Biology subjects

Clifford, S.

Publications and source records attributed to Clifford, S..

5 recordsLinked to original sources

bioRxiv2023

Cell division machinery drives cell-specific gene activation during bacterial differentiation

When faced with starvation, the bacterium Bacillus subtilis transforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor {sigma}F is exclusively activated in the smaller daughter cell. Compartment specific activation of {sigma}F requires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates {sigma}F in both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that a unique feature of the sporulation septum, defined by the cell division machinery, drives the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program.

microbiology↗

bioRxiv2023

High pathogenicity avian influenza (H5N1) in Northern Gannets: Global spread, clinical signs, and demographic consequences

During 2021-22 High Pathogenicity Avian Influenza (HPAI) killed thousands of wild birds across Europe and North America, suggesting a change in infection dynamics and a shift to new hosts, including seabirds. Northern Gannets (Morus bassanus) appeared especially severely impacted, but limited understanding of how the virus spread across the metapopulation, or the demographic consequences of mass mortality limit our understanding of its severity. Accordingly, we collate information on HPAIV outbreaks across most North Atlantic gannet colonies and for the largest colony (Bass Rock, UK), provide impacts on population size, breeding success, adult survival, and preliminary results on serology. Unusually high numbers of dead gannets were first noted in Iceland during April 2022. Outbreaks in May occurred in many Scottish colonies, followed by colonies in Canada, Germany and Norway. By the end of June, outbreaks had occurred in five Canadian colonies and in the Channel Islands. Outbreaks in 12 UK and Ireland colonies appeared to follow a clockwise pattern with the last infected colonies recorded in late August/September. Unusually high mortality was recorded at 40 colonies (75% of global total colonies). Dead birds testing positive for HPAIV H5N1 were associated with 58% of these colonies. At Bass Rock, the number of occupied sites decreased by at least 71%, breeding success declined by [~]66% compared to the long-term UK mean and adult survival between 2021 and 2022 was 42% lower than the preceding 10-year average. Serological investigation detected antibodies specific to H5 in apparently healthy birds indicating that some gannets recover from HPAIV infection. Further, most of these recovered birds had black irises, suggestive of a phenotypic indicator of previous infection. Untangling the impacts of HPAIV infection from other key pressures faced by seabirds is key to establishing effective conservation strategies for threatened seabird populations, HPAIV being a novel and pandemic threat.

ecology↗

bioRxiv2019

Using virtual reality and thermal imagery to improve statistical modelling of vulnerable and protected species

Biodiversity loss and sparse observational data mean that critical conservation decisions may be based on little to no information. Emerging technologies, such as airborne thermal imaging and virtual reality, may facilitate species monitoring and improve predictions of species distribution. Here we combined these two technologies to predict the distribution of koalas, specialized arboreal foliovores facing population declines in many parts of eastern Australia. For a study area in southeast Australia, we complemented ground-survey records with presence and absence observations from thermal-imagery obtained using Remotely-Piloted Aircraft Systems. These field observations were further complemented with information elicited from koala experts, who were immersed in 360-degree images of the study area. The experts were asked to state the probability of observing a koala at sites they viewed and to assign each probability a confidence rating. We fit logistic regression models to the ground survey data and the ground plus thermal-imagery survey data and a beta regression model to the expert elicitation data. We then combined parameter estimates from the expert-elicitation model with those from each of the survey models to predict koala presence and absence in the study area. The model that combined the ground, thermal-imagery and expert-elicitation data substantially reduced the uncertainty around parameter estimates and increased the accuracy of classifications (koala presence vs absence), relative to the model based on ground-survey data alone. Our findings suggest that data elicited from experts using virtual reality technology can be combined with data from other emerging technologies, such as airborne thermal-imagery, using traditional statistical models, to increase the information available for species distribution modelling and the conservation of vulnerable and protected species.

ecology↗

bioRxiv2019

Serostatus Testing & Dengue Vaccine Cost-Benefit Thresholds

The World Health Organisation currently recommends pre-screening for past infection prior to administration of the only licensed dengue vaccine, CYD-TDV. Using a bounding analysis, we show that despite additional testing costs, this approach can improve the economic viability of CYD-TDV: effective testing reduces unnecessary vaccination costs while increasing the health benefit for vaccine recipients. When testing is cheap enough, those trends outweigh additional screening costs and make test-then-vaccinate strategies net-beneficial in many settings.\n\nWe derived these results using a general approach for determining price thresholds for testing and vaccination, as well as indicating optimal start and end ages of routine test-then-vaccinate programs. This approach only requires age-specific seroprevalence and a cost estimate for second infections. We demonstrate this approach across settings commonly used to evaluate CYD-TDV economics, and highlight implications of our simple model for more detailed studies. We found trends showing test-then-vaccinate strategies are generally more beneficial starting at younger ages, and that in some settings multiple years of testing can be more beneficial than only testing once, despite increased investment in testing.

epidemiology↗

bioRxiv2018

A population of bang-bang switches of defective interfering particles makes within-host dynamics of dengue virus controllable

The titre of virus in a dengue patient and the duration of this viraemia has a profound effect on whether or not a mosquito will become infected when it feeds on the patient and this, in turn is a key driver of the magnitude of a dengue outbreak. As mosquitoes require 100-1000 times more virus to become infected than a patient, the transmission of dengue virus from a patient to a mosquito is a vulnerability that may be able to be targeted to improve disease control. The intrinsic variability in the within-host dynamics of viraemias is explored for a population of patients using the method of population of models (POMs). A dataset from 207 patients is used to calibrate 20,000 models for the infection kinetics for each of the four dengue virus serotypes. The effect of adding defective dengue virus interfering particles to patients as a therapeutic is evaluated using the calibrated POMs in a bang-bang optimal control setting.\n\nAuthor summaryDengue virions with deletions or defects in their genomes can be recovered from dengue patients. These defective viruses can only replicate with the assistance of fully functional viruses and they reduce the yield of the fully functional viruses. They are known as defective interfering (DI) particles. By administering additional, defined, DI particles to patients it may be possible to reduce the titre and duration of their viraemia. This, in turn may reduce the severity of the disease and the likelihood that dengue virus will be passed from the patient to a mosquito vector. This study estimates the number of DI particles that would need to be administered, and over what period, to have a significant effect on patient viraemia and subsequent dengue fever severity.

systems biology↗