The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating

WIN 51711 and WIN 52084 are structurally related, antiviral compounds that inhibit the replication of rhino (common cold) viruses and related picornaviruses. They prevent the pH-mediated uncoating of the viral RNA. The compounds consist of a 3-methylisoxazole group that inserts itself into the hydrophobic interior of the VP1 beta-barrel, a connecting seven-membered aliphatic chain, and a 4-oxazolinylphenoxy group (OP) that covers the entrance to an ion channel in the floor of the "canyon." Viral disassembly may be inhibited by preventing the collapse of the VP1 hydrophobic pocket or by blocking the flow of ions into the virus interior.     

Involvement of mammalian Mus81 in genome integrity and tumor suppression

Mus81-Eme1 endonuclease has been implicated in the rescue of stalled replication forks and the resolution of meiotic recombination intermediates in yeast. We used gene targeting to study the physiological requirements of Mus81 in mammals. Mus81-/- mice are viable and fertile, which indicates that mammalian Mus81 is not essential for recombination processes associated with meiosis. Mus81-deficient mice and cells were hypersensitive to the DNA cross-linking agent mitomycin C but not to gamma-irradiation. Remarkably, both homozygous Mus81-/- and heterozygous Mus81+/- mice exhibited a similar susceptibility to spontaneous chromosomal damage and a profound and equivalent predisposition to lymphomas and other cancers. These studies demonstrate a critical role for the proper biallelic expression of the mammalian Mus81 in the maintenance of genomic integrity and tumor suppression.     

A conserved family of enzymes that phosphorylate inositol hexakisphosphate

Inositol pyrophosphates are a diverse group of high-energy signaling molecules whose cellular roles remain an active area of study. We report a previously uncharacterized class of inositol pyrophosphate synthase and find it is identical to yeast Vip1 and Asp1 proteins, regulators of actin-related protein-2/3 (ARP 2/3) complexes. Vip1 and Asp1 acted as enzymes that encode inositol hexakisphosphate (IP6) and inositol heptakisphosphate (IP7) kinase activities. Alterations in kinase activity led to defects in cell growth, morphology, and interactions with ARP complex members. The functionality of Asp1 and Vip1 may provide cells with increased signaling capacity through metabolism of IP6.     

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.     

Sexual selection can resolve sex-linked sexual antagonism

Sexual selection is a potent evolutionary force. However, very few models have considered the evolution of female preferences for traits expressed in both sexes. Here we explore how female preferences coevolve with sexually antagonistic traits, which involve alleles that are beneficial to one sex but harmful to the other. We show that with a sexually antagonistic trait on the X chromosome (males XY, females XX), females evolve to prefer mates carrying alleles beneficial to daughters. In contrast, with a Z-linked trait (males ZZ, females ZW), females more often evolve mating preferences for mates carrying alleles beneficial to sons (that is, flashy displays).     

Imaging nucleophilic substitution dynamics

Anion-molecule nucleophilic substitution (S(N)2) reactions are known for their rich reaction dynamics, caused by a complex potential energy surface with a submerged barrier and by weak coupling of the relevant rotational-vibrational quantum states. The dynamics of the S(N)2 reaction of Cl- + CH3I were uncovered in detail by using crossed molecular beam imaging. As a function of the collision energy, the transition from a complex-mediated reaction mechanism to direct backward scattering of the I- product was observed experimentally. Chemical dynamics calculations were performed that explain the observed energy transfer and reveal an indirect roundabout reaction mechanism involving CH3 rotation.     

Traces of human migrations in Helicobacter pylori populations

Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.     

Spatial and temporal genetic variation of Drosophila suzukii in Germany

Native to Southeast Asia, the spotted wing drosophila (SWD), Drosophila suzukii Matsumura, rapidly invaded America and Europe in the past 20 years. As a crop pest of soft-skinned fruits with a wide range of host plants, it threatens the fruit industry worldwide, causing enormous economic losses. To control this invasive pest species, an understanding of its population dynamics and structure is necessary. Here, we report the population genetics and development of SWD in Germany from 2017–19 using microsatellite markers over 11 different sample sites. It is the first study that examines SWD’s genetic changes over 3 years compared to multiple international SWD laboratory strains. Results show that SWD populations in Germany are highly homogenous without differences between populations or years, which indicates that populations are well adapted, migrate freely, and multiple invasions from outside Germany either did not take place or are negligible. Such high genetic variability and migration between populations could allow for a fast establishment of the pest species. This is especially problematic with regard to the ongoing spread of this invasive species and could bear a potential for developing pesticide resistance, which could increase the impact of the SWD further in the future.

     

Stress steroid levels and the short-term impact of routine dehorning in female southern white rhinoceroses (Ceratotherium simum simum)

Rhinoceros populations in Africa are under severe threat as a result of surging poaching rates and risk-mitigation strategies are continuously adapted in an attempt to ensure the survival of the species. This study compared faecal glucocorticoid metabolite (fGCM) levels of two age classes of limited free-ranging female white rhinos with fGCM levels of adult free-ranging female white rhinos. Subsequently, fGCM alterations in the limited free-ranging animals were monitored following routine dehorning as a measure of the animals’ short-term physiological stress response. Baseline fGCM levels differed significantly between tested groups, with both free-ranging and limited free-ranging adult animals showing significantly higher fGCM levels compared with limited free-ranging juvenile females. In contrast, baseline fGCM levels did not differ significantly between limited free-ranging and free-ranging adult individuals. Routine dehorning procedures resulted in a short-term stress response expressed by a significant increase in fGCM levels 48 h post-dehorning, with stress steroid levels returning to pre-dehorning concentrations 72 h after the procedure.