Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease

Background Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with disease progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor dysfunctions, there are currently no interventions capable of adequately targeting these non-motor deficits. Objectives Utilizing a rodent model of PD, we investigated whether cell replacement therapy, using intrastriatal transplants of human-derived ventral mesencephalic (hVM) grafts, could alleviate cognitive and neuropsychiatric, as well as motor, dysfunctions. Methods Rats with unilateral 6-hydroxydopamine lesions to the medial forebrain bundle were tested on a complex operant task that dissociates motivational, visuospatial and motor impairments sensitive to the loss of dopamine. A subset of lesioned rats received intrastriatal hVM grafts of ~ 9 weeks gestation. Post-graft, rats underwent repeated drug-induced rotation tests and were tested on two versions of the complex operant task, before post-mortem analysis of the hVM tissue grafts. Results Post-graft behavioural testing revealed that hVM grafts improved non-motor aspects of task performance, specifically visuospatial function and motivational processing, as well as alleviating motor dysfunctions. Conclusions We report the first evidence of human VM cell grafts alleviating both non-motor and motor dysfunctions in an animal model of PD. This intervention, therefore, is the first to improve cognitive and neuropsychiatric symptoms long-term in a model of PD

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

Jejunal immunoglobulin and antigliadin antibody secretion in adult coeliac disease.

We compared the local intestinal immunoglobulin (Ig) secretion in six adult patients with coeliac disease and nine control subjects by perfusion of a small bowel segment under an occluding balloon and analysis of the perfusion fluid for the content of Ig and secretory component. The results were compared to the number of Ig-containing plasma cells in the test segment. There was, respectively, a two-fold and a fivefold increase in jejunal secretion rates of IgA (both monomeric and polymeric) and IgM in patients with coeliac disease compared with control subjects. The high IgA and IgM secretion rates parallel the increase of Ig-containing plasma cells in the lamina propria. In contrast, the IgG plasma cell density increase was barely significant in patients with coeliac disease and did not result in a high IgG secretion rate. The jejunal secretion rate of secretory component was significantly increased in patients with coeliac disease and no free dimeric IgA was present in the jejunal fluid. Antigliadin-IgA was detected in the serum and jejunal fluid of the six patients with coeliac disease. Antigliadin-IgA, however, was almost entirely polymeric IgA linked to secretory component in jejunal fluid, whereas 61% was dimeric IgA not linked to secretory component in serum. This result, combined with a raised secretory component secretion rate with no evidence of secretory component saturation, suggests that serum and intestinal antigliadin IgA might be of different origins in coeliac disease