The use of proteomics in identifying differentially expressed serum proteins in humans with type 2 diabetes

BACKGROUND: The aim of the study was to optimize protocols for finding and identifying serum proteins that are differentially expressed in persons with normal glucose tolerance (NGT) compared to individuals with type 2 diabetes mellitus (T2DM). Serum from persons with NGT and persons with T2DM was profiled using ProteinChip arrays and time-of-flight mass spectra were generated by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). RESULTS: Mass spectra from NGT- and T2DM-groups were compared. Fifteen proteins ranging from 5 to 79 kDa were differentially expressed (p < 0.05). Five of these proteins showed decreased and ten showed increased serum levels in individuals with T2DM. To be able to identify the proteins, the complexity of the sample was reduced by fractionation approaches. Subsequently, the purified fractions containing biomarkers were separated by one-dimensional SDS-polyacrylamide gel electrophoresis (SDS-PAGE) in two identical lanes. Protein bands of the first lane were excised and subjected to passive elution to recapture the biomarkers on ProteinChip arrays. The corresponding bands of the second lane were subjected to peptide-mass fingerprinting (PMF). Using this approach four of the differentially expressed proteins were identified as apolipoprotein C3 (9.4 kDa), transthyretin (13.9 kDa), albumin (66 kDa) and transferrin (79 kDa). Whereas apolipoprotein C3 and transthyretin were up-regulated, albumin and transferrin were down-regulated in T2DM. CONCLUSION: Protocols for protein profiling by SELDI-TOF MS and protein identification by fractionation, SDS-PAGE and PMF were optimized for serum from humans with T2DM. With these protocols differentially expressed proteins were discovered and identified when serum from NGT- and T2DM-individuals was analyzed

Quantification of Normal Cell Fraction and Copy Number Neutral LOH in Clinical Lung Cancer Samples Using SNP Array Data

Technologies based on DNA microarrays have the potential to provide detailed information on genomic aberrations in tumor cells. In practice a major obstacle for quantitative detection of aberrations is the heterogeneity of clinical tumor tissue. Since tumor tissue invariably contains genetically normal stromal cells, this may lead to a failure to detect aberrations in the tumor cells.Using SNP array data from 44 non-small cell lung cancer samples we have developed a bioinformatic algorithm that accurately models the fractions of normal and tumor cells in clinical tumor samples. The proportion of normal cells in combination with SNP array data can be used to detect and quantify copy number neutral loss-of-heterozygosity (CNNLOH) in the tumor cells both in crude tumor tissue and in samples enriched for tumor cells by laser capture microdissection.Genome-wide quantitative analysis of CNNLOH using the CNNLOH Quantifier method can help to identify recurrent aberrations contributing to tumor development in clinical tumor samples. In addition, SNP-array based analysis of CNNLOH may become important for detection of aberrations that can be used for diagnostic and prognostic purposes

Democratization and gender-neutrality in English(es)

"Democratization" and "gender-neutrality" are two concepts commonly used in recent studies on language variation. While both concepts link linguistic phenomena to sociocultural changes, the extent to which they overlap and/or interact has not been studied in detail. In particular, not much is known about how linguistic changes related to democratization and gender-neutrality spread across registers or varieties of English, as well as whether speakers are aware of the changes that are taking place. In this paper we review the main theoretical issues regarding these concepts and relate them to the main findings in the articles in this issue, all of which study lexical and grammatical variation from a corpus-based perspective. Taken together, they help unveil some of the conscious and unconscious mechanisms that operate at the interface between democratization and gender-neutrality.Peer reviewe

Improved distance measures for “mixed-content miscellanies” : An adaptation for the collections of sayings of the desert fathers and mothers

Collections of sayings of the desert fathers and mothers are extant in manuscripts in many languages and are organized differently. They are ‘fixed-content miscellanies’ (FCM): they include material that belongs to the same genre, but is variable both when it comes to appearance and order. Distance measurement methods are particularly suitable for large text traditions including variable content in the so-called mixed-content miscellanies, such as recipes, anthological compilations of shorter text passages, or catalogues, but can also be suitable for text genres like collections of sayings, that are equally variable in appearance and order of sayings, even though the genre is fixed; hence ‘fixed-content miscellanies’. In the article, collections of sayings in seven languages were compared using four distance measures methods. Each segment of the sayings was given a unique id to be comparable. The first method used, the Jaccard distance measure, disregards the linear order of items and instead considers each collection compared only as a ‘bag of stories’. In two other methods used (Birnbaum and Levenshtein methods), the order in which the narratives of each saying appear is compared. All three methods yielded interesting results, but the collections that were apparently closely related were clustered together so tightly that it was not possible to make more nuanced analyses. In order to remove false negatives, particulars concerning lacunes in the material were taken into account in the proposed modified Levenshtein method, the fixed-content miscellanies (FCM)-Levenshtein method. By applying the FCM-Levenshtein method, previously unknown relations between collections witnessed in different languages could be detected

Improved distance measures for “mixed-content miscellanies" : an adaptation for the collections of sayings of the desert fathers and mothers

Collections of sayings of the desert fathers and mothers are extant in manuscripts in many languages and are organized differently. They are ‘fixed-content miscellanies’ (FCM): they include material that belongs to the same genre, but is variable both when it comes to appearance and order. Distance measurement methods are particularly suitable for large text traditions including variable content in the so-called mixed-content miscellanies, such as recipes, anthological compilations of shorter text passages, or catalogues, but can also be suitable for text genres like collections of sayings, that are equally variable in appearance and order of sayings, even though the genre is fixed; hence ‘fixed-content miscellanies’. In the article, collections of sayings in seven languages were compared using four distance measures methods. Each segment of the sayings was given a unique id to be comparable. The first method used, the Jaccard distance measure, disregards the linear order of items and instead considers each collection compared only as a ‘bag of stories’. In two other methods used (Birnbaum and Levenshtein methods), the order in which the narratives of each saying appear is compared. All three methods yielded interesting results, but the collections that were apparently closely related were clustered together so tightly that it was not possible to make more nuanced analyses. In order to remove false negatives, particulars concerning lacunes in the material were taken into account in the proposed modified Levenshtein method, the fixed-content miscellanies (FCM)-Levenshtein method. By applying the FCM-Levenshtein method, previously unknown relations between collections witnessed in different languages could be detected.MXM19-1087:

Gene copy number aberrations are associated with survival in histologic subgroups of non-small cell lung cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.INTRODUCTION: Non-small cell lung cancer (NSCLC) is characterized by a multitude of genetic aberrations with unknown clinical impact. In this study, we aimed to identify gene copy number changes that correlate with clinical outcome in NSCLC. To maximize the chance to identify clinically relevant events, we applied a strategy involving two prognostically extreme patient groups. METHODS: Short-term (58 month; n = 47) were selected from a clinically well-characterized NSCLC patient cohort with available fresh frozen tumor specimens. The samples were analyzed using high-resolution single-nucleotide polymorphism array technology to assess gene copy number variations and array-based gene expression profiling. The molecular data were combined with information on clinical parameters. RESULTS: Genetic aberrations were strongly associated with tumor histology. In adenocarcinoma (n = 50), gene copy number gains on chromosome 8q21-q24.3 (177 genes) were more frequent in long-term than in short-term survivors. In squamous cell carcinoma (n = 28), gains on chromosome 14q23.1-24.3 (133 genes) were associated with shorter survival, whereas losses in a neighboring region, 14q31.1-32.33 (110 genes), correlated with favorable outcome. In accordance with copy number gains and losses, messenger RNA expression levels of corresponding genes were increased or decreased, respectively. CONCLUSION: Comprehensive tumor profiling permits the integration of genomic, histologic, and clinical data. We identified gene copy number gains and losses, with corresponding changes in messenger RNA levels that were associated with prognosis in adenocarcinoma and squamous cell carcinoma of the lung.AstraZeneca AstraZeneca UK Lions Cancerforskningsfond Selander Foundation Swedish Cancer Societ