The absorption of orally supplied β-alanine and its effect on muscle carnosine synthesis in human vastus lateralis

Summary. β-Alanine in blood-plasma when administered as A) histidine dipeptides (equivalent to 40 mg · kg⁻¹ bwt of β-alanine) in chicken broth, or B) 10, C) 20 and D) 40 mg · kg⁻¹ bwt β-alanine (CarnoSyn™, NAI, USA), peaked at 428 ± SE 66, 47 ± 13, 374 ± 68 and 833 ± 43 μM. Concentrations regained baseline at 2 h. Carnosine was not detected in plasma with A) although traces of this and anserine were found in urine. Loss of β-alanine in urine with B) to D) was <5%. Plasma taurine was increased by β-alanine ingestion but this did not result in any increased loss via urine. Pharmacodynamics were further investigated with 3 × B) per day given for 15 d. Dietary supplementation with I) 3.2 and II) 6.4 g · d⁻¹ β-alanine (as multiple doses of 400 or 800 mg) or III) L-carnosine (isomolar to II) for 4 w resulted in significant increases in muscle carnosine estimated at 42.1, 64.2 and 65.8%.     

Thermodynamic and kinetic characterization of ligand binding to the purine riboswitch aptamer domain

Riboswitches are cis-acting genetic regulatory elements found commonly in bacterial mRNAs that consist of a metabolite-responsive aptamer domain coupled to a regulatory switch. Purine riboswitches respond to intracellular concentrations of either adenine or guanine/hypoxanthine to control gene expression. The aptamer domain of the purine riboswitch contains a pyrimidine residue (Y74) that forms a Watson-Crick base-pairing interaction with the bound purine nucleobase ligand that discriminates between adenine and guanine. We sought to understand the structural basis of this specificity and the mechanism of ligand recognition by the purine riboswitch. Here, we present the 2,6-diaminopurine-bound structure of a C74U mutant of the xpt-pbuX guanine riboswitch, along with a detailed thermodynamic and kinetic analysis of nucleobase recognition by both the native and mutant riboswitches. These studies demonstrate clearly that the pyrimidine at position 74 is the sole determinant of purine riboswitch specificity. In addition, the mutant riboswitch binds adenine and adenine derivatives well compared with the guanine-responsive riboswitch. Under our experimental conditions, 2,6-diaminopurine binds the RNA with DeltaH=-40.3 kcal mol(-1), DeltaS=-97.6 cal mol(-1)K(-1), and DeltaG=-10.73 kcal mol(-1). A kinetic determination of the slow rate (0.15 x 10(5)M(-1)s(-1) and 2.1 x 10(5)mM(-1)s(-1) for 2-aminopurine binding the adenine-responsive mutant riboswitch and 7-deazaguanine-binding guanine riboswitch, respectively) of association under varying experimental conditions allowed us to propose a mechanism for ligand recognition by the purine riboswitch. A conformationally dynamic unliganded state for the binding pocket is stabilized first by the Watson-Crick base pairing between the ligand and Y74, and by the subsequent ordering of the J2/3 loop, enclosing the ligand within the three-way junction.     

The clastogenic effects of chronic exposure to particulate and soluble Cr(VI) in human lung cells

Hexavalent chromium (Cr(VI)) is a well-designated human lung carcinogen, with solubility playing an important role in its carcinogenic potential. Although it is known that particulate or water-insoluble Cr(VI) compounds are more potent than the soluble species of this metal, the mechanisms of action are not fully elucidated. In this study, we investigated the hypothesis that the difference in potency between particulate and soluble Cr(VI) is due to more chronic exposures with particulate chromate because it can deposit and persist in the lungs while soluble chromate is rapidly cleared. Chronic exposure to both insoluble lead chromate and soluble sodium chromate induced a concentration and time-dependent increase in intracellular Cr ion concentrations in cultured human lung fibroblasts. Intracellular Pb levels after chronic exposure to lead chromate increased in a concentration-dependent manner but did not increase with longer exposure times up to 72 h. We also investigated the effects of chronic exposure to Cr(VI) on clastogenicity and found that chronic exposure to lead chromate induces persistent or increasing chromosome damage. Specifically, exposure to 0.5 μg/cm² lead chromate for 24, 48 and 72 h induced 23, 23 and 27% damaged metaphases, respectively. Contrary to lead chromate, the amount of chromosome damage after chronic exposure to sodium chromate decreased with time. For example, cells exposed to 1 μM sodium chromate for 24, 48 and 72 h induced 23, 13 and 17% damaged metaphases, respectively. Our data suggest a possible mechanism for the observed potency difference between soluble and insoluble Cr(VI) compounds is that chronic exposure to particulate Cr(VI) induces persistent chromosome damage and chromosome instability while chromosome damage is repaired with chronic exposure to soluble Cr(VI).     

Mapping multiple disease resistance genes using a barley mapping population evaluated in Peru, Mexico, and the USA

We used a well-characterized barley mapping population (BCD 47 × Baronesse) to determine if barley stripe rust (BSR) resistance quantitative trait loci (QTL) mapped in Mexico and the USA were effective against a reported new race in Peru. Essentially the same resistance QTL were detected using data from each of the three environments, indicating that these resistance alleles are effective against the spectrum of naturally occurring races at these sites. In addition to the mapping population, we evaluated a germplasm array consisting of lines with different numbers of mapped BSR resistance alleles. A higher BSR disease severity on CI10587, which has a single qualitative resistance gene, in Peru versus Mexico suggests there are differences in pathogen virulence between the two locations. Confirmation of a new race in Peru will require characterization using a standard set of differentials, an experiment that is underway. The highest levels of resistance in Peru were observed when the qualitative resistance gene was pyramided with quantitative resistance alleles. We also used the mapping population to locate QTL conferring resistance to barley leaf rust and barley powdery mildew. For mildew, we identified resistance QTL under field conditions in Peru that are distinct from the Mla resistance that we mapped using specific isolates under controlled conditions. These results demonstrate the long-term utility of a reference mapping population and a well-characterized germplasm array for locating and validating genes conferring quantitative and qualitative resistance to multiple pathogens.     

Ossicular density in golden moles (Chrysochloridae)

The densities of middle ear ossicles of golden moles (family Chrysochloridae, order Afrosoricida) were measured using the buoyancy method. The internal structure of the malleus was examined by high-resolution computed tomography, and solid-state NMR was used to determine relative phosphorus content. The malleus density of the desert golden mole Eremitalpa granti (2.44 g/cm³) was found to be higher than that reported in the literature for any other terrestrial mammal, whereas the ossicles of other golden mole species are not unusually dense. The increased density in Eremitalpa mallei is apparently related both to a relative paucity of internal vascularization and to a high level of mineralization. This high density is expected to augment inertial bone conduction, used for the detection of seismic vibrations, while limiting the skull modifications needed to accommodate the disproportionately large malleus. The mallei of the two subspecies of E. granti, E. g. granti and E. g. namibensis, were found to differ considerably from one another in both size and shape.     

Calcareous nannofossil biostratigraphic framework for middle Eocene sediments from ODP Hole 1260A, Demerara Rise

Ocean Drilling Program (ODP) Site 1260 recovered a near-continuous and expanded (187-m thick) middle Eocene carbonate sequence at mid-bathyal depths on Demerara Rise off Suriname, South America. A calcareous nannofossil biostratigraphic framework has been established for the sequence to aid multi-proxy cyclostratigraphic analyses. The diversity of calcareous nannofossils is reasonably high and preservation moderate throughout most of the section, and the proximity to the continent is indicated by the occurrence of braarudosphaerids in the lower three quarters of the section. The species richness of sphenoliths is particularly high, and our data confirm the occurrence of new sphenoliths during the middle Eocene as shown recently by Bown and Dunkley Jones (2006). In particular we corroborate the occurrences of Sphenolithus strigosus and S. runus that these authors found in their Zone NP16 Tanzania sediments, however we extend the ranges of these taxa down into Zone NP15 (CP13). Moreover we document the occurrence of Bramletteius serraculoides in Zone NP15 (CP13b) and the occurrence of Sphenolithus predistentus in NP16 (CP14a), extending their known ranges down column.     

Inter-and intraspecific effects of density manipulations upon females of two orb-weaving spiders (araneae: araneidae)

Summary A field experiment was conducted to establish whether or not inter-and intraspecific competition occurs between two syntopic species of orb-weaving spiders. Replicated single-species and mixed-species adult populations of the basilica spider, Mecynogea lemniscata, and the labyrinth spider, Metepeira labyrinthea, were established at a range of densities on open experimental units in the species' natural habitat. Each experimental unit was a 4mx1.6mx1m wood frame supporting branches upon which introduced spiders built webs. Survival and reproduction on the units were monitored from 1 August through 1 November 1978,There were no significant negative interspecific effects of density upon either survival or reproduction, which indicates that interspecific competition was not occurring during the experiment. There was statistically significant evidence of intraspecific competition between females for both species, but the negative density effects were small. They explained 5% of the variance in Mecynogea web height, 2% of the variance in Metepeira survival, and 1% of the variation in number of eggs per sac for Mecynogea.Hence inter-and intraspecific competition was either absent or weak in 1978, despite the fact that a field experiment conducted the previous year (Wise 1979) demonstrated that prey abundance was limiting the egg production of both species. Evidence of food limitation in 1977 followed by only weak competitive interactions the following year suggests that the significance of resource limitation and competition may vary temporally for the basilica and labyrinth spiders.     

Individual differences in the chemical senses: is there a common sensitivity?

Taste, smell, and chemical irritation (so-called trigeminal sensation) combine in our daily experience to produce the supramodal sensation of flavor, are processed by partly overlapping neural mechanisms, and show functional interconnectivity in experiments. Given their collaboration in flavor formation and the well-established connections between these senses, it is plausible that polymodal detection mechanisms might contribute to individual differences in measured sensitivity. One would expect the existence of a general chemosensory sensitivity factor to result in associations among taste, smell, and trigeminal stimulation thresholds. Measures of 5 detection thresholds from all the chemical senses were assessed in the same group of young healthy subjects (n=57). An unbiased principal components analysis (PCA) yielded a 2-component solution. Component 1, on which taste thresholds loaded strongly, accounted for 29.4% of the total variance. Component 2, on which the odor and trigeminal lateralization thresholds loaded strongly, accounted for 26.9% of the total variance. A subsequent PCA restricted to a 3-component solution cleanly separated the 3 sensory modalities and accounted for 75% of the total variance. Thus, though there may be a common underlying factor that determines some individual differences in odor and trigeminal lateralization thresholds, a general chemical sensitivity that spans chemosensory modalities seems unlikely.     

Encoding goals but not abstract magnitude in the primate prefrontal cortex

Functional neuroimaging studies show that perceptual judgments about time and space activate similar prefrontal and parietal areas, and it is known that perceptions in these two cognitive domains interfere with each other. These findings have led to the theory that temporal and spatial perceptions, among other metrics, draw on a common representation of magnitude. Our results indicate that an alternative principle applies to the prefrontal cortex. Analysis at the single-cell level shows that separate, domain-specific populations of neurons encode relative magnitude in time and space. These neurons are intermixed with each other in the prefrontal cortex, along with a separate intermixed population that encodes the goal chosen on the basis of these perceptual decisions. As a result, domain-specific neural processing at the single-cell level seems to underlie domain generality as observed at the regional level, with a common representation of prospective goals rather than a common representation of magnitude.