How many markers or how many alleles per system are appropriate in zygosity testing?

Due to the development in DNA-PCR-technique more and more systems with a high number of alleles have been established in twin diagnosis. Because of their high effectiveness in resolving of genetic questions it is not amazing that some authors have postulated the thesis that typing of 5 to 10 DNA-PCR systems can prove monozygosity. For this paper the use of different systems (conventional and PCR systems) has been tested for twin diagnosis and the observed effects are discussed.     

How many signal peptides are there in bacteria?

Over the last 5 years proteogenomics (using mass spectroscopy to identify proteins predicted from genomic sequences) has emerged as a promising approach to the high‐throughput identification of protein N‐termini, which remains a problem in genome annotation. Comparison of the experimentally determined N‐termini with those predicted by sequence analysis tools allows identification of the signal peptides and therefore conclusions on the cytoplasmic or extracytoplasmic (periplasmic or extracellular) localization of the respective proteins. We present here the results of a proteogenomic study of the signal peptides in Escherichia coli K‐12 and compare its results with the available experimental data and predictions by such software tools as SignalP and Phobius. A single proteogenomics experiment recovered more than a third of all signal peptides that had been experimentally determined during the past three decades and confirmed at least 31 additional signal peptides, mostly in the known exported proteins, which had been previously predicted but not validated. The filtering of putative signal peptides for the peptide length and the presence of an eight‐residue hydrophobic patch and a typical signal peptidase cleavage site proved sufficient to eliminate the false‐positive hits. Surprisingly, the results of this proteogenomics study, as well as a re‐analysis of the E. coli genome with the latest version of SignalP program, show that the fraction of proteins containing signal peptides is only about 10%, or half of previous estimates.     

Interpreting ‘favourable conservation status’ for large carnivores in Europe: how many are needed and how many are wanted?

The EU Habitats Directive is a key biodiversity conservation instrument. It contains legal obligations for the 28 EU member states in order to safeguard a ‘favourable conservation status’ (FCS) for selected species and habitat types. The crucial FCS concept itself, however, remains subject to considerable confusion regarding its proper interpretation and operationalization, impairing the Directive’s effective implementation. Diminishing this confusion is the purpose of this review. It focuses specifically on large carnivores—wolf (Canis lupus), brown bear (Ursus arctos), Eurasian lynx (Lynx lynx) and wolverine (Gulo gulo). These pose particular challenges, given their low densities, transboundary populations, and human-wildlife conflict potential. Large carnivores are also the only species for which specific guidance has been adopted by the European Commission—and subsequently contested. Our methodology combines legal analysis with an understanding of the species’ ecology and associated social, economic and cultural dimensions. We analyze the methods and processes through which EU law is interpreted, implemented, and enforced, by member states, European Commission, and EU Court of Justice—which is the ultimate authority regarding EU law interpretation. On that basis, we engage three particularly complex interpretation questions which are also of great practical significance: (1) the appropriate scale to achieve FCS (national or transboundary population level); (2) the respective roles of demographic, genetic and ecological factors in determining FCS; and (3) the use of extinction versus carrying capacity as benchmark. Regarding these questions, we identify approaches that are workable and effective, as well as likely to be endorsed by the EU Court.     

Quantifying HDL proteins by mass spectrometry: how many proteins are there and what are their functions?

Introduction: Many lines of evidence indicate that low levels of HDL cholesterol increase the risk of cardiovascular disease (CVD). However, recent clinical studies of statin-treated subjects with established atherosclerosis cast doubt on the hypothesis that elevating HDL cholesterol levels reduces CVD risk.

Areas covered: It is critical to identify new HDL metrics that capture HDL’s proposed cardioprotective effects. One promising approach is quantitative MS/MS-based HDL proteomics. This article focuses on recent studies of the feasibility and challenges of using this strategy in translational studies. It also discusses how lipid-lowering therapy and renal disease alter HDL’s functions and proteome, and how HDL might serve as a platform for binding proteins with specific functional properties.

Expert commentary: It is clear that HDL has a diverse protein cargo and that its functions extend well beyond its classic role in lipid transport and reverse cholesterol transport. MS/MS analysis has demonstrated that HDL might contain >80 different proteins. Key challenges are demonstrating that these proteins truly associate with HDL, are functionally important, and that MS-based HDL proteomics can reproducibly detect biomarkers in translational studies of disease risk.     

Chagas heart disease pathogenesis: one mechanism or many?

Chagas heart disease (CHD), caused by the protozoan parasite Trypanosoma cruzi, is the leading cause of infectious myocarditis in the world. The etiology of CHD is unclear and multiple mechanisms have been proposed to explain the pathogenesis of the disease. This review describes the proposed mechanisms of CHD pathogenesis and evaluates the historical significance and evidence supporting each. Although the majority of CHD-related pathologies are currently attributed to parasite persistence in the myocardium and autoimmunity, there is strong evidence that CHD develops as a result of additive and even synergistic effects of several distinct mechanisms rather than one factor.     

How many fold types of protein are there in nature?

Many protein structures have now been determined and reveal that protein molecules can adopt the same fold despite having very different sequences. It has been suggested that, owing to different stereochemical constraints, the number of ways that a sequence can fold may be limited. Therefore, it is reasonable to ask how many fold types exist in nature. Several groups have tackled this problem with very different results. In the present study, a novel statistical sampling approach is used to reestimate this number. The results suggest that the number of protein folds in nature is probably several hundreds. © 1996 Wiley-Liss, Inc.     

Why are there so many carbohydrate-active enzyme-related genes in plants?

Plants contain far more carbohydrate-active enzyme-encoding genes than any other organism sequenced to date. The extremely large number of glycosidase and glycosyltransferase-related genes in plant genomes can be explained by the complex structure of the plant cell wall, by ancient genome duplication and by recent local duplications, but also by the recent emergence of novel and unrelated protein functions based on widely available pre-existing scaffolds.     

SNARE complexes and neuroexocytosis: how many, how close?

Regulated secretion is an essential process in all eukaryotic cells. The release of molecules contained inside exocytic granules and synaptic vesicles is mediated by the assembly of a SNARE complex formed by the coil-coiling of three proteins: SNAP-25, syntaxin and VAMP/synaptobrevin. It seems that SNARE complexes assemble together in rosette-shaped super-complexes but there is controversy on the actual number (N) of copies of SNARE complexes that are necessary to mediate exocytosis. We discuss attempts to determine the value of N and suggest that N varies with the type of exocytic vesicles. In addition, we propose that the N value in neuroexocytosis can be estimated by the comparative use of different types of botulinum neurotoxins.     

Nucleosome remodeling: one mechanism, many phenomena?

The term 'nucleosome remodeling' subsumes a large number of energy-dependent alterations of canonical nucleosome structure, catalyzed by dedicated ATPases in large multiprotein complexes. The importance of these factors for gene regulation and other processes with chromatin substrate have emerged from genetic studies. Mechanistic analyses of nucleosome remodeling by different enzymes provided a diverse, almost confusing phenomenology of ATP-dependent derangement of nucleosomes in vitro, suggesting that different remodeling machines follow different strategies to disrupt histone-DNA interactions. This review explores the alternative possibility that the rich phenomenology of nucleosome remodeling may be brought about by variations of one basic remodeling reaction.     

Canine babesiosis in Europe: how many diseases?

Babesiosis, recognized since ancient times as an important disease of livestock and more recently as an emerging disease in dogs worldwide, is caused by intraerythrocytic protozoa of the genus Babesia and is transmitted by ticks. The pathophysiology of canine babesiosis has been extensively studied but many questions remain unanswered, especially regarding the diversity of disease manifestations in different European countries. Continued investigation of the similarities and differences in host-parasite interplay in canine babesiosis in different European countries should lead to a better understanding of the disease process, potentially leading to better prediction of disease outcome and the development of new treatment modalities. From the European point of view it is important to conduct these studies on Babesia canis.     

Phosphorylation during mitosis: How many kinases are out there?

Comment on: Rizkallah R, et al. Cell Cycle 2011; 10: 3327-36.     

How many species of cichlid fishes are there in African lakes?

The endemic cichlid fishes of Lakes Malawi, Tanganyika and Victoria are textbook examples of explosive speciation and adaptive radiation, and their study promises to yield important insights into these processes. Accurate estimates of species richness of lineages in these lakes, and elsewhere, will be a necessary prerequisite for a thorough comparative analysis of the intrinsic and extrinsic factors influencing rates of diversification. This review presents recent findings on the discoveries of new species and species flocks and critically appraises the relevant evidence on species richness from recent studies of polymorphism and assortative mating, generally using behavioural and molecular methods. Within the haplochromines, the most species-rich lineage, there are few reported cases of postzygotic isolation, and these are generally among allopatric taxa that are likely to have diverged a relatively long time in the past. However, many taxa, including many which occur sympatrically and do not interbreed in nature, produce viable, fertile hybrids. Prezygotic barriers are more important, and persist in laboratory conditions in which environmental factors have been controlled, indicating the primary importance of direct mate preferences. Studies to date indicate that estimates of alpha (within-site) diversity appear to be robust. Although within-species colour polymorphisms are common, these have been taken into account in previous estimates of species richness. However, overall estimates of species richness in Lakes Malawi and Victoria are heavily dependent on the assignation of species status to allopatric populations differing in male colour. Appropriate methods for testing the specific status of allopatric cichlid taxa are reviewed and preliminary results presented.