Neurally Mediated Airway Constriction in Human and Other Species: A Comparative Study Using Precision-Cut Lung Slices (PCLS)

The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS) respond to electric field stimulation (EFS) and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM) caused bronchoconstriction in human (4 from 7) and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC). However, this effect was notably smaller in human responder (30±7.1%) than in guinea pig (79±5.1%) PCLS. The transient receptor potential (TRP) channel blockers {"type":"entrez-protein","attrs":{"text":"SKF96365","term_id":"1156357400","term_text":"SKF96365"}}SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.     

COP9 signalosome subunit 3 is essential for maintenance of cell proliferation in the mouse embryonic epiblast

Csn3 (Cops3) maps to the mouse chromosome 11 region syntenic to the common deletion interval for the Smith-Magenis syndrome, a contiguous gene deletion syndrome. It encodes the third subunit of an eight-subunit protein complex, the COP9 signalosome (CSN), which controls a wide variety of molecules of different functions. Mutants of this complex caused lethality at early development of both plants and Drosophila melanogaster. CSN function in vivo in mammals is unknown. We disrupted the murine Csn3 gene in three independent ways with insertional vectors, including constructing a approximately 3-Mb inversion chromosome. The heterozygous mice appeared normal, although the protein level was reduced. Csn3(-/-) embryos arrested after 5.5 days postcoitum (dpc) and resorbed by 8.5 dpc. Mutant embryos form an abnormal egg cylinder which does not gastrulate. They have reduced numbers of epiblast cells, mainly due to increased cell death. In the Csn3(-/-) mice, subunit 8 of the COP9 complex was not detected by immunohistochemical techniques, suggesting that the absence of Csn3 may disrupt the entire COP9 complex. Therefore, Csn3 is important for maintaining the integrity of the COP9 signalosome and is crucial to maintain the survival of epiblast cells and thus the development of the postimplantation embryo in mice.     

Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance

Contiguous gene syndromes (CGS) are a group of disorders associated with chromosomal rearrangements of which the phenotype is thought to result from altered copy numbers of physically linked dosage-sensitive genes. Smith-Magenis syndrome (SMS) is a CGS associated with a deletion within band p11.2 of chromosome 17. Recently, patients harboring the predicted reciprocal duplication product [dup(17)(p11.2p11.2)] have been described as having a relatively mild phenotype. By chromosomal engineering, we created rearranged chromosomes carrying the deletion [Df(11)17] or duplication [Dp(11)17] of the syntenic region on mouse chromosome 11 that spans the genomic interval commonly deleted in SMS patients. Df(11)17/+ mice exhibit craniofacial abnormalities, seizures, marked obesity, and male-specific reduced fertility. Dp(11)17/+ animals are underweight and do not have seizures, craniofacial abnormalities, or reduced fertility. Examination of Df(11)17/Dp(11)17 animals suggests that most of the observed phenotypes result from gene dosage effects. Our murine models represent a powerful tool to analyze the consequences of gene dosage imbalance in this genomic interval and to investigate the molecular genetic bases of both SMS and dup(17)(p11.2p11.2).     

Dynamic effects of ground-layer plant communities on beetles in a fragmented farming landscape

Vegetation effects on arthropods are well recognized, but it is unclear how different vegetation attributes might influence arthropod assemblages across mixed-agricultural landscapes. Understanding how plant communities influence arthropods under different habitat and seasonal contexts can identify vegetation management options for arthropod biodiversity. We examined relationships between vegetation structure, plant species richness and plant species composition, and the diversity and composition of beetles in different habitats and time periods. We asked: (1) What is the relative importance of plant species richness, vegetation structure and plant composition in explaining beetle species richness, activity-density and composition? (2) How do plant-beetle relationships vary between different habitats over time? We sampled beetles using pitfall traps and surveyed vegetation in three habitats (woodland, farmland, their edges) during peak crop growth in spring and post-harvest in summer. Plant composition better predicted beetle composition than vegetation structure. Both plant richness and vegetation structure significantly and positively affected beetle activity-density. The influence of all vegetation attributes often varied in strength and direction between habitats and seasons for all trophic groups. The variable nature of plant-beetle relationships suggests that vegetation management could be targeted at specific habitats and time periods to maximize positive outcomes for beetle diversity. In particular, management that promotes plant richness at edges, and promotes herbaceous cover during summer, can support beetle diversity. Conserving ground cover in all habitats may improve activity-density of all beetle trophic groups. The impacts of existing weed control strategies in Australian crop margins on arthropod biodiversity require further study.     

Multi‐trophic guilds respond differently to changing elevation in a subtropical forest

Negative relationships between species richness and elevation are common and attributed to changes in single environmental properties associated to elevation, such as temperature and habitat area. However, research has lacked taxonomic breadth and comprehensive elevation studies that consider multiple groups from different trophic levels are rare. We thus analysed 24 groups of plants, arthropods, and microorganisms grouped into six trophic guilds (predators, detritivores, herbivores, plants, bacteria and fungi) along a relatively short elevational gradient (~600 m) in a subtropical forest in south‐east China. The total species richness of all organisms was not related to elevation, nor was the richness of plants, herbivores or microorganisms. However, species richness and abundance in two major trophic guilds of arthropods changed with elevation, which was mediated by changes in elevation‐associated habitat properties. Specifically, deadwood mass increased with elevation, which increased detritivore richness indirectly via detritivore abundance, thus supporting the ‘more individuals hypothesis’. In contrast, lower predator richness at higher elevations was directly related to lower mean temperatures, which had no effect on abundance. Our study demonstrates that even along relatively short gradients, elevation can have strong direct and abundance‐mediated effects on species richness, but with effects varying from positive to negative signs depending on local resource availability and the characteristics of groups or trophic guilds. If elevation positively influences local environmental properties that benefit a given group, richness can increase towards higher elevations. Thus, the effect of global change in mountainous regions should be evaluated within the local environmental context using multi‐taxon approaches.     

Temperature‐driven changes in the diet preference of omnivorous copepods: no more meat when it's hot? A response to Winder et al.

The study of environmental impact on feeding preferences of omnivores is a rapidly growing field. Here, we show that the criticism put forward in a comment on our original study is largely unfounded.     

Differential Sensitivity of Differentiated Epithelial Cells to Respiratory Viruses Reveals Different Viral Strategies of Host Infection

To address the initiation of virus infection in the respiratory tract, we established two culture systems for differentiated bovine airway epithelial cells (BAEC). Filter-grown BAEC differentiated under air-liquid interface (ALI) conditions to generate a pseudo-stratified mucociliary epithelium. Alternatively, precision-cut lung slices (PCLS) from the bovine airways were generated that retained the original composition and distribution of differentiated epithelial cells. With both systems, epithelial cells were readily infected by bovine parainfluenza virus 3 (BPIV3). Ciliated cells were the most prominent cell type affected by BPIV3. Surprisingly, differentiated BAEC were resistant to infection by bovine respiratory syncytial virus (BRSV), when the virus was applied at the same multiplicity of infection that was sufficient for infection by BPIV3. In the case of PCLS, infection by BRSV was observed in cells located in lower cell layers but not in epithelial cells facing the lumen of the airways. The identity of the infected cells could not be determined because of a lack of specific antibodies. Increasing the virus titer 30-fold resulted in infection of the ALI cultures of BAEC, whereas in PCLS the ciliated epithelium was still refractory to infection by BRSV. These results indicate that differentiated BAEC are readily infected by BPIV3 but rather resistant to infection by BRSV. Disease caused by BRSV may require that calves encounter environmental stimuli that render BAEC susceptible to infection.