Temperature passively affects biological processes involved in plant growth. Therefore, it is challenging to study the dedicated temperature signalling pathways that orchestrate thermomorphogenesis, a suite of elongation growth-based adaptations that enhance leaf-cooling capacity. We screened a chemical library for compounds that restored hypocotyl elongation in the pif4-2-deficient mutant background at warm temperature conditions in Arabidopsis thaliana to identify modulators of thermomorphogenesis. The small aromatic compound 'Heatin', containing 1-iminomethyl-2-naphthol as a pharmacophore, was selected as an enhancer of elongation growth. We show that ARABIDOPSIS ALDEHYDE OXIDASES redundantly contribute to Heatin-mediated hypocotyl elongation. Following a chemical proteomics approach, the members of the NITRILASE1-subfamily of auxin biosynthesis enzymes were identified among the molecular targets of Heatin. Our data reveal that nitrilases are involved in promotion of hypocotyl elongation in response to high temperature and Heatin-mediated hypocotyl elongation requires the NITRILASE1-subfamily members, NIT1 and NIT2. Heatin inhibits NIT1-subfamily enzymatic activity in vitro and the application of Heatin accordingly results in the accumulation of NIT1-subfamily substrate indole-3-acetonitrile in vivo. However, levels of the NIT1-subfamily product, bioactive auxin (indole-3-acetic acid), were also significantly increased. It is likely that the stimulation of hypocotyl elongation by Heatin might be independent of its observed interaction with NITRILASE1-subfamily members. However, nitrilases may contribute to the Heatin response by stimulating indole-3-acetic acid biosynthesis in an indirect way. Heatin and its functional analogues present novel chemical entities for studying auxin biology.

• Klíčová slova
• 1-iminomethyl-2-naphthol, Arabidopsis, Heatin, IAN, NIT1-subfamily, PIF4, aldehyde oxidase, chemical genetics, indole-3-acetonitrile, nitrilases, thermomorphogenesis,
• MeSH
• aldehydoxidasa genetika   metabolismus   MeSH
• aminohydrolasy genetika   metabolismus   MeSH
• apomorfin analogy a deriváty   farmakologie   MeSH
• Arabidopsis účinky léků   růst a vývoj   MeSH
• herbicidy farmakologie   MeSH
• hypokotyl účinky léků   růst a vývoj   MeSH
• inhibitory enzymů aplikace a dávkování   chemie   farmakologie   MeSH
• kyseliny indoloctové MeSH
• molekulární struktura MeSH
• pikloram farmakologie   MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• regulace genové exprese u rostlin účinky léků   MeSH
• transkriptom účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 10,11-dihydroxy-N-n-propylnorapomorphine MeSH Prohlížeč
• AAO1 protein, Arabidopsis MeSH Prohlížeč
• aldehydoxidasa MeSH
• aminohydrolasy MeSH
• apomorfin MeSH
• herbicidy MeSH
• inhibitory enzymů MeSH
• kyseliny indoloctové MeSH
• nitrilase MeSH Prohlížeč
• pikloram MeSH
• proteiny huseníčku MeSH

The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI.

• Klíčová slova
• airway microbiome, antibiotics, hematological malignancies, indole-3-aldehyde, invasive fungal infection, metabolomics, tryptophan,
• MeSH
• antifungální látky farmakologie   terapeutické užití   MeSH
• farynx mikrobiologie   MeSH
• hematologické nádory komplikace   MeSH
• hodnocení rizik MeSH
• krevní nemoci komplikace   MeSH
• lidé MeSH
• metagenom MeSH
• metagenomika metody   MeSH
• mikrobiota * MeSH
• modely nemocí na zvířatech MeSH
• mykózy diagnóza   farmakoterapie   etiologie   MeSH
• myši MeSH
• pneumonie diagnóza   farmakoterapie   etiologie   MeSH
• rizikové faktory MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antifungální látky MeSH

National screening programs use dried blood specimens to detect metabolic disorders or aberrant protein functions that are not clinically evident in the neonatal period. Similarly, gut microbiota metabolites and immunological acute-phase proteins may reveal latent immune aberrations. Microbial metabolites interact with xenobiotic receptors (i.e., aryl hydrocarbon and pregnane-X) to maintain gastrointestinal tissue health, supported by acute-phase proteins, functioning as sensors of microbial immunomodulation and homeostasis. The delivery (vaginal or cesarean section) shapes the microbial colonization, which substantially modulates both the immune system's response and mucosal homeostasis. This study profiled microbial metabolites of the kynurenine and tryptophan pathway and acute-phase proteins in 134 neonatal dried blood specimens. We newly established neonatal blood levels of microbial xenobiotic receptors ligands (i.e., indole-3-aldehyde, indole-3-butyric acid, and indole-3-acetamide) on the second day of life. Furthermore, we observed diverse microbial metabolic profiles in neonates born vaginally and via cesarean section, potentially due to microbial immunomodulatory influence. In summary, these findings suggest the supportive role of human gut microbiota in developing and maintaining immune system homeostasis.

• Klíčová slova
• acute-phase proteins, dried blood specimens, human gut microbiota, immunomodulation, tryptophan and kynurenine metabolism,
• Publikační typ
• časopisecké články MeSH

The participation of reactants undergoing a polarity inversion along a multicomponent reaction allows the continuation of the transformation with productive domino processes. Thus, indole aldehydes in Groebke-Blackburn-Bienaymé reactions lead to an initial adduct which spontaneously triggers a series of events leading to the discovery of novel reaction pathways together with direct access to a variety of linked, fused, and bridged polyheterocyclic scaffolds. Indole 3- and 4-carbaldehydes with suitable isocyanides and aminoazines afford fused adducts through oxidative Pictet-Spengler processes, whereas indole 2-carbaldehyde yields linked indolocarbazoles under mild conditions, and a bridged macrocycle at high temperature. These novel structures are potent activators of the human aryl hydrocarbon receptor signaling pathway.

• Klíčová slova
• domino reactions, multicomponent reactions, nitrogen heterocycles, receptors, synthetic methods,
• MeSH
• aldehydy chemie   MeSH
• cyklizace MeSH
• indoly chemie   MeSH
• lidé MeSH
• ligandy MeSH
• molekulární struktura MeSH
• receptory aromatických uhlovodíků chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aldehydy MeSH
• indoly MeSH
• ligandy MeSH
• receptory aromatických uhlovodíků MeSH