Atrial and ventricular myocytes were exposed to Ca2+- and K+-free solutions containing blockers of gated channel and exchange currents. Replacement of external sodium by large organic cations ...revealed a background sodium current ib, Na. In atrial cells, the average conductance was 5.0 pS pF-1. In ventricular cells the conductance was 2.3 pS pF-1. Together with previous results, these figures reveal a strong gradient of background current density: sinus > atrium > ventricle. Replacement of sodium with inorganic cations showed that the channel selectivity behaves like an Eisenman group III/IV sequence, in agreement with previous results. The permeability of the channel to TMA was found to be pH dependent, suggesting that protonation of the channel is a factor determining permeation in addition to ionic size. The values of gb, Na obtained from these experiments are very similar to those assumed in computer modelling of cardiac cell electrical activity.
A series of
O
4-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies ...with
O
6-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4′-position were potent inhibitors, with IC
50 values against CDK2 of 1.1±0.3 and 34±8 nM, respectively. The crystal structure of the 4′-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.
A series of
O
4-cyclohexylmethyl-5-nitroso-6-aminopyrimidines bearing 2-arylamino substituents was synthesised and evaluated for CDK1 and CDK2 inhibitory activity. Consistent with analogous studies with
O
6-cyclohexylmethylpurines, 2-arylaminopyrimidines with a sulfonamide or carboxamide group at the 4′-position were potent inhibitors, with IC
50 values against CDK2 of 1.1±0.3 and 35±8 nM, respectively. The crystal structure of the 4′-carboxamide derivative, in complex with phospho-Thr160 CDK2/cyclin A, confirmed the expected binding mode of the inhibitor, and revealed an additional interaction between the carboxamide function and an aspartate residue.
The importance of sexual compatibility between mates has only recently been realized in zoological research into sexual selection, yet its study has been central to botanical research for many ...decades. The reproductive characteristics of remote mating, an absence of precopulatory mate screening, internal fertilization and embryonic brooding are shared between passively pollinated plants and a phylogenetically diverse group of sessile aquatic invertebrates. Here, we further characterize the sexual compatibility system of one such invertebrate, the colonial ascidian Diplosoma listerianum. All 66 reciprocal pairings of 12 genetic individuals were carried out. Fecundities of crosses varied widely and suggested a continuous scale of sexual compatibility. Of the 11 animals from the same population c. 40% of crosses were completely incompatible with a further c. 20% having obvious partial compatibility (reduced fecundity). We are unaware of other studies documenting such high levels of sexual incompatibility in unrelated individuals. RAPD fingerprinting was used to estimate relatedness among the 12 individuals after a known pedigree was successfully reconstructed to validate the technique. In contrast to previous results, no correlation between genetic similarity and sexual compatibility was detected. The blocking of many genotypes of sperm is expected to severely modify realized paternity away from ‘fair raffle’ expectations and probably reduce levels of intra‐brood genetic diversity in this obligatorily promiscuous mating system. One adaptive benefit may be to reduce the bombardment of the female reproductive system by outcrossed sperm with conflicting evolutionary interests, so as to maintain female control of somatic : gametic investment.
A significant portion of the Earth’s carbon is in forested terrestrial ecosystems. Carbon fluxes to and from these ecosystems in response to climate change have the potential to alter global climate. ...To understand how forest carbon budgets may be affected by climate, we observed patterns of carbon storage, forest structure, and composition in Scots pine forest ecosystems at nine sites along a northern latitudinal gradient (50–70°N) crossing Poland, Lithuania, Latvia, Estonia, and Finland. This gradient is characterized by a northward decline in average annual temperature (Δ
=
ca. 9°C) and precipitation (Δ
=
ca. 300
mm). Total ecosystem carbon, decomposition rates, and litterfall amounts all decreased nonlinearly with increasing latitude. Plant species richness in the ground flora also decreased with increasing latitude. However, the percent cover of lower canopy vegetation varied asystematically with respect to latitude, temperature, or precipitation. Our results are largely consistent with models and analyses indicating that northern latitude forests may respond to predicted climate changes with increased carbon sequestration. In the short term, however, these forests may be a source rather than a sink for atmospheric carbon as the relative distribution of C among ecosystem components adjusts in response to changing climatic conditions.
Cold cores are an early step of star formation, characterized by densities > 10\(^4\) cm\(^{-3}\), low temperatures (< 15 K), and very low external UV radiation. We investigate the physico-chemical ...processes at play to tracing the origin of molecules that are predominantly formed via reactions on dust grain surfaces. We observed the cold core LDN 429-C with the NOEMA interferometer and the IRAM 30m single dish telescope in order to obtain the gas-phase abundances of key species, including CO and CH\(_3\)OH. Comparing the observed gas phase of methanol to its solid phase previously observed with Spitzer allows us to put quantitative constraints on the efficiency of the non-thermal desorption of this species. With physical parameters determined from available Herschel data, we computed abundance maps of 11 detected molecules with a non-local thermal equilibrium radiative transfer model. These observations allowed us to probe the molecular abundances as a function of density and visual extinction, with the variation in temperature being restrained between 12 and 18 K. We then compared the observed abundances to the predictions of the Nautilus astrochemical model. We find that all molecules have lower abundances at high densities and visual extinctions with respect to lower density regions, except for methanol. Comparing these observations with a grid of chemical models based on the local physical conditions, we were able to reproduce these observations, allowing only the parameter time to vary. Comparing the observed gas-phase abundance of methanol with previous measurements of the methanol ice, we estimate a non-thermal desorption efficiency between 0.002% and 0.09%, increasing with density. The apparent increase in the desorption efficiency cannot be reproduced by our model unless the yield of cosmic-ray sputtering is altered due to the ice composition varying as a function of density.
Alternaria alternata, Aspergillus spp., Bipolaris spicifera, Curvularia lunata, Epicoccum nigrum and Fusarium solani were isolated repeatedly from groups of patients among 96 diagnosed with allergic ...fungal sinusitis (AFS). Epicoccum nigrum was obtained consistently from four patients, one of whom yielded mycelial masses consistent in morphology with E. nigrum. Fifteen of the predominant fungi recovered from air samples from selected patients' residences included the same species isolated from the mucin of its inhabitants. Air samples from other buildings, whose occupants (non-AFS individuals) complained of poor indoor air quality or of symptoms of the sick building syndrome (SBS), yielded some of the same species involved in AFS. An association of SBS with AFS was not established. Eight of the species implicated in AFS were found to colonize the surfaces of indoor construction and finishing materials at sites other than the residence of the patient. To our knowledge, this is the first report that E. nigrum can colonize nasal sinuses and cause AFS.
The efficacy of gene therapy mediated by plasmid DNA (pDNA) depends on the selection of suitable vectors and doses. Using hydrodynamic limb vein (HLV) injection to deliver naked pDNA to skeletal ...muscles of the limbs, we evaluated key parameters that affect expression in muscle from genes encoded in pDNA. Short-term and long-term promoter comparisons demonstrated that kinetics of expression differed between cytomegalovirus (CMV), muscle creatine kinase, and desmin promoters, but all gave stable expression from 2 to 49 weeks after delivery to mouse muscle. Expression from the CMV promoter was highest. For mice, rats, and rhesus monkeys, the linear range for pDNA dose response could be defined by the mass of pDNA relative to the mass of target muscle. Correlation between pDNA dose and expression was linear between a threshold dose of 75 μg/g and maximal expression at approximately 400 μg/g. One HLV injection into rats of a dose of CMV-LacZ yielding maximal expression resulted in an average transfection of 28% of all hind leg muscle and 40% of the gastrocnemius and soleus. Despite an immune reaction to the reporter gene in monkeys, a single injection transfected an average of 10% of all myofibers in the targeted muscle of the arms and legs and an average of 15% of myofibers in the gastrocnemius and soleus.
Rupture of the Greendale Fault during the 4 September 2010, M
W
7.1 Darfield (Canterbury) earthquake produced a zone of ground-surface rupture that severely damaged several houses, buildings and ...lifelines. Immediately after the earthquake, surface rupture features were mapped in the field and from digital terrain models developed from airborne Light Detection and Ranging (lidar) data. To enable rebuild decisions to be made and for future land use planning, a fault avoidance zone was defined for the Greendale Fault following the Ministry for the Environment guidelines on 'Planning for the Development of Land on or Close to Active Faults'. We present here the most detailed map to date of the fault trace and describe how this was used to define and characterise the fault avoidance zone for land use planning purposes.
We have peformed three searches for high-frequency signals in the solar neutrino flux measured by the Sudbury Neutrino Observatory (SNO), motivated by the possibility that solar g-mode oscillations ...could affect the production or propagation of solar {sup 8}B neutrinos. The first search looked for any significant peak in the frequency range l/day to 144/day, with a sensitivity to sinusoidal signals with amplitudes of 12% or greater. The second search focused on regions in which g-mode signals have been claimed by experiments aboard the SoHO satellite, and was sensitive to signals with amplitudes of 10% or greater. The third search looked for extra power across the entire frequency band. No statistically significant signal was detected in any of the three searches.
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