Sonic hedgehog control of size and shape in midbrain pattern formation

Little is known about how patterns of cell types are organized to form brain structures of appropriate size and shape. To study this process, we employed in vivo electroporation during midbrain development to create ectopic sources of Sonic Hedgehog, a signaling molecule previously shown to specify different neuronal cell types in a concentration-dependent manner in vitro. We provide direct evidence that a Sonic Hedgehog source can control pattern at a distance in brain development and demonstrate that the size, shape, and orientation of the cell populations produced depend on the geometry of the morphogen source. Thus, a single regulatory molecule can coordinate tissue size and shape with cell-type identity in brain development.     

Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing

Variants of NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP), increase susceptibility to Crohn's disease (CD). These variants are thought to be defective in activation of nuclear factor kappaB (NF-kappaB) and antibacterial defenses, but CD clinical specimens display elevated NF-kappaB activity. To illuminate the pathophysiological function of NOD2, we introduced such a variant to the mouse Nod2 locus. Mutant mice exhibited elevated NF-kappaB activation in response to MDP and more efficient processing and secretion of the cytokine interleukin-1beta (IL-1beta). These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion.     

Amplification of acetylcholine-binding catenanes from dynamic combinatorial libraries

Directed chemical synthesis can produce a vast range of molecular structures, but the intended product must be known at the outset. In contrast, evolution in nature can lead to efficient receptors and catalysts whose structures defy prediction. To access such unpredictable structures, we prepared dynamic combinatorial libraries in which reversibly binding building blocks assemble around a receptor target. We selected for an acetylcholine receptor by adding the neurotransmitter to solutions of dipeptide hydrazones [proline-phenylalanine or proline-(cyclohexyl)alanine], which reversibly combine through hydrazone linkages. At thermodynamic equilibrium, the dominant receptor structure was an elaborate [2]-catenane consisting of two interlocked macrocyclic trimers. This complex receptor with a 100 nM affinity for acetylcholine could be isolated on a preparative scale in 67% yield.     

Confirmation of hybrid origin in Arisaema (Araceae) using molecular markers

A population of hybrids between Arisaema triphyllum subsp. stewardsonii and A. dracontium was investigated using molecular markers to document the hybrid origin. Total genomic DNA was extracted from A. triphyllum, A. dracontium, and the hybrids, and subjected to sequence analysis of various regions of intergenic spacer and genes of chloroplast or intergenic spacer and genes of nuclear ribosome for single nucleotide polymorphisms (SNPs). Clustering was performed using the unweighted pair group method with averages (UPGMA) tested by bootstrap (BS). Hybrid origin could not be easily confirmed in some regions. However, dendrograms constructed with a combined sequence analysis of A. triphyllum 26S ribosomal RNA gene [sequence identification (SI) 467] plus A. tortuosum phytochrome C-like (phyC) gene (SI 468) were very similar to dendrograms constructed from sequences of all regions. This suggests that selecting SI 467 and SI 468 would be practical to identify hybrid origins involving two parental species. Clustering of hybrids together with the female parent in most target regions suggests that, in Arisaema, cpDNA is considered maternally inherited.     

Analyzing the effect of stepping stones on target patch colonisation in structured landscapes for Eurasian lynx

With habitat loss and fragmentation having become two of the major threats to the viability of species, the question of how to manage landscapes for species conservation has attracted much attention. In this context, the planning of stepping stones has been proposed to increase connectivity in fragmented landscapes. We present a simulation study with a neutral landscape approach to assess the effects of stepping stones on colonization success. To that end, we used a spatially explicit, calibrated population model of the European lynx (Lynx lynx) coupled with structured landscapes, in which we could control the landscape parameters of dispersal habitat coverage and contagion, as well as the number and size of stepping stones available for breeding. In general, we found that colonization success increased with increasing habitat coverage but decreased with increasing habitat contagion, while the introduction of stepping stones had significant effects in critical situations. Especially at low to medium dispersal habitat coverage and high disperser mortality, stepping stones had a positive effect on colonization success when they were large enough to produce new dispersers, but negative effects when they were small and located in a way that dispersers would be distracted from more suitable breeding habitat patches. The latter clearly constituted a shading effect and argues for a thorough consideration of the trade-offs related to stepping stone size and location when implementing stepping stones as a conservation measure, especially when the number of individuals of conservation concern is low.     

Wind dispersal of oribatid mites as a mode of migration

Oribatid mites are important colonizers of young soils, but little is known about their immigration pathways. In this study, one often-stated hypothesis was tested quantitatively: that wind is an important dispersal pathway. The aim was (1) to detect wind dispersal in oribatid mites (using sticky traps at different heights above ground level) and to determine factors influencing wind dispersal, (2) to investigate whether oribatids can survive wind dispersal and immigrate by wind into young soils (using mini-pitfall traps in test plots with oribatid-free substrate, active immigration being prohibited) and (3) to find out whether those oribatids are able to colonize young soils (using soil cores from the test plots). The results demonstrate (1) that mainly arboreal oribatid species were dispersed by wind - even at 160 m height - and can therefore be spread over large distances. Nevertheless, about 10% of the wind-dispersed oribatid mites belonged to species able to live in the soil and may therefore be potential colonizers of young soils. The number of specimen and species transported by wind was the highest close to the soil surface and the number of dispersed individuals was mainly influenced by seasonality and humidity. The results also suggest that the probability of a soil oribatid being dispersed by wind depends on its original microhabitat (tree habitats > soil surface > deeper soil layers) and its body weight. It was also shown that soil-dwelling oribatid mites survived wind dispersal and immigrated by wind into the test plots and that colonization of the test plots took at least 2 months longer than immigration. However, colonization success was low during the first 2 years of investigation and only Trichoribates incisellus was found several times in the nutrient-poor substrate. Therefore, wind dispersal is an important migration pathway, especially for arboreal oribatids. We suggest that immigration into young soils most likely occurs by repeated short-distance dispersal. Only some species are able to survive the hostile conditions of wind dispersal as well as of pioneer soils, but those that do are potentially the founders of new populations.     

Preliminary investigation of concurrent administration of phenylbutazone and romifidine in healthy horses

ObjectiveTo characterize the cardiorespiratory and electrocardiographic effects of the combined administration of phenylbutazone and romifidine.Study designProspective four-period, four-treatment, blinded, randomized, crossover trial.AnimalsFive, healthy, mixed breed horses.MethodsPrior to treatment administration, a catheter was introduced into the intra-thoracic cranial vena cava via the jugular vein and a subcutaneously located carotid artery was catheterised. All treatments were administered intravenously (IV) and consisted of saline placebo (PLC), phenylbutazone (PBZ, 4.4 mg kg^?1) romifidine (ROM, 80 μg kg^?1) and a combination of phenylbutazone (4.4 mg kg^?1) and romifidine (80 μg kg^?1). There was at least a 1 week washout period between treatments. Heart rate (HR), respiratory rate (f_R), systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures and central venous pressure (CVP) were recorded for baseline (prior to drug administration) and at 5 minute intervals thereafter for 30 minutes. Electrocardiographic abnormalities were recorded. Data were analyzed by anova.ResultsFor the cardiovascular variables there were no statistically significant (p > 0.05) differences between horses treated with ROM and PBZ_ROM. Statistically significant (p < 0.05) differences only occurred between treatments with romifidine (ROM and PBZ_ROM) and without romifidine (PLC and PBZ). Within treatments, for ROM, changes over time were statistically significant (p < 0.05) for HR, SAP, DAP, MAP and CVP. For PBZ_ROM, changes over time were statistically significant (p < 0.05) for CVP. Sino-atrial and atrio-ventricular blocks occurred in horses treated with ROM and PBZ_ROM.Conclusions and clinical relevanceThe combined IV administration of phenylbutazone and romifidine had no statistically significant effect on cardiorespiratory variables. These limited data suggest no evidence why both agents should not be included in a preoperative medication protocol for healthy horses but do not exclude the possibility of interactions occurring in a larger population.