Biology subjects

Krawchuk, M.

Publications and source records attributed to Krawchuk, M..

2 recordsLinked to original sources

bioRxiv2023

Astrocyte sensitivity to glymphatic shear stress is amplified by albumin and mediated by the interaction of sphingosine 1 phosphate with Piezo1

Astrocyte endfeet enwrap brain vasculature, forming a boundary for perivascular glymphatic flow of fluid and solutes along and across the astrocyte endfeet into the brain parenchyma. To determine whether astrocytes may sense and respond to the shear forces generated by glymphatic flow, we examined intracellular calcium (Ca2+) changes evoked in astrocytes to brief fluid flow applied in calibrated microfluidic chambers. Shear stresses < 20 dyn/cm2 failed to evoke Ca2+ responses in the absence of albumin, but cells responded to shear stress below 1 dyn/cm2 when as little as 5 M albumin was present in flow medium. A role for extracellular matrix in mechanotransduction was indicated by reduced sensitivity after degradation of heparan sulfate proteoglycan. Sphingosine-1-phosphate (S1P) amplified shear responses in the absence of albumin, whereas mechanosensitivity was attenuated by the S1P receptor blocker fingolimod. Piezo1 participated in the transduction as revealed by blockade by the spider toxin GsMTX and amplification by the chemical modulator Yoda1, even in absence of albumin or S1P. Our findings that astrocytes are exquisitely sensitive to shear stress and that sensitivity is greatly amplified by albumin concentrations encountered in normal and pathological CSF predict that perivascular astrocytes are responsive to glymphatic shear stress and that responsiveness is augmented by elevated CSF protein. S1P receptor signaling thus establishes a setpoint for Piezo1 activation that is finely tuned to coincide with albumin level in CSF and to the low shear forces resulting from glymphatic flow. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/565884v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@17086e6org.highwire.dtl.DTLVardef@a89f32org.highwire.dtl.DTLVardef@6baed5org.highwire.dtl.DTLVardef@1a32f80_HPS_FORMAT_FIGEXP M_FIG C_FIG Astrocyte endfoot responds to glymphatic shear stress when albumin is present. Mechanism involves sphingosine-1-phosphate (S1P) binding to its receptor (S1PR), activating phospholipase C (PLC) and thereby sensitizing the response of Piezo1 to flow. Ca2+ influx triggers Ca2+ release from intracellular stores and further downstream signaling, thereby modulating parenchymal perfusion. Illustration created using BioRender.com

neuroscience↗

bioRxiv2020

Comparing global and regional maps of intactness in the boreal region of North America: Implications for conservation planning in one of the world's remaining wilderness areas

Though North Americas boreal forest contains some of the largest remaining intact and wild ecosystems in the world, human activities are systematically reducing its extent. Consequently, forest intactness and human influence maps are increasingly used for monitoring and conservation planning in the boreal region. We compare eight forest intactness and human impact maps to provide a multi-model assessment of intactness in the boreal region. All maps are global in extent except for Global Forest Watch Canadas Human Access (2000) and Intact Forest Landscapes (2000, 2013) maps, although some global maps are restricted to areas that were at least 20% treed. As a function of each maps spatial coverage in North America, the area identified as intact ranged from 55% to 79% in Canada and from 32% to 96% in Alaska. Likewise, the similarity between pairs of datasets in the Canadian boreal ranged from 0.58 to 0.86 on a scale of 0-1. In total, 45% of the region was identified as intact by the seven most recent datasets. There was also variation in the ability of the datasets to account for anthropogenic disturbances that are increasingly common in the boreal region, such as those associated with resource extraction. In comparison to a recently developed high resolution regional disturbance dataset, the four human influence datasets (Human Footprint, Global Human Modification, Large Intact Areas, and Anthropogenic Biomes), in particular, omitted 59-85% of all linear disturbances and 54-89% of all polygonal disturbances. In contrast, the global IFL, Canadian IFL, and Human Access maps omitted 2-7% of linear disturbances and 0.1-5% of polygonal disturbances. Several differences in map characteristics, including input datasets and methods used to develop the maps may help explain these differences. Ultimately, the decision on which dataset to use will depend on the objectives of each specific conservation planning project, but we recommend using datasets that 1) incorporate regional anthropogenic activities, 2) are updated regularly, 3) provide detailed information of the methods and input data used, and 4) can be replicated and adapted for local use. This is especially important in landscapes that are undergoing rapid change due to development, such as the boreal forest of North America.

ecology↗