Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/1/feb213699.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153088/2/feb213699_am.pd

Exposure of patients to ionising radiation during lung cancer diagnostic work-up

We examined the dose of radiation received during diagnosis of lung cancer as this may add to the risk of a second primary cancer. Patients undergoing surgery (n=40) or (chemo)radiotherapy (n=40) received comparable doses (28.6 and 25.8 mSv, respectively), significantly higher than that for supportive care (n=40; 15.1 mSv). The effective dose of radiation received was higher for early stage disease than for those with metastatic disease. The mean lifetime attributable risk of malignancy for those receiving treatment with curative intent in our cohort was 0.059%, and lung-specific risk 0.019%.RCR is part funded by the Cambridge Biomedical Research Centre

Should prospective dental students be screened for colour vision deficits?

A perennial question in dental education is: what skills and aptitudes should be assessed in prospective dental students? Intellectual capacity and manual dexterity understandably rank highly, but are there minimum thresholds for visual perception that applicants need be able to demonstrate before they enter the profession? We have recently flagged this issue with regard to the thresholds of stereoscopic acuity required for a dentist when operating on teeth. In the present article, we highlight the issue of identifying a minimum acceptable level of colour vision

The cultural capitalists: notes on the ongoing reconfiguration of trafficking culture in Asia

Most analysis of the international flows of the illicit art market has described a global situation in which a postcolonial legacy of acquisition and collection exploits cultural heritage by pulling it westwards towards major international trade nodes in the USA and Europe. As the locus of consumptive global economic power shifts, however, these traditional flows are pulled in other directions: notably for the present commentary, towards and within Asia

On the Importance of Countergradients for the Development of Retinotopy: Insights from a Generalised Gierer Model

During the development of the topographic map from vertebrate retina to superior colliculus (SC), EphA receptors are expressed in a gradient along the nasotemporal retinal axis. Their ligands, ephrin-As, are expressed in a gradient along the rostrocaudal axis of the SC. Countergradients of ephrin-As in the retina and EphAs in the SC are also expressed. Disruption of any of these gradients leads to mapping errors. Gierer's (1981) model, which uses well-matched pairs of gradients and countergradients to establish the mapping, can account for the formation of wild type maps, but not the double maps found in EphA knock-in experiments. I show that these maps can be explained by models, such as Gierer's (1983), which have gradients and no countergradients, together with a powerful compensatory mechanism that helps to distribute connections evenly over the target region. However, this type of model cannot explain mapping errors found when the countergradients are knocked out partially. I examine the relative importance of countergradients as against compensatory mechanisms by generalising Gierer's (1983) model so that the strength of compensation is adjustable. Either matching gradients and countergradients alone or poorly matching gradients and countergradients together with a strong compensatory mechanism are sufficient to establish an ordered mapping. With a weaker compensatory mechanism, gradients without countergradients lead to a poorer map, but the addition of countergradients improves the mapping. This model produces the double maps in simulated EphA knock-in experiments and a map consistent with the Math5 knock-out phenotype. Simulations of a set of phenotypes from the literature substantiate the finding that countergradients and compensation can be traded off against each other to give similar maps. I conclude that a successful model of retinotopy should contain countergradients and some form of compensation mechanism, but not in the strong form put forward by Gierer

"You've got a friend in me": can social networks mediate the relationship between mood and MCI?

engagement is beneficial to both mental health and cognition, and represents a potentially modifiable factor. Consequently this study explored this association and assessed whether the relationship between mild cognitive impairment (MCI) and mood problems was mediated by social networks. Methods: This study includes an analysis of data from the Cognitive Function and Ageing Study Wales (CFAS Wales). CFAS Wales Phase 1 data were collected from 2010-2013 by conducting structured interviews with older people aged over 65 years of age living in urban and rural areas of Wales, and included questions that assessed cognitive functioning, mood, and social networks. Regression analyses were used to investigate the associations between individual variables and the mediating role of social networks. Results: Having richer social networks was beneficial to both mood and cognition. Participants in the MCI category had weaker social networks than participants without cognitive impairment, whereas stronger social networks were associated with a decrease in the odds of experiencing mood problems, suggesting that they may offer a protective effect against anxiety and depression. Regression analyses revealed that social networks are a significant mediator of the relationship between MCI and mood problems. Conclusions: These findings are important, as mood problems are a risk factor for progression from MCI to dementia, so interventions that increase and strengthen social networks may have beneficial effects on slowing the progression of cognitive decline

In vitro growth environment produces lipidomic and electron transport chain abnormalities in mitochondria from non-tumorigenic astrocytes and brain tumours

The mitochondrial lipidome influences ETC (electron transport chain) and cellular bioenergetic efficiency. Brain tumours are largely dependent on glycolysis for energy due to defects in mitochondria and oxidative phosphorylation. In the present study, we used shotgun lipidomics to compare the lipidome in highly purified mitochondria isolated from normal brain, from brain tumour tissue, from cultured tumour cells and from non-tumorigenic astrocytes. The tumours included the CT-2A astrocytoma and an EPEN (ependymoblastoma), both syngeneic with the C57BL/6J (B6) mouse strain. The mitochondrial lipidome in cultured CT-2A and EPEN tumour cells were compared with those in cultured astrocytes and in solid tumours grown in vivo. Major differences were found between normal tissue and tumour tissue and between in vivo and in vitro growth environments for the content or composition of ethanolamine glycerophospholipids, phosphatidylglycerol and cardiolipin. The mitochondrial lipid abnormalities in solid tumours and in cultured cells were associated with reductions in multiple ETC activities, especially Complex I. The in vitro growth environment produced lipid and ETC abnormalities in cultured non-tumorigenic astrocytes that were similar to those associated with tumorigenicity. It appears that the culture environment obscures the boundaries of the Crabtree and the Warburg effects. These results indicate that in vitro growth environments can produce abnormalities in mitochondrial lipids and ETC activities, thus contributing to a dependency on glycolysis for ATP production

Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin

Metastasis is a multi-step process wherein tumour cells detach from the primary mass, migrate through barrier matrices, gain access to conduits to disseminate, and subsequently survive and proliferate in an ectopic site. During the initial invasion stage, prostate carcinoma cells undergo epithelial–mesenchymal-like transition with gain of autocrine signalling and loss of E-cadherin, hallmarks that appear to enable invasion and dissemination. However, some metastases express E-cadherin, and we found close connections between prostate carcinoma cells and hepatocytes in a liver microtissue bioreactor. We hypothesise that phenotypic plasticity occurs late in prostate cancer progression at the site of ectopic seeding. Immunofluorescence staining for E-cadherin in co-cultures of hepatocytes and DU-145 prostate cancer cells revealed E-cadherin upregulation at peripheral sites of contact by day 2 of co-culture; E-cadherin expression also increased in PC-3 cells in co-culture. These carcinoma cells bound to hepatocytes in an E-cadherin-dependent manner. Although the signals by which the hepatocytes elicited E-cadherin expression remain undetermined, it appeared related to downregulation of epidermal growth factor receptor (EGFR) signalling. Inhibition of autocrine EGFR signalling increased E-cadherin expression and cell–cell heterotypic adhesion; further, expression of a downregulation-resistant EGFR variant prevented E-cadherin upregulation. These findings were supported by finding E-cadherin and catenins but not activated EGFR in human prostate metastases to the liver. We conclude that the term epithelial–mesenchymal transition only summarises the transient downregulation of E-cadherin for invasion with re-expression of E-cadherin being a physiological consequence of metastatic seeding

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization