Small-scale Environmental Heterogeneity and Spatiotemporal Dynamics of Seedling Establishment in a Semiarid Degraded Ecosystem

In semiarid environments, surface soil properties play a major role in ecosystem dynamics, through their influence on processes such as runoff, infiltration, seed germination, and seedling establishment. Surface soil properties usually show a high degree of spatial heterogeneity in semiarid areas, but direct tests to evaluate the consequences of this heterogeneity on seedling establishment are limited. Using a combination of spatial analysis by distance indices (SADIE) and principal components analysis (PCA) we quantified the spatiotemporal patterns of seedling survival of a Mediterranean native shrub (Pistacia lentiscus) during the first 3 years after planting on a semiarid degraded site in southeastern Spain. We used a variation partitioning method to identify environmental variables associated with seedling survival patterns. Three years after planting, only 36% of the seedlings survived. During the first summer, one-third of the seedlings died, with secondary major mortality in the 3rd summer after planting. The spatial pattern of survival became strongly clumped by the end of the first summer, with clearly defined patches (areas of high survival) and gaps (areas of low survival). The intensity of this pattern increased after subsequent high-mortality periods. Of the 14 variables, the ones most strongly coupled to seedling survival were bare soil cover, sand content, and soil compaction. These findings contribute to our understanding of the linkages between the spatial heterogeneity of abiotic factors and the response of plant populations in semiarid degraded ecosystems and can be used to optimize restoration practices in these areas.     

Charged residues at the 2' position of human GABAC rho 1 receptors invert ion selectivity and influence open state probability

The ability of members of the nicotinicoid superfamily of ligand-gated ion channels to selectively conduct anions or cations is critical to their function within the central nervous system. Recent work has demonstrated that residues at the intracellular end of the second transmembrane domain, between the -3' and 2' positions, form the ion selectivity filter of these receptors. In this study, the proline residue at the 2' position (Pro-2') at the intracellular end of the second transmembrane domain of the gamma-aminobutyric acid type C rho 1 subunit was mutated to glutamate (rho 1P2'E) and arginine (rho 1P2'R). Dilution potential experiments indicated that the charge selectivity of the rho 1P2'E receptor channels had been inverted, with the channels now becoming predominantly cation selective, indicating the ability of negatively charged residues at this 2' position to control charge selectivity. The mutation was also seen to have significantly decreased agonist potency and intrinsic efficacy. In contrast, the rho 1P2'R receptor channels were anion-selective but were now found to be constitutively open with high holding currents (inhibited by low gamma-aminobutyric acid doses and the competitive antagonist, 1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid alone) and increased agonist activity. Hill coefficients of both mutants were decreased, but competitive antagonist studies indicated that their binding sites were not significantly affected.     

Quantitative autoradiography of Na+-dependent [3H]L-aspartate binding to L-glutamate transporters in rat brain: structure-activity studies using L-trans-pyrrolidine-2,4-dicarboxylate (L-t-PDC) and 2-(carboxycyclopropyl)-glycine (CCG)

Sodium-dependent binding of [3H]L-aspartate was studied in thaw-mounted horizontal sections of fresh-frozen (i.e. not fixed) rat brain. After the incubation with [3H]L-aspartate, the sections were exposed against a 3H-sensitive film and the resulting autoradiograms were evaluated by quantitative densitometry. Effects of several inhibitors were examined and their potency expressed as IC50 and nH. Together with previously published data, the present study supports the view that [3H]L-aspartate binding to fresh-frozen sections of rat brain represents interaction of the radioligand with the substrate-binding sites on glutamate transporters. The most potent inhibitors were (2S,3S,4R)-2-(carboxycyclopropyl)-glycine (L-CCG III) and (2S,4R)-4-methylglutamate. In contrast, L-anti,endo-3,4-methanopyrrolidine dicarboxylate (L-a,e-MPDC) was about an order of magnitude less potent. Only subtle regional variations in the characteristics of inhibitors of [3H]L-aspartate binding were detected. It is not certain whether these differences reflect regional variations in the distribution of individual glutamate transporters or regional peculiarities in their pharmacological characteristics. In particular, (2S,4R)-4-methylglutamate, shown previously to differentiate between GLT-1 (principal glutamate transporter in the forebrain) and GLAST (expressed mainly in the cerebellum), did not strongly differentiate between the binding of [3H]L-aspartate in forebrain and cerebellum. Computer-assisted molecular modelling using selected glutamate analogues with restricted conformation (L-trans-pyrrolidine-2,4-dicarboxylate and four isomers of 2-(carboxycyclopropyl)-glycine: L- and D-CCG I, L-CCG III and L-CCG IV) identified at least one area of unfavourable steric interaction. We conclude that the quantitative autoradiographic studies using [3H]L-aspartate or other transporter-specific ligands, will be a useful tool to study the pharmacology of substrate binding sites on glutamate transporters in the mammalian brain in situ.     

1-Phenylpyrazolo[3,4-d]pyrimidines; structure-ac:tivity relationships for C6 substituents at A1 and A2A adenosine receptors

Substitution of I-phenylpyrazolo[3,4-d]pyrimidines at C6 with N-alkyl-2-thiopropionamide groups has resulted in a series of 18 compounds which have been evaluated for binding at A1 and A2A adenosine receptors. Introduction of an N-ethyl group gave increased affinity at both A1 and A2A receptors for the amino compound 7b compared to the primary amide 7a. An additional hydrophobic pocket exists for substituents on the amide. This pocket allows an N-ethyl group for increased affinity at both A1 and A2A receptors, allows larger alkyl groups at A2A receptors but not at A1 receptors and there is an H-bond interaction requiring one H-bond donor. Molecular modeling studies have also enabled a proposal of the amino acid residues involved in ligand binding at both the A1 and A2A receptors.     

Global Alzheimer Research Summit: Basic and clinical research Present and future Alzheimer research

We report here on the proceedings of the Global Alzheimer Summit that took place September 22–23, 2011 in Madrid, Spain. As Alzheimer disease (AD) is the leading cause of neurodegeneration in elderly individuals and, as yet, has no effective therapeutic option, it continues to stimulate global research interests. At the conference, leaders in the field of AD research provided insights into current developments in various areas of research, namely molecular mechanisms, genetics, novel aspects of AD research and translational research. Emphasis was also placed on the importance of biomarkers in the diagnosis of AD and development of current therapeutic strategies.     

Modulation of Ionotropic GABA Receptors by 6-Methoxyflavanone and 6-Methoxyflavone

We evaluated the effects of 6-methoxyflavanone and 6-methoxyflavone on wild-type α1/α2β2γ2L GABA_A and ρ1 GABA_C receptors and on mutant ρ1I307S, ρ1W328 M, ρ1I307S/W328 M GABA_C receptors expressed in Xenopus oocytes using two-electrode voltage clamp and radioligand binding. 6-Methoxyflavanone and 6-methoxyflavone act as a flumazenil-insensitive positive allosteric modulator of GABA responses at human recombinant α1β2γ2L and α2β2γ2L GABA_A receptors. However, unlike 6-methoxyflavone, 6-methoxyflavanone was relatively inactive at α1β2 GABA_A receptors. 6-Methoxyflavanone inhibited [³H]-flunitrazepam binding to rat brain membranes. Both flavonoids were found to be inactive as modulators at ρ1, ρ1I307S and ρ1W328 M GABA receptors but acted as positive allosteric modulators of GABA at the benzodiazepine sensitive ρ1I307S/W328 M GABA receptors. This double mutant retains ρ1 properties of being insensitive to bicuculline and antagonised by TPMPA and THIP. Additionally, 6-methoxyflavanone was also a partial agonist at ρ1W328 M GABA receptors. The relative inactivity of 6-methoxyflavanone at α1β2 GABA_A receptors and it’s partial agonist action at ρ1W328 M GABA receptors suggest that it exhibits a unique profile not matched by other flavonoids.     

Neurochemicals for the Investigation of GABA<Subscript>C</Subscript> Receptors

GABA_C receptors are being investigated for their role in many aspects of nervous system function including memory, myopia, pain and sleep. There is evidence for functional GABA_C receptors in many tissues such as retina, hippocampus, spinal cord, superior colliculus, pituitary and the gut. This review describes a variety of neurochemicals that have been shown to be useful in distinguishing GABA_C receptors from other receptors for the major inhibitory neurotransmitter GABA. Some selective agonists (including (+)-CAMP and 5-methyl-IAA), competitive antagonists (such as TPMPA, (±)-cis-3-ACPBPA and aza-THIP), positive (allopregnanolone) and negative modulators (epipregnanolone, loreclezole) are described. Neurochemicals that may assist in distinguishing between homomeric ρ1 and ρ2 GABA_C receptors (2-methyl-TACA and cyclothiazide) are also covered. Given their less widespread distribution, lower abundance and relative structural simplicity compared to GABA_A and GABA_B receptors, GABA_C receptors are attractive drug targets.     

Cosine analysis of heart beat data of children in a stressful situation

The EKG of twenty-four children (mean age = = 5.7 years) was individually and continuously recorded in a dental situation. Measures of cardiac activity (heart rate [HR] and heart rate variability [HRV]) were computed by means of a CDC 1,700 and an IBM 360 computer. Histograms of heart rate (HR) and heart rate variability (HRV) measures were generated. -Successive cosine fits were fitted for each 70 beats within an interval for each individual and these cosine fits were also presented in a histogram which represented a frequency analysis of cyclic functions within individuals. Within and between subject correlations were also computed for all measures. Sinus arrhythmia seemed to account for less of the variance than a yet unexplained cosine fit function having a lower limit of 18.6 seconds in this child population. In this population many measures of HRV seem to be negatively correlated with HR.     

Inbred lab mice are not isogenic: genetic variation within inbred strains used to infer the mutation rate per nucleotide site

For over a century, inbred mice have been used in many areas of genetics research to gain insight into the genetic variation underlying traits of interest. The generalizability of any genetic research study in inbred mice is dependent upon all individual mice being genetically identical, which in turn is dependent on the breeding designs of companies that supply inbred mice to researchers. Here, we compare whole-genome sequences from individuals of four commonly used inbred strains that were procured from either the colony nucleus or from a production colony (which can be as many as ten generations removed from the nucleus) of a large commercial breeder, in order to investigate the extent and nature of genetic variation within and between individuals. We found that individuals within strains are not isogenic, and there are differences in the levels of genetic variation that are explained by differences in the genetic distance from the colony nucleus. In addition, we employ a novel approach to mutation rate estimation based on the observed genetic variation and the expected site frequency spectrum at equilibrium, given a fully inbred breeding design. We find that it provides a reasonable per nucleotide mutation rate estimate when mice come from the colony nucleus (~7.9 × 10⁻⁹ in C3H/HeN), but substantially inflated estimates when mice come from production colonies.Subject terms: Evolutionary genetics, Evolutionary biology, Inbreeding, Genetic variation, Mutation