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The notion of “engagement,” which plays an important role in various domains of psychology, is gaining increased currency as a concept that is critical to the success of digital interventions. However, engagement remains an ill-defined construct, with different fields generating their own domain-specific definitions. Moreover, given that digital interactions in real-world settings are characterized by multiple demands and choice alternatives competing for an individual’s effort and attention, they involve fast and often impulsive decision-making. Prior research seeking to uncover the mechanisms underlying engagement has nonetheless focused mainly on psychological factors and social influences and neglected to account for the role of neural mechanisms that shape individual choices. This article aims to integrate theories and empirical evidence across multiple domains to define engagement and discuss opportunities and challenges to promote effective engagement in digital interventions. We also propose the affect–integration–motivation and attention–context–translation (AIM–ACT) framework, which is based on a neurophysiological account of engagement, to shed new light on how in-the-moment engagement unfolds in response to a digital stimulus. Building on this framework, we provide recommendations for designing strategies to promote engagement in digital interventions and highlight directions for future research.

Many bacteria produce polysaccharide-based capsules that protect them from environmental insults and play a role in virulence, host invasion, and other functions. Understanding how the polysaccharide components are synthesized could provide new means to combat bacterial infections. We have previously characterized two pairs of homologous enzymes involved in the biosynthesis of capsular sugar precursors GDP-6- d eoxy- D - a ltro - h eptose and GDP-6-O M e- L - g luco - h eptose in Campylobacter jejuni . However, the substrate specificity and mechanism of action of these enzymes—C3 and/or C5 epimerases DdahB and MlghB and C4 reductases DdahC and MlghC—are unknown. Here, we demonstrate that these enzymes are highly specific for heptose substrates, using mannose substrates inefficiently with the exception of MlghB. We show that DdahB and MlghB feature a jellyroll fold typical of cupins, which possess a range of activities including epimerizations, GDP occupying a similar position as in cupins. DdahC and MlghC contain a Rossman fold, a catalytic triad, and a small C-terminal domain typical of short-chain dehydratase reductase enzymes. Integrating structural information with site-directed mutagenesis allowed us to identify features unique to each enzyme and provide mechanistic insight. In the epimerases, mutagenesis of H67, D173, N121, Y134, and Y132 suggested the presence of alternative catalytic residues. We showed that the reductases could reduce GDP-4-keto-6-deoxy-mannulose without prior epimerization although DdahC preferred the pre-epimerized substrate and identified T110 and H180 as important for substrate specificity and catalytic efficacy. This information can be exploited to identify inhibitors for therapeutic applications or to tailor these enzymes to synthesize novel sugars useful as glycobiology tools.

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Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive disorder that is caused by mutations in SCL34A2 that encodes for the type IIb sodium-dependent phosphate cotransporter (Npt2b). The loss of Npt2b transporter function from alveolar epithelial cells results in failure to export inorganic phosphate from the alveolar lining fluid, which then accumulates, binds to calcium, and forms hydroxyapatite microliths. Radiographs and computed tomography of the chest demonstrate hyperdense infiltrates that are often quite dramatic and distinctive, and in many cases, the diagnosis can be made without invasive measures. The most common presenting symptom of PAM is dyspnea on exertion, but the disease is frequently first noted as an incidental finding in asymptomatic patients who have chest films performed for unrelated reasons. Pulmonary fibrosis, pulmonary hypertension, and respiratory failure can develop as the disease progresses, and treatment remains supportive. Lung transplantation is an option for those with end stage disease.

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