Durand, Maxime*
Dotaz
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Element content and expression of genes of interest on single cell types, such as stomata, provide valuable insights into their specific physiology, improving our understanding of leaf gas exchange regulation. We investigated how far differences in stomatal conductance (gs ) can be ascribed to changes in guard cells functioning in amphistomateous leaves. gs was measured during the day on both leaf sides, on well-watered and drought-stressed trees (two Populus euramericana Moench and two Populus nigra L. genotypes). In parallel, guard cells were dissected for element content and gene expressions analyses. Both were strongly arranged according to genotype, and drought had the lowest impact overall. Normalizing the data by genotype highlighted a structure on the basis of leaf sides and time of day both for element content and gene expression. Guard cells magnesium, phosphorus, and chlorine were the most abundant on the abaxial side in the morning, where gs was at the highest. In contrast, genes encoding H+ -ATPase and aquaporins were usually more abundant in the afternoon, whereas genes encoding Ca2+ -vacuolar antiporters, K+ channels, and ABA-related genes were in general more abundant on the adaxial side. Our work highlights the unique physiology of each leaf side and their analogous rhythmicity through the day.
- MeSH
- genotyp MeSH
- komplementární DNA genetika izolace a purifikace MeSH
- listy rostlin genetika metabolismus MeSH
- mikroanalýza elektronovou sondou MeSH
- období sucha MeSH
- Populus klasifikace genetika metabolismus MeSH
- protonové ATPasy genetika metabolismus MeSH
- průduchy rostlin genetika metabolismus MeSH
- regulace genové exprese u rostlin MeSH
- RNA rostlin genetika izolace a purifikace MeSH
- rostlinné proteiny genetika metabolismus MeSH
- stromy genetika metabolismus MeSH
- transpirace rostlin fyziologie MeSH
- voda fyziologie MeSH
- vývoj rostlin MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The utility of KRAS mutations in plasma circulating cell-free DNA (cfDNA) samples as non-invasive biomarkers for the detection of pancreatic cancer has never been evaluated in a large case-control series. We applied a KRAS amplicon-based deep sequencing strategy combined with analytical pipeline specifically designed for the detection of low-abundance mutations to screen plasma samples of 437 pancreatic cancer cases, 141 chronic pancreatitis subjects, and 394 healthy controls. We detected mutations in 21.1% (N=92) of cases, of whom 82 (89.1%) carried at least one mutation at hotspot codons 12, 13 or 61, with mutant allelic fractions from 0.08% to 79%. Advanced stages were associated with an increased proportion of detection, with KRAS cfDNA mutations detected in 10.3%, 17,5% and 33.3% of cases with local, regional and systemic stages, respectively. We also detected KRAS cfDNA mutations in 3.7% (N=14) of healthy controls and in 4.3% (N=6) of subjects with chronic pancreatitis, but at significantly lower allelic fractions than in cases. Combining cfDNA KRAS mutations and CA19-9 plasma levels on a limited set of case-control samples did not improve the overall performance of the biomarkers as compared to CA19-9 alone. Whether the limited sensitivity and specificity observed in our series of KRAS mutations in plasma cfDNA as biomarkers for pancreatic cancer detection are attributable to methodological limitations or to the biology of cfDNA should be further assessed in large case-control series.
- MeSH
- antigen CA-19-9 krev MeSH
- cirkulující nádorová DNA krev genetika MeSH
- duktální karcinom slinivky břišní krev genetika patologie MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery krev genetika MeSH
- nádory slinivky břišní krev genetika patologie MeSH
- pilotní projekty MeSH
- prediktivní hodnota testů MeSH
- protoonkogenní proteiny p21(ras) krev genetika MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- validační studie MeSH
- Geografické názvy
- Česká republika MeSH
- Slovenská republika MeSH
The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (≥1 and ≤3 Gy) and on the metabolic and immune host-microbiota interaction at baseline allowing CD8+ T cell activation without exhaustion. Various strains of Christensenella minuta selectively boost the anti-cancer efficacy of ILDR and PD-L1 blockade, allowing emigration of intestinal PD-L1-expressing dendritic cells to tumor-draining lymph nodes. An interventional phase 2 study provides the proof-of-concept that ILDR can circumvent resistance to first- or second-line immunotherapy in cancer patients. Prospective clinical trials are warranted to define optimal dosimetry and indications for ILDR to maximize its therapeutic potential.
- MeSH
- antigeny CD274 * antagonisté a inhibitory metabolismus imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů * farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory imunologie radioterapie terapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- střeva patologie účinky záření MeSH
- střevní mikroflóra MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH