Thermodynamic rarity of electrical and electronic waste: Assessment and policy implications for critical materials

The strategic relevance of extracting raw materials from waste from electrical and electronic equipment (WEEE) in the EU is increasing due to value chain risks caused by geopolitical instability, accessibility of specific minerals, and decreasing reserves due to growing extraction rates. This article examines the quantities of so-called critical raw materials (CRMs) originating within WEEE streams from a depletion perspective. Presently, current recycling targets are based solely on mass collection and recycling rates. We examine the potential limitations of this approach using an exergy-based indicator named thermodynamic rarity. This indicator represents the exergy costs needed for producing materials from the bare rock to market. The case of Italy is used to explore the application of the indicator at the macro (national) and micro (company) level for the product categories “small electronics” and “screens and monitors.” Our estimations show significant differences between the mass and rarity of materials within Italian WEEE streams. While iron accounts for more than 70% of the weight of the product categories analyzed, it accounts for less than 15% of the rarity. Similarly, several CRMs with a small mass have a higher rarity value, for example, tungsten with less than 0.1% of the mass and over 6% of the rarity. The policy context is reflected upon, where it is argued that thermodynamic rarity can provide novel insights to support end-of-life WEEE decision-making processes, for example, target development and recycling standards setting to help prioritize material monitoring and recovery options.     

Cyclophilin A regulates secretion of tumour-derived extracellular vesicles

Extracellular Vesicles (EVs) are a heterogenous population of particles that play an important role in cell-cell communication in physiological and pathophysiological situations. In this study we reveal that the peptidyl prolyl isomerase Cyclophilin A (CypA) is enriched in cancer-derived EVs from a range of haematopoietic malignancies. CypA-enriched blood cancer EVs were taken up by normal monocytes independent of EV surface trypsin-sensitive proteins and potently stimulated pro-inflammatory MMP9 and IL-6 secretion. Further characterisation revealed that CypA is intravesicular, however, it is not present in all EVs derived from the haematopoietic cells, instead, it is predominantly located in high density EVs with a range of 1.15–1.18 g/ml. Furthermore, loss of CypA expression in haematological cancer cells attenuates high density EV-induced pro-inflammatory MMP9 and IL-6 secretion from monocytes. Mechanistically, we reveal that homozygous loss or siRNA knockdown of CypA expression significantly reduced the secretion of EVs in the range of 100–200 nm from blood cancer cells under normal and hypoxic conditions. Overall, this work reveals a novel role for CypA in cancer cell EV biogenesis.     

Cyclic Nucleotide-dependent Protein Kinases Target ARHGAP17 and ARHGEF6 Complexes in Platelets

Endothelial cells release prostacyclin (PGI₂) and nitric oxide (NO) to inhibit platelet functions. PGI₂ and NO effects are mediated by cyclic nucleotides, cAMP- and cGMP-dependent protein kinases (PKA, PKG), and largely unknown PKA and PKG substrate proteins. The small G-protein Rac1 plays a key role in platelets and was suggested to be a target of cyclic nucleotide signaling. We confirm that PKA and PKG activation reduces Rac1-GTP levels. Screening for potential mediators of this effect resulted in the identification of the Rac1-specific GTPase-activating protein ARHGAP17 and the guanine nucleotide exchange factor ARHGEF6 as new PKA and PKG substrates in platelets. We mapped the PKA/PKG phosphorylation sites to serine 702 on ARHGAP17 using Phos-tag gels and to serine 684 on ARHGEF6. We show that ARHGAP17 binds to the actin-regulating CIP4 protein in platelets and that Ser-702 phosphorylation interferes with this interaction. Reduced CIP4 binding results in enhanced inhibition of cell migration by ARHGAP17. Furthermore, we show that ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and that ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex. PKA and PKG induced rearrangement of ARHGAP17- and ARHGEF6-associated protein complexes might contribute to Rac1 regulation and platelet inhibition.