Hepatic Insulin-Positive Cells and Major Transcription Factors (PDX1, MAFA,NGN3) in Rat Models of Type 1 and Type 2 Diabetes Mellitus

Journal of Evolutionary Biochemistry and Physiology - Due to a high occurrence of diabetes mellitus (DM) and its complications, insulin-positive cells detected in different organs are of great...     

Prion Properties of Alpha-Synuclein

Molecular Biology - The prion properties of alpha-synuclein, a key aggregating protein involved in the pathogenesis of so-called synucleinopathies, including Parkinson’s disease (PD),...     

Rickettsiaceae, rickettsia-like endosymbionts, and the origin of mitochondria

Accumulating evolutionary data point to a monophyletic origin of mitochondria from the order Rickettsiales. This large group of obligate intracellular -Proteobacteria includes the family Rickettsiaceae and several rickettsia-like endosymbionts (RLEs). Detailed phylogenetic analysis of small subunit (SSU) rRNA and chaperonin 60 (Cpn60) sequences testify to polyphyly of the Rickettsiales, and consistently indicate a sisterhood of Rickettsiaceae and mitochondria that excludes RLEs. Thus RLEs are considered as the nearest extant relatives of an extinct last common ancestor of mitochondria and rickettsiae. Phylogenetic inferences prompt the following assumptions. (1) Mitochondrial origin has been predisposed by the long-term endosymbiotic relationship between rickettsia-like bacteria and proto-eukaryotes, in which many endosymbiont genes have been lost while some indispensable genes have been transferred to the host genome. (2) The obligate dependence of rickettsiae upon a eukaryotic host rests on the import of proteins encoded by these transferred genes.The nature of a proto-eukaryotic cell still remains elusive. The divergence of Rickettsiaceae and mitochondria based on Cpn60, and the evolutionary history of two aminoacyl-tRNA synthetases favor the hypothesis that it was a chimera created by fusion of an archaebacterium and a eubacterium not long before an endosymbiotic event. These and other, mostly biochemical data suggest that all the mitochondrion-related organelles, i.e., both aerobically and anaerobically respiring mitochondria and hydrogenosomes, have originated from the same RLE, while hydrogenosomal energy metabolism may have a separate origin resulting from a eubacterial fusion partner.     

fgfr3 and regionalization of anterior neural tube in zebrafish

Here we describe the isolation of the zebrafish fgfr3 gene, its structure and chromosomal location. Expression in wild type embryos occurs in the axial mesoderm, the diencephalon, the anterior hindbrain and the anterior spinal cord. In the hindbrain, a differential expression of fgfr3 was detected at several levels of intensity, with the highest expression in the posterior rhombomere 1 that is morphologically distinct from the anterior part, which develops into the cerebellum. Further, analysis of fgfr3 expression in mutants deficient in the formation of the midbrain-hindbrain boundary (MHB), noi(-/-) and ace(-/-), demonstrated that in the absence of Pax2.1 and FGF8 activity, the expression domains of FGFR3 expand into the MHB, tegmentum, cerebellum and optic tectum, which are the affected structures in these mutants.     

Suggested mitochondrial ancestry of nonmitochondrial ATP/ADP carrier

One of the major evolutionary events that transformed an endosymbiotic bacterium into a mitochondrion was the acquisition of the ATP/ADP carrier (AAC) in order to supply the host with respiration-derived ATP. Along with the mitochondrial carrier, an unrelated carrier is known, which is characteristic of intracellular chlamydiae, plastids, parasitic intracellular eukaryote Encephalitozoon cuniculi, and the genus Rickettsia of obligate endosymbiotic α-proteobacteria. This nonmitochondrial carrier was recently described in rickettsia-like endosymbionts (RLE), a group of obligate intracellular bacteria classified with the order Rickettsiales, which have diverged after free-living α-proteobacteria but before sister groups of the Rickettsiaceae assemblage (true rickettsiae) and mitochondria. Published controversial phylogenetic data on nonmitochondrial AAC were re-analyzed in the present work, using both DNA and protein sequences and various methods including Bayesian analysis. The data presented are consistent with the classic endosymbiont theory for the origin of mitochondria and suggest that even the last but one common ancestor of rickettsiae and organelles was an endosymbiotic bacterium, in which AAC first originated.     

One step forward: the use of transgenic zebrafish tumor model in drug screens

The zebrafish (Danio rerio) has been an experimental model in the developmental biology and toxicology since the 1950s. In recent years, with the aid of transgenic technology, it has also gained an increasing popularity to model human diseases, including various cancers. As a feasible vertebrate model for large-scale chemical screens, the zebrafish has also given us a new option for the search of potential anticancer drugs. It is hopeful that in the near future with automation and analytical tools, drug development processes will be significantly shortened for quick and effective identification of candidate drugs.     

Zebrafish transgenic Enhancer TRAP line database (ZETRAP)

Background  

The zebrafish, Danio rerio, is used as a model organism to study vertebrate genetics and development. An effective enhancer trap (ET) in zebrafish using the Tol2 transposon has been demonstrated. This approach could be used to study embryogenesis of a vertebrate species in real time and with high resolution.     

Apoptosis of peripheral blood lymphocytes in patients with <Emphasis Type="Italic">LRRK2</Emphasis>-associated Parkinson’s disease

Mutations in the Leucine Reach Repeat Kinase 2 (LRRK2) gene are the most frequent cause of familial Parkinson’s disease (PD). Although the precise physiological and pathological roles of LRRK2 are unclear, a direct link between mutant LRRK2 and programmed cell death (apoptosis) has been suggested. By using flow cytometry (PI+Annexin V(FITC)), we showed an increased level of spontaneous lymphocyte apoptosis in patients with LRRK2-associated PD compared to controls after 24 h (p < 0.016) and 48 h (p < 0.031) of incubation (5% CO₂, 37°C). We found an increased FAS mRNA level in peripheral blood lymphocytes of patients with LRRK2-associated PD compared to controls (p < 0.05) and to sporadic PD (sPD) (p < 0.002). A significant difference in FAS expression between patients with LRRK2-associated PD and controls remained after 3 years and was detected after 1 and 24 h during lymphocyte incubation (p < 0.03 and 0.05, respectively). Increased spontaneous lymphocyte apoptosis, along with increased FAS expression, in patients with LRRK2-associated PD suggests that LRRK2 mutations may lead to preferable activation of extrinsic apoptotic way.