Bioremediation of PCP by Trichoderma and Cunninghamella Strains Isolated from Sawdust

Four fungal isolates, SD12, SD14, SD19 and SD20 isolated from the aged sawdust grew on agar plates supplemented with PCP up to a concentration of 100 mg L-1. At high PCP concentration, isolate SD12 showed the highest radial growth rate of 10 mm day-1, followed by SD14 and SD19 both with 4.5 mm day-1 and SD20 with 4.2 mm day-1. Ultrastructural study on the effect of PCP on the PCP tolerant fungi using scanning electron microscope showed that high concentration of PCP caused the collapse of both fungal hyphae and spores. Among the four PCP tolerant fungi examined, isolate SD12 showed the least structural damage at high PCP concentration of 100 mg L-1. This fungal isolate was further characterized and identified as Cunninghamella sp. UMAS SD12. Preliminary PCP biodegradation trial performed in liquid minimal medium supplemented with 20 mg L-1 of PCP using Cunninghamella sp. UMAS SD12 showed that the degradation up to 51.7% of PCP in 15 days under static growth condition

Computational Models of HIV-1 Resistance to Gene Therapy Elucidate Therapy Design Principles

Gene therapy is an emerging alternative to conventional anti-HIV-1 drugs, and can potentially control the virus while alleviating major limitations of current approaches. Yet, HIV-1's ability to rapidly acquire mutations and escape therapy presents a critical challenge to any novel treatment paradigm. Viral escape is thus a key consideration in the design of any gene-based technique. We develop a computational model of HIV's evolutionary dynamics in vivo in the presence of a genetic therapy to explore the impact of therapy parameters and strategies on the development of resistance. Our model is generic and captures the properties of a broad class of gene-based agents that inhibit early stages of the viral life cycle. We highlight the differences in viral resistance dynamics between gene and standard antiretroviral therapies, and identify key factors that impact long-term viral suppression. In particular, we underscore the importance of mutationally-induced viral fitness losses in cells that are not genetically modified, as these can severely constrain the replication of resistant virus. We also propose and investigate a novel treatment strategy that leverages upon gene therapy's unique capacity to deliver different genes to distinct cell populations, and we find that such a strategy can dramatically improve efficacy when used judiciously within a certain parametric regime. Finally, we revisit a previously-suggested idea of improving clinical outcomes by boosting the proliferation of the genetically-modified cells, but we find that such an approach has mixed effects on resistance dynamics. Our results provide insights into the short- and long-term effects of gene therapy and the role of its key properties in the evolution of resistance, which can serve as guidelines for the choice and optimization of effective therapeutic agents