Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin.

Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands. Known components of heterochromatin such as nucleosomes and DNA preferentially partition into the HP1α droplets, but molecules such as the transcription factor TFIIB show no preference. Using a single-molecule DNA curtain assay, we find that both unmodified and phosphorylated HP1α induce rapid compaction of DNA strands into puncta, although with different characteristics. We show by direct protein delivery into mammalian cells that an HP1α mutant incapable of phase separation in vitro forms smaller and fewer nuclear puncta than phosphorylated HP1α. These findings suggest that heterochromatin-mediated gene silencing may occur in part through sequestration of compacted chromatin in phase-separated HP1 droplets, which are dissolved or formed by specific ligands on the basis of nuclear context

Phenotypic Transition of the Collecting Duct Epithelium in Congenital Urinary Tract Obstruction

Epithelial-mesenchymal transition (EMT) has emerged in recent years as an important process in the development of organ fibrosis in many human diseases. Our previous experience in a nonhuman primate model of obstructive nephropathy suggested that EMT of collecting duct epithelium contributes to the development of interstitial fibrosis. In this study we demonstrate for the first time in humans that obstructed fetal collecting duct epithelium undergoes transition to mesenchymal phenotype, characterized by decreased expression of epithelial markers, de novo expression of mesenchymal markers with subsequent loss of cell-cell interaction, disruption of the basement membrane, and increased deposition of extracellular matrix into the expanded interstitium of the obstructed kidney. The results of this study therefore support the previous findings from animal studies and suggest that EMT of the collecting duct epithelium might contribute to the development of interstitial fibrosis in human fetal obstructive nephropathy

The IPCC’s reductive Common Era temperature history

J.E. acknowledges support by the Gutenberg Research College, J.E. M.T. and U.B. by the project AdAgrif (CZ.02.01.01/00/22_008/0004635) and ERC (AdG 882727), J.E.S. by the US NSF (OISE-1743738, AGS-2101214 and AGS-2303352), K.J.A. by the US NSF (AGS-1803946 and AGS-2102993), K.A. by the ARC (FT200100102), R.D. by the US NSF (OPP-2112314, OPP-2124885, and AGS-2102759), S.G and M. Stoffel by the SNSF (Sinergia CRSII5_183571), F.C.L. by the SRC (grant no. 2018-01272), Marianne and Marcus Wallenberg Foundation (grant no. MMW 2022-0114) and Swedish Collegium for Advanced Study (Pro Futura Scientia XIII Fellow), LS by the German Research Foundation (SCHN 1645/1-1), M. Sigl by the ERC (CoG 820047), and R.W. by the NSF-NERC (NE/W007223/1).Common Era temperature variability has been a prominent component in Intergovernmental Panel on Climate Change reports over the last several decades and was twice featured in their Summary for Policymakers. A single reconstruction of mean Northern Hemisphere temperature variability was first highlighted in the 2001 Summary for Policymakers, despite other estimates that existed at the time. Subsequent reports assessed many large-scale temperature reconstructions, but the entirety of Common Era temperature history in the most recent Sixth Assessment Report of the Intergovernmental Panel on Climate Change was restricted to a single estimate of mean annual global temperatures. We argue that this focus on a single reconstruction is an insufficient summary of our understanding of temperature variability over the Common Era. We provide a complementary perspective by offering an alternative assessment of the state of our understanding in high-resolution paleoclimatology for the Common Era and call for future reports to present a more accurate and comprehensive assessment of our knowledge about this important period of human and climate history.Peer reviewe

Lockdown Ibuism: experiences of Indonesian migrant mothers during the COVID-19 pandemic in Aotearoa New Zealand

Lockdowns imposed to curb the spread of COVID-19 have been widely shown to heighten care burdens within households and ‘bubbles.’ Responsibility for meeting such burdens often falls disproportionately upon women. It is nevertheless important for research on gendered inequalities during COVID-19 to attend to the particularities of how such care work was experienced by differently positioned women. In Aotearoa New Zealand, Indonesian migrant mothers’ experiences of lockdown were mediated by the disadvantages they faced as ‘non-native’ speakers of English, as well as by the ideology of Ibuism (‘motherism’) they were socialised into during their lives in Indonesia. This socialisation led many to find life under lockdown life both rewarding and stressful in ways distinct from other women and mothers in Aotearoa New Zealand who were confronting similar demands. We thus argue for the importance of a qualitative and intersectional approach

Antioxidant properties of MitoTEMPOL and its hydroxylamine

Piperidine nitroxides such as TEMPOL have been widely used as antioxidants in vitro and in vivo. MitoTEMPOL is a mitochondria-targeted derivative of TEMPOL designed to protect mitochondria from the oxidative damage that they accumulate, but once there is rapidly reduced to its hydroxylamine, MitoTEMPOL-H. As little is known about the antioxidant efficacy of hydroxylamines, this study has assessed the antioxidant activity of both MitoTEMPOL and MitoTEMPOL-H. The hydroxylamine was more effective at preventing lipid-peroxidation than MitoTEMPOL and decreased oxidative damage to mitochondrial DNA caused by menadione. In contrast to MitoTEMPOL, MitoTEMPOL-H has no superoxide dismutase activity and its antioxidant actions are likely to be mediated by hydrogen atom donation. Therefore, even though MitoTEMPOL is rapidly reduced to MitoTEMPOL-H in cells, it remains an effective antioxidant. Furthermore, as TEMPOL is also reduced to a hydroxylamine in vivo, many of its antioxidant effects may also be mediated by its hydroxylamine

Steroid-refractory ulcerative colitis treated with corticosteroids, metronidazole and vancomycin: a case report

BACKGROUND: Increasing evidence elucidating the pathogenic mechanisms of ulcerative colitis (UC) has accumulated and the disease is widely assumed to be the consequence of genetic susceptibility and an abnormal immune response to commensal bacteria. However evidence regarding an infectious etiology in UC remains elusive. CASE PRESENTATION: We report a provocative case of UC with profound rheumatologic involvement directly preceded by Clostridium difficile infection and accompanying fever, vomiting, bloody diarrhea, and arthritis. Colonic biopsy revealed a histopathology suggestive of UC. Antibiotic treatment eliminated detectable levels of enteric pathogens but did not abate symptoms. Resolution of symptoms was procurable with oral prednisone, but tapering of corticosteroids was only achievable in combination therapy with vancomycin and metronidazole. CONCLUSIONS: An infectious pathogen may have both precipitated and exacerbated autoimmune disease attributes in UC, symptoms of which could be resolved only with a combination of corticosteroids, vancomycin and metronidazole. This may warrant the need for more perceptive scrutiny of C. difficile and the like in patients with UC

The SAGEX Review on Scattering Amplitudes

This is an introduction to, and invitation to read, a series of review articles on scattering amplitudes in gauge theory, gravity, and superstring theory. Our aim is to provide an overview of the field, from basic aspects to a selection of current (2022) research and developments.Comment: 15 pages, overview articl

Priority questions in multidisciplinary drought research

Addressing timely and relevant questions across a multitude of spatio-temporal scales, state-of-the-art interdisciplinary drought research will likely increase in importance under projected climate change. Given the complexity of the various direct and indirect causes and consequences of a drier world, scientific tasks need to be coordinated efficiently. Drought-related research endeavors ranging from individual projects to global initiatives therefore require prioritization. Here, we present 60 priority questions for optimizing future drought research. This topical catalogue reflects the experience of 65 scholars from 21 countries and almost 20 fields of research in both natural sciences and the humanities. The set of drought-related questions primarily covers drought monitoring, impacts, forecasting, climatology, adaptation, as well as planning and policy. The questions highlight the increasingly important role of remote sensing techniques in drought monitoring, importance of drought forecasting and understanding the relationships between drought parameters and drought impacts, but also challenges of drought adaptation and preparedness policies