Targeted Disruption of the PME-1 Gene Causes Loss of Demethylated PP2A and Perinatal Lethality in Mice

Phosphoprotein phosphatase 2A (PP2A), a major serine-threonine protein phosphatase in eukaryotes, is an oligomeric protein comprised of structural (A) and catalytic (C) subunits to which a variable regulatory subunit (B) can associate. The C subunit contains a methyl ester post-translational modification on its C-terminal leucine residue, which is removed by a specific methylesterase (PME-1). Methylesterification is thought to control the binding of different B subunits to AC dimers, but little is known about its physiological significance in vivo.Here, we show that targeted disruption of the PME-1 gene causes perinatal lethality in mice, a phenotype that correlates with a virtually complete loss of the demethylated form of PP2A in the nervous system and peripheral tissues. Interestingly, PP2A catalytic activity over a peptide substrate was dramatically reduced in PME-1(-/-) tissues, which also displayed alterations in phosphoproteome content.These findings suggest a role for the demethylated form of PP2A in maintenance of enzyme function and phosphorylation networks in vivo

The Rare Earth Elements: demand, global resources, and challenges for resourcing future generations

The rare earth elements (REE) have attracted much attention in recent years, being viewed as critical metals because of China’s domination of their supply chain. This is despite the fact that REE enrichments are known to exist in a wide range of settings, and have been the subject of much recent exploration. Although the REE are often referred to as a single group, in practice each individual element has a specific set of end-uses, and so demand varies between them. Future demand growth to 2026 is likely to be mainly linked to the use of NdFeB magnets, particularly in hybrid and electric vehicles and wind turbines, and in erbium-doped glass fiber for communications. Supply of lanthanum and cerium is forecast to exceed demand. There are several different types of natural (primary) REE resources, including those formed by high-temperature geological processes (carbonatites, alkaline rocks, vein and skarn deposits) and those formed by low-temperature processes (placers, laterites, bauxites and ion-adsorption clays). In this paper, we consider the balance of the individual REE in each deposit type and how that matches demand, and look at some of the issues associated with developing these deposits. This assessment and overview indicate that while each type of REE deposit has different advantages and disadvantages, light rare earth-enriched ion adsorption types appear to have the best match to future REE needs. Production of REE as by-products from, for example, bauxite or phosphate, is potentially the most rapid way to produce additional REE. There are still significant technical and economic challenges to be overcome to create substantial REE supply chains outside China

R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling

R-spondins (RSPOs) amplify WNT signaling during development and regenerative responses. We previously demonstrated that RSPOs 2 and 3 potentiate WNT/β-catenin signaling in cells lacking leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4, 5 and 6 (Lebensohn and Rohatgi, 2018). We now show that heparan sulfate proteoglycans (HSPGs) act as alternative co-receptors for RSPO3 using a combination of ligand mutagenesis and ligand engineering. Mutations in RSPO3 residues predicted to contact HSPGs impair its signaling capacity. Conversely, the HSPG-binding domains of RSPO3 can be entirely replaced with an antibody that recognizes heparan sulfate (HS) chains attached to multiple HSPGs without diminishing WNT-potentiating activity in cultured cells and intestinal organoids. A genome-wide screen for mediators of RSPO3 signaling in cells lacking LGRs 4, 5 and 6 failed to reveal other receptors. We conclude that HSPGs are RSPO co-receptors that potentiate WNT signaling in the presence and absence of LGRs

Unsettling Post-War Settlement: Remembering Unassimilable Families in the Space of the Migrant Camp

Migrant camps were unsettling spaces for newly arrived families in post-war Australia. Post-WWII refugees and assisted migrants arriving from 1947 to the early 1970s labelled these temporary accommodation centres run by the Department of Immigration �camps�. Their ambiguity as spaces of refuge and containment persists in memory. Hundreds of thousands of assisted migrants and refugees passed through these camps, which were established from 1947 and progressively shut down from the late 1960s. This chapter will analyse memories of migrant camps by mothers, sons and daughters. They have grappled with their own contentious and contradictory family histories in the migrant camp and the ongoing legacies of being �received� and temporarily housed in a place of containment and control. As temporary and transient places, migrant camps were never intended to be long-term �homes� for migrant families. However, many families, particularly those with single mothers or with heads of households unable to secure ongoing and full-time work, found themselves living in camps for years. A substantial cohort of post-war migrant children grew up in centres like Benalla in Victoria or Greta in New South Wales. Family life was structured around the restrictions of communal and bureaucratised living�which had many implications for how each family member related to each other and to their new country of settlement. Constraints were also placed on their employment and movements by the Department of Immigration. This paper will tie together competing theories around migrant home-building, family memory and generational memory to argue that the place of the migrant centre has come to feature prominently in the meaning-making practice of family history, particularly for child migrants grappling with unsettled and unsettling family histories. The migrant camp is a difficult heritage place from which to build family memories, especially given the spectre of the camp-as-detention-centre. Nonetheless, many who arrived as children have seen it as their task to rescue these unsettling places of settlement from obscurity and to assert their dark heritage, their place in a more intimate and diverse history of Australian migration, which shines a light on discrimination and complicates public histories of the post-war immigration scheme and settlement