Distinct activation mechanisms of NF-κB regulator inhibitor of NF-κB Kinase (IKK) by isoforms of the Cell Death Regulator Cellular FLICE-like Inhibitory Protein (cFLIP)*

The vFLIP protein from Kaposis sarcoma-associated herpesvirus activates the NF-kB pathway by forming a stable complex with a central region (amino acids 150-272) of the IKKgamma subunit, thereby activating IKK. Cellular FLIP forms are also known to activate the NF-kB pathway via IKK activation. Here we demonstrate that cFLIPL, cFLIPS, and their proteolytic product p22-FLIP, all require the C-terminal region of NEMO/IKKgamma (amino acids 272-419) and its ubiquitin binding function for activation of the IKK kinase (or kinase complex), but none form a stable complex with IKKgamma. Our results further reveal that cFLIPL requires the linear ubiquitination complex LUBAC and the kinase TAK1 for activation of the IKK kinase. Similarly, cFLIPS and p22-FLIP also require TAK1 but do not require LUBAC. In contrast, these isoforms are both components of complexes that incorporate FADD and RIP1 which appear essential for kinase activation. This conservation of IKK activation among the cFLIP family using different mechanisms suggests that the mechanism plays a critical role in their function

Expressing one’s feelings and listening to others increases emotional intelligence: a pilot study of Asian medical students

<p>Background: There has been considerable interest in Emotional Intelligence (EI) in undergraduate medical education, with respect to student selection and admissions, health and well-being and academic performance. EI is a significant component of the physician-patient relationship. The emotional well-being of the physician is, therefore, a significant component in patient care. The aim is to examine the measurement of TEIQue-SF in Asian medical students and to explore how the practice of listening to the feelings of others and expressing one’s own feelings influences an individual’s EI, set in the context of the emotional well-being of a medical practitioner.</p> <p>Methods: A group of 183 international undergraduate medical students attended a half-day workshop (WS) about mental-health and well-being. They completed a self-reported measure of EI on three occasions, pre- and post-workshop, and a 1-year follow-up.</p> <p>Result: The reliability of TEIQue-SF was high and the reliabilities of its four factors were acceptable. There were strong correlations between the TEIQue-SF and personality traits. A paired t-test indicated significant positive changes after the WS for all students (n=181, p= .014), male students (n=78, p= .015) and non-Japanese students (n=112, p= .007), but a repeated measures analysis showed that one year post-workshop there were significant positive changes for all students (n=55, p= .034), female students (n=31, p= .007), especially Japanese female students (n=13, p= .023). Moreover, 80% of the students reported that they were more attentive listeners, and 60% agreed that they were more confident in dealing with emotional issues, both within themselves and in others, as a result of the workshop.</p> <p>Conclusion: This study found the measurement of TEIQue-SF is appropriate and reliable to use for Asian medical students. The mental health workshop was helpful to develop medical students’ EI but showed different results for gender and nationality. The immediate impact on the emotional awareness of individuals was particularly significant for male students and the non-Japanese group. The impact over the long term was notable for the significant increase in EI for females and Japanese. Japanese female students were more conscious about emotionality. Emotion-driven communication exercises might strongly influence the development of students’ EI over a year.</p&gt

Evidence for the formation of comet 67P/Churyumov-Gerasimenko through gravitational collapse of a bound clump of pebbles

The processes that led to the formation of the planetary bodies in the Solar System are still not fully understood. Using the results obtained with the comprehensive suite of instruments on-board ESA’s Rosetta mission, we present evidence that comet 67P/Churyumov-Gerasimenko likely formed through the gentle gravitational collapse of a bound clump of mm-sized dust aggregates (“pebbles”), intermixed with microscopic ice particles. This formation scenario leads to a cometary make-up that is simultaneously compatible with the global porosity, homogeneity, tensile strength, thermal inertia, vertical temperature profiles, sizes and porosities of emitted dust, and the steep increase in water-vapour production rate with decreasing heliocentric distance, measured by the instruments on-board the Rosetta spacecraft and the Philae lander. Our findings suggest that the pebbles observed to be abundant in protoplanetary discs around young stars provide the building material for comets and other minor bodies

A Helicity-Based Method to Infer the CME Magnetic Field Magnitude in Sun and Geospace: Generalization and Extension to Sun-Like and M-Dwarf Stars and Implications for Exoplanet Habitability

Patsourakos et al. (Astrophys. J. 817, 14, 2016) and Patsourakos and Georgoulis (Astron. Astrophys. 595, A121, 2016) introduced a method to infer the axial magnetic field in flux-rope coronal mass ejections (CMEs) in the solar corona and farther away in the interplanetary medium. The method, based on the conservation principle of magnetic helicity, uses the relative magnetic helicity of the solar source region as input estimates, along with the radius and length of the corresponding CME flux rope. The method was initially applied to cylindrical force-free flux ropes, with encouraging results. We hereby extend our framework along two distinct lines. First, we generalize our formalism to several possible flux-rope configurations (linear and nonlinear force-free, non-force-free, spheromak, and torus) to investigate the dependence of the resulting CME axial magnetic field on input parameters and the employed flux-rope configuration. Second, we generalize our framework to both Sun-like and active M-dwarf stars hosting superflares. In a qualitative sense, we find that Earth may not experience severe atmosphere-eroding magnetospheric compression even for eruptive solar superflares with energies ~ 10^4 times higher than those of the largest Geostationary Operational Environmental Satellite (GOES) X-class flares currently observed. In addition, the two recently discovered exoplanets with the highest Earth-similarity index, Kepler 438b and Proxima b, seem to lie in the prohibitive zone of atmospheric erosion due to interplanetary CMEs (ICMEs), except when they possess planetary magnetic fields that are much higher than that of Earth.Comment: http://adsabs.harvard.edu/abs/2017SoPh..292...89

CD8+ T cell concentration determines their efficiency in killing cognate antigen–expressing syngeneic mammalian cells in vitro and in mouse tissues

We describe a quantitative model for assessing the cytolytic activity of antigen-specific CD8+ T cells in vitro and in vivo in which the concentration of antigen-specific CD8+ T cells determines the efficiency with which these cells kill cognate antigen–expressing melanoma cells in packed cell pellets, in three-dimensional collagen-fibrin gels in vitro, and in established melanomas in vivo. In combination with a clonogenic assay for melanoma cells, collagen-fibrin gels are 4,500–5,500-fold more sensitive than the packed cell pellet–type assays generally used to measure CD8+ T cell cytolytic activity. An equation previously used to describe neutrophil bactericidal activity in vitro and in vivo also describes antigen-specific CD8+ T cell–mediated cytolysis of cognate antigen-expressing melanoma cells in collagen-fibrin gels in vitro and in transplanted tumors in vivo. We have used this equation to calculate the critical concentration of antigen-specific CD8+ T cells, which is the concentration of these cells required to hold constant the concentration of a growing population of cognate antigen-expressing melanoma cells. It is ∼3.5 × 105/ml collagen-fibrin gel in vitro and ∼3 × 106/ml or /g melanoma for previously published studies of ex vivo–activated adoptively transferred tumor antigen–specific CD8+ T cell killing of cognate antigen–expressing melanoma cells in established tumors in vivo. The antigen-specific CD8+ T cell concentration required to kill 100% of 2 × 107/ml cognate antigen-expressing melanoma cells in collagen fibrin gels is ≥107/ml of gel

Optical Variability and Colour Behaviour of 3C 345

The colour behaviour of blazars is a subject of much debate. One argument is that the BL Lac objects show bluer-when-brighter chromatism while the flat-spectrum radio quasars (FSRQs) display redder-when-brighter trend. Base on a 3.5-year three-colour monitoring programme, we studied the optical variability and colour behaviour of one FSRQ, 3C 345. There is at least one outburst in this period. The overall variation amplitude is 2.640 mags in the $i$ band. Intra-night variability was observed on two nights. The bluer-when-brighter and redder-when-brighter chromatisms were simultaneously observed in this object when using different pairs of passbands to compute the colours. The bluer-when-brighter chromatism is a shared property with the BL Lacs, while the redder-when-brighter trend is likely due to two less variable emission features, the Mg\,{\sc ii} line and the blue bump, at short wavelengths. With numerical simulations, we show that some other strong but less variable emission lines in the spectrum of FSRQs may also significantly alter their colour behaviour. Then the colour behaviour of an FSRQ is linked not only to the emission process in the relativistic jet, but also to the redshift, the passbands used for computing the colour and the strengths of the less variable emission features relative to the strength of the non-thermal continuum.Comment: 9 pages, 9 figures, Accepted by MNRA

Empathy in senior year and first year medical students: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The importance of fostering the development of empathy in undergraduate students is continuously emphasized in international recommendations for medical education. Paradoxically, some studies in the North-American context using self-reported measures have found that empathy declines during undergraduate medical training. Empathy is also known to be gender dependent- (highest for female medical students) and related to specialty preference - (higher in patient-oriented than technology-oriented specialties). This factor has not been studied in Portuguese medical schools.</p> <p>Methods</p> <p>This is a cross-sectional study of undergraduate medical students on self-rated measures of empathy collected at entrance and at the conclusion of the medical degree, and on the association of empathy measures with gender and specialty preferences in one medical school in Portugal. Empathy was assessed using the Portuguese adaptation of the Jefferson Scale of Physician Empathy-students version (JSPE-spv) among three cohorts of undergraduate medical students in the first (N = 356) and last (N = 120) year. The construct validity of JSPE-spv was cross-validated with Principal Component Analysis and Confirmatory Factor Analysis. Reliability was assessed using Cronbach' Alpha. Global JSPE-spv score differences were examined by year of medical school, gender and specialty preferences (people-oriented vs technology-oriented specialties).</p> <p>Results</p> <p>The empathy scores of students in the final year were higher as compared to first year students (F (1,387) = 19.33, p < .001, ɳ²_p= 0.48; π = 0.99). Female students had higher empathy scores than male students (F (1,387) = 8.82, p < .01, ɳ ²_p= 0.23; π = 0.84). Significant differences in empathy were not found between the students who prefer people-oriented specialties compared to those who favor the technology-oriented specialties (F (1,387) = 2.44, p = .12, ɳ ²_p= 0.06; π = 0.06).</p> <p>Conclusions</p> <p>This cross-sectional study in one medical school in Portugal showed that the empathy measures of senior year students were higher than the scores of freshmen. A longitudinal cohort study is needed to test variations in students' empathy measures throughout medical school.</p

A defect of sphingolipid metabolism modifies the properties of normal appearing white matter in multiple sclerosis

Maintaining the appropriate complement and content of lipids in cellular membranes is critical for normal neural function. Accumulating evidence suggests that even subtle perturbations in the lipid content of neurons and myelin can disrupt their function and may contribute to myelin and axonal degradation. In this study, we determined the composition and quantified the content of lipids and sterols in normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) from control and multiple sclerosis brain tissues by electrospray ionization tandem mass spectrometry. Our results suggest that in active-multiple sclerosis, there is a shift in the lipid composition of NAWM and NAGM to a higher phospholipid and lower sphingolipid content. We found that this disturbance in lipid composition was reduced in NAGM but not in NAWM of inactive-multiple sclerosis. The pattern of disturbance in lipid composition suggests a metabolic defect that causes sphingolipids to be shuttled to phospholipid production. Modelling the biophysical consequence of this change in lipid composition of NAWM indicated an increase in the repulsive force between opposing bilayers that could explain decompaction and disruption of myelin structure