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ISTA Thesis
No full textImmune responses depend on the coordinated and efficient migration of leukocytes. These
cells, which are embedded and tightly confined within tissues, must navigate and traverse
diverse and complex three-dimensional environments. Leukocytes adapt their locomotory
behavior to the mechanical, geometrical, and biochemical characteristics of their
surroundings. In low-density environments, where the pore size of the interstitial matrix
allows free passage, these cells position the nucleus directly behind the lamellipodium, the
protrusive actin structure that forms the leading front of the cell. In this configuration, they
use the nucleus as a gauge to identify the path of least resistance.
Here, we show that in high-density environments, where the pore size precludes free passage
of the cell body, leukocytes reposition the microtubule-organizing center (MTOC) and
associated organelles in front of the nucleus. In this configuration, they use actin structures
protruding orthogonally to the direction of migration in order to open a path for the cell body.
We identify two distinct actin populations that serve this purpose at different subcellular
localizations. At the leading edge, local indentation of the plasma membrane leads to
recruitment of the Wiskott-Aldrich syndrome protein (WASp), which, via Arp2/3, results in
the formation of individual actin foci. At the cell body, actin polymerization is triggered by
DOCK8, a Cdc42 exchange factor, resulting in the formation of a central actin pool.
We demonstrate that the central and peripheral actin pools are functionally communicating
and that depletion of the central actin pool leads to increased actin accumulation at the cell
front, resulting in excessive extension of the leading edge
Phenotypic divergence and genomic architecture between parallel ecotypes at two different points on the speciation continuum in a marine snail
No full textSpeciation is rarely observable directly. A way forward is to compare pairs of ecotypes that evolved in parallel in similar contexts but have reached different degrees of reproductive isolation. Such comparisons are possible in the marine snail Littorina saxatilis by contrasting barriers to gene flow between parallel ecotypes in Spain and Sweden. In both countries, divergent ecotypes have evolved to withstand either crab predation or wave action. Here, we explore transects spanning contact zones between the Crab and the Wave ecotypes using low-coverage whole-genome sequencing, morphological and behavioural traits. Despite parallel phenotypic divergence, distinct patterns of differentiation between the ecotypes emerged: a continuous cline in Sweden indicating a weak barrier to gene flow, but two highly genetically and phenotypically divergent, and partly spatially overlapping clusters in Spain suggesting a much stronger barrier to gene flow. The absence of Spanish early-generation hybrids supported strong isolation, but a low level of gene flow is evident from molecular data. In both countries, highly differentiated loci were located in both shared and country-specific chromosomal inversions but were also present in collinear regions. Despite being considered the same species and showing similar levels of phenotypic divergence, the Spanish ecotypes are much closer to full reproductive isolation than the Swedish ones. Barriers to gene flow of very different strengths between ecotypes within the same species might be explained by dissimilarities in the spatial arrangement of habitats, the selection gradients or the ages of the systems
The low-fidelity DNA Pol IV accelerates evolution of pathogenicity genes in Pseudomonas aeruginosa
No full textSpecialized DNA polymerases facilitate various cellular processes. Despite extensive research, the mutagenic effects of these error-prone enzymes on genomes are not fully understood. Here we show that Pol IV promotes genomic instability in Pseudomonas aeruginosa by misincorporating oxidized guanine nucleotides. This activity led to a distinctive mutational signature, characterized by A-to-C transversions occurring preferentially at AT sites flanked by a 5’G and/or 3’C. Furthermore, Pol IV preferentially targeted pathogenicity genes located at specific chromosomal locations near the replication termination region and rRNA-encoding operons. Half of the mutation events catalyzed by Pol IV impaired gene function. This can be attributed to the bias of Pol IV for mutating codons with its preferred sequence contexts, leading to substitutions to unreactive alanine and glycine residues. Remarkably, mutation signatures identified for Pol IV were found in clinical isolate genomes of P. aeruginosa, providing compelling evidence for its role in genetic diversification during pathogen adaptation
Roadmap for animate matter
No full textHumanity has long sought inspiration from nature to innovate materials and devices. As science advances, nature-inspired materials are becoming part of our lives. Animate materials, characterized by their activity, adaptability, and autonomy, emulate properties of living systems. While only biological materials fully embody these principles, artificial versions are advancing rapidly, promising transformative impacts in the circular economy, health and climate resilience within a generation. This roadmap presents authoritative perspectives on animate materials across different disciplines and scales, highlighting their interdisciplinary nature and potential applications in diverse fields including nanotechnology, robotics and the built environment. It underscores the need for concerted efforts to address shared challenges such as complexity management, scalability, evolvability, interdisciplinary collaboration, and ethical and environmental considerations. The framework defined by classifying materials based on their level of animacy can guide this emerging field to encourage cooperation and responsible development. By unravelling the mysteries of living matter and leveraging its principles, we can design materials and systems that will transform our world in a more sustainable manner
A post-starburst pathway for the formation of massive galaxies and black holes at z > 6
No full textUnderstanding the rapid formation of supermassive black holes in the early Universe requires insights into stellar mass growth in host galaxies. Here we present NIRSpec rest-frame optical spectra and NIRCam imaging from JWST of two galaxies at z > 6, both hosting moderate-luminosity quasars. These galaxies exhibit Balmer absorption lines, like low-redshift post-starburst galaxies. Our analyses of the medium-resolution spectra and multiband photometry show that the bulk of the stellar mass (log(M*/M☉) ≥ 10.6) formed in starburst episodes at redshift 9 and 7. One of the galaxies shows a clear Balmer break and lacks spatially resolved Hα emission. It falls well below the star-formation main sequence at z = 6, indicating quiescence. The other is transitioning to quiescence; together, these massive galaxies are among the most distant post-starburst systems known. The blueshifted wings of the quasar [O iii] emission lines indicate quasar-driven outflow, which possibly influences star formation. Direct stellar velocity dispersion measurements reveal that one galaxy follows the local black hole mass versus σ* relation whereas the other is overmassive. The existence of massive post-starburst galaxies hosting billion-solar-mass black holes in short-lived quasar phases indicates that supermassive black holes and host galaxies played a principal role in each other’s rapid early formation
Integral points on cubic surfaces: heuristics and numerics
No full textWe develop a heuristic for the density of integer points on affine cubic surfaces. Our heuristic applies to smooth surfaces defined by cubic polynomials that are log K3, but it can also be adjusted to handle singular cubic surfaces. We compare our heuristic to Heath-Brown’s prediction for sums of three cubes, as well as to asymptotic formulae in the literature around Zagier’s work on the Markoff cubic surface, and work of Baragar and Umeda on further surfaces of Markoff-type. We also test our heuristic against numerical data for several families of cubic surfaces
Dual relaxation oscillations in a Josephson-junction array
No full textWe report relaxation oscillations in a one-dimensional array of Josephson junctions, wherein the array dynamically switches between low-current and high-current states. The oscillations are current-voltage dual to those ordinarily observed in single junctions. The current-voltage dual circuit quantitatively accounts for temporal dynamics of the array, including the dependence on biasing conditions. Injection locking of the oscillations results in well-developed current plateaux. A thermal model explains the self-consistent reduction of the superconducting gap due to overheating of the array in the high-current state. Our work suggests that overheating determines the switching from the high-current state to the low-current state
A remarkable ruby: Absorption in dense gas, rather than evolved stars, drives the extreme Balmer break of a little red dot at z = 3.5
No full textThe origin of the rest-optical emission of compact, red, high-redshift sources known as little red dots (LRDs) poses a major puzzle. If interpreted as starlight, it would imply that LRDs constitute the densest stellar systems in the Universe. However, alternative models suggest active galactic nuclei (AGN) may instead power the rest-optical continuum. Here, we present JWST/NIRSpec, NIRCam, and MIRI observations from the RUBIES and PRIMER programs of The Cliff: a bright LRD at z = 3.55 with an exceptional Balmer break, twice as strong as that of any high-redshift source previously observed. The spectra also reveal broad hydrogen (Hα FWHM ∼ 1500 km s−1) and He I emission, but no significant metal lines. We demonstrate that massive evolved stellar populations cannot explain the observed spectrum, even when considering unusually steep and strong dust attenuation or reasonable variations in the initial mass function. Moreover, the formally best-fit stellar mass and compact size (M* ∼ 1010.5 M⊙, re ∼ 40 pc) would imply densities at which near-monthly stellar collisions might lead to significant X-ray emission. We argue that the Balmer break, emission lines, and Hα absorption line are instead most plausibly explained by a black hole star (BH*) scenario, in which dense gas surrounds a powerful ionising source. In contrast to recently proposed BH* models of dust-reddened AGN, we show that spectral fits in the rest UV to near-infrared favour an intrinsically redder continuum over strong dust reddening. This may point to a super-Eddington accreting massive black hole or, possibly, the presence of (super)massive stars in a nuclear star cluster. The Cliff is the clearest evidence to date that at least some LRDs are not ultra-dense massive galaxies, and are instead powered by a central ionising source embedded in dense, absorbing gas
Biosynthesis of very long-chain fatty acids is required for Arabidopsis auxin-mediated embryonic and post-embryonic development
No full textVery long-chain fatty acids (VLCFAs), being constituents of different types of lipids, are critical factors in plant development, presumably due to their impact on the endomembrane system. The VLCFAs are synthesized in the endoplasmic reticulum by a heterotetrameric enzymatic complex including β-ketoacyl CoA reductase 1 (KCR1), whose mutant is lethal. Here, we describe the ectopic shoot meristems (esm) mutant, a viable kcr1 allele presumably affecting surface properties of the KCR1 protein. This kcr1-2 mutant shows reduced fatty acyl elongation that impacts VLCFAs. The kcr1-2 plants show severe defects during different stages of development, which all correlate with defects in polar localization and subcellular trafficking of PIN auxin transporters and resulting asymmetric auxin distribution. Detailed analysis of KCR1 expression and patterning defects in kcr1-2 suggests that KCR1 plays a role in delineating boundaries around meristematic and specialized differentiating tissues, including root and shoot meristems, initiating lateral roots, lateral root primordia, and trichomes. In these contexts, KCR1-produced VLCFAs may act in a non-cell-autonomous manner. Viable kcr1-2 represents a useful tool to study VLCFA roles in plant development and highlights VLCFAs as critical developmental factors at the interface of cell polarity and tissue development
Eigenvector decorrelation for random matrices
No full textWe study the sensitivity of the eigenvectors of random matrices, showing that
even small perturbations make the eigenvectors almost orthogonal. More
precisely, we consider two deformed Wigner matrices , and show
that their bulk eigenvectors become asymptotically orthogonal as soon as
, or their respective energies are separated on a
scale much bigger than the local eigenvalue spacing. Furthermore, we show that
quadratic forms of eigenvectors of , with any deterministic
matrix in a specific subspace of codimension one
are of size . This proves a generalization of the Eigenstate
Thermalization Hypothesis to eigenvectors belonging to two different spectral
families