Olfactory function in Australian aboriginal children and chronic otitis media

Chronic suppurative otitis media (CSOM), a severe form of middle ear infection, affects most Australian Aboriginal children with up to 50% in some communities suffering hearing loss as a consequence. To date, there is no information on whether repeated exposure to the pathogens that characterize CSOM and that are present in the upper respiratory airway affect olfactory function. Accordingly, this study aimed to determine whether 1) there was a high prevalence of olfactory loss in Aboriginal children and 2) hearing loss is a predictor of olfactory loss. Two hundred and sixty one 9- to 12-year-old Aboriginal children from 16 rural communities reported to have high prevalences of CSOM and hearing loss were assessed for olfactory loss using a 16-odor identification test and hearing loss. One child was found to be anosmic, 4 were slightly hyposmic, and 42 had hearing loss. No relationship was found between olfactory loss and hearing loss. The test-retest reliability of the 16-odor identification test was 0.98. It was concluded that CSOM does not appear to affect olfactory function in the long term and that hearing loss in Aboriginal children is not a predictor of olfactory loss.     

Molecular and genetic analysis of condensin function in vertebrate cells

We engineered mutants into residues of SMC2 to dissect the role of ATPase function in the condensin complex. These residues are predicted to be involved in ATP binding or hydrolysis and in the Q-loop, which is thought to act as a mediator of conformational changes induced by substrate binding. All the engineered ATPase mutations resulted in lethality when introduced into SMC2 null cells. We found that ATP binding, but not hydrolysis, is essential to allow stable condensin association with chromosomes. How SMC proteins bind and interact with DNA is still a major question. Cohesin may form a ring structure that topologically encircles DNA. We examined whether condensin behaves in an analogous way to its cohesin counterpart, and we have generated a cleavable form of biologically active condensin with PreScission protease sites engineered into the SMC2 protein. This has allowed us to demonstrate that topological integrity of the SMC2-SMC4 heterodimer is not necessary for the stability of the condensin complex in vitro or for its stable association with mitotic chromosomes. Thus, despite their similar molecular organization, condensin and cohesin exhibit fundamental differences in their structure and function.     

Befriending carers of people with dementia: randomised controlled trial

Objective To evaluate the effectiveness of a voluntary sector based befriending scheme in improving psychological wellbeing and quality of life for family carers of people with dementia.Design Single blind randomised controlled trial.Setting Community settings in East Anglia and London.Participants 236 family carers of people with primary progressive dementia.Intervention Contact with a befriender facilitator and offer of match with a trained lay volunteer befriender compared with no befriender facilitator contact; all participants continued to receive “usual care.”Main outcome measures Carers’ mood (hospital anxiety and depression scale—depression) and health related quality of life (EuroQoL) at 15 months post-randomisation.Results The intention to treat analysis showed no benefit for the intervention “access to a befriender facilitator” on the primary outcome measure or on any of the secondary outcome measures.Conclusions In common with many carers’ services, befriending schemes are not taken up by all carers, and providing access to a befriending scheme is not effective in improving wellbeing.Trial registration Current Controlled Trials ISRCTN08130075.     

Gene Ontology annotation quality analysis in model eukaryotes

Functional analysis using the Gene Ontology (GO) is crucial for array analysis, but it is often difficult for researchers to assess the amount and quality of GO annotations associated with different sets of gene products. In many cases the source of the GO annotations and the date the GO annotations were last updated is not apparent, further complicating a researchers’ ability to assess the quality of the GO data provided. Moreover, GO biocurators need to ensure that the GO quality is maintained and optimal for the functional processes that are most relevant for their research community. We report the GO Annotation Quality (GAQ) score, a quantitative measure of GO quality that includes breadth of GO annotation, the level of detail of annotation and the type of evidence used to make the annotation. As a case study, we apply the GAQ scoring method to a set of diverse eukaryotes and demonstrate how the GAQ score can be used to track changes in GO annotations over time and to assess the quality of GO annotations available for specific biological processes. The GAQ score also allows researchers to quantitatively assess the functional data available for their experimental systems (arrays or databases).     

Synthetic GPI array to study antitoxic malaria response

Parasite glycosylphosphatidylinositol (GPI) is an important toxin in malaria disease, and people living in malaria-endemic regions often produce high levels of anti-GPI antibodies. The natural anti-GPI antibody response needs to be understood to aid the design of an efficient carbohydrate-based antitoxin vaccine. We present a versatile approach based on a synthetic GPI glycan array to correlate anti-GPI antibody levels and protection from severe malaria.     

Parasite burden and CD36-mediated sequestration are determinants of acute lung injury in an experimental malaria model

Although acute lung injury (ALI) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM); however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar-capillary membrane barrier-the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36(-/-) mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality.