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.     

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.     

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.     

A slowly progressive retinopathy in the Shetland Sheepdog

Objective To describe a slowly progressive retinopathy (SPR) in Shetland Sheepdogs. Animals Forty adult Shetlands Sheepdogs with ophthalmoscopic signs of SPR and six normal Shetland Sheepdogs were included in the study. Procedure Ophthalmic examination including slit‐lamp biomicroscopy and ophthalmoscopy was performed in all dogs. Electroretinograms and obstacle course‐test were performed in 13 affected and 6 normal dogs. The SPR dogs were subdivided into two groups according to their dark‐adapted b‐wave amplitudes. SPR1‐dogs had ophthalmoscopic signs of SPR, but normal dark‐adapted b‐wave amplitudes. Dogs with both ophthalmoscopic signs and subnormal, dark‐adapted b‐wave amplitudes were assigned to group SPR2. Eyes from two SPR2 dogs were obtained for microscopic examination. Results The ophthalmoscopic changes included bilateral, symmetrical, greyish discoloration in the peripheral tapetal fundus with normal or marginally attenuated vessels. Repeated examination showed that the ophthalmoscopic changes slowly spread across the central parts of the tapetal fundus, but did not progress to obvious neuroretinal thinning presenting as tapetal hyper‐reflectivity. The dogs did not appear seriously visually impaired. SPR2 showed significantly reduced b‐wave amplitudes throughout dark‐adaptation. Microscopy showed thinning of the outer nuclear layer and abnormal appearance of rod and cone outer segments. Testing for the progressive rod–cone degeneration ( prcd )‐mutation in three dogs with SPR was negative. Conclusion Slowly progressive retinopathy is a generalized rod–cone degeneration that on ophthalmoscopy looks similar to early stages of progressive retinal atrophy. The ophthalmoscopic findings are slowly progressive without tapetal hyper‐reflectivity. Visual impairment is not obvious and the electroretinogram is more subtly altered than in progressive retinal atrophy. The etiology remains unclear. SPR is not caused by the prcd‐mutation.     

Predictions of soil water and crop growth dynamics using the agroecosystem models THESEUS and OPUS

The agroecosystem models THESEUS and OPUS were tested with data obtained from three agricultural experimental field plots on sandy soils without groundwater located at the moraine landscape in East Brandenburg, Germany. At each of these plots, a separate agricultural management practice was applied. Measurements of soil water contents, pressure heads, above‐ground crop biomass, and crop yield from these three plots were compared with the corresponding simulation results of both models. The comparisons of simulated with measured outputs were analyzed using the modeling‐efficiency index IA. According to these analyses, both models simulated adequately the time courses of volumetric soil water contents and above‐ground crop biomass, but the time courses of pressure heads were predicted with a lower quality by both models. As for the pressure heads, the yields simulated with both models showed greater discrepancies in comparison with the observed ones. This indicates the need of a site‐specific parameter calibration of the crop‐growth modules, especially for that included in OPUS .     

Quantitative und qualitative Veränderungen im A-Horizont von Sandböden nach Umwandlung von Dauergrünland in Ackerland

Quantitative and qualitative changes in soil properties of A- horizons of sandy soils caused by conversion of grassland to arable land Changes in physical soil properties and in soil organic matter of the A-horizons due to the conversion of permanent grassland to arable land are quantified and described as a function of time for sandy soils. The study was carried out in an area northeast of Hannover. A decrease of about 100 t/ha C_org (- 57%), 5 – 6 t/ha N_org (- 58%) and 1 t/ha S_t (- 58%) was measured for a period of 2 – 4 years after grassland conversion. Thereby the quality of the soil organic matter remains unchanged (no changes of the C/N ratio and of the distribution of N_org in 5 N-fractions). However, an increase of soil bulk density from 1.0 to 1.3 g/cm³ and a decrease of total pore volume from 0.59 to 0.47 were observed. The fast mineralization of soil organic matter in the A-horizon following the conversion of grassland soils results in a temporary heavily increased nitrate input into the groundwater. Furthermore mineralization and leaching of nitrate and sulfate induces an acidification push in the soil by a proton release in the order of 350 keq/ha during a 2 – 4 years period. However, this proton production is compensated quantitatively by several applications of lime or marl by farmers and by the buffering of bases cations released from mineralized soil organic matter.     

Nitrogen supply to cereals and sugar beet by mass flow and diffusion on a silty loam soil

In a four-year field study the nitrogen supply by mass flow and diffusion to cereals (spring wheat, winter barley, winter wheat) and sugar beet was investigated on a silty loam soil. The rates of water withdrawal, N mass flow and N diffusion were determined as a function of soil depth and time. The contribution to the N supply to roots by mass flow was 15–33% and mainly confined to the topsoil layer. The N supply by diffusion plays with 67–85% the dominant role, particularly in deeper rootzone layers. During periods of high N uptake, the N inflow (per unit root length and time) ranges between 0.26–2.07 μmol/(m · d) at various rootzone layers for cereal, and between 3.80–8.98 μmol/(m · d) for sugar beet, respectively. As a consequence of the high proportion of diffusion supply, at harvest the whole rootzone was largely depleted of nitrate. Thus, nitrate leaching losses during winter were small, the average nitrate concentration of the yearly groundwater recharge being only 7.9 mg N/l. Additionally, some results on supply of K, Ca, Mg and Cl for spring wheat and sugar beet are given. Diffusion supply prevails for K, and in the case of sugar beet for Mg and Cl also. Mass flow of Ca exceeded uptake considerably.