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Biology subjects

Diehl, S.

Publications and source records attributed to Diehl, S..

3 recordsLinked to original sources

Can whole-lake algal biomass be captured by one-dimensional modeling approaches? An exploration using 'Lake2D'

Basin morphometry can strongly affect lake-internal processes relevant for productivity, such as turbulent mixing, photosynthetic energy acquisition, sedimentation, and nutrient recycling. Yet, in both empirical and theoretical studies of whole-lake primary production, lake morphometry is often simplified to a single 1-dimensional measure - lake mean depth. Using the conceptual, process-based model Lake2D, we addressed the question: To what extent can pelagic and benthic producer dynamics, integrated over a lake basin, be captured by approaches that use mean depth as the only morphometrical variable? We created two models of algal biomass dynamics in a radially symmetric, cone-shaped lake - one preserving the lakes vertical and radial dimensions and one preserving only the lakes mean depth - and compared model predictions of algal biomass dynamics across a wide range of lake sizes, mixing conditions, water transparency, and nutrient content. Our analyses reveal that model predictions differ substantially but predictably in much of the investigated parameter space, and identifies the light environment set by lake depth, water clarity and pelagic nutrients, but also lake area, as main drivers of the differences. Most commonly, the model based on mean depth underestimates benthic algal biomass and overestimates pelagic algal biomass, the net effect on total biomass being a 5-50% underestimate in shallow lakes and a 5-20% overestimate in many deeper lakes. Since gross primary production (GPP) in our model scales with algal biomass, we believe that global estimates of lake GPP should be corrected for the systematic errors inflicted by the prevailing 1-dimensional approaches.

ecology↗

Phosphatidylinositol 4-kinase III alpha governs cytoskeletal organization for invasiveness of liver cancer cells

Background and AimsHigh expression of phosphatidylinositol 4-kinase III alpha (PI4KIII) correlates with poor survival rates in patients with hepatocellular carcinoma (HCC). In addition, Hepatitis C virus (HCV) infections activate PI4KIII and contribute to HCC progression. We aimed at mechanistically understanding the impact of PI4KIII on the progression of liver cancer and the potential contribution of HCV in this process. MethodsSeveral hepatic cell culture and mouse models were used to study functional importance of PI4KIII on liver pathogenesis. Antibody arrays, gene silencing and PI4KIII specific inhibitor were applied to identify the involved signaling pathways. The contribution of HCV was examined by using HCV infection or overexpression of its nonstructural protein. ResultsHigh PI4KIII expression and/or activity induced cytoskeletal rearrangements via increased-phosphorylation of paxillin and cofilin. This led to morphological alterations and higher migratory and invasive properties of liver cancer cells. We further identified the liver specific lipid kinase phosphatidylinositol 3-kinase C2 domain-containing subunit gamma (PIK3C2{gamma}) working downstream of PI4KIII in regulation of the cytoskeleton. PIK3C2{gamma} generates plasma membrane (PM) phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]- enriched, invadopodia-like structures which regulate cytoskeletal reorganization by promoting Akt2 phosphorylation. ConclusionsPI4KIII regulates cytoskeleton organization via PIK3C2{gamma}/Akt2/paxillin-cofilin to favor migration and invasion of liver cancer cells. These findings provide mechanistic insight into the contribution of PI4KIII and HCV to progression of liver cancer and identify promising targets for therapeutic intervention. IMPACT AND IMPLICATIONSUnderstanding mechanistically how high PI4KIII expression are associated with poor clinical outcomes of liver cancer is important to develop pharmaceutical interventions. Our study sheds light on the importance of the two lipid kinases PI4KIII and PIK3C2{gamma} as well as the contribution of HCV on liver cancer progression, unraveling the signaling pathway governing this process. This preclinical study contributes to better understanding the complex connection of phospholipids, cytoskeleton and liver cancer and suggests strategies to improve therapeutic outcomes by targeting important signaling molecules. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=161 SRC="FIGDIR/small/541742v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@16ba717org.highwire.dtl.DTLVardef@a6f681org.highwire.dtl.DTLVardef@181c3cdorg.highwire.dtl.DTLVardef@5df6aa_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

Spatial omics imaging of fresh-frozen tissue and routine FFPE histopathology on a single cancer needle core biopsy: freezing device and multimodal workflow

Complex molecular alterations underlying cancer pathophysiology are intensely studied with omics methods using bulk tissue extracts. For spatially resolved tissue diagnostics using needle biopsy cores, however, histopathological analysis using stained FFPE tissue and immuno-histochemistry (IHC) of few marker proteins is currently the main clinical focus. Today, spatial omics imaging using MSI or IRI are emerging diagnostic technologies for identification and classification of various cancer types. However, to conserve tissue-specific metabolomic states, fast, reliable and precise methods for preparation of fresh-frozen (FF) tissue sections are crucial. Such methods are often incompatible with clinical practice, since spatial metabolomics and routine histopathology of needle biopsies currently require two biopsies for FF and FFPE sampling, respectively. Therefore, we developed a device and corresponding laboratory and computational workflows for multimodal spatial omics analysis of fresh-frozen, longitudinally sectioned needle biopsies to accompany standard FFPE histopathology on the same biopsy core. As proof-of-concept, we analyzed surgical human liver cancer specimen by IRI and MSI with precise co-registration and, following FFPE processing, by sequential clinical pathology analysis on the same biopsy core. This workflow allowed spatial comparison between different spectral profiles and alterations in tissue histology, as well as direct comparison to histological diagnosis without the need of an extra biopsy. SIMPLE SUMMARYRoutine clinical approaches for cancer diagnosis demand fast, cost-efficient, and reliable methods, and their implementation within clinical settings. Currently, histopathology is the golden standard for tissue-based clinical diagnosis. Recently, spatially resolved molecular profiling techniques like mass spectrometry imaging (MSI) or infrared spectroscopy imaging (IRI) have increasingly contributed to clinical research, e.g., by differentiation of cancer subtypes using molecular fingerprints. However, adoption of the corresponding workflows in clinical routine remains challenging, especially for fresh-frozen tissue specimen. Here, we present a novel device based on 3D-printing technology, which facilitates sample preparation of needle biopsies for correlated clinical tissue analysis. It enables combination of MSI and IRI on fresh-frozen clinical samples with histopathological examination of the same needle core after formalin-fixation and paraffin-embedding (FFPE). This device and workflow can pave the way for a more profound understanding of biomolecular processes in cancer and, thus, aid more accurate diagnosis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/528125v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@1da99aborg.highwire.dtl.DTLVardef@9ee706org.highwire.dtl.DTLVardef@5153daorg.highwire.dtl.DTLVardef@1581594_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗