Organization and repair of the trigeminal system in the lamprey using fluorescent double labeling [abstract]

Abstract only availableFaculty Mentor: Andrew McClellan, Biological ScienceIn the CNS, many sensory and motor systems are topologically organized relative to various body structures.  For example, in humans, sensory inputs from the lower, middle, and upper parts of the body are received by the anterior, middle, and posterior somatosensory cortex, respectively.  Following injury in the CNS of higher vertebrates, such as birds and mammals, there is very little regeneration and recovery of function.  In contrast, in lower vertebrates, including lamprey, fish, and certain amphibians, substantial axonal regeneration occurs following CNS injuries, and there is virtually complete recovery of functions.  However, it is not known whether axonal regeneration restores the topological organization that may have existed prior to injury.  The trigeminal system is responsible for transmitting sensory and motor information from the head via axons in the trigeminal cranial nerve.  In the lamprey following injury of the trigeminal nerve, sensory and motor axons regenerate.  The purpose of the present study was to determine whether the trigeminal system of normal lamprey is topologically organized and whether regeneration of axons in injured trigeminal nerve restores this organization.  In normal larval lamprey, Alexa 488 dextran amine (Alexa) and Texas red dextran amine (TRDA), two different anatomical fluorescent tracers, were applied to the medial and lateral parts of the head, respectively.  This resulted in clear labeling of the medial and lateral parts of the trigeminal system in the brain with Alexa and TRDA, respectively.  Thus, in normal lamprey, the trigeminal system appears to be topologically organized.  If following injury of the trigeminal nerve, axonal regeneration restores this topological organization, this will indicate that regeneration in the lamprey is relatively precise and possibly controlled by specific guidance factors.  Identification of these guidance factors would greatly improve our understanding of the mechanisms that regulate axonal regeneration following CNS injury in vertebrate animals, including humans.

Human Tra2 proteins jointly control a CHEK1 splicing switch among alternative and constitutive target exons

Alternative splicing—the production of multiple messenger RNA isoforms from a single gene—is regulated in part by RNA binding proteins. While the RBPs transformer2 alpha (Tra2α) and Tra2β have both been implicated in the regulation of alternative splicing, their relative contributions to this process are not well understood. Here we find simultaneous—but not individual—depletion of Tra2α and Tra2β induces substantial shifts in splicing of endogenous Tra2β target exons, and that both constitutive and alternative target exons are under dual Tra2α–Tra2β control. Target exons are enriched in genes associated with chromosome biology including CHEK1, which encodes a key DNA damage response protein. Dual Tra2 protein depletion reduces expression of full-length CHK1 protein, results in the accumulation of the DNA damage marker γH2AX and decreased cell viability. We conclude Tra2 proteins jointly control constitutive and alternative splicing patterns via paralog compensation to control pathways essential to the maintenance of cell viability

Poverty alleviation policies and action in Hong Kong : an analysis of public engagement strategies

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis

Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2 + monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development

Evidence for a pervasive 'idling-mode' activity template in flying and pedestrian insects

Understanding the complex movement patterns of animals in natural environments is a key objective of ‘movement ecology’. Complexity results from behavioural responses to external stimuli but can also arise spontaneously in their absence. Drawing on theoretical arguments about decision-making circuitry, we predict that the spontaneous patterns will be scale-free and universal, being independent of taxon and mode of locomotion. To test this hypothesis, we examined the activity patterns of the European honeybee, and multiple species of noctuid moth, tethered to flight mills and exposed to minimal external cues. We also reanalysed pre-existing data for Drosophila flies walking in featureless environments. Across these species, we found evidence of common scale-invariant properties in their movement patterns; pause and movement durations were typically power law distributed over a range of scales and characterized by exponents close to 3/2. Our analyses are suggestive of the presence of a pervasive scale-invariant template for locomotion which, when acted on by environmental cues, produces the movements with characteristic scales observed in nature. Our results indicate that scale-finite complexity as embodied, for instance, in correlated random walk models, may be the result of environmental cues overriding innate behaviour, and that scale-free movements may be intrinsic and not limited to ‘blind’ foragers as previously thought

A reassuring presence: An evaluation of Bradford District Hospice at Home service

Within the United Kingdom, a developing role for primary care services in cancer and palliative care has resulted in an increase in palliative home care teams. The provision of professional care in the home setting seeks to provide necessary services and enhanced choice for patients whose preference is to die at home. A mismatch between patient preference for home death and the actual number of people who died at home was identified within Bradford, the locality of this study. In response to this mismatch, and reflecting the policy environment of wishing to enhance community service provision, the four Primary Care Trusts (PCTs) in the city sought to offer support to patients who wished to remain in their own homes through the final stages of a terminal illness. To offer this support they set up a dedicated hospice at home team. This would provide services and support for patients in achieving a dignified, symptom free and peaceful death, allowing families to maximise time spent together. The aim of the study was to evaluate the Bradford hospice at home service from the perspective of carers, nurses and General Practitioners. Postal questionnaires were sent to carers (n = 289), district nurses (n = 508) and GP's (n = 444) using Bradford's hospice at home service. Resulting quantitative data was analysed using the Statical Package for Social Sciences (SPSS) and qualitative data was analysed using grounded theory techniques. The data from carers, district nurses and GPs provide general support for the Bradford hospice at home service. Carers valued highly the opportunity to 'fulfil a promise' to the individual who wished to be cared for at home. District nurses and GPs cited the positive impact of access to specialist expertise. This was a 'reassuring presence' for primary healthcare teams and offered 'relief of carer anxiety' by providing prompt, accessible and sensitive care. Carers and health professionals welcomed the increased possibility of patients being cared for at home. The study identified the need to focus on improving skill levels of staff and on ensuring continuity of care

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The illusion of competency versus the desirability of expertise: Seeking a common standard for support professions in sport

In this paper we examine and challenge the competency-based models which currently dominate accreditation and development systems in sport support disciplines, largely the sciences and coaching. Through consideration of exemplar shortcomings, the limitations of competency-based systems are presented as failing to cater for the complexity of decision making and the need for proactive experimentation essential to effective practice. To provide a better fit with the challenges of the various disciplines in their work with performers, an alternative approach is presented which focuses on the promotion, evaluation and elaboration of expertise. Such an approach resonates with important characteristics of professions, whilst also providing for the essential ‘shades of grey’ inherent in work with human participants. Key differences between the approaches are considered through exemplars of evaluation processes. The expertise-focused method, although inherently more complex, is seen as offering a less ambiguous and more positive route, both through more accurate representation of essential professional competence and through facilitation of future growth in proficiency and evolution of expertise in practice. Examples from the literature are also presented, offering further support for the practicalities of this approach

Transiting Disintegrating Planetary Debris around WD 1145+017

More than a decade after astronomers realized that disrupted planetary material likely pollutes the surfaces of many white dwarf stars, the discovery of transiting debris orbiting the white dwarf WD 1145+017 has opened the door to new explorations of this process. We describe the observational evidence for transiting planetary material and the current theoretical understanding (and in some cases lack thereof) of the phenomenon.Comment: Invited review chapter. Accepted March 23, 2017 and published October 7, 2017 in the Handbook of Exoplanets. 15 pages, 10 figure