LIMPIC: a computational method for the separation of protein MALDI-TOF-MS signals from noise

Background  

Mass spectrometry protein profiling is a promising tool for biomarker discovery in clinical proteomics. However, the development of a reliable approach for the separation of protein signals from noise is required. In this paper, LIMPIC, a computational method for the detection of protein peaks from linear-mode MALDI-TOF data is proposed. LIMPIC is based on novel techniques for background noise reduction and baseline removal. Peak detection is performed considering the presence of a non-homogeneous noise level in the mass spectrum. A comparison of the peaks collected from multiple spectra is used to classify them on the basis of a detection rate parameter, and hence to separate the protein signals from other disturbances.     

Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma

Primary open angle (POAG) and pseudoexfoliative glaucoma (PXG) are the most common primary and secondary forms of glaucoma, respectively. Even though the patho-physiology, aqueous humor composition, risk factors, clinical features, therapy and drug induced ocular surface changes in POAG and PXG have been widely studied, to date information concerning tear protein characterization is lacking. Tears are a source of nourishment for ocular surface tissues and a vehicle to remove local waste products, metabolized drugs and inflammatory mediators produced in several ophthalmic diseases. In glaucoma, the proteomic definition of tears may provide insights concerning patho-physiology of the disease and ocular surface modifications induced by topical therapy. Our study aimed at characterizing protein patterns in tears of patients with medically controlled POAG and PXG. A comparative tears proteomic analysis by label-free LC-MS(E) highlighted differences in the expression of several proteins in the two glaucoma sub-types and control subjects, highlighting inflammation pathways expressed in both diseases. Results were independently reconfirmed by SDS-PAGE and linear MALDI-TOF MS, validating altered levels of Lysozyme C, Lipocalin-1, Protein S100, Immunoglobulins and Prolactin Inducible Protein. Moreover, we found a differential pattern of phosphorylated Cystatin-S that distinguishes the two pathologies. The most relevant results suggest that in both pathologies there may be active inflammation pathways related to the disease and/or induced by therapy. We show, for the first time, tear protein patterns expressed under controlled intraocular pressure conditions in POAG and PXG subjects. These findings could help in the understanding of molecular machinery underlying these ophthalmologic diseases, resulting in early diagnosis and more specific therapy.     

Habitat fragmentation: A long and tangled tale

In this essay: I provide a brief history of habitat fragmentation research; I describe why its “non‐questions” (‘Is habitat fragmentation a big problem for wildlife species?” and, “Are the effects of habitat fragmentation generally negative or positive?”) are important to conservation; I outline my role in tackling these questions; I discuss reasons why the culture of habitat fragmentation research is largely incapable of accepting the answers; and I speculate on the future of habitat fragmentation research.     

Tea, flavonoids and stroke in man and mouse

Background and purpose

To evaluate the strength of the in vivo evidence of relationships between flavonoids and risk of stroke.

Methods

We reviewed the literature more broadly for flavonoids and stroke and conducted an evidence-based review of original publication experiments on tea or tea components on induced coronary occlusion in animal models and on the observational epidemiology on stroke and either tea or flavonoids in man. Each of the studies was evaluated by two independent reviewers. The evidence in total was compared with the Bradford Hill [1] and Stroke Therapy Academic Industry Roundtable (STAIR)¹ quality-assessment criteria [2].

Results

The search of epidemiologic publications revealed 7 cohort studies on flavonoid intake and stroke and 7 cohort studies and 3 case control studies on tea and stroke. In studies of tea there was a consistent protective effect. However, the epidemiologic research on flavonoids and stroke was much less consistent. Eleven animal experiments were identified that examined tea or tea components and stroke relevant sequelae, eight of which reported on infarct volume. All studies demonstrated reduced infarct volumes in animals exposed either to tea extracts, theanine or tea catechins prior to or shortly after reperfusion.

Conclusions

Hill’s criteria of causality are largely met in the case of tea and stroke. A high level of consistency across preclinical studies, of the effect of tea components as single agents effective in reducing stroke volume after middle cerebral artery occlusion, is noted in all rodent models (rat, mouse, and gerbil). Reductions in infarct volume are seen with both tea extracts consumed orally and tea components introduced intra-peritoneally. Observational epidemiology supports this finding in man for tea - the studies are consistent across countries and type of tea and the relative risks are moderately strong. That is not the case for the body of evidence on flavonoid intakes and stroke.     

The impairment of CD8 responses limits the selection of escape mutations in acute hepatitis C virus infection

Evasion from protective CD8 responses by mutations within immunodominant epitopes represents a potential strategy of HCV persistence. To investigate the pathogenetic relevance of this mechanism, a careful search for immunodominant CD8 epitopes was conducted in six patients with chronic evolution of HCV infection by analyzing their global CD8 response with a panel of overlapping synthetic peptides covering the overall HCV sequence and by studying the CD8 frequency by tetramer staining. Immunodominant responses were followed longitudinally from the time of acute onset in relation to the evolution of the epitopic sequences. Although intensity of CD8 responses and frequency of HCV-specific CD8 cells declined over time in all patients, mutations emerged in only three of the six acute patients studied. Variant sequences were less efficiently recognized by CD8 cells than parental epitopes and were poorly efficient in inducing a CD8 response in vitro. CD8 epitopes undergoing mutations were targeted by high avidity CD8 cells more efficient in effector function. Our data support the view that immunodominant CD8 responses are affected by inhibitory mechanisms operating early after infection and that the emergence of escape mutations represents an additional mechanism of virus evasion from those CD8 responses that are functionally preserved.     

A statistical table for the degree of coexistence between two species

Summary The well known Jaccard's association coefficient has been calculated on perfectly random infinite samples of different n size and a statistical table with the corresponding probability values is presented.The drawing for this paper has been prepared by Mr. Armin Coray with a grant of the Swiss National Science Foundation (No. 3.5.581.-0.75)