With their brilliance and temporal structure, X-ray free-electron laser can unveil atomic-scale details of ultrafast phenomena. Recent progress in split-and-delay optics (SDO), which produces two X-ray pulses with time-delays, offers bright prospects for observing dynamics at the atomic-scale. However, their insufficient pulse energy has limited its application either to phenomena with longer correlation length or to measurement with a fixed delay-time. Here we show that the combination of the SDO and self-seeding of X-rays increases the pulse energy and makes it possible to observe the atomic-scale dynamics in a timescale of picoseconds. We show that the speckle contrast in scattering from water depends on the delay-time as expected. Our results demonstrate the capability of measurement using the SDO with seeded X-rays for resolving the dynamics in temporal and spatial scales that are not accessible by other techniques, opening opportunities for studying the atomic-level dynamics.Bipolar disorder and schizophrenia are associated with brain morphometry alterations. This study investigates inter-individual variability in brain structural profiles, both within diagnostic groups and between patients and healthy individuals. Brain morphometric measures from three independent samples of patients with schizophrenia (n = 168), bipolar disorder (n = 122), and healthy individuals (n = 180) were modeled as single vectors to generated individualized profiles of subcortical volumes and regional cortical thickness. These profiles were then used to compute a person-based similarity index (PBSI) for subcortical volumes and for regional cortical thickness, to quantify the within-group similarity of the morphometric profile of each individual to that of the other participants in the same diagnostic group. There was no effect of diagnosis on the PBSI for subcortical volumes. In contrast, compared to healthy individuals, the PBSI for cortical thickness was lower in patients with schizophrenia (effect size = 0.4, p ≤ 0.0002), but not in patients with bipolar disorder. The results were robust and reproducible across samples. We conclude that disease mechanisms for these disorders produce modest inter-individual variations in brain morphometry that should be considered in future studies attempting to cluster patients in subgroups.Intensive chemotherapy for acute leukemia can usually induce complete remission, but fails in many patients to eradicate the leukemia stem cells responsible for relapse. There is accumulating evidence that these relapse-inducing cells are maintained and protected by signals provided by the microenvironment. Thus, inhibition of niche signals is a proposed strategy to target leukemia stem cells but this requires knowledge of the critical signals and may be subject to compensatory mechanisms. Signals from the niche require receptor-mediated endocytosis, a generic process dependent on the Dynamin family of large GTPases. Here, we show that Dynole 34-2, a potent inhibitor of Dynamin GTPase activity, can block transduction of key signalling pathways and overcome chemoresistance of leukemia stem cells. https://www.selleckchem.com/products/sulfosuccinimidyl-oleate-sodium.html Our results provide a significant conceptual advance in therapeutic strategies for acute leukemia that may be applicable to other malignancies in which signals from the niche are involved in disease progression and chemoresistance.The severe "Snowball Earth" glaciations proposed to have existed during the Cryogenian period (720 to 635 million years ago) coincided with the breakup of one supercontinent and assembly of another. Whereas the presence of extensive continental ice sheets predicts a tidally energetic Snowball ocean due to the reduced ocean depth, the supercontinent palaeogeography predicts weak tides because the surrounding ocean is too large to host tidal resonances. Here we show, using an established numerical global tidal model and paleogeographic reconstructions, that the Cryogenian ocean hosted diminished tidal amplitudes and associated energy dissipation rates, reaching 10-50% of today's rates, during the Snowball glaciations. We argue that the near-absence of Cryogenian tidal processes may have been one contributor to the prolonged glaciations if these were near-global. These results also constrain lunar distance and orbital evolution throughout the Cryogenian, and highlight that simulations of past oceans should include explicit tidally driven mixing processes.Histone 3 Lys 27 trimethylation (H3K27me3)-mediated epigenetic silencing plays a critical role in multiple biological processes. However, the H3K27me3 recognition and transcriptional repression mechanisms are only partially understood. Here, we report a mechanism for H3K27me3 recognition and transcriptional repression. Our structural and biochemical data showed that the BAH domain protein AIPP3 and the PHD proteins AIPP2 and PAIPP2 cooperate to read H3K27me3 and unmodified H3K4 histone marks, respectively, in Arabidopsis. The BAH-PHD bivalent histone reader complex silences a substantial subset of H3K27me3-enriched loci, including a number of development and stress response-related genes such as the RNA silencing effector gene ARGONAUTE 5 (AGO5). We found that the BAH-PHD module associates with CPL2, a plant-specific Pol II carboxyl terminal domain (CTD) phosphatase, to form the BAH-PHD-CPL2 complex (BPC) for transcriptional repression. The BPC complex represses transcription through CPL2-mediated CTD dephosphorylation, thereby causing inhibition of Pol II release from the transcriptional start site. Our work reveals a mechanism coupling H3K27me3 recognition with transcriptional repression through the alteration of Pol II phosphorylation states, thereby contributing to our understanding of the mechanism of H3K27me3-dependent silencing.As the COVID-19 pandemic progresses, obtaining information on symptoms dynamics is of essence. Here, we extracted data from primary-care electronic health records and nationwide distributed surveys to assess the longitudinal dynamics of symptoms prior to and throughout SARS-CoV-2 infection. Information was available for 206,377 individuals, including 2471 positive cases. The two datasources were discordant, with survey data capturing most of the symptoms more sensitively. The most prevalent symptoms included fever, cough and fatigue. Loss of taste and smell 3 weeks prior to testing, either self-reported or recorded by physicians, were the most discriminative symptoms for COVID-19. Additional discriminative symptoms included self-reported headache and fatigue and a documentation of syncope, rhinorrhea and fever. Children had a significantly shorter disease duration. Several symptoms were reported weeks after recovery. By a unique integration of two datasources, our study shed light on the longitudinal course of symptoms experienced by cases in primary care.