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1.
Semin Respir Crit Care Med ; 41(2): 280-287, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32279298

RESUMO

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.


Assuntos
Calcinose/diagnóstico , Calcinose/terapia , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/terapia , Pneumopatias/diagnóstico , Pneumopatias/terapia , Calcinose/complicações , Calcinose/genética , Ensaios Clínicos como Assunto , Progressão da Doença , Dispneia/etiologia , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/genética , Humanos , Hipertensão Pulmonar/etiologia , Pneumopatias/complicações , Pneumopatias/genética , Transplante de Pulmão , Mutação , Fibrose Pulmonar , Radiografia Torácica , Insuficiência Respiratória/etiologia , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIb/genética , Tomografia Computadorizada por Raios X
2.
J Biol Chem ; 287(35): 29776-88, 2012 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-22787156

RESUMO

The Campylobacter jejuni capsule is important for colonization and virulence in various infection models. In most strains, the capsule includes a modified heptose whose biological role and biosynthetic pathway are unknown. To decipher the biosynthesis pathway for the 6-deoxy-D-altro-heptose of strain 81-176, we previously showed that the 4,6-dehydratase WcbK and the reductase WcaG generated GDP-6-deoxy-D-manno-heptose, but the C3 epimerase necessary to form GDP-6-deoxy-D-altro-heptose was not identified. Herein, we characterized the putative C3/C5 epimerase Cjj1430 and C3/C5 epimerase/C4 reductase Cjj1427 from the capsular cluster. We demonstrate that GDP-6-deoxy-D-altro-heptose biosynthesis is more complex than anticipated and requires the sequential action of WcbK, Cjj1430, and Cjj1427. We show that Cjj1430 serves as C3 epimerase devoid of C5 epimerization activity and that Cjj1427 has no epimerization activity and only serves as a reductase to produce GDP-6-deoxy-D-altro-heptose. Cjj1430 and Cjj1427 are the only members of the C3/C5 epimerases and C3/C5 epimerase/C4 reductase families shown to have activity on a heptose substrate and to exhibit only one of their two to three potential activities, respectively. Furthermore, we show that although the reductase WcaG is not part of the main pathway, its presence and its product affect the outcome of the pathway in a complex regulatory loop involving Cjj1427. This work provides the grounds for the elucidation of similar pathways found in other C. jejuni strains and other pathogens. It provides new molecular tools for the synthesis of carbohydrate antigens useful for vaccination and for the screening of enzymatic inhibitors that may have antibacterial effects.


Assuntos
Proteínas de Bactérias/metabolismo , Campylobacter jejuni/metabolismo , Metabolismo dos Carboidratos/fisiologia , Heptoses/biossíntese , Proteínas de Bactérias/genética , Campylobacter jejuni/genética , Heptoses/genética
3.
Am Psychol ; 77(7): 836-852, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35298199

RESUMO

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. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Motivação
4.
Proc ACM Int Conf Ubiquitous Comput ; 2017: 790-798, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29362728

RESUMO

The advancement of digital technologies particularly in the domain of mobile health (mHealth) holds great promise in the promotion of health behavior. However, keeping users engaged remains a central challenge. This paper proposes a novel approach to address this issue by supplementing existing and future mHealth applications with an engagement wrapper - a collection of engagement strategies integrated into a single, coherent model. The engagement wrapper is operationalized within the format of an ambient display on the lock screen of mobile devices.

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