Thorough clinical evaluation of skin, as well as oral, genital and anal mucosa is beneficial in lichen planus patients

Lichen planus (LP) is a common mucocutaneous disease of unknown aetiology with various geographical prevalence, may be related to some serious disorders such as squamous cell carcinoma and often remains underdiagnosed. The aim of this retrospective study was to thoroughly determine localization and clinical characteristics of LP lesions in a cohort of 173 Slovenian patients in association to the presence of accompanying symptoms and history of potential stressful events. Isolated cutaneous lesions of LP were found in 56.6% and isolated oral LP in 3.5% of patients. Thirty-four percent presented orocutaneous LP, whereas genitocutaneous LP was noted in 1.2%, orogenito-cutaneous LP in 4% and orogenital LP in 0.5% of patients. Underlying stressful events were noted in 36 out of 137 (26.3%) patients. Despite obviously visible localization of the lesions various medical specialists should be familiar with LP and thoroughly examine the complete skin, as well as oral, genital and anal mucosa in each LP patient to avoid a delay in diagnosing this disease and possibly disclose a much serious underlying condition. Psychological support should be offered, if needed.     

Conservation of a domestic metapopulation structured into related and partly admixed strains

Preservation of genetic diversity is one of the most pressing challenges in the planetary boundaries concept. Within this context, we focused on genetic diversity in a native, unselected and highly admixed domesticated metapopulation. A set of 1,828 individuals from 60 different cattle breeds was analysed using a medium density SNP chip. Among these breeds, 14 Bu?a strains formed a metapopulation represented by 350 individuals, while the remaining 46 breeds represented the global cattle population. Genetic analyses showed that the scarcely selected and less differentiated Bu?a metapopulation contributed a substantial proportion (52.6%) of the neutral allelic diversity to this global taurine population. Consequently, there is an urgent need for synchronized maintenance of this highly fragmented domestic metapopulation, which is distributed over several countries without sophisticated infrastructure and highly endangered by continuous replacement crossing as part of the global genetic homogenization process. This study collected and evaluated samples, data and genomewide information and developed genome‐assisted cross‐border conservation concepts. To detect and maintain genetic integrity of the metapopulation strains, we designed and applied a composite test that combines six metrics based on additive genetic relationships, a nearest neighbour graph and the distribution of semiprivate alleles. Each metric provides distinct information components about past admixture events and offers an objective and powerful tool for the detection of admixed outliers. The here developed conservation methods and presented experiences could easily be adapted to comparable conservation programmes of domesticated or other metapopulations bred and kept in captivity or under some other sort of human control.     

New inhibitors of fungal 17beta-hydroxysteroid dehydrogenase based on the [1,5]-benzodiazepine scaffold

The synthesis and activity of a new series of non-steroidal inhibitors of 17beta-hydroxysteroid dehydrogenase that are based on a 1,5-benzodiazepine scaffold are presented. Their inhibitory potential was screened against 17beta-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17beta-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. Some of these compounds are potent inhibitors of 17beta-HSDcl activity, with IC50 values in the low micromolar range and represent promising lead compounds that should be further developed and investigated as inhibitors of human 17beta-HSD isoforms, which are the enzymes associated with the development of many hormone-dependent and neuronal diseases.     

Metabolomic profiling of CHO fed-batch growth phases at 10, 100, and 1,000 L

Established bioprocess monitoring is based on quick and reliable methods, including cell count and viability measurement, extracellular metabolite measurement, and the measurement of physicochemical qualities of the cultivation medium. These methods are sufficient for monitoring of process performance, but rarely give insight into the actual physiological states of the cell culture. However, understanding of the latter is essential for optimization of bioprocess development. Our study used LC-MS metabolomics as a tool for additional resolution of bioprocess monitoring and was designed at three bioreactors scales (10 L, 100 L, and 1,000 L) to gain insight into the basal metabolic states of the Chinese hamster ovary (CHO) cell culture during fed-batch. Metabolites characteristics of the four growth stages (early and late exponential phase, stationary phase, and the phase of decline) were identified by multivariate analysis. Enriched metabolic pathways were then established for each growth phase using the CHO metabolic network model. Biomass generation and nucleotide synthesis were enriched in early exponential phase, followed by increased protein production and imbalanced glutathione metabolism in late exponential phase. Glycolysis became downregulated in stationary phase and amino-acid metabolism increased. Phase of culture decline resulted in rise of oxidized glutathione and fatty acid concentrations. Intracellular metabolic profiles of the CHO fed-batch culture were also shown to be consistent with scale and thus demonstrate metabolomic profiling as an informative method to gain physiological insight into the cell culture states during bioprocess regardless of scale.     

Evidence for the activation of 6-phosphofructo-1-kinase by cAMP-dependent protein kinase in Aspergillus niger

Abstract The change from pentose phosphate pathway to glycolysis plays a significant role in the physiology of Aspergillus niger during the induction of citric acid accumulation. Evidence is shown for the importance of 6-phophofructo-1-kinase in this process since it is activated by phosphorylation. By incubating a purified active form of enzyme together with commercially available alkaline phosphatase, 6-phosphofructo-1-kinase activity was lost after a certain time suggesting that the enzyme was dephosphorylated. Inactive 6-phosphofructo-1-kinase could be isolated from the cells in the early stage of growth in a high citric acid yielding medium. The enzyme was 'in vitro' activated by isolated protein kinase in the presence of cAMP, ATP and Mg²⁺ ions. Additional evidence for covalent phosphorylation of inactive 6-phosphofructo-1-kinase was obtained by incubating both enzymes together with labelled [ γ −³²P]ATP. The activating enzyme was partially purified from A. niger mycelium.