27 research outputs found
Passive phloem loading and long-distance transport in a synthetic tree-on-a-chip
Vascular plants rely on differences of osmotic pressure to export sugars from
regions of synthesis (mature leaves) to sugar sinks (roots, fruits). In this
process, known as M\"unch pressure flow, the loading of sugars from
photosynthetic cells to the export conduit (the phloem) is crucial, as it sets
the pressure head necessary to power long-distance transport. Whereas most
herbaceous plants use active mechanisms to increase phloem concentration above
that of the photosynthetic cells, in most tree species, for which transport
distances are largest, loading seems to occur via passive symplastic diffusion
from the mesophyll to the phloem. Here, we use a synthetic microfluidic model
of a passive loader to explore the nonlinear dynamics that arise during export
and determine the ability of passive loading to drive long-distance transport.
We first demonstrate that in our device, phloem concentration is set by the
balance between the resistances to diffusive loading from the source and
convective export through the phloem. Convection-limited export corresponds to
classical models of M\"unch transport, where phloem concentration is close to
that of the source; in contrast, diffusion-limited export leads to small phloem
concentrations and weak scaling of flow rates with the hydraulic resistance. We
then show that the effective regime of convection-limited export is predominant
in plants with large transport resistances and low xylem pressures. Moreover,
hydrostatic pressures developed in our synthetic passive loader can reach
botanically relevant values as high as 10 bars. We conclude that passive
loading is sufficient to drive long-distance transport in large plants, and
that trees are well suited to take full advantage of passive phloem loading
strategies
The intratumoral heterogeneity reflects the intertumoral subtypes of glioblastoma multiforme: A regional immunohistochemistry analysis.
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor in adults. Despite extensive therapy the prognosis for GBM patients remains poor and the extraordinary therapy resistance has been attributed to intertumoral heterogeneity of glioblastoma. Different prognostic relevant GBM tumor subtypes have been identified based on their molecular profile. This approach, however, neglects the heterogeneity within individual tumors, that is, the intratumoral heterogeneity. Here, we detected the regional immunoreactivity by immunohistochemistry and immunofluorescence using nine different markers on resected GBM specimens (IDH wildtype, WHO grade IV). We found repetitive expression profiles, that could be classified into clusters. These clusters could then be assigned to five pathophysiologically relevant groups that reflect the previously described subclasses of GBM, including mesenchymal, classical, and proneural subtype. Our data indicate the presence of tumor differentiations and tumor subclasses that occur within individual tumors, and might therefore contribute to develop adapted, individual-based therapies
Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas
Purpose!#!Imaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-L-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer-weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas.!##!Methods!#!Preoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging.!##!Results!#!In glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw-HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET.!##!Conclusions!#!We found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas