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Entrepreneurship may be associated with independence and profit, but it may also be a precarious type of employment. Self-employment is often a strategy for those groups of workers who face marginalisation and disadvantages on the labour market, such as mothers of young children or migrants. In this paper we use an intersectional approach and draw on the theory of precarity to analyse how Czech and Ukrainian entrepreneurs with small children (in the Czech Republic) describe and perceive precarity in self-employment. Our analysis shows that entrepreneurship is a form of precarious work, especially for mothers of young children. Their social position, which forms on the intersection of gender, caring commitments, and/or migration status, serves to constrain or allow certain career choices. While the main source of disadvantage for Czech entrepreneurs is the intersection of gender and caring commitments (e.g. in work-life balance), the social position of Ukrainian entrepreneurs (in the Czech Republic) is much more precarious because of their status as migrants (e.g. their low income from business is further reduced by the cost of private insurance, the paying of remittances, or the repayment of debts for migrating to the Czech Republic).

A series of thirty-one hydrazones of aminoguanidine, nitroaminoguanidine, 1,3-diaminoguanidine, and (thio)semicarbazide were prepared from various aldehydes, mainly chlorobenzaldehydes, halogenated salicylaldehydes, 5-nitrofurfural, and isatin (yields of 50–99%). They were characterized by spectral methods. Primarily, they were designed and evaluated as potential broad-spectrum antimicrobial agents. The compounds were effective against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus with minimum inhibitory concentrations (MIC) from 7.8 µM, as well as Gram-negative strains with higher MIC. Antifungal evaluation against yeasts and Trichophyton mentagrophytes found MIC from 62.5 µM. We also evaluated inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The compounds inhibited both enzymes with IC50 values of 17.95–54.93 µM for AChE and ≥1.69 µM for BuChE. Based on the substitution, it is possible to modify selectivity for a particular cholinesterase as we obtained selective inhibitors of either AChE or BuChE, as well as balanced inhibitors. The compounds act via mixed-type inhibition. Their interactions with enzymes were studied by molecular docking. Cytotoxicity was assessed in HepG2 cells. The hydrazones differ in their toxicity (IC50 from 5.27 to >500 µM). Some of the derivatives represent promising hits for further development. Based on the substitution pattern, it is possible to modulate bioactivity to the desired one.

Background: Hydrazide-hydrazones have been known as scaffold with various biological activities including inhibition of acetyl- (AChE) and butyrylcholinesterase (BuChE). Cholinesterase inhibitors are mainstays of dementias’ treatment. Objective: Twenty-five iodinated hydrazide-hydrazones and their analogues were designed as potential central AChE and BuChE inhibitors. Methods: Hydrazide-hydrazones were synthesized from 4-substituted benzohydrazides and 2-/4- hydroxy-3,5-diiodobenzaldehydes. The compounds were investigated in vitro for their potency to inhibit AChE from electric eel and BuChE from equine serum using Ellman’s method. We calculated also physicochemical and structural parameters for CNS delivery. Results: The derivatives exhibited a moderate dual inhibition with IC50 values ranging from 15.1-140.5 and 35.5 to 170.5 μmol.L-1 for AChE and BuChE, respectively. Generally, the compounds produced a balanced or more potent inhibition of AChE. N'-[(E)-(4-Hydroxy-3,5-diiodophenyl)methylidene]-4- nitrobenzohydrazide 2k and 4-fluoro-N'-(2-hydroxy-3,5-diiodobenzyl)benzohydrazide 3a were the most potent inhibitors of AChE and BuChE, respectively. Structure-activity relationships were established, and molecular docking studies confirmed interaction with enzymes. Conclusion: Many novel hydrazide-hydrazones showed lower IC50 values than rivastigmine against AChE and some of them were comparable for BuChE to this drug used for the treatment of dementia. They interact with cholinesterases via non-covalent binding into the active site. Based on the BOILEDEgg approach, the majority of the derivatives met the criteria for blood-brain-barrier permeability.

The development of novel drugs is essential for the treatment of tuberculosis and other mycobacterial infections in future. A series of N-alkyl-2-isonicotinoylhydrazine-1-carboxamides was synthesized from isoniazid (INH) and then cyclized to N-alkyl-5-(pyridin-4-yl)-1,3,4-oxadiazole-2-amines. All derivatives were characterised spectroscopically. The compounds were screened for their in vitro antimycobacterial activity against susceptible and multidrug-resistant Mycobacterium tuberculosis (Mtb.) and nontuberculous mycobacteria (NTM; M. avium, M. kansasii). The most active carboxamides were substituted by a short n-alkyl, their activity was comparable to INH with minimum inhibitory concentrations (MICs) against Mtb. of 0.5–2 μM. Moreover, they are non-toxic for HepG2, and some of them are highly active against INH-resistant NTM (MICs ≥4 μM). Their cyclization to 1,3,4-oxadiazoles did not increase the activity. The experimentally proved mechanism of action of 2-isonicotinoylhydrazine-1-carboxamides consists of the inhibition of enoyl-ACP reductase (InhA) in a way similar to INH, which is blocking the biosynthesis of mycolic acids. N-Dodecyl-5-(pyridin-4-yl)-1,3,4-oxadiazol-2-amine as the most efficacious oxadiazole inhibits growth of both susceptible and drug-resistant Mtb. strains with uniform MIC values of 4–8 μM with no cross-resistance to antitubercular drugs including INH. The mechanism of action is not elucidated but it is different from INH. Obtained results qualify these promising derivatives for further investigation.

Multiproxy palaeoecological evidence from a sandstone region in northern Czech Republic was collected to explore the impact of fire disturbances on the decline of the broadleaved forests during the Late Bronze Age (3250–3050 cal. BP). It has been hypothesized that human-accelerated soil leaching affected the nutrient availability in the sandstone area, thus promoting the expansion of oligotrophic-adapted plant communities in the late-Holocene. Little is known about the mechanisms which induced such large-scale vegetation transformation. We sought to determine which driving forces were involved using independent proxy records – soil and sedimentary charcoal, pollen and fungal spores. Local fire history was derived from the variation in charcoal accumulation rates (CHAR) preserved in Eustach peatbog. The fire frequency (FF) estimation over the past ~7500 years revealed distinct phases of increased burning between 3100 and 2120 cal. BP (3.0 fires 1000 yr−1) and 1400–600 cal. BP (4.3 fires 1000 yr−1). Rapid c...

Forests cover approximately one-third of Central Europe. Oak (Quercus) and European beech (Fagus sylvatica) are considered the natural dominants at low and middle elevations, respectively. Many coniferous forests (especially of Picea abies) occur primarily at midelevations, but these are thought to have resulted from forestry plantations planted over the past 200 years. Nature conservation and forestry policy seek to promote broadleaved trees over conifers. However, there are discrepancies between conservation guidelines (included in Natura 2000) and historical and palaeoecological data with regard to the distribution of conifers. Our aim was to bring new evidence to the debate on the conservation of conifers versus broadleaved trees at midelevations in Central Europe. We created a vegetation and land-cover model based on pollen data for a highland area of 11,300 km2 in the Czech Republic and assessed tree species composition in the forests before the onset of modern forestry based on 18th-century archival sources. Conifers dominated the study region throughout the entire Holocene (approximately 40-60% of the area). Broadleaved trees were present in a much smaller area than envisaged by current ideas of natural vegetation. Rather than casting doubt on the principles of Central European nature conservation in general, our results highlight the necessity of detailed regional investigations and the importance of historical data in challenging established notions on the natural distribution of tree species.

Antimycobacterially active salicylanilide diethyl phosphates were evaluated to identify their potential drug target(s) for the inhibition of several mycobacterial enzymes, including isocitrate lyase, L-alanine dehydrogenase (MtAlaDH), lysineε-aminotransferase, chorismate mutase, and pantothenate synthetase. The enzymes are related to the nongrowing state ofMycobacterium tuberculosis. Salicylanilide diethyl phosphates represent new candidates with significant inhibitory activity especially against L-alanine dehydrogenase. The most activeMtAlaDH inhibitor, 5-chloro-2-[(3-chlorophenyl)carbamoyl]phenyl diethyl phosphate, has an IC50of 4.96 µM and the best docking results. Other mycobacterial enzymes were mostly inhibited by some derivatives but at higher concentrations; isocitrate lyase showed the highest resistance to salicylanilide diethyl phosphates.

Fire occurrence is driven by a complex interplay between vegetation, climatic, landform and human factors making it challenging to separate the individual effect of each variable. Here we present a reconstruction of the Holocene biomass burning history of two regions located in the Central European temperate zone that differ in the timing of the Middle Holocene expansion of broadleaf-dominated forest communities. This allowed us to investigate the effect of biotic changes on past fire activity. Multiple-site charcoal accumulation records were used to estimate regional-scale trends in biomass burning and to compare them with major trajectories of vegetation development. Extensive 14C-dated soil charcoal records collected within both regions were amalgamated using a cumulative probability function to identify a stand-scale proxy of past fire occurrence. Our results suggest that rising vegetation productivity driven by rapid Early Holocene climate amelioration enhanced biomass burning. The increased fire activity during this period was driven by both a drier- and warmer-than-present climate and easily flammable fuels produced by conifer-dominated vegetation. We identified an inhibiting effect of the concomitant Fagus sylvatica expansion on levels of biomass burning that occurred asynchronously between our mountain and mid-elevation sandstone regions 6500 cal yr BP and 4900 cal yr BP, respectively. The amount of compositional change in plant communities was more related to the transformation of major vegetation types than to fluctuations in fire activity levels. The divergent timing of the fire decline in response to the Fagus sylvatica expansion implies biotic control over biomass burning that is independent of a direct climatic influence.

Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thio)carbamates were investigated using Ellman’s method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 μM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thio)carbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)- phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenyl)carbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 μM), while 2-(phenylcarbamoyl)phenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 μM). Results from molecular docking studies suggest that carbamate compounds, especially N,Ndiphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization. Pomocí Ellmanovy metody byla sledována schopnost 20 nových salicylanilidových karbamátů a thiokarbamátů inhibovat acetylcholinesterázu a butyrylcholinesterázu.

Chorismate-utilizing enzymes (CUE) such as chorismate mutase, anthranilate synthase, chorismate pyruvate-lyase, 4-amino-4-deoxychorismate synthase, isochorismate synthase and salicylate synthase are responsible for converting chorismate into various products necessary for the survival of bacteria. The absence of these enzymes in humans and their importance in the virulence and survival of bacteria make them suitable targets for potential antimicrobial compounds. Furthermore, the CUE have significant structural homology and similar catalytic mechanisms, enabling the strategy of affecting multiple enzymes with one single inhibitor. This review follows up the investigation of mechanisms of CUE-catalysed reactions and the concurrent development of CUE inhibitors. Many active compounds were found amongst the structures mimicking the transition state of chorismate during the reaction. Most recently, high nanomolar and low micromolar inhibitors against isochorismate-pyruvate lyase were identified, which were also effective against chorismate mutase and salicylate synthase and belong to the most active inhibitors reported up to date.