Biology subjects

Williamson, C.

Publications and source records attributed to Williamson, C..

22 records · Page 2Linked to original sources

bioRxiv2019

The little caterpillar that could - Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy

The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients world-wide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37{degrees}C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, fungal burden can be assessed daily throughout the course of infection in a single caterpillars faeces and haemolymph. Infected caterpillars can be rescued by treatment with antifungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of fungal disease. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of fungal virulence.

microbiology↗

bioRxiv2019

The Replication-Competent HIV-1 Latent Reservoir is Primarily Established Near the Time of Therapy Initiation

Although antiretroviral therapy (ART) is highly effective at suppressing HIV-1 replication, the virus persists as a latent reservoir in resting CD4+ T cells during therapy. Little is known about the dynamics of reservoir formation and this reservoir forms even when ART is initiated early after infection. The reservoir of individuals who initiate therapy in chronic infection is generally larger and genetically more diverse than that of individuals who initiate in acute infection, suggesting the reservoir is formed continuously throughout untreated infection. To determine when viruses enter the latent reservoir, we compared sequences of replication-competent viruses from resting CD4+ T cells from nine women on therapy to viral sequences circulating in blood collected longitudinally prior to therapy. We found that 78% of viruses from the latent reservoir were most genetically similar to viruses replicating just prior to therapy initiation. This proportion is far greater than expected if the reservoir forms continuously and is always long-lived. Thus, therapy alters the host environment in a way that allows the formation of a majority of the long-lived latent HIV-1 reservoir.\n\nOne Sentence SummaryMost of the long-lived, replication-competent HIV-1 reservoir is formed at the time of therapy initiation.

microbiology↗

bioRxiv2018

Different analysis methods of Scottish and English child physical activity data explain the majority of the difference between the national prevalence estimates

BackgroundThe percentage of children in Scotland and England meeting the aerobic physical activity recommendation differ greatly according to the estimates derived from the respective national health surveys. The Scottish Health Survey (SHeS) usually estimates that over 70% meet the guidelines; Health Survey for England (HSE) estimates are usually below 25%. It is plausible that these differences originate from different analysis methods. The HSE monitor the percentage of children that undertake 60 minutes of moderate-to-vigorous physical activity on each day of the week ( the daily minimum method (DMM)). The SHeS monitor the proportion that undertake at least seven sessions of moderate-to-vigorous physical activity, with an average daily duration over 60 minutes ( the average method (WAM)). We aimed to establish how great an influence this difference in analysis methods has on the prevalence estimates.\n\nMethodsPhysical activity data from 5-15 year olds in the 2015 HSE and SHeS were reanalysed (weighted n=3840 and 965, respectively). Two comparable pairs of estimates were derived: a DMM and WAM estimate from the HSE not including travel to/from school, and WAM estimates from the HSE and the SHeS including travel to/from school. It is not possible to calculate a DMM estimate from the SHeS due to the way the questions are asked. Results were presented for the total samples, and by sex and age sub-groups.\n\nResultsThe HSE WAM estimate was 31.7 (95% CI: 30.2-33.3) percentage points higher than the DMM estimate (54.3% (95% CI: 52.6-56.0) and 22.6% (95% CI: 21.2-24.1) respectively). The magnitude of this difference differed by age group but not sex. When comparable WAM estimates were derived from the SHeS and the HSE, the SHeS was 11.8 percentage points higher (73.6% (95% CI: 69.8-77.1) and 61.8% (95% CI: 60.2-63.5) respectively). The magnitude of this difference differed by age group and sex.\n\nConclusionsThe results indicate that the difference in the analysis method explains the majority (approximately 30 percentage points) of the difference in the child physical activity prevalence estimates between Scotland and England. These results will help those involved in national surveillance to determine how to increase comparability between the U.K. home nations.

epidemiology↗

bioRxiv2018

Neuregulin 1 type III reduces severity in a mouse model of Congenital Hypomyelinating Neuropathy

Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the axonal protein neuregulin 1 type III regulate Schwann cell fate and myelination. Here we ask if modulating neuregulin 1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Using a mouse model of CHN, we rescued the myelination defects by early overexpression of neuregulin 1 type III. Surprisingly, the rescue was independent from the upregulation of Egr2 or essential myelin genes. Rather, we observed the activation of MAPK/ERK and other myelin genes such as peripheral myelin protein 2 (Pmp2) and oligodendrocyte myelin glycoprotein (Omg). We also confirmed that the permanent activation of MAPK/ERK in Schwann cells has detrimental effects on myelination. Our findings demonstrate that the modulation of axon-to-glial neuregulin 1 type III signaling has beneficial effects and restores myelination defects during development in a model of CHN.\n\n\n\nO_TBL View this table:\norg.highwire.dtl.DTLVardef@103281aorg.highwire.dtl.DTLVardef@3dc68eorg.highwire.dtl.DTLVardef@1b6c5feorg.highwire.dtl.DTLVardef@80e419org.highwire.dtl.DTLVardef@1ff2591_HPS_FORMAT_FIGEXP M_TBL C_TBL

neuroscience↗