Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
The HD-ZIP class I transcription factor, HvHOX1 (Homeobox 1) or VRS1 (Vulgare Row-type Spike 1 or Six-rowed Spike 1), regulates lateral spikelet fertility in barley (Hordeum vulgare L.). It was shown that HvHOX1 has a high expression only in lateral spikelets, while its paralog HvHOX2 was found to be expressed in different plant organs. Yet, the mechanistic function of HvHOX1 and HvHOX2 during spikelet development is still fragmentary. Here, we show that compared to HvHOX1, HvHOX2 is more highly conserved across different barley genotypes and Hordeum species, hinting at a possibly vital but still unclarified biological role. Using bimolecular fluorescence complementation, DNA-binding, and transactivation assays, we validate that HvHOX1 and HvHOX2 are bona fide transcriptional activators that may potentially heterodimerize. Accordingly, both genes exhibit similar spatiotemporal expression patterns during spike development and growth, albeit their mRNA levels differ quantitatively. We show that HvHOX1 delays the lateral spikelet meristem differentiation and affects fertility by aborting the reproductive organs. Interestingly, the ancestral relationship of these genes inferred from their co-expressed gene networks suggested that HvHOX1 and HvHOX2 might play a similar role during barley spikelet development. However, CRISPR-derived mutants of HvHOX1 and HvHOX2 demonstrated the suppressive role of HvHOX1 on lateral spikelets, while the loss of HvHOX2 does not influence spikelet development. Collectively, our study shows that through the suppression of reproductive organs, lateral spikelet fertility is regulated by HvHOX1, whereas HvHOX2 is dispensable for spikelet development in barley.
Publikation
Smolková, R.; Smolko, L.; Samoľová, E.; Morgan, I.; Rennert, R.; Kaluđerović, G. N.;Novel Zn(ii), Co(ii) and Cu(ii) diflunisalato complexes with neocuproine and their exceptional antiproliferative activity against cancer cell linesDalton Trans.5317595-17607(2024)DOI: 10.1039/d4dt01736f
Three novel complexes of deprotonated diflunisal (dif) with neocuproine (neo) were synthesized and characterized via elemental, spectral (UV-vis, FTIR, fluorescence, and mass spectrometry), and single-crystal X-ray diffraction analyses. Although the compounds shared a similar composition of [MCl(dif)(neo)], where M represents Zn(II) (1), Co(II) (2) and Cu(II) (3), only 1 and 2 were isostructural, while 3 differed in both the molecular and supramolecular structures. In all three complex molecules, the central atom is coordinated by two nitrogen atoms of neo in a bidentate chelate mode, and one chlorido ligand and dif is bonded in either a monodentate mode via one oxygen atom of the carboxylate in 1 and 2 or in a bidentate chelate mode via both carboxylate oxygen atoms in 3. All three compounds demonstrated remarkable antiproliferative activity against human prostate (PC-3), colon (HCT116) and breast (MDA-MB-468) cancer cell lines with IC50 values in the nanomolar range, with the lowest values observed in the case of PC-3 and MDA-MB-468 with 2 (20.0 nM) and 3 (31.1 nM), respectively. Moreover, complex 2, as the most active, was further investigated for its potential to induce perturbations in the cell cycle of PC-3 cells. The results indicated an induction of caspase-independent apoptosis. The interaction of the complexes with genomic DNA isolated from the respective cancer cell lines was evaluated for the intercalative mode, with binding strength correlated with the antiproliferative activity against PC-3 and MDA-MB-468 cancer cell lines.
Publikation
Predarska, I.; Saoud, M.; Morgan, I.; Eichhorn, T.; Kaluđerović, G. N.; Hey-Hawkins, E.;Cisplatin−cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell lineDalton Trans.51857–869(2022)DOI: 10.1039/d1dt03265h
For the development of anticancer drugs with higher activity and reduced
toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II)
counterparts and loading them into mesoporous silica SBA-15 with the
aim to utilise the passive enhanced permeability and retention (EPR)
effect of nanoparticles for accumulation in tumour tissues. Three
conjugates based on a cisplatin scaffold bearing the anti-inflammatory
drugs naproxen, ibuprofen or flurbiprofen in the axial positions (1, 2 and 3, respectively) were synthesised and loaded into SBA-15 to afford the mesoporous silica nanoparticles (MSNs) SBA-15|1, SBA-15|2 and SBA-15|3.
Superior antiproliferative activity of both free and immobilised
conjugates in a panel of four breast cancer cell lines (MDA-MB-468,
HCC1937, MCF-7 and BT-474) with markedly increased cytotoxicity with
respect to cisplatin was demonstrated. All compounds exhibit highest
activity against the triple-negative cell line MDA-MB-468, with
conjugate 1 being the most potent. However, against MCF-7 and BT-474 cell lines, the most notable improvement was found, with IC50
values up to 240-fold lower than cisplatin. Flow cytometry assays
clearly show that all compounds induce apoptotic cell death elevating
the levels of both early and late apoptotic cells. Furthermore,
autophagy as well as formation of reactive oxygen species (ROS) and
nitric oxide (NO) were elevated to a similar or greater extent than with
cisplatin.
Publikation
Bittner, A.; Hause, B.; Baier, M.;Cold-priming causes oxylipin dampening during the early cold and light response of Arabidopsis thalianaJ. Exp. Bot.727163-7179(2021)DOI: 10.1093/jxb/erab314
Abstract
The comparison of transcriptome time-courses of the first 2 h of the cold or highlight response of 24 h cold primed and naive Arabidopsis thaliana showed that priming quickly modifies gene expression in a trigger-specific manner. It dampened up- as well as down-regulation of genes in the cold and in the light. 1/3 of the priming-regulated genes were jasmonate sensitive, including the full set of genes required for oxylipin biosynthesis. qPCR-based analysis in wildtype plants and mutants demonstrated that OPDA (12-oxo phytenoic acid) biosynthesis relative to the jasmonic acid (JA) availability controls dampening of the genes for oxylipin biosynthetic enzymes: Gene regulation in oxylipin biosynthesis mutants more strongly depended on the biosynthesis of the JA precursor OPDA than on its conversion to JA. Additionally, priming-dependent dampening during triggering was more linked to OPDA than to JA level regulation and spray application of OPDA prior to triggering counteracted gene dampening. In contrast to cold-priming induced dampening of ZAT10, priming regulation of the oxylipin hub was insensitive to priming-induced accumulation of thylakoid ascorbate peroxidase and mediated by modulation of the oxylipin sensitivity of genes for OPDA biosynthesis.