Energy Landscape and Global Optimization for a Frustrated Model Protein

The three-color (BLN) 69-residue model protein was designed to exhibit frustrated folding. We investigate the energy landscape of this protein using disconnectivity graphs and compare it to a Go model, which is designed to reduce the frustration by removing all non-native attractive interactions. Finding the global minimum on a frustrated energy landscape is a good test of global optimization techniques, and we present calculations evaluating the performance of basin-hopping and genetic algorithms for this system.Comparisons are made with the widely studied 46-residue BLN protein.We show that the energy landscape of the 69-residue BLN protein contains several deep funnels, each of which corresponds to a different β-barrel structure

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

Living with hope: developing a psychosocial supportive program for rural women caregivers of persons with advanced cancer

<p>Abstract</p> <p>Background</p> <p>Hope is defined by caregivers as the inner strength to achieve future good and to continue care giving. Pilot test findings of a Living with Hope Program (LWHP) suggested it is an acceptable and feasible intervention for use by family caregivers. Although it shows promise in potentially increasing hope and quality of life, further testing and development is needed. Questions remain as to: a) what are the mechanisms through which the LWHP affects outcomes and b) how long it is effective? <it>The overall purpose of this time series mixed method study is the further development and testing of the LWHP by</it>:</p> <p indent="1">a. Determining the mechanisms of the LWHP by testing a LWHP conceptual model in which self-efficacy, and loss/grief are hypothesized intermediary variables for changes in hope, and subsequently quality of life among rural women caring for persons with advanced cancer, and;</p> <p indent="1">b. Exploring the longitudinal effects of the LWHP on hope, quality of life and health services utilization among rural women caring for persons with advanced cancer.</p> <p>Methods/Design</p> <p>Using a time-series embedded mixed method design, data will be collected from 200 rural women caregivers. Following the collection of baseline and outcome variables, the intervention (LWHP) is applied to all subjects. Subjects are followed over time with repeated measures of outcome variables (1 wk, 2 wk, 3, 6 and 12 months). The journals that are completed as part of the LWHP comprise the qualitative data. Health services utilization data will be collected from the Saskatchewan Health Administrative Database for all subjects one year prior and one year after study enrolment.</p> <p>Path analysis will be used to test the model post LWHP, at 1 and 2 weeks. Two-factor ANCOVA will determine patterns over time and Cortazzi's narrative analysis will be used to analyze subjects journals completed as part of the LWHP.</p> <p>Discussion</p> <p>Data Collection began January 2009 and is expected to be completed within 2 years time. Monthly meetings with data collectors and site collaborators have been instrumental in revisions to the original study protocol such as identifying and adding additional study sites.</p> <p>Trial Registration</p> <p>Trial Registration; Clinical Trials.Gov. NCT01081301</p

Using Shifts in Amino Acid Frequency and Substitution Rate to Identify Latent Structural Characters in Base-Excision Repair Enzymes

Protein evolution includes the birth and death of structural motifs. For example, a zinc finger or a salt bridge may be present in some, but not all, members of a protein family. We propose that such transitions are manifest in sequence phylogenies as concerted shifts in substitution rates of amino acids that are neighbors in a representative structure. First, we identified rate shifts in a quartet from the Fpg/Nei family of base excision repair enzymes using a method developed by Xun Gu and coworkers. We found the shifts to be spatially correlated, more precisely, associated with a flexible loop involved in bacterial Fpg substrate specificity. Consistent with our result, sequences and structures provide convincing evidence that this loop plays a very different role in other family members. Second, then, we developed a method for identifying latent protein structural characters (LSC) given a set of homologous sequences based on Gu's method and proximity in a high-resolution structure. Third, we identified LSC and assigned states of LSC to clades within the Fpg/Nei family of base excision repair enzymes. We describe seven LSC; an accompanying Proteopedia page (http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family) describes these in greater detail and facilitates 3D viewing. The LSC we found provided a surprisingly complete picture of the interaction of the protein with the DNA capturing familiar examples, such as a Zn finger, as well as more subtle interactions. Their preponderance is consistent with an important role as phylogenetic characters. Phylogenetic inference based on LSC provided convincing evidence of independent losses of Zn fingers. Structural motifs may serve as important phylogenetic characters and modeling transitions involving structural motifs may provide a much deeper understanding of protein evolution

Early Evolution of Ionotropic GABA Receptors and Selective Regimes Acting on the Mammalian-Specific Theta and Epsilon Subunits

BACKGROUND: The amino acid neurotransmitter GABA is abundant in the central nervous system (CNS) of both invertebrates and vertebrates. Receptors of this neurotransmitter play a key role in important processes such as learning and memory. Yet, little is known about the mode and tempo of evolution of the receptors of this neurotransmitter. Here, we investigate the phylogenetic relationships of GABA receptor subunits across the chordates and detail their mode of evolution among mammals. PRINCIPAL FINDINGS: Our analyses support two major monophyletic clades: one clade containing GABA(A) receptor alpha, gamma, and epsilon subunits, and another one containing GABA(A) receptor rho, beta, delta, theta, and pi subunits. The presence of GABA receptor subunits from each of the major clades in the Ciona intestinalis genome suggests that these ancestral duplication events occurred before the divergence of urochordates. However, while gene divergence proceeded at similar rates on most receptor subunits, we show that the mammalian-specific subunits theta and epsilon experienced an episode of positive selection and of relaxed constraints, respectively, after the duplication event. Sites putatively under positive selection are placed on a three-dimensional model obtained by homology-modeling. CONCLUSIONS: Our results suggest an early divergence of the GABA receptor subunits, before the split from urochordates. We show that functional changes occurred in the lineages leading to the mammalian-specific subunit theta, and we identify the amino acid sites putatively responsible for the functional divergence. We discuss potential consequences for the evolution of mammals and of their CNS

The power of civilizational nationalism in Russian foreign policy making

The article draws upon theories of identity to understand Russian foreign policy towards Ukraine since 2000. The article argues that contemporary Russian foreign policy can be best understood as an articulation of ‘civilizational nationalism’ which relies on the myth of cultural superiority. The focus is on not only treating Russia as an imperial power, but on the cultural claims that this relies upon and its configuration within changing historical ideas of ‘Russianness’. Since the Orange Revolution, Russian presidents have accused Ukraine of following anti-Russian policies. This has been aided by a discourse of ‘civilizational nationalism’ where Ukraine is described as being part of a ‘Greater Russia’, rather than as a sovereign territory. This article analyses how imagined civilization and greatness of Russian culture is driving foreign policy making towards the Ukraine. Rather than an external territory, Ukraine is constructed as a ‘little brother’ which renders interventions legitimate