Structural and mechanistic consequences of polypeptide binding by GroEL

The remarkable ability of the chaperonin GroEL to recognise a diverse range of non-native states of proteins constitutes one of the most fascinating molecular recognition events in protein chemistry. Recent structural studies have revealed a possible model for substrate binding by GroEL and a high-resolution image of the GroEL–GroES folding machinery has provided important new insights into our understanding of the mechanism of action of this chaperonin. Studies with a variety of model substrates reveal that the binding of substrate proteins to GroEL is not just a passive event, but can result in significant changes in the structure and stability of the bound polypeptide. The potential impact of this on the mechanism of chaperonin-assisted folding is not fully understood, but provides exciting scope for further experiment

Fat quantification in MRI-defined lumbar muscles

Some studies suggest fat infiltration in the lumbar muscles (LM) is associated with lower back pain (LBP) in adults. Usually fat in MRI-defined lumbar muscles is qualitatively valuated by visual grading via a 3 point scale, whereas a quantitative continuous (0 - 100%) approach may provide a greater insight. In this paper, we propose a method to precisely quantify the fat content / infiltration in a user-defined region of the lumbar muscles, which may aid better diagnosis. The key steps are segmenting the region of interest (ROI) from the lumbar muscles, identifying the fatty regions in the segmented region based on the selected threshold and softness levels, computing the parameters (such as total and region-wise fat content percentage, total-cross sectional area (TCSA), functional cross- sectional area (FCSA)) and exporting the computations and associated patient information from the MRI, into a atabase. A standalone application using MATLAB R2010a was developed to perform the required computations along with an intuitive GUI

An interactive segmentation tool for quantifying fat in lumbar muscles using axial lumbar-spine MRI

In this paper we present an interactive tool that can be used to quantify fat infiltration in lumbar muscles, which is useful in studying fat infiltration and lower back pain (LBP) in adults. Currently, a qualitative assessment by visual grading via a 5-point scale is used to study fat infiltration in lumbar muscles from an axial view of lumbar-spine MR Images. However, a quantitative approach (on a continuous scale of 0–100%) may provide a greater insight. In this paper, we propose a method to precisely quantify the fat deposition/infiltration in a user-defined region of the lumbar muscles, which may aid better diagnosis and analysis. The key steps are interactively segmenting the region of interest (ROI) from the lumbar muscles using the well known livewire technique, identifying fatty regions in the segmented region based on variable-selection of threshold and softness levels, automatically detecting the center of the spinal column and fragmenting the lumbar muscles into smaller regions with reference to the center of the spinal column, computing key parameters [such as total and region-wise fat content percentage, total-cross sectional area (TCSA) and functional cross-sectional area (FCSA)] and exporting the computations and associated patient information from the MRI, into a database. A standalone application using MATLAB R2014a was developed to perform the required computations along with an intuitive graphical user interface (GUI)

Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia.

We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development

"Arabic is the language of the Muslims–that's how it was supposed to be": exploring language and religious identity through reflective accounts from young British-born South Asians

This study explores how a group of young British-born South Asians understood and defined their religious and linguistic identities, focusing upon the role played by heritage languages and liturgical languages and by religious socialisation. Twelve British-born South Asians were interviewed using a semi-structured interview schedule. Interview transcripts were subjected to interpretative phenomenological analysis. Four superordinate themes are reported. These addressed participants' meaning-making regarding "the sanctification of language" and the consequential suitability of "the liturgical language as a symbol of religious community"; the themes of "ethnic pride versus religious identity" and "linguistic Otherness and religious alienation" concerned potential ethno-linguistic barriers to a positive religious identity. Findings are interpreted in terms of concepts drawn from relevant identity theories and tentative recommendations are offered concerning the facilitation of positive religious and ethnic identities

Developing and testing an instrument for identifying performance incentives in the Greek health care sector

BACKGROUND: In the era of cost containment, managers are constantly pursuing increased organizational performance and productivity by aiming at the obvious target, i.e. the workforce. The health care sector, in which production processes are more complicated compared to other industries, is not an exception. In light of recent legislation in Greece in which efficiency improvement and achievement of specific performance targets are identified as undisputable health system goals, the purpose of this study was to develop a reliable and valid instrument for investigating the attitudes of Greek physicians, nurses and administrative personnel towards job-related aspects, and the extent to which these motivate them to improve performance and increase productivity. METHODS: A methodological exploratory design was employed in three phases: a) content development and assessment, which resulted in a 28-item instrument, b) pilot testing (N = 74) and c) field testing (N = 353). Internal consistency reliability was tested via Cronbach's alpha coefficient and factor analysis was used to identify the underlying constructs. Tests of scaling assumptions, according to the Multitrait-Multimethod Matrix, were used to confirm the hypothesized component structure. RESULTS: Four components, referring to intrinsic individual needs and external job-related aspects, were revealed and explain 59.61% of the variability. They were subsequently labeled: job attributes, remuneration, co-workers and achievement. Nine items not meeting item-scale criteria were removed, resulting in a 19-item instrument. Scale reliability ranged from 0.782 to 0.901 and internal item consistency and discriminant validity criteria were satisfied. CONCLUSION: Overall, the instrument appears to be a promising tool for hospital administrations in their attempt to identify job-related factors, which motivate their employees. The psychometric properties were good and warrant administration to a larger sample of employees in the Greek healthcare system

Functional Polymorphisms in PRODH Are Associated with Risk and Protection for Schizophrenia and Fronto-Striatal Structure and Function

PRODH, encoding proline oxidase (POX), has been associated with schizophrenia through linkage, association, and the 22q11 deletion syndrome (Velo-Cardio-Facial syndrome). Here, we show in a family-based sample that functional polymorphisms in PRODH are associated with schizophrenia, with protective and risk alleles having opposite effects on POX activity. Using a multimodal imaging genetics approach, we demonstrate that haplotypes constructed from these risk and protective functional polymorphisms have dissociable correlations with structure, function, and connectivity of striatum and prefrontal cortex, impacting critical circuitry implicated in the pathophysiology of schizophrenia. Specifically, the schizophrenia risk haplotype was associated with decreased striatal volume and increased striatal-frontal functional connectivity, while the protective haplotype was associated with decreased striatal-frontal functional connectivity. Our findings suggest a role for functional genetic variation in POX on neostriatal-frontal circuits mediating risk and protection for schizophrenia