Biology subjects

Zimmermann, F.

Publications and source records attributed to Zimmermann, F..

14 recordsLinked to original sources

bioRxiv2026

Continent-wide calibration of camera-trap metrics reveals low population densities in the European wildcat

Effective conservation depends on demographic metrics that reliably reflect species status, particularly population abundance. For elusive species occurring at low densities, however, such metrics remain difficult to obtain. Spatial capture-recapture (SCR) models are the standardized approach for estimating density in marked populations, but their data requirements, especially the need for multiple spatial recaptures across individuals, often limit applicability in small or data-poor populations. This constraint has resulted in knowledge gaps for some of the most vulnerable species, undermining evidence-based conservation planning and management. Using camera-trap data and SCR-derived density estimates from data-rich populations, we evaluated alternative, less data-demanding metrics and tested the hypothesis: Space to Event (STE), Mean Local Abundance (MLA), and Relative Abundance Index (RAI) exhibit predictable relationships with SCR-derived density; if supported, these metrics can reliably estimate density in populations where SCR models cannot be implemented. We applied this framework to the European wildcat (Felis silvestris), an elusive small felid with highly fragmented populations across Europe, for which density estimates are largely lacking despite growing conservation concern. Across 21 study areas spanning most of the species range, our results indicate that European wildcats generally occur at lower densities than previously reported. SCR-derived estimates (n=10) averaged 10.32 {+/-} 11.56 inds/100km2, while STE enabled density estimation in five additional data-poor areas (mean 5.52 {+/-} 5.33 inds/100km2). STE showed a strong linear relationship with SCR-derived density (R2=0.98), supporting its use as a viable alternative when SCR is infeasible, although it tended to underestimate compared to SCR, especially at higher densities. In contrast, MLA and RAI showed weaker and non-linear relationships with SCR-derived density (R2=0.65), indicating substantially lower explanatory power and suggesting their estimates are more strongly influenced by confounding processes. By explicitly calibrating alternative metrics across a wide density gradient throughout most of the species distribution, this study provides a transferable methodological framework for estimating density in low-density wildlife populations and the first continent-wide, standardized density assessment of a carnivore species. From a management perspective, our findings identify populations that may be most vulnerable, particularly those with the lowest densities, and highlight the need to prioritize absolute abundance monitoring.

ecology↗

bioRxiv2025

Precise generation of bystander-free mouse models with ABE9-SpRY.

Point mutations cause many genetic disorders, but modelling them in organisms is technically challenging. Creating mouse models that mimic these mutations is crucial for establishing a causal relationship between mutations and disease phenotype, thereby supporting the development of therapeutic strategies. Adenine base editors (ABEs) can correct single-nucleotide variants (SNVs) in disease modelling without double-stranded breaks (DSBs) or donor DNA, achieving higher product purity than traditional Cas9 methods. Earlier ABE techniques faced issues like limited targetability, bystander editing, and off-target effects. By combining two editor advancements, we introduced and tested ABE9-SpRY, an improved ABE variant fused with a PAM-flexible SpRY-Cas9 nickase. Our results show that ABE9-SpRY effectively generates three out of four targeted A-to-G mutations in mouse embryos, with significantly fewer off-target effects than ABE8e-SpRY, achieving desired editing efficiencies of up to 96% in individual adult founder mice.ABE9-SpRY also enhances product purity in mouse embryos and human induced pluripotent stem cells (hiPSCs) compared to ABE8e-SpRY. Our findings showcase ABE9-SpRYs precision and versatility, highlighting it as a powerful tool for accurate in vivo point mutation modelling.

genetics↗

bioRxiv2025

What if wildlife health surveillance was not just for veterinarians? - Opportunistic use of population monitoring by camera traps for syndromic surveillance of the Eurasian lynx (Lynx lynx)

Fifty years after the reintroduction of the Eurasian lynx Lynx lynx to the Vosges and Swiss Jura mountains, the species remains in danger of extinction in France. The main threats it faces are habitat fragmentation, high anthropogenic mortality (mainly vehicle collision but also illegal killing) and low genetic diversity, but little is known about the importance of disease. Camera trapping surveillance provides crucial information for understanding population health status but includes many biases. To be more efficient, surveillance must combine several modalities. This work first presents the development of a protocol for clinical data collection by camera trapping, intended for biologists in charge of the populations monitoring. This method was then applied to the 3574 events, i.e. 270 identified individuals, present between 1997 and 2020 in the lynx photo identification database of the Wolf-Lynx Network (Reseau Loup-Lynx) of the French Biodiversity Agency (Office Francais de la Biodiversite). Seventeen percent of the lynx studied showed at least one change indicative of disease. The most common changes were skin disorders. The others were body condition, ocular or locomotor changes, lack of auriculas and rarely respiratory, behavioral, or digestive troubles. The latter changes were concentrated at the end of the study period, which also corresponded to the period with the most camera traps and therefore the most data. Finally, these observations complemented postmortem surveillance of the French lynx population carried out by the French network of epidemiological surveillance (Reseau SAGIR).

ecology↗

bioRxiv2025

Annotating opportunistic camera-trap images with conditions ofrecording, for the disease surveillance of Eurasian lynx (Lynxlynx)

The French population of the Eurasian lynx (Lynx lynx) is small and fragmented. Any emerging disease would endanger it even further, so health surveillance is crucial. Currently, health monitoring relies on lynx carcass surveillance. In parallel, the Eurasian lynx population is being monitored since 1997 through a large network of observers in different regions and this trove of camera-trap images could allow for the opportunistic detection of clinical signs. Camera traps have been used for a very long time in ecology and, more recently, in epidemiology to study e.g. sarcoptic mange. However, the quality of the images from camera traps varies, the details of the animals body are more or less clearly visible. This work examines how the quality of the images relates to the ability to detect cutaneous changes and abnormal body conditions. Different factors affect image quality and the detection of changes: intrinsic camera parameters like the type and settings of the camera trap, extrinsic factors like the external lighting conditions or the position of the animal in relation to the camera. In our data set, clearly visible cutaneous changes were associated with a different set of factors than visible abnormal body conditions. The camera-trap conditions currently used for ecological monitoring of the lynx are sufficiently diverse to allow for the general surveillance of abnormal health signs. However, for monitoring specific health signs, the camera settings as well as the shooting context should be optimized to ensure the best possible sensitivity and specificity of the detection.

ecology↗

bioRxiv2022

The spatial distribution and temporal trends of livestock damages caused by wolves in Europe

Wolf populations are recovering and expanding across Europe, causing conflicts with livestock owners. To mitigate these conflicts and reduce livestock damages, authorities spend considerable resources to compensate damages, support damage prevention measures, and manage wolf populations. However, the effectiveness of these measures remains largely unknown, especially at larger geographic scales. Here we compiled incident-based livestock damage data across 21 countries for the years 2018, 2019 and 2020, during which 39,262 wolf-caused incidents were reported from 470 administrative regions. We found substantial regional variation in all aspects of the data, including the primary target species, the density of damages, their seasonal distribution, and their temporal trend. More than half of the variation in damage densities across regions is explained by the area of extensively cultivated habitats occupied by wolves and namely natural grasslands and broad-leaved forests. Regional variation in husbandry practices and damage prevention, while difficult to quantify at a continental scale, appear important factors to further modulate these incidents. As illustrated with detailed data from Germany, for instance, the relationship between the number of wolf units and damages is diminishing over time, suggesting some adaptation of livestock owners and local authorities to their presence, for example by increasing prevention efforts. As we argue, temporal trends of damage incidents, which are robust to variation in data collection across regions, are thus informative about the local intensity of the wolf-human conflict. We estimated increasing trends for the majority of regions, reflecting the current expansion of wolves across the continent. Nonetheless, many of these increases were moderate and for more than one third of all regions, trends were negative despite growing wolf populations, thus indicating that wolf-livestock conflicts can be successfully mitigated with proper management.

ecology↗

bioRxiv2021

CDK1 and PLK1 cooperate to regulate BICD2, dynein activation and recruitment to the nucleus as well as centrosome separation in G2/M

The activity of dynein is regulated by a number of adaptors that mediate its interaction with dynactin, effectively activating the motor complex while also connecting it to different cargos. The regulation of adaptors is consequently central to dynein physiology, but remains largely unexplored. We now describe that one of the best-known dynein adaptors, BICD2, is effectively activated through phosphorylation. In G2 phosphorylation of BICD2 by CDK1 promotes its interaction with PLK1. In turn, PLK1 phosphorylation of a single residue in the N-terminus of BICD2 results in a conformational change that facilitates interaction with dynein and dynactin, allowing the formation of active motor complexes. BICD2 phosphorylation is central for dynein recruitment to the nuclear envelope, centrosome tethering to the nucleus and centrosome separation in G2/M. This work reveals adaptor activation through phosphorylation as crucial for the spatiotemporal regulation of dynein activity.

cell biology↗

bioRxiv2021

Eurasian lynx populations in Western Europe: What prospects for the next 50 years?

Persistence of populations may be uncertain for large carnivore species, especially for those established in human-dominated landscapes. Here, we studied the Eurasian lynx in Western Europe established in the Upper Rhine meta-population (i.e., Jura, Vosges-Palatinian and Black Forest populations) and the Alpine population. These populations are currently considered endangered or critically endangered due to high anthropogenic mortality, small population size and low genetic diversity, and isolation. We assessed lynx persistence over a 50-year time horizon by implementing a spatially-explicit individual-based model, while accounting for road mortality and habitat selection. Forecasts showed a steady growth rapidly reaching a more stable phase for the Alpine and Jura populations, and a more heterogeneous positive growth with less precision for the Vosges-Palatinian and Black Forest populations. Exchanges of individuals between populations were limited, the Jura population playing the role of a crossroad. Finally, the persistence of lynx in Western Europe seems likely on a large scale over the next 50 years. Indeed, simulations showed high female occupancy as well as average lynx density over the core areas of the four studied populations. Nevertheless, these results should be interpreted with the model limitations in mind, concerning the absence of movement barriers and inbreeding depression.

ecology↗

bioRxiv2021

Efficient single copy integration via homology-directed repair (scHDR) by 5'modification of large DNA donor fragments in mice

CRISPR/Cas approaches have largely replaced conventional gene targeting strategies. However, homology-directed repair (HDR) in the mouse genome is not very efficient, and precisely inserting longer sequences using HDR remains challenging, given that donor constructs preferentially integrate as concatemers. Here, we show that injecting 5biotinylated donor DNA in mouse embryos at the two-cell stage leads to efficient single-copy HDR (scHDR) alleles. Our dedicated genotyping strategy showed that these alleles occurred with a frequency of 19%, 20%, and 26%, respectively, in three independent gene loci, indicating that scHDR is dramatically boosted by 5biotinylation. Thus, we suggest that a combination of a 5biotinylated donor and diligent analysis of concatemer integration are prerequisites for efficiently and reliably generating conditional alleles or other large fragment knock-ins into the mouse genome.

molecular biology↗

bioRxiv2021

In-depth analysis of Bacillus anthracis 16S rRNA genes and transcripts reveals intra- and intergenomic diversity and facilitates anthrax detection

Analysis of 16S ribosomal RNA (rRNA) genes provides a central means of taxonomic classification of bacterial species. Based on presumed sequence identity among species of the Bacillus cereus sensu lato group, the 16S rRNA genes of B. anthracis have been considered unsuitable for diagnosis of the anthrax pathogen. With the recent identification of a single nucleotide polymorphism in some 16S rRNA gene copies, specific identification of B. anthracis becomes feasible. Here, we designed and evaluated a set of in situ-, in vitro- and in silico-assays to assess the yet unknown 16S-state of B. anthracis from different perspectives. Using a combination of digital PCR, fluorescence in situ hybridization, long-read genome sequencing and bioinformatics we were able to detect and quantify a unique 16S rRNA gene allele of B. anthracis (16S-BA-allele). This allele was found in all available B.anthracis genomes and may facilitate differentiation of the pathogen from any close relative. Bioinformatics analysis of 959 B. anthracis genome data-sets inferred that abundances and genomic arrangements of the 16S-BA-allele and the entire rRNA operon copy-numbers differ considerably between strains. Expression ratios of 16S-BA-alleles were proportional to the respective genomic allele copy-numbers. The findings and experimental tools presented here provide detailed insights into the intra- and intergenomic diversity of 16S rRNA genes and may pave the way for improved identification of B. anthracis and other pathogens with diverse rRNA operons.

microbiology↗

bioRxiv2021

In vitro evaluation of the effect of mutations in primer binding sites on detection of SARS-CoV-2 by RT-qPCR

A number of RT-qPCR assays for the detection of SARS-CoV-2 have been published and are listed by the WHO as recommended assays. Furthermore, numerous commercial assays with undisclosed primer and probe sequences are on the market. As the SARS-CoV-2 pandemic progresses, the virus accrues mutations, which in some cases - as seen with the B.1.1.7 variant - can outperform and push back other strains of SARS-CoV-2. If mutations occur in primer or probe binding sites, this can impact RT-qPCR results and impede SARS-CoV-2 diagnostics. Here we tested the effect of primer mismatches on RT-qPCR performance in vitro using synthetic mismatch in vitro transcripts. The effects of the mismatches ranged from a shift in ct values from -0.13 to +7.61. Crucially, we found that a mismatch in the forward primer has a more detrimental effect for PCR performance than a mismatch in the reverse primer. Furthermore, we compared the performance of the original Charite RdRP primer set, which has several ambiguities, with a primer version without ambiguities and found that without ambiguities the ct values are ca. 3 ct lower. Finally, we investigated the shift in ct values observed with the Seegene Allplex kit with the B.1.1.7 SARS-CoV-2 variant and found a three-nucleotide mismatch in the forward primer of the N target.

molecular biology↗

bioRxiv2020

Illegal hunting threatens the establishment of a lynx population and highlights the need of a centralized judiciary approach

O_LIIllegal hunting (poaching) represents a major threat to the conservation of large predators. Yet, its impact remains difficult to quantify as there are strong incentives to conceal this criminal activity. Attributing changes in the population status of large carnivores in part to poaching is therefore an important conservation challenge. C_LIO_LIWe present a case study of lynx (Lynx lynx) in southwestern Switzerland (canton of Valais) where the current distribution range is much smaller than it was in the recent past and population density is now >80% lower than in other lynx populations in the Swiss Alps, particularly in the adjacent Pre-Alps. We tested four hypotheses to explain this far lower density: 1) a too low density of trail camera-traps deployed for lynx surveys in Valais compared to the Pre-Alps (i.e. a methodological artefact); 2) less favourable environmental conditions around the camera-trap sites; 3) lower densities of the main prey; and 4) poaching. C_LIO_LIWe estimated lynx and ungulate densities and environmental conditions at trail camera sites, and were able to clearly reject the first three hypotheses: 1) the monitoring protocol was similarly effective; 2) environmental conditions around the trapping sites in Valais were even more favourable to lynx detection than in the Pre-Alps; and 3) prey supply was even larger. Concerning hypothesis 4, we discovered a local, but dense network of 17 illegal lynx traps in the narrow main immigration corridor into Valais from the thriving adjacent lynx population in the Pre-Alps, suggesting intense local poaching. C_LIO_LIOur findings substantiate the suspicions of long-lasting lynx poaching as a threat to the establishment and survival of the Valais population. The fact that instances of poaching were publicly known since 1995 but remained unabated for at least two decades, until a first conviction occurred, questions the commitment of local authorities to address this case of wildlife crime. Our study shows that inquiries about wildlife crime such as top predator poaching may need to be carried out at the highest levels of jurisdiction to avoid any risk of collusion between law enforcement agents and poachers. C_LI

ecology↗

bioRxiv2020

The biomedical sensor Cell-Fit-HD4D, reveals individual tumor cell fate in response to microscopic ion deposition.

Here we present the biomedical sensor cell-fluorescent ion track hybrid detector4D (Cell-Fit-HD4D) to reveal individual tumor cell fate in response to microscopic ion deposition in ion beam therapy. The sensor enables long-term monitoring of single tumor cells after clinical ion beam irradiation in combination with single-cell dosimetry. Cell-Fit-HD4D is read out in-situ by conventional optical microscopy. Direct visualization of a clinical ion beam is hereby possible for the first time. The possibility to reveal fate of individual cells from a cell cohort demonstrates that our biomedical sensor clearly differs from conventional experiments that characterize cellular response after radiation on a population level. Cell-Fit-HD4D is therefore used to mimics the clinical situation of a defined tumor depth during tumor treatment by ion beam therapy. Our biomedical sensor is able to provide crucial input for current mechanistic approaches to biophysical modelling of the effect of ionizing radiation on biological matter. In the clinical context, obtaining multi-dimensional physical and biological information on individual tumor cells is an important step to further transform ion beam therapy into a highly precise discipline within oncology.

cancer biology↗

bioRxiv2020

A novel Ataxin-3 knock-in mouse model mimics the human SCA3 disease phenotype including neuropathological, behavioral, and transcriptional abnormalities

BackgroundSpinocerebellar ataxia type 3 is the most common autosomal dominant inherited ataxia worldwide and is caused by a CAG repeat expansion in the Ataxin-3 gene resulting in a polyQ expansion in the corresponding protein. The disease is characterized by neuropathological (aggregate formation, cell loss), phenotypical (gait instability, body weight reduction), and specific transcriptional changes in affected brain regions. So far, there is no mouse model available representing all the different aspects of the disease, yet highly needed to gain a better understanding of the disease pathomechanism. MethodsHere, we characterized a novel Ataxin-3 knock-in mouse model, expressing either a heterozygous or homozygous expansion of 304 CAG/CAAs in the murine Ataxin-3 locus using biochemical, behavioral, and transcriptomic approaches. Further, we compared the transcriptional changes of the knock-in mice to those found in human SCA3 patients, to evaluate the comparability of our model. ResultsThe novel Ataxin-3 knock-in mouse is characterized by the expression of a polyQ-expansion in the murine Ataxin-3 protein, leading to massive aggregate formation, especially in brain regions known to be vulnerable in SCA3 patients, and impairment of Purkinje cells. Along these neuropathological changes, mice showed a reduction in body weight accompanied by gait and balance instability. Transcriptomic analysis of cerebellar tissue revealed age-dependent differential expression, enriched for genes attributed to myelinating oligodendrocytes. Comparing these transcriptional changes with those found in cerebellar tissue of SCA3 patients, we discovered an overlap of differentially expressed genes pointing towards similar gene expression perturbances in several genes linked to myelin sheaths and myelinating oligodendrocytes. ConclusionThe novel Ataxin-3 knock-in model shares neuropathological, behavioral, and transcriptomic features with human SCA3 patients and, therefore, represents an ideal model to investigate early-onset developments, therapy studies, or longitudinal biomarker alterations.

neuroscience↗

bioRxiv2019

Spatial density estimates of Eurasian lynx (Lynx lynx) in the French Jura and Vosges Mountains

Obtaining estimates of animal population density is a key step in providing sound conservation and management strategies for wildlife. For many large carnivores however, estimating density is difficult because these species are elusive and wide-ranging. Here, we focus on providing the first density estimates of the Eurasian lynx (Lynx lynx) in the French Jura and Vosges mountains. We sampled a total of 413 camera trapping sites (with 2 cameras per site) between January 2011 and April 2016 in seven study areas across seven counties of the French Jura and Vosges mountains. We obtained 592 lynx detections over 19,035 trap days in the Jura mountain and 0 detection over 6,804 trap days in the Vosges mountain. Based on coat patterns, we identified a total number of 92 unique individuals from photographs, including 16 females, 13 males and 63 individuals of unknown sex. Using spatial capture-recapture (SCR) models, we estimated abundance in the study areas between 5 (SE = 0.1) and 29 (0.2) lynx and density between 0.24 (SE = 0.02) and 0.91 (SE = 0.03) lynx per 100 km2. We also provide a comparison with non-spatial density estimates and discuss the expected discrepancies. Our study is yet another example of the advantage of combining SCR methods and non-invasive sampling techniques to estimate density for elusive and wide-ranging species, like large carnivores. While the estimated densities in the French Jura mountain are comparable to other lynx populations in Europe, the fact that we detected no lynx in the Vosges mountain is alarming. Connectivity should be encouraged between the French Jura mountain, the Vosges mountain and the Palatinate Forest in Germany where a reintroduction program is currently ongoing. Our density estimates will help in setting a baseline conservation status for the lynx population in France.

ecology↗