Geomagnetic Field Behavior at High Latitudes from a Paleomagnetic Record from Eltanin Core 27-21 in the Ross Sea Sector, Antarctica

We present a high-resolution paleomagnetic record from 682 discrete samples from Eltanin 27-21 (69.03°S 179.83°E), a 16-meter long piston core recovered in 1968 at a water depth of 3456 meters by the USNS Eltanin as part of Operation Deep Freeze. After removal of a low-coercivity overprint, most samples yield stable characteristic remanent magnetization directions. The downhole variation in the magnetic inclination provides a well-resolved magnetostratigraphy from the Brunhes Chron (0-0.78 Ma), through the Reunion Subchron (2.128-2.148 Ma), and into Chron C2r.2r. The sedimentation rates are sufficiently high that even short-term geomagnetic features, like the Cobb Mountain excursion, are resolved. The record from Eltanin 27-21 provides new insights into the behavior of the geomagnetic field at high latitudes, about which very little is currently known. Using the variability in the inclinations during stable polarity intervals, we estimate that the dispersion in the paleomagnetic pole position over the past ~2 Myr is 30.3°±4.3°, which is significantly greater than observed at low to mid latitude sites. The higher dispersion observed at Eltanin 27-21 is consistent with numerical modeling of the geodynamo. That modeling has shown that polar vortices can develop in the Earth’s core within the tangent cylinder, defined as the cylinder coaxial with the Earth’s rotation axis and tangent to the inner core/outer core boundary. The polar vortices produce vigorous fluid motion in the core, which creates greater geomagnetic field variability above the tangent cylinder at the surface of the Earth. The tangent cylinder intersects the Earth’s surface in the polar regions at 69.6° latitude, which is very close to the latitude of Eltanin 27-21

The prebiotic inulin modulates gut microbiota but does not ameliorate atherosclerosis in hypercholesterolemic APOE*3-Leiden. CETP mice

Functional Genomics of Systemic Disorder

The role of MORC3 in silencing transposable elements in mouse embryonic stem cells

Background Microrchidia proteins (MORCs) are involved in epigenetic gene silencing in a variety of eukaryotic organisms. Deletion of MORCs result in several developmental abnormalities and their dysregulation has been implicated in developmental disease and multiple cancers. Specifically, mammalian MORC3 mutations are associated with immune system defects and human cancers such as bladder, uterine, stomach, lung, and diffuse large B cell lymphomas. While previous studies have shown that MORC3 binds to H3K4me3 in vitro and overlaps with H3K4me3 ChIP-seq peaks in mouse embryonic stem cells, the mechanism by which MORC3 regulates gene expression is unknown. Results In this study, we identified that mutation in Morc3 results in a suppressor of variegation phenotype in a Modifiers of murine metastable epialleles Dominant (MommeD) screen. We also find that MORC3 functions as an epigenetic silencer of transposable elements (TEs) in mouse embryonic stem cells (mESCs). Loss of Morc3 results in upregulation of TEs, specifically those belonging to the LTR class of retrotransposons also referred to as endogenous retroviruses (ERVs). Using ChIP-seq we found that MORC3, in addition to its known localization at H3K4me3 sites, also binds to ERVs, suggesting a direct role in regulating their expression. Previous studies have shown that these ERVs are marked by the repressive histone mark H3K9me3 which plays a key role in their silencing. However, we found that levels of H3K9me3 showed only minor losses in Morc3 mutant mES cells. Instead, we found that loss of Morc3 resulted in increased chromatin accessibility at ERVs as measured by ATAC-seq. Conclusions Our results reveal MORC3 as a novel regulator of ERV silencing in mouse embryonic stem cells. The relatively minor changes of H3K9me3 in the Morc3 mutant suggests that MORC3 acts mainly downstream of, or in a parallel pathway with, the TRIM28/SETDB1 complex that deposits H3K9me3 at these loci. The increased chromatin accessibility of ERVs in the Morc3 mutant suggests that MORC3 may act at the level of chromatin compaction to effect TE silencing.Molecular Technology and Informatics for Personalised Medicine and Healt

A functional assay to classify ZBTB24 missense variants of unknown significance

Increasing use of next-generation sequencing technologies in clinical diagnostics allows large-scale discovery of genetic variants, but also results in frequent identification of variants of unknown significance (VUSs). Their classification into disease-causing and neutral variants is often hampered by the absence of robust functional tests. Here, we demonstrate that a luciferase reporter assay, in combination with ChIP-qPCR, reliably separates pathogenic ZBTB24 missense variants in the context of immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome from natural variants in healthy individuals and patients of other diseases. Application of our assay to two published ZBTB24 missense VUSs indicates that they are likely not to cause ICF2 syndrome. Furthermore, we show that rare gnomAD ZBTB24 missense variants in key residues of the C2H2-ZF domain lead to a loss of function phenotype that resembles ICF2, suggesting that these individuals are carriers of ICF syndrome. In summary, we have developed a robust functional test to validate missense variants in ZBTB24.Molecular Technology and Informatics for Personalised Medicine and HealthFunctional Genomics of Muscle, Nerve and Brain Disorder

Converging disease genes in ICF syndrome: ZBTB24 controls expression of CDCA7 in mammals

Molecular Technology and Informatics for Personalised Medicine and Healt