Intersection of selenoproteins and kinase signalling

The small, obscure group of selenoprotein oxidoreductases and the huge clan of kinases, the workhorses of cellular signalling, are rarely discussed together. Focusing on selenoproteins of unknown structures, we predict a thioredoxin-like fold for the Selenoprotein N (SelN) family and use the structure to rationalise effects of the muscular myopathy-linked mutations in the gene coding SelN. Discussing the recent prediction of a protein kinase-like domain in the Selenoprotein O (SelO), we reiterate evidence for an oxidoreductase function alongside the predicted kinase domain. Thus, we propose that SelO, the strongly conserved kinase-cum-tentative-oxidoreductase may reflect oxidoreductase regulation of kinase networks. Also, we use bibliometric and systems biology approach to explore the kinase–selenoprotein relationships that begin to emerge from the literature. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012).     

Human Alveolar Echinococcosis in Poland: 1990–2011

Background

Alveolar echinococcosis (AE) caused by Echinococcus multilocularis infections is a dangerous old disease in the Northern Hemisphere. The aim of the paper was to collect and analyze data on human AE in Poland in the last two decades.

Methodology/Principal Findings

The sources of data were both the cases officially registered and detected by an active field and laboratory surveillance. The cases were verified by clinical, epidemiological, and laboratory criteria. Altogether 121 human cases of AE were detected. Among these 83 (68,6%) cases were classified as confirmed, 16 as probable and 22 as possible. During the two decades a continuous increase in detection rate was noticed. The cases were 6–82 years old at the time of diagnosis (mean - 47.7 years). Sex ratio M/F was 0.86/1.0. The AE was fatal in 23 (19%) patients (mean age at death - 54.1 years). Family agglomeration of AE was found in 4 foci, involving 9 patients. Seventy six of the cases were diagnosed in an advanced stage of disease. In all cases the liver was the primary location of AE. In 30 (24.8%) patients a spread to other organs was observed. Ninety four of the patients were treated with albendazole. In 73 (60%) patients a surgical operation was performed, including 15 liver transplantations.

Conclusions/Significance

The studies confirmed that AE is an emerging disease in Poland, which is the fourth country in Europe with over 120 cases detected. The results also indicate the need of a wider national programme for implementation of screening in the highest AE risk areas (north-eastern Poland) with an effort to increase the public awareness of the possibility of contracting E. multilocularis, and above all, training of the primary care physicians in the recognition of the risk of AE to allow for an early detection of this dangerous disease.     

In silico characterization of a novel pathogenic deletion mutation identified in XPA gene in a Pakistani family with severe xeroderma pigmentosum

Background

Xeroderma Pigmentosum (XP) is a rare skin disorder characterized by skin hypersensitivity to sunlight and abnormal pigmentation. The aim of this study was to investigate the genetic cause of a severe XP phenotype in a consanguineous Pakistani family and in silico characterization of any identified disease-associated mutation.

Results

The XP complementation group was assigned by genotyping of family for known XP loci. Genotyping data mapped the family to complementation group A locus, involving XPA gene. Mutation analysis of the candidate XP gene by DNA sequencing revealed a novel deletion mutation (c.654del A) in exon 5 of XPA gene. The c.654del A, causes frameshift, which pre-maturely terminates protein and result into a truncated product of 222 amino acid (aa) residues instead of 273 (p.Lys218AsnfsX5). In silico tools were applied to study the likelihood of changes in structural motifs and thus interaction of mutated protein with binding partners. In silico analysis of mutant protein sequence, predicted to affect the aa residue which attains coiled coil structure. The coiled coil structure has an important role in key cellular interactions, especially with DNA damage-binding protein 2 (DDB2), which has important role in DDB-mediated nucleotide excision repair (NER) system.

Conclusions

Our findings support the fact of genetic and clinical heterogeneity in XP. The study also predicts the critical role of DDB2 binding region of XPA protein in NER pathway and opens an avenue for further research to study the functional role of the mutated protein domain.     

Corpora amylacea from multiple sclerosis brain tissue consists of aggregated neuronal cells

In this report, we describe proteomic analysis of corpora amylacea collected by postmortem laser microdissection from multiple sclerosis (MS) brain lesions. Using low level protein loads (about 30 microg), a combination of two-dimensional electrophoresis with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and database interrogations we identified 24 proteins of suspected neuronal origin. In addition to major cytoskeletal proteins like actin, tubulin, and vimentin, we identified a variety of proteins implicated specifically in cellular motility and plasticity (F-actin capping protein), regulation of apoptosis and senescence (tumor rejection antigen-1, heat shock proteins, valosin-containing protein, and ubiquitin-activating enzyme E1), and enzymatic pathways (glyceraldehyde-3-dehydrogenase, protein disulfide isomerase, protein disulfide isomerase related protein 5, lactate dehydrogenase). Samples taken from regions in the vicinity of corpora amylacea showed only traces of cellular proteins suggesting that these bodies may represent remnants of neuronal aggregates with highly polymerized cytoskeletal material. Our data provide evidence supporting the concept that biogenesis of corpora amylacea involves degeneration and aggregation of cells of neuronal origin.     

Optimized perfusion‐based CUBIC protocol for the efficient whole‐body clearing and imaging of rat organs

Whole‐organ and whole‐body optical tissue clearing methods allowing imaging in 3 dimensions are an area of profound research interest. Originally developed to study nervous tissue, they have been successfully applied to all murine organs, yet clearing and imaging of rat peripheral organs is less advanced. Here, a modification of CUBIC clearing protocol is presented. It provides a rapid and simple approach to clear the entire adult rat organism and thus all organs within as little as 4 days. Upgraded perfusion‐based rat CUBIC protocol preserves both anatomical structure of organs and signal from proteinaceous fluorophores, and furthermore is compatible with antibody staining. Finally, it enables also volumetric cells analyses and is tailored for staining of calcium deposits within unsectioned soft tissues.      

Cladoceran Densities,Day-to-Day Variability in Food Selection by Smelt,and the Birth-Rate-Compensation Hypothesis

Late-evening gut inspection of a dominant planktivore (smelt) and evaluation of densities, fecundities, and body-size distributions in dominant zooplankton prey (cladocerans) were made in day-to-day sequences in June–July (24 days in 1999 and 24 days in 2000). This was conducted as a field test of the hypothesis that species-specific population densities in cladocerans result from size-selective predation by a dominant fish assumed to be a general predator, switching from one prey to another as relative abundance changes. Little of the expected coincidence has been revealed between population density declines and increased numbers of a given prey in smelt diet. However, the data were consistent with the notion that fish would switch from one prey to another depending on the prey relative abundance (the number of prey a fish would see in its reaction field volume). Each cladoceran population fluctuated around its species-specific density level, lower or higher, depending on individual susceptibility to smelt predation, from 0.2 ind. l^–1 in large-bodied Daphnia hyalina and Leptodora kindtii, to 30.0 ind. l^–1 in small-bodied Daphnia cucullata andBosmina thersites. In spite of high fish-to-fish and day-to-day variability in both smelt diet and smelt selectivity for different prey, all cladocerans (also copepods and midge larvae) were equally persistent in smelt diet, and smelt selectivity was similar for small- and large-bodied prey categories, but lower for elongated-(Daphnia, Diaphanosoma) than for compact-body (Bosmina, Chydorus) species, when integrated for the entire sampling time. Closer examination of D. cucullata and B. thersites revealed strong smelt selection for later instars and females with greater clutches, showing that size distribution in a cladoceran population might be structured by fish predation in a similar way to that a cladoceran community (species relative abundance) is structured in a lake habitat. The birth-rate-compensation hypothesis is offered to explain why the value of food selectivity index in a planktivorous fish would remain the same for alternate prey categories with similar life-history traits, unless they differ in susceptibility to predation before the time of first reproduction.