EGL-20/Wnt and MAB-5/Hox Act Sequentially to Inhibit Anterior Migration of Neuroblasts in C. elegans

Directed neuroblast and neuronal migration is important in the proper development of nervous systems. In C. elegans the bilateral Q neuroblasts QR (on the right) and QL (on the left) undergo an identical pattern of cell division and differentiation but migrate in opposite directions (QR and descendants anteriorly and QL and descendants posteriorly). EGL-20/ Wnt, via canonical Wnt signaling, drives the expression of MAB-5/Hox in QL but not QR. MAB-5 acts as a determinant of posterior migration, and mab-5 and egl-20 mutants display anterior QL descendant migrations. Here we analyze the behaviors of QR and QL descendants as they begin their anterior and posterior migrations, and the effects of EGL-20 and MAB-5 on these behaviors. The anterior and posterior daughters of QR (QR.a/p) after the first division immediately polarize and begin anterior migration, whereas QL.a/p remain rounded and non-migratory. After ~1 hour, QL.a migrates posteriorly over QL.p. We find that in egl-20/Wnt, bar-1/β-catenin, and mab-5/Hox mutants, QL.a/p polarize and migrate anteriorly, indicating that these molecules normally inhibit anterior migration of QL.a/p. In egl-20/Wnt mutants, QL.a/p immediately polarize and begin migration, whereas in bar-1/β- catenin and mab-5/Hox, the cells transiently retain a rounded, non-migratory morphology before anterior migration. Thus, EGL-20/Wnt mediates an acute inhibition of anterior migration independently of BAR-1/β-catenin and MAB-5/Hox, and a later, possible transcriptional response mediated by BAR-1/β-catenin and MAB-5/Hox. In addition to inhibiting anterior migration, MAB-5/Hox also cell-autonomously promotes posterior migration of QL.a (and QR.a in a mab-5 gain-of-function)

Universal point contact resistance between thin-film superconductors

A system comprising two superconducting thin films connected by a point contact is considered. The contact resistance is calculated as a function of temperature and film geometry, and is found to vanish rapidly with temperature, according to a universal, nearly activated form, becoming strictly zero only at zero temperature. At the lowest temperatures, the activation barrier is set primarily by the superfluid stiffness in the films, and displays only a weak (i.e., logarithmic) temperature dependence. The Josephson effect is thus destroyed, albeit only weakly, as a consequence of the power-law-correlated superconducting fluctuations present in the films below the Berezinskii-Kosterlitz-Thouless transition temperature. The behavior of the resistance is discussed, both in various limiting regimes and as it crosses over between these regimes. Details are presented of a minimal model of the films and the contact, and of the calculation of the resistance. A formulation in terms of quantum phase-slip events is employed, which is natural and effective in the limit of a good contact. However, it is also shown to be effective even when the contact is poor and is, indeed, indispensable, as the system always behaves as if it were in the good-contact limit at low enough temperature. A simple mechanical analogy is introduced to provide some heuristic understanding of the nearly-activated temperature dependence of the resistance. Prospects for experimental tests of the predicted behavior are discussed, and numerical estimates relevant to anticipated experimental settings are provided.Comment: 29 pages (single column format), 7 figure

Heterogeneous histories of recombination suppression on stickleback sex chromosomes

How consistent are the evolutionary trajectories of sex chromosomes shortly after they form? Insights into the evolution of recombination, differentiation, and degeneration can be provided by comparing closely related species with homologous sex chromosomes. The sex chromosomes of the threespine stickleback (Gasterosteus aculeatus) and its sister species, the Japan Sea stickleback (G. nipponicus), have been well characterized. Little is known, however, about the sex chromosomes of their congener, the blackspotted stickleback (G. wheatlandi). We used pedigrees to obtain experimentally phased whole genome sequences from blackspotted stickleback X and Y chromosomes. Using multispecies gene trees and analysis of shared duplications, we demonstrate that Chromosome 19 is the ancestral sex chromosome and that its oldest stratum evolved in the common ancestor of the genus. After the blackspotted lineage diverged, its sex chromosomes experienced independent and more extensive recombination suppression, greater X–Y differentiation, and a much higher rate of Y degeneration than the other two species. These patterns may result from a smaller effective population size in the blackspotted stickleback. A recent fusion between the ancestral blackspotted stickleback Y chromosome and Chromosome 12, which produced a neo-X and neo-Y, may have been favored by the very small size of the recombining region on the ancestral sex chromosome. We identify six strata on the ancestral and neo-sex chromosomes where recombination between the X and Y ceased at different times. These results confirm that sex chromosomes can evolve large differences within and between species over short evolutionary timescales

Searching for signatures of sexually antagonistic selection on stickleback sex chromosomes.

Intralocus sexually antagonistic selection occurs when an allele is beneficial to one sex but detrimental to the other. This form of selection is thought to be key to the evolution of sex chromosomes but is hard to detect. Here we perform an analysis of phased young sex chromosomes to look for signals of sexually antagonistic selection in the Japan Sea stickleback (Gasterosteus nipponicus). Phasing allows us to date the suppression of recombination on the sex chromosome and provides unprecedented resolution to identify sexually antagonistic selection in the recombining region of the chromosome. We identify four windows with elevated divergence between the X and Y in the recombining region, all in or very near genes associated with phenotypes potentially under sexually antagonistic selection in humans. We are unable, however, to rule out the alternative hypothesis that the peaks of divergence result from demographic effects. Thus, although sexually antagonistic selection is a key hypothesis for the formation of supergenes on sex chromosomes, it remains challenging to detect. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'

Vortex Collisions: Crossing or Recombination?

We investigate the collision of two vortex lines moving with viscous dynamics and driven towards each other by an applied current. Using London theory in the approach phase we observe a non-trivial vortex conformation producing anti-parallel segments; their attractive interaction triggers a violent collision. The collision region is analyzed using the time-dependent Ginzburg-Landau equation. While we find vortices will always recombine through exchange of segments, a crossing channel appears naturally through a double collision process.Comment: 4 pages, 3 figure

The contribution of refractoriness to arrhythmic substrate in hypokalemic Langendorff-perfused murine hearts

The clinical effects of hypokalemia including action potential prolongation and arrhythmogenicity suppressible by lidocaine were reproduced in hypokalemic (3.0 mM K(+)) Langendorff-perfused murine hearts before and after exposure to lidocaine (10 μM). Novel limiting criteria for local and transmural, epicardial, and endocardial re-excitation involving action potential duration (at 90% repolarization, APD(90)), ventricular effective refractory period (VERP), and transmural conduction time (Δlatency), where appropriate, were applied to normokalemic (5.2 mM K(+)) and hypokalemic hearts. Hypokalemia increased epicardial APD(90) from 46.6 ± 1.2 to 53.1 ± 0.7 ms yet decreased epicardial VERP from 41 ± 4 to 29 ± 1 ms, left endocardial APD(90) unchanged (58.2 ± 3.7 to 56.9 ± 4.0 ms) yet decreased endocardial VERP from 48 ± 4 to 29 ± 2 ms, and left Δlatency unchanged (1.6 ± 1.4 to 1.1 ± 1.1 ms; eight normokalemic and five hypokalemic hearts). These findings precisely matched computational predictions based on previous reports of altered ion channel gating and membrane hyperpolarization. Hypokalemia thus shifted all re-excitation criteria in the positive direction. In contrast, hypokalemia spared epicardial APD(90) (54.8 ± 2.7 to 60.6 ± 2.7 ms), epicardial VERP (84 ± 5 to 81 ± 7 ms), endocardial APD(90) (56.6 ± 4.2 to 63.7 ± 6.4 ms), endocardial VERP (80 ± 2 to 84 ± 4 ms), and Δlatency (12.5 ± 6.2 to 7.6 ± 3.4 ms; five hearts in each case) in lidocaine-treated hearts. Exposure to lidocaine thus consistently shifted all re-excitation criteria in the negative direction, again precisely agreeing with the arrhythmogenic findings. In contrast, established analyses invoking transmural dispersion of repolarization failed to account for any of these findings. We thus establish novel, more general, criteria predictive of arrhythmogenicity that may be particularly useful where APD(90) might diverge sharply from VERP

Population Structure of Humpback Whales from Their Breeding Grounds in the South Atlantic and Indian Oceans

Although humpback whales are among the best-studied of the large whales, population boundaries in the Southern Hemisphere (SH) have remained largely untested. We assess population structure of SH humpback whales using 1,527 samples collected from whales at fourteen sampling sites within the Southwestern and Southeastern Atlantic, the Southwestern Indian Ocean, and Northern Indian Ocean (Breeding Stocks A, B, C and X, respectively). Evaluation of mtDNA population structure and migration rates was carried out under different statistical frameworks. Using all genetic evidence, the results suggest significant degrees of population structure between all ocean basins, with the Southwestern and Northern Indian Ocean most differentiated from each other. Effective migration rates were highest between the Southeastern Atlantic and the Southwestern Indian Ocean, followed by rates within the Southeastern Atlantic, and the lowest between the Southwestern and Northern Indian Ocean. At finer scales, very low gene flow was detected between the two neighbouring sub-regions in the Southeastern Atlantic, compared to high gene flow for whales within the Southwestern Indian Ocean. Our genetic results support the current management designations proposed by the International Whaling Commission of Breeding Stocks A, B, C, and X as four strongly structured populations. The population structure patterns found in this study are likely to have been influenced by a combination of long-term maternally directed fidelity of migratory destinations, along with other ecological and oceanographic features in the region

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

A model of EGL-20/Wnt and MAB-5/Hox function in QL migration.

<p>Data presented here indicate that both EGL-20/Wnt and MAB-5/Hox are required to inhibit anterior migration of QL.a/p. EGL-20 might immediately inhibit QL.a/p anterior migration via an “acute” mechanisms independent of BAR-1/β-catenin and MAB-5/Hox, as well as through a later “maintenance” phase that requires BAR-1 and MAB-5 and might require changes in gene expression. MAB-5 might also promote posterior migration.</p