Ubiquitin Ser65 phosphorylation affects ubiquitin structure,chain assembly and hydrolysis

The protein kinase PINK1 was recently shown to phosphorylate ubiquitin (Ub) on Ser65, and phosphoUb activates the E3 ligase Parkin allosterically. Here, we show that PINK1 can phosphorylate every Ub in Ub chains. Moreover, Ser65 phosphorylation alters Ub structure, generating two conformations in solution. A crystal structure of the major conformation resembles Ub but has altered surface properties. NMR reveals a second phosphoUb conformation in which β5-strand slippage retracts the C-terminal tail by two residues into the Ub core. We further show that phosphoUb has no effect on E1-mediated E2 charging but can affect discharging of E2 enzymes to form polyUb chains. Notably, UBE2R1- (CDC34), UBE2N/UBE2V1- (UBC13/UEV1A), TRAF6- and HOIP-mediated chain assembly is inhibited by phosphoUb. While Lys63-linked poly-phosphoUb is recognized by the TAB2 NZF Ub binding domain (UBD), 10 out of 12 deubiquitinases (DUBs), including USP8, USP15 and USP30, are impaired in hydrolyzing phosphoUb chains. Hence, Ub phosphorylation has repercussions for ubiquitination and deubiquitination cascades beyond Parkin activation and may provide an independent layer of regulation in the Ub system.     

Optimization of mycophenolic acid production in solid state fermentation using response surface methodology

Mycophenolic acid (MPA) can be produced in solid state fermentation. An isolate of Penicillium brevi-compactum ATCC 16024 grown on moist wheat bran produced a titre of 425 mg per kg of wheat bran. Central composite rotatable design and response surface methodology were employed to derive a statistical model for media optimization towards production of mycophenolic acid. Five levels with a five factorial design were adopted. The correlation coefficient was 0.82, ensuring a satisfactory adjustment of the model to the experimental values. This statistical design was very effective in improving the titre of mycophenolic acid up to 3286 mg per kg of wheat bran. Received 24 July 1998/ Accepted in revised form 4 December 1998     

The structure of extracellular heteroglycans in various Cryptococcus species

Extracellular polysaccharides produced by some Cryptococcus species have been structurally investigated. These polymers have identical core structure, which was found to be alpha-1,3-mannan and different degrees of substitution of mannose in the core by xylose and glucuronic acid residues of side chains and different composition of side chains. Heteropolysaccharide from Cr. humicolus, the simplest one, has the same structure as the Cr. neoformans serotype D capsular polysaccharide. The Cr. skinneri polymer proved to be the most branched among Cryptococcus polysaccharides.     

Burden of hereditary diseases in residents of the Sakh republic (Iakutiia)

Summarized data of medical genetic survey of the population of Republic of Sakha (Yakutia) are presented. The number of the population examined constituted 1000700 individuals (including 424500000 of urban and 576,200 of rural population, respectively). Regarding the ethnicity, 33 regions of the Republic examined were at most inhabited by Yakuts (36%) and Russians (55%). A total of 400 families (606 patients) with autosomal dominant, 274 families (369 patients) with autosomal recessive, and 42 families (53 patients) with X-linked pathologies were detected. The segregation analysis performed showed good correlation with the expected type of inheritance for both dominant and recessive diseases. The prevalence rate of monogenic hereditary diseases for rural and urban populations, as well as for solely Yakuts, was calculated. It was shown that weighted average prevalence of dominant (0.68; 1.44) and recessive (0.43; 0.86) disorders in Yakuts was two times higher than in total population examined.     

Congenital deformity of the paw in a captive tiger: case report

Background

Although Morbillivirus and Toxoplasma gondii have emerged as important pathogens for several cetaceans populations over the last 20 years, they have never been identified together in a Mysticete. In particular, morbilliviral infection has been never described in the Mediterranean fin whale population.

Case presentation

On January 2011 an adult male of fin whale (Balaenoptera physalus) stranded along the Tyrrhenian coastline of Italy. During necropsy, tissue samples from heart, skeletal muscle, mesenteric lymph nodes, liver, spleen, lung, and kidney were collected and subsequently analyzed for Morbillivirus and Toxoplasma gondii by microscopic and molecular methods. Following the detailed necropsy carried out on this whale, molecular analysis revealed, for the first time, the simultaneous presence of a Dolphin Morbillivirus (DMV) and T. gondii infection coexisting with each other, along with high organochlorine pollutant concentrations, with special reference to DDT.

Conclusion

This report, besides confirming the possibility for Mysticetes to be infected with DMV, highlights the risk of toxoplasmosis in sea water for mammals, already immunodepressed by concurrent factors as infections and environmental contaminants.