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Biology subjects

Krause, T.

Publications and source records attributed to Krause, T..

3 recordsLinked to original sources

Oncogenic and tumor-suppressive forces converge on a progenitor-orchestrated niche to shape early tumorigenesis

The benign-to-malignant transition is a defining step in cancer progression. To investigate when and how malignancy initiation occurs and tissue reorganization proceeds, we combine single-cell and spatial transcriptomic profiling in mouse models of pancreatic ductal adenocarcinoma (PDAC) that capture spontaneous p53 loss. Among Kras-mutant cells, we find that oncogenic and tumor-suppressive programs, including those controlled by p53, CDKN2A, and SMAD4, are co-activated in a discrete progenitor-like population, engaging senescence-like responses. Using a framework we develop for spatial analysis, we show that a niche centered on these cells undergoes stepwise remodeling during tumor progression, mirroring invasive PDAC. Transient KRAS inhibition depletes progenitor-like cells and dismantles their niche, delaying malignancy initiation. Conversely, p53 suppression enables progenitor cell expansion, epithelial-mesenchymal reprogramming, and immune-privileged niche formation. These findings position the progenitor-like state at the convergence of cancer-driving mutations, plasticity and tissue remodeling, revealing a critical window for intercepting malignancy.

cancer biology↗

Experimental insights on the behaviour and development of Near Eastern Fire salamanders (Salamandra infraimmaculata) indicate general strategies to cope with aquatic predators

Fishes are key predators of amphibian larvae with often devastating consequences for their abundance and survival. In Israel, the Near Eastern Fire salamander (Salamandra infraimmaculata) reaches the southern limit of the geographic distribution of the whole genus and has to cope with xeric terrestrial habitats- and a scarcity of suitable sites for the deposition of larvae with permanent springs and streams are being rare. One such location is the Tel Dan National Park in the North of Israel, were, surprisingly salamander larvae and fishes coexist successfully in a system of larger and smaller streams. In three experiments we tested different anti-predator behaviour with salamanders from Tel Dan and other locations. We analysed whether gravid females avoid the presence of fish when depositing their larvae; if the presence of fish impacts larval development and if salamander larvae show active hiding behaviour when confronted with fish cues. While females from Tel Dan showed a bet-hedging strategy in site selection irrespective of fish presence, larval developmental rate was reduced in the presence of fish probably due to a lower feeding activity. Lastly, larvae from different sites displayed hiding behaviour in the presence of fish, irrespective whether they naturally coexist with fish or not. We infer from our results and existing studies that S. infraimmaculata has general rather than site-specific adaptations to cope with the presence of fish. We conclude that the general adaptations are essential to sustain this species in a range of extreme habitats at the southern limit of the s distribution.

animal behavior and cognition↗

Novelty at second glance: A critical appraisal of the novel-object paradigm based onmeta-analysis.

The study of consistent individual differences in behaviour has become an important focus in research on animal behaviour. Behavioural phenotypes are typically measured through standardized testing paradigms and one frequently used paradigm is the novel object test. In novel object tests, animals are exposed to new (unknown) objects and their reaction is quantified. When repeating trials to assess the temporal consistency of individual differences, researchers face the dilemma of whether to use the same or different novel objects, since the same stimulus can result in habituation, while exposure to different objects can result in context-dependent responses. We performed a quantitative assessment of 254 effect sizes from 113 studies on novel-object trials to evaluate the properties of this testing paradigm, in particular the effect of object novelty and time interval between novel-object trials on estimates of individual consistency. We found an increase of sample sizes and an increase of estimates of repeatabilities with time. The vast majority of short-term studies ( one month) used either the same or different novel objects about equally often. The average estimate for individual consistency was r = 0.47 (short-term r = 0.52, long-term r = 0.44). Novelty, time interval between trials and their interaction together explained only 3% of the total heterogeneity. Overall, novelobject trials reliably estimate individual differences in behaviour, but results were very heterogeneous even within the same study species, suggesting susceptibility to unknown details in testing conditions. Most studies that measure novel-object responses in association with food label the trait as neophobia, while novel-object trials in a neutral context are labelled variously as boldness/shyness, exploratory behaviour or neophobia/neophilia. Neophobia/neophilia is also the term most specific to novel object presentations. To avoid ambiguity, we suggest object neophobia/neophilia as the most specific label for novel-object responses.

animal behavior and cognition↗