Martian channels and the search for extraterrestrial life

Summary The origin of the channels on Mars has been a subject of intense interest since they were first recognized on early Mariner 9 images (Driscoll, 1972; Masursky, 1973). Their presence on the planet, and their striking resemblance to terrestrial flood channels related to glacial outbursts or to dendritic river systems has suggested to most investigators (Baker, 1974, 1977; Nummedal, 1978; Carr, 1979; Masursky et al., 1977) that they were formed by running water. Because life as we know it is dependent on water, the discovery by the Mariner cameras, of watercut channels and volcanoes as a source for water, and water ice in the residual north polar cap by Viking, has reaffirmed the choice of Mars as the best target for the search for extraterrestrial life.     

Bioinformatic-driven search for metabolic biomarkers in disease

The search and validation of novel disease biomarkers requires the complementary power of professional study planning and execution, modern profiling technologies and related bioinformatics tools for data analysis and interpretation. Biomarkers have considerable impact on the care of patients and are urgently needed for advancing diagnostics, prognostics and treatment of disease. This survey article highlights emerging bioinformatics methods for biomarker discovery in clinical metabolomics, focusing on the problem of data preprocessing and consolidation, the data-driven search, verification, prioritization and biological interpretation of putative metabolic candidate biomarkers in disease. In particular, data mining tools suitable for the application to omic data gathered from most frequently-used type of experimental designs, such as case-control or longitudinal biomarker cohort studies, are reviewed and case examples of selected discovery steps are delineated in more detail. This review demonstrates that clinical bioinformatics has evolved into an essential element of biomarker discovery, translating new innovations and successes in profiling technologies and bioinformatics to clinical application.     

Proteomic approaches in the search for disease biomarkers

Significant technological advances in protein chemistry, physics and computer sciences in the last two decades have greatly improved protein separation methodologies, such as electrophoresis and chromatography, and have established mass spectrometry (MS) as an indispensable tool for protein study. The goal of this review is to provide a brief overview of the recent improvements in these methodologies and present examples from their application in proteome analysis and search for disease biomarkers.     

The search for novel diagnostic and prognostic biomarkers in cholangiocarcinoma

The poor prognosis of cholangiocarcinoma (CCA) is in part due to late diagnosis, which is currently achieved by a combination of clinical, radiological and histological approaches. Available biomarkers determined in serum and biopsy samples to assist in CCA diagnosis are not sufficiently sensitive and specific. Therefore, the identification of new biomarkers, preferably those obtained by minimally invasive methods, such as liquid biopsy, is important. The development of innovative technologies has permitted to identify a significant number of genetic, epigenetic, proteomic and metabolomic CCA features with potential clinical usefulness in early diagnosis, prognosis or prediction of treatment response. Potential new candidates must be rigorously evaluated prior to entering routine clinical application. Unfortunately, to date, no such biomarker has achieved validation for these purposes. This review is an up-to-date of currently used biomarkers and the candidates with promising characteristics that could be included in the clinical practice in the next future. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.     

A search for protein biomarkers links olfactory signal transduction to social immunity

Background

The Western honey bee (Apis mellifera L.) is a critical component of human agriculture through its pollination activities. For years, beekeepers have controlled deadly pathogens such as Paenibacillus larvae, Nosema spp. and Varroa destructor with antibiotics and pesticides but widespread chemical resistance is appearing and most beekeepers would prefer to eliminate or reduce the use of in-hive chemicals. While such treatments are likely to still be needed, an alternate management strategy is to identify and select bees with heritable traits that allow them to resist mites and diseases. Breeding such bees is difficult as the tests involved to identify disease-resistance are complicated, time-consuming, expensive and can misidentify desirable genotypes. Additionally, we do not yet fully understand the mechanisms behind social immunity. Here we have set out to discover the molecular mechanism behind hygienic behavior (HB), a trait known to confer disease resistance in bees.

Results

After confirming that HB could be selectively bred for, we correlated measurements of this behavior with protein expression over a period of three years, at two geographically distinct sites, using several hundred bee colonies. By correlating the expression patterns of individual proteins with HB scores, we identified seven putative biomarkers of HB that survived stringent control for multiple hypothesis testing. Intriguingly, these proteins were all involved in semiochemical sensing (odorant binding proteins), nerve signal transmission or signal decay, indicative of the series of events required to respond to an olfactory signal from dead or diseased larvae. We then used recombinant versions of two odorant-binding proteins to identify the classes of ligands that these proteins might be helping bees detect.

Conclusions

Our data suggest that neurosensory detection of odors emitted by dead or diseased larvae is the likely mechanism behind a complex and important social immunity behavior that allows bees to co-exist with pathogens.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-014-1193-6) contains supplementary material, which is available to authorized users.     

Differential proteomics in the search for biomarkers of radiotherapy resistance

The individualization of radiotherapy treatment would be beneficial for cancer patients; however, there are no predictive biomarkers of radiotherapy resistance in routine clinical use. This article describes the body of work in this field where comparative proteomics methods have been used for the discovery of putative biomarkers associated with radiotherapy resistance. A large number of differentially expressed proteins have been reported, mostly from the study of novel radiotherapy-resistant cell lines. Here, we have assessed these putative biomarkers through the discovery, confirmation and validation phases of the biomarker pipeline, and inform the reader on the current status of proteomics-based findings. Suggested avenues for future work are discussed.     

Current status and future prospects in the search for protein biomarkers of immunosenescence

Complex adaptations including changes in cellular redox status, the production of high levels of pro-inflammatory cytokines and alterations in immunity occur as the result of aging of the immune system (immunosenescence). These events are thought to underlie the progression of chronic degenerative diseases of aging, such as atherosclerosis, Type 2 diabetes and Alzheimer’s disease. It is envisaged that identifying early biomarkers of immune aging would aid in identifying individuals at risk of age-related disease and would allow the discovery of novel intervention strategies. Proteomics has emerged as a rapidly expanding and innovative field, investigating protein expression, interaction and function at a global level. Several proteomic strategies, including use of mass spectrometry and non-mass spectrometry-based detection systems (including secondary antibody labeling with fluorescent tags) may be particularly advantageous in identifying biomarkers of immune health. Application of these approaches may identify factors that both contribute to (and define) age-dependent deregulation of the immune system.     

Current status and future prospects in the search for protein biomarkers of immunosenescence

Complex adaptations including changes in cellular redox status, the production of high levels of pro-inflammatory cytokines and alterations in immunity occur as the result of aging of the immune system (immunosenescence). These events are thought to underlie the progression of chronic degenerative diseases of aging, such as atherosclerosis, Type 2 diabetes and Alzheimer's disease. It is envisaged that identifying early biomarkers of immune aging would aid in identifying individuals at risk of age-related disease and would allow the discovery of novel intervention strategies. Proteomics has emerged as a rapidly expanding and innovative field, investigating protein expression, interaction and function at a global level. Several proteomic strategies, including use of mass spectrometry and non-mass spectrometry-based detection systems (including secondary antibody labeling with fluorescent tags) may be particularly advantageous in identifying biomarkers of immune health. Application of these approaches may identify factors that both contribute to (and define) age-dependent deregulation of the immune system.     

How industry is approaching the search for new diagnostic markers and biomarkers

In the diagnostic and the pharmaceutical industry there is a constant need for new diagnostic markers and biomarkers with improved sensitivity and specificity. During the last 5 years, only a few novel diagnostic markers have been introduced into the market. Proteomics technologies are now offering unique chances to identify new candidate markers. Before a marker can be introduced into the market, three successive developmental phases have to be completed: the discovery phase, in which a variety of proteomics technologies are applied to identify marker candidates; the prototype developmental phase, in which immunological assays are established and validated in defined sample collectives; and finally the product development phase, with assay formats suitable for automated platforms. The hurdles that a potential candidate marker has to pass in each developmental phase before reaching the market are considerable. The costs are increasing from phase to phase, and in industry a number of questions concerning the medical need and the potential return on investment have to be answered before a proteomics discovery project is started. In this review, we will cover aspects of all three developmental phases including the repertoire of discovery tools for protein separation as well as giving an outline of modern principles of mass spectrometry for the identification of proteins.     

Progress in the search for circulating biomarkers of nonalcoholic fatty liver disease

Abstract

Context: The definitive standard for the diagnosis of nonalcoholic fatty liver disease (NAFLD) is clinico-pathological correlation, but frequently the only laboratory abnormality is an elevation of serum aminotransferases.

Objective: This has resulted in the search for more specific laboratory biomarkers.

Methods: The literature was searched for novel plasma/serum markers of NAFLD.

Results: Studies reviewed here included histologically-confirmed patients presenting some stage of NAFLD and monitored one or more novel serum/plasma biomarkers.

Conclusion: The most promising application of some of these novel biomarkers for the detection and quantification of NAFLD and particularly NASH appears to be in the combination of several into diagnostic panels.     

Proteomic analysis of traumatic brain injury: the search for biomarkers

Although there are a number of causes of traumatic brain injury (TBI), the armed conflict in Iraq and Afghanistan has brought this disorder to the attention of the global community. A biomarker that would enable army medics to rapidly diagnose the severity of TBI on the battle-field would be a huge asset. Unfortunately, the study of TBI has not historically attracted the proteomic research community's interest as other disorders have, such as cancer. On the positive side, however, many of the analytical and technological challenges that were overcome in the development of biofluid proteomic methods are now being applied to the study of TBI. In this review, we discuss and highlight select examples of discovery-driven proteomic studies focused on finding effective biomarkers for TBI.     

Proteomic analysis of traumatic brain injury: the search for biomarkers

Although there are a number of causes of traumatic brain injury (TBI), the armed conflict in Iraq and Afghanistan has brought this disorder to the attention of the global community. A biomarker that would enable army medics to rapidly diagnose the severity of TBI on the battle-field would be a huge asset. Unfortunately, the study of TBI has not historically attracted the proteomic research community’s interest as other disorders have, such as cancer. On the positive side, however, many of the analytical and technological challenges that were overcome in the development of biofluid proteomic methods are now being applied to the study of TBI. In this review, we discuss and highlight select examples of discovery-driven proteomic studies focused on finding effective biomarkers for TBI.     

Sequential depletion of human serum for the search of osteoarthritis biomarkers

ABSTRACT: BACKGROUND: The field of biomarker discovery, development and application has been the subject of intense interest and activity, especially with the recent emergence of new technologies, such as proteomics-based approaches. In proteomics, search for biomarkers in biological fluids such as human serum is a challenging issue, mainly due to the high dynamic range of proteins present in these types of samples. Methods for reducing the content of most highly abundant proteins have been developed, including immunodepletion or protein equalization. In this work, we report for the first time the combination of a chemical sequential depletion method based in two protein precipitations with acetonitrile and DTT, with a subsequent two-dimensional difference in-gel electrophoresis (2D-DIGE) analysis for the search of osteoarthritis (OA) biomarkers in human serum. The depletion method proposed is non-expensive, of easy implementation and allows fast sample throughput. RESULTS: Following this workflow, we have compared sample pools of human serum obtained from 20 OA patients and 20 healthy controls. The DIGE study led to the identification of 16 protein forms (corresponding to 14 different proteins) that were significantly (p < 0.05) altered in OA when compared to controls (8 increased and 7 decreased). Immunoblot analyses confirmed for the first time the increase of an isoform of Haptoglobin beta chain (HPT) in sera from OA patients. CONCLUSIONS: Altogether, these data demonstrate the utility of the proposed chemical sequential depletion for the analysis of sera in protein biomarker discovery approaches, exhibit the usefulness of quantitative 2D gel-based strategies for the characterization of disease-specific patterns of protein modifications, and also provide a list of OA biomarker candidates for validation.     

In search of biomarkers for autism: scientific, social and ethical challenges

There is widespread hope that the discovery of valid biomarkers for autism will both reveal the causes of autism and enable earlier and more targeted methods for diagnosis and intervention. However, growing enthusiasm about recent advances in this area of autism research needs to be tempered by an awareness of the major scientific challenges and the important social and ethical concerns arising from the development of biomarkers and their clinical application. Collaborative approaches involving scientists and other stakeholders must combine the search for valid, clinically useful autism biomarkers with efforts to ensure that individuals with autism and their families are treated with respect and understanding.     

A search for the indianapolis-variant of human alcohol dehydrogenase in liver autopsy samples from North Germany and Japan

Summary Human liver alcohol dehydrogenase (ADH) variants were screened in random autopsy specimens from 53 North German and 34 Japanese individuals. Based on pH-activity profile and electrophoretic pattern, only ADH₂ and ADH₃ variants were detected. In relatively fresh specimens, an anodic band or -ADH band was also observed. The recently reported new molecular forms collectively called ADH_Indianapolis (Bosron et al. 1980) could not be demonstrated and therefore may be confined hitherto only to the American black population.This paper is dedicated to Professor Dr. Dr. H. Baitsch on his 60th birthday