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Biology subjects

Zeller, A.

Publications and source records attributed to Zeller, A..

5 recordsLinked to original sources

Post-transcriptional glucocorticoid receptor signalling synchronises circadian rhythms

Keeping cellular circadian clocks synchronised is critical for cellular and physiological health. Glucocorticoid (GC) hormones are the most potent systemic timing signal for cellular clocks, acting via the glucocorticoid receptor (GR), a transcription factor conventionally thought to synchronise cells by translocating into the nucleus and activating the transcription of clock genes. Our findings overturn this model: acute changes in GR translocation and nascent transcription are both dispensable for GC-resetting of the circadian clock. Instead, physiological GC pulses act post-transcriptionally to rapidly increase Period1 mRNA through enhanced RNA processing, not synthesis. This elevates PER1 protein production which, alone, is sufficient to reset the clock. Yet each pulse resets only a subset of cells, explaining why, in vivo, repeated daily hormonal cues are required for full re-entrainment after jet lag or shift work. We propose a new model for hormonal signalling to the circadian clock and identify RNA processing kinetics as a general regulatory lever for nuclear receptor signalling.

molecular biology↗

DNA supercoiling links transcription and chromatin architecture during human stem cell differentiation

Transcription imposes torsional stress on chromatin, leading to over- or under-winding of the DNA helix. Yet, how supercoiling evolves during dynamic changes in gene expression, and how it influences three-dimensional chromatin contacts in the densely packed human genome, remains unclear. Here, we map genome-wide negative supercoiling and chromatin interactions at high resolution in human embryonic stem cells, using the transcriptional changes that drive differentiation to explore their interplay at multiple scales. We demonstrate that gene activation increases negative supercoiling despite enhanced topoisomerase recruitment. Moreover, elevated negative supercoiling correlates with increased DNA contacts within domains at multiple scales, from genes to topologically associating domains, consistent with transcription-generated torsional stress enhancing contact frequency. Thus, negative supercoiling likely contributes to the genome architectural remodelling that accompanies the execution of developmental programs.

genomics↗

Why they occur here but not there - a case study of Great Spotted Woodpeckers in the city of Munich

O_LIMany animal species can occur in the urban environment. The factors determining whether a particular species can live in a particular place in the city are, however, often not known. Such knowledge is needed to be able to design a built environment that is suitable for species. C_LIO_LIThe Great Spotted Woodpecker, Dendrocopos major, breeds in self-made cavities in trees and regularly occurs in cities. Here, we used a number of approaches to elucidate the factors that influence the occurrence of woodpeckers in the build-up area of the city. C_LIO_LIWe studied the occurrence of D. major on 103 squares in Munich, Germany and linked their presence to a number of square features such as square size, position in the city, tree occurrences, and a number of other variables. We also observed the presence of woodpecker cavities and undertook behavioural observations to study tree use. C_LIO_LIWoodpeckers were observed on 60% of the squares. A random forest model showed that the number of humans on squares negatively affected woodpecker occurrence, while a number of tree-related variables, such as tree density, tree diversity, the number of old trees (>60 cm DBH), and the sum of DBH of trees on the square, positively affected occurrence. Some other variables were also important, such as the amount of green in the surroundings and the distance to the city centre. C_LIO_LINests were found only in trees with a DBH>20 cm, and there was a distinct preference for larger trees, whereby a range of species was accepted. Behavioural observations showed that woodpeckers used a wide variety of trees, including small ones. Particular species and trees with a DBH>20 cm are preferred. C_LIO_LIOur study shows that humans can design public places for the presence of the Great Spotted Woodpecker by providing a locally high abundance of trees of different species with total DBH close to 25m. Trees in the surroundings and the presence of softwood trees with >40 cm will make it more likely that woodpeckers will use such sites in the city. C_LI Statement on inclusionOur study brings both established scientists with permanent faculty positions with Ph.D.-students and students of the 2nd year of their B.Sc.-studies or 1st or 2nd year of their M.Sc.-studies for whom this work is the first experience in the publication of scientific results. Students were particularly encouraged to contribute to question and hypothesis development as well as analysis and interpretation.

ecology↗

Characterising the epidemic spread of Influenza A/H3N2 within a city through phylogenetics

Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, its local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. We find trends in transmission dynamics correlated positively with trends in temperature, but not relative humidity nor school holidays. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network, while school children likely drove the spread within the remaining transmission network. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities. Author summaryAs shown with the current SARS-CoV-2 pandemic, respiratory diseases can quickly spread around the globe. While it can be hugely important to understand how diseases spread around the globe, local spread is most often the main driver of novel infections of respiratory diseases such as SARS-CoV-2 or influenza. We here use genetic sequence data alongside patient information to better understand what the drives the local spread of influenza by looking at the 2016/2017 influenza season in Basel, Switzerland as an example. The genetic sequence data allows us to reconstruct the how the transmission dynamics changed over the course of the season, which we correlate to changes, but not humidity or school holidays. Additionally, the genetic sequence data allows us to see how individual cases are connected. Using patient information, such as age and household status our analyses suggest that the elderly mainly transmit within their own transmission network. Additionally, they suggest that school aged children, but not pre-school aged children are important drivers of the local spread of influenza.

evolutionary biology↗

High-resolution influenza mapping of a city reveals socioeconomic determinants of transmission within and between urban quarters

With two-thirds of the global population projected to be living in urban areas by 2050, understanding the transmission patterns of viral pathogens within cities is crucial for effective prevention strategies. Here, in unprecedented spatial resolution, we analysed the socioeconomic determinants of influenza transmission in a European city. We combined geographical and epidemiological data with whole genome sequencing of influenza viruses at the scale of urban quarters and statistical blocks, the smallest geographic subdivisions within a city. We observed annually re-occurring geographic clusters of influenza incidences, mainly associated with net income, and independent of population density and living space. Vaccination against influenza was also mainly associated with household income and was linked to the likelihood of influenza-like illness within an urban quarter. Transmissions patterns within and between quarters were complex. High-resolution city-level epidemiological studies combined with social science surveys such as this will be essential for understanding seasonal and pandemic transmission chains and delivering tailored public health information and vaccination programs at the municipal level.

microbiology↗