Cryptosporidium PI(4)K inhibitor EDI048 is a gut-restricted parasiticidal agent to treat paediatric enteric cryptosporidiosis.

Diarrhoeal disease caused by Cryptosporidium is a major cause of morbidity and mortality in young and malnourished children from low- and middle-income countries, with no vaccine or effective treatment. Here we describe the discovery of EDI048, a Cryptosporidium PI(4)K inhibitor, designed to be active at the infection site in the gastrointestinal tract and undergo rapid metabolism in the liver. By using mutational analysis and crystal structure, we show that EDI048 binds to highly conserved amino acid residues in the ATP-binding site.

Norm conflicts and epistemic modals.

Statements containing epistemic modals (e.g., "by spring 2023 most European countries may have the Covid-19 pandemic under control") are common expressions of epistemic uncertainty.

Navigating a medical mystery in an elite athlete-severe dystonia induced by swimming.

Dystonia is a state of involuntary muscle contractions that cause repetitive or twisting movements. It may affect one or more parts of the body and sometimes the entire body. The condition can be mild or severe.

The local co-evolution of firms and governments in the Information Age.

The governance structures of the value-creating activities of MNEs have evolved towards more networked forms that are geographically highly concentrated and involve partnering with diverse actors. The experimentation that takes place within these corporate networks has a parallel on the government side, where subnational governments, and particularly cities as hubs of economic activity, have increased their profile and level of cooperative activity. We argue that engagement in these partnerships is an essential way in which firms and governments co-evolve and create the basis for sustainable economic growth in the Information Age.

Biochemical Characterization of Respiratory Syncytial Virus RNA-Dependent RNA Polymerase Complex.

RNA-dependent RNA polymerases (RdRPs) from nonsegmented negative strand (NNS) RNA viruses perform both mRNA transcription and genome replication, and these activities are regulated by their interactions with RNA and other accessory proteins within the ribonucleoprotein (RNP) complex. Detailed biochemical characterization of these enzymatic activities and their regulation is essential for understanding the life cycles of many pathogenic RNA viruses and for antiviral drug discovery. We developed biochemical and biophysical kinetic methods to study the RNA synthesis and RNA binding activities of respiratory syncytial virus (RSV) L/P RdRP.

A young woman with a symptomatic patent foramen ovale: Natasha's fascinating story.

A young Amerasian woman developed transient ischemic attacks related to a patent foramen ovale. Her background personal story, involving being willed from her dying grandmother to a US photographer and attempting to find her serviceman father, has led to a book and a TED talk.

A great-grandfather's account of the Irish potato famine (1845-1850).

My great-grandfather, Rodger Cantwell, and his family managed to survive the Irish famine that began in 1845. Blending what family records we have with Kelly's outstanding 2012 book about the era, the following is an historical fictional account of Rodger's saga.