Impacts of the Last Glacial Cycle on ground surface temperature reconstructions over the last millennium

Borehole temperature profiles provide robust estimates of past ground surface temperature changes, in agreement with meteorological data. Nevertheless, past climatic changes such as the Last Glacial Cycle (LGC) generated thermal effects in the subsurface that affect estimates of recent climatic change from geothermal data. We use an ensemble of ice sheet simulations spanning the last 120 ka to assess the impact of the Laurentide Ice Sheet on recent ground surface temperature histories reconstructed from borehole temperature profiles over North America. When the thermal remnants of the LGC are removed, we find larger amounts of subsurface heat storage (2.8 times) and an increased warming of the ground surface over North America by 0.75 K, both relative to uncorrected borehole estimates

Lessons from LIMK1 enzymology and their impact on inhibitor design

LIM domain kinase 1 (LIMK1) is a key regulator of actin dynamics. It is thereby a potential therapeutic target for the prevention of fragile X syndrome and amyotrophic lateral sclerosis. Herein, we use X-ray crystallography and activity assays to describe how LIMK1 accomplishes substrate specificity, to suggest a unique ‘rock-and-poke’ mechanism of catalysis and to explore the regulation of the kinase by activation loop phosphorylation. Based on these findings, a differential scanning fluorimetry assay and a RapidFire mass spectrometry activity assay were established, leading to the discovery and confirmation of a set of small-molecule LIMK1 inhibitors. Interestingly, several of the inhibitors were inactive towards the closely related isoform LIMK2. Finally, crystal structures of the LIMK1 kinase domain in complex with inhibitors (PF-477736 and staurosporine, respectively) are presented, providing insights into LIMK1 plasticity upon inhibitor binding

A human neuronal model of Niemann Pick C disease developed from stem cells isolated from patient's skin.

Niemann Pick C (NPC) disease is a neurovisceral lysosomal storage disorder due to mutations in NPC1 or NPC2 genes, characterized by the accumulation of endocytosed unesterified cholesterol, gangliosides and other lipids within the lysosomes/late endosomes. Even if the neurodegeneration is the main feature of the disease, the analysis of the molecular pathways linking the lipid accumulation and cellular damage in the brain has been challenging due to the limited availability of human neuronal models.The aim of this study was to develop a human neuronal model of NPC disease by inducing neuronal differentiation of multipotent adult stem cells (MASC) isolated from NPC patients.Stem cells were isolated from 3 NPC patients and 3 controls both from skin biopsies and previously established skin fibroblast cultures. Cells were induced to differentiate along a neuronal fate adapting methods previously described by Beltrami et al, 2007. The surface immunophenotype of stem cells was analyzed by FACS. Stem cell and neuronal markers expression were evaluated by immunofluorescence. Intracellular accumulation of cholesterol and gangliosides were assessed by filipin staining and immunofluorescence, respectively. A morphometric analysis was performed using a Neurite outgrowth image program.After 3 passages in selective medium, MASC isolated either from skin biopsies or previously established skin fibroblast cultures displayed an antigenic pattern characteristic of mesenchymal stem cells and expressed the stem cell markers Oct-4, Nanog, Sox-2 and nestin. A massive lysosomal accumulation of cholesterol was observed only in cells isolated from NPC patients. After the induction of neural differentiation, remarkable morphologic changes were observed and cells became positive to markers of the neuronal lineage NeuN and MAP2. Differentiated cells from NPC patients displayed characteristic features of NPC disease, they showed intracellular accumulation of unesterified cholesterol and GM2 ganglioside and presented morphological differences with respect to cells derived from healthy donors.In conclusion, we generated a human neuronal model of NPC disease through the induction of differentiation of stem cells obtained from patient's easily accessible sources. The strategy described here may be applied to easily generate human neuronal models of other neurodegenerative diseases

Ground surface temperature and continental heat gain: uncertainties from underground

Temperature changes at the Earthʼs surface propagate and are recorded underground as perturbations to the equilibrium thermal regime associated with the heat flow from the Earthʼs interior. Borehole climatology is concerned with the analysis and interpretation of these downward propagating subsurface temperature anomalies in terms of surface climate. Proper determination of the steady-state geothermal regime is therefore crucial because it is the reference against which climate-induced subsurface temperature anomalies are estimated. Here, we examine the effects of data noise on the determination of the steady-state geothermal regime of the subsurface and the subsequent impact on estimates of ground surface temperature (GST) history and heat gain. We carry out a series of Monte Carlo experiments using 1000 Gaussian noise realizations and depth sections of 100 and 200 m as for steady-state estimates depth intervals, as well as a range of data sampling intervals from 10 m to 0.02 m. Results indicate that typical uncertainties for 50 year averages are on the order of ±0.02 K for the most recent 100 year period. These uncertainties grow with decreasing sampling intervals, reaching about ±0.1 K for a 10 m sampling interval under identical conditions and target period. Uncertainties increase for progressively older periods, reaching ±0.3 K at 500 years before present for a 10 m sampling interval. The uncertainties in reconstructed GST histories for the Northern Hemisphere for the most recent 50 year period can reach a maximum of ±0.5 K in some areas. We suggest that continuous logging should be the preferred approach when measuring geothermal data for climate reconstructions, and that for those using the International Heat Flow Commission database for borehole climatology, the steady-state thermal conditions should be estimated from boreholes as deep as possible and using a large fitting depth range (~100 m)

Impact of borehole depths on reconstructed estimates of ground surface temperature histories and energy storage

Estimates of ground surface temperature changes and continental energy storage from geothermal data have become well-accepted indicators of climatic changes. These estimates are independent contributions to the ensemble of paleoclimatic reconstructions and have been used for the validation of general circulation models, and as a component of the energy budget accounting of the global climate system. Recent global and hemispheric analyses of geothermal data were based on data available in the borehole paleoclimatology database, which contains subsurface temperature profiles from a minimum depth of 200 m to about 600 m. Because of the nature of heat conduction, different depth ranges contain the record of past and persistent changes in the energy balance between the lower atmosphere and the ground for different time periods. Here we examine the dependency of estimated ground surface temperature histories and the magnitude of the subsurface heat content on the depth of borehole temperature profiles. Our results show that uncertainties in the estimates of the long-term surface temperature are in the range of ±0.5K. We conclude that previous estimates of ground surface temperature change remain valid for the period since industrialization, but longer-term estimates are subject to considerable uncertainties. The subsurface heat content shows a larger range of variability arising from differences in depth of the borehole temperature profiles, as well as from differences in the time of data acquisition, spanning four decades. These results indicate that estimates of subsurface heat should be carried out with caution to decrease cumulative errors in any spatial analysis

Impact of maximum borehole depths on inverted temperature histories in borehole paleoclimatology

A quantitative assessment is presented for the impact of the maximum depth of a temperature-depth profile on the estimate of the climatic transient and the resultant ground surface temperature (GST) reconstruction used in borehole paleoclimatology. The depth of the profile is important because the downwelling climatic signal must be separated from the quasi-steady state thermal regime established by the energy in the Earth's interior. This component of the signal is estimated as a linear increase in temperature with depth from the lower section of a borehole temperature profile, which is assumed to be unperturbed by recent changes in climate at the surface. The validity of this assumption is dependent on both the subsurface thermophysical properties and the character of the downwelling climatic signal. Such uncertainties can significantly impact the determination of the quasi-steady state thermal regime, and consequently the magnitude of the temperature anomaly interpreted as a climatic signal. The quantitative effects and uncertainties that arise from the analysis of temperature-depth profiles of different depths are presented. Results demonstrate that widely different GST histories can be derived from a single temperature profile truncated at different depths. Borehole temperature measurements approaching 500-600 m depths are shown to provide the most robust GST reconstructions spanning 500 to 1000 yr BP. It is further shown that the bias introduced by a temperature profile of depths shallower than 500-600 m remains even if the time span of the reconstruction target is shortened

Active Mass Under Pressure

After a historical introduction to Poisson's equation for Newtonian gravity, its analog for static gravitational fields in Einstein's theory is reviewed. It appears that the pressure contribution to the active mass density in Einstein's theory might also be noticeable at the Newtonian level. A form of its surprising appearance, first noticed by Richard Chase Tolman, was discussed half a century ago in the Hamburg Relativity Seminar and is resolved here.Comment: 28 pages, 4 figure

Improvement in fruit yield and tolerance to salinity of tomato plants fertigated with micronutrient amounts of iodine

Iodine is an essential micronutrient for humans, but its role in plant physiology was debated for nearly a century. Recently its functional involvement in plant nutrition and stress-protection collected the first experimental evidence. This study wanted to examine in depth the involvement of iodine in tomato plant nutrition, also evaluating its potential on salt stress tolerance. To this end, iodine was administered at dosages effective for micronutrients to plants grown in different experimental systems (growth chamber and greenhouse), alone or in presence of a mild-moderate NaCl-salinity stress. Plant vegetative fitness, fruit yield and quality, biochemical parameters and transcriptional activity of selected stress-responsive genes were evaluated. In unstressed plants, iodine increased plant growth and fruit yield, as well as some fruit qualitative parameters. In presence of salt stress, iodine mitigated some of the negative effects observed, according to the iodine/NaCl concentrations used. Some fruit parameters and the expressions of the stress marker genes analyzed were affected by the treatments, explaining, at least in part, the increased plant tolerance to the salinity. This study thus reconfirms the functional involvement of iodine in plant nutrition and offers evidence towards the use of minute amounts of it as a beneficial nutrient for crop production