Structural characterization of the Myxococcusxanthus encapsulin and ferritin-like cargo system gives insight into its iron storage mechanism

Encapsulins are bacterial organelle-like cages involved in various aspects of metabolism, especially protection from oxidative stress. They can serve as vehicles for a wide range of medical applications. Encapsulin shell proteins are structurally similar to HK97 bacteriophage capsid protein and their function depends on the encapsulated cargos. The Myxococcus xanthus encapsulin system comprises EncA and three cargos: EncB, EncC, and EncD. EncB and EncC are similar to bacterial ferritins that can oxidize Fe+2 to less toxic Fe+3.
We analyzed EncA, EncB, and EncC by cryo-EM and X-ray crystallography. Cryo-EM shows that EncA cages can have T = 3 and T = 1 symmetry and that EncA T = 1 has a unique protomer arrangement. Also, we define EncB and EncC binding sites on EncA. X-ray crystallography of EncB and EncC reveals conformational changes at the ferroxidase center and additional metal binding sites, suggesting a mechanism for Fe oxidation and storage within the encapsulin shell.

Promoting GAINs (Give Attention to Limitations in Assays) over PAINs Alerts: no PAINS, more GAINs

Many concepts and guidelines in medicinal chemistry have been introduced to aid in successful drug discovery and development. An example is the concept of Pan-Assay Interference Compounds (PAINS) and the elimination of such nuisance compounds from high-throughput screening (HTS) libraries. PAINs, along with other guidelines in medicinal chemistry, are like double-edged swords. If used appropriately, they may be beneficial for drug discovery and development. However, rigid and blind use of such concepts can hinder productivity. In this perspective, we introduce GAINS (give attention to limitations in assays) and highlight its relevance for successful drug discovery.

‘Blurred boundaries’: When nurses and midwives give anti-vaccination advice on Facebook

Background: Nurses and midwives have a professional obligation to promote health and prevent disease, and therefore they have an essential role to play in vaccination. Despite this, some nurses and midwives have been found to take an anti-vaccination stance and promulgate misinformation about vaccines, often using Facebook as a platform to do so.
Research question: This article reports on one component and dataset from a larger study – ‘the positives, perils and pitfalls of Facebook for nurses’. It explores the specific issue of nurses and midwives who take an anti-vaccination stance, deemed to be unprofessional by crossing professional boundaries and by providing medical information on Facebook that is not within their scope of practice.
Participants: Data were collected via an online worldwide survey from nurse and midwife participants, distributed and ‘snowballed’ through relevant nursing and midwifery groups on Facebook. In total, 1644 Registered Nurses and Midwives, and Enrolled Nurses worldwide attempted the online survey. There were 1100 (66.9%) completed surveys and 54 partially (33.1%) completed surveys. Semi-structured interviews were also conducted online using Skype® with 17 participants in Australia.
Ethical considerations: Ethical processes and procedures have been adhered to relating to privacy, confidentiality and anonymity of the participants.
Findings/results: A mixed-methods approach was used, including descriptive and content analysis of the quantitative survey data and thematic analysis of the qualitative interview data. The main theme ‘blurred boundaries’ was generated, which comprised three sub-themes: ‘follow the science, ‘abuse of power and erosion of trust’ and ‘the moral and ethical responsibility to safeguard public health’. The results offer an important and unique understanding of how nurses and midwives interpret the conduct of fellow health professionals as unprofessional and crossing the professional boundary if they used Facebook to promulgate anti-vaccination messages and/or give medical advice online.
Conclusion: There are many positives and negatives for nurses and midwives associated with using Facebook for personal and professional communication, which is in keeping with the results of the larger study from which this article is taken. Professional behaviour is a key theme in the larger research as is the ethical construct of ‘every act has a consequence’; however, in this article, the theme ‘blurred boundaries’ offers an overall understanding of how nurses and midwives interpret the behaviour of their colleagues who espouse anti-vaccination sentiment and/or give medical advice online that is outside their scope of practice and education.

Assessing the knower-level framework: How reliable is the Give-a-Number task?

  • The Give-a-Number task has become a gold standard of children’s number word comprehension in developmental psychology. Recently, researchers have begun to use the task as a predictor of other developmental milestones. This raises the question of how reliable the task is, since test-retest reliability of any measure places an upper bound on the size of reliable correlations that can be found between it and other measures. In Experiment 1, we presented 81 2- to 5-year-old children with Wynn (1992) titrated version of the Give-a-Number task twice within a single session.
  • We found that the reliability of this version of the task was high overall, but varied importantly across different assigned knower levels, and was very low for some knower levels. In Experiment 2, we assessed the test-retest reliability of the non-titrated version of the Give-a-Number task with another group of 81 children and found a similar pattern of results. Finally, in Experiment 3, we asked whether the two versions of Give-a-Number generated different knower levels within-subjects, by testing 75 children with both tasks. Also, we asked how both tasks relate to another commonly used test of number knowledge, the “What’s-On-This-Card” task.
  • We found that overall, the titrated and non-titrated versions of Give-a-Number yielded similar knower levels, though the non-titrated version was slightly more conservative than the titrated version, which produced modestly higher knower levels. Neither was more closely related to “What’s-On-This-Card” than the other. We discuss the theoretical and practical implications of these results.
Observing effects in various contexts won’t give us general psychological theories

Generalization does not come from repeatedly observing phenomena in numerous settings, but from theories explaining what is general in those phenomena. Expecting future behavior to look like past observations is especially problematic in psychology, where behaviors change when people’s knowledge changes. Psychology should thus focus on theories of people’s capacity to create and apply new representations of their environments.

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The Few yet Fab p4 ulous Pancreatic Stellate Cells Give Rise to Protumoral CAFs

Cancer-associated fibroblast (CAF) pro- and anti-pancreatic cancer functional dichotomy has been at the center of numerous studies. In this issue of Cancer Discovery, Helms and colleagues demonstrate that although pancreatic stellate cell-derived CAFs constitute a desmoplastic cell minority, these cells play a protumorigenic role via microenvironmental mechanomodulation.

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