Biology subjects

Langendorf, C.

Publications and source records attributed to Langendorf, C..

3 recordsLinked to original sources

bioRxiv2025

Long-read sequencing-based atlas of tissue-specific expression of Drp1 transcript variants

Dynamin-related protein 1 (Drp1), encoded by DNM1L, is essential for mitochondrial fission, but its functional roles remain unclear due to isoform-specific effects from alternative splicing. Short-read RNA sequencing fails to resolve full-length isoforms involving distant exons, limiting our understanding. Here, we applied targeted long-read sequencing to profile full-length DNM1L transcripts in human left ventricle and iPSC-derived cardiomyocytes, recovering all annotated isoforms with conserved expression patterns and isoforms 1-4 being most abundant. Functional assays revealed that isoform abundance does not predict enzymatic activity. Extending this to six mouse tissues, we identified distinct, tissue-enriched expression profiles. Functional rescue in Drp1-knockout mouse embryonic fibroblasts showed isoform-dependent differences in mitochondrial fission. Isoforms lacking the A-insert (e.g., b and d) robustly rescued fission, while isoforms enriched in brain or muscle showed only partial rescue, suggesting exons 2 and 3 negatively regulate Drp1 activity. Our cross-species atlas integrates long-read transcriptomics with functional validation, revealing how isoform diversity underpins tissue-specific mitochondrial dynamics and physiological roles of Drp1. SummaryUsing long-read sequencing, we mapped full-length DNM1L/Dnm1l isoforms in human and mouse tissues, uncovering tissue-specific expression and isoform-dependent mitochondrial fission activity. This reveals how alternative splicing shapes Drp1 function, with implications for understanding its role in health and disease.

cell biology↗

bioRxiv2022

Faecal carriage of ESBL-producing Escherichia coli in a remote region of Niger

ObjectiveWhole genome sequencing (WGS) of extended-spectrum {beta}-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger. MethodsStools of 383 healthy participants were collected among which 92.4% were ESBL-E. coli carriers; 90 of these ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads. ResultsMost isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome. ConclusionsMassive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.

microbiology↗

bioRxiv2017

Identifying Human Encounters That Shape The Transmission Of Streptococcus Pneumoniae And Other Respiratory Infections

Although patterns of social contacts are believed to be an important determinant of infectious disease transmission, there is little empirical evidence to back this up. Indeed, no previous study has linked individuals risk of respiratory infection with their current pattern of social contacts. We explored whether the frequency of different types of social encounters were associated with current pneumococcal carriage and self-reported acute respiratory symptoms (ARS), though a survey in Uganda in 2014. In total 566 participants were asked about their daily social encounters and about symptoms of ARS in the last two weeks. A nasopharyngeal specimen was also taken from each participant. We found that the frequency of physical (i.e. skin-to-skin), long ([≥]1h) and household contacts - which capture some measure of close (i.e. relatively intimate) contact -, was higher among pneumococcal carriers than non-carriers, and among people with ARS compared to those without, irrespective of their age. With each additional physical encounter the age-adjusted risk of carriage and ARS increased by 6% (95%CI 2-9%) and 9% (1-18%) respectively. In contrast, the number of casual contacts (<5 minutes long) was not associated with either pneumococcal carriage or ARS. A detailed analysis by age of contacts showed that the number of close contacts with young children (<5 years) was particularly higher among older children and adult carriers than non-carriers, while the higher number of contacts among people with ARS was more homogeneous across contacts of all ages. Our findings provide key evidence that the frequency of close interpersonal contact is important for transmission of respiratory infections, but not that of casual contacts. Such results strengthen the evidence for public health measures based upon assumptions of what contacts are important for transmission, and are important to improve disease prevention and control efforts, as well as inform research on infectious disease dynamics.\n\nAuthor summaryAlthough social contacts are an important determinant for the transmission of many infectious diseases it is not clear how the nature and frequency of contacts shape individual infection risk. We explored whether frequency, duration and type of social encounters were associated with someones risk of respiratory infection, using nasopharyngeal carriage (NP) of Streptococcus pneumoniae and acute respiratory symptoms as endpoints. To do so, we conducted a survey in South-West Uganda collecting information on peoples social encounters, respiratory symptoms, and pneumococcal carriage status. Our results show that both pneumococcal carriage and respiratory symptoms are independently associated with a higher number of social encounters, irrespective of a persons age. More specifically, our findings strongly suggest that the frequency of close contacts is important for transmission of respiratory infections, particularly pneumococcal carriage. In contrast, our study showed no association with the frequency of short casual contacts. Those results are essential for both improving disease prevention and control efforts as well as informing research on infectious disease dynamics and transmission models.

epidemiology↗