Carbohydrate recognition by Clostridium difficile toxin A

Clostridium difficile TcdA is a large toxin that binds carbohydrates on intestinal epithelial cells. A 2-A resolution cocrystal structure reveals two molecules of alpha-Gal-(1,3)-beta-Gal-(1,4)-beta-GlcNAcO(CH(2))(8)CO(2)CH(3) binding in an extended conformation to TcdA. Residues forming key contacts with the trisaccharides are conserved in all seven putative binding sites in TcdA, suggesting a mode of multivalent binding that may be exploited for the rational design of novel therapeutics.     

Increasing confidence of protein interactomes using network topological metrics

MOTIVATION: Experimental limitations in high-throughput protein-protein interaction detection methods have resulted in low quality interaction datasets that contained sizable fractions of false positives and false negatives. Small-scale, focused experiments are then needed to complement the high-throughput methods to extract true protein interactions. However, the naturally vast interactomes would require much more scalable approaches. RESULTS: We describe a novel method called IRAP* as a computational complement for repurification of the highly erroneous experimentally derived protein interactomes. Our method involves an iterative process of removing interactions that are confidently identified as false positives and adding interactions detected as false negatives into the interactomes. Identification of both false positives and false negatives are performed in IRAP* using interaction confidence measures based on network topological metrics. Potential false positives are identified amongst the detected interactions as those with very low computed confidence values, while potential false negatives are discovered as the undetected interactions with high computed confidence values. Our results from applying IRAP* on large-scale interaction datasets generated by the popular yeast-two-hybrid assays for yeast, fruit fly and worm showed that the computationally repurified interaction datasets contained potentially lower fractions of false positive and false negative errors based on functional homogeneity. AVAILABILITY: The confidence indices for PPIs in yeast, fruit fly and worm as computed by our method can be found at our website http://www.comp.nus.edu.sg/~chenjin/fpfn.     

Genome-wide SNPs confirm plumage polymorphism and hybridisation within a Cyornis flycatcher species complex

Morphology has been a leading taxonomic guiding light to systematists for the last couple of hundred years. However, the genetic and – more recently – genomic revolution have produced numerous demonstrations of erroneous classifications that were based on labile morphological traits. We used thousands of genome-wide markers to shed light on evolutionary dynamics in a confusing and taxonomically obscure group of Asian Cyornis flycatchers. Using genomic data, we corroborated recent findings based on three mitochrondrial and five nuclear genes that the two taxa hainanus and klossi which were previously treated as separate species (Cyornis hainanus and Cyornis rubeculoides klossi, respectively) are genomically homogeneous and form a single species, C. hainanus. We also uncovered a novel case of interbreeding between C. hainanus and a non-sister species, C. glaucicomans, illustrating these flycatchers' ability to hybridise in marginal situations even after substantial times of divergence. Our study illustrates how genome-wide loci can shed light on complicated taxonomic problems, resulting in a better integration of phenotypic and genotypic data.     

Selection of building thermal insulation materials using robust optimization

The International Journal of Life Cycle Assessment - Life cycle assessment (LCA) is commonly used to analyze the environmental profile of a material and product. For example, the selection of...     

The mind and the Devil: porosity and discernment in two Chinese charismatic-style churches

This essay explores otherworldly encounters and notions of mind across two charismatic-style churches in China. In Zhao Village Church in rural Henan province, Christian congregants more often approached the mind as porous to the Devil's corruption. In Living Church in Shanghai, congregants were more influenced by bounded, psychological notions of the mind as an entity; although the mind was also held to be permeable to spiritual personae, its interior workings stood as the central hindrance to discernment, rather than the externality of the Devil. And while those in Shanghai stressed a gradual, retroactive verification of potential spiritual signs, those in Henan strove for a rhythm of immediate response. Meanwhile, Shanghai congregants described fewer sensory and embodied encounters with divine voice, pain, and healing than congregants in Henan. Such divergent theories of mind, virtuous rhythms, and distributions within the Christian spiritual sensorium might be understood in part through styles of engagement accentuated at these churches, and in part through the uneven unfolding of religious abolition and revival in China, including the heightened urban presence of psychotherapeutic genres and the rural presence of spirit mediumship in recent decades. These variations in personhood and otherworldly encounter, including deeply porous ones, were thus co-present in an atheist secular milieu, after what have been seen as some of the most thorough secularization campaigns conducted by a modern state.     

Isolation of cucurmoschin, a novel antifungal peptide abundant in arginine, glutamate and glycine residues from black pumpkin seeds

A novel antifungal peptide, with a molecular mass of 8 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and in gel filtration on Superdex 75 and designated cucurmoschin, was isolated from the seeds of the black pumpkin. The peptide was unadsorbed on DEAE-cellulose but adsorbed on Affi-gel blue gel. Cucurmoschin inhibited mycelial growth in the fungi Botrytis cinerea, Fusarium oxysporum and Mycosphaerella oxysporum. It inhibited translation in a cell-free rabbit reticulocyte lysate system with an IC50 of 1.2 microM. The N-terminal sequence of cucurmoschin was rich in arginine, glutamate and glycine residues.     

Exploring Patient Values in Medical Decision Making: A Qualitative Study

Background

Patient decisions are influenced by their personal values. However, there is a lack of clarity and attention on the concept of patient values in the clinical context despite clear emphasis on patient values in evidence-based medicine and shared decision making. The aim of the study was to explore the concept of patient values in the context of making decisions about insulin initiation among people with type 2 diabetes.

Methods and Findings

We conducted individual in-depth interviews with people with type 2 diabetes who were making decisions about insulin treatment. Participants were selected purposively to achieve maximum variation. A semi-structured topic guide was used to guide the interviews which were audio-recorded and analysed using a thematic approach. We interviewed 21 participants between January 2011 and March 2012. The age range of participants was 28–67 years old. Our sample comprised 9 women and 12 men. Three main themes, ‘treatment-specific values’, ‘life goals and philosophies’, and ‘personal and social background’, emerged from the analysis. The patients reported a variety of insulin-specific values, which were negative and/or positive beliefs about insulin. They framed insulin according to their priorities and philosophies in life. Patients’ decisions were influenced by sociocultural (e.g. religious background) and personal backgrounds (e.g. family situations).

Conclusions

This study highlighted the need for expanding the current concept of patient values in medical decision making. Clinicians should address more than just values related to treatment options. Patient values should include patients’ priorities, life philosophy and their background. Current decision support tools, such as patient decision aids, should consider these new dimensions when clarifying patient values.