Biology subjects

Mueller, W.

Publications and source records attributed to Mueller, W..

5 recordsLinked to original sources

bioRxiv2025

Evaluating wildlife rehabilitation: Successful return of rehabilitated gulls in the wild

The expansion of human activities has increased the need for animal rehabilitation, especially for urban-breeding species such as herring gulls (Larus argentatus) and lesser black-backed gulls (L. fuscus), which now commonly nest on buildings and industrial sites. This study evaluates rehabilitation effectiveness by comparing survival and post-release reintegration, measured through habitat use and the degree of association with human-dominated environments, between rehabilitated and wild juvenile gulls along the Belgian coast. From 2012 to 2023, 3443 juveniles were ringed and monitored. Estimated survival rates varied significantly with age, but there was no difference between rehabilitated and wild birds. Differences in habitat use and association with local human population density were largely confined to juveniles: rehabilitated juveniles were resighted more often in rural green areas with lower human population densities, with patterns converging in older age classes. Our results suggest rehabilitation can support urban gull populations by yielding wild-like survival and space use.

ecology↗

bioRxiv2021

Combining dictionary- and rule-based approximate entity linking with tuned BioBERT

Chemical named entity recognition (NER) is a significant step for many downstream applications like entity linking for the chemical text-mining pipeline. However, the identification of chemical entities in a biomedical text is a challenging task due to the diverse morphology of chemical entities and the different types of chemical nomenclature. In this work, we describe our approach that was submitted for BioCreative version 7 challenge Track 2, focusing on the Chemical Identification task for identifying chemical entities and entity linking, using MeSH. For this purpose, we have applied a two-stage approach as follows (a) usage of fine-tuned BioBERT for identification of chemical entities (b) semantic approximate search in MeSH and PubChem databases for entity linking. There was some friction between the two approaches, as our rule-based approach did not harmonise optimally with partially recognized words forwarded by the BERT component. For our future work, we aim to resolve the issue of the artefacts arising from BERT tokenizers and develop joint learning of chemical named entity recognition and entity linking using pre-trained transformer-based models and compare their performance with our preliminary approach. Next, we will improve the efficiency of our approximate search in reference databases during entity linking. This task is non-trivial as it entails determining similarity scores of large sets of trees with respect to a query tree. Ideally, this will enable flexible parametrization and rule selection for the entity linking search.

bioinformatics↗

bioRxiv2021

A kinase-dead Csf1r mutation associated with adult-onset leukoencephalopathy has a dominant-negative impact on CSF1R signaling.

Amino acid substitutions in the kinase domain of the human CSF1R gene are associated with autosomal dominant adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). To model the human disease, we created a disease-associated mutation (Glu631Lys; E631K) in the mouse Csf1r locus. Homozygous mutation (Csf1rE631K/E631K) phenocopied the Csf1r knockout; with prenatal mortality or severe postnatal growth retardation and hydrocephalus. Heterozygous mutation delayed the postnatal expansion of tissue macrophage populations in most organs. Bone marrow cells from Csf1rE631K/+ mice were resistant to CSF1 stimulation in vitro, and Csf1rE631K/+ mice were unresponsive to administration of a CSF1-Fc fusion protein which expands tissue macrophage populations in controls. In the brain, microglial cell numbers and dendritic arborization were reduced in the Csf1rE631K/+ mice as in ALSP patients. The microglial phenotype is the opposite of microgliosis observed in Csf1r+/- mice. However, we found no evidence of brain pathology or impacts on motor function in aged Csf1rE631K/+ mice. We conclude that disease-associated CSF1R mutations encode dominant negative repressors of CSF1R signaling. We speculate that leukoencephalopathy associated with human CSF1R mutations requires an environmental trigger and/or epistatic interaction with common neurodegenerative disease-associated alleles. Summary StatementThis study describes the effect of a human disease-associated mutation in the mouse CSF1R gene on postnatal development and growth factor responsiveness of cells of the macrophage lineage.

developmental biology↗

bioRxiv2017

Identifiers for the 21st century:How to design, provision, and reuse persistent identifiers to maximize utility and impact of life science data

In many disciplines, data is highly decentralized across thousands of online databases (repositories, registries, and knowledgebases). Wringing value from such databases depends on the discipline of data science and on the humble bricks and mortar that make integration possible; identifiers are a core component of this integration infrastructure. Drawing on our experience and on work by other groups, we outline ten lessons we have learned about the identifier qualities and best practices that facilitate large-scale data integration. Specifically, we propose actions that identifier practitioners (database providers) should take in the design, provision and reuse of identifiers; we also outline important considerations for those referencing identifiers in various circumstances, including by authors and data generators. While the importance and relevance of each lesson will vary by context, there is a need for increased awareness about how to avoid and manage common identifier problems, especially those related to persistence and web-accessibility/resolvability. We focus strongly on web-based identifiers in the life sciences; however, the principles are broadly relevant to other disciplines.

bioinformatics↗

bioRxiv2017

Gene fusion between CDKN1A and RAB44 caused by exon skipping like mechanism due to disruption of a splice site

Splicing contributes to gene regulation and protein diversity, while abnormal splicing underlies both hereditary diseases and cancers. Various mutations that disrupt splicing factors, exonic or intronic splicing enhancers or silencers, as well as splice sites, could be responsible for abnormal splicing. Characterization of abnormal splicing events is not only helpful for understanding the molecular processes linking mutations to disease phenotypes, but also provides promising targets for targeted therapies. In addition, CRISPR/Cas9 editing could be benefited once more attention is given to potential abnormal splicing outcomes other than off-target effects at the DNA level. Although large-scale multiplexed genome editing has been demonstrated in yeast, and has also been attempted for particular exons or genes in other eukaryotic cells to achieve saturation, in practice it is much more difficult to measure splicing consequences with genome-wide saturation editing in human cells. Instead, massive somatic mutations accumulated in cancer cohorts provide invaluable opportunities to study somatic mutation-associated splicing events. Abnormal splicing is not necessarily limited to single genes. Transcript fusion is a special form of abnormal splicing that connects two or more genes due to splicing on a transcriptional level (rather than chromosomal translocations such as BCR-ABL in chronic myeloid leukemia). It could arise from conventional splicing on read-through transcripts when the two genes are next to each other and on the same strand, or from trans-splicing when two genes are on different chromosomes, strands or far away - a few cases had been reported. However, it was found that these fusions not only occurred in tumors but also in normal tissues; there was limited investigation regarding how the fusion could happen, whether it be due to mutations or not, and what the downstream perturbations were. Here, in an effort to characterize somatic mutation-associated abnormal splicing (especially in its simplest form, exon skipping events), we identified over one hundred such events in various tumors, including those in MET, PTEN and TP53. Surprisingly, we detected a recurrent, but previously undescribed, tumor-specific transcript fusion event between the cyclin-dependent kinase inhibitor CDKN1A and the RAS oncogene family gene RAB44. By creating genome-edited cell lines, we demonstrate a causal relationship between splice-site mutations in CDKN1A and the fusion to the RAB44 transcript. We further provide evidence that the fusion arises from a readthrough transcript that escapes exosome-mediated degradation when the splice-site mutation occurred, and we show that the presence of the fusion transcript correlates with TP53 inactivation and CDK activation. The strong tissue specificity of RAB44 and the relatively high prevalence of this transcript fusion in multiple types of cancers warrants further study which could inform subclassifications of these cancers and the development of targeted therapies.

genetics↗