Biology subjects

Rojas, R.

Publications and source records attributed to Rojas, R..

3 recordsLinked to original sources

bioRxiv2024

BETA-HYDROXYBUTYRATE COUNTERACTS THE DELETERIOUS EFFECTS OF A SATURATED HIGH-FAT DIET ON SYNAPTIC AMPA RECEPTORS AND COGNITIVE PERFORMANCE

The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the livers production of ketone bodies, primarily {beta}-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200M) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and {omega}-3 docosahexaenoic acid (200M), and BHB (5mM) increased them. Furthermore, BHB countered the adverse effects of palmitic acid on synaptic GluA1 levels in hippocampal neurons, as well as excitability and plasticity in hippocampal slices. Additionally, daily intragastric administration of BHB (100 mg/kg/day) for two months reversed cognitive impairment induced by a saturated high-fat diet (49% of calories from fat) in a mouse experimental model of obesity. In summary, our findings underscore the significant impact of fatty acids and ketone bodies on AMPA receptors abundance, synaptic function and neuroplasticity, shedding light on the potential use of BHB to delay cognitive impairments associated with metabolic diseases.

neuroscience↗

bioRxiv2022

Population genomics, resistance, pathogenic potential, and mobile genetic elements of carbapenem-resistant Klebsiella pneumoniae causing infections in Chile

Multidrug and carbapenem-resistant K. pneumoniae (CR-Kp) are considered critical threats to global health and key traffickers of resistance genes to other pathogens. In Chile, although a sustained increase in CR-Kp infections has been observed, few strains have been described at the genomic level, lacking molecular details of their resistance and virulence determinants and the mobile elements mediating their dissemination. In this work, we studied the antimicrobial resistance and performed a comparative genomics analysis of ten CR-Kp isolates from the Chilean surveillance of carbapenem-resistant Enterobacteriaceae. High resistance to most of the antibiotics tested was observed among the isolates, five ST25, three ST11, one ST45, and one ST505, which harbored a total of 44 plasmids, many of them predicted to be conjugative and carrying genes conferring resistance to a variety of antibiotic, metals, and disinfectants. Ten plasmids encoding either KPC-2, NDM-1, or NDM-7 carbapenemases were characterized, including novel plasmids with increased resistance gene load and a novel genetic environment for blaKPC-2 gene. This corresponds to the first report of ST25 and ST45 Kp producing NDM-7 in South America, and of an ST505 CR-Kp worldwide, producing both NDM-7 and KPC-2. Moreover, we characterized a variety of genomic islands carrying virulence and fitness factors. These results provide baseline knowledge for the detailed understanding of molecular and genetic determinants behind antibiotic resistance and virulence of K. pneumoniae in Chile and South America.

microbiology↗

bioRxiv2019

Left Ventricular Chamber Shape During Vena Caval Occlusion: Improved MRI-based Measurement of the End-Systolic Pressure-Volume Relationship in Normal Sheep

The left ventricular (LV) end-systolic pressure volume relationship (ES; ESPVR) is the cornerstone of systolic LV function analysis. Recently, it became possible to measure 2D LV chamber shape during vena cava occlusion (VCO) with MRI. We used an improved level-set semi-automatic segmentation method (LSSM) to determine the effect of VCO on LV geometry, ES pressure area (PA) and ESPVR. 10 healthy adult sheep were anesthetized. LV pressure transducer and inferior vena cava (IVC) balloon catheter were percutaneously inserted. Ferumoxytol (0.125 ml/kg iv; AMAG Pharmaceuticals, Waltham, MA) was given to enhance blood pool contrast. LV pressure and 2D retrospectively-gated cine MRI of LV cross sections 25 (Apex), 50 (Mid) and 75% (Base) of the distance from the apex to the base of the LV were obtained during separate IVC balloon inflations (VCO). LV pressure was digitally filtered and LV chamber segmented with the LSSM. Cross sectional area, major and minor axes, major axis orientation, ESPAR and ESPVR were calculated. The LSSM had excellent reliability. All cross sections became more elliptical during VCO. The orientation (angle) of each major axis relative to the anterior RV insertion shifted during VCO. However, the orientation remained toward the septum. There was chamber collapse (LV area < 0.25 cm2) at the apical level during VCO (7 cases). ESPAR was non-linear at all levels. ESPVR was non-linear because of apical collapse. In conclusion, MRI-based measurement of LV geometry, ESPAR and ESPVR during VCO is a valuable method that may lead to improved understanding of systolic LV function. New and NoteworthyReal-time MRI was used to continuously measure the LV PA relationship as loading conditions were transiently varied in anesthetized sheep. All three examined cross-sections became more elliptical during VCO. The ESPAR were non-linear at all three cross-sections. Chamber collapse at the apical level during VCO resulted in a non-linear ESPVR. The heart contracted in a non-concentric manner during VCO which could inform modeling studies and elucidate mechanisms underlying LV adaptations to sudden load changes.

bioengineering↗