Johansson, B. | bioRxiv Science

bioRxiv2021

Bleeding in patients and mice with Alagille syndrome: sex differences and risk factors

Spontaneous lethal bleeds are major cause of death in the pediatric liver disease Alagille syndrome (ALGS), yet risk factors and screening methods have not been established. We performed a systematic review and identified significantly more female than male patients with idiopathic intracranial hemorrhage (10:1). We investigated bleeding and vasculature in patients and a mouse model for ALGS (Jag1Ndr/Ndr mice) and asked whether phenotypes identified in mice could be detected in patients non-invasively. Jag1Ndr/Ndr mice bled spontaneously, exhibiting a thin skull and vascular defects including artery-vein crossings, tortuous vessels, capillary breakdown and CADASIL-like sparse vascular smooth muscle cell coverage which was aggravated by hypertension. Retinographs from patients confirmed tortuous blood vessels and artery-vein crossings in ALGS. In conclusion, Jag1Ndr/Ndr mice could be used to develop interventions for vascular defects in ALGS, and retinography could provide a non-invasive method for vascular analysis in these pediatric patients.

developmental biology↗

bioRxiv2020

Consolidated bioprocessing of corn cob-derived hemicellulose: engineered industrial Saccharomyces cerevisiae as efficient whole cell biocatalysts

Consolidated bioprocessing, which combines saccharolytic and fermentative abilities in a single microorganism, is receiving increased attention to decrease environmental and economic costs in lignocellulosic biorefineries. Nevertheless, the economic viability of lignocellulosic ethanol is also dependent of an efficient utilization of the hemicellulosic fraction, which is mainly composed of xylose and may comprise up to 40 % of the total biomass. This major bottleneck is mainly due to the necessity of chemical/enzymatic treatments to hydrolyze hemicellulose into fermentable sugars and to the fact that xylose is not readily consumed by Saccharomyces cerevisiae – the most used organism for large-scale ethanol production. In this work, industrial S. cerevisiae strains, presenting robust traits such as thermotolerance and improved resistance to inhibitors, were evaluated as hosts for the cell-surface display of hemicellulolytic enzymes and optimized xylose assimilation, aiming at the development of whole-cell biocatalysts for consolidated bioprocessing of corn cob-derived hemicellulose. These modifications allowed the direct production of ethanol from non-detoxified hemicellulosic liquor obtained by hydrothermal pretreatment of corn cob, reaching an ethanol titer of 11.1 g/L corresponding to a yield of 0.328 gram per gram of potential xylose and glucose, without the need for external hydrolytic catalysts. Also, consolidated bioprocessing of pretreated corn cob was found to be more efficient for hemicellulosic ethanol production than simultaneous saccharification and fermentation with addition of commercial hemicellulases. These results show the potential of industrial S. cerevisiae strains for the design of whole-cell biocatalysts and paves the way for the development of more efficient consolidated bioprocesses for lignocellulosic biomass valorization, further decreasing environmental and economic costs.Competing Interest StatementThe authors have declared no competing interest.View Full Text

bioengineering↗