present study, we have investigated the role of CLEC-2 in platelet aggregation and thrombus formation using platelets from a novel mutant mouse model that lacks functional CLEC-2.

The environmental setting of Epipalaeolithic aggregation site Kharaneh IV

The archaeological site of Kharaneh IV in Jordan's Azraq Basin, and its relatively near neighbour Jilat 6 show evidence of sustained occupation of substantial size through the Early to Middle Epipalaeolithic (c. 24,000 - 15,000 cal BP). Here we review the geomorphological evidence for the environmental setting in which Kharaneh IV was established. The on-site stratigraphy is clearly differentiated from surrounding sediments, marked visually as well as by higher magnetic susceptibility values. Dating and analysis of off-site sediments show that a significant wetland existed at the site prior to and during early site occupation (~ 23,000 - 19,000 BP). This may explain why such a substantial site existed at this location. This wetland dating to the Last Glacial Maximum also provides important information on the palaeoenvironments and potential palaeoclimatic scenarios for today's eastern Jordanian desert, from where such evidence is scarce.

The sensitivity of convective aggregation to diabatic processes in idealized radiative-convective equilibrium simulations

Idealized explicit convection simulations of the Met Office Unified Model exhibit spontaneous self-aggregation in radiative-convective equilibrium, as seen in other models in previous studies. This self-aggregation is linked to feedbacks between radiation, surface fluxes, and convection, and the organization is intimately related to the evolution of the column water vapor field. Analysis of the budget of the spatial variance of column-integrated frozen moist static energy (MSE), following Wing and Emanuel [2014], reveals that the direct radiative feedback (including significant cloud longwave effects) is dominant in both the initial development of self-aggregation and the maintenance of an aggregated state. A low-level circulation at intermediate stages of aggregation does appear to transport MSE from drier to moister regions, but this circulation is mostly balanced by other advective effects of opposite sign and is forced by horizontal anomalies of convective heating (not radiation). Sensitivity studies with either fixed prescribed radiative cooling, fixed prescribed surface fluxes, or both do not show full self-aggregation from homogeneous initial conditions, though fixed surface fluxes do not disaggregate an initialized aggregated state. A sensitivity study in which rain evaporation is turned off shows more rapid self-aggregation, while a run with this change plus fixed radiative cooling still shows strong self-aggregation, supporting a “moisture memory” effect found in Muller and Bony [2015]. Interestingly, self-aggregation occurs even in simulations with sea surface temperatures (SSTs) of 295 K and 290 K, with direct radiative feedbacks dominating the budget of MSE variance, in contrast to results in some previous studies.

The effects of acute fluoxetine administration on temporal discounting in youth with ADHD

Background Serotonin is under-researched in attention deficit hyperactivity disorder (ADHD), despite accumulating evidence for its involvement in impulsiveness and the disorder. Serotonin further modulates temporal discounting (TD), which is typically abnormal in ADHD relative to healthy subjects, underpinned by reduced fronto-striato-limbic activation. This study tested whether a single acute dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine up-regulates and normalizes reduced fronto-striato-limbic neurofunctional activation in ADHD during TD. Method Twelve boys with ADHD were scanned twice in a placebo-controlled randomized design under either fluoxetine (between 8 and 15 mg, titrated to weight) or placebo while performing an individually adjusted functional magnetic resonance imaging TD task. Twenty healthy controls were scanned once. Brain activation was compared in patients under either drug condition and compared to controls to test for normalization effects. Results Repeated-measures whole-brain analysis in patients revealed significant up-regulation with fluoxetine in a large cluster comprising right inferior frontal cortex, insula, premotor cortex and basal ganglia, which further correlated trend-wise with TD performance, which was impaired relative to controls under placebo, but normalized under fluoxetine. Fluoxetine further down-regulated default mode areas of posterior cingulate and precuneus. Comparisons between controls and patients under either drug condition revealed normalization with fluoxetine in right premotor-insular-parietal activation, which was reduced in patients under placebo. Conclusions The findings show that a serotonin agonist up-regulates activation in typical ADHD dysfunctional areas in right inferior frontal cortex, insula and striatum as well as down-regulating default mode network regions in the context of impulsivity and TD.

Fine-scale temporal characterization of trends in soil water dissolved organic carbon and potential drivers

Long-term monitoring of surface water quality has shown increasing concentrations of Dissolved Organic Carbon (DOC) across a large part of the Northern Hemisphere. Several drivers have been implicated including climate change, land management change, nitrogen and sulphur deposition and CO2 enrichment. Analysis of stream water data, supported by evidence from laboratory studies, indicates that an effect of declining sulphur deposition on catchment soil chemistry is likely to be the primary mechanism, but there are relatively few long term soil water chemistry records in the UK with which to investigate this, and other, hypotheses directly. In this paper, we assess temporal relationships between soil solution chemistry and parameters that have been argued to regulate DOC production and, using a unique set of co-located measurements of weather and bulk deposition and soil solution chemistry provided by the UK Environmental Change Network and the Intensive Forest Monitoring Level II Network . We used statistical non-linear trend analysis to investigate these relationships at 5 forested and 4 non-forested sites from 1993 to 2011. Most trends in soil solution DOC concentration were found to be non-linear. Significant increases in DOC occurred mostly prior to 2005. The magnitude and sign of the trends was associated qualitatively with changes in acid deposition, the presence/absence of a forest canopy, soil depth and soil properties. The strongest increases in DOC were seen in acidic forest soils and were most clearly linked to declining anthropogenic acid deposition, while DOC trends at some sites with westerly locations appeared to have been influenced by shorter-term hydrological variation. The results indicate that widespread DOC increases in surface waters observed elsewhere, are most likely dominated by enhanced mobilization of DOC in surficial organic horizons, rather than changes in the soil water chemistry of deeper horizons. While trends in DOC concentrations in surface horizons have flattened out in recent years, further increases may be expected as soil chemistry continues to adjust to declining inputs of acidity.

Spatio-temporal variability of polynya dynamics and ice production in the Laptev Sea between the winters of 1979/80 and 2007/08

Polynyas in the Laptev Sea are examined with respect to recurrence and interannual wintertime ice production.We use a polynya classification method based on passive microwave satellite data to derive daily polynya area from long-term sea-ice concentrations. This provides insight into the spatial and temporal variability of open-water and thin-ice regions on the Laptev Sea Shelf. Using thermal infrared satellite data to derive an empirical thin-ice distribution within the thickness range from 0 to 20 cm, we calculate daily average surface heat loss and the resulting wintertime ice formation within the Laptev Sea polynyas between 1979 and 2008 using reanalysis data supplied by the National Centers for Environmental Prediction, USA, as atmospheric forcing. Results indicate that previous studies significantly overestimate the contribution of polynyas to the ice production in the Laptev Sea. Average wintertime ice production in polynyas amounts to approximately 55 km39 27% and is mostly determined by the polynya area, wind speed and associated large-scale circulation patterns. No trend in ice production could be detected in the period from 1979/80 to 2007/08.

Temporal and spatial variability of surface fluxes over the ice edge zone in the northern Baltic Sea

Three land-fast ice stations (one of them was the Finnish research ice breaker Aranda) and the German research aircraft Falcon were applied to measure the turbulent and radiation fluxes over the ice edge zone in the northern Baltic Sea during the Baltic Air-Sea-Ice Study (BASIS) field experiment from 16 February to 6 March 1998. The temporal and spatial variability of the surface fluxes is discussed. Synoptic weather systems passed the experimental area in a rapid sequence and dominated the conditions (wind speed, airsurface temperature difference, cloud field) for the variability of the turbulent and radiation fluxes. At the ice stations, the largest upward sensible heat fluxes of about 100 Wm�2 were measured during the passage of a cold front when the air cooled faster (�5 K per hour) than the surface. The largest downward flux of about �200 Wm�2 occurred during warm air advection when the air temperature reached +10�C but the surface temperature remained at 0�C. Spatial variability of fluxes was observed from the small scale (scale of ice floes and open water spots) to the mesoscale (width of the ice edge zone). The degree of spatial variability depends on the synoptic situation: during melting conditions downward heat fluxes were the same over ice and open water, whereas during strong cold-air advection upward heat fluxes differed by more than 100 Wm�2. A remarkable amount of grey ice with intermediate surface temperature was observed. The ice in the Baltic Sea cannot be described by one ice type only.

Spatial and temporal variability of the concentration field from localized releases in a regular building array

Spatial and temporal fluctuations in the concentration field from an ensemble of continuous point-source releases in a regular building array are analyzed from data generated by direct numerical simulations. The release is of a passive scalar under conditions of neutral stability. Results are related to the underlying flow structure by contrasting data for an imposed wind direction of 0 deg and 45 deg relative to the buildings. Furthermore, the effects of distance from the source and vicinity to the plume centreline on the spatial and temporal variability are documented. The general picture that emerges is that this particular geometry splits the flow domain into segments (e.g. “streets” and “intersections”) in each of which the air is, to a first approximation, well mixed. Notable exceptions to this general rule include regions close to the source, near the plume edge, and in unobstructed channels when the flow is aligned. In the oblique (45 deg) case the strongly three-dimensional nature of the flow enhances mixing of a scalar within the canopy leading to reduced temporal and spatial concentration fluctuations within the plume core. These fluctuations are in general larger for the parallel flow (0 deg) case, especially so in the long unobstructed channels. Due to the more complex flow structure in the canyon-type streets behind buildings, fluctuations are lower than in the open channels, though still substantially larger than for oblique flow. These results are relevant to the formulation of simple models for dispersion in urban areas and to the quantification of the uncertainties in their predictions.