X-ray diffraction analysis and in vitro characterization of the UAM2 protein from Oryza sativa

The role of seemingly non-enzymatic proteins in complexes interconverting UDP-arabinopyranose and UDP-arabinofuranose (UDP-arabinosemutases; UAMs) in the plant cytosol remains unknown. To shed light on their function, crystallographic and functional studies of the seemingly non-enzymatic UAM2 protein from Oryza sativa (OsUAM2) were undertaken. Here, X-ray diffraction data are reported, as well as analysis of the oligomeric state in the crystal and in solution. OsUAM2 crystallizes readily but forms highly radiation-sensitive crystals with limited diffraction power, requiring careful low-dose vector data acquisition. Using size-exclusion chromatography, it is shown that the protein is monomeric in solution. Finally, limited proteolysis was employed to demonstrate DTT-enhanced proteolytic digestion, indicating the existence of at least one intramolecular disulfide bridge or, alternatively, a requirement for a structural metal ion

Factors associated with youth gang membership in low and middle-income countries: a systematic review.

Youth gang membership is associated with delinquency, violent crime and trafficking – and gang members are themselves frequently the victims of these offences. Yet youth gangs can also provide a form of social capital, a sense of belonging and purpose to disenfranchised youth. This review identifies the factors associated with young people joining gangs, and the differences between gang-involved and non-gang-involved youth. Understanding these associations is essential to reduce the levels of gang membership and the incidence of related violence

The Center for Integrated Molecular Brain Imaging (Cimbi) database

AbstractWe here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes.The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies.The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank

Insulin Resistance Is Not Conserved in Myotubes Established from Women with PCOS

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among premenopausal women, who often develop insulin resistance. We tested the hypothesis that insulin resistance in skeletal muscle of patients with polycystic ovary syndrome (PCOS) is an intrinsic defect, by investigating the metabolic characteristics and gene expression of in vitro differentiated myotubes established from well characterized PCOS subjects.Using radiotracer techniques, RT-PCR and enzyme kinetic analysis we examined myotubes established from PCOS subjects with or without pioglitazone treatment, versus healthy control subjects who had been extensively metabolically characterized in vivo. Results. Myotubes established from PCOS and matched control subjects comprehensively expressed all insulin-sensitive biomarkers; glucose uptake and oxidation, glycogen synthesis and lipid uptake. There were no significant differences between groups either at baseline or during acute insulin stimulation, although in vivo skeletal muscle was insulin resistant. In particular, we found no evidence for defects in insulin-stimulated glycogen synthase activity between groups. Myotubes established from PCOS patients with or without pioglitazone treatment also showed no significant differences between groups, neither at baseline nor during acute insulin stimulation, although in vivo pioglitazone treatment significantly improved insulin sensitivity. Consistently, the myotube cultures failed to show differences in mRNA levels of genes previously demonstrated to differ in PCOS patients with or without pioglitazone treatment (PLEK, SLC22A16, and TTBK).These results suggest that the mechanisms governing insulin resistance in skeletal muscle of PCOS patients in vivo are not primary, but rather adaptive.ClinicalTrials.gov NCT00145340

Does Diving Limit Brain Size in Cetaceans?

We test the longstanding hypothesis, known as the dive constraint hypothesis, that the oxygenation demands of diving pose a constraint on aquatic mammal brain size.Using a sample of 23 cetacean species we examine the relationship among six different measures of relative brain size, body size, and maximum diving duration. Unlike previous tests we include body size as a covariate and perform independent contrast analyses to control for phylogeny. We show that diving does not limit brain size in cetaceans and therefore provide no support for the dive constraint hypothesis. Instead, body size is the main predictor of maximum diving duration in cetaceans. Furthermore, our findings show that it is important to conduct robust tests of evolutionary hypotheses by employing a variety of measures of the dependent variable, in this case, relative brain size

AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder:COORDINATE-MDD consortium design and rationale

BACKGROUND: Efforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states. METHODS: We describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level. International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants. RESULTS: We are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites. CONCLUSION: We describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project

Movement control exercise versus general exercise to reduce disability in patients with low back pain and movement control impairment. A randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Non-specific low back pain (NSLBP) in subacute and chronic stages can be treated effectively with exercise therapy. Research guidelines recommend evaluating different treatments in defined subgroups of patients with NSLBP. A subgroup of patients with movement control impairment (MCI) improved significantly on patient specific function and disability in a previous case series after movement control exercises.</p> <p>Methods/Design</p> <p>In a randomised controlled trial (RCT) we will compare the effectiveness of movement control and general exercise in patients with MCI. 106 participants aged 18 - 75 will be recruited in 5 outpatient hospital departments and 7 private practices.</p> <p>Patients randomly assigned to the movement control exercise group will be instructed to perform exercises according to their MCI. The general exercise group will follow an exercise protocol aimed at improving endurance and flexibility. Patients in both groups will receive 9 - 18 treatments and will be instructed to do additional exercises at home.</p> <p>The primary outcome is the level of disability assessed using the patient specific functional scale (PSFS) which links the perceived pain to functional situations and is measured before treatment and at 6 and 12 months follow-up. Secondary outcomes concern low back pain related disability (Roland Morris questionnaire, RMQ), graded chronic pain scale (GCPS), range of motion and tactile acuity.</p> <p>Discussion</p> <p>To our knowledge this study will be the first to compare two exercise programs for a specific subgroup of patients with NSLBP and MCI. Results of this study will provide insight into the effectiveness of movement control exercise and contribute to our understanding of the mechanisms behind MCI and its relation to NSLBP.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN80064281">ISRCTN80064281</a></p