Function and localization within rostral prefrontal cortex (area 10)

We propose that rostral prefrontal cortex (PFC; approximating area 10) supports a cognitive system that facilitates either stimulus-oriented (SO) or stimulus-independent (SI) attending. SO attending is the behaviour required to concentrate on current sensory input, whereas SI attending is the mental processing that accompanies self-generated or self-maintained thought. Regions of medial area 10 support processes related to the former, whilst areas of lateral area 10 support processes that enable the latter. Three lines of evidence for this 'gateway hypothesis' are presented. First, we demonstrate the predicted patterns of activation in area 10 during the performance of new tests designed to stress the hypothetical function. Second, we demonstrate area 10 activations during the performance of established functions (prospective memory, context memory), which should hypothetically involve the proposed attentional system. Third, we examine predictions about behaviour-activation patterns within rostral PFC that follow from the hypothesis. We show with meta-analysis of neuroimaging investigations that these predictions are supported across a wide variety of tasks, thus establishing a general principle for functional imaging studies of this large brain region. We then show that while the gateway hypothesis accommodates a large range of findings relating to the functional organization of area 10 along a medial-lateral dimension, there are further principles relating to other dimensions and functions. In particular, there is a functional dissociation between the anterior medial area 10, which supports processes required for SO attending, and the caudal medial area 10, which supports processes relating to mentalizing.     

Visualizing the localization of sulfoglycolipids in lipid raft domains in model membranes and sperm membrane extracts

Sulfogalactosylglycerolipid (SGG) is found in detergent-resistant lipid raft fractions isolated from sperm plasma membranes and has been shown to be important in sperm-egg adhesion. In order to provide more direct evidence for the association of sulfoglycolipids with lipid raft domains, we have examined the distribution of two sulfoglycolipids in supported membranes prepared from artificial lipid mixtures and cellular lipid extracts. Atomic force microscopy has been used to visualize the localization of SGG and sulfogalactosylceramide (SGC) in liquid-ordered domains in supported bilayers of ternary lipid mixtures comprised of dipalmitoylphosphatidylcholine, cholesterol and palmitoyldocosahexaenoylphosphatidylcholine. The localization of SGC/SGG in the liquid-ordered raft domains is demonstrated by changes in bilayer morphology in the presence of sulfoglycolipid, by selective antibody labeling of the domains with anti-SGC/SGG and by the effects of the cholesterol-sequestering agent, methyl-β-cyclodextrin, on the supported membranes. In addition, we use a combination of atomic force microscopy and immunofluorescence to show that supported bilayers made from lipids extracted from sperm anterior head plasma membranes (APM) and isolated APM vesicles exhibit small SGG-rich domains that are similar to those observed in bilayers of artificial lipid mixtures. The possible implications of these results for the involvement of SGG-rich lipid rafts in modulating sperm-egg interactions in vivo and the utility of model membranes for studying the behavior of lipid rafts are discussed.     

Aging effects of motor prediction on protective balance and startle responses to sudden drop perturbations

This pilot study investigated the effect of age on the ability of motor prediction during self-triggered drop perturbations (SLF) to modulate startle-like first trial response (FTR) magnitude during externally-triggered (EXT) drop perturbations. Ten healthy older (71.4 ± 1.44 years) and younger adults (26.2 ± 1.63 years) stood atop a moveable platform and received blocks of twelve consecutive EXT and SLF drop perturbations. Following the last SLF trial, participants received an additional EXT trial spaced 20 min apart to assess retention (EXT RTN) of any modulation effects. Electromyographic (EMG) activity was recorded bilaterally over the sternocleidomastoid (SCM), vastus lateralis (VL), biceps femoris (BF), medial gastrocnemius (MG), and tibialis anterior (TA). Whole-body kinematics and kinetic data were recorded. Stability in the antero-posterior direction was quantified using the margin of stability (MoS). Compared with EXT trials, both groups reduced SCM peak amplitude responses during SLF and EXT RTN trials. VL/BF and TA/MG coactivation were reduced during SLF FTR compared to EXT FTR (p < 0.05) with reduced peak vertical ground reaction forces (vGRF) in both younger and older adults (p < 0.05). Older adults increased their MoS during SLF FTR compared to EXT FTR (p < 0.05). Both groups performed more eccentric work during SLF trials compared to EXT (p < 0.05). These findings indicate that abnormal startle effects with aging may interfere with balance recovery and increase risk of injury with external balance perturbations. Motor prediction may be used to acutely mitigate abnormal startle/postural responses with aging.     

Der p 1 is the primary activator of Der p 3, Der p 6 and Der p 9 the proteolytic allergens produced by the house dust mite Dermatophagoides pteronyssinus

Background

The enzymatic activity of the four proteases found in the house dust mite Dermatophagoides pteronyssinus is involved in the pathogenesis of allergy. Our aim was to elucidate the activation cascade of their corresponding precursor forms and particularly to highlight the interconnection between proteases during this cascade.

Methods

The cleavage of the four peptides corresponding to the mite zymogen activation sites was studied on the basis of the Förster Resonance Energy Transfer method. The proDer p 6 zymogen was then produced in Pichia pastoris to elucidate its activation mechanism by mite proteases, especially Der p 1. The role of the propeptide in the inhibition of the enzymatic activity of Der p 6 was also examined. Finally, the Der p 1 and Der p 6 proteases were localised via immunolocalisation in D. pteronyssinus.

Results

All peptides were specifically cleaved by Der p 1, such as proDer p 6. The propeptide of proDer p 6 inhibited the proteolytic activity of Der p 6, but once cleaved, it was degraded by the protease. The Der p 1 and Der p 6 proteases were both localised to the midgut of the mite.

Conclusions

Der p 1 in either its recombinant form or in the natural context of house dust mite extracts specifically cleaves all zymogens, thus establishing its role as a major activator of both mite cysteine and serine proteases.

General significance

This finding suggests that Der p 1 may be valuable target against mites.     

The G protein-coupled receptor GPR162 is widely distributed in the CNS and highly expressed in the hypothalamus and in hedonic feeding areas

The Rhodopsin family is a class of integral membrane proteins belonging to G protein-coupled receptors (GPCRs). To date, several orphan GPCRs are still uncharacterized and in this study we present an anatomical characterization of the GPR162 protein and an attempt to describe its functional role. Our results show that GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in areas related to energy homeostasis and hedonic feeding such as hypothalamus, amygdala and ventral tegmental area, regions known to be involved in the regulation of palatable food consumption.     

Heading forwards: anterior visceral endoderm migration in patterning the mouse embryo

The elaboration of anterior–posterior (A–P) pattern is one of the earliest events during development and requires the precisely coordinated action of several players at the level of molecules, cells and tissues. In mammals, it is controlled by a specialized population of migratory extraembryonic epithelial cells, the anterior visceral endoderm (AVE). The AVE is a signalling centre that is responsible for several important patterning events during early development, including specifying the orientation of the A–P axis and the position of the heart with respect to the brain. AVE cells undergo a characteristic stereotypical migration which is crucial to their functions.