RNA interference approaches for treatment of HIV-1 infection

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery

Applications of MALDI-TOF Mass Spectrometry in Clinical Diagnostic Microbiology

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) represents one of the most accurate, reliable, and fast methods for the identification of bacterial strains from positive cultures, and therefore it has largely replaced all other previously used approaches for microbial identification. The main application of MALDI-TOF MS in clinical microbiology laboratories is the identification of bacteria from colonies recovered from solid culture media. This chapter discusses specific identification procedures that are needed for some bacteria, such as Actinomycetes and Mycobacteria. The performance of MALDI-TOF MS identification relies on the number of mass spectra that reach the quality allowing identification and the number of correct identifications. MALDI-TOF MS has also been proposed for Staphylococcus aureus strain typing or for the detection of biomarkers of the most virulent toxigenic isolates. MALDI-TOF MS could also be used for Mycobacterium

Patterning droplets with durotaxis

Numerous cell types have shown a remarkable ability to detect and move along gradients in stiffness of an underlying substrate-a process known as durotaxis. The mechanisms underlying durotaxis are still unresolved, but generally believed to involve active sensing and locomotion. Here, we show that simple liquid droplets also undergo durotaxis. By modulating substrate stiffness, we obtain fine control of droplet position on soft, flat substrates. Unlike other control mechanisms, droplet durotaxis works without imposing chemical, thermal, electrical, or topographical gradients. We show that droplet durotaxis can be used to create large-scale droplet patterns and is potentially useful for many applications, such as microfluidics, thermal control, and microfabrication.open117577sciescopu

Challenges in integrating short-term behaviour in a mixed-fishery Management Strategies Evaluation frame: a case study of the North Sea flatfish fishery

This study presents a fleet-based bioeconomic simulation model to the international mixed flatfish fishery in the North Sea. The model uses a Management Strategies Evaluation framework including a discrete choice model accounting for short-term temporal changes in effort allocation across fisheries. A simplified random utility model was used based on the expected revenue (or economic attractiveness) and two tradition parameters related to short and long term historical fishing patterns. All three parameters were significant. Even though reactions and adaptations vary between fleets, the estimated conservative behaviour of the main fleets led to only marginal effect at the stock level. The importance of accounting for fleet behaviour was then evaluated using an elasticity analysis to explore how increased weight of economic attractiveness contributes to changes in the biological output and positive increase in the economic performance of the individual fleets. This showed the existence of a window of sensitivity of the model to the behaviour assumptions. The study highlights the challenge of implementing an effort allocation model in a general framework of Management Strategies Evaluation for mixed-fisheries, and illustrates the necessary trade-offs between very detailed numerical relationships and the representation of aggregated processes