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Ketola, K.

Publications and source records attributed to Ketola, K..

3 recordsLinked to original sources

Aerobic anoxygenic phototrophic bacteria are ubiquitous in phyllo- and endosphere microbiomes of boreal and subarctic plants

In addition to oxygenic photosynthetic systems, solar radiation is utilized for energy by diverse anoxygenic photosynthetic systems. Aerobic anoxygenic phototrophic bacteria (AAPB) perform photosynthesis without producing oxygen but still live in aerobic conditions. Typically they have been reported from aquatic ecosystems, but they can also be found from polar and desert soil ecosystems and primary succession communities like soil crusts. Recently, AAPB have been discovered in the metagenomic data of several plant phyllospheres. By utilizing citizen science, we screened plant foliar samples from eleven different locations in Finland for AAPB by near infrared fluorescence imaging of culturable phyllosphere and endosphere bacteria. Near infrared fluorescence reports the presence of AAPB which contain Bacteriochlorophyll a molecules, embedded in Light Harvesting 1 - Reaction Center complex. We found that AAPB were ubiquotous in phyllosphere communities of diverse plant species in all sampling locations. They were also consistently present in the endosphere of plant species with perennial leaves. Most of the AAPB isolated represent alphaproteobacterial genera Sphingomonas and Methylobacterium, but several isolates from genus Lichenihabitans as well as putative novel alphaproteobacterial taxa were also identified. Methylobacterial isolates were mostly detected in the phyllosphere with weak host specificity, while Sphingomonas AAPB were detected also in the endosphere of several plant species, with clear host specific taxa. We studied also the fluorescence spectral properties of several AAPBs. All the observed spectra resemble typical fluorescence spectral properties of Light Harvesting complex 1. Still, slight variation among each spectra could be obtained, revealing some physical difference among the complexes. Our results demonstrate for the first time, that AAPB are common in cold climate plant endophytic as well as epiphytic microbiomes and they build up substantial amounts of Bacteriochlorophyll a containing Light Harvesting complexes. Their putative role in plant adaptation to strong seasonality in light and temperature or tolerance of abiotic stressors remains to be investigated in future studies.

microbiology↗

Microglial amyloid beta clearance is driven by PIEZO1 channels

BackgroundMicroglia are the endogenous immune cells of the brain and act as sensors of pathology to maintain brain homeostasis and eliminate potential threats. In Alzheimers disease (AD), toxic amyloid beta (A{beta}) accumulates in the brain and forms stiff plaques. In late-onset AD accounting for 95% of all cases, this is thought to be due to reduced clearance of A{beta}. Human genome-wide association studies and animal models suggest that reduced clearance results from aberrant function of microglia. While the impact of neurochemical pathways on microglia have been broadly studied, mechanical receptors regulating microglial functions remain largely unexplored. MethodsHere we showed that a mechanotransduction ion channel, PIEZO1, is expressed and functional in human and mouse microglia. We used a small molecule agonist, Yoda1, to study how activation of PIEZO1 affects AD-related functions in human induced pluripotent stem cell (iPSC) -derived microglia-like cells (iMGL) under controlled laboratory experiments. Cell survival, metabolism, phagocytosis and lysosomal activity were assessed using real-time functional assays. To evaluate the effect of activation of PIEZO1 in vivo, 5-month-old 5xFAD male mice were infused daily with Yoda1 for two weeks through intracranial cannulas. Microglial Iba1 expression and A{beta} pathology were quantified with immunohistochemistry and confocal microscopy. Published human and mouse AD datasets were used for in-depth analysis of PIEZO1 gene expression and related pathways in microglial subpopulations. ResultsWe show that PIEZO1 orchestrates A{beta} clearance by enhancing microglial survival, phagocytosis, and lysosomal activity. A{beta} inhibited PIEZO1-mediated calcium transients, whereas activation of PIEZO1 with a selective agonist, Yoda1, improved microglial phagocytosis resulting in A{beta} clearance both in human and mouse models of AD. Moreover, PIEZO1 expression was associated with a unique microglial transcriptional phenotype in AD as indicated by assessment of cellular metabolism, and human and mouse single cell datasets. ConclusionThese results indicate that the compromised function of microglia in AD could be improved by controlled activation of PIEZO1 channels resulting in alleviated A{beta} burden. Pharmacological regulation of these mechanoreceptors in microglia could represent a novel therapeutic paradigm for AD. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/484831v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@832eadorg.highwire.dtl.DTLVardef@6d8719org.highwire.dtl.DTLVardef@c09740org.highwire.dtl.DTLVardef@9fa85_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Single-cell ATAC and RNA sequencing reveal pre-existing and persistent subpopulations of cells associated with relapse of prostate cancer

Prostate cancer is profoundly heterogeneous and patients would benefit from methods that stratify clinically indolent from more aggressive forms of the disease. We employed single-cell assay for transposase-accessible chromatin (ATAC) and RNA sequencing in models of early treatment response and resistance to enzalutamide. In doing so, we identified pre-existing and treatment-persistent cell subpopulations that possess transcriptional stem-like features and regenerative potential when subjected to treatment. We found distinct chromatin landscapes associated with enzalutamide treatment and resistance that are linked to alternative transcriptional programs. Transcriptional profiles characteristic of persistent stem-like cells were able to stratify the treatment response of patients. Ultimately, we show that defining changes in chromatin and gene expression in single-cell populations from pre-clinical models can reveal hitherto unrecognized molecular predictors of treatment response. This suggests that high analytical resolution of pre-clinical models may powerfully inform clinical decision-making.

cancer biology↗