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Keller, S. A.

Publications and source records attributed to Keller, S. A..

2 recordsLinked to original sources

Analysis of a European general wildlife health surveillance program: chances, challenges and recommendations

In the context of a One Health perspective general wildlife health surveillance (GWHS) gains importance worldwide, as pathogen transmission among wildlife, domestic animals and humans raises health, conservation and economic concerns. However, GWHS programs operate in the face of legal, geographical, financial, or administrative conditions. The present study uses a multi-tiered approach to understand the current characteristics, strengths and gaps of a European GWHS that operates in a fragmented legislative and multi-stakeholder environment. The aim is to support the implementation or improvement of other GWHS systems by managers, surveillance experts, and administrations. To assess the current state of wildlife health investigations and trends within the GWHS, we analyzed 20 years of wildlife diagnostic data, conducted an online survey and phone interviews with official field partners (hunting administrators, game wardens and hunters), and performed a time-per-task analysis. Firstly, we found that infectious disease dynamics, the level of public awareness for specific diseases, research activities and increasing population sizes of in depth-monitored protected species, together with biogeographical and political boundaries all impacted case numbers and can present unexpected challenges to a GWHS. Secondly, we found that even a seemingly comprehensive GWHS can feature pronounced information gaps, with underrepresentation of common or easily recognizable diseases, blind spots in non-hunted species and only a fraction of discovered carcasses being submitted. Thirdly, we found that substantial amounts of wildlife health data may be available at local hunting administrations or disease specialist centers, but outside the reach of the GWHS and its processes. In conclusion, we recommend that fragmented and federalist GWHS programs like the one addressed require a central, consistent and accessible collection of wildlife health data. Also, considering the growing role of citizen observers in environmental research, we recommend using online reporting systems to harness decentrally available information and fill wildlife health information gaps.

zoology↗

Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization

Differentiation is critical for cell fate decisions, but the signals involved remain unclear. The kidney proximal tubule (PT) cells reabsorb disulphide-rich proteins through endocytosis, generating cystine via lysosomal proteolysis. Here we report that defective cystine mobilization from lysosomes through cystinosin (CTNS), which is mutated in cystinosis, diverts PT cells towards growth and proliferation, disrupting their functions. Mechanistically, cystine storage stimulates Ragulator-Rag GTPase-dependent recruitment of mechanistic target of rapamycin complex 1 (mTORC1) and its constitutive activation. Re-introduction of CTNS restores nutrient-dependent regulation of mTORC1 in knockout cells, whereas cell-permeant analogues of L-cystine, accumulating within lysosomes, render wild-type cells resistant to nutrient withdrawal. Therapeutic mTORC1 inhibition corrects lysosome and differentiation downstream of cystine storage, and phenotypes in a zebrafish model of cystinosis. Thus, cystine serves as a lysosomal signal that tailors mTORC1 and metabolism to direct epithelial cell fate decisions. These results identify mechanisms and therapeutic targets for dysregulated homeostasis in cystinosis.

cell biology↗