6-Hydroxydopamine-induced inhibition of brain catecholamine synthesis without ultrastructural damage

Zusammenfassung Intraventrikulär verabreichtes 6-Hydroxydopamin in Dosen, die keine ultrastrukturellen Hirnveränderungen erzeugen, vermindert bei Ratten die durch¹⁴C-Tyrosin bedingte Zunahme von¹⁴C-Catecholaminen und von desaminierten¹⁴C-Catecholaminmetaboliten im Gehirn. Die¹⁴C-Dopa bedingte Anhäufung von cerebralen¹⁴C-Catecholaminen wird durch Vorbehandlung mit 6-Hydroxydopamin leicht vermindert, während der Anstieg von¹⁴C-Catecholamin-Metaboliten keine signifikante Veränderung erfährt. Es wird geschlossen, dass 6-Hydroxydopamin wahrscheinlich neben einer Verdrängung von Catecholaminen auch eine Hemmung der Hydroxylierung von Tyrosin bewirkt.     

An ultrastructural investigation of the effects of perinatal malnutrition on E-PTA-stained synaptic junctions.

The effect of protein-deficient diet on E-PTA stained synapses in rat cerebral cortex was studied by electron microscopy. No significant difference was observed in synaptic morphology between control and malnourished animals at 35 days postnatal.     

A candidate prostate cancer susceptibility gene at chromosome 17p

It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73).     

Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states

Familial Mediterranean fever (FMF; MIM 249100) is an autosomal recessive disease characterized by recurrent attacks of fever with synovial, pleural or peritoneal inflammation. The disease is caused by mutations in the gene encoding the pyrin protein. Human population studies have revealed extremely high allele frequencies for several different pyrin mutations, leading to the conclusion that the mutant alleles confer a selective advantage. Here we examine the ret finger protein (rfp) domain (which contains most of the disease-causing mutations) of pyrin during primate evolution. Amino acids that cause human disease are often present as wild type in other species. This is true at positions 653 (a novel mutation), 680, 681, 726, 744 and 761. For several of these human mutations, the mutant represents the reappearance of an ancestral amino acid state. Examination of lineage-specific dN/dS ratios revealed a pattern consistent with the signature of episodic positive selection. Our data, together with previous human population studies, indicate that selective pressures may have caused functional evolution of pyrin in humans and other primates.     

Discovery of novel intermediate forms redefines the fungal tree of life

Fungi are the principal degraders of biomass in terrestrial ecosystems and establish important interactions with plants and animals. However, our current understanding of fungal evolutionary diversity is incomplete and is based upon species amenable to growth in culture. These culturable fungi are typically yeast or filamentous forms, bound by a rigid cell wall rich in chitin. Evolution of this body plan was thought critical for the success of the Fungi, enabling them to adapt to heterogeneous habitats and live by osmotrophy: extracellular digestion followed by nutrient uptake. Here we investigate the ecology and cell biology of a previously undescribed and highly diverse form of eukaryotic life that branches with the Fungi, using environmental DNA analyses combined with fluorescent detection via DNA probes. This clade is present in numerous ecosystems including soil, freshwater and aquatic sediments. Phylogenetic analyses using multiple ribosomal RNA genes place this clade with Rozella, the putative primary branch of the fungal kingdom. Tyramide signal amplification coupled with group-specific fluorescence in situ hybridization reveals that the target cells are small eukaryotes of 3-5?μm in length, capable of forming a microtubule-based flagellum. Co-staining with cell wall markers demonstrates that representatives from the clade do not produce a chitin-rich cell wall during any of the life cycle stages observed and therefore do not conform to the standard fungal body plan. We name this highly diverse clade the cryptomycota in anticipation of formal classification.