Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor

Imidazo[1,2-a]pyridines were identified via their shape and electrostatic similarity as novel positive allosteric modulators of the metabotropic glutamate 2 receptor. The subsequent synthesis and SAR are described. Potent, selective and metabolically stable compounds were found representing a promising avenue for current further studies.     

Nested diets: a novel pattern of individual-level resource use

Many generalist populations may actually be composed of relatively specialist individuals. This 'individual specialization' may have important ecological and evolutionary implications. Although this phenomenon has been documented in more than one hundred taxa, it is still unclear how individuals within a population actually partition resources. Here we applied several methods based on network theory to investigate the intrapopulation patterns of resource use in the gracile mouse opossum Gracilinanus microtarsus . We found evidence of significant individual specialization in this species and that the diets of specialists are nested within the diets of generalists. This novel pattern is consistent with a recently proposed model of optimal foraging and implies strong asymmetry in the interactions among individuals of a population.     

Sodium exclusion QTL associated with improved seedling growth in bread wheat under salinity stress

Worldwide, dryland salinity is a major limitation to crop production. Breeding for salinity tolerance could be an effective way of improving yield and yield stability on saline-sodic soils of dryland agriculture. However, this requires a good understanding of inheritance of this quantitative trait. In the present study, a doubled-haploid bread wheat population (Berkut/Krichauff) was grown in supported hydroponics to identify quantitative trait loci (QTL) associated with salinity tolerance traits commonly reported in the literature (leaf symptoms, tiller number, seedling biomass, chlorophyll content, and shoot Na⁺ and K⁺ concentrations), understand the relationships amongst these traits, and determine their genetic value for marker-assisted selection. There was considerable segregation within the population for all traits measured. With a genetic map of 527 SSR-, DArT- and gene-based markers, a total of 40 QTL were detected for all seven traits. For the first time in a cereal species, a QTL interval for Na⁺ exclusion (wPt-3114-wmc170) was associated with an increase (10%) in seedling biomass. Of the five QTL identified for Na⁺ exclusion, two were co-located with seedling biomass (2A and 6A). The 2A QTL appears to coincide with the previously reported Na⁺ exclusion locus in durum wheat that hosts one active HKT1;4 (Nax1) and one inactive HKT1;4 gene. Using these sequences as template for primer design enabled mapping of at least three HKT1;4 genes onto chromosome 2AL in bread wheat, suggesting that bread wheat carries more HKT1;4 gene family members than durum wheat. However, the combined effects of all Na⁺ exclusion loci only accounted for 18% of the variation in seedling biomass under salinity stress indicating that there were other mechanisms of salinity tolerance operative at the seedling stage in this population. Na⁺ and K⁺ accumulation appear under separate genetic control. The molecular markers wmc170 (2A) and cfd080 (6A) are expected to facilitate breeding for salinity tolerance in bread wheat, the latter being associated with seedling vigour.     

Complexation of cadmium in seeds and vegetative tissues of the cadmium hyperaccumulator Thlaspi praecox as studied by X-ray absorption spectroscopy

The cadmium hyperaccumulator Thlaspi praecox Wulfen (Brassicaceae) can accumulate unusually high amounts of Cd (>1,000 μg g^?1 dry weight) in its seeds without drastically affecting seed viability. As embryonic tissues are the most sensitive to Cd toxicity, the aim of this study was to investigate the Cd coordination and ligand environment in seeds of field collected T. praecox using extended X-ray absorption fine structure (EXAFS), and to compare the Cd ligand environment to that in the vegetative tissues of the plant. In intact seeds and isolated embryos, almost two thirds of the Cd ligands were thiol groups (Cd-S-C-). In addition, there was coordination to phosphate groups via bridging oxygens (Cd-O-P-), as for phytate, although this ligand was not observed in the vegetative organs and tissues. In roots and shoots up to 80% of the Cd ligands were oxygen ligands that are provided by the cell walls and by organic acids stored in vacuoles. In leaf epidermis only a slightly higher percentage of oxygen ligands was detected, as compared to the mesophyll, making vacuolar compartmentation and binding to the cell walls the main detoxification mechanisms in both of these leaf tissues.     

Sleep stage and obstructive apneaic epoch classification using single-lead ECG

Background  

Polysomnography (PSG) is used to define physiological sleep and different physiological sleep stages, to assess sleep quality and diagnose many types of sleep disorders such as obstructive sleep apnea. However, PSG requires not only the connection of various sensors and electrodes to the subject but also spending the night in a bed that is different from the subject's own bed. This study is designed to investigate the feasibility of automatic classification of sleep stages and obstructive apneaic epochs using only the features derived from a single-lead electrocardiography (ECG) signal.     

Influence of day-night and tidal cycles on phenol content and antioxidant capacity in three temperate intertidal brown seaweeds

The daily variations of phenol contents and antioxidant capacities were surveyed in a 32-h field experiment in three temperate brown seaweeds belonging to Fucales - Pelvetia canaliculata, Ascophyllum nodosum and Bifurcaria bifurcata - living at different intertidal levels — high-, mid- and low-tide level, respectively. Phenolic compounds of brown seaweeds are secondary metabolites involved in many different protection mechanisms, as for example against grazer and pathogen attack as well as UV damage. This study was thus aimed at understanding the influence of both day/night and tidal cycles on the brown seaweed phenol pool with respect to their bathymetric level on the shore. These cycles affect the quantity and quality of light received by intertidal seaweeds (protection via the water layer during immersion), and the photoprotective role of phlorotannins was thus evaluated. Phenol levels and antioxidant capacities were monitored every hour during a tidal cycle and a half at the equinox spring tide, in March 2003. The three species contained rather high phenol levels, i.e. about 3, 6 and 4% DW in P. canaliculata, A. nodosum and B. bifurcata, respectively. Antioxidant capacities globally paralleled phenol contents in the three species under study. Moreover, the measured antioxidant capacities and the phenol contents of the extracts were significantly and positively correlated in the three species. Significant effect of neither cycles nor their interaction was observed in any species despite a trend to follow day/night alternation for P. canaliculata, and emersion/immersion cycle for A. nodosum. No trend was observed for the third species. However, significant correlations between phenol levels of P. canaliculata and A. nodosum and measured air-temperature were found. Our results suggested an effect of aerial, aquatic and both conditions on the phenolic pool of P. canaliculata, B. bifurcata and A. nodosum, respectively, and a fast evolution of the phenolic pool on a day time scale.     

Interleukin-2 induces the proliferation of mouse primordial germ cells in vitro

Primordial germ cells (PGCs) are the stem cell precursors of the germ line. Several growth factors contribute to enlarging the PGC population by acting as mitogens, survival factors or both. Interleukin-2 (IL-2) has a growth-promoting activity for T and B-lymphocytes, but its role in PGCs had not yet been studied. Here, we show that PGCs isolated from 10.5, 11.5 and 12.5 day postcoitum (dpc) mouse embryos constitutively express the three subunits (alpha, beta and gamma) of the IL-2 receptor (IL-2R). In contrast, IL-2 mRNA was not detected in these cells. However, the addition of recombinant IL-2 to the culture medium increased the number of PGCs in vitro via a mitogenic effect, as indicated by bromodeoxyuridine incorporation assays. Neutralization of the IL-2 receptor using anti-IL-2R subunit antibodies inhibited this IL-2-mediated proliferative effect on PGCs from 11.5 dpc embryos. Together, these data are indicative of a paracrine effect of IL-2 on PGC proliferation. In this regard, we also compared the effect of IL-2 with other compounds such as basic fibroblast growth factor (bFGF), steel factor, leukemia inhibitory factor and forskolin, and found that the degree of proliferation induced by IL-2 was similar to that induced by bFGF and forskolin. These observations support the notion that similar patterns of molecular signaling may underlie the developmental pathways of hematopoietic and germ stem cell precursors.     

Description of Tischeria gouaniae sp. n. from the tropical forest of Belize - an exotic new addition to the American fauna of Tischeria (Insecta: Lepidoptera: Tischeriidae)

We describe Tischeria gouaniae sp. n. from the tropical forests of Belize. The new species is a leaf-miner of Gouania polygama (Rhamnaceae). Together with the related T. bifurcata Braun, it is among the most striking representatives of Tischeria. Both species possess a pseudognathos and very broad aedeagus fused with extremely long lateral processes of the juxta. The new species differs from T. bifurcata in the broadly rounded vinculum, spiny juxta, and slender apical processes of the aedeagus, and in its host plant. The external features and male genitalia of Tischeria gouaniae sp. n. are figured and described. A checklist and distribution map for all nine currently known Tischeria species from North and South America are given. Most American species are known from USA, but others are now known from tropical forest habitats of Central America, the Caribbean, and Guyana. Host-plants are known for five of the nine species reviewed here, belonging to four genera and two plant families (Fagaceae and Rhamnaceae).     

Analysis of DNA damage induced by aflatoxin B1 in Dunkin–Hartley guinea pigs

Aflatoxin B1 (AFB1) is among the most potent naturally occurring carcinogens and classified as a group I carcinogen. Since the ingestion of aflatoxin-contaminated food is associated with several liver diseases, the aim of the present study was to evaluate the effect of 2, 20, and 200 ppb of AFB1 on DNA damage in peripheral blood lymphocytes and liver cells in Dunkin-Hartley guinea pigs. The animals were divided into four groups according to the given diet. After the treatment the lymphocytes and liver cells were isolated and DNA damage determined by Comet assay. The levels of DNA damage in lymphocytes were higher animals treated with 200 ppb of AFB1-enriched diet (P = 0.02). In the liver cells there were a relationship between the levels of DNA damage and the consumption of AFB1 in all studied groups. These results suggest that Comet assay performed on lymphocytes is a valuable genotoxic marker for high levels of exposure to AFB1 in guinea pig. Additionally our results indicate that the exposure to this toxin increases significantly and increases the level of DNA damage in liver cells, which is a key step on liver cancer development. We also suggest that the Comet assay is an useful tool for monitoring the genotoxicity of AFB1 in liver.