Diterpenes,taxonomic markers?

The chemosystematic potential of the 15 more common diterpene types in vascular plants was evaluated. Oxidation levels and skeletal specializations indicate diterpene biosynthesis to involve contrasting modes in pteridophytes and angiosperms on one hand, and in gymnosperms on the other. In angiosperm lineages diterpene diversification accompanies trends towards increase of herbaceousness and depletion of polyphenols, i.e., towards evolutionary advance. Nevertheless, even closely related families may display disjunctions of diterpene type and substitution. Thus the taxonomic value of this metabolic class remains confined to single (advanced) families.Part 36 in the series Plant chemosystematics and phylogeny. For Part 35 seeBorin & Gottlieb (1993). Based in part on the doctoral thesis presented byM. R. Figueiredo to Universidade de São Paulo in 1992.     

Steroids,taxonomic markers?

The use of steroids as taxonomic markers of the angiosperms was evaluated. To this end evolutionary advancement parameters, based on oxidation state and skeletal specialization of each steroid were calculated. The averages of these values for the steroids registered for a particular plant group were assumed to represent the evolutionary parameters of the plant group. Positive correlations of these chemical parameters and of morphological Sporne indices, as well as of herbacity indices, were observed to constitute a general trend. Furthermore, steroids are not uniformly distributed within a morphologically homogeneous plant group, but are replacement characters. Thus, in spite of their functional importance, steroids can be considered, analogously to many other classes of secondary metabolites, for chemosystematic purposes.Part 35 in the series Plant chemosystematics and phylogeny. For Part 34 seeKaplan & al. (1991). Based in part on the MSc. — Thesis presented byBorin (1988) to Universidade de São Paulo. Dedicated to Univ.-Prof. DrF. Ehrendorfer on the occasion of his 65th birthday.     

Potential markers of preeclampsia – a review

Preeclampsia is a leading cause of maternal and fetal/neonatal mortality and morbidity worldwide. The early identification of patients with an increased risk for preeclampsia is therefore one of the most important goals in obstetrics. The availability of highly sensitive and specific physiologic and biochemical markers would allow not only the detection of patients at risk but also permit a close surveillance, an exact diagnosis, timely intervention (e.g. lung maturation), as well as simplified recruitment for future studies looking at therapeutic medications and additional prospective markers. Today, several markers may offer the potential to be used, most likely in a combinatory analysis, as predictors or diagnostic tools. We present here the current knowledge on the biology of preeclampsia and review several biochemical markers which may be used to monitor preeclampsia in a future, that, we hope, is not to distant from today.     

Immunoglobulin haplotypes: markers of reproductive success?

Immunoglobulin haplotypes are highly polymorphic and are useful for analyses of both macro- and microdifferentiation of populations. The origins of this diversity are not known, but recent reports suggest strong selection at this locus. Increased rates of first-trimester spontaneous abortions have been reported when parents share GM phenotypes. Reduced fertility has been observed in mixed European descent white and Hutterite populations when both parents share immunoglobulin haplotypes. Population samples with completed family information and GM haplotype data are rare; the objective here is to provide this information on another sample. A sample of 242 Mennonite couples with mothers older than 40 years was divided into 3 groups of matings based on how many haplotypes were shared: 0, 1, or 2. The distribution of mean completed family sizes for the three groups were 3.35 +/- 1.85 (n = 23), 3.47 +/- 1.69 (n = 128), and 3.37 +/- 1.60 (n = 91), respectively; these values were not significantly different (F = 0.145, p = 0.865). The log-rank test was used to compare the time-to-next-birth curves. The intervals between first and later births (2-4 births) were not significantly different for the three subgroups either. There is also only limited evidence for segregation distortion in another sample of 923 offspring (in which at least one parent is heterozygous.     

Malarial parasites as geographical markers in migratory birds?

We tested the hypothesis that malarial parasites (Plasmodium and Haemoproteus) of black-throated blue warblers (Dendroica caerulescens) provide sufficient geographical signal to track population movements between the warbler's breeding and wintering habitats in North America. Our results from 1083 warblers sampled across the species' breeding range indicate that parasite lineages are geographically widespread and do not provide site-specific information. The wide distribution of malarial parasites probably reflects postnatal dispersal of their hosts as well as mixing of breeding populations on the wintering range. When compared to geographically structured parasites of sedentary Caribbean songbirds, patterns of malarial infections in black-throated blue warblers suggest that host-malaria dynamics of migratory and sedentary bird populations may be subject to contrasting selection pressures.     

Serum tumor markers in bile duct cancer – a review

Abstract

Context: Bile duct cancer (BDC) is a disease with a very grave prognosis, often diagnosed too late.

Objective: The aim of this review is to evaluate available literature on tumor markers in serum from patients with BDC.

Methods: Using the search words “serum markers”, “bile duct cancer”, “cholangiocarcinoma”, “biomarker” and “tumor marker”, a search was carried out.

Results: Seventy-five studies were included in the review.

Conclusion: CA19-9 is by far the most studied and most promising diagnostic and/or prognostic marker in BDC. But also the different mucins are interesting as new markers of BDC in serum.     

Proteomics-derived cerebrospinal fluid markers of autopsy-confirmed Alzheimer’s disease

The diagnostic performance of several candidate cerebrospinal fluid (CSF) protein biomarkers in neuropathologically confirmed Alzheimer’s disease (AD), non-demented (ND) elderly controls and non-AD dementias (NADD) was assessed. Candidate markers were selected on the basis of initial two-dimensional gel electrophoresis studies or by literature review. Markers selected by the former method included apolipoprotein A-1 (ApoA1), haemopexin (HPX), transthyretin (TTR) and pigment epithelium-derived factor (PEDF), while markers identified from the literature included Aβ1-40, Aβ1-42, total tau, phosphorylated tau, α-1 acid glycoprotein (A1GP), haptoglobin, zinc α-2 glycoprotein (Z2GP) and apolipoprotein E (ApoE). Ventricular CSF concentrations of the markers were measured by enzyme-linked immunosorbent assay (ELISA). The concentrations of Aβ1-42, ApoA1, A1GP, ApoE, HPX and Z2GP differed significantly among AD, ND and NADD subjects. Logistic regression analysis for the diagnostic discrimination of AD from ND found that Aβ1-42, ApoA1 and HPX each had significant and independent associations with diagnosis. The CSF concentrations of these three markers distinguished AD from ND subjects with 84% sensitivity and 72% specificity, with 78% of subjects correctly classified. By comparison, using Aβ1-42 alone gave 79% sensitivity and 61% specificity, with 68% of subjects correctly classified. For the diagnostic discrimination of AD from NADD, only the concentration of Aβ1-42 was significantly related to diagnosis, with a sensitivity of 58%, specificity of 86% and 86% correctly classified. The results indicate that for the discrimination of AD from ND control subjects, measurement of a set of markers including Aβ1-42, ApoA1 and HPX improved diagnostic performance over that obtained by measurement of Aβ1-42 alone. For the discrimination of AD from NADD subjects, measurement of Aβ1-42 alone was superior.     

TGF-β signalling-related markers in cancer patients with bone metastasis

Abstract

We measured transforming growth factor (TGF)-β-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-β inhibitors. Forty-nine patients with bone metastasis were enrolled in the study, including patients with breast (n=23) and prostate cancer (n=15). Plasma TGF-β1 levels were elevated in more than half of the cancer patients (geometric mean 2.63 ng ml^?1) and positively correlated with increased platelet factor 4 (PF4) levels, parathyroid-related protein (PTHrP), von Willebrand Factor (vWF) and interleukin (IL)-10. PBMC were stimulated ex vivo to determine the individual biological variability of an ex vivo assay measuring pSMAD expression. This assay performed sufficiently well to allow its future use in a clinical trial of a TGF-β inhibitor.     

Genomic markers to tailor treatments: waiting or initiating?

The decade since the publication of the Human Genome Project draft has ended with the discovery of hundreds of genomic markers related to diseases and phenotypes. However, the project has not yet delivered on its promise to tailor treatments for individuals. The number of genomic markers in clinical practice is very small. The number of markers to guide treatment decisions is even smaller. In order to speed up discovery and validation of genomic treatment selection markers, we call for considering the brilliant potential of randomized clinical trials. If biomedical research community can collaborate in organizing large-scale consortium of clinical trials associated with well-designed biobanks, these studies would soon act as huge laboratories for investigating genomic medicine; a big step forward towards personalizing medicine.     

Are mapped markers more useful for assessing genetic diversity?

Genetic diversity within populations of organisms and species is commonly measured using molecular-marker data. It has been claimed that more reliable diversity measurements can be obtained using selected genetically mapped markers to ensure that all regions of the genome are represented in the data sets employed. However, this has not been tested. In the present study, using rice (Oryza sativa L.) as a model species, we have shown that the use of unmapped AFLP markers reveals a pattern of diversity that is very similar to that obtained using a range of other marker types and which reflects the known crossability groups within this species. In contrast, we show that use of mapped-marker data can, in some cases, result in highly misleading patterns of diversity; the results obtained are critically related to the choice ofparents used in the cross from which the mapping population was produced. For diversity analyses, we propose that it is appropriate to use unmapped markers provided that the marker-type has been shown to have a wide distribution over the genome. Received: 13 November 1998 / Accepted: 17 June 1999     

Proteomic profiling identifies markers for inflammation-related tumor–fibroblast interaction

Background

Cancer associated fibroblasts are activated in the tumor microenvironment and contribute to tumor progression, angiogenesis, extracellular matrix remodeling, and inflammation.

Methods

To identify proteins characteristic for fibroblasts in colorectal cancer we used liquid chromatography-tandem mass spectrometry to derive protein abundance from whole-tissue homogenates of human colorectal cancer/normal mucosa pairs. Alterations of protein levels were determined by two-sided t test with greater than threefold difference and an FDR of < 0.05. Public available datasets were used to predict proteins of stromal origin and link protein with mRNA regulation. Immunohistochemistry confirmed the localization of selected proteins.

Results

We identified a set of 24 proteins associated with inflammation, matrix organization, TGFβ receptor signaling and angiogenesis mainly originating from the stroma. Most prominent were increased abundance of SerpinB5 in the parenchyme and latent transforming growth factor β-binding protein, thrombospondin-B2, and secreted protein acidic-and-cysteine-rich in the stroma. Extracellular matrix remodeling involved collagens type VIII, XII, XIV, and VI as well as lysyl-oxidase-2. In silico analysis of mRNA levels demonstrated altered expression in the tumor and the adjacent normal tissue as compared to mucosa of healthy individuals indicating that inflammatory activation affected the surrounding tissue. Immunohistochemistry of 26 tumor specimen confirmed upregulation of SerpinB5, thrombospondin B2 and secreted protein acidic-and-cysteine-rich.

Conclusions

This study demonstrates the feasibility of detecting tumor- and compartment-specific protein-signatures that are functionally meaningful by proteomic profiling of whole-tissue extracts together with mining of RNA expression datasets. The results provide the basis for further exploration of inflammation-related stromal markers in larger patient cohorts and experimental models.

     

Constructing a linkage–linkage disequilibrium map using dominant-segregating markers

The relationship between linkage disequilibrium (LD) and recombination fraction can be used to infer the pattern of genetic variation and evolutionary process in humans and other systems. We described a computational framework to construct a linkage–LD map from commonly used biallelic, single-nucleotide polymorphism (SNP) markers for outcrossing plants by which the decline of LD is visualized with genetic distance. The framework was derived from an open-pollinated (OP) design composed of plants randomly sampled from a natural population and seeds from each sampled plant, enabling simultaneous estimation of the LD in the natural population and recombination fraction due to allelic co-segregation during meiosis. We modified the framework to infer evolutionary pasts of natural populations using those marker types that are segregating in a dominant manner, given their role in creating and maintaining population genetic diversity. A sophisticated two-level EM algorithm was implemented to estimate and retrieve the missing information of segregation characterized by dominant-segregating markers such as single methylation polymorphisms. The model was applied to study the relationship between linkage and LD for a non-model outcrossing species, a gymnosperm species, Torreya grandis, naturally distributed in mountains of the southeastern China. The linkage–LD map constructed from various types of molecular markers opens a powerful gateway for studying the history of plant evolution.     

Where intestinal epithelial stem cells are localized? About molecular markers

Using stem cells as an example the review considers a new history and methodology of search for stem cells (SC), found in tissues of adult Homo sapiens and Drosophila melanogaster organisms. These studies of SC resulted in several original hypotheses explaining their unusual features. Impressive progress recently achieved in this direction (2008–2010) is associated with employment of new methods of somatic recombination for long-term registration of various strains of differentiated cells, early and distant SC progeny. 1) Although anatomic localization of intestinal epithelium cells lacking marked morphological and biochemical differentiation markers (the lower third of intestinal and colon crypts) is known for about 40 years results of their experimental identification, isolation and detection of their functional characteristics still represent the subject for discussions. Particularly, it remains unclear, which SC are involved in crypt regeneration: the same as those involved into homeostatic renewal or their various subpopulations or early SC progenies acquired stem features by reprogramming? 2) In addition, most detected biochemical markers of potential SC are common for SC from other tissues of embryonic and mature organisms so it is possible to apply method developed for intestinal epithelium for their isolation. 3) Data on induction of intestinal epithelium polyps and neoplasias by mutations in genes encoding SC markers and identification of biochemical characteristics of potential SC in these tumors support the hypothesis of stem tumor cell origination from normal SC or their earliest progeny. In general, facts considered in this review may be useful for both development of optimal methods for the use of SC in cell therapy (as the source of humoral factors), regenerative medicine (as the source of differentiated cells for restoration of injured tissue), and also for targeted search of antitumor drugs (SC as the target) and preparations modifying genetic and epigenetic reactions of SC to genotoxic and stress treatments.     

Integrative computational evaluation of genetic markers for Alzheimer’s disease

Recent studies have reported hundreds of genes linked to Alzheimer’s Disease (AD). However, many of these candidate genes may be not identified in different studies when analyses were replicated. Moreover, results could be controversial. Here, we proposed a computational workflow to curate and evaluate AD related genes. The method integrates large scale literature knowledge data and gene expression data that were acquired from postmortem human brain regions (AD case/control: 31/32 and 22/8). Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analysis were conducted to study the pathogenic profile of the candidate genes, with 4 metrics proposed and validated for each gene. By using our approach, a scalable AD genetic database was developed, including AD related genes, pathways, diseases and info of supporting references. The AD case/control classification supported the effectiveness of the 4 proposed metrics, which successfully identified 21 well-studied AD genes (i.g. TGFB1, CTNNB1, APP, IL1B, PSEN1, PTGS2, IL6, VEGFA, SOD1, AKT1, CDK5, TNF, GSK3B, TP53, CCL2, BDNF, NGF, IGF1, SIRT1, AGER and TLR) and highlighted one recently reported AD gene (i.g. ITGB1). The computational biology approach and the AD database developed in this study provide a valuable resource which may facilitate the understanding of the AD genetic profile.     

Do hunters target auxiliary markers? An example using black brant

Auxiliary markers play an essential role in understanding migration, movement, demography, and behavior of migratory birds. Use of such markers relies on the assumption that the markers do not affect the traits of interest. Neck collars, among the most conspicuous of markers, substantially affect risk of harvest, and survival even in the absence of harvest. Effects of less-conspicuous markers, such as colored plastic tarsal bands, are not well understood. We used 30 years (1986–2015) of banding, recovery, and recapture data from the Yukon-Kuskokwim Delta in Alaska, USA, to assess differences in direct band recovery rates (DRRs) between black plastic and brightly colored plastic bands applied to black brant (Branta bernicla nigricans). We also assessed the effect of the color of plastic tarsal bands on annual survival, risks of natural mortality harvest, and fidelity to the breeding colony of adult female black brant. When assessing only DRRs we found that brightly colored bands were recovered at higher rates than black plastic bands in the early 2000s, but DRRs for black bands increased more rapidly through time, resulting in similar DRRs for the 2 band colors at the end of the study. Using a Burnham model structure, our results demonstrated that individuals fitted with colored bands had slightly lower hazards of dying from natural causes or hunting than individuals carrying less-conspicuous black tarsal bands. Differences on annual probability scales were small and credible intervals broadly overlapped between band types, indicating minimal differences between individuals with different band types; however, we could not resolve all confounding in our study design and we suggest that specific studies directed at assessing marker effects are warranted. We encourage education of hunters about their roles as citizen scientists and the potentially detrimental effect of targeting birds with auxiliary markers.     

Neuronal markers in the rodent pineal gland — an immunohistochemical investigation

Summary Although some embryological and morphological features speak in favour of a neuronal character of rodent pinealocytes, histochemistry and ultrastructure let this issue appear controversial. Using antibodies to different neurofilaments, the neural adhesion molecule L1, synaptophysin and tubulin as neuronal markers, the pineal glands of rat and guinea-pig were studied by means of immunfluorescence. Neurofilament-immunoreactivity was present in some rat pineal nerve fibers and in the majority of guinea-pig pinealocytes, L1 decorated rat intrapineal nerve fibers, synaptophysin was almost ubiquitously distributed in the pineal of both species, while tubulin-immunofluorescence was seen in nerve fibers of rat and guinea-pig pineal and in some pinealocytes of the latter. These findings speak in favour of the neuronal character of guinea-pig pinealocytes. The lack of neurofilament- and tubulin-immunoreactivity in rat pinealocytes might be attributable to very low concentrations of these proteins or species differences as to their expression. Further studies including in situhybridisation of relevant mRNAs will be necessary to answer these questions definitely.The data presented in this study form part of a thesis presented by A. Bendig in partial fulfillment for the degree of M.D..Supported by the Deutsche Forschungsgemeinschaft, grant Schr 283/2-1     

Epigenetic diagnostics of cancer — the application of DNA methylation markers

In recent years it has become apparent that epigenetic events are potentially equally responsible for cancer initiation and progression as genetic abnormalities. DNA methylation is the main epigenetic modification in humans. Two DNA methylation lesions coexist in human neoplasms: hypermethylation of promoter regions of specific genes within a context of genomic hypomethylation. Aberrant methylation is found at early stages of carcinogenesis and distinct types of cancer exhibit specific patterns of methylation changes. Tumor specific DNA is readily obtainable from different clinical samples and methylation status analysis often permits sensitive disease detection. Methylation markers may also serve for prognostic and predictive purposes as they often reflect the metastatic potential and sensitivity to therapy. As current findings show a great potential of recently characterised methylation markers, more studies in the field are needed in the future. Large clinical studies of newly developed markers are especially needed. The review describes the diagnostic potential of DNA methylation markers.