Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters

Our study focuses on a family of ubiquitously expressed human C₂H₂ zinc finger proteins comprised of ZFX, ZFY and ZNF711. Although their protein structure suggests that ZFX, ZFY and ZNF711 are transcriptional regulators, the mechanisms by which they influence transcription have not yet been elucidated. We used CRISPR-mediated deletion to create bi-allelic knockouts of ZFX and/or ZNF711 in female HEK293T cells (which naturally lack ZFY). We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation. RNA-seq analysis revealed that thousands of genes showed altered expression in the double knockout clones, suggesting that these TFs are critical regulators of the transcriptome. To gain insight into how these TFs regulate transcription, we created mutant ZFX proteins and analyzed them for DNA binding and transactivation capability. We found that zinc fingers 11–13 are necessary and sufficient for DNA binding and, in combination with the N terminal region, constitute a functional transactivator. Our functional analyses of the ZFX family provides important new insights into transcriptional regulation in human cells by members of the large, but under-studied family of C₂H₂ zinc finger proteins

dCas9-based epigenome editing suggests acquisition of histone methylation is not sufficient for target gene repression.

Distinct epigenomic profiles of histone marks have been associated with gene expression, but questions regarding the causal relationship remain. Here we investigated the activity of a broad collection of genomically targeted epigenetic regulators that could write epigenetic marks associated with a repressed chromatin state (G9A, SUV39H1, Krüppel-associated box (KRAB), DNMT3A as well as the first targetable versions of Ezh2 and Friend of GATA-1 (FOG1)). dCas9 fusions produced target gene repression over a range of 0- to 10-fold that varied by locus and cell type. dCpf1 fusions were unable to repress gene expression. The most persistent gene repression required the action of several effector domains; however, KRAB-dCas9 did not contribute to persistence in contrast to previous reports. A 'direct tethering' strategy attaching the Ezh2 methyltransferase enzyme to dCas9, as well as a 'recruitment' strategy attaching the N-terminal 45 residues of FOG1 to dCas9 to recruit the endogenous nucleosome remodeling and deacetylase complex, were both successful in targeted deposition of H3K27me3. Surprisingly, however, repression was not correlated with deposition of either H3K9me3 or H3K27me3. Our results suggest that so-called repressive histone modifications are not sufficient for gene repression. The easily programmable dCas9 toolkit allowed precise control of epigenetic information and dissection of the relationship between the epigenome and gene regulation

Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters

Our study focuses on a family of ubiquitously expressed human C₂H₂ zinc finger proteins comprised of ZFX, ZFY and ZNF711. Although their protein structure suggests that ZFX, ZFY and ZNF711 are transcriptional regulators, the mechanisms by which they influence transcription have not yet been elucidated. We used CRISPR-mediated deletion to create bi-allelic knockouts of ZFX and/or ZNF711 in female HEK293T cells (which naturally lack ZFY). We found that loss of either ZFX or ZNF711 reduced cell growth and that the double knockout cells have major defects in proliferation. RNA-seq analysis revealed that thousands of genes showed altered expression in the double knockout clones, suggesting that these TFs are critical regulators of the transcriptome. To gain insight into how these TFs regulate transcription, we created mutant ZFX proteins and analyzed them for DNA binding and transactivation capability. We found that zinc fingers 11–13 are necessary and sufficient for DNA binding and, in combination with the N terminal region, constitute a functional transactivator. Our functional analyses of the ZFX family provides important new insights into transcriptional regulation in human cells by members of the large, but under-studied family of C₂H₂ zinc finger proteins

Sub-seasonal forecasts of demand and wind power and solar power generation for 28 European countries

Electricity systems are becoming increasingly exposed to weather. The need for high-quality meteorological forecasts for managing risk across all timescales has therefore never been greater. This paper seeks to extend the uptake of meteorological data in the power systems modelling community to include probabilistic meteorological forecasts at sub-seasonal lead-times. Such forecasts are growing in skill and are receiving considerable attention in power system risk management and energy trading. Despite this interest, these forecasts are rarely evaluated in power system terms and technical barriers frequently prohibit use by non-meteorological specialists. This paper therefore presents data produced through a new EU climate services program Subseasonal-to-seasonal forecasting for Energy (S2S4E). The data corresponds to a suite of well-documented, easy-to-use, self-consistent daily- and nationally aggregated time-series for wind power, solar power and electricity demand across 28 European countries. The data is accessible from http://dx.doi.org/10.17864/1947.275, (Gonzalez et al., 2020). The data includes a set of daily ensemble reforecasts from two leading forecast systems spanning 20-years (ECMWF, an 11 member ensemble, with twice weekly starts for 1996-2016, totalling 21,210 forecasts) and 11 years (NCEP, a 12 member lagged-ensemble, constructed to match the start dates from the ECMWF forecast. from 1999-2010, totalling 4608 forecasts). The reforecasts containing multiple plausible realisations of daily-weather and power data for up to 6 weeks in the future. To the authors’ knowledge, this is the first time fully calibrated and post-processed daily power system forecast set has been published, and this is the primary purpose of this paper. A brief review of forecast skill in each of the individual primary power system properties and a composite property is presented, focusing on the winter season. The forecast systems contain additional skill over climatological expectation for weekly-average forecasts at extended lead-times, though this skill depends on the nature of the forecast metric considered. This highlights the need for greater collaboration between the energy- and meteorological research communities to develop applications, and it is hoped that publishing these data and tools will support this

Vortex splitting on a planetary scale in the stratosphere by cyclogenesis on a subplanetary scale in the troposphere

It is hypothesized that a splitting of the stratospheric polar vortex and a sudden warming can result when the polar vortex is elongated and a closed cyclonic circulation develops on a subplanetary scale in the troposphere beneath one of its tips. The hypothesis is supported by studying the splitting event in the Southern Hemisphere during spring 2002. Potential vorticity inversion and an inverse modelling technique using the adjoint of a fully nonlinear dynamical model are used to confirm that splitting is sensitive to subplanetary-scale cyclogenesis when it is strong. Examples of stratospheric vortex-splitting events in the Northern Hemisphere are consistent with the hypothesis. The proposed mechanism for splitting contrasts with the commonly accepted one that it is caused by the upward propagation of a planetary wave from the troposphere. It is suggested that the phenomenon is better understood as an example of a vortex interaction rather than as a wave–mean flow interaction

Soil health -- a new challenge for microbiologists and chemists.

The original publication is available on LINK at http://revistes.iec.cat/index.php/IM/article/view/4c457c718d531.002 This work, including photographs and other illustrations, unless the contrary is indicated, is subject to an Attributions–Non-Commercial–ShareAlike 3.0 Creative Commons License, the full text of which can be consulted at http://creativecommons.org/licenses/by-nc-sa/3.0/. You are free to share, copy, distribute and transmit the work provided that the author is credited and reuse of the material is restricted to non-commercial purposes only and that if you alter, transform, or build upon this work, you may distribute the resulting work only under the same or similar license to this on

MICROGRID RESILIENCE ANALYSIS SOFTWARE DEVELOPMENT

Military installation microgrids need to be resilient to a variety of potential disruptions (storms, attacks, et cetera). Various metrics for assessing microgrid resilience have been described in literature, and multiple tools for simulating microgrid performance have been constructed; however, it is often left to system owners and maintainers to bring these efforts together to identify and realize effective, efficient improvement strategies. Military microgrid stakeholders have expressed a desire for an integrated, unified platform that provides these multiple capabilities in a coordinated fashion. In support of these endeavors, analysis methods developed by NPS and NAVFAC Expeditionary Warfare Center researchers for measuring microgrid resilience have been integrated into an existing web-based microgrid power flow simulation and distributed energy resource rightsizing software tool. This was achieved by the development of additional functions and methods within the existing software platform code base, and expansion of the application programming interface (API). These API additions enabled access to the new calculation and analysis capabilities, as well as increased control over power flow simulation parameters. These analytical and functional contributions were validated through a design of experiments, including comparison to independently generated data, and factorial analysis.Outstanding ThesisCivilian, Department of the NavyCivilian, Department of the NavyCivilian, Department of the NavyCivilian, Department of the NavyCivilian, Department of the NavyApproved for public release. Distribution is unlimited