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Nowak, B.

Publications and source records attributed to Nowak, B..

5 recordsLinked to original sources

Modeling ATN1 mutations in human iPSCs reveals early developmental roles of atrophin-1

Atrophin-1 (ATN1), encoded by the ATN1 gene, is an evolutionarily conserved transcriptional corepressor implicated in neuronal development and severe incurable disorders, including the polyglutamine (polyQ) disease - dentatorubral-pallidoluysian atrophy (DRPLA), and the neurodevelopmental syndrome CHEDDA. However, the cellular function of ATN1 and its role during early human development remain largely uncharacterized. Here, we generated an isogenic panel of human induced pluripotent stem cell (iPSC) lines, establishing a novel resource for comprehensive studies of ATN1 function and dysfunction. This panel includes a DRPLA patient-derived line (wt/mut), CRISPR-Cas9-corrected wild-type controls (wt/wt), complete ATN1 knock-out clones (-/-), and heterozygous lines expressing either a wild-type or a mutant allele (wt/- and -/mut). While pluripotency markers remained unaffected across all variants, further characterization revealed marked proliferation deficits in ATN1 knock-out lines and heterozygous iPSCs without wild-type allele expression. Moreover, the formation of punctate ATN1 assemblies was enhanced in iPSCs with -/mut variants. The pronounced phenotype observed in cells expressing only the mutant ATN1 allele may result from a combination of loss-of-function and toxic gain-of-function mechanisms. Overall, the generated panel of iPSC lines provides a unique cellular platform for investigating ATN1-dependent molecular mechanisms and their contribution to neuronal development and disease.

cell biology↗

Assessment of population exposure to pesticide applications with a high-resolution map of pesticide use intensity for mainland France

While there is a lively debate about the potential harmful effects of pesticide use, the multiplication of data sources offers new ways of assessing these effects. To facilitate future studies, this article sets out a method for obtaining a map of pesticide use intensity for mainland France, taking into account the effect of each plot. To do so, a number of pesticide treatments was assigned to each plot based on statistical data concerning the average number of treatments per crop and per region. The final result is a raster with a resolution of 100m, which takes into account the average of treatments for the years 2019, 2020 and 2021. A first application conducted in this study showed that 25% of the French population was exposed to at least 1 pesticide treatment per year in their place of residence (5% exposed to at least 10 treatments per year). There were marked differences in exposure between regions, with particularly high exposure in the west and north of France, for example. The map of pesticide use intensity in France produced in this study is freely accessible for future studies.

plant biology↗

Characterization of bacteria colonizing the mucosal layer of the gastrointestinal tract of Atlantic salmon farmed in a warm water region

Atlantic salmon (Salmo salar) farmed in seawater in Tasmania (lutruwita) can experience temperatures close to their thermotolerance limit during summer. Gut microbiome data from eight successive annual surveys and a specific survey of GI tract mucosa and digesta bacterial cross-sectional distributions indicated members of the genus Aliivibrio, Vibrio, and an unclassified Mycoplasmoidaceae are the main colonizers of the gut mucosal layer in Tasmanian farmed salmon. Peak abundance levels are reached after 7-8 months, corresponding to the late summer, following the transfer of hatchery smolt to seawater farms. Salmon Aliivibrio isolates comprise three novel non-bioluminescent species distinct from species found in the northern hemisphere growing regions. Along with other Aliivibrio species these species share many genes required for host colonization and biofilm formation and also include species and strain-level dependent features. Two of the novel Aliivibrio species surprisingly possessed genes for cytolethal distending toxin while the more predominant species lacked any known virulence genes. The overall observations suggest a small number of species actively colonize the mucosal layer of Atlantic salmon farmed in Tasmania and that this process is strongly influenced by the environmental temperature.

microbiology↗

The Southern Bluefin Tuna mucosal microbiome is influenced by husbandry method, net pen location, and anti-parasite treatment

Aquaculture is the fastest growing primary industry worldwide. Marine finfish culture in open ocean net pens, or pontoons, is one of the largest growth areas and is currently the only way to rear high value fish such as bluefin tuna. Ranching involves catching wild juveniles, stocking in floating net pens and fattening for four to eight months. Tuna experience several parasite-induced disease challenges in culture that can be mitigated by application of praziquantel (PZQ) as a therapeutic. In this study, we characterized the microbiome of ranched southern Bluefin Tuna, Thunnus maccoyii, across four anatomic sites (gill, skin, digesta, and anterior kidney) and evaluated environmental and pathological factors that influence microbiome composition, including the impact of PZQ treatment on microbiome stability. Southern bluefin tuna gill, skin, and digesta microbiome communities are unique and potentially influenced by husbandry practices, location of pontoon growout pens, and treatment with the antiparasitic PZQ. There was no significant relationship between the fish mucosal microbiome and incidence or abundance of adult blood fluke in the heart or fluke egg density in the gill. An enhanced understanding of microbiome diversity and function in high-value farmed fish species such as bluefin tuna is needed to optimize fish health and improve aquaculture yield. Comparison of the bluefin tuna microbiome to other fish species, including Seriola lalandi (yellowtail kingfish), a common farmed species from Australia, and Scomber japonicus (Pacific mackerel), a wild caught Scombrid relative of tuna, showed the two Scombrids had more similar microbial communities compared to other families. The finding that mucosal microbial communities are more similar in phylogenetically related fish species exposes an opportunity to develop mackerel as a model for tuna microbiome and parasite research.

genomics↗

Microbial ecology of Atlantic salmon, Salmo salar, hatcheries: impacts of the built environment on fish mucosal microbiota

Successful rearing of fish in hatcheries is critical for conservation, recreational fishing, and commercial fishing through wild stock enhancements, and aquaculture production. Flow through (FT) hatcheries require more water than Recirculating-Aquaculture-Systems (RAS) which enable up to 99% of water to be recycled thus significantly reducing environmental impacts. Here, we evaluated the biological and physical microbiome interactions of the built environment of a hatchery from three Atl salmon hatcheries (RAS n=2, FT n=1). Six juvenile fish were sampled from tanks in each of the hatcheries for a total of 60 fish across 10 tanks. Water and tank side biofilm samples were collected from each of the tanks along with three salmon body sites (gill, skin, and digesta) to assess mucosal microbiota using 16S rRNA sequencing. The water and tank biofilm had more microbial richness than fish mucus while skin and digesta from RAS fish had 2x the richness of FT fish. Body sites each had unique microbial communities (P<0.001) and were influenced by the various hatchery systems (P<0.001) with RAS systems more similar. Water and especially tank biofilm richness was positively correlated with skin and digesta richness. Strikingly, the gill, skin and digesta communities were more similar to the origin tank biofilm vs. all other experimental tanks suggesting that the tank biofilm has a direct influence on fish-associated microbial communities. The results from this study provide evidence for a link between the tank microbiome and the fish microbiome with the skin microbiome as an important intermediate.\n\nIMPORTANCEAtlantic salmon, Salmo salar, is the most farmed marine fish worldwide with an annual production of 2,248 million metric tonnes in 2016. Salmon hatcheries are increasingly changing from flow through towards RAS design to accommodate more control over production along with improved environmental sustainability due to lower impacts on water consumption. To date, microbiome studies on hatcheries have focused either on the fish mucosal microbiota or the built environment microbiota, but have not combined the two to understand interactions. Our study evaluates how water and tank biofilm microbiota influences fish microbiota across three mucosal environments (gill, skin, and digesta). Results from this study highlight how the built environment is a unique source of microbes to colonize fish mucus and furthermore how this can influence the fish health. Further studies can use this knowledge to engineer built environments to modulate fish microbiota for a beneficial phenotype.

microbiology↗