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  • Springer Science and Business Media LLC  (12)
  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-01-15)
    Abstract: Postoperative delirium is the most common complication among older adults undergoing major surgery. The pathophysiology of delirium is poorly understood, and no blood-based, predictive markers are available. We characterized the plasma metabolome of 52 delirium cases and 52 matched controls from the Successful Aging after Elective Surgery (SAGES) cohort (N = 560) of patients ≥ 70 years old without dementia undergoing scheduled major non-cardiac surgery. We applied targeted mass spectrometry with internal standards and pooled controls using a nested matched case-control study preoperatively (PREOP) and on postoperative day 2 (POD2) to identify potential delirium risk and disease markers. Univariate analyses identified 37 PREOP and 53 POD2 metabolites associated with delirium and multivariate analyses achieved significant separation between the two groups with an 11-metabolite prediction model at PREOP (AUC = 83.80%). Systems biology analysis using the metabolites with differential concentrations rendered “valine, leucine, and isoleucine biosynthesis” at PREOP and “citrate cycle” at POD2 as the most significantly enriched pathways (false discovery rate  〈  0.05). Perturbations in energy metabolism and amino acid synthesis pathways may be associated with postoperative delirium and suggest potential mechanisms for delirium pathogenesis. Our results could lead to the development of a metabolomic delirium predictor.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2019
    In:  BMC Bioinformatics Vol. 20, No. 1 ( 2019-12)
    In: BMC Bioinformatics, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2019-12)
    Type of Medium: Online Resource
    ISSN: 1471-2105
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2041484-5
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2010
    In:  BMC Bioinformatics Vol. 11, No. 1 ( 2010-12)
    In: BMC Bioinformatics, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2010-12)
    Abstract: Phylogenetic analysis can be used to divide a protein family into subfamilies in the absence of experimental information. Most phylogenetic analysis methods utilize multiple alignment of sequences and are based on an evolutionary model. However, multiple alignment is not an automated procedure and requires human intervention to maintain alignment integrity and to produce phylogenies consistent with the functional splits in underlying sequences. To address this problem, we propose to use the alignment-free Relative Complexity Measure (RCM) combined with reduced amino acid alphabets to cluster protein families into functional subtypes purely on sequence criteria. Comparison with an alignment-based approach was also carried out to test the quality of the clustering. Results We demonstrate the robustness of RCM with reduced alphabets in clustering of protein sequences into families in a simulated dataset and seven well-characterized protein datasets. On protein datasets, crotonases, mandelate racemases, nucleotidyl cyclases and glycoside hydrolase family 2 were clustered into subfamilies with 100% accuracy whereas acyl transferase domains, haloacid dehalogenases, and vicinal oxygen chelates could be assigned to subfamilies with 97.2%, 96.9% and 92.2% accuracies, respectively. Conclusions The overall combination of methods in this paper is useful for clustering protein families into subtypes based on solely protein sequence information. The method is also flexible and computationally fast because it does not require multiple alignment of sequences.
    Type of Medium: Online Resource
    ISSN: 1471-2105
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2041484-5
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  • 4
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2016-12-05)
    Abstract: The realization of personalized medicine through human induced pluripotent stem cell (iPSC) technology can be advanced by transcriptomics, epigenomics, and bioinformatics that inform on genetic pathways directing tissue development and function. When possible, population diversity should be included in new studies as resources become available. Previously we derived replicate iPSC lines of African American, Hispanic-Latino and Asian self-designated ethnically diverse (ED) origins with normal karyotype, verified teratoma formation, pluripotency biomarkers, and tri-lineage in vitro commitment. Here we perform bioinformatics of RNA-Seq and ChIP-seq pluripotency data sets for two replicate Asian and Hispanic-Latino ED-iPSC lines that reveal differences in generation of contractile cardiomyocytes but similar and robust differentiation to multiple neural, pancreatic, and smooth muscle cell types. We identify shared and distinct genes and contributing pathways in the replicate ED-iPSC lines to enhance our ability to understand how reprogramming to iPSC impacts genes and pathways contributing to cardiomyocyte contractility potential.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2615211-3
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  • 5
    In: BMC Bioinformatics, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2013-12)
    Type of Medium: Online Resource
    ISSN: 1471-2105
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2041484-5
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2013
    In:  BMC Bioinformatics Vol. 14, No. S2 ( 2013-01)
    In: BMC Bioinformatics, Springer Science and Business Media LLC, Vol. 14, No. S2 ( 2013-01)
    Abstract: MHC (Major Histocompatibility Complex) is a key player in the immune response of most vertebrates. The computational prediction of whether a given antigenic peptide will bind to a specific MHC allele is important in the development of vaccines for emerging pathogens, the creation of possibilities for controlling immune response, and for the applications of immunotherapy. One of the problems that make this computational prediction difficult is the detection of the binding core region in peptides, coupled with the presence of bulges and loops causing variations in the total sequence length. Most machine learning methods require the sequences to be of the same length to successfully discover the binding motifs, ignoring the length variance in both motif mining and prediction steps. In order to overcome this limitation, we propose the use of time-based motif mining methods that work position-independently. Results The prediction method was tested on a benchmark set of 28 different alleles for MHC class I and 27 different alleles for MHC class II. The obtained results are comparable to the state of the art methods for both MHC classes, surpassing the published results for some alleles. The average prediction AUC values are 0.897 for class I, and 0.858 for class II. Conclusions Temporal motif mining using partial periodic patterns can capture information about the sequences well enough to predict the binding of the peptides and is comparable to state of the art methods in the literature. Unlike neural networks or matrix based predictors, our proposed method does not depend on peptide length and can work with both short and long fragments. This advantage allows better use of the available training data and the prediction of peptides of uncommon lengths.
    Type of Medium: Online Resource
    ISSN: 1471-2105
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2041484-5
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2010
    In:  BMC Genomics Vol. 11, No. 1 ( 2010-12)
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2010-12)
    Abstract: In this study, we used a systematic bioinformatics analysis approach to elucidate genes that exhibit an endothelial cell (EC) restricted expression pattern, and began to define their regulation, tissue distribution, and potential biological role. Results Using a high throughput microarray platform, a primary set of 1,191 transcripts that are enriched in different primary ECs compared to non-ECs was identified (LCB 〉 3, FDR 〈 2%). Further refinement of this initial subset of transcripts, using published data, yielded 152 transcripts (representing 109 genes) with different degrees of EC-specificity. Several interesting patterns emerged among these genes: some were expressed in all ECs and several were restricted to microvascular ECs. Pathway analysis and gene ontology demonstrated that several of the identified genes are known to be involved in vasculature development, angiogenesis, and endothelial function (P 〈 0.01). These genes are enriched in cardiovascular diseases, hemorrhage and ischemia gene sets (P 〈 0.001). Most of the identified genes are ubiquitously expressed in many different tissues. Analysis of the proximal promoter revealed the enrichment of conserved binding sites for 26 different transcription factors and analysis of the untranslated regions suggests that a subset of the EC-restricted genes are targets of 15 microRNAs. While many of the identified genes are known for their regulatory role in ECs, we have also identified several novel EC-restricted genes, the function of which have yet to be fully defined. Conclusion The study provides an initial catalogue of EC-restricted genes most of which are ubiquitously expressed in different endothelial cells.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2041499-7
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2008
    In:  BMC Genomics Vol. 9, No. 1 ( 2008-12)
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2008-12)
    Abstract: Endothelial differentiation occurs during normal vascular development in the developing embryo. This process is recapitulated in the adult when endothelial progenitor cells are generated in the bone marrow and can contribute to vascular repair or angiogenesis at sites of vascular injury or ischemia. The molecular mechanisms of endothelial differentiation remain incompletely understood. Novel approaches are needed to identify the factors that regulate endothelial differentiation. Methods Mouse embryonic stem (ES) cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2 + cells, that were CD41 positive at 3.5 days. A separate population of VEGF-R2 + stem cells expressing the endothelial-specific marker CD144 (VE-cadherin) was also identified at this same time point. Channels lined by VE-cadherin positive cells developed within the embryoid bodies (EBs) formed by differentiating ES cells. VE-cadherin and CD41 expressing cells differentiate in close proximity to each other within the EBs, supporting the concept of a common origin for cells of hematopoietic and endothelial lineages. Results Microarray analysis of 〉 45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2 + , CD41 + , and CD144 + and VEGF-R2 - , CD41 - , and CD144 - . All microarray experiments were performed in duplicate using RNA obtained from independent experiments, for each subset of cells. Expression profiling confirmed the role of several genes involved in hematopoiesis, and identified several putative genes involved in endothelial differentiation. Conclusion The isolation of CD144 + cells during ES cell differentiation from embryoid bodies provides an excellent model system and method for identifying genes that are expressed during endothelial differentiation and that are distinct from hematopoiesis.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2020
    In:  BMC Genomics Vol. 21, No. 1 ( 2020-12)
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2020-12)
    Abstract: Zebrafish is a popular model organism, which is widely used in developmental biology research. Despite its general use, the direct comparison of the zebrafish and human oocyte transcriptomes has not been well studied. It is significant to see if the similarity observed between the two organisms at the gene sequence level is also observed at the expression level in key cell types such as the oocyte. Results We performed single-cell RNA-seq of the zebrafish oocyte and compared it with two studies that have performed single-cell RNA-seq of the human oocyte. We carried out a comparative analysis of genes expressed in the oocyte and genes highly expressed in the oocyte across the three studies. Overall, we found high consistency between the human studies and high concordance in expression for the orthologous genes in the two organisms. According to the Ensembl database, about 60% of the human protein coding genes are orthologous to the zebrafish genes. Our results showed that a higher percentage of the genes that are highly expressed in both organisms show orthology compared to the lower expressed genes. Systems biology analysis of the genes highly expressed in the three studies showed significant overlap of the enriched pathways and GO terms. Moreover, orthologous genes that are commonly overexpressed in both organisms were involved in biological mechanisms that are functionally essential to the oocyte. Conclusions Orthologous genes are concurrently highly expressed in the oocytes of the two organisms and these genes belong to similar functional categories. Our results provide evidence that zebrafish could serve as a valid model organism to study the oocyte with direct implications in human.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041499-7
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  • 10
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2013
    In:  Journal of Assisted Reproduction and Genetics Vol. 30, No. 3 ( 2013-3), p. 341-352
    In: Journal of Assisted Reproduction and Genetics, Springer Science and Business Media LLC, Vol. 30, No. 3 ( 2013-3), p. 341-352
    Type of Medium: Online Resource
    ISSN: 1058-0468 , 1573-7330
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2016722-2
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