Recombining your way out of trouble: the genetic architecture of hybrid fitness under environmental stress

Hybridization between species is a fundamental evolutionary force that can both promote and delay adaptation. There is a deficit in our understanding of the genetic basis of hybrid fitness, especially in non-domesticated organisms. We also know little about how hybrid fitness changes as a function of environmental stress. Here, we made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species, exposed populations to ten toxins, and sequenced the most resilient hybrids on low coverage using ddRADseq. We expected to find strong negative epistasis and heterozygote advantage in the hybrid genomes. We investigated three aspects of hybridness: 1) hybridity, 2) interspecific heterozygosity, and 3) epistasis (positive or negative associations between non-homologous chromosomes). Linear mixed effect models revealed strong genotype-by-environment interactions with many chromosomes and chromosomal interactions showing species-biased content depending on the environment. Against our predictions, we found extensive selection against heterozygosity such that homozygous allelic combinations from the same species were strongly overrepresented in an otherwise hybrid genomic background. We also observed multiple cases of positive epistasis between chromosomes from opposite species, confirmed by epistasis- and selection-free simulations, which is surprising given the large divergence of the parental species (~15% genome-wide). Together, these results suggest that stress-resilient hybrid genomes can be assembled from the best features of both parents, without paying high costs of negative epistasis across large evolutionary distances. Our findings illustrate the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of hybrid populations

Particle alignments and shape change in 66^{66}Ge and 68^{68}Ge

The structure of the $N \approx Z$ nuclei $^{66}$Ge and $^{68}$Ge is studied by the shell model on a spherical basis. The calculations with an extended $P+QQ$ Hamiltonian in the configuration space ($2p_{3/2}$, $1f_{5/2}$, $2p_{1/2}$, $1g_{9/2}$) succeed in reproducing experimental energy levels, moments of inertia and $Q$ moments in Ge isotopes. Using the reliable wave functions, this paper investigates particle alignments and nuclear shapes in $^{66}$Ge and $^{68}$Ge. It is shown that structural changes in the four sequences of the positive- and negative-parity yrast states with even $J$ and odd $J$ are caused by various types of particle alignments in the $g_{9/2}$ orbit. The nuclear shape is investigated by calculating spectroscopic $Q$ moments of the first and second $2^+$ states, and moreover the triaxiality is examined by the constrained Hatree-Fock method. The changes of the first band crossing and the nuclear deformation depending on the neutron number are discussed.Comment: 18 pages, 21 figures; submitted to Phys. Rev.

Mechanisms of C5a and C3a complement fragment-induced [Ca2+]i signaling in mouse microglia

Microglial cells are activated in response to brain insults; the mechanisms of this process are not yet understood. One of the important signaling mechanisms that might be involved in microglia activation is related to changes in the intracellular calcium concentration ([Ca2+]i). Using fluo-3 microfluorimetry, we have found that external application of the complement fragment C5a (4-10 nM) induced [Ca2+]i elevation in microglial cells in situ in corpus callosum slices. Similarly, application of complement fragments C5a (0.1-10.0 nM) or C3a (100 nM) generates biphasic [Ca2+]i transients composed of an initial peak followed by a plateau in cultured microglia. Incubation of microglial cells for 30 min with pertussis toxin (PTX; 1 microgram/ml) inhibited both C5a- and C3a-triggered [Ca2+]i responses, suggesting the involvement of PTX-sensitive G-proteins in the signal transduction chain. Removal of Ca2+ ions from the extracellular solution eliminated the plateau phase and limited the response to the initial peak. The restoration of the extracellular Ca2+ concentration within 30-60 sec after the beginning of the complement fragment-induced [Ca2+]i elevation led to the recovery of the plateau phase. Inhibition of the endoplasmic reticulum Ca2+ pumps with 500 nM thapsigargin transiently increased the [Ca2+]i and blocked the [Ca2+]i signals in response to subsequent complement fragment application. Our data suggest that complement factors induce [Ca2+]i responses by Ca2+ release from internal pools and subsequent activation of Ca2+ entry controlled by the filling state of the intracellular Ca2+ depots

Recombining your way out of trouble: The genetic architecture of hybrid fitness under environmental stress

Hybridization between species can either promote or impede adaptation. But there is a deficit in our understanding of the genetic basis of hybrid fitness, especially in non-domesticated organisms, and when populations are facing environmental stress. We made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species. We exposed populations to ten toxins and sequenced the most resilient hybrids on low coverage using ddRADseq to investigate four aspects of their genomes: 1) hybridity, 2) interspecific heterozygosity, 3) epistasis (positive or negative associations between non-homologous chromosomes) and 4) ploidy. We used linear mixed effect models and simulations to measure to which extent hybrid genome composition was contingent on the environment. Genomes grown in different environments varied in every aspect of hybridness measured, revealing strong genotype-environment interactions. We also found selection against heterozygosity or directional selection for one of the parental alleles, with larger fitness of genomes carrying more homozygous allelic combinations in an otherwise hybrid genomic background. In addition, individual chromosomes and chromosomal interactions showed significant species biases and pervasive aneuploidies. Against our expectations, we observed multiple beneficial, opposite-species chromosome associations, confirmed by epistasis- and selection-free computer simulations, which is surprising given the large divergence of parental genomes (∼15%). Together, these results suggest that successful, stress-resilient hybrid genomes can be assembled from the best features of both parents without paying high costs of negative epistasis. This illustrates the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of genetically diverse hybrid populations

Novel π-Extended Quinazoline-Ferrocene Conjugates: Synthesis, Structure, and Redox Behavior

Novel ferrocene conjugates of tricyclic quinazoline derivatives are prepared by condensation of active C-6 methylene groups of mackinazolinones with ferrocenecarbaldehyde. Following this route the conjugated parent alkaloid as well as derivatives with nitro, amino, and alkanoylamino groups at C-2 were attached at the ferrocene moiety, thereby significantly extending the delocalized π system. In addition, the parent compound was subjected to the reaction with ferrocene-1,1'-dicarbaldehyde, giving rise to the symmetrical and unsymmetrical double condensation products – 1,1'-disubstituted ferrocene derivatives, which bear two alkaloid substituents. Some of the compounds obtained were subjected to X-ray crystallographic analyses. The influence of the substituents at C-2 through the extended conjugated π system on the iron atom is reflected by results of cyclovoltammetric measurements

Compressive strength of interbody cages in the lumbar spine: the effect of cage shape, posterior instrumentation and bone density

One goal of interbody fusion is to increase the height of the degenerated disc space. Interbody cages in particular have been promoted with the claim that they can maintain the disc space better than other methods. There are many factors that can affect the disc height maintenance, including graft or cage design, the quality of the surrounding bone and the presence of supplementary posterior fixation. The present study is an in vitro biomechanical investigation of the compressive behaviour of three different interbody cage designs in a human cadaveric model. The effect of bone density and posterior instrumentation were assessed. Thirty-six lumbar functional spinal units were instrumented with one of three interbody cages: (1) a porous titanium implant with endplate fit (Stratec), (2) a porous, rectangular carbon-fibre implant (Brantigan) and (3) a porous, cylindrical threaded implant (Ray). Posterior instrumentation (USS) was applied to half of the specimens. All specimens were subjected to axial compression displacement until failure. Correlations between both the failure load and the load at 3 mm displacement with the bone density measurements were observed. Neither the cage design nor the presence of posterior instrumentation had a significant effect on the failure load. The loads at 3 mm were slightly less for the Stratec cage, implying lower axial stiffness, but were not different with posterior instrumentation. The large range of observed failure loads overlaps the potential in vivo compressive loads, implying that failure of the bone-implant interface may occur clinically. Preoperative measurements of bone density may be an effective tool to predict settling around interbody cages

Management options for restoring estuarine dynamics and implications for ecosystems: a quantitative approach for the Southwest Delta in the Netherlands

The Delta Works, a series of dams and barriers constructed in the 1960's–1980's changed the estuarine landscape of the Rhine-Meuse-Scheldt delta (SW Netherlands) into more stagnant and disengaged freshwater, brackish water or saltwater lakes. The remaining tidal systems were adapted by building a storm surge barrier in the Oosterschelde and dike reinforcement works along the Westerschelde. The Delta Works brought protection against flooding, but at the same time resulted in environmental and socio-economic problems, such as degradation of ecological quality and ecosystem functioning, disruption of fish migration routes, water and sediment quality problems.In this study we explore in an integrated, quantitative way the consequences of a number of management options for the Southwest Delta and their implications for the occurrence and distribution of aquatic and estuarine habitats, considering the mutual coherence between the water basins. Five scenarios were evaluated using a 1D hydraulic, water quality and primary production numerical model and GIS habitat mapping. Scenarios vary from small-scale interventions, such as changes in day-to-day management of hydraulic infrastructures or creation of small inlets in dams, feasible in the short term, to restoration of an open delta by removing dams and barriers, as a long term potential. We evaluate the outcomes in relation to the restoration of estuarine dynamics, as this is in policy plans proposed as a generic solution for the current ecological and environmental problems. Net water flow rates show more complex patterns when connectivity between water basins is increased and when sluice management is less strict. Estuarine transition zones and fish migration routes are partly restored, but only fully develop when basins are in open connection with each other. Area of intertidal habitats, tidal flats and tidal marshes, increases in each scenario, ranging between 7 and 83%, 1–56%, and 8–100% respectively, depending on scenario. Large scale infrastructural adaptations are needed to restore estuarine dynamics at large scale.The use of a 1D numerical model allowed to quantify the effect of different management measures for all water basins simultaneously, but also has its limitations. The model does not resolve more complex processes such as vertical mixing and morphodynamic changes. This requires expert judgment and more detailed 3D modelling

Nondegenerate Fermions in the Background of the Sphaleron Barrier

We consider level crossing in the background of the sphaleron barrier for nondegenerate fermions. The mass splitting within the fermion doublets allows only for an axially symmetric ansatz for the fermion fields. In the background of the sphaleron we solve the partial differential equations for the fermion functions. We find little angular dependence for our choice of ansatz. We therefore propose a good approximate ansatz with radial functions only. We generalize this approximate ansatz with radial functions only to fermions in the background of the sphaleron barrier and argue, that it is a good approximation there, too.Comment: LATEX, 20 pages, 11 figure

On a Covariant Determination of Mass Scales in Warped Backgrounds

We propose a method of determining masses in brane scenarios which is independent of coordinate transformations. We apply our method to the scenario of Randall and Sundrum (RS) with two branes, which provides a solution to the hierarchy problem. The core of our proposal is the use of covariant equations and expressing all coordinate quantities in terms of invariant distances. In the RS model we find that massive brane fields propagate proper distances inversely proportional to masses that are not exponentially suppressed. The hierarchy between the gravitational and weak interactions is nevertheless preserved on the visible brane due to suppression of gravitational interactions on that brane. The towers of Kaluza-Klein states for bulk fields are observed to have different spacings on different branes when all masses are measured in units of the fundamental scale. Ratios of masses on each brane are the same in our covariant and the standard interpretations. Since masses of brane fields are not exponentiated, the fundamental scale of higher-dimensional gravity must be of the order of the weak scale.Comment: 14 page