Tilleymcmahan2583

Pyrimidine synthetic genes peaked during DNA replication, and their depletion caused a filamentation phenotype that phenocopied defects in this process. In contrast, the inosine monophasphate dehydrogenase dedicated to guanosine synthesis, GuaB2, displayed the opposite expression pattern and its depletion perturbed septation. Together, these data imply obligate coordination between primary metabolism and cell division and identify periodically regulated genes that can be related to specific cell biological functions.Checkpoint cascades link cell cycle progression with essential chromosomal processes. During meiotic prophase, recombination and chromosome synapsis are monitored by what are considered distinct checkpoints. In budding yeast, cells that lack the AAA+ ATPase Pch2 show an impaired cell cycle arrest in response to synapsis defects. However, unperturbed pch2Δ cells are delayed in meiotic prophase, suggesting paradoxical roles for Pch2 in cell cycle progression. Here, we provide insight into the checkpoint roles of Pch2 and its connection to Hop1, a HORMA domain-containing client protein. Contrary to current understanding, we find that Pch2 (together with Hop1) is crucial for checkpoint function in response to both recombination and synapsis defects, thus revealing a shared meiotic checkpoint cascade. check details Meiotic checkpoint responses are transduced by DNA break-dependent phosphorylation of Hop1. Based on our data and on the described effect of Pch2 on HORMA topology, we propose that Pch2 promotes checkpoint proficiency by catalyzing the availability of signaling-competent Hop1. Conversely, we demonstrate that Pch2 can act as a checkpoint silencer, also in the face of persistent DNA repair defects. We establish a framework in which Pch2 and Hop1 form a homeostatic module that governs general meiotic checkpoint function. We show that this module can-depending on the cellular context-fuel or extinguish meiotic checkpoint function, which explains the contradictory roles of Pch2 in cell cycle control. Within the meiotic prophase checkpoint, the Pch2-Hop1 module thus operates analogous to the Pch2/TRIP13-Mad2 module in the spindle assembly checkpoint that monitors chromosome segregation.Plant organs can adopt a wide range of shapes, resulting from highly directional cell growth and divisions. We focus here on leaves and leaf-like organs in Arabidopsis and tomato, characterized by the formation of thin, flat laminae. Combining experimental approaches with 3D mechanical modeling, we provide evidence that leaf shape depends on cortical microtubule mediated cellulose deposition along the main predicted stress orientations, in particular, along the adaxial-abaxial axis in internal cell walls. This behavior can be explained by a mechanical feedback and has the potential to sustain and even amplify a preexisting degree of flatness, which in turn depends on genes involved in the control of organ polarity and leaf margin formation.Primary cilia are ubiquitous antenna-like organelles that mediate cellular signaling and represent hotspots for human diseases termed ciliopathies. Within cilia, subcompartments are established to support signal transduction pathways, including Hedgehog signaling. How these compartments are formed and maintained remains largely unknown. Cilia use two mechanisms, a trafficking system and a diffusion barrier, to regulate the trafficking of proteins into, within, and out of cilia. The main ciliary trafficking machinery, intraflagellar transport (IFT), facilitates bidirectional transport of cargo, including signaling proteins, from the base (basal body) to the tip of the axoneme [1]. Anterograde IFT to the tip relies on kinesins, and cytoplasmic dynein enables retrograde transport back [2, 3]. To help confine proteins to cilia, a subdomain immediately distal to the basal body, called the transition zone (TZ), acts as a diffusion barrier for both membrane and soluble proteins [4-6]. Here, we show that in Caenorhabditis elegans a salt-sensing receptor-type guanylate cyclase, GCY-22, accumulates at a high concentration within a subcompartment at the distal region of the cilium. Targeting of GCY-22 to the ciliary tip is dynamic, requiring the IFT system. Disruption of the TZ barrier or IFT trafficking causes GCY-22 protein mislocalization and defects in the formation and maintenance of the ciliary tip compartment. Structure-function studies uncovered GCY-22 protein domains needed for entry and tip localization. Together, our findings provide mechanistic insights into the formation and maintenance of a novel subdomain at the cilium tip that contributes to the behavioral response to NaCl.Many pregnancy-related deaths remain preventable, particularly those associated with postpartum hemorrhage (PPH). The use of bundles for care of women during the perinatal period has been shown to improve maternal and neonatal outcomes. Drills or simulation-based learning are an integral part of a broader implementation of postpartum hemorrhage bundles. In addition, The Joint Commission has cited drills as one of the required performance elements of accreditation. It is therefore incumbent upon perinatal clinical teams to conduct PPH simulations as a readiness tool. This article is intended to help nurses and other clinicians enhance the realism of low- and medium-fidelity PPH simulations.Osteoporosis is the most prevalent metabolic bone disease, characterized by low bone mass and microarchitectural deterioration. Here, we show that warmth exposure (34°C) protects against ovariectomy-induced bone loss by increasing trabecular bone volume, connectivity density, and thickness, leading to improved biomechanical bone strength in adult female, as well as in young male mice. Transplantation of the warm-adapted microbiota phenocopies the warmth-induced bone effects. Both warmth and warm microbiota transplantation revert the ovariectomy-induced transcriptomics changes of the tibia and increase periosteal bone formation. Combinatorial metagenomics/metabolomics analysis shows that warmth enhances bacterial polyamine biosynthesis, resulting in higher total polyamine levels in vivo. Spermine and spermidine supplementation increases bone strength, while inhibiting polyamine biosynthesis in vivo limits the beneficial warmth effects on the bone. Our data suggest warmth exposure as a potential treatment option for osteoporosis while providing a mechanistic framework for its benefits in bone disease.