Notes

Neuro-Behçet Condition, Neuro-Sweet Condition, and also Range Disorders.
In several metazoans, the number of active replication origins in embryonic nuclei is higher than in somatic ones, ensuring rapid genome duplication during synchronous embryonic cell divisions. High replication origin density can be restored by somatic nuclear reprogramming. However, mechanisms underlying high replication origin density formation coupled to rapid cell cycles are poorly understood. Here, using Xenopus laevis, we show that SSRP1 stimulates replication origin assembly on somatic chromatin by promoting eviction of histone H1 through its N-terminal domain. Histone H1 removal derepresses ORC and MCM chromatin binding, allowing efficient replication origin assembly. LY2874455 inhibitor SSRP1 protein decays at mid-blastula transition (MBT) when asynchronous somatic cell cycles start. Increasing levels of SSRP1 delay MBT and, surprisingly, accelerate post-MBT cell cycle speed and embryo development. These findings identify a major epigenetic mechanism regulating DNA replication and directly linking replication origin assembly, cell cycle duration and embryo development in vertebrates.Transition metal-catalysed C-H hydroxylation is one of the most notable advances in synthetic chemistry during the past few decades and it has been widely employed in the preparation of alcohols and phenols. The site-selective hydroxylation of aromatic C-H bonds under mild conditions, especially in the context of substituted (hetero)arenes with diverse functional groups, remains a challenge. Here, we report a general and mild chelation-assisted C-H hydroxylation of (hetero)arenes mediated by boron species without the use of any transition metals. Diverse (hetero)arenes bearing amide directing groups can be utilized for ortho C-H hydroxylation under mild reaction conditions and with broad functional group compatibility. Additionally, this transition metal-free strategy can be extended to synthesize C7 and C4-hydroxylated indoles. By utilizing the present method, the formal synthesis of several phenol intermediates to bioactive molecules is demonstrated.Proper membrane physiology requires maintenance of biophysical properties, which must be buffered from external perturbations. While homeostatic adaptation of membrane fluidity to temperature variation is a ubiquitous feature of ectothermic organisms, such responsive membrane adaptation to external inputs has not been directly observed in mammals. Here, we report that challenging mammalian membranes by dietary lipids leads to robust lipidomic remodeling to preserve membrane physical properties. Specifically, exogenous polyunsaturated fatty acids are rapidly incorporated into membrane lipids, inducing a reduction in membrane packing. These effects are rapidly compensated both in culture and in vivo by lipidome-wide remodeling, most notably upregulation of saturated lipids and cholesterol, resulting in recovery of membrane packing and permeability. Abrogation of this response results in cytotoxicity when membrane homeostasis is challenged by dietary lipids. These results reveal an essential mammalian mechanism for membrane homeostasis wherein lipidome remodeling in response to dietary lipid inputs preserves functional membrane phenotypes.UV-B constitutes a critical part of the sunlight reaching the earth surface. The homodimeric plant UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) monomerizes in response to UV-B and induces photomorphogenic responses, including UV-B acclimation and tolerance. REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 (RUP1) and RUP2 are negative feedback regulators that operate by facilitating UVR8 ground state reversion through re-dimerization. Here we show that RUP1 and RUP2 are transcriptionally induced by cryptochrome photoreceptors in response to blue light, which is dependent on the bZIP transcriptional regulator ELONGATED HYPOCOTYL 5 (HY5). Elevated RUP1 and RUP2 levels under blue light enhance UVR8 re-dimerization, thereby negatively regulating UVR8 signalling and providing photoreceptor pathway cross-regulation in a polychromatic light environment, as is the case in nature. We further show that cryptochrome 1, as well as the red-light photoreceptor phytochrome B, contribute to UV-B tolerance redundantly with UVR8. Thus, photoreceptors for both visible light and UV-B regulate UV-B tolerance through an intricate interplay allowing the integration of diverse sunlight signals.Macrophages have important protective functions during infection with herpes simplex virus type 1 (HSV-1). However, molecular mechanisms that restrict viral propagation and protect from severe disease are unclear. Here we show that macrophages take up HSV-1 via endocytosis and transport the virions into multivesicular bodies (MVBs). In MVBs, acid ceramidase (aCDase) converts ceramide into sphingosine and increases the formation of sphingosine-rich intraluminal vesicles (ILVs). Once HSV-1 particles reach MVBs, sphingosine-rich ILVs bind to HSV-1 particles, which restricts fusion with the limiting endosomal membrane and prevents cellular infection. Lack of aCDase in macrophage cultures or in Asah1-/- mice results in replication of HSV-1 and Asah1-/- mice die soon after systemic or intravaginal inoculation. The treatment of macrophages with sphingosine enhancing compounds blocks HSV-1 propagation, suggesting a therapeutic potential of this pathway. In conclusion, aCDase loads ILVs with sphingosine, which prevents HSV-1 capsids from penetrating into the cytosol.Protein-dominant cellular processes cannot be fully decoded without precise manipulation of their activity and localization in living cells. Advances in optogenetics have allowed spatiotemporal control over cellular proteins with molecular specificity; however, these methods require recombinant expression of fusion proteins, possibly leading to conflicting results. Instead of modifying proteins of interest, in this work, we focus on design of a tunable recognition unit and develop an aptamer-based near-infrared (NIR) light-responsive nanoplatform for manipulating the subcellular localization of specific proteins in their native states. Our results demonstrate that this nanoplatform allows photocontrol over the cytoplasmic-nuclear shuttling behavior of the target RelA protein (a member of the NF-κβ family), enabling regulation of RelA-related signaling pathways. With a modular design, this aptamer-based nanoplatform can be readily extended for the manipulation of different proteins (e.g., lysozyme and p53), holding great potential to develop a variety of label-free protein photoregulation strategies for studying complex biological events.
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