Macrocyclic inhibitors of 3C and 3C-like proteases of picornavirus,norovirus, and coronavirus

The design, synthesis, and in vitro evaluation of the first macrocyclic inhibitor of 3C and 3C-like proteases of picornavirus, norovirus, and coronavirus are reported. The in vitro inhibitory activity (50% effective concentration) of the macrocyclic inhibitor toward enterovirus 3C protease (CVB3 Nancy strain), and coronavirus (SARS-CoV) and norovirus 3C-like proteases, was determined to be 1.8, 15.5 and 5.1 μM, respectively.     

Potent inhibition of norovirus by dipeptidyl α-hydroxyphosphonate transition state mimics

The design, synthesis, and evaluation of a series of dipeptidyl α-hydroxyphosphonates is reported. The synthesized compounds displayed high anti-norovirus activity in a cell-based replicon system, as well as high enzyme selectivity.     

Tropical forest recovery from logging: a 24 year silvicultural experiment from Central Africa

Large areas of African moist forests are being logged in the context of supposedly sustainable management plans. It remains however controversial whether harvesting a few trees per hectare can be maintained in the long term while preserving other forest services as well. We used a unique 24 year silvicultural experiment, encompassing 10 4 ha plots established in the Central African Republic, to assess the effect of disturbance linked to logging (two to nine trees ha⁻¹ greater than or equal to 80 cm DBH) and thinning (11–41 trees ha⁻¹ greater than or equal to 50 cm DBH) on the structure and dynamics of the forest. Before silvicultural treatments, above-ground biomass (AGB) and timber stock (i.e. the volume of commercial trees greater than or equal to 80 cm DBH) in the plots amounted 374.5 ± 58.2 Mg ha⁻¹ and 79.7 ± 45.9 m³ ha⁻¹, respectively. We found that (i) natural control forest was increasing in AGB (2.58 ± 1.73 Mg dry mass ha⁻¹ yr⁻¹) and decreasing in timber stock (−0.33 ± 1.57 m³ ha⁻¹ yr⁻¹); (ii) the AGB recovered very quickly after logging and thinning, at a rate proportional to the disturbance intensity (mean recovery after 24 years: 144%). Compared with controls, the gain almost doubled in the logged plots (4.82 ± 1.22 Mg ha⁻¹ yr⁻¹) and tripled in the logged + thinned plots (8.03 ± 1.41 Mg ha⁻¹ yr⁻¹); (iii) the timber stock recovered slowly (mean recovery after 24 years: 41%), at a rate of 0.75 ± 0.51 m³ ha⁻¹ yr⁻¹ in the logged plots, and 0.81 ± 0.74 m³ ha⁻¹ yr⁻¹ in the logged + thinned plots. Although thinning significantly increased the gain in biomass, it had no effect on the gain in timber stock. However, thinning did foster the growth and survival of small- and medium-sized timber trees and should have a positive effect over the next felling cycle.     

Long‐distance dispersal maximizes evolutionary potential during rapid geographic range expansion

Conventional wisdom predicts that sequential founder events will cause genetic diversity to erode in species with expanding geographic ranges, limiting evolutionary potential at the range margin. Here, we show that invasive European starlings (Sturnus vulgaris) in South Africa preserve genetic diversity during range expansion, possibly as a result of frequent long‐distance dispersal events. We further show that unfavourable environmental conditions trigger enhanced dispersal, as indicated by signatures of selection detected across the expanding range. This brings genetic variation to the expansion front, counterbalancing the cumulative effects of sequential founding events and optimizing standing genetic diversity and thus evolutionary potential at range margins during spread. Therefore, dispersal strategies should be highlighted as key determinants of the ecological and evolutionary performances of species in novel environments and in response to global environmental change.     

Biotic interactions drive species occurrence and richness in dynamic beach environments

Biotic interactions are predicted to have the strongest influence on species assemblages in extreme environments. We therefore test the hypothesis that in abiotically-severe beaches plant–plant interactions, specifically facilitation, are important relative to abiotic conditions. This hypothesis is tested by assessing the influence of dominant vascular plant species on the fine-scale occurrence and richness of vascular and cryptogam species using a unique dataset of boreal beaches along the Finnish Baltic Sea, characterized by strong post-glacial land uplift and large environmental gradients. We studied three different levels of vegetation patterns across a broad geographical scale; individual species, functional groups and the entire community. Results showed that dominant vascular species strongly drive species occurrence and richness in dynamic beach environments, with some species having an influence similar to that of key abiotic variables. In contrast to expectations, facilitative effects did not dominate in these harsh environments. Instead, the outcomes of biotic interactions were species-specific, and also differed between vascular and cryptogam species, with the former group most strongly influenced by a pioneer species and the latter by a late succession generalist. Our study highlights the importance of incorporating biotic interaction effects into models of multiple vegetation properties and cautions against overly simplistic generalizations to describe relatively idiosyncratic interaction effects.     

Why join groups? Lessons from parasite‐manipulated Artemia

Grouping behaviours (e.g. schooling, shoaling and swarming) are commonly explicated through adaptive hypotheses such as protection against predation, access to mates or improved foraging. However, the hypothesis that aggregation can result from manipulation by parasites to increase their transmission has never been demonstrated. We investigated this hypothesis using natural populations of two crustacean hosts (Artemia franciscana and Artemia parthenogenetica) infected with one cestode and two microsporidian parasites. We found that swarming propensity increased in cestode‐infected hosts and that red colour intensity was higher in swarming compared with non‐swarming infected hosts. These effects likely result in increased cestode transmission to its final avian host. Furthermore, we found that microsporidian‐infected hosts had both increased swarming propensity and surfacing behaviour. Finally, we demonstrated using experimental infections that these concurrent manipulations result in increased spore transmission to new hosts. Hence, this study suggests that parasites can play a prominent role in host grouping behaviours.     

Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy

Mutations in POLR3A encoding the largest subunit of RNA polymerase III (Pol III) were found to be responsible for the majority of cases presenting with three clinically overlapping hypomyelinating leukodystrophy phenotypes. We uncovered in three cases without POLR3A mutation recessive mutations in POLR3B, which codes for the second largest subunit of Pol III. Mutations in genes coding for Pol III subunits are a major cause of childhood-onset hypomyelinating leukodystrophies with prominent cerebellar dysfunction, oligodontia, and hypogonadotropic hypogonadism.     

A unified approach to the estimation and interpretation of resistance costs in plants

Plants exhibit a number of adaptive defence traits that endow resistance to past and current abiotic and biotic stresses. It is generally accepted that these adaptations will incur a cost when plants are not challenged by the stress to which they have become adapted--the so-called 'cost of adaptation'. The need to minimise or account for allelic variation at other fitness-related loci (genetic background control) is frequently overlooked when assessing resistance costs associated with plant defence traits. We provide a synthesis of the various experimental protocols that accomplish this essential requirement. We also differentiate those methods that enable the identification of the trait-specific or mechanistic basis of costs (direct methods) from those that provide an estimate of the impact of costs by examining the evolutionary trajectories of resistance allele frequencies at the population level (indirect methods). The advantages and disadvantages for each proposed experimental design are discussed. We conclude that plant resistance systems provide an ideal model to address fundamental questions about the cost of adaptation to stress. We also propose some ways to expand the scope of future studies for further fundamental and applied insight into the significance of adaptation costs.