DNA methylation modulates nucleosome retention in sperm and H3K4 methylation deposition in early mouse embryos.

In the germ line and during early embryogenesis, DNA methylation (DNAme) undergoes global erasure and re-establishment to support germ cell and embryonic development. While DNAme acquisition during male germ cell development is essential for setting genomic DNA methylation imprints, other intergenerational roles for paternal DNAme in defining embryonic chromatin are unknown. Through conditional gene deletion of the de novo DNA methyltransferases Dnmt3a and/or Dnmt3b, we observe that DNMT3A primarily safeguards against DNA hypomethylation in undifferentiated spermatogonia, while DNMT3B catalyzes de novo DNAme during spermatogonial differentiation.

mRNA export factors store nascent transcripts within nuclear speckles as an adaptive response to transient global inhibition of transcription.

Several transcription inhibitors have been developed as cancer therapies. However, they show modest clinical activity, highlighting that our understanding of the cellular response to transcriptional inhibition remains incomplete. Here we report that potent inhibitors of transcription not only impact mRNA output but also markedly impair mRNA transcript localization and nuclear export.

Structural insights into distinct mechanisms of RNA polymerase II and III recruitment to snRNA promoters.

RNA polymerase III (Pol III) transcribes short, essential RNAs, including the U6 small nuclear RNA (snRNA). At U6 snRNA genes, Pol III is recruited by the snRNA Activating Protein Complex (SNAPc) and a Brf2-containing TFIIIB complex, forming a pre-initiation complex (PIC). Uniquely, SNAPc also recruits Pol II at the remaining splicesosomal snRNA genes (U1, 2, 4 and 5).

Amygdala intercalated cells form an evolutionarily conserved system orchestrating brain networks.

The amygdala attributes valence and emotional salience to environmental stimuli and regulates how these stimuli affect behavior. Within the amygdala, a distinct class of evolutionarily conserved neurons form the intercalated cell (ITC) clusters, mainly located around the boundaries of the lateral and basal nuclei. Here, we review the anatomical, physiological and molecular characteristics of ITCs, and detail the organization of ITC clusters and their connectivity with one another and other brain regions.

Ecological diversification in sexual and asexual lineages.

The presence or absence of sex can have a strong influence on the processes whereby species arise. Yet, the mechanistic underpinnings of this influence are poorly understood. To gain insights into the mechanisms whereby the reproductive mode may influence ecological diversification, we investigate how natural selection, genetic mixing, and the reproductive mode interact and how this interaction affects the evolutionary dynamics of diversifying lineages.

Microglial Lyzl4 Facilitates β-Amyloid Clearance in Alzheimer's Disease.

Alzheimer's Disease (AD) is a neurodegenerative condition characterized by the accumulation and deposition of amyloid-β (Aβ) aggregates in the brain. Despite a wealth of research on the toxicity of Aβ and its role in synaptic damage, the mechanisms facilitating Aβ clearance are not yet fully understood. However, microglia, the primary immune cells of the central nervous system, are known to maintain homeostasis through the phagocytic clearance of protein aggregates and cellular debris.

The human gestational sac as a choriovitelline placenta during early pregnancy; the secondary yolk sac and organoid models.

The yolk sac is phylogenetically the oldest of the extra-embryonic membranes and plays important roles in nutrient transfer during early pregnancy in many species. In the human this function is considered largely vestigial, in part because the secondary yolk sac never makes contact with the inner surface of the chorionic sac. Instead, it is separated from the chorion by the fluid-filled extra-embryonic coelom and attached to the developing embryo by a relatively long vitelline duct.

TORC2 inhibition triggers yeast chromosome fragmentation through misregulated Base Excision Repair of clustered oxidation events.

Combinational therapies provoking cell death are of major interest in oncology. Combining TORC2 kinase inhibition with the radiomimetic drug Zeocin results in a rapid accumulation of double-strand breaks (DSB) in the budding yeast genome. This lethal Yeast Chromosome Shattering (YCS) requires conserved enzymes of base excision repair.

Loss of cytoplasmic actin filaments raises nuclear actin levels to drive INO80C-dependent chromosome fragmentation.

Loss of cytosolic actin filaments upon TORC2 inhibition triggers chromosome fragmentation in yeast, which results from altered base excision repair of Zeocin-induced lesions. To find the link between TORC2 kinase and this yeast chromosome shattering (YCS) we performed phosphoproteomics. YCS-relevant phospho-targets included plasma membrane-associated regulators of actin polymerization, such as Las17, the yeast Wiscott-Aldrich Syndrome protein.

In vitro gametogenesis: Towards competent oocytes: Limitations and future improvements for generating oocytes from pluripotent stem cells in culture.

Production of oocytes from pluripotent cell cultures in a dish represents a new paradigm in stem cell and developmental biology and has implications for how we think about life. The spark of life for the next generation occurs at fertilization when sperm and oocyte fuse. In animals, gametes are the only cells that transmit their genomes to the next generation.

The genetic architecture of protein interaction affinity and specificity.

The encoding and evolution of specificity and affinity in protein-protein interactions is poorly understood. Here, we address this question by quantifying how all mutations in one protein, JUN, alter binding to all other members of a protein family, the 54 human basic leucine zipper transcription factors. We fit a global thermodynamic model to the data to reveal that most affinity changing mutations equally affect JUN's affinity to all its interaction partners.

SciJava Ops: an improved algorithms framework for Fiji and beyond.

Decades of iteration on scientific imaging hardware and software has yielded an explosion in not only the size, complexity, and heterogeneity of image datasets but also in the tooling used to analyze this data. This wealth of image analysis tools, spanning different programming languages, frameworks, and data structures, is itself a problem for data analysts who must adapt to new technologies and integrate established routines to solve increasingly complex problems. While many "bridge" layers exist to unify pairs of popular tools, there exists a need for a general solution to unify new and existing toolkits.

Antagonism between H3K27me3 and genome-lamina association drives atypical spatial genome organization in the totipotent embryo.

In mammals, early embryonic development exhibits highly unusual spatial positioning of genomic regions at the nuclear lamina, but the mechanisms underpinning this atypical genome organization remain elusive. Here, we generated single-cell profiles of lamina-associated domains (LADs) coupled with transcriptomics, which revealed a striking overlap between preimplantation-specific LAD dissociation and noncanonical broad domains of H3K27me3. Loss of H3K27me3 resulted in a restoration of canonical LAD profiles, suggesting an antagonistic relationship between lamina association and H3K27me3.

Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning.

Perception can be refined by experience, up to certain limits. It is unclear whether perceptual limits are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest that peripheral nerve stimulation, specifically vagus nerve stimulation (VNS), can alter neural activity and augment experience-dependent plasticity, although little is known about central mechanisms recruited by VNS.