Biology subjects

Garcia, X.

Publications and source records attributed to Garcia, X..

3 recordsLinked to original sources

bioRxiv2023

Cochlear dysfunction as an early biomarker for cognitive decline in normal hearing and mild hearing loss

Age-related hearing loss (presbycusis) at moderate levels (>40 dB HL) has been recognized as an important risk factor for cognitive decline. However, whether individuals with mild hearing loss (audiogram thresholds between 25 and 40 dB HL) or even those with normal audiograms (<25 dB HL) have a higher risk of dementia, is still debated. Importantly, these early stages of presbycusis are the most common among the elderly, indicating the need to screen and identify individuals with early presbycusis that have an increased risk of cognitive decline. Unfortunately, in this group of patients, audiogram thresholds are not sufficiently sensitive to detect all the hearing impairments that are related to cognitive decline. Consequently, at the individual level, audiogram thresholds are not good estimators of the dementia risk in the group with mild hearing loss or normal hearing thresholds. Here, we propose to use distortion product otoacoustic emissions (DPOAE), as an objective and sensitive tool to estimate the risk of clinically relevant cognitive decline in elders with normal hearing o mild hearing loss. We assessed neuropsychological, brain magnetic resonance imaging, and auditory analyses on 94 subjects aged >64 years old. In addition, cognitive and functional performance was evaluated with the Clinical Dementia Rating Sum of Boxes (CDR SoB), assessed through structured interviews conducted by neurologists, who were blind to the DPOAE results. We found that cochlear dysfunction, measured by DPOAE -and not by conventional audiometry-, was associated with CDR SoB classification and brain atrophy in the group with mild hearing loss (25 to 40 dB), and normal hearing (<25 dB). Our findings suggest that DPOAE may be a non-invasive tool for detecting neurodegeneration and cognitive decline in the elderly, potentially allowing for early intervention.

neuroscience↗

bioRxiv2022

Killer Toxins for the Control of Diastatic Yeasts in Brewing

Secondary fermentation in craft beers by diastatic yeasts can result in undesirable consequences, such as off-flavors, increased alcohol content, gushing, and the explosion of packaging. Currently, there are no strategies for inhibiting diastatic yeasts once they have invaded a commercial brewing process. Many strains of yeasts can naturally produce "killer" toxins that inhibit the growth of competing yeasts. Testing the effectiveness of canonical toxins against diastatic yeasts revealed that most (90%) strains are susceptible to the K1 killer toxin. Only two diastatic strains resistance to killer toxins was due to toxin production and associated immunity. Four diastatic strains resistant to K1 and K2 toxins were screened against a library of 192 novel killer yeasts to discover novel antifungal activities. This identified novel K2 killer yeasts that were more potent at inhibiting diastatic yeasts than the canonical killer yeast. As proof-of-principle for the control of diastatic yeasts during fermentation, killer yeasts were found to be effective at inhibiting hyperattenuation after a simulated diastatic contamination in a 1,000-liter industrial-style fermentation.

microbiology↗

bioRxiv2018

Aggregates dramatically alter fibrin ultrastructure.

Among the many factors influencing fibrin formation and structure (concentration, temperature, composition, pH,...), it has been suggested that the polydispersity of fibrinogen may play an important role. We propose here a detailed investigation of the influence of this parameter on fibrin multiscale structure.\n\nTwo commercial fibrinogen preparations were used, a monodisperse and a polydisperse one. First, the respective compositions of both fibrinogen preparations were thoroughly determined by measuring the FXIII, fibronectin, ,{beta} and {gamma} intact-chains contents, the{gamma}/{gamma} chains ratio, the N-glycosylation and the post-translational modifications. Slight variations between the composition of the two fibrinogen preparations were found which are much smaller than the compositional variations necessary to alter significantly fibrin multiscale structure as observed in the literature. Conversely, MALLS coupled SEC and DLS measurements showed that the polydisperse preparation contains significant amounts of aggregates while the other preparation is essentially monodisperse.\n\nThe multiscale structure of the fibrins produced from those two fibrinogen preparations was determined by using X-ray scattering, spectrophotometry, and confocal microscopy. Results show that fibers from the monodisperse fibrinogen present a crystalline longitudinal and lateral structure and form a needle-like network. The internal structure of fibers produced from the polydisperse fibrinogen looks amorphous with star-like branching nodes. The multiscale structure of mixtures between the two preparations shows a smooth evolution, demonstrating that the quantity of aggregates is a major determining factor for fibrin multiscale structure. Indeed, the effect of a few percent in mass of aggregates is larger than any other effect due to compositional differences under the same reaction conditions. Finally we propose a mechanistic interpretation of our results which points at a direct role of the aggregates during polymerization which disrupt the ideal ordering of monomers inside fibrin protofibrils and fibers.

biophysics↗