Phosphorylation of the Arp2/3 complex is necessary to nucleate actin filaments

The actin-related protein 2/3 (Arp2/3) complex is the primary nucleator of new actin filaments in most crawling cells. Nucleation-promoting factors (NPFs) of the Wiskott-Aldrich syndrome protein (WASP)/Scar family are the currently recognized activators of the Arp2/3 complex. We now report that the Arp2/3 complex must be phosphorylated on either threonine or tyrosine residues to be activated by NPFs. Phosphorylation of the Arp2/3 complex is not necessary to bind NPFs or the sides of actin filaments but is critical for binding the pointed end of actin filaments and nucleating actin filaments. Mass spectrometry revealed phosphorylated Thr237 and Thr238 in Arp2, which are evolutionarily conserved residues. In cells, phosphorylation of only the Arp2 subunit increases in response to growth factors, and alanine substitutions of Arp2 T237 and T238 or Y202 inhibits membrane protrusion. These findings reveal an additional level of regulation of actin filament assembly independent of WASP proteins, and show that phosphorylation of the Arp2/3 complex provides a logical “or gate” capable integrating diverse upstream signals

Sex moderates the effects of total sleep deprivation and sleep restriction on risk preference

Sleep loss has been shown to alter risk preference during decision-making. However, research in this area has largely focussed on the effects of total sleep deprivation (TSD), while evidence on the effects of sleep restriction (SR) or the potentially moderating role of sex on risk preference remains scarce and unclear. The present study investigated risky decision-making in 47 healthy young adults who were assigned to either of two counterbalanced protocols: well-rested (WR) and TSD, or WR and SR. Participants were assessed on the Lottery Choice Task (LCT), which requires a series of choices between two risky gambles with varying risk levels. Analyses on the pooled dataset indicated across all sleep conditions, participants were generally more risk-seeking when trying to minimise financial loss (LOSSES) than while trying to maximise financial gain (GAINS). On GAINS trials, female participants were more risk-averse during TSD and SR, whereas male participants remained unchanged. On LOSSES trials, female participants remained unchanged during TSD and SR, whereas male participants became more risk-seeking during TSD. Our findings suggest the relationship between sleep loss and risk preference is moderated by sex, whereby changes in risk preference after TSD or SR differ in men and women depending on whether the decision is framed in terms of gains or losses

In Silico Reconstitution of Actin-Based Symmetry Breaking and Motility

Computational modeling and experimentation in a model system for actin-based force generation explain how actin networks initiate and maintain directional movement

Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.This work was supported by grants from the National Institutes of Health, an American Heart Association Predoctoral Fellowship (J.B.Z.), the Robert Day Allen Fellowship Fund (J.B.Z.), and a National Science Foundation Predoctoral Fellowship (B.B.)

Medical students’ creative projects on a third year pediatrics clerkship: a qualitative analysis of patient-centeredness and emotional connection

BACKGROUND: Increasingly, medical educators are incorporating reflective writing and original creative work into educational practices with the goals of stimulating student self-awareness, appreciation of multiple perspectives, and comfort with ambiguity and uncertainty. This study investigated students’ creative projects to assess the extent to which they adopted a patient/relationship-centered, emotionally connected position toward patients and families. METHODS: Over a 10 year period, students on a required third year pediatrics clerkship individually or in groups completed either a reflection or an education project using a creative medium. 520 projects (representing 595 students, 74.7 % of total eligible students) were qualitatively analyzed according to various thematic and emotion-based dimensions. RESULTS: The majority of projects were personal narrative essays and poetry. The largest number of project themes related to the importance of patient/relationship-centered medicine with patients. The next largest number of projects focused on health education of parents, patients, or classmates. In telling their stories, students were more likely to use a personal voice representing either their or the patient’s perspective than an objective, impersonal one. In terms of emotional tone, projects were more likely to be serious than humorous. The largest number of students’ emotions expressed an empathic tone. Students identified a large number and wide range of both negative and positive feelings in themselves and their patients. The majority of student emotions were positive, while the majority of patient and family emotions were negative. CONCLUSIONS: Students’ preference for patient-centered, relational themes, as well as their tendency to favor the first voice, empathic tone, and willingness to express a range of positive and negative emotions in presenting their projects, suggests that they valued emotional connection with patients and families during the pediatrics clerkship experience

Examining Sense of Community among Medical Professionals in an Online Graduate Program

As the number of online degree programs continues to grow, one of the greatest challenges is developing a sense of community among learners who do not convene at the same time and place. This study examined the sense of community among medical professionals in an online graduate program for healthcare professionals. We took the sample from a fully online program delivered jointly by a state university and a local children's hospital in the Midwest. We administered Rovai's Classroom Community Survey with 11 additional demographic questions. We also utilized online interviews to further explore students’ understanding of sense of community. A bi-factor model was fitted to the online sense of community survey data. Using multivariate analysis of variance (MANOVA) and univariate analysis of variance (ANOVA) we identified potential group differences. The qualitative data were analyzed thematically in a recursive and iterative process. Study results suggested that a dominant factor existed: sense of community with two sub-domain factors including sense of learning and sense of connectedness. No significant differences in sense of community with regard to gender, native language, or area of medical practice were detected. However, results showed a difference in sense of community between the three courses examined. This study is the first to examine the sense of community among online medical professionals. Since our findings are in contrast to those of previous studies, this opens the door to additional studies around the possible differences between the community characteristics and needs of medical professionals as online students