Rosenberg, A. | Search bioRxiv

bioRxiv2018

Real-time experimental control using network-based parallel processing

Modern neuroscience research often requires the coordination of multiple processes such as stimulus generation, real-time experimental control, as well as behavioral and neural measurements. The technical demands required to simultaneously manage these processes with high temporal fidelity limits the number of labs capable of performing such work. Here we present an open-source network-based parallel processing framework that eliminates these barriers. The Real-Time Experimental Control with Graphical User Interface (REC-GUI) framework offers multiple advantages: (i) a modular design agnostic to coding language(s) and operating system(s) that maximizes experimental flexibility and minimizes researcher effort, (ii) simple interfacing to connect measurement and recording devices, (iii) high temporal fidelity by dividing task demands across CPUs, and (iv) real-time control using a fully customizable and intuitive GUI. Testing results demonstrate that the REC-GUI framework facilitates technically demanding, behavior-contingent neuroscience research. Sample code and hardware configurations are downloadable, and future developments will be regularly released.

neuroscience↗

bioRxiv2017

Clearing the Fungal FoG: Perseverance, a property distinct from resistance, is associated with clinical persistence

Drug susceptibility, defined by the minimal inhibitory concentration (MIC), often does not predict whether fungal infections will respond to therapy in the clinic. Tolerance at supra-MIC antifungal drug concentrations is rarely quantified and current clinical recommendations suggest it be ignored. Here, we measured and characterized drug-response variables that could influence the outcomes of fungal infections and be generalizable across major clades of Candida albicans, one of the most frequently isolated human fungal pathogens. We quantified antifungal tolerance as the fraction of growth (FoG) above the MIC and found that it is clearly distinct from susceptibility/resistance measured as MIC. Instead, tolerance is due to the slow growth of subpopulations of cells that overcome drug stress more efficiently than the rest of the population, and correlates inversely with the accumulation of intracellular drug. Importantly, many adjuvant drugs used together with fluconazole, a fungistatic drug, reduce tolerance without affecting resistance. These include inhibitors of major stress response hubs such as Hsp90, calcineurin, PKC1 and TOR. Accordingly, in an invertebrate infection model, adjuvant combination therapy was significantly more effective than fluconazole alone in treating highly tolerant isolates and did not improve the treatment of isolates with low tolerance levels. Furthermore, isolates recovered from immunocompetent patients with persistent candidemia displayed significantly higher tolerance than isolates that were readily cleared by fluconazole. Thus, tolerance correlates with the response to fluconazole therapy in patients and may help predict whether infections will respond to fluconazole alone. Similarly, measuring tolerance may provide a useful clinical parameter for choosing appropriate therapeutic strategies to overcome persistent clinical candidemia.

microbiology↗