[Nuclear receptors PPAR as a drug target in metabolic disorders]. / Receptory jadrowe PPAR jako miejsce dzialania leków w zaburzeniach metabolicznych.

Nuclear receptors regulate many basic cellular processes and their malfunction can lead to serious consequences including metabolic disorders, obesity and type 2 diabetes. Among many nuclear receptor families, the best known for their therapeutic use are the PPARs. These are key transcription factors determining, proper cellular metabolism of glucose and lipids, tissue sensitivity to insulin, appropriate immune responses including inflammatory processes and finally cell division and differentiation. Currently two types of PPAR activators are in medical use: in the therapy of type 2 diabetes--thiazolidinediones (TZDs), which act via PPARgamma receptors and in the treatment of dyslipidemia-fibrates, which act via PPARalpha receptors. The search for new drugs acting through PPAR mechanism consists in the design of new molecules with tissue specific proprieties, which would selectively bind and modulate the activity of appropriate receptors, thus reducing the number of adverse events typically observed with the use of full agonists. These molecules have been named selective nuclear receptor modulators (SNuRMs).

The genome sequence of the North-European cucumber (Cucumis sativus L.) unravels evolutionary adaptation mechanisms in plants.

Cucumber (Cucumis sativus L.), a widely cultivated crop, has originated from Eastern Himalayas and secondary domestication regions includes highly divergent climate conditions e.g. temperate and subtropical. We wanted to uncover adaptive genome differences between the cucumber cultivars and what sort of evolutionary molecular mechanisms regulate genetic adaptation of plants to different ecosystems and organism biodiversity. Here we present the draft genome sequence of the Cucumis sativus genome of the North-European Borszczagowski cultivar (line B10) and comparative genomics studies with the known genomes of: C. sativus (Chinese cultivar--Chinese Long (line 9930)), Arabidopsis thaliana, Populus trichocarpa and Oryza sativa. Cucumber genomes show extensive chromosomal rearrangements, distinct differences in quantity of the particular genes (e.g. involved in photosynthesis, respiration, sugar metabolism, chlorophyll degradation, regulation of gene expression, photooxidative stress tolerance, higher non-optimal temperatures tolerance and ammonium ion assimilation) as well as in distributions of abscisic acid-, dehydration- and ethylene-responsive cis-regulatory elements (CREs) in promoters of orthologous group of genes, which lead to the specific adaptation features. Abscisic acid treatment of non-acclimated Arabidopsis and C. sativus seedlings induced moderate freezing tolerance in Arabidopsis but not in C. sativus. This experiment together with analysis of abscisic acid-specific CRE distributions give a clue why C. sativus is much more susceptible to moderate freezing stresses than A. thaliana. Comparative analysis of all the five genomes showed that, each species and/or cultivars has a specific profile of CRE content in promoters of orthologous genes. Our results constitute the substantial and original resource for the basic and applied research on environmental adaptations of plants, which could facilitate creation of new crops with improved growth and yield in divergent conditions.

The construction and characteristics of a BAC library for Cucumis sativus L. 'B10'.

Cloning using bacterial artificial chromosomes (BACs) can yield high quality genomic libraries, which are used for the physical mapping, identification and isolation of genes, and for gene sequencing. A BAC genomic library was constructed from high molecular weight DNA (HMW DNA) obtained from nuclei of the cucumber (Cucumis sativus L. cv. Borszczagowski; B10 line). The DNA was digested with the HindIII restriction enzyme and ligated into the pCC1BAC vector. The library consists of 34,560 BAC clones with an average insert size of 135 kb, and 12.7x genome coverage. Screening the library for chloroplast and mitochondrial DNA content indicated an exceptionally low 0.26% contamination with chloroplast DNA and 0.3% with mitochondrial DNA.