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Nucleosomes specify co-factor access to p53
No full textPioneer transcription factors (TFs) engage chromatinized DNA motifs. However, it is unclear how the resultant TF-nucleosome complexes are decoded by co-factors. In humans, the TF p53 regulates cell-cycle progression, apoptosis, and the DNA damage response, with a large fraction of p53-bound sites residing in nucleosome-harboring inaccessible chromatin. We examined the interaction of chromatin-bound p53 with co-factors belonging to the ubiquitin proteasome system (UPS). At two distinct motif locations on the nucleosome (super-helical location [SHL]−5.7 and SHL+5.9), the E3 ubiquitin ligase E6-E6AP was unable to bind nucleosome-engaged p53. The deubiquitinase USP7, on the other hand, readily engages nucleosome-bound p53 in vitro and in cells. A corresponding cryo-electron microscopy (cryo-EM) structure shows USP7 engaged with p53 and nucleosomes. Our work illustrates how chromatin imposes a co-factor-selective barrier for p53 interactors, whereby flexibly tethered interaction domains of co-factors and TFs govern compatibility between co-factors, TFs, and chromatin
Evidence for the major role of PH4⍺EFB in the prolyl 4-hydroxylation of Drosophila collagen IV
No full textCollagens are fundamental components of extracellular matrices, requiring precise intracellular post-translational modifications for proper function. Among the modifications, prolyl 4-hydroxylation is critical to stabilise the collagen triple helix. In humans, this reaction is mediated by collagen prolyl 4-hydroxylases (P4Hs). While humans possess three genes encoding these enzymes (P4H⍺s), Drosophila melanogaster harbour at least 26 candidates for collagen P4H⍺s despite its simple genome, and it is poorly understood which of them are actually working on collagen in the fly. In this study, we addressed this question by carrying out thorough bioinformatic and biochemical analyses. We demonstrate that among the 26 potential collagen P4H⍺s, PH4⍺EFB shares the highest homology with vertebrate collagen P4H⍺s. Furthermore, while collagen P4Hs and their substrates must exist in the same cells, our transcriptomic analyses at the tissue and single cell levels showed a global co-expression of PH4⍺EFB but not the other P4H⍺-related genes with the collagen IV genes. Moreover, expression of PH4⍺EFB during embryogenesis was found to precede that of collagen IV, presumably enabling efficient collagen modification by PH4⍺EFB. Finally, biochemical assays confirm that PH4⍺EFB binds collagen, supporting its direct role in collagen IV modification. Collectively, we identify PH4⍺EFB as the primary and potentially constitutive prolyl 4-hydroxylase responsible for collagen IV biosynthesis in Drosophila. Our findings highlight the remarkably simple nature of Drosophila collagen IV biosynthesis, which may serve as a blueprint for defining the minimal requirements for collagen engineering
The JWST Emission-Line Survey: Extending rest-optical narrow-band emission-line selection into the Epoch of Reionization
No full textWe present the JWST Emission-Line Survey (JELS), a JWST imaging programme exploiting the wavelength coverage and sensitivity of the Near-Infrared Camera (NIRCam) to extend narrow-band rest-optical emission-line selection into the Epoch of Reionization (EoR) for the first time, and to enable unique studies of the resolved ionized gas morphology in individual galaxies across cosmic history. The primary JELS observations comprise ∼ 4.7 μm narrow-band imaging over ∼ 63 arcmin2 designed to enable selection of H α emitters at z ∼ 6.1 and a host of novel emission-line samples, including [O III] (z ∼ 8.3) and Paschen α/β (z ∼ 1.5/2.8). For the F466N/F470N narrow-band observations, the emission-line sensitivities achieved are up to ∼ 2× more sensitive than current slitless spectroscopy surveys (5σ limits of 0.8–1.2×10−18 erg s−1cm−2), corresponding to unobscured H α star formation rates (SFRs) of 0.9–1.3 M yr−1 at z ∼ 6.1, extending emission-line selections in the EoR to fainter populations. Simultaneously, JELS also adds F200W broad-band and F212N narrow-band imaging (H α at z ∼ 2.23) that probes SFRs 5× fainter than previous ground-based narrow-band studies (∼ 0.2 M yr−1), offering an unprecedented resolved view of star formation at cosmic noon. We present the detailed JELS design, key data processing steps specific to the survey observations, and demonstrate the exceptional data quality and imaging sensitivity achieved. We then summarize the key scientific goals of JELS, demonstrate the precision and accuracy of the expected redshift and measured emission-line recovery through detailed simulations, and present examples of spectroscopically confirmed H α and [O III] emitters discovered by JELS that illustrate the novel parameter space probed
Brief announcement: Minimizing energy solves relative majority with a cubic number of states in population protocols
No full textThis paper revisits a fundamental distributed computing problem in the population protocol model. Provided n agents each starting with an input color in [k], the relative majority problem asks to find the predominant color. In the population protocol model, at each time step, a scheduler selects two agents that first learn each other's states and then update their states based on what they learned.
We present the Circles protocol that solves the relative majority problem with k3 states. It is always-correct under weakly fair scheduling. Not only does it improve upon the best known upper bound of O(k7), but it also shows a strikingly simpler design inspired by energy minimization in chemical settings
Genealogical analysis of replicate flower colour hybrid zones in Antirrhinum
No full textA major goal of speciation research is identifying loci that underpin barriers to gene flow. Population genomics takes a ‘bottom-up’ approach, scanning the genome for molecular signatures of processes that drive or maintain divergence. However, interpreting the ‘genomic landscape’ of speciation is complicated, because genome scans conflate multiple processes, most of which are not informative about gene flow. However, studying replicated population contrasts, including multiple incidences of secondary contact, can strengthen inferences. In this paper, we use linked-read sequencing (haplotagging), FST scans and genealogical methods to characterise the genomic landscape associated with replicate hybrid zone formation. We studied two flower colour varieties of the common snapdragon, Antirrhinum majus subspecies majus, that form secondary hybrid zones in multiple independent valleys in the Pyrenees. Consistent with past work, we found very low differentiation at one well-studied zone (Planoles). However, at a second zone (Avellanet), we found stronger differentiation and greater heterogeneity, which we argue is due to differences in the amount of introgression following secondary contact. Topology weighting of genealogical trees identified loci where haplotype diversity was associated with the two snapdragon varieties. Two of the strongest associations were at previously identified flower colour loci: Flavia, that affects yellow pigmentation, and Rosea/Eluta, two linked loci that affect magenta pigmentation. Preliminary analysis of coalescence times provides additional evidence for selective sweeps at these loci and barriers to gene flow. Our study highlights the impact of demographic history on the differentiation landscape, emphasising the need to distinguish between historical divergence and recent introgression
Universal behavior of the BCS energy gap
No full textWe consider the BCS energy gap „.T / (essentially given by „.T / .T; p/,
the BCS order parameter) at all temperatures 0 T Tc up to the critical one, Tc, and show
that, in the limit of weak coupling, the ratio „.T /=Tc is given by a universal function of the relative temperature T =Tc. On the one hand, this recovers a recent result by Langmann and Triola
[Phys. Rev. B 108 (2023), no. 10, article no. 104503] on three-dimensional s-wave superconductors for temperatures bounded uniformly away from Tc. On the other hand, our result lifts these
restrictions, as we consider arbitrary spatial dimensions d 2 ¹1; 2; 3º, discuss superconductors
with non-zero angular momentum (primarily in two dimensions), and treat the perhaps physically most interesting (due to the occurrence of the superconducting phase transition) regime of
temperatures close to Tc.
Magnetic excitations in Ndn+1Nin O3n+1 Ruddlesden-Popper nickelates observed via resonant inelastic x-ray scattering
No full textMagnetic interactions are thought to play a key role in the properties of many unconventional superconductors, including cuprates, iron pnictides, and square-planar nickelates. Superconductivity was also recently observed in the bilayer and trilayer Ruddlesden-Popper nickelates, the electronic structure of which is expected to differ from that of cuprates and square-planar nickelates. Here we study how electronic structure and magnetic interactions evolve with the number of layers, , in thin film Ruddlesden-Popper nickelates Nd+1NiO3+1 with =1,3, and 5 using resonant inelastic x-ray scattering (RIXS). The RIXS spectra are consistent with a high-spin |38 ̲⟩ electronic configuration, resembling that of La2−SrNiO4 and the parent perovskite, NdNiO3. The magnetic excitations soften to lower energy in the structurally self-doped, higher- films. Our observations confirm that structural tuning is an effective route for altering electronic properties, such as magnetic superexchange, in this prominent family of materials
Phase behavior of Cacio e Pepe sauce
No full text“Pasta alla Cacio e pepe” is a traditional Italian dish made with pasta, pecorino cheese, and pepper. Despite its simple ingredient list, achieving the perfect texture and creaminess of the sauce can be challenging. In this study, we systematically explore the phase behavior of Cacio e pepe sauce, focusing on its stability at increasing temperatures for various proportions of cheese, water, and starch. We identify starch concentration as the key factor influencing sauce stability, with direct implications for practical cooking. Specifically, we delineate a regime where starch concentrations below 1% (relative to cheese mass) lead to the formation of system-wide clumps, a condition determining what we term the “Mozzarella Phase” and corresponding to an unpleasant and separated sauce. Additionally, we examine the impact of cheese concentration relative to water at a fixed starch level, observing a lower critical solution temperature that we theoretically rationalized by means of a minimal effective free-energy model. We further analyze the effect of a less traditional stabilizer, trisodium citrate, and observe a sharp transition from the Mozzarella Phase to a completely smooth and stable sauce, in contrast to starch-stabilized mixtures, where the transition is more gradual. Finally, we present a scientifically optimized recipe based on our findings, enabling a consistently flawless execution of this classic dish
Neural control and certificate repair via runtime monitoring
No full textLearning-based methods provide a promising approach to solving highly non-linear control tasks that are often challenging for classical control methods. To ensure the satisfaction of a safety property, learning-based methods jointly learn a control policy together with a certificate function for the property. Popular examples include barrier functions for safety and Lyapunov functions for asymptotic stability. While there has been significant progress on learning-based control with certificate functions in the white-box setting, where the correctness of the certificate function can be formally verified, there has been little work on ensuring their reliability in the black-box setting where the system dynamics are unknown. In this work, we consider the problems of certifying and repairing neural network control policies and certificate functions in the black-box setting. We propose a novel framework that utilizes runtime monitoring to detect system behaviors that violate the property of interest under some initially trained neural network policy and certificate. These violating behaviors are used to extract new training data, that is used to re-train the neural network policy and the certificate function and to ultimately repair them. We demonstrate the effectiveness of our approach empirically by using it to repair and to boost the safety rate of neural network policies learned by a state-of-the-art method for learning-based control on two autonomous system control tasks
6-torision and integral points on quartic threefolds
No full textWe prove matching upper and lower bounds for the average of the6-torsionof class groups of quadratic fields. Furthermore, we count the number of integer solutions on an affine quartic threefold