The role of Arkadia2C and the BMP signalling pathway in motor neuron development

Motor neurons elongate axons over great distances during development, with some extending from the spinal cord to the distal limb, but little is known about extracellular signals that control this growth. The TGF-β superfamily includes two major classes of ligands: Nodallike and BMP. BMP signalling is essential for neuromuscular synaptic growth and plasticity in Drosophila; however, a similar role for the pathway in mammalian motor neurons has not been described. It has previously been shown that the E3-RING ubiquitin ligase Arkadia enhances signalling through the Nodal branch of TGF-β signalling. A second Arkadia locus was previously found to contain two isoforms; the C-terminal isoform (Arkadia2C) contains domains critical for Arkadia’s activity. This project addresses the in vivo function of Arkadia2C in mice. Arkadia2C was found to be expressed specifically in the nervous system throughout embryonic development and adulthood. In a neuronal context Arkadia2C enhances signalling through the Smad1/5/8 branch of the TGF-β pathway in a RING domain-dependent manner. Mice null for Arkadia2C display motor neuron disease-like symptoms including weak motor control and difficulties breathing and eating, leading to postnatal mortality in the majority of mice. A subset of Arkadia2C null embryonic innervation defects was analysed; the majority of the motor axons of the dorsal forelimb fail to form synapses with their target muscles while the phrenic nerve exhibits shorter terminal branches. Postnatally, a failure to maintain neuromuscular junctions was observed leading to atrophy of several muscles. Active BMP signalling was observed in the neurons that innervate the limb and diaphragm and genetic reduction of BMP signalling in asymptomatic Arkadia2C heterozygous mice caused the appearance of the same muscle innervation defects observed in the null individuals. Together, these findings suggest that Arkadia2C’s enhancement of the BMP signalling pathway is critical for the growth and connectivity of certain motor neurons

Consistent left gaze bias in processing different facial cues

While viewing faces, humans often demonstrate a natural gaze bias towards the left visual field, that is, the right side of the viewee’s face is often inspected first and for longer periods. Previous studies have suggested that this gaze asymmetry is part of the gaze pattern associated with face exploration, but its relation with perceptual processing of facial cues is unclear. In this study we recorded participants’ saccadic eye movements while exploring face images under different task instructions (free-viewing, judging familiarity and judging facial expression). We observed a consistent left gaze bias in face viewing irrespective of task demands. The probability of the first fixation and the proportion of overall fixations directed at the left hemiface were indistinguishable across different task instructions or across different facial expressions. It seems that the left gaze bias is an automatic reflection of hemispheric lateralisation in face processing, and is not necessarily correlated with the perceptual processing of a specific type of facial information

Sympathetic nerve-derived ATP regulates renal medullary vasa recta diameter via pericyte cells: a role for regulating medullary blood flow?

Pericyte cells are now known to be a novel locus of blood flow control, being able to regulate capillary diameter via their unique morphology and expression of contractile proteins. We have previously shown that exogenous ATP causes constriction of vasa recta via renal pericytes, acting at a variety of membrane bound P2 receptors on descending vasa recta (DVR), and therefore may be able to regulate medullary blood flow (MBF). Regulation of MBF is essential for appropriate urine concentration and providing essential oxygen and nutrients to this region of high, and variable, metabolic demand. Various sources of endogenous ATP have been proposed, including from epithelial, endothelial, and red blood cells in response to stimuli such as mechanical stimulation, local acidosis, hypoxia, and exposure to various hormones. Extensive sympathetic innervation of the nephron has previously been shown, however the innervation reported has focused around the proximal and distal tubules, and ascending loop of Henle. We hypothesize that sympathetic nerves are an additional source of ATP acting at renal pericytes and therefore regulate MBF. Using a rat live kidney slice model in combination with video imaging and confocal microscopy techniques we firstly show sympathetic nerves in close proximity to vasa recta pericytes in both the outer and inner medulla. Secondly, we demonstrate pharmacological stimulation of sympathetic nerves in situ (by tyramine) evokes pericyte-mediated vasoconstriction of vasa recta capillaries; inhibited by the application of the P2 receptor antagonist suramin. Lastly, tyramine-evoked vasoconstriction of vasa recta by pericytes is significantly less than ATP-evoked vasoconstriction. Sympathetic innervation may provide an additional level of functional regulation in the renal medulla that is highly localized. It now needs to be determined under which physiological/pathophysiological circumstances that sympathetic innervation of renal pericytes is important

The role of motivation, glucose and self-control in the antisaccade task

Research shows that self-control is resource limited and there is a gradual weakening in consecutive self-control task performance akin to muscle fatigue. A body of evidence suggests that the resource is glucose and consuming glucose reduces this effect. This study examined the effect of glucose on performance in the antisaccade task - which requires self-control through generating a voluntary eye movement away from a target - following self-control exertion in the Stroop task. The effects of motivation and individual differences in self-control were also explored. In a double-blind design, 67 young healthy adults received a 25g glucose or inert placebo drink. Glucose did not enhance antisaccade performance following self-control exertion in the Stroop task. Motivation however, predicted performance on the antisaccade task; more specifically high motivation ameliorated performance decrements observed after initial self-control exertion. In addition, individuals with high levels of self-control performed better on certain aspects of the antisaccade task after administration of a glucose drink. The results of this study suggest that the antisaccade task might be a powerful paradigm, which could be used as a more objective measure of self-control. Moreover, the results indicate that level of motivation and individual differences in self-control should be taken into account when investigating deficiencies in self-control following prior exertion

"We Really Help, Taking Care of Each Other": Older Homeless Adults as Caregivers.

Objectives:Many older homeless adults maintain contact with family. We conducted a qualitative study examining the role of family caregiving for older homeless adults. Method:We conducted semi-structured qualitative interviews with a sample of 46 homeless participants who reported spending at least one night with a housed family member in the prior 6 months. Results:A total of 13 of 46 older adult participants provided caregiving. Themes included (a) the death of the care recipient led to the participant's homelessness; (b) feeling a duty to act as caregivers; (c) providing care in exchange for housing; (d) caregivers' ability to stay was tenuous; (e) providing care conflicted with the caregiver's needs; and (f) resentment when family was ungrateful. Discussion:In a sample of older homeless adults in contact with family, many provided caregiving for housed family. For some, caregiving precipitated homelessness; for others, caregiving provided temporary respite from homelessness, and for others, caregiving continued during homelessness

Charcoal reflectance reveals early Holocene boreal deciduous forests burned at high intensities

Published onlineJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Wildfire size, frequency, and severity are increasing in the Alaskan boreal forest in response to climate warming. One of the potential impacts of this changing fire regime is the alteration of successional trajectories, from black spruce to mixed stands dominated by aspen, a vegetation composition not experienced since the early Holocene. Such changes in vegetation composition may consequently alter the intensity of fires, influencing fire feedbacks to the ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such, are imperative for our understanding of how these ecosystems will respond to future climate warming. For the first time, we have used reflectance measurements of macroscopic charcoal particles (>180μm) from an Alaskan lake-sediment record to estimate ancient charring temperatures (termed pyrolysis intensity). We demonstrate that pyrolysis intensity increased markedly from an interval of birch tundra 11 ky ago (mean 1.52%Ro; 485°C), to the expansion of trees on the landscape ~10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640°C) irrespective of stand composition. Despite differing flammabilities and adaptations to fire, the highest pyrolysis intensities derive from two intervals with distinct vegetation compositions. 1) the expansion of mixed aspen and spruce woodland at 10 cal. kyr BP, and 2) the establishment of black spruce, and the modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that predicted expansion of deciduous trees into the boreal forest in the future could lead to high intensity, but low severity fires, potentially moderating future climate-fire feedbacks

Characterisation of a pucBA deletion mutant from Rhodopseudomonas palustris lacking all but the pucBAd genes

Rhodopseudomonas palustris is a species of purple photosynthetic bacteria that has a multigene family of puc genes that encode the alpha and beta apoproteins, which form the LH2 complexes. A genetic dissection strategy has been adopted in order to try and understand which spectroscopic form of LH2 these different genes produce. This paper presents a characterisation of one of the deletion mutants generated in this program, the pucBAd only mutant. This mutant produces an unusual spectroscopic form of LH2 that only has a single large NIR absorption band at 800 nm. Spectroscopic and pigment analyses on this complex suggest that it has basically a similar overall structure as that of the wild-type HL LH2 complex. The mutant has the unique phenotype where the mutant LH2 complex is only produced when cells are grown at LL. At HL the mutant only produces the LH1-RC core complex