Halobacteria (henceforth Haloarchaea) are predominantly aerobic halophiles that are thought to have evolved from anaerobic methanogens. This remarkable transformation most likely involved an extensive influx of bacterial genes. Whether it entailed a single massive transfer event or a gradual stream of transfers remains a matter of debate. To address this, genomes that descend from methanogen-to-halophile intermediates are necessary. Here, we present five such near-complete genomes of Marine Group IV archaea (Hikarchaeia), the closest known relatives of Haloarchaea. Their inclusion in gene tree-aware ancestral reconstructions reveals an intermediate stage that had already lost a large number of genes, including nearly all of those involved in methanogenesis and the Wood-Ljungdahl pathway. In contrast, the last Haloarchaea common ancestor gained a large number of genes and expanded its aerobic respiration and salt/UV resistance gene repertoire. Our results suggest that complex and gradual patterns of gain and loss shaped the methanogen-to-halophile transition.Critical systems represent physical boundaries between different phases of matter and have been intensely studied for their universality and rich physics. Yet, with the rise of non-Hermitian studies, fundamental concepts underpinning critical systems - like band gaps and locality - are increasingly called into question. This work uncovers a new class of criticality where eigenenergies and eigenstates of non-Hermitian lattice systems jump discontinuously across a critical point in the thermodynamic limit, unlike established critical scenarios with spectrum remaining continuous across a transition. Such critical behavior, dubbed the "critical non-Hermitian skin effect", arises whenever subsystems with dissimilar non-reciprocal accumulations are coupled, however weakly. This indicates, as elaborated with the generalized Brillouin zone approach, that the thermodynamic and zero-coupling limits are not exchangeable, and that even a large system can be qualitatively different from its thermodynamic limit. Examples with anomalous scaling behavior are presented as manifestations of the critical non-Hermitian skin effect in finite-size systems. More spectacularly, topological in-gap modes can even be induced by changing the system size. We provide an explicit proposal for detecting the critical non-Hermitian skin effect in an RLC circuit setup, which also directly carries over to established setups in non-Hermitian optics and mechanics.Protecting replication fork integrity during DNA replication is essential for maintaining genome stability. Here, we report that SDE2, a PCNA-associated protein, plays a key role in maintaining active replication and counteracting replication stress by regulating the replication fork protection complex (FPC). SDE2 directly interacts with the FPC component TIMELESS (TIM) and enhances its stability, thereby aiding TIM localization to replication forks and the coordination of replisome progression. Like TIM deficiency, knockdown of SDE2 leads to impaired fork progression and stalled fork recovery, along with a failure to activate CHK1 phosphorylation. Moreover, loss of SDE2 or TIM results in an excessive MRE11-dependent degradation of reversed forks. Together, our study uncovers an essential role for SDE2 in maintaining genomic integrity by stabilizing the FPC and describes a new role for TIM in protecting stalled replication forks. We propose that TIM-mediated fork protection may represent a way to cooperate with BRCA-dependent fork stabilization.The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.Mice lacking IκB-ζ, a protein encoded by the Nfkbiz gene, spontaneously develop a Sjögren's syndrome-like disease involving the lachrymal glands, but no salivary gland symptoms have been reported. We found that Nfkbiz-/- female mice presented a significantly reduced salivary flow rate, focal lymphocytic sialadenitis (FLS), and a dysbiotic oral microbiota at week 24. To dissect the contributions of genetic and environmental factors to the salivary gland phenotype, Nfkbiz+/+ and Nfkbiz-/- mice were cohoused after weaning and evaluated at week 20. Cohousing alleviated the salivary gland phenotype of Nfkbiz-/- mice but did not induce any disease phenotype in Nfkbiz+/+ mice. Additionally, the oral microbiota in the cohoused mice was synchronized toward that in Nfkbiz+/+ mice. In conclusion, IκB-ζ-deficient mice developed hyposalivation and FLS, in which a dysbiotic oral microbiota played an important role. This finding suggests that the dysbiotic oral microbiota could be a therapeutic target.Diverse methods have been developed to tailor the number of metal atoms in metal nanoclusters, but control of surface ligand number at a given cluster size is rare. Here we demonstrate that reversible addition and elimination of a single surface thiolate ligand (-SR) on gold nanoclusters can be realized, opening the door to precision ligand engineering on atomically precise nanoclusters. We find that oxidative etching of [Au25SR18]- nanoclusters adds an excess thiolate ligand and generates a new species, [Au25SR19]0. The addition reaction can be reversed by CO reduction of [Au25SR19]0, leading back to [Au25SR18]- and eliminating precisely one surface ligand.  https://www.selleckchem.com/products/kpt-330.html  Intriguingly, we show that the ligand shell of Au25 nanoclusters becomes more fragile and rigid after ligand addition. This reversible addition/elimination reaction of a single surface ligand on gold nanoclusters shows potential to precisely control the number of surface ligands and to explore new ligand space at each nuclearity.