AbstractHelper data algorithms reliably extract secrets from physical unclonable functions. The necessary helper data can leak information, though. One state-of-the-art approach to assess the remaining min-entropy is limited to homogeneous bias or correlation, not both. Another one extends this to only local bias without correlation but is limited to short code lengths. This work presents a new approach for determining the min-entropy based on convolving histograms. It provides a better bound and good approximation given arbitrary bias, more realistic correlation effects, and practically relevant code sizes. Experiments on real-world and synthetic data show the benefit of the new method compared with state-of-the-art ones. This work also facilitates a better understanding of how the error correction as post-processing impacts the min-entropy.

Intrinsically disordered protein regions form condensates and mediate interactions with factors that regulate gene activity. Patil etal.1 decode how such regions within the chromatin remodeler cBAF choreograph self-condensation and non-self interactions with transcriptional regulators, potentially impacting disease.

All vertebrate genomes encode for three large histone H2A variants that have an additional metabolite-binding globular macrodomain module, macroH2A. MacroH2A variants impact heterochromatin organization and transcription regulation and establish a barrier for cellular reprogramming. However, the mechanisms of how macroH2A is incorporated into chromatin and the identity of any chaperones required for histone deposition remain elusive. Here, we develop a split-GFP-based assay for chromatin incorporation and use it to conduct a genome-wide mutagenesis screen in haploid human cells to identify proteins that regulate macroH2A dynamics. We show that the histone chaperone ANP32B is a regulator of macroH2A deposition. ANP32B associates with macroH2A in cells and invitro binds to histones with low nanomolar affinity. Invitro nucleosome assembly assays show that ANP32B stimulates deposition of macroH2A-H2B and not of H2A-H2B onto tetrasomes. In cells, depletion of ANP32B strongly affects global macroH2A chromatin incorporation, revealing ANP32B as a macroH2A histone chaperone.

In an abandoned sand pit near Ballendorf (Alb-Donau District, Baden-Württemberg), sediments of the Upper Marine Molasse (Lower Miocene) are present. In these sediments, 39 shark and ray species belonging to 29 genera were identified (Aetobatus, Alopias, Araloselachus, Carcharhinus, Carcharias, Centrophorus, Chaenogaleus, Dasyatis, Galeocerdo, Hemipristis, Iago, Isistius, Keasius, Notorynchus, Pachyscyllium, Paragaleus, Physogaleus, Pristiophorus, Raja, Rhinobatos, Rhinoptera, Rhizoprionodon, Rhynchobatus, Scyliorhinus, Sphyrna, Squalus, Squatina, Taeniurops, Triakis). However, in this paper we only illustrate and describe the 23 taxa not already discussed in previous publications on the Upper Marine Molasse deposits of Äpfingen, Rengetsweiler and Ursendorf, apart from two exceptions: teeth from jaw positions not previously illustrated, and specimens that are better preserved than those in previous publications. Specimens only determined as “sp.” were illustrated because it cannot be ruled out that they represent different species to the ones published earlier. Nearly all of the taxa found have Recent relatives; only Araloselachus, Keasius and Physogaleus are extinct. Most of the recovered taxa lived on or near the bottom in the shelf region. Alopias and possibly also Keasius lived higher in the water column. With Isistius, a taxon living in the oceanic realm was present, and the Recent representatives of Centrophorus live in deeper waters. Nearly all taxa fed on invertebrates and/or fishes; Isistius also fed as an ectoparasite. Additionally, two generalist feeders (Galeocerdo, Notorynchus) and one filter feeder (Keasius) were identified. The species Carcharias crassidens, which is not common in the Upper Marine Molasse, was also verified. Other fossils found in this deposit include remnants of odontocete cetaceans, molluscs, balanid barnacles, algae, and teeth of terrestrial mammals. The palaeoenvironment was a warm, shallow-water habitat. Based on greater proximity to the palaeo-coastline, the water depth was probably less than in other Upper Marine Molasse deposits.

Cells employ global genome nucleotide excision repair (GGR) to eliminate a broad spectrum of DNA lesions, including those induced by UV light. The lesion-recognition factor XPC initiates repair of helix-destabilizing DNA lesions, but binds poorly to lesions such as CPDs that do not destabilize DNA. How difficult-to-repair lesions are detected in chromatin is unknown. Here, we identify the poly-(ADP-ribose) polymerases PARP1 and PARP2 as constitutive interactors of XPC. Their interaction results in the XPC-stimulated synthesis of poly-(ADP-ribose) (PAR) by PARP1 at UV lesions, which in turn enables the recruitment and activation of the PAR-regulated chromatin remodeler ALC1. PARP2, on the other hand, modulates the retention of ALC1 at DNA damage sites. Notably, ALC1 mediates chromatin expansion at UV-induced DNA lesions, leading to the timely clearing of CPD lesions. Thus, we reveal how chromatin containing difficult-to-repair DNA lesions is primed for repair, providing insight into mechanisms of chromatin plasticity during GGR.

NAD metabolism is essential for all forms of life. Compartmental regulation of NAD+ consumption, especially between the nucleus and the mitochondria, is required for energy homeostasis. However, how compartmental regulation evolved remains unclear. In the present study, we investigated the evolution of the macrodomain-containing histone variant macroH2A1.1, an integral chromatin component that limits nuclear NAD+ consumption by inhibiting poly(ADP-ribose) polymerase 1 in vertebrate cells. We found that macroH2A originated in premetazoan protists. The crystal structure of the macroH2A macrodomain from the protist Capsaspora owczarzaki allowed us to identify highly conserved principles of ligand binding and pinpoint key residue substitutions, selected for during the evolution of the vertebrate stem lineage. Metabolic characterization of the Capsaspora lifecycle suggested that the metabolic function of macroH2A was associated with nonproliferative stages. Taken together, we provide insight into the evolution of a chromatin element involved in compartmental NAD regulation, relevant for understanding its metabolism and potential therapeutic applications.

Ants are a major ecological group in tropical rainforests. Few studies in the Neotropics have documented the distribution of ants from the ground to the canopy, and none have included the understorey. A previous analysis of an intensive arthropod study in Panama, involving 11 sampling methods, showed that the factors influencing ant β diversity (i.e., changes in assemblage composition) were, in decreasing order of importance, the vertical (height), temporal (season), and horizontal (geographic distance) dimensions. In the present study, we went one step further and aimed (1) to identify the best sampling methods to study the entire ant assemblage across the three strata, (2) to test if all strata show a similar horizontal β diversity and (3) to analyze the functional structure of the entire ant assemblage. We identified 405 ant species from 11 subfamilies and 68 genera. Slightly more species were sampled in the canopy than on the ground; they belonged to distinct sub-assemblages. The understorey fauna was mainly a mixture of species found in the other two strata. The horizontal β diversity between sites was similar for the three strata. About half of the ant species foraged in two (29%) or three (25%) strata. A single method, aerial flight interception traps placed alongside tree trunks, acting as arboreal pitfall traps, collected half of the species and reflected the vertical stratification. Using the functional traits approach, we observed that generalist species with mid-sized colonies were by far the most numerous (31%), followed by ground- or litter-dwelling species, either specialists (20%), or generalists (16%), and arboreal species, either generalists (19%) or territorially dominant (8%), and finally army ants (5%). Our results reinforce the idea that a proper understanding of the functioning of ant assemblages requires the inclusion of arboreal ants in survey programs.

The severity of coronavirus disease 2019 (COVID-19) varies significantly with cases spanning from asymptomatic to lethal with a subset of individuals developing Severe Acute Respiratory Syndrome (SARS) and death from respiratory failure. To determine whether global nucleosome and citrullinated nucleosome levels were elevated in COVID-19 patients, we tested two independent cohorts of COVID-19 positive patients with quantitative nucleosome immunoassays and found that nucleosomes were highly elevated in plasma of COVID-19 patients with a severe course of the disease relative to healthy controls and that both histone 3.1 variant and citrullinated nucleosomes increase with disease severity. Elevated citrullination of circulating nucleosomes is indicative of neutrophil extracellular trap formation, neutrophil activation and NETosis in severely affected individuals. Importantly, using hospital setting (outpatient, inpatient or ICU) as a proxy for disease severity, nucleosome levels increased with disease severity and may serve as a guiding biomarker for treatment. Owing to the limited availability of mechanical ventilators and extracorporal membrane oxygenation (ECMO) equipment, there is an urgent need for effective tools to rapidly assess disease severity and guide treatment selection. Based on our studies of two independent cohorts of COVID-19 patients from Belgium and Germany, we suggest further investigation of circulating nucleosomes and citrullination as biomarkers for clinical triage, treatment allocation and clinical drug discovery.

ADP-ribosylation is a pivotal post-translational modification that mediates various important cellular processes producing negatively charged biopolymer, poly (ADP-ribose), the functions of which need further elucidation. Toward this end, the availability of well-defined ADP-ribose (ADPr) oligomers in sufficient quantities is a necessity. In this work, we demonstrate the chemical synthesis of linear ADPr oligomers of defined, increasing length using a modified solid phase synthesis method. An advanced phosphoramidite building block temporarily protected with the base sensitive Fm-group was designed and implemented in the repeating pyrophosphate formation via a P(v)–P(iii) coupling procedure on Tentagel solid support. Linear ADPr oligomers up to a pentamer were successfully synthesized and their affinity for the poly-(ADP-ribose)-binding macrodomain of the human oncogenic helicase and chromatin remodeling enzyme ALC1 was determined. Our data reveal a length-dependent binding manner of the nucleic acid, with larger ADPr oligomers exhibiting higher binding enthalpies for ALC1, illustrating how the activity of this molecular machine is gated by PAR.

The anti-tumor potency of poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) has been linked to trapping of PARP1 on damaged chromatin. However, little is known about their impact on PARP2, an isoform with overlapping functions at DNA lesions. Whether the release of PARP1/2 from DNA lesions is actively catalyzed by molecular machines is also not known. We found that PARPis robustly trap PARP2 and that the helicase ALC1 (CHD1L) is strictly required for PARP2 release. Catalytic inactivation of ALC1 quantitatively traps PARP2 but not PARP1. ALC1 manipulation impacts the response to single-strand DNA breaks through PARP2 trapping, potentiates PARPi-induced cancer cell killing, and mediates synthetic lethality upon BRCA deficiency. The chromatin remodeler ALC1 actively drives PARP2 turnover from DNA lesions, and PARP2 contributes to the cellular responses of PARPi. This suggests that disrupting the ATP-fueled remodeling forces of ALC1 might enable therapies that selectively target the DNA repair functions of PARPs in cancer.