Peck McAllister (carpshape0)

Plasmodium parasites possess a translocon that exports parasite proteins into the infected erythrocyte. Although the translocon components are also expressed during the mosquito and liver stage of infection, their function remains unexplored. Here, using a combination of genetic and chemical assays, we show that the translocon component Exported Protein 2 (EXP2) is critical for invasion of hepatocytes. EXP2 is a pore-forming protein that is secreted from the sporozoite upon contact with the host cell milieu. EXP2-deficient sporozoites are impaired in invasion, which can be rescued by the exogenous administration of recombinant EXP2 and alpha-hemolysin (an S. aureus pore-forming protein), as well as by acid sphingomyelinase. The latter, together with the negative impact of chemical and genetic inhibition of acid sphingomyelinase on invasion, reveals that EXP2 pore-forming activity induces hepatocyte membrane repair, which plays a key role in parasite invasion. Overall, our findings establish a novel and critical function for EXP2 that leads to an active participation of the host cell in Plasmodium sporozoite invasion, challenging the current view of the establishment of liver stage infection.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Cities and regions have become increasingly engaged in global climate change governance. They are pledging their own climate mitigation targets and participating in membership networks that typically are transnational in nature and engage thousands of subnational governments. Researching these growing trends in participation has been difficult due to the disparate and inconsistent nature of this self-reported data. To facilitate future analyses of these actors, we introduce ClimActor, the largest harmonized global dataset of more than 10,000 city and regional governments participating in networks like the Global Covenant of Mayors for Climate and Energy, C40 Cities for Climate Leadership, ICLEI Local Leaders for Sustainability, among others. We include key contextual information on each actor's population, geographic location, and administrative jurisdiction to facilitate disambiguation of potential overlaps in actions or emissions. We also provide a series of cleaning functions based on phonetic and fuzzy string matching algorithms within an open-source R package to make it easy for anyone to immediately use the ClimActor dataset with other relevant data.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The formation of hair follicles, a landmark of mammals, requires complex mesenchymal-epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. Here, we demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. When exposed to a newborn skin microenvironment, these cells express hair-follicle lineage markers and contribute to hair follicles, sebaceous glands and/or epidermis renewal. Our results demonstrate that lineage restriction is not immutable and support the notion that all Tp63-expressing epithelial stem cells, independently of their embryonic origin, have latent skin competence explaining why aberrant hair follicles or sebaceous glands are sometimes observed in non-skin tissues (e.g. in cornea, vagina or thymus).An amendment to this paper has been published and can be accessed via a link at the top of the paper.Building autonomous artificial cells capable of homeostasis requires regulatory networks to gather information and make decisions that take time and cost energy. Decisions based on few molecules may be inaccurate but are cheap and fast. Realizing decision-ma