Biology subjects

Francisco, E.

Publications and source records attributed to Francisco, E..

3 recordsLinked to original sources

bioRxiv2024

Fungal pathogens exposed - genomic and phenotypic insights into Candida auris and its relatives of the Candida haemulonii species complex

Candida auris showed the world the ability of fungi to rapidly emerge as an urgent threat to public health. Close relatives of the Candida haemulonii complex exhibit also a similar multi-drug resistant nature and are increasingly reported as nosocomial pathogens. Here, we analyze both complete genomes assemblies and extensive phenotypic data for the five C. auris clades and pathogenic and non-pathogenic species related to the C. haemulonii species complex. First, we resolved the phylogeny of the species complex. Next, comparing C. auris to its pathogenic and non-pathogenic relatives we identified a pathogenic potential for the whole C. haemulonii species complex by shared gene content and phenotypic traits linked to drug resistance and virulence. In vivo virulence assays using the Galleria mellonella fungal infection model show that C. auris strains are significantly more virulent than any of the sibling species in the C. haemulonii complex. Phenotypic analysis links the increased virulence of C. auris to a more stress resistant phenotype compared to its siblings.

microbiology↗

bioRxiv2019

Accuracy of different modalities of reaction time testing: Implications for online cognitive assessment tools.

Reaction time testing is widely used in computerized cognitive assessments, and clinical studies have repeatedly shown it to be a sensitive indicator of cognitive function. Typically, the reaction time test is administered by presenting a subject with a visual stimulus on a computer monitor and prompting the individual to respond (via keypad or computer mouse) as quickly as possible. The individuals reaction time is calculated as the interval between presentation of the stimulus and the time recorded from the mechanical response. However, there are many inherent latencies and variabilities that may be introduced to the measure by both hardware (computer monitor and mouse) and software (operating system). Because of these delays, we hypothesized that a comparison of hardware protocols (excluding human response) would demonstrate significant differences in the resulting reaction time measures. To simulate the delays of various components of the common systems used to obtain reaction time, we conducted a simple experiment in which either a visual or tactile stimulus evoked a movement from a mechanical transducer to respond to a computer peripheral or a dedicated response device. In the first condition, a simulated visual reaction time test was conducted by flashing a visual stimulus on a computer monitor. The stimulus was detected by a dedicated light sensor, and a linear actuator delivered the mechanical response via computer mouse. The second test condition employed a mobile device as the medium for the visual stimulus, and the mechanical response was delivered to the mobile devices touchscreen. The third and fourth test conditions simulated tactile reaction time tests in which the stimulus was generated by a dedicated hardware device. The third condition simulated a tactile stimulus, which was detected by a mechanical switch, and again a hardware device delivered the response via computer mouse. The fourth condition also simulated a tactile stimulus, but the response was delivered by a dedicated hardware device designed to store the interval between stimulus delivery and stimulus response. There were significant differences in the range of responses recorded from the four different conditions with the reaction time collected from a visual stimulus on a mobile device being the worst and the device with dedicated hardware designed for the task being the best. The results suggest that some of the commonly used visual tasks on consumer grade computers could be introducing significant errors for reaction time testing and that dedicated hardware designed for the reaction time task is needed to minimize testing errors.

bioengineering↗

bioRxiv2018

Role of RIG-I-like receptors in innate immune sensing of Coxsackievirus B3 and encephalomyocarditis virus in murine macrophages and fibroblasts

Viral infections are sensed by pattern recognition receptors that trigger an innate immune response through the expression of interferons (IFNs) and other cytokines. Most RNA viruses are sensed by the RIG-I like receptors (RLR)s. The contributions of these receptors to sensing viruses of the Picornaviridae family were investigated. Encephalomyocarditis virus (EMCV) and Coxsackievirus B3 (CVB3), picornaviruses of the Cardiovirus and Enterovirus genera, are detected by both MDA5 and RIG-I in bone marrow derived macrophages. In macrophages from wild type mice, type I IFN is produced early after infection; IFN{beta} synthesis is reduced in the absence of each sensor, while IFN production is reduced in the absence of MDA5. EMCV and CVB3 do not replicate in murine macrophages, and their detection is different in murine embryonic fibroblasts (MEFs), in which the viruses replicate to high titers. In MEFs RIG-I was essential for the expression of type I IFNs but contributes to increased yields of CVB3, while MDA5 inhibited CVB3 replication but in an IFN independent manner. These observations demonstrate that innate sensing of similar viruses by RLRs depends upon the cell type.\n\nImportanceEnteroviruses such as Coxsackieviruses are the most common human respiratory pathogens. The hosts innate immune response, in particular that modulated by the production of type I and III interferons, is thought to restrict picornavirus infection. Two cytoplasmic proteins, MDA5 and RIG-I, are critical for initiating the early innate immune response against these viruses. Mutations within MDA5 encoding gene have been associated with the development of severe enterovirus associated respiratory illnesses in healthy children. To further understand how the innate immune response dependent upon MDA5 and Rig-I is initiated during picornavirus infection, macrophages from mice lacking MDA5 or RIG-I were infected with Coxsackievirus B3 (CVB3) and a related animal virus. RIG-I is essential for type I IFN production during CVB3 infection; when MDA5 is present, viral titers are reduced by an IFN-independent pathway. These observations demonstrate that innate sensing of viruses by MDA5 and RIG-I depends upon the cell type.

microbiology↗