Force Sensitivity in Saccharomyces cerevisiae Flocculins

Many fungal adhesins have short, -aggregation-prone sequences that play important functional roles, and in the Candida albicans adhesin Als5p, these sequences cluster the adhesins after exposure to shear force. Here, we report that Saccharomyces cerevisiae flocculins Flo11p and Flo1p have similar -aggregation-prone sequences and are similarly stimulated by shear force, despite being nonhomologous. Shear from vortex mixing induced the formation of small flocs in cells expressing either adhesin. After the addition of Ca2, yeast cells from vortex-sheared populations showed greatly enhanced flocculation and displayed more pronounced thioflavin-bright surface nanodomains. At high concentrations, amyloidophilic dyes inhibited Flo1p- and Flo11p-mediated agar invasion and the shear-induced increase in flocculation. Consistent with these results, atomic force microscopy of Flo11p showed successive force-distance peaks characteristic of sequentially unfolding tandem repeat domains, like Flo1p and Als5p. Flo11p-expressing cells bound together through homophilic interactions with adhesion forces of up to 700 pN and rupture lengths of up to 600 nm. These results are consistent with the potentiation of yeast flocculation by shear-induced formation of high-avidity domains of clustered adhesins at the cell surface, similar to the activation of Candida albicans adhesin Als5p. Thus, yeast adhesins from three independent gene families use similar force dependent interactions to drive cell adhesion

Hydrometeorological, glaciological and geospatial research data from the Peyto Glacier Research Basin in the Canadian Rockies

Canada First Research Excellent Fund’s Global Water Futures Programme, the National Sciences and Engineering Research Council of Canada’s Changing Cold Regions Network and Discovery Grants programme, the Canada Foundation for Innovation’s Canadian Rockies Hydrological Observatory, the Canada Research Chairs and Canada Excellence Research Chairs programmes, the Canadian Foundation for Climate and Atmospheric Sciences IP3 and WC2N networks, Natural Resources Canada, Environment Canada, Columbia Basin Trust, BC HydroPeer ReviewedThis paper presents hydrometeorological, glaciological and geospatial data from the Peyto Glacier Research Basin (PGRB) in the Canadian Rockies. Peyto Glacier has been of interest to glaciological and hydrological researchers since the 1960s, when it was chosen as one of five glacier basins in Canada for the study of mass and water balance during the International Hydrological Decade (IHD, 1965–1974). Intensive studies of the glacier and observations of the glacier mass balance continued after the IHD, when the initial seasonal meteorological stations were discontinued, then restarted as continuous stations in the late 1980s. The corresponding hydrometric observations were discontinued in 1977 and restarted in 2013. Datasets presented in this paper include high-resolution, co-registered digital elevation models (DEMs) derived from original air photos and lidar surveys; hourly off-glacier meteorological data recorded from 1987 to the present; precipitation data from the nearby Bow Summit weather station; and long-term hydrological and glaciological model forcing datasets derived from bias-corrected reanalysis products. These data are crucial for studying climate change and variability in the basin and understanding the hydrological responses of the basin to both glacier and climate change. The comprehensive dataset for the PGRB is a valuable and exceptionally long-standing testament to the impacts of climate change on the cryosphere in the high-mountain environment. The dataset is publicly available from Federated Research Data Repository at https://doi.org/10.20383/101.0259 (Pradhananga et al., 2020)

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Phospholipid dependent mechanism of smp24, an α-helical antimicrobial peptide from scorpion venom

Determining the mechanism of action of antimicrobial peptides (AMPs) is critical if they are to be developed into the clinical setting. In recent years high resolution techniques such as atomic force microscopy (AFM) have increasingly been utilised to determine AMP mechanism of action on planar lipid bilayers and live bacteria. Here we present the biophysical characterisation of a prototypical AMP from the venom of the North African scorpion Scorpio maurus palmatus termed Smp24. Smp24 is an amphipathic helical peptide containing 24 residues with a charge of + 3 and exhibits both antimicrobial and cytotoxic activity and we aim to elucidate the mechanism of action of this peptide on both membrane systems. Using AFM, quartz crystal microbalance-dissipation (QCM-D) and liposomal leakage assays the effect of Smp24 on prototypical synthetic prokaryotic (DOPG:DOPC) and eukaryotic (DOPE:DOPC) membranes has been determined. Our data points to a toroidal pore mechanism against the prokaryotic like membrane whilst the formation of hexagonal phase non-lamellar phase structures is seen in eukaryotic like membrane. Also, phase segregation is observed against the eukaryotic membrane and this study provides direct evidence of the same peptide having multiple mechanisms of action depending on the membrane lipid composition

The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs

Drug transporters are recognized as key players in the processes of drug absorption, distribution, metabolism, and elimination. The localization of uptake and efflux transporters in organs responsible for drug biotransformation and excretion gives transporter proteins a unique gatekeeper function in controlling drug access to metabolizing enzymes and excretory pathways. This review seeks to discuss the influence intestinal and hepatic drug transporters have on pharmacokinetic parameters, including bioavailability, exposure, clearance, volume of distribution, and half-life, for orally dosed drugs. This review also describes in detail the Biopharmaceutics Drug Disposition Classification System (BDDCS) and explains how many of the effects drug transporters exert on oral drug pharmacokinetic parameters can be predicted by this classification scheme

Regional heterogeneity and firms’ innovation: the role of regional factors in industrial R&D in India

This study makes an early attempt to estimate the magnitude and intensity of manufacturing firms’ R&D by Indian states during the period 1991‒2008 and analyses the role of regional factors on firm-level R&D activities. As there is little research on state-wise R&D performance of firms in India, this study serves an important contribution to the academic and policy realm. It has brought out the fact the total manufacturing R&D investment in India is unevenly distributed regionally with a few states accounting for disproportionate share of it. Regional heterogeneity or inter-state disparities in R&D has increased between the 1990s and the first decade of the twenty-first century. In view of this persistent regional heterogeneity in R&D, the study has developed and estimated an empirical model for a sample of 4545 Indian manufacturing firms with R&D facilities located in single state and that explicitly includes regional factors as probable factors affecting R&D. The three-step Censored Quantitle Regression results confirm that regional factors play an important role in shaping the R&D intensity of the sample of firms. This led us to some useful policy suggestions for regional governments to promote local firms’ R&D activities