Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells.

The six-subunit origin recognition complex (ORC) loads excess MCM2-7 on chromosomes to promote initiation of DNA replication and is believed to be important for origin specification. Mapping of origins in cancer cell lines engineered to delete three of the subunits, ORC1, ORC2, or ORC5, shows that specific origins are still used and are mostly at the same sites in the genome as in wild-type cells. The few thousand origins that were upregulated in the absence of ORC suggest that GC/TA skewness and simple repeat sequences facilitate, but are not essential for, origin selection in the absence of the six-subunit ORC.

MINFLUX achieves molecular resolution with minimal photons.

Optical super-resolution microscopy is a key technology for structural biology that offers high imaging contrast and live-cell compatibility. Minimal (fluorescence) photon flux microscopy, or MINFLUX, is an emerging super-resolution technique that localizes single fluorophores with high spatiotemporal precision by targeted scanning of a patterned excitation beam featuring a minimum. MINFLUX offers super-resolution imaging with nanometre resolution.

Cohesin supercoils DNA during loop extrusion.

Cohesin extrudes genomic DNA into loops that promote chromatin assembly, gene regulation, and gene recombination. Loop extrusion depends on large-scale conformational changes in cohesin, but how these translocate DNA is poorly understood. Here, we provide evidence that cohesin negatively supercoils DNA during loop extrusion.

SP140-RESIST pathway regulates interferon mRNA stability and antiviral immunity.

Type I interferons are essential for antiviral immunity but must be tightly regulated. The conserved transcriptional repressor SP140 inhibits interferon-β (Ifnb1) expression through an unknown mechanism. Here we report that SP140 does not directly repress Ifnb1 transcription.

A dynamic histone-based chromatin regulatory toolkit underpins genome and developmental evolution in an invertebrate clade.

Background: The dynamic addition and removal of posttranslational modifications on eukaryotic histones define regulatory regions that play a central role in genome and chromatin biology. However, our understanding of these regulatory mechanisms in animals is primarily based on a few model systems, preventing a general understanding of how histone-based regulation directs and promotes phenotypic variation during animal embryogenesis.

Results: Here, we apply a comprehensive multi-omics approach to dissect the histone-based regulatory complement in Annelida, one of the largest invertebrate clades.

An ex vivo study on the correlation between lesion size and resin infiltration area in natural proximal subsurface carious lesions deproteinized with sodium hypochlorite.

Objective: This ex vivo study investigated the effects of pre-treatment either with or without a deproteinization procedure using a sodium hypochlorite (NaOCl) solution on percentage resin infiltration in natural non-cavitated proximal subsurface carious lesions of (pre)molars. Moreover, we studied whether a correlation exists between lesion size and infiltration area.

Methods: Extracted human premolars and permanent molars (n = 40 each) with macroscopically non-cavitated proximal subsurface carious lesions (ICDAS code 2/radiographic E2 and D1 lesions) were randomly divided into two groups.

Inducible protein degradation reveals inflammation-dependent function of the T cell lineage-defining transcription factor Foxp3.

Regulatory T cells (T cells) are immunosuppressive CD4 T cells defined by expression of the transcription factor Foxp3. Genetic loss-of-function mutations in cause lethal multiorgan autoimmune inflammation resulting from defects in T cell development and suppressive activity. Whether T cells are continuously dependent on Foxp3 is still unclear.

Life-history trade-offs explain local adaptation in .

Local adaptation has been demonstrated in many organisms, but the traits involved, and the temporal and spatial scales at which selection acts are generally unknown. We carried out a multi-year study of 200 accessions (natural inbred lines) of Swedish using local field sites and a combination of common-garden experiments that measured adult survival and fecundity, and selection experiments that measured fitness over the full life cycle. We found evidence of strong and variable selection, with particular genotypes favored more than five-fold in certain years and locations.

Co-evolving infectivity and expression patterns drive the diversification of endogenous retroviruses.

Transposable elements are major contributors to the evolution of their hosts, but the mechanisms driving their own diversification remain poorly understood. Here, we reveal key principles governing the evolution of insect endogenous retroviruses (ERVs), a class of infectious LTR-retrotransposons that encode an Envelope protein. Through comparative analyses and experimental studies of transposon replication cycles in Drosophila, we demonstrate how two crucial ERV traits-infectivity and spatiotemporal expression-co-evolve.

A maize near-isogenic line population designed for gene discovery and characterization of allelic effects.

In this study, we characterized a panel of 1264 maize near-isogenic lines (NILs), developed from crosses between 18 diverse inbred lines and the recurrent parent B73, referred to as nested NILs (nNILs). In this study, 888 of the nNILs were genotyped using genotyping-by-sequencing (GBS). Subsequently, 24 of these nNILs, and all the parental lines, were re-genotyped using a high-density single nucleotide polymorphism (SNP) chip.

Proteomic and metabolomic profiling of extracellular vesicles produced by human gut archaea.

Gastrointestinal bacteria interact with the host and each other through various mechanisms, including the production of extracellular vesicles (EVs). However, the composition and potential roles of EVs released by gut archaea are poorly understood. Here, we study EVs produced by four strains of human gut-derived methanogenic archaea: Methanobrevibacter smithii ALI, M.

Symmetries and synchronization from whole-neural activity in the connectome: Integration of functional and structural networks.

Understanding the dynamical behavior of complex systems from their underlying network architectures is a long-standing question in complexity theory. Therefore, many metrics have been devised to extract network features like motifs, centrality, and modularity measures. It has previously been proposed that network symmetries are of particular importance since they are expected to underlie the synchronization of a system's units, which is ubiquitously observed in nervous system activity patterns.

Multiplex PCR for identification and β-lactam resistance gene detection in clinical isolates of Acinetobacter baumannii.

Introduction: Acinetobacter baumannii (A. baumannii) is a major cause of hospital-acquired infections and frequently harbors antibiotic-resistance genes that complicate treatment. Rapid identification and resistance gene detection are essential for effective antibiotic use and infection control.

NMR-driven structure-based drug discovery by unveiling molecular interactions.

High-resolution 3D structural information is crucial for drug discovery and routinely used in structure-guided optimization to improve initial hits from screening campaigns to clinical drug candidates. X-ray crystallography is commonly the method of choice to guide medicinal chemistry in the design process, but it has its limitations and shortcomings. Here, we discuss the use of solution-state NMR spectroscopy in combination with selective side-chain labeling and advanced computational workflows to generate protein-ligand ensembles.

Purinergic receptors play a key role in shock wave-induced proliferation.

Shock wave treatment (SWT) is a non-invasive therapy applied in musculoskeletal and urological disorders, as well as in chronic wound regeneration. As the use of medical SWT broadens, it is important to better understand the molecular mechanisms underlying its success. Here, we identified P2X4 and P2Y2 purinergic receptors to be primarily expressed in C3H/10T1/2 mouse mesenchymal stromal cells and investigated their role in the initiation of the signaling events following SWT using single- and double-receptor knock-out (KO) cell lines.

Cell-context response to germ layer differentiation signals is predetermined by the epigenome in regionalized epiblast populations.

Stem cells hold promise in regenerative medicine as they have the potential to differentiate into a variety of specialized cell types. However, mechanisms underlying stem cell potency and lineage acquisition remain elusive. Epigenetic modifications and genome accessibility prime cellular feedback to signalling cues, influencing lineage differentiation outcomes.

When the Past Fades: Detecting Phylogenetic Signal with SatuTe.

In phylogenetics, the phenomenon of saturation is well known, although its influence on tree reconstruction lacks a systematic and well-founded method. Here, we propose a new measure of the phylogenetic information shared between two subtrees connected by a branch in a phylogeny. This measure generalizes the concept of saturation between two sequences to a theory of saturation between subtrees, whose implementation we provide as the versatile program SatuTe.

At-RS31 orchestrates hierarchical cross-regulation of splicing factors and integrates alternative splicing with TOR-ABA pathways.

Alternative splicing is essential for plants, enabling a single gene to produce multiple transcript variants to boost functional diversity and fine-tune responses to environmental and developmental cues. Arabidopsis thaliana At-RS31, a plant-specific splicing factor in the Serine/Arginine-rich (SR) protein family, responds to light and the Target of Rapamycin (TOR) signalling pathway, yet its downstream targets and regulatory impact remain unknown. To identify At-RS31 targets, we applied individual-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) and RNAcompete assays.

Crystal structures of the mycolic acid methyl transferase 1 (MmaA1) from in the apo-form and in complex with different cofactors reveal unique features for substrate binding.

Mycolic acid methyl transferase 1 (MmaA1) protein from plays a crucial role in the biosynthesis of cell wall mycolic acids that aid in survival of the bacteria under adverse conditions. The enzyme converts a to a olefin and adds a methyl group at the proximal position of both methoxy and keto-mycolic acid chains. Here we report the crystal structures of apo-MmaA1 and complexes with the cofactor S-adenosylmethionine (SAM), the end-product of methylation reactions - S-adenosylhomocysteine (SAH), and the nucleoside analog Sinefungin (SFG) at 1.

Molecular basis of positional memory in limb regeneration.

The amputation of a salamander limb triggers anterior and posterior connective tissue cells to form distinct signalling centres that together fuel regeneration. Anterior and posterior identities are established during development and are thought to persist for the whole life in the form of positional memory. However, the molecular basis of positional memory and whether positional memory can be altered remain unknown.

Bat organoids reveal antiviral responses at epithelial surfaces.

Bats can host viruses of pandemic concern without developing disease. The mechanisms underlying their exceptional resilience to viral infections are largely unresolved, necessitating the development of physiologically relevant and genetically tractable research models. Here, we developed respiratory and intestinal organoids that recapitulated the cellular diversity of the in vivo epithelium present in Rousettus aegyptiacus, the natural reservoir for the highly pathogenic Marburg virus (MARV).

Bisulphite sequencing in the presence of cytosine-conversion errors.

'Tagmentation' approaches to bisulphite sequencing use a transposase to simultaneously make double-stranded breaks and ligate adaptors to the resulting fragments, allowing for higher throughput with less starting material. However, it has also been noted that certain tagmentation protocols have an unusually high number unmethylated cytosines that are not converted to thymine. Here we describe this phenomenon in detail, and find that results are consistent with single strand nicks by the transposase, followed by strand displacement of part or all of the DNA fragment, leading to erroneous incorporation of methylated cytosines.

A conserved role for centriolar satellites in translation of centrosomal and ciliary proteins.

Centriolar satellites are cytoplasmic particles found in the vicinity of centrosomes and cilia whose specific functional contribution has long been unclear. Here, we identify Combover as the Drosophila ortholog of the main scaffolding component of satellites, PCM1. Like PCM1, Combover localizes to cytoplasmic foci containing centrosomal proteins and its depletion or mutation results in centrosomal and ciliary phenotypes.

Autophagy in plants.

Autophagy is a process of cellular self-eating, which allows organisms to eliminate and recycle unwanted components and damaged organelles to maintain cellular homeostasis. It is an important process in the development of eukaryotic organisms. Autophagy plays a critical role in many physiological processes in plants such as nutrient remobilization, cell death, immunity, and abiotic stress responses.