Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

A network of molecular chaperones is known to bind proteins ('clients') and balance their folding, function and turnover. However, it is often unclear which chaperones are critical for selective recognition of individual clients. It is also not clear why these key chaperones might fail in protein-aggregation diseases. Here, we utilized human microtubule-associated protein tau (MAPT or tau) as a model client to survey interactions between ~30 purified chaperones and ~20 disease-associated tau variants (~600 combinations). From this large-scale analysis, we identified human DnaJA2 as an unexpected, but potent, inhibitor of tau aggregation. DnaJA2 levels were correlated with tau pathology in human brains, supporting the idea that it is an important regulator of tau homeostasis. Of note, we found that some disease-associated tau variants were relatively immune to interactions with chaperones, suggesting a model in which avoiding physical recognition by chaperone networks may contribute to disease

A calibration protocol for population-specific accelerometer cut-points in children

PurposeTo test a field-based protocol using intermittent activities representative of children\u27s physical activity behaviours, to generate behaviourally valid, population-specific accelerometer cut-points for sedentary behaviour, moderate, and vigorous physical activity.MethodsTwenty-eight children (46% boys) aged 10&ndash;11 years wore a hip-mounted uniaxial GT1M ActiGraph and engaged in 6 activities representative of children\u27s play. A validated direct observation protocol was used as the criterion measure of physical activity. Receiver Operating Characteristics (ROC) curve analyses were conducted with four semi-structured activities to determine the accelerometer cut-points. To examine classification differences, cut-points were cross-validated with free-play and DVD viewing activities.ResultsCut-points of &le;372, &gt;2160 and &gt;4806 counts&bull;min&minus;1 representing sedentary, moderate and vigorous intensity thresholds, respectively, provided the optimal balance between the related needs for sensitivity (accurately detecting activity) and specificity (limiting misclassification of the activity). Cross-validation data demonstrated that these values yielded the best overall kappa scores (0.97; 0.71; 0.62), and a high classification agreement (98.6%; 89.0%; 87.2%), respectively. Specificity values of 96&ndash;97% showed that the developed cut-points accurately detected physical activity, and sensitivity values (89&ndash;99%) indicated that minutes of activity were seldom incorrectly classified as inactivity.ConclusionThe development of an inexpensive and replicable field-based protocol to generate behaviourally valid and population-specific accelerometer cut-points may improve the classification of physical activity levels in children, which could enhance subsequent intervention and observational studies.<br /

Vacuolar organization in the nodule parenchyma is important for the functioning of pea root nodules

Different models have been proposed to explain the operation of oxygen diffusion barrier in root nodules of leguminous plants. This barrier participates in protection of oxygen-sensitive nitrogenase, the key enzyme in nitrogen fixation, from inactivation. Details concerning structural and biochemical properties of the barrier are still lacking. Here, the properties of pea root nodule cortical cells were examined under normal conditions and after shoot removal. Microscopic observations, including neutral red staining and epifluorescence investigations, showed that the inner and outer nodule parenchyma cells exhibit different patterns of the central vacuole development. In opposition to the inner part, the outer parenchyma cells exhibited vacuolar shrinkage and formed cell wall infoldings. Shoot removal induced vacuolar shrinkage and formation of infoldings in the inner parenchyma and uninfected cells of the symbiotic tissue, as well. It is postulated that cells which possess shrinking vacuoles are sensitive to the external osmotic pressure. The cells can give an additional resistance to oxygen diffusion by release of water to the intercellular spaces

Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component.

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurode- generative disorders are very complicated and multifacto- rial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very di cult to be interpretated and often useless. Mouse models could be condiderated a ‘pathway models’, rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high eld Magnetic resonance, Optical Imaging scanners and of highly speci c contrast agents. Behavioral test are useful tool to characterize di erent ani- mal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the di erent neurodegenerative disorders. Aim of this review is to focus on the di erent existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases

Capillary gas chromatography/mass spectrometry of oxazaphosphorines

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