Hair follicle development is initiated by reciprocal molecular interactions between the placode-forming epithelium and the underlying mesenchyme. Cell fate transformation in dermal fibroblasts generates a cell niche for placode induction by activation of signaling pathways WNT, EDA, and FGF in the epithelium. These successive paracrine epithelial signals initiate dermal condensation in the underlying mesenchyme. Although epithelial signaling from the placode to mesenchyme is better described, little is known about primary mesenchymal signals resulting in placode induction. Using genetic approach in mice, we show that Meis2 expression in cells derived from the neural crest is critical for whisker formation and also for branching of trigeminal nerves. While whisker formation is independent of the trigeminal sensory innervation, MEIS2 in mesenchymal dermal cells orchestrates the initial steps of epithelial placode formation and subsequent dermal condensation. MEIS2 regulates the expression of transcription factor Foxd1, which is typical of pre-dermal condensation. However, deletion of Foxd1 does not affect whisker development. Overall, our data suggest an early role of mesenchymal MEIS2 during whisker formation and provide evidence that whiskers can normally develop in the absence of sensory innervation or Foxd1 expression.
- MeSH
- Neural Crest MeSH
- Forkhead Transcription Factors metabolism genetics MeSH
- Homeodomain Proteins * metabolism genetics MeSH
- Mesoderm * metabolism MeSH
- Mice MeSH
- Trigeminal Nerve * MeSH
- Vibrissae * innervation growth & development embryology MeSH
- Gene Expression Regulation, Developmental MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Studies have correlated living close to major roads with Alzheimer's disease (AD) risk. However, the mechanisms responsible for this link remain unclear. METHODS: We exposed olfactory mucosa (OM) cells of healthy individuals and AD patients to diesel emissions (DE). Cytotoxicity of exposure was assessed, mRNA, miRNA expression, and DNA methylation analyses were performed. The discovered altered pathways were validated using data from the human population-based Rotterdam Study. RESULTS: DE exposure resulted in an almost four-fold higher response in AD OM cells, indicating increased susceptibility to DE effects. Methylation analysis detected different DNA methylation patterns, revealing new exposure targets. Findings were validated by analyzing data from the Rotterdam Study cohort and demonstrated a key role of nuclear factor erythroid 2-related factor 2 signaling in responses to air pollutants. DISCUSSION: This study identifies air pollution exposure biomarkers and pinpoints key pathways activated by exposure. The data suggest that AD individuals may face heightened risks due to impaired cellular defenses. HIGHLIGHTS: Healthy and AD olfactory cells respond differently to DE exposure. AD cells are highly susceptible to DE exposure. The NRF2 oxidative stress response is highly activated upon air pollution exposure. DE-exposed AD cells activate the unfolded protein response pathway. Key findings are also confirmed in a population-based study.
- MeSH
- Alzheimer Disease * genetics metabolism MeSH
- Olfactory Mucosa metabolism MeSH
- Epigenomics MeSH
- NF-E2-Related Factor 2 genetics metabolism MeSH
- Air Pollutants adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- DNA Methylation * MeSH
- MicroRNAs metabolism genetics MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Transcriptome MeSH
- Vehicle Emissions * toxicity MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Magnetic resonance imaging (MRI) relies on appropriate contrast agents, especially for visualizing transplanted cells within host tissue. In recent years, compounds containing fluorine-19 have gained significant attention as MRI probe, particularly in dual 1H/19F-MR imaging. However, various factors affecting probe sensitivity, such as fluorine content and the equivalency of fluorine atoms, must be considered. In this study, we synthesized fluorinated micelles with adjustable surface positive charge density and investigated their physicochemical properties and MRI efficacy in phantoms and labeled cells. While the micelles exhibited clear signals in 19F-MR spectra and imaging, the concentrations required for MRI visualization of labeled cells were relatively high, adversely affecting cell viability. Despite their favourable physicochemical properties, achieving higher labeling rates without compromising cell viability during labeling remains a challenge for potential in vivo applications.
- MeSH
- Staining and Labeling methods MeSH
- Phantoms, Imaging MeSH
- Fluorine chemistry MeSH
- Halogenation MeSH
- Cations * chemistry MeSH
- Contrast Media chemistry MeSH
- Humans MeSH
- Magnetic Resonance Imaging methods MeSH
- Micelles * MeSH
- Mice MeSH
- Cell Survival * drug effects MeSH
- Fluorine-19 Magnetic Resonance Imaging methods MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD. METHODS: To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the air-liquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing. RESULTS: Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation. CONCLUSIONS: The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection.
- MeSH
- Alzheimer Disease * metabolism MeSH
- Anosmia metabolism MeSH
- Olfactory Mucosa metabolism MeSH
- COVID-19 * MeSH
- Humans MeSH
- Neuroinflammatory Diseases MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The microbial biofilms are ubiquitous in nature and represent important biological entities that affect various aspects of human life. As such, they attracted considerable attention during last decades, with the factors affecting the biofilm development being among the frequently studied topics. In our work, the biofilm was cultivated on the surface of polypropylene fibers in a nutrient medium inoculated by the suspension of two unsterile soils. The effects of ionic strength and valence of salt on the amount of the produced biofilm and on composition of biofilm microbial communities were investigated. The effect of valence was significant in some OTUs: Arthrobacter/Pseudarthrobacter/Paenarthrobacter and Bacillus with positive response to monovalent salt (KCl) and Streptomyces, Lysinibacillus, Pseudomonas, and Ensifer with positive response to divalent salt (MgSO4). The significant preference for a certain concentration of salts was observed in the case of OTUs Agrobacterium, Bacillus (both 100 mM), and Brevundimonas (30 mM). A new quantification method based on measuring of oxidizable organic carbon in biofilm biomass, based on dichromate oxidation, was used. We compared the results obtained using this method with results of crystal violet destaining and measuring of extracted DNA concentration as proxies of the biofilm biomass. The dichromate oxidation is simple, inexpensive, and fast, and our results show that it may be more sensitive than crystal violet destaining. The highest biomass values tended to associate with high concentrations of the divalent salt. This trend was not observed in treatments where the monovalent salt was added. Our data confirm the importance of inorganic ions for biofilm composition and biomass accumulation.
- MeSH
- Bacteria classification drug effects genetics isolation & purification MeSH
- Bacteriological Techniques MeSH
- Biofilms drug effects growth & development MeSH
- Biomass MeSH
- Culture Media chemistry MeSH
- Microbiota drug effects MeSH
- Minerals analysis pharmacology MeSH
- Polypropylenes MeSH
- Soil Microbiology MeSH
- Salts analysis pharmacology MeSH
- Publication type
- Journal Article MeSH
Biofilm formation is a typical life strategy used by microorganisms populating acidic water systems. The same strategy might be used by microbes in highly acidic soils that are, however, neglected in this regard. In the present study, the microbial community in such highly acidic soil in the Soos National Nature Reserve (Czech Republic) has been investigated using high-throughput DNA sequencing and the organisms associated with biofilm life mode and those preferring planktonic life were distinguished using the biofilm trap technique. Our data show the differences between biofilm and planktonic microbiota fraction, although the majority of the organisms were capable of using both life modes. The by far most abundant prokaryotic genus was Acidiphilium and fungi were identified among the most abundant eukaryotic elements in biofilm formations. On the other hand, small flagellates from diverse taxonomical groups predominated in plankton. The application of cellulose amendment as well as the depth of sampling significantly influenced the composition of the detected microbial community.
- MeSH
- Biofilms MeSH
- Hydrogen-Ion Concentration MeSH
- Microbiota * MeSH
- Plankton * MeSH
- Soil MeSH
- Soil Microbiology MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
