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The filamentary nature of accretion streams found around embedded sources suggests that protostellar disks experience heterogenous infall from the star-forming environment, consistent with the accretion behavior onto star-forming cores in top-down star-cluster formation simulations. This may produce disk substructures in the form of rings, gaps, and spirals that continue to be identified by high-resolution imaging surveys in both embedded Class 0/I and later Class II sources. We present a parameter study of anisotropic infall, informed by the properties of accretion flows onto protostellar cores in numerical simulations, and varying the relative specific angular momentum of incoming flows as well as their flow geometry. Our results show that anisotropic infall perturbs the disk and readily launches the Rossby wave instability. It forms vortices at the inner and outer edges of the infall zone where material is deposited. These vortices drive spiral waves and angular momentum transport, with some models able to drive stresses corresponding to a viscosity parameter on the order of α ∼ 10−2. The resulting azimuthal shear forms robust pressure bumps that act as barriers to radial drift of dust grains, as demonstrated by postprocessing calculations of drift-dominated dust evolution. We discuss how a self-consistent model of anisotropic infall can account for the formation of millimeter rings in the outer disk as well as producing compact dust disks, consistent with observations of embedded sources.

DNA polymerases catalyze DNA synthesis during the replication, repair, and recombination of DNA. Based on phylogenetic analysis and primary protein sequences, DNA polymerases have been categorized into seven families: A, B, C, D, X, Y, and RT. This review presents generalized data on the catalytic mechanism of action of DNA polymerases. The structural features of different DNA polymerase families are described in detail. The discussion highlights the kinetics and conformational dynamics of DNA polymerases from all known polymerase families during DNA synthesis.

Alkyladenine DNA glycosylase (AAG) is a critical enzyme in the base excision repair (BER) pathway, responsible for removing a broad spectrum of alkylated DNA lesions. While AAG maintains genomic stability, dysregulated activity has been implicated in cancer development, drug resistance, and neurodegenerative diseases. This review synthesizes the current knowledge on AAG’s structure, catalytic mechanism, and polymorphic variants, highlighting their potential roles in disease pathogenesis. A comprehensive bioinformatics analysis of over 370 AAG single-nucleotide polymorphisms (SNPs) is presented, identifying ~40% as high-risk variants likely to impair enzymatic function. Notably, 151 SNPs were predicted to be damaging by multiple algorithms, including substitutions at catalytic residues and non-conserved sites with unknown functional consequences. Analysis of cancer databases (COSMIC, cBioPortal, NCBI) revealed 93 tumor-associated AAG variants, with 18 classified as high-impact mutations. This work underscores the need for mechanistic studies of AAG variants using structural biology, cellular models, and clinical correlation analyses. Deciphering AAG’s polymorphic landscape may unlock personalized strategies for cancer prevention and treatment.

DNA-deaminase AID plays a pivotal role in adaptive immunity, antibody diversification and epigenetic regulation. AID catalyzes cytidine deamination in immunoglobulin genes, facilitating somatic hypermutation (SHM), class-switch recombination (CSR) and gene conversion (GC). However, the dysregulation of AID activity can lead to oncogenic mutations and immune disorders such as hyper-IgM syndrome type 2 (HIGM2). At present the number of studies investigating the role of AID polymorphic variants in the promotion of pathology is low. The current review examines the structural and functional aspects of AID, focusing on the impact of amino acid substitutions—both natural polymorphisms and artificial mutations—on its catalytic activity, substrate binding and interactions with regulatory proteins. Additionally, a bioinformatic analysis of single-nucleotide polymorphisms of AID deposited in the dbSNP database was performed. SNPs leading to amino acid substitutions in the primary protein structure were analyzed. The bioinformatic analysis of SNPs in the AID gene predicts that among 208 SNPs causing amino acid substitutions in the primary protein structure, 62 substitutions may have significant negative impact on the functioning of AID. The integration of computational predictions with experimental data underscores the importance of AID regulation in maintaining immune homeostasis and highlights potential markers for immune-related pathologies. This comprehensive analysis provides insights into the molecular mechanisms of AID dysfunction and its implications for disease.

Magnetoencephalography (MEG) is a neuroimaging method ideally suited for non-invasive studies of brain dynamics. MEG’s spatial resolution critically depends on the approach used to solve the ill-posed inverse problem in order to transform sensor signals into cortical activation maps. Over recent years non-globally optimized solutions based on the use of adaptive beamformers (BF) gained popularity. When operating in the environment with a small number of uncorrelated sources the BFs perform optimally and yield high spatial resolution. However, the BFs are known to fail when dealing with correlated sources acting like poorly tuned spatial filters with low signal-to-noise ratio (SNR) of the output timeseries and often meaningless cortical maps of power distribution. This fact poses a serious limitation on the broader use of this promising technique especially since fundamental mechanisms of brain functioning, its inherent symmetry and task-based experimental paradigms result into a great deal of correlation in the activity of cortical sources. To cope with this problem, we developed a novel data covariance modification approach that allows for building beamformers that maintain high spatial resolution when operating in the environments with correlated sources. At the core of our method is a projection operation applied to the vectorized sensor-space covariance matrix. This projection does not remove the activity of the correlated sources from the sensor-space covariance matrix but rather selectively handles their contributions to the covariance matrix and creates a sufficiently accurate approximation of an ideal data covariance that could hypothetically be observed should these sources be uncorrelated. Since the projection operation is reciprocal to the PSIICOS method developed by us earlier (Ossadtchi et al., 2018) we refer to the family of algorithms presented here as ReciPSIICOS. We assess the performance of the novel approach using realistically simulated MEG data and show its superior performance in comparison to the classical BF approaches and well established MNE as a method immune to source synchrony by design. We have also applied our approach to the MEG datasets from the two experiments involving two different auditory tasks. The analysis of experimental MEG datasets showed that beamformers from ReciPSIICOS family, but not the classical BF, discovered the expected bilateral focal sources in the primary auditory cortex and detected motor cortex activity associated with the audio-motor task. In most cases MNE managed well but as expected produced more spatially diffuse source distributions. Notably, ReciPSIICOS beamformers yielded cortical activity estimates with SNR several times higher than that obtained with the classical BF, which may indirectly indicate the severeness of the signal cancellation problem when applying classical beamformers to MEG signals generated by synchronous sources.

Chondrules are iconic sub-millimeter spheroids representing the most abundant high-temperature dust formed during the evolution of the circumsolar disk. Chondrules have been the subject of a great deal of research, but no consensus has yet emerged as to their formation conditions. In particular, the question of whether chondrules are of nebular or planetary origin remains largely debated. Building upon decades of chondrule investigation and recent headways in combining petrographic observations and O−Ti−Cr isotopic compositions, we here propose a comprehensive vision of chondrule formation. This holistic approach points toward a nebular origin of both NC and CC chondrules, with repetitive high-temperature recycling processes controlling the petrographic and isotopic diversities shown by chondrules. Chondrule precursors correspond to mixing between (i) early-formed refractory inclusions ± NC-like dust and (ii) previous generation of chondrules ± CI-like material. Chondrule formation took place under open conditions with gas-melt interactions with multi-species gas (H 2 O, Mg, SiO) playing a key role for establishing their characteristics. Petrographic and isotopic systematics do not support disk-wide transport of chondrules but point toward local formation of chondrules within their respective accretion reservoirs. Altogether, this shows that several generations of genetically-related chondrules (i.e., deriving from each other) co-exist in chondrites. In addition to supporting the nebular brand of chondrule-forming scenarios, this argues for repetitive and extremely localized heating events for producing chondrules.

Hyperthermophilic archaea such as Pyrococcus furiosus survive under very aggressive environmental conditions by occupying niches inaccessible to representatives of other domains of life. The ability to survive such severe living conditions must be ensured by extraordinarily efficient mechanisms of DNA processing, including repair. Therefore, in this study, we compared kinetics of conformational changes of DNA Endonuclease Q from P. furiosus during its interaction with various DNA substrates containing an analog of an apurinic/apyrimidinic site (F-site), hypoxanthine, uracil, 5,6-dihydrouracil, the α-anomer of adenosine, or 1,N6-ethenoadenosine. Our examination of DNA cleavage activity and fluorescence time courses characterizing conformational changes of the dye-labeled DNA substrates during the interaction with EndoQ revealed that the enzyme induces multiple conformational changes of DNA in the course of binding. Moreover, the obtained data suggested that the formation of the enzyme–substrate complex can proceed through dissimilar kinetic pathways, resulting in different types of DNA conformational changes, which probably allow the enzyme to perform its biological function at an extreme temperature.

We present the Atacama Large Millimeter/submillimeter Array Survey of Gas Evolution of PROtoplanetary Disks (AGE-PRO), a large program of the ALMA. AGE-PRO aims to systematically trace the evolution of gas disk mass and size throughout the lifetime of protoplanetary disks. It uses a carefully selected sample of 30 disks around M3-K6 stars in three nearby star-forming regions: Ophiuchus (0.5–1 Myr), Lupus (1–3 Myr), and Upper Sco (2–6 Myr). Assuming the three regions had similar initial conditions and evolutionary paths, we find the median gas disk mass appears to decrease with age. Ophiuchus disks have the highest median gas mass (6 MJup), while the Lupus and Upper Sco disks have significantly lower median masses (0.68 and 0.44 MJup, respectively). Notably, the gas and dust disk masses appear to evolve on different timescales. This is evidenced by the median gas-to-dust mass ratio, which decreases from 122 in the youngest disks (<1 Myr) to 46 in Lupus disks, and then increases to 120 in the Upper Sco disks. The median gas disk sizes range between 74 and 110 au, suggesting that typical gas disks are much smaller than those of well-studied, massive disks. Population synthesis models suggest that magnetohydrodynamic wind-driven accretion can reproduce median disk properties across all three regions, when assuming compact disks with a declining magnetic field over time. In contrast, turbulent-driven models overestimate gas masses of >1 Myr disks by an order of magnitude. Here, we discuss the program’s motivation, survey design, sample selection, observation and data calibration processes, and highlight the initial results.

We perform visibility fitting to the dust continuum Band 6 1.3 mm data of the 30 protoplanetary disks in the Atacama Large Millimeter/submillimeter Array Survey of Gas Evolution of PROtoplanetary Disks (AGE-PRO) Large Program. We obtain disk geometries, dust-disk radii, and azimuthally symmetric radial profiles of the intensity of the dust continuum emission. We examine the presence of continuum substructures in the AGE-PRO sample by using these radial profiles and their residuals. We detect substructures in 15 out of 30 disks. We report five disks with large (>15 au) inner dust cavities. The Ophiuchus Class I disks show dust-disk substructures in ∼80% of the resolved sources. This evidences the early formation of substructures in protoplanetary disks. A spiral is identified in IRS 63, hinting to gravitational instability in this massive disk. We compare our dust-disk brightness radial profiles with gas-disk brightness radial profiles and discuss colocal substructures in both tracers. In addition, we discuss the evolution of dust-disk radii and substructures across Ophiuchus, Lupus, and Upper Scorpius. We find that disks in Lupus and Upper Scorpius with large inner dust cavities have typical gas-disk masses, suggesting an abundance of dust cavities in these regions. The prevalence of pressure dust traps at later ages is supported by a potential trend with time with more disks with large inner dust cavities (or transition disks) in Upper Scorpius and the absence of evolution of dust-disk sizes with time in the AGE-PRO sample. We propose this is caused by an evolutionary sequence with a high fraction of protoplanetary disks with inner protoplanets carving dust cavities.

The evolution of the gas mass of planet-forming disks around young stars is crucial for our understanding of planet formation, yet it has proven hard to constrain observationally, due both to the difficulties of measuring gas masses and the lack of a homogeneous sample. Here we present a large grid of thermochemical models that we use to measure protoplanetary gas disk masses of AGE-PRO, the Atacama Large Millimeter/submillimeter Array survey of Gas Evolution in PROtoplanetary disks. AGE-PRO covers a sample of 30 disks around similar spectral type (M3-K6) stars with ages between 0.1 and 10 Myr. Our approach is to simultaneously fit observations of CO isotopologues and N2H+, a complementary molecule produced when CO freezes out. We find that the median gas mass of the three regions decreases over time, from 7.0−2.6+4.4×10−3M⊙ in Ophiuchus (≲1 Myr) to 9.4−3.4+5.4×10−4M⊙ for Lupus (∼1–3 Myr) and 6.8−2.8+5.1×10−4M⊙ for Upper Sco (∼2–6 Myr), with ∼1 dex scatter in gas mass in each region. We note that the gas mass distributions for Lupus and Upper Sco look very similar, which could be due to survivorship bias for the latter. The median bulk CO abundance in the CO emitting layer is found to be a factor ∼10 lower than the interstellar medium value but does not significantly change between Lupus and Upper Sco. From Lupus to Upper Sco, the median gas-to-dust mass ratio increases by a factor ∼3 from ∼40 to ∼120, suggesting efficient inward pebble drift and/or the formation of planetesimals.