Streptomyces sp. TR1341 was isolated from the sputum of a man with a history of lung and kidney tuberculosis, recurrent respiratory infections, and COPD. It produces secondary metabolites associated with cytotoxicity and immune response modulation. In this study, we complement our previous results by identifying the genetic features associated with the production of these secondary metabolites and other characteristics that could benefit the strain during its colonization of human tissues (virulence factors, modification of the host immune response, or the production of siderophores). We performed a comparative phylogenetic analysis to identify the genetic features that are shared by environmental isolates and human respiratory pathogens. The results showed a high genomic similarity of Streptomyces sp. TR1341 to the plant-associated Streptomyces sp. endophyte_N2, inferring a soil origin of the strain. Putative virulence genes, such as mammalian cell entry (mce) genes were not detected in the TR1341's genome. The presence of a type VII secretion system, distinct from the ones found in Mycobacterium species, suggests a different colonization strategy than the one used by other actinomycete lung pathogens. We identified a higher diversity of genes related to iron acquisition and demonstrated that the strain produces ferrioxamine B in vitro. These results indicate that TR1341 may have an advantage in colonizing environments that are low in iron, such as human tissue.

• MeSH
• Phylogeny MeSH
• Genetic Techniques MeSH
• Genome genetics   MeSH
• Genes genetics   MeSH
• Humans MeSH
• Lung microbiology   MeSH
• Colony Count, Microbial methods   MeSH
• Streptomyces * genetics   isolation & purification   MeSH
• Tissues microbiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cancer cell invasion through tissue barriers is the intrinsic feature of metastasis, the most life-threatening aspect of cancer. Detailed observation and analysis of cancer cell behaviour in a 3D environment is essential for a full understanding of the mechanisms of cancer cell invasion. The inherent limits of optical microscopy resolution do not allow to for in-depth observation of intracellular structures, such as invadopodia of invading cancer cells. The required resolution can be achieved using electron microscopy techniques such as FIB-SEM. However, visualising cells in a 3D matrix using FIB-SEM is challenging due to difficulties with localisation of a specific cell deep within the resin block. We have developed a new protocol based on the near-infrared branding (NIRB) procedure that extends the pattern from the surface grid deep inside the resin. This 3D burned pattern allows for precise trimming followed by targeted 3D FIB-SEM. Here we present detailed 3D CLEM results combining confocal and FIB-SEM imaging of cancer cell invadopodia that extend deep into the collagen meshwork.

• MeSH
• Spectroscopy, Near-Infrared methods   MeSH
• Fibrosarcoma pathology   MeSH
• Neoplasm Invasiveness MeSH
• Humans MeSH
• Microscopy, Electron, Scanning methods   MeSH
• Tumor Cells, Cultured MeSH
• Breast Neoplasms pathology   MeSH
• Image Processing, Computer-Assisted MeSH
• Podosomes pathology   MeSH
• Imaging, Three-Dimensional methods   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Methamphetamine (METH) abuse is known to increase the risk of Parkinson's disease (PD) due to its dopaminergic neurotoxicity. This is the rationale for the METH model of PD developed by toxic METH dosing (10 mg/kg four times every 2 h) which features robust neurodegeneration and typical motor impairment in mice. In this study, we used diffusion kurtosis imaging to reveal microstructural brain changes caused by METH-induced neurodegeneration. The METH-treated mice and saline-treated controls underwent diffusion kurtosis imaging scanning using the Bruker Avance 9.4 Tesla MRI system at two time-points: 5 days and 1 month to capture both early and late changes induced by METH. At 5 days, we found a decrease in kurtosis in substantia nigra, striatum and sensorimotor cortex, which is likely to indicate loss of DAergic neurons. At 1 month, we found an increase of kurtosis in striatum and sensorimotor cortex and hippocampus, which may reflect certain recovery processes. Furthermore, we performed tract-based spatial statistics analysis in the white matter and at 1 month, we observed increased kurtosis in ventral nucleus of the lateral lemniscus and some of the lateral thalamic nuclei. No changes were present at the early stage. This study confirms the ability of diffusion kurtosis imaging to detect microstructural pathological processes in both grey and white matter in the METH model of PD. The exact mechanisms underlying the kurtosis changes remain to be elucidated but kurtosis seems to be a valuable biomarker for tracking microstructural brain changes in PD and potentially other neurodegenerative disorders.

• MeSH
• Behavior, Animal drug effects   MeSH
• Diffusion Magnetic Resonance Imaging MeSH
• Dopamine Agents toxicity   MeSH
• Methamphetamine toxicity   MeSH
• Disease Models, Animal MeSH
• Brain diagnostic imaging   drug effects   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Parkinson Disease, Secondary diagnostic imaging   pathology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH