MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis.

MICALs (molecules interacting with CasL) are atypical multidomain flavoenzymes with diverse cellular functions. The molecular pathways employed by MICAL proteins to exert their cellular effects remain largely uncharacterized. Via an unbiased proteomics approach, we identify MICAL-1 as a binding partner of NDR (nuclear Dbf2-related) kinases. NDR1/2 kinases are known to mediate apoptosis downstream of the mammalian Ste-20-like kinase MST1, and ablation of NDR1 in mice predisposes the mice to cancer as a result of compromised apoptosis. MST1 phosphorylates NDR1/2 kinases at their hydrophobic motif, thereby facilitating full NDR kinase activity and function. However, if and how this key phosphorylation event is regulated are unknown. Here we show that MICAL-1 interacts with the hydrophobic motif of NDR1/2 and that overexpression or knockdown of MICAL-1 reduces or augments NDR kinase activation or activity, respectively. Surprisingly, MICAL-1 is a phosphoprotein but not an NDR or MST1 substrate. Rather, MICAL-1 competes with MST1 for NDR binding and thereby antagonizes MST1-induced NDR activation. In line with this inhibitory effect, overexpression or knockdown of MICAL-1 inhibits or enhances, respectively, NDR-dependent proapoptotic signaling induced by extrinsic stimuli. Our findings unveil a previously unknown biological role for MICAL-1 in apoptosis and define a novel negative regulatory mechanism of MST-NDR signaling.

Synoptic-scale controls of persistent low temperature and icy weather over southern China in January 2008

In January 2008, central and southern China experienced persistent low temperatures, freezing rain, and snow. The large-scale conditions associated with the occurrence and development of these snowstorms are examined in order to identify the key synoptic controls leading to this event. Three main factors are identified: 1) the persistent blocking high over Siberia, which remained quasi-stationary around 65°E for 3 weeks, led to advection of dry and cold Siberian air down to central and southern China; 2) a strong persistent southwesterly flow associated with the western Pacific subtropical high led to enhanced moisture advection from the Bay of Bengal into central and southern China; and 3) the deep inversion layer in the lower troposphere associated with the extended snow cover over most of central and southern China. The combination of these three factors is likely responsible for the unusual severity of the event, and hence a long return period

Radiative forcing of the direct aerosol effect from AeroCom Phase II simulations

We report on the AeroCom Phase II direct aerosol effect (DAE) experiment where 16 detailed global aerosol models have been used to simulate the changes in the aerosol distribution over the industrial era. All 16 models have estimated the radiative forcing (RF) of the anthropogenic DAE, and have taken into account anthropogenic sulphate, black carbon (BC) and organic aerosols (OA) from fossil fuel, biofuel, and biomass burning emissions. In addition several models have simulated the DAE of anthropogenic nitrate and anthropogenic influenced secondary organic aerosols (SOA). The model simulated all-sky RF of the DAE from total anthropogenic aerosols has a range from −0.58 to −0.02Wm−2, with a mean of −0.27Wm−2 for the 16 models. Several models did not include nitrate or SOA and modifying the estimate by accounting for this with information from the other AeroCom models reduces the range and slightly strengthens the mean. Modifying the model estimates for missing aerosol components and for the time period 1750 to 2010 results in a mean RF for the DAE of −0.35Wm−2. Compared to AeroCom Phase I (Schulz et al., 2006) we find very similar spreads in both total DAE and aerosol component RF. However, the RF of the total DAE is stronger negative and RF from BC from fossil fuel and biofuel emissions are stronger positive in the present study than in the previous AeroCom study.We find a tendency for models having a strong (positive) BC RF to also have strong (negative) sulphate or OA RF. This relationship leads to smaller uncertainty in the total RF of the DAE compared to the RF of the sum of the individual aerosol components. The spread in results for the individual aerosol components is substantial, and can be divided into diversities in burden, mass extinction coefficient (MEC), and normalized RF with respect to AOD. We find that these three factors give similar contributions to the spread in results.

Host model uncertainties in aerosol radiative forcing estimates: results from the AeroCom Prescribed intercomparison study

Simulated multi-model “diversity” in aerosol direct radiative forcing estimates is often perceived as a measure of aerosol uncertainty. However, current models used for aerosol radiative forcing calculations vary considerably in model components relevant for forcing calculations and the associated “host-model uncertainties” are generally convoluted with the actual aerosol uncertainty. In this AeroCom Prescribed intercomparison study we systematically isolate and quantify host model uncertainties on aerosol forcing experiments through prescription of identical aerosol radiative properties in twelve participating models. Even with prescribed aerosol radiative properties, simulated clear-sky and all-sky aerosol radiative forcings show significant diversity. For a purely scattering case with globally constant optical depth of 0.2, the global-mean all-sky top-of-atmosphere radiative forcing is −4.47Wm−2 and the inter-model standard deviation is 0.55Wm−2, corresponding to a relative standard deviation of 12 %. For a case with partially absorbing aerosol with an aerosol optical depth of 0.2 and single scattering albedo of 0.8, the forcing changes to 1.04Wm−2, and the standard deviation increases to 1.01W−2, corresponding to a significant relative standard deviation of 97 %. However, the top-of-atmosphere forcing variability owing to absorption (subtracting the scattering case from the case with scattering and absorption) is low, with absolute (relative) standard deviations of 0.45Wm−2 (8 %) clear-sky and 0.62Wm−2 (11 %) all-sky. Scaling the forcing standard deviation for a purely scattering case to match the sulfate radiative forcing in the Aero- Com Direct Effect experiment demonstrates that host model uncertainties could explain about 36% of the overall sulfate forcing diversity of 0.11Wm−2 in the AeroCom Direct Radiative Effect experiment.

A review of measurement-based assessments of the aerosol direct radiative effect and forcing

Aerosols affect the Earth's energy budget directly by scattering and absorbing radiation and indirectly by acting as cloud condensation nuclei and, thereby, affecting cloud properties. However, large uncertainties exist in current estimates of aerosol forcing because of incomplete knowledge concerning the distribution and the physical and chemical properties of aerosols as well as aerosol-cloud interactions. In recent years, a great deal of effort has gone into improving measurements and datasets. It is thus feasible to shift the estimates of aerosol forcing from largely model-based to increasingly measurement-based. Our goal is to assess current observational capabilities and identify uncertainties in the aerosol direct forcing through comparisons of different methods with independent sources of uncertainties. Here we assess the aerosol optical depth (τ), direct radiative effect (DRE) by natural and anthropogenic aerosols, and direct climate forcing (DCF) by anthropogenic aerosols, focusing on satellite and ground-based measurements supplemented by global chemical transport model (CTM) simulations. The multi-spectral MODIS measures global distributions of aerosol optical depth (τ) on a daily scale, with a high accuracy of ±0.03±0.05τ over ocean. The annual average τ is about 0.14 over global ocean, of which about 21%±7% is contributed by human activities, as estimated by MODIS fine-mode fraction. The multi-angle MISR derives an annual average AOD of 0.23 over global land with an uncertainty of ~20% or ±0.05. These high-accuracy aerosol products and broadband flux measurements from CERES make it feasible to obtain observational constraints for the aerosol direct effect, especially over global the ocean. A number of measurement-based approaches estimate the clear-sky DRE (on solar radiation) at the top-of-atmosphere (TOA) to be about -5.5±0.2 Wm-2 (median ± standard error from various methods) over the global ocean. Accounting for thin cirrus contamination of the satellite derived aerosol field will reduce the TOA DRE to -5.0 Wm-2. Because of a lack of measurements of aerosol absorption and difficulty in characterizing land surface reflection, estimates of DRE over land and at the ocean surface are currently realized through a combination of satellite retrievals, surface measurements, and model simulations, and are less constrained. Over the oceans the surface DRE is estimated to be -8.8±0.7 Wm-2. Over land, an integration of satellite retrievals and model simulations derives a DRE of -4.9±0.7 Wm-2 and -11.8±1.9 Wm-2 at the TOA and surface, respectively. CTM simulations derive a wide range of DRE estimates that on average are smaller than the measurement-based DRE by about 30-40%, even after accounting for thin cirrus and cloud contamination. A number of issues remain. Current estimates of the aerosol direct effect over land are poorly constrained. Uncertainties of DRE estimates are also larger on regional scales than on a global scale and large discrepancies exist between different approaches. The characterization of aerosol absorption and vertical distribution remains challenging. The aerosol direct effect in the thermal infrared range and in cloudy conditions remains relatively unexplored and quite uncertain, because of a lack of global systematic aerosol vertical profile measurements. A coordinated research strategy needs to be developed for integration and assimilation of satellite measurements into models to constrain model simulations. Enhanced measurement capabilities in the next few years and high-level scientific cooperation will further advance our knowledge.

A cross-cultural examination of the psychometric properties of responses to the Achievement Goal Questionnaire

The psychometric properties of scores from the Achievement Goal Questionnaire were examined in samples of Japanese (N = 326) and Canadian (N = 307) post secondary students. Previous research found evidence of a four-factor structure of achievement goals in U.S. samples. Using confirmatory factor-analytic techniques, the authors found strong evidence for the four-factor structure of achievement goals in both the Canadian and Japanese populations. Subsequent multi group structural equation modeling indicated the metric invariance of this four-factor structure across the two populations.

Rheological and electrical properties of NaY zeolite electrorheological fluid

The relations between the rheological and electrical properties of NaY zeolite electrorheological fluid and its solid phase are studied. It is found that then exist complex relations between its electrical and theological properties. The temperature spectra of dielectric properties of the fluid under high AC electric field are strongly field strength dependent. The relation between the DC conductivity of the fluid and the exciting electric field is experimentally presented as log sigma =A+BE1/2, when A is a strong function, but B, a very weak function of temperature. The shear stress of the fluid under a fixed electric field and temperature decreases with shear rate. A relaxation time for the adsorbed charges is estimated to be about 0.3 to 6.6 s in the temperature range from 280 to 380 K. The relaxation time qualitatively corresponds to the shear rate at which the shear stress begins to drop. The time dependent leaking current of the ER fluids under DC electric field is also measured. The conductivity increase is mainly caused by the structure evolution of particles. The experimental results can he explained with the calculations of Davis (J. Appl. Phys. 81(1997) pp.1985-1991) and Martin (J. Chem. Phys. 110(1999) pp.4854-4866). It is predicted that the NaY zeolite ER fluid strength would get degraded slowly.

Dynamic simulation studies of structural formation and transition in electro-magneto-rheological fluids

The computer simulation method has been used to study the structural formation and transition of electro-magneto-rheological (EMR) fluids under compatible electric and magnetic fields. When the fields are applied simultaneously and perpendicularly to each other, the particles rapidly arrange into two-dimensional close-packed layer structures parallel to both fields. The layers then combine together to form thicker sheet-like structures, which finally relax into three-dimensional close-packed structures with the help of the thermal fluctuations. On the other hand, if the electric field is applied firstly to induce the body-centered tetragonal (BCT) columns in the system, and then the magnetic field is applied in the perpendicular direction. the BCT to face-centered cubic (FCC) structure transition is observed in very short time. Following that. the structure keeps on evolving due to the demagnetization effect and finally form the three-dimensional close-packed structures.

Resonance response of electrorheological fluids in vertical oscillation squeeze flow

The resonance effect of microcrystalline cellulose/castor oil electrorheological (ER) suspensions was studied in a compressed oscillatory squeeze flow under external electric fields. The resonance frequency first increases linearly with increasing external held, and then shift to high-field plateau. The amplitudes of resonance peak increase sharply with the applied fields in the range of 0.17-1.67kV/mm. The phase difference of the reduced displacement relative to the excitation force inverses in the case of resonance. A viscoelasticity model of the ER suspensions, which offers both the equivalent stiffness and the viscous damping, should be responsible for the appearance of resonance. The influence of the electric field on the resonance frequency and the resonance hump is consistent qualitatively with the interpretation of our proposed model. Storage modulus G' was presented for the purpose of investigating this influence.

Squeeze flow viscoelasticity of electrorheological fluids based on microcrystalline cellulose

Dynamic viscoelasticity of electrorheological fluids based on microcrystalline cellulose/castor oil suspensions was experimentally investigated in squeeze flow. The dependence of storage modulus G' and loss modulus G" parallel to external electric field on electric fields and strain amplitudes is presented. The experiments show that, when external electric field is higher than the critical field, the viscoelasticity of the ER fluids converts from linear to nonlinear, and the ER fluids transfer from solid-like state to fluid state with the growth of strain amplitude. The influences of strain amplitude and oscillatory frequency on the nonlinearity of viscoelasticity were also studied.

Simulation of field-induced structural formation and transition in electromagnetorheological suspensions

A computer simulation method has been used to study the three-dimensional structural formation and transition of eleetromagnetorheological (EMR) suspensions under compatible electric and magnetic fields. When the fields are applied simultaneously and perpendicularly to each other, the particles rapidly arrange into single layer structures parallel to both fields. In each layer, there is a two-dimensional hexagonal lattice. The single layers then combine together to form thicker sheetlike structures. With the help of the thermal fluctuations, the thicker structures relax into three-dimensional close-packed structures, which may be face-centered cubic (fcc), hexagonal close-packed (hup) lattices, or, more probably, the mixture of them, depending on the initial configurations and the thermal fluctuations. On the other hand, if the electric field is applied first to induce the body-centered tetragonal (bct) columns in the system, and then the magnetic field is applied in the perpendicular direction, the bet to fee structure transition is observed in a very short time. Following that, the structure keeps on evolving due to the demagnetization effect and finally forms close-packed structures with fee and hcp lattice character. The simulation results are in agreement with the theoretical and experimental results.

The source population for the cusp and cleft/LLBL for southward IMF

The distinction between plasma properties in different dayside regions in the Earth's magnetosphere is of strong interest as it is often indicative of specific physical processes. This is certainly true for the distinction between low latitude boundary layer (LLBL) and cusp plasma, which has been attributed to the effects of plasma diffusion across the magnetopause (LLBL) versus more direct entry of magnetosheath plasma(cusp). It is also the case, however, that quite different plasma regions can result more simply from a common source plasma, and from different stages of temporal evolution of the plasma associated with magnetospheric convection. In this paper, we show that, for southward interplanetary magnetic field (IMF) conditions, the distinction between the cusp and cleft/LLBL at low altitudes may result from;the single process of magnetosheath plasma entry into the magnetosphere on reconnected field lines. The different plasma characteristics of the two regions result from the properties of the source magnetosheath ion distribution and the effects of magnetic reconnection. Using well known properties of the magnetosheath, several predictions concerning the cusp and cleft/ LLBL precipitation are readily derived.

Identification of domestication-related loci associated with flowering time and seed size in soybean with the RAD-seq genotyping method

Flowering time and seed size are traits related to domestication. However, identification of domestication-related loci/genes of controlling the traits in soybean is rarely reported. In this study, we identified a total of 48 domestication-related loci based on RAD-seq genotyping of a natural population comprising 286 accessions. Among these, four on chromosome 12 and additional two on chromosomes 11 and 15 were associated with flowering time, and four on chromosomes 11 and 16 were associated with seed size. Of the five genes associated with flowering time and the three genes associated with seed size, three genes Glyma11g18720, Glyma11g15480 and Glyma15g35080 were homologous to Arabidopsis genes, additional five genes were found for the first time to be associated with these two traits. Glyma11g18720 and Glyma05g28130 were co-expressed with five genes homologous to flowering time genes in Arabidopsis, and Glyma11g15480 was co-expressed with 24 genes homologous to seed development genes in Arabidopsis. This study indicates that integration of population divergence analysis, genome-wide association study and expression analysis is an efficient approach to identify candidate domestication-related genes.

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.