Biology subjects

Sommer, U.

Publications and source records attributed to Sommer, U..

3 recordsLinked to original sources

bioRxiv2021

GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy

Radiotherapy is one of the curative treatment options for localized prostate cancer (PCa). The curative potential of radiotherapy is mediated by irradiation-induced oxidative stress and DNA damage in tumor cells. However, PCa radiocurability can be impeded by tumor resistance mechanisms and normal tissue toxicity. Metabolic reprogramming is one of the major hallmarks of tumor progression and therapy resistance. Here, we found that radioresistant PCa cells and prostate cancer stem cells (CSCs) have a high glutamine demand. Glutaminase (GLS)-driven catabolism of glutamine serves not only for energy production but also for the maintenance of the redox state. Consequently, glutamine depletion or inhibition of critical regulators of glutamine utilization, such as glutaminase (GLS) and the transcription factor MYC results in PCa radiosensitization. On the contrary, we found that a combination of glutamine metabolism inhibitors with irradiation does not cause toxic effects on nonmalignant prostate cells. Glutamine catabolism contributes to the maintenance of CSCs through regulation of the alpha-ketoglutarate (-KG)-dependent chromatin-modifying dioxygenase. The lack of glutamine results in the inhibition of CSCs with a high aldehyde dehydrogenase (ALDH) activity, decreases the frequency of the CSC populations in vivo and reduces tumor formation in xenograft mouse models. Moreover, this study shows that activation of the ATG5-mediated autophagy in response to a lack of glutamine is a tumor survival strategy to withstand radiation-mediated cell damage. In combination with autophagy inhibition, the blockade of glutamine metabolism might be a promising strategy for PCa radiosensitization. High blood levels of glutamine in PCa patients significantly correlate with a shorter prostate-specific antigen (PSA) doubling time. Furthermore, high expression of critical regulators of glutamine metabolism, GLS1 and MYC, is significantly associated with a decreased progression-free survival in PCa patients treated with radiotherapy. Our findings demonstrate that GLS-driven glutaminolysis is a prognostic biomarker and therapeutic target for PCa radiosensitization.

cancer biology↗

bioRxiv2018

Implementation of the Water Framework Directive: Lessons learned and future perspectives for an ecologically meaningful classification of the status of Greek lakes, Mediterranean region

The enactment of the Water Framework Directive (WFD) initiated scientific efforts to develop reliable methods for comparing prevailing lake conditions against reference (or non-impaired) states, using the state of a set biological elements. Drawing a distinction between impaired and natural conditions can be a challenging exercise, as it stipulates the robust delineation of reference conditions along with the establishment of threshold values for key environmental variables used as proxies for the degree of system impairment. Another important aspect is to ensure that water quality assessment is comparable among the different Member States. In this context, the present paper offers a constructive critique of the practices followed during the WFD implementation in Greece by pinpointing methodological weaknesses and knowledge gaps that undermine our ability to classify the ecological status of Greek lakes. One of the pillars of WDF is a valid lake typology that sets ecological standards transcending geographic regions and national boundaries. The national typology of Greek lakes has failed to take into account essential components (e.g. surface area, altitude, salinity). WFD compliance assessments based on descriptions of phytoplankton communities are oversimplified and as such should be revisited. Exclusion of most chroococcal species from the analysis of cyanobacteria biovolume in Greek lakes and most reservoirs in the Mediterranean Geographical Intercalibration Group (Greece, Spain, Portugal and Cyprus) is not consistent with the distribution of those taxa in lakes. Similarly, the total biovolume reference values and the indices used in their classification schemes reflect misunderstandings of WFD core principles. This hampers the comparability of ecological status across Europe and leads to quality standards that are too relaxed to provide an efficient target especially for the protection and management of Greek/transboundary lakes such as Lake Megali Prespa, one of the oldest lakes in Europe.

ecology↗

bioRxiv2017

A temperature dependent trophic cascade modifies temperature dependence of ecosystem function

Ecological communities and their ecosystem functions are sensitive to temperature, and aquatic habitats worldwide continue to experience unprecedented warming. Understanding ecological effects of warming requires linking empirical evidence to theories that allow projection to unobserved conditions. Metabolic scaling theory and its tests suggest that warming accelerates ecosystem functions (e.g., oxygen flux), yet this prediction apparently contradicts community-level studies suggesting warming is a stressor that can reduce ecosystem function. We sought to reconcile these predictions with an experimental test of the hypothesis that cascading trophic interactions modify the temperature-dependence of community structure and ecosystem fluxes. In a series of independent freshwater ecosystems exposed to a thermal gradient, we found that warmer temperatures strengthened the trophic cascade increased and indirectly changed community structure by altering grazer species composition and phytoplankton biomass. Temperature-driven community shifts only modestly affected the temperature dependence of net ecosystem oxygen fluxes. Over the 10 {degrees}C thermal gradient, NPP and ER increased [~]2.7-fold among ecosystems, while standing phytoplankton biomass declined by 85-95%. The exponential increase in oxygen flux over the thermal gradient, as well as monotonic declines in phytoplankton standing stock, suggested no threshold effects of warming across systems. We also observed temperature variation over time, within ecosystems. For phytoplankton biomass, temporal variation had the opposite effect to spatial variation, suggesting that within-community temporal change in community structure was not predicted by space-for-time substitution. We conclude that food chain length can modify effects of temperature on ecosystem fluxes, but that temperature can still have continuous and positive effects on ecosystem fluxes, consistent with patterns based on large-scale, macroecological comparisons. Changes in community structure, including temperature dependent trophic cascades, may be compatible with prevailing and predictable effects of temperature on ecosystem functions related to fundamental effects of temperature on metabolism.\n\nStatement of authorshipJG & MIO designed the study, MIO & US provided materials, JG & SJC performed research and collected data, JG performed zooplankton analysis, SJC performed phytoplankton analysis, JG & MIO performed modeling work, analyzed data output, and wrote the first draft, and all authors contributed substantially to reviews

ecology↗