PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription

How steroid hormone receptors (SHRs) regulate transcriptional activity remains partly understood. Upon activation, SHRs bind the genome together with a co-regulator repertoire, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited co-regulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we functionally dissected the Glucocorticoid Receptor (GR) complex. We describe a functional cross-talk between PAXIP1 and the cohesin subunit STAG2, critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on chromatin, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. In lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.</p

Empire's Violent End

In Empire's Violent End, Thijs Brocades Zaalberg and Bart Luttikhuis, along with expert contributors, present comparative research focused specifically on excessive violence in Indonesia, Algeria, Vietnam, Malaysia, Kenya, and other areas during the wars of decolonization. In the last two decades, there have been heated public and scholarly debates in France, the United Kingdom, and the Netherlands on the violent end of empire. Nevertheless, the broader comparative investigations into colonial counterinsurgency tend to leave atrocities such as torture, execution, and rape in the margins. The editors describe how such comparisons mostly focus on the differences by engaging in "guilt ranking." Moreover, the dramas that have unfolded in Algeria and Kenya tend to overshadow similar violent events in Indonesia, the very first nation to declare independence directly after World War II. Empire's Violent End is the first book to place the Dutch-Indonesian case at the heart of a comparison with focused, thematic analysis on a diverse range of topics to demonstrate that despite variation in scale, combat intensity, and international dynamics, there were more similarities than differences in the ways colonial powers used extreme forms of violence. By delving into the causes and nature of the abuse, Brocades Zaalberg and Luttikhuis conclude that all cases involved some form of institutionalized impunity, which enabled the type of situation in which the forces in the service of the colonial rulers were able to use extreme violence

Not an Afterthought: Accountability for Colonial Violence in the Dutch and British Metropoles

An analysis of impunity in colonial warfar

Extraction of volatile fatty acids from fermented wastewater

Valorization of wastewater streams can be done by fermentation to produce volatile fatty acids (VFAs) which are applied as platform chemicals for synthesis of value-added chemicals. Since VFA concentration in fermented wastewater is very low (∼1 wt%) and fermented wastewater contains considerable amounts of dissolved salts, recovery of VFAs from fermented wastewater is challenging. To study the potential of some ionic liquids compared to traditional solvents for extraction of VFAs from fermented wastewater, a detailed study on the effects of various salt-originating ions on VFA extraction was performed. Ion exchange and intermolecular interactions (e.g. hydrogen bonding) were found to be responsible for extraction of VFAs. The presence of salts (e.g. KCl) resulted in extraction of acidic forms of salt-originating anions (e.g. H+ + Cl−). 20 wt% trioctylamine (TOA) in n-octanol (representing conventional solvents) and [P666,14][Phos] (an ionic liquid) were found to be the most promising VFA-extracting solvents. Their maximum VFA loadings while being in equilibrium with an artificial fermented wastewater were determined by performing cross-current extractions. [P666,14][Phos] achieved a higher maximum VFA loading which enables it to deliver a much more concentrated VFA stream at a lower solvent to feed ratio (S/F)