Parkinson’s disease: what the model systems have taught us so far

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder, for which people above the age of 60 show an increased risk. Although there has been great advancement in understanding the disease-related abnormalities in brain circuitry and development of symptomatic treatments, a cure for PD remains elusive. The discovery of PD associated gene mutations and environmental toxins have yielded animal models of the disease. These models could recapitulate several key aspects of PD, and provide more insights into the disease pathogenesis. They have also revealed novel aspects of the disease mechanism including noncell autonomous events and spreading of pathogenic protein species across the brain. Nevertheless, none of these models so far can comprehensively represent all aspects of the human disease. While the field is still searching for the perfect model system, recent developments in stem cell biology have provided a new dimension to modelling PD, especially doing it in a patient-specific manner. In the current review, we attempt to summarize the key findings in the areas discussed above, and highlight how the core PD pathology distinguishes itself from other neurodegenerative disorders while also resembling them in many aspects.     

Phylogenetic Analysis of Clinically Relevant Fusarium Species in Iran

Mycopathologia - Fungi of the genus Fusarium are well known as major plant pathogens but also cause a broad spectrum of human infections. Sixty-three clinical isolates, collected during...     

Molecular aspects on the interaction of quercetin and its metal complexes with DNA

Flavonoids occupy an important position in chemistry and pharmacology. Various flavonoids, particularly quercetin have potential to form molecular complexes with nucleic acid structure and have attracted recent attention for their prospective clinical and pharmacological utility. This review highlights the properties of quercetin and its different metal complexes as well as their interactions with DNA reported by several research groups. Various analytical techniques were employed including absorbance, fluorescence and circular dichroism spectroscopies, viscosity and voltammetry to provide more details about binding mechanism of these materials with DNA.     

Detection and identification of opportunistic Exophiala species using the rolling circle amplification of ribosomal internal transcribed spacers

Deep infections by melanized fungi deserve special attention because of a potentially fatal, cerebral or disseminated course of disease in otherwise healthy patients. Timely diagnostics are a major problem with these infections. Rolling circle amplification (RCA) is a sensitive, specific and reproducible isothermal DNA amplification technique for rapid molecular identification of microorganisms. RCA-based diagnostics are characterized by good reproducibility, with few amplification errors compared to PCR. The method is applied here to species of Exophiala known to cause systemic infections in humans. The ITS rDNA region of five Exophiala species (E. dermatitidis, E. oligosperma, E. spinifera, E. xenobiotica, and E. jeanselmei) was sequenced and aligned in view of designing specific padlock probes to be used for the detection of single nucleotide polymorphisms (SNPs) of the Exophiala species concerned. The assay proved to successfully amplify DNA of the target fungi at the level of species; while no cross-reactivity was observed. Amplification products were visualized on 1% agarose gels to verify the specificity of probe-template binding. Amounts of reagents were minimized to avoid the generation of false positive results. The sensitivity of RCA may help to improve early diagnostics of these difficult to diagnose infections.     

Preparation, characterization, and DNA binding studies of water-soluble quercetin--molybdenum(VI) complex

DNA binding studies of flavonoids are needed to understand the reaction mechanism and improve drugs that target DNA. Quercetin (Q) is one of the most common flavonoids that can chelate metal ions and interact with double-stranded DNA. In the present work, UV absorption spectrophotometry, viscosimetry, circular dichroism, and fluorescence spectroscopic techniques were employed to study the interaction of water-soluble quercetin--molybdenum(VI) complex [Q-Mo(VI)] with calf thymus DNA. The binding constants (K(b)) for the complex with DNA were estimated to be 2.9?×?10(3) through spectroscopic titrations. Upon addition of the complex, significant decreases were observed in the viscosity of calf thymus DNA. Circular dichroic spectra indicated that there are certain detectable conformational changes in the DNA double helix when complex was added. Further, competitive methylene blue binding studies with fluorescence spectroscopy have shown that the complex can bind to DNA through nonintercalative mode. The experimental results suggest that Q-Mo(VI) binds to DNA via an outside binding mode.     

Normal and Functional TP53 in Genetically Stable Myxoid/Round Cell Liposarcoma

Myxoid/round-cell liposarcoma (MLS/RCLS) is characterized by either the fusion gene FUS-DDIT3 or the less commonly occurring EWSR1-DDIT3 and most cases carry few or no additional cytogenetic changes. There are conflicting reports concerning the status and role of TP53 in MLS/RCLS. Here we analysed four MLS/RCLS derived cell lines for TP53 mutations, expression and function. Three SV40 transformed cell lines expressed normal TP53 proteins. Irradiation caused normal posttranslational modifications of TP53 and induced P21 expression in two of these cell lines. Transfection experiments showed that the FUS-DDIT3 fusion protein had no effects on irradiation induced TP53 responses. Ion Torrent AmpliSeq screening, using the Cancer Hotspot panel, showed no dysfunctional or disease associated alleles/mutations. In conclusion, our results suggest that most MLS/RCLS cases carry functional TP53 genes and this is consistent with the low numbers of secondary mutations observed in this tumor entity.     

Global Spread of Human Chromoblastomycosis Is Driven by Recombinant Cladophialophora carrionii and Predominantly Clonal Fonsecaea Species

Global distribution patterns of Cladophialophora carrionii, agent of human chromoblastomycosis in arid climates of Africa, Asia, Australia, Central-and South-America, were compared with similar data of the vicarious Fonsecaea spp., agents of the disease in tropical rain forests. Population diversities among 73 C. carrionii strains and 60 strains of three Fonsecaea species were analyzed for rDNA ITS, partial β-tubulin, and amplified fragment-length polymorphism (AFLP) fingerprints. Populations differed significantly between continents. Lowest haplotype diversity was found in South American populations, while African strains were the most diverse. Gene flow was noted between the African population and all other continents. The general pattern of Fonsecaea agents of chromoblastomycosis differed significantly from that of C. carrionii and revealed deeper divergence among three differentiated species with smaller numbers of haplotypes, indicating a longer evolutionary history.