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  • 1
    Keywords: Medicine ; Human Genetics ; Bioinformatics ; Biomathematics ; Biomedicine ; Human Genetics ; Bioinformatics ; Genetics and Population Dynamics ; Springer eBooks
    Description / Table of Contents: Introduction -- Distribution of length of ancestral chromosomal segments in admixed genomes -- Exploring population admixture dynamics via distribution of LACS -- Genome-wide search for signatures of natural selection in African Americans -- Complex selective forces shaping the genes underlying human diseases -- Materials and Methods
    Abstract: In this thesis, Dr. Jin presents the distribution of ancestral chromosomal segments in the admixed genome, which could provide the information needed to explore population admixture dynamics. The author derives accurate population histories of African Americans and Mexicans using genome-wide single nucleotide polymorphisms (SNPs) data. Mapping the genetic background facilitates the study of natural selection in the admixed population, and the author identifies the signals of selection in African Americans since their African ancestors left for America. He further demonstrates that many of the selection signals were associated with African American-specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to their new environment. Lastly, the author reveals the complexity of natural selection in shapinghuman susceptibility to disease. The thesis significantly advances our understanding of the recent population admixture, adaptation to local environment and its health implications
    Pages: XIX, 114 p. 32 illus., 29 illus. in color. : online resource.
    Edition: 1st ed. 2015.
    ISBN: 9789401774086
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  • 2
    Keywords: Life sciences ; Biochemistry ; Plant anatomy ; Plant physiology ; Life sciences ; Plant Biochemistry ; Plant physiology ; Plant Anatomy/Development ; Springer eBooks
    Abstract: The functional characterization of a key enzyme in the phosphatidylinositol (PI) signaling pathway in the model plant Arabidopsis thaliana is the focus of this thesis. Moreover, a particular focus is the exploration of the biological functions of Arabidopsis phosphatidylinositol monophosphate 5-kinase 2 (PIP5K2), which catalyzes the synthesis of phosphatidylinositol (4,5) bisphosphate, the precursor of two important second messengers (inositol 1,4,5-trisphosphate and diacylglycerol). Employing molecular and genetic approaches, the author isolates and characterizes the expression pattern, physiological functions and underlying mechanism of Arabidopsis PIP5K2. In doing so, he reveals that PIP5K2 is involved in regulating lateral root formation and root gravity response through modulating auxin accumulation and polar auxin transport, and also plays a critical part in salt tolerance. These findings shed new light on the crosstalk between PI signaling and auxin response, both of which fulfill crucial regulatory roles in plant development
    Pages: XIX, 77 p. 33 illus. : online resource.
    ISBN: 9789401793735
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  • 3
    Keywords: Life sciences ; Immunology ; Biochemistry ; Cell Cycle ; Life sciences ; Protein Science ; Cell Cycle Analysis ; Immunology ; Springer eBooks
    Description / Table of Contents: 1 Immune homeostasis: Activation and Downregulation of NF-κB -- 2 Regulation of NF-κB signaling by regulatory ubiquitination: specific pathways and A20 -- 3 The deubiquitinase activity of A20 is dispensable for its role in NF-κB signaling -- 4 Perspectives on regulatory ubiquitination
    Abstract: This thesis examines the evidence for regulatory ubiquitination by focusing on A20. It provides an insightful and in-depth evaluation of the current literature by critically examining the evidence of K63-linked regulatory ubiquitination in regulating cell-signalling. It is also the first thesis to directly test the role of regulatory ubiquitination in NF-kB signaling in vivo. The case for regulatory ubiquitination has been to a large extent predicated upon the presumed deubiquitinase activity of A20, long considered a key regulator of inflammatory responses as mice lacking A20 die from multi-organ inflammation and cachexia. The theses reports the creation and characterization of a knock-in mouse that expresses a mutated form of A20 which selectively lacks the deubiquitinase activity. The knock-in mice surprisingly display completely normal NF-ÎðB activation with no accompanying inflammatory phenotype. Given that the presumed role of A20 as a deubiquitinase has been used to support the importance of regulatory K63-linked ubiquitination in NF-kB signaling, this study will help focus future research efforts into alternative target pathways that do not depend on K63 ubiquitination. In fact, the work suggests that it might be important to revisit the role of K63-linked polyubiquitination in cell-signalling. Ubiquitin Chains: Degradation and Beyond is essential reading for anyone conducting research in cell-signalling and immunology. Dr. Arnab De received his PhD from the Department of Microbiology & Immunology at Columbia University. During his PhD, he developed transgenic mice to study the mechanism of action of a critical tumor-suppressor called A20. He is also well known for having developed peptide-based prodrugs as therapeutics for diabetes. His work has been reported by the media, and has resulted in multiple patents℗ and publications in peer reviewed journals. He presented his findings at the American Peptide Symposium and was awarded the Young Investigatoŕ€™s Award. He is the author of the book entitled Application of Peptide-Based Prodrug Chemistry in Drug Development, with a foreword written by Professor Jean Martinez (Former President, European Peptide Society) and published in the series SpringerBriefs in Pharmaceutical Science & Drug Development. His research interests lie at the intersection of chemistry and medicine.℗ Besides biomedical research, he is also generally interested in public health policy and general scientific outreach
    Pages: XV, 103 p. 45 illus., 33 illus. in color. : online resource.
    ISBN: 9783319149653
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  • 4
    Keywords: Life sciences ; Stem Cells ; Cell Culture ; Developmental Biology ; Life sciences ; Stem Cells ; Cell Culture ; Regenerative Medicine/Tissue Engineering ; Developmental Biology ; Springer eBooks
    Description / Table of Contents: Abstract -- Introduction -- Establishment of highly efficient somatic cell reprogramming system to generate iPSC lines- Establishment of highly efficient somatic cell reprogramming system and establishment of iPSC lines -- Pluripotency of iPSC and underlining mechanism -- Developmental potential of mouse iPSC -- Conclusions
    Abstract: Stem cells have the ability to differentiate into all types of cells within the body, thus have great therapeutic potential for regenerative medicine to treat complicated disorders, like Parkinson’s disease and spinal cord injury. There will also be many applications in drug development. However, several roadblocks, such as safety issues and low efficiency of pluripotent stem cell (PSC) line derivation need to be resolved before their clinical application. This thesis focuses on these two areas, so as to find methods to overcome the limitation. It covers deriving embryonic stem cells (ESCs) from several different species, and reports an efficient system to generate induced pluripotent stem cells (iPSCs), and the first iPSC mice in the world. The results in this thesis confirm that somatic cells can be fully reprogrammed with the four Yamanaka factors. In addition, we have found that the Dlk1-Dio3 region can be a potential molecular marker to distinguish the fully reprogrammed iPSCs from partially reprogrammed ones. All of these results will help improve the safety of PSCs in the clinical applications, and increase the current low induction efficiency of their production
    Pages: XV, 92 p. 21 illus., 18 illus. in color. : online resource.
    ISBN: 9789401788199
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  • 5
    Keywords: Biomedical Engineering ; Nanotechnology ; Oncology ; Biomedical Engineering/Biotechnology ; Nanotechnology ; Biomedical Engineering and Bioengineering ; Cancer Research ; Springer eBooks
    Description / Table of Contents: Unifying Next-Generation Biomarkers and Nanodiagnostic Platforms for Precision Prostate Cancer (PCa) Management -- Colorimetric Gene Fusion Diagnostics for Visual Binary Readout -- Label –Free Surface-Enhanced Raman Scattering Detection System for Clinical Biomarker Targets -- Amplification-Free Electrochemical RNA Biomarker Sensing -- Simultaneous Analysis of Multiple Biomarkers via High-Throughput Parallel Profiling
    Abstract: This book presents a unique concept of merging nanotechnology and novel urinary biomarkers for accurate early prostate cancer detection, discussing an entire progressive pipeline of innovative new strategies in biosensor development, from a simple colorimetric system to a complex system for simultaneous multiple biomarker sensing. For newcomers to the field of nucleic acid biosensing, it also describes various isothermal amplification and amplification-free strategies, which are currently the main research areas. Lastly, the book introduces and demonstrates the notion of clinical nanobiosensor validation toward clinical translation: the ultimate aim of researchers in the biosensor field. This book is a valuable reference resource learners seeking inspiration for cancer biosensor development
    Pages: XIII, 102 p. : online resource.
    Edition: 1st ed. 2019.
    ISBN: 9783030310004
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  • 6
    Keywords: Life sciences ; Spectroscopy ; Nucleic Acids ; Cell Biology ; Microscopy ; Life sciences ; Cell Biology ; Spectroscopy and Microscopy ; Nucleic Acid Chemistry ; Spectroscopy/Spectrometry ; Springer eBooks
    Description / Table of Contents: A Condensed History of Chromatin Research -- Investigating Chromatin Organisation Using Single Molecule Localisation Microscopy -- Structure, Function and Dynamics of Chromatin -- Periodic and Symmetric Organisation of Meiotic Chromosomes -- Conclusions -- Appendices
    Abstract: This book sheds new light on the current state of knowledge concerning chromatin organization. Particular emphasis is given to the new imaging potential offered by super-resolution microscopy, which allows DNA imaging with a very high labeling density. From the early work on chromosomes by Walther Flemming in the nineteenth century to recent advances in genomics, the history of chromatin research now spans more than a century. The various milestones, such as the discovery of the double helix structure, the sequencing of the human genome, and the recent description of the genome in 3D space, show that understanding chromatin and chromosome function requires a clear understanding of its structure. Presenting cutting-edge data from super-resolution single molecule microscopy, the book demonstrates that chromatin manifests several levels of folding, from nucleosomes to chromosomes. Chromatin domains emerge as a new fundamental building block of chromatin architecture, with functions possibly related to gene regulation. A detailed description of chromatin folding in the pachytene stage of meiosis serves as a model for exploring this functionality, showing the apparent interplay between structure, function, and epigenetic regulation. Lastly, the book discusses possible new avenues of innovation to describe chromatin’s organization and functions. Gathering essential insights on chromatin architecture, the book offers students an introduction to microscopy and its application to chromatin organization, while also providing advanced readers with new ideas for future research
    Pages: LIII, 152 p. 101 illus., 50 illus. in color. : online resource.
    ISBN: 9783319521831
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  • 7
    Keywords: Medicine ; Human Genetics ; Antibodies ; Genetic Engineering ; Biochemistry ; Cell Biology ; Biomedicine ; Antibodies ; Genetic Engineering ; Human Genetics ; Cell Biology ; Biochemistry, general ; Springer eBooks
    Description / Table of Contents: Background -- High-throughput Sequencing of the Paired Human Immunoglobulin Heavy and Light Chain Repertoire -- In-Depth Determination and Analysis of the Human Paired Heavy and Light Chain Antibody Repertoire -- Paired VH:VL Analysis of Naïve B Cell Repertoires and Comparison to Antigen-Experienced B Cell Repertoires in Healthy Human Donors -- Conclusions and Future Perspectives -- Appendices
    Abstract: This thesis outlines the development of the very first technology for high-throughput analysis of paired heavy and light-chain antibody sequences, opening the door for the discovery of new antibodies and the investigation of adaptive immune responses to vaccines and diseases. By designing two new technologies for sequencing multiple mRNA transcripts from up to 10 million isolated, single cells, the author directly addresses the limitations to provide information on the identity of immune receptor pairs encoded by individual B or T lymphocytes. Previous methods for high-throughput immune repertoire sequencing have been unable to provide such information. The techniques developed in this thesis have enabled comprehensive investigation of human B-cell repertoires and have been applied for the rapid discovery of new human antibodies, to gain new insights into the development of human antibody repertoires, and for analysis of human immune responses to vaccination and disease
    Pages: XXVIII, 87 p. 34 illus. : online resource.
    ISBN: 9783319585185
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