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Dewar, J.

Publications and source records attributed to Dewar, J..

2 recordsLinked to original sources

Using an agent-based sexual-network model to guide mitigation efforts for controlling chlamydia

We create and analyze a stochastic heterosexual agent-based bipartite network model to help understand the spread of chlamydia trachomatis. Chlamydia is the most common sexually transmitted infection in the United States and is major cause of infertility, pelvic inflammatory disease, and ectopic pregnancy among women. We use an agent-based network model to capture the complex heterogeneous assortative sexual mixing network of men and women. Both long-term and casual partnerships are modeled with different sexual contact frequencies and condom use. We use simulations to compare the effectiveness of intervention strategies based on randomly screening people for infection, treating the partners of infected people, and rescreening for infection after treatment. We compare the difference between treating the partners of an infected person both with, and without, testing them first for infection. The highest prevalence is among young sexually active individuals. We calibrate the model parameters to agree with recent survey data showing chlamydia prevalence of 14% of the women and 9% of the men in the 15 - 25 year-old African American residents of New Orleans, Louisiana. We observed that although increased chlamydia screening and treating most of the partners of infected people will reduce the incidence, these mitigations alone are not sufficient to control the epidemic. The model predicts that the current epidemic can brought under control once over half of the partners of infected people are tested and treated.

epidemiology

Initiation of DNA replication requires actin dynamics and formin activity

Nuclear actin influences transcription in a manner dependent on its dynamics of polymerisation and nucleocytoplasmic translocation. Using human somatic cells and transcriptionally-silent Xenopus egg extracts, we show that actin dynamics is also required for DNA replication. We identify many actin regulators in replicating nuclei from Xenopus egg extracts, and show that in human cells, nuclear actin filaments form in early G1 and disassemble prior to S-phase. In either system, treatments that stabilise nuclear actin filaments abrogate nuclear transport and initiation of DNA replication. Mechanistically, actin directly binds RanGTP-importin complexes and disruption of its dynamics hinders cargo release. This prevents both nuclear pore complex (NPC) formation and active nuclear transport, which we show is required throughout DNA replication. Nuclear formin activity is required for two further steps: loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin and initiation of DNA replication. Thus, actin dynamics and formins are involved in several nuclear processes essential for cell proliferation.

cell biology