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  • Cell & Developmental Biology  (5)
  • Alternative splicing  (1)
  • Medical sciences.  (1)
  • 1
    Keywords: Medical sciences. ; Electronic books.
    Type of Medium: Online Resource
    Pages: 1 online resource (583 pages)
    Edition: 2nd ed.
    ISBN: 9780128001547
    DDC: 570.72
    Language: English
    Note: Front Cover -- Research in Medical and Biological Sciences -- Copyright Page -- Contents -- List of Contributors -- Preface -- 1 Philosophy of Science -- 1.1 Introduction -- 1.2 Philosophy of the Natural Sciences -- 1.3 What Is Science? Differentiating Science from Nonscience -- 1.4 Knowledge and Truth: What is Knowledge and What Constitutes a Scientific Fact? -- 1.5 The Glue That Holds the World Together: Causation -- 1.5.1 Necessary Conditions -- 1.5.2 Sufficient Conditions -- 1.5.3 Combination of Conditions that Together are Necessary and Sufficient -- 1.5.4 Combination of Conditions that Together are Sufficient -- 1.5.5 Probabilistic Causation -- 1.5.6 Counterfactual Conditions -- 1.6 Scientific Explanation -- 1.7 Modes of Inference -- 1.8 What Science Is About -- 1.9 Scientific Rationality -- 1.10 Hypothesis Testing -- 1.10.1 Hypothetical-Deductive Method -- 1.11 The Aim of Science: Reducing Uncertainty -- 1.12 The Empirical Turn in the Philosophy of Science: Science in Society -- 1.13 Philosophy of the Social Sciences -- 1.14 Interpretation, Understanding, and Explanation -- 1.14.1 Explanation and Understanding -- 1.14.2 Interpretation -- 1.15 The Hermeneutic Circle, Horizon of Understanding, and "Double Hermeneutics" -- 1.16 Power, Ideology, and Interests -- 1.17 Validity -- 1.18 Reductionism and Emergence -- 1.19 Generalization -- Questions to Discuss -- Acknowledgments -- References -- Further Reading -- 2 Ethics and Scientific Conduct -- 2.1 Why the Current Focus on Scientific Misconduct? -- 2.2 What Do We Know About Scientific Misconduct? -- 2.3 What Is Wrong with Scientific Misconduct? -- 2.3.1 Consequentialism -- 2.3.2 Deontological Ethics -- 2.3.3 Virtue Ethics -- 2.4 Scientific Conduct and Misconduct -- 2.4.1 Internal Norms -- 2.4.2 Linkage Norms and External Norms. , 2.5 Scientific Misconduct That Affects the Truth Claims of Scientific Findings -- 2.5.1 Wrong Observations and Wrong Analysis -- 2.5.2 Plagiarism -- 2.5.3 Fabrication -- 2.6 Authorship -- 2.6.1 Exclusion from Authorship -- 2.6.2 Gift Authorship -- 2.6.3 Authorship by Coercion -- 2.6.4 Unsolicited Authorship -- 2.6.5 Ghost Authorship -- 2.6.6 Refusal to Accept Responsibility -- 2.7 Salami, Imalas, and Duplicate Publication -- 2.8 The Investigation, Prevention, and Punishment of Scientific Misconduct -- Questions to Discuss -- Appendix 1 ICMJE Recommendations on the Role of Authors and Contributors -- Why Authorship Matters -- Who Is an Author? -- Nonauthor Contributors -- References -- Further Reading -- 3 Ethics in Human and Animal Studies -- 3.1 Basic Principles of Human Biomedical Research Ethics -- 3.2 International Regulation -- 3.2.1 Consent -- 3.2.2 Inability to Consent -- 3.2.3 Randomized Controlled Trials -- 3.2.4 Vulnerable Research Participants -- 3.2.5 Epidemiological Research, "Big Data," and Biobank Research -- 3.2.6 The Role of RECs -- 3.2.7 Data Protection, Good Clinical Practice, and Other Regulations Influencing Biomedical Research Ethics -- 3.3 The Ethics of Animal Research -- 3.3.1 Animal Research and Other Human Uses of Animals -- Questions to Discuss -- References -- Further Reading -- 4 Research Strategies, Planning, and Analysis -- 4.1 Introduction -- 4.2 Identifying Scientific Problems -- 4.3 The Experimental Design -- 4.4 Data Types -- 4.5 Methods and Experimental Techniques -- 4.6 Experimental Research Checklist -- 4.7 Repeatability, Reproducibility, and Reliability -- 4.8 Multifactorial Relationships and Observational Studies -- 4.9 Validity, Effect Estimate, and Choice of Statistical Test -- 4.10 Research Protocol -- 4.11 Experimental Routines -- Acknowledgments -- Questions to Discuss -- References -- Further Reading. , 5 Literature Searches and Reference Management -- 5.1 Information Literacy -- 5.2 Literature Searches -- 5.2.1 Bibliographic Databases -- 5.2.2 Sources of Information -- 5.2.2.1 Primary Sources of Information and Primary Studies -- 5.2.2.2 Secondary Sources of Information and Secondary Studies -- 5.2.3 The Evidence Pyramid -- 5.2.4 Search Strategy -- 5.3 Establishment of a Search Query -- 5.3.1 PICO: A Focused Approach -- 5.3.2 Boolean Operator -- 5.4 Selection of Relevant Sources of Information -- 5.5 Search Techniques -- 5.5.1 Thesaurus Mapping -- 5.5.2 Federated Search -- 5.5.3 Free-Text Search -- 5.5.4 Searching by Index Term Versus Publication Type -- 5.5.5 Methodology Filters -- 5.5.5.1 PubMed Filters-Clinical Queries -- 5.5.5.2 Searching for Qualitative Research -- 5.6 Critical Assessment -- 5.6.1 Abstracts -- 5.6.2 Errata and Retracted Publications -- 5.7 Bibliometric Measures -- 5.7.1 Impact Factors -- 5.7.2 The Highly-Cited Index -- 5.8 Principal Scientific Bibliographic Databases -- 5.8.1 Medline -- 5.8.2 PubMed -- 5.8.3 EMBASE -- 5.8.4 Web of Science -- 5.8.5 BIOSIS Previews -- 5.8.6 PsycINFO -- 5.8.7 Cumulative Index to Nursing and Allied Health Literature -- 5.8.8 Cochrane Library -- 5.8.8.1 Cochrane Reviews -- 5.8.8.2 Other Reviews -- 5.8.8.3 Trials -- 5.8.8.4 Economic Evaluation -- 5.9 Staying Up to Date -- 5.9.1 Saving Search Strategies -- 5.9.2 Alert Services -- 5.9.3 Awareness Tools: Apps for Mobile Devices -- 5.9.3.1 BrowZine (for iOS and Android Devices) -- 5.9.3.2 Docphin (for iOS and Android Devices) -- 5.9.3.3 Read by QxMD (for iOS Devices, Coming on Android) -- 5.10 Medical and Scientific Internet Search Engines -- 5.10.1 Google Scholar -- 5.10.2 MacPLUS -- 5.10.3 SUMSearch2 -- 5.10.4 General Guidelines for Internet Searches -- 5.11 Finding Research Protocols and Ongoing Projects -- 5.12 Reference Management. , 5.12.1 Efficient Handling of References, Publications, and Manuscripts -- 5.12.2 EndNote -- 5.12.2.1 Settings for an EndNote Library -- 5.12.2.2 Journal Index -- 5.12.2.3 Entering References -- 5.12.2.4 Organizing References -- 5.12.2.5 Cite While You Write -- 5.12.2.6 Reference Lists-"Output Styles" -- 5.13 Open Access Publication, Copyright, and Self-Archiving -- 5.13.1 Open Access Publication -- 5.13.2 Retaining Copyright and Self-Archiving -- 5.13.3 Citing -- Questions to Discuss -- References -- Further Reading -- 6 Basic Medical Science -- 6.1 Introduction -- 6.2 Long-Term Goals and Specific Aims -- 6.3 Background and Significance -- 6.4 Experimental Strategies and Methods -- 6.5 Levels of Research-from Organisms to Cells -- 6.6 Research on Experimental Animals -- 6.7 The Three rs -- 6.8 Animal Models -- 6.9 Mouse Models for Studies of Mammalian Development and Disease -- 6.10 Legislation -- 6.11 Notes on the Use of Experimental Animals -- 6.12 Commonly Used Experimental Animals -- 6.13 Cell and Tissue Culture -- 6.14 An Overview of Selected Technical Developments -- 6.15 Applications of Cell Culture -- 6.16 Manipulation of Cultured Cells -- 6.17 Possibilities Provided by Molecular Biological Techniques -- Questions to Discuss -- References -- Further Reading -- 7 Translational Medical Research -- 7.1 Introduction -- 7.2 An Old Success Story-Aspirin -- 7.3 Research Provides a Path to Understanding Mechanisms and New Drugs -- 7.4 The Importance of Understanding Drug Metabolism-The Rise and Fall of Clopidogrel (Plavix) -- 7.5 The Need for More Translational Medical Research -- 7.6 Translational Medical Research and the Development of Orphan Drugs -- 7.7 From Rare Disorders to Common Disorders -- 7.8 Target-Based Drug Development-Aquaporins -- 7.9 Training of Investigators for Translational Medical Research. , 7.10 Collaboration Between Academia and the Pharmaceutical Industry -- Questions to Discuss -- References -- Further Reading -- 8 Clinical Research -- 8.1 Introduction -- 8.2 The Research Process-Important Steps -- 8.3 Controlled Clinical Trials -- 8.4 Drug Development -- 8.5 Clinical Trial Protocol -- 8.6 Trial Designs -- 8.7 Target Population -- 8.8 Historical Controls -- 8.9 Randomization -- 8.9.1 Stratification -- 8.9.2 Minimization -- 8.10 Blinding -- 8.11 Choice of Endpoints -- 8.12 Sample Size Estimation -- 8.12.1 Power -- 8.12.2 Sample Size Estimation for Categorical Outcomes -- 8.12.3 Sample Size Estimation for Continuous Outcomes -- 8.12.3.1 Pairs of Observations -- 8.12.3.2 Two Independent Samples (Parallel Group Trials) -- 8.12.3.3 Unequal Group Size -- 8.12.4 Sample Size Estimation Based on Precision of Estimates -- 8.12.4.1 Categorical Outcome -- 8.12.4.2 Continuous Outcome -- 8.13 Statistical Analysis -- 8.13.1 Analysis Sets -- 8.13.2 Handling of Missing Values -- 8.13.3 Analysis Strategies -- 8.13.3.1 Factorial Trials -- 8.13.3.2 Repeated Measurements -- 8.13.4 Multiple Endpoints -- 8.13.5 Interim Analyses -- 8.13.6 Subgroup Analyses -- 8.14 Personalized Medicine -- 8.15 Noninferiority Trials -- 8.16 Sources and Control of Bias -- 8.17 Generalization of Trial Results -- 8.18 Regulatory Issues -- Questions to Discuss -- Acknowledgments -- References -- 9 Epidemiology -- 9.1 Introduction -- 9.2 The Definition of Epidemiology -- 9.3 The Role of Epidemiology -- 9.3.1 Study Designs -- 9.4 Target Population, Source Population, and Study Sample -- 9.5 Disease Occurrence, Risk, Association, Importance, and Implication -- 9.5.1 Denominators, Numerators, and Time -- 9.5.2 Measures of Disease Occurrence and Risk (Incidence and Prevalence) -- 9.5.3 The Importance of Vital Statistics in an Epidemiological Setting -- 9.5.4 Mortality Rates. , 9.5.5 Cause of Death Statistics.
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  • 2
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: We examined the spatio-temporal pattern of type X collagen mRNA and its protein in the embryonic chick vertebrae undergoing ossification by in situ hybridization and immunohistochemistry. Hypertrophic chondrocytes, producing type X collagen, were developed as islands of cells in a few vertebral body segments of stage 36 embryos. These cells were increased in number at stages 37 and 38 and they expressed high levels of type X collagen mRNA and deposited its protein in the matrix. Blood vessels entered from the perichondrium at stage 37 and invaded deeply into hypertrophic cartilage at stage 38. As the vertebrae grew further at stage 40, the leading front of active hypertrophic chondrocytes with high levels of type X mRNA shifted from the midvertebral perivascular area towards intervertebral borders, while the perivascular area retained a number of inactive hypertrophic chondrocytes with low levels of type X mRNA. Type X collagen was found in large amounts throughout the matrix areas containing both active and inactive hypertrophic chondrocytes. Calcium was detected by von Kossa's technique in hypertrophic cartilage matrix in a small amount at stage 37, in parts of the matrix with type X collagen deposition in succeeding stages, and finally in almost the entire area of type X collagen deposition at stage 45. The vertebral segments of stage 45 embryos also showed a clearly reversed pattern of expression between type X collagen mRNA and types II and IX collagen mRNAs. The results demonstrate that the production of type X collagen by hypertrophic chondrocytes precedes both vascular invasion and mineralization of the matrix, suggesting that hypertrophic chondrocytes have an important role in regulating these events.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Developmental Dynamics 196 (1993), S. 37-46 
    ISSN: 1058-8388
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Polyclonal antibodies were raised in rabbits against a fusion peptide representing a portion of the amino-terminal non-triplehelical domain of mouse type XII collagen. The antibodies reacted with bands of 220 and 350 kDa on Western blots of mouse tissue extracts. Immunohistochemical analyses of mouse embryos demonstrated that type XII collagen is expressed mainly in dense connective tissues of tendons, ligaments, dermis, cornea, blood vessel walls, meninges, and developing membranous bones. Comparison of skin extracts and medium of cultured mouse skin fibroblasts by Western blotting showed that while tissues contain short 220 kDa type XII collagen polypeptides as well as the long form, cultured cells produce mainly the long form with 350 kDa polypeptides. © 1993 wiley-Liss, Inc.
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  • 4
    ISSN: 1058-8388
    Keywords: Collagen XII ; Alternative splicing ; Mouse development ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Type XII collagen, a member of the FACIT group of extracellular matrix proteins, consists of molecules that are trimers of α1(XII) chains. The three chains in each molecule form a cross-shaped structure with a central globule from which a triple-helical tail and three finger-like regions (containing von Willebrand factor A-like domains and fibronectin type III repeats) extend. cDNA cloning/sequencing of chicken α1(XII) collagen and protein studies with mouse, bovine, and human material suggest that the α1(XII) collagen gene gives rise to two molecular variants, differing in the length of the finger-like regions, by alternative splicing of the primary transcript. To provide a basis for studies of the function of the two variants in an organism that can be genetically manipulated, we have isolated and sequenced mouse cDNAs encoding both splice variants. The sequence provides the first complete nucleotide and amino acid sequence of mammalian type XII collagen. From these cDNAs we have generated digoxigenin-labeled RNA probes for in situ hybridization of developing mouse embryos to find out whether the splicing mechanism responsible for generation of the two forms is developmentally regulated. The results, combined with Northern blot and RT-PCR analysis of RNA from embryos at various developmental stages, demonstrate that the long form of collagen XII, XIIA, is the predominant form at early stages (ED7 and 11); at later stages of development (ED15 and 17) the short form, XIIB, becomes the major form. As the short form becomes the major product, the long splice variant continues to be expressed in several tissues, even after birth. An exception is dermis, which is positive for the long form up to embryonic day 15, but negative at day 18, when only the short form RNA can be detected. © 1995 wiley-Liss, Inc.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Developmental Dynamics 198 (1993), S. 150-157 
    ISSN: 1058-8388
    Keywords: Mouse development ; Retina ; Non-pigmented ciliary epithelium ; Col9a1 gene ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Northern blot hybridization, reverse-transcription polymerase chain reaction (RT-PCR), and RNase protection assays were used to examine the expression of twoα1(IX) collagen mRNA species (long and short form) in developing mouse tissues. Furthermore, in situ hybridization was used to identify cells expressing the Col9a1 gene during eye development. The results indicate that during embryonic development eye and heart preferentially express the short form; lung and cartilage express the long form; whereas liver expresses a very low level of long formα1(IX) mRNA which can only be detected by RT-PCR. In situ hybridization demonstrated that at 10.5 day postcoitum (d.p.c.), theα1(IX) collagen mRNAs were first expressed in optic cup (neural ectoderm) but not in lens vesicle (surface ectoderm). By 13.5 d.p.c., the cells that express theα1(IX) mRNA progressively were concentrated to ward the anterior part of the neural retina. By 16.5-18.5 d.p.c., the hybridization signals were found exclusively in the inner non-pigmented layer of the presumptive ciliary epithelium. As ciliary epithelial cells become well differentiated 3 weeks after birth, cells expressing the Col9a1 gene were limited to the junction between mature ciliary folds and the neural retina. No hybridization signal could be detected in ocular tissues of mouse older than 6 weeks. It is of interest to note that a hybridization signal was not detected in cornea at the various developmental stages examined, suggesting that mouse cornea does not significantly expressα1(IX) mRNA during embyronic development. This differs from that of chick cornea development. In summary, the expression of the Col9a1 gene shows a temporospatial pattern throughout mouse eye development. It is suggested that the short form collagen IX may play an important role in eye development. © 1993 Wiley-Liss, Inc.
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  • 6
    ISSN: 1058-8388
    Keywords: TIMP-3 ; Metalloproteinases ; Extracellular matrix ; Epithelium ; Cartilage ; Muscle ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Remodeling of the extracellular matrix (ECM) is an essential component of normal development and is also involved in the pathogenesis of arthritis and the spread of cancer. The matrix metalloproteinases and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play an important role in this context. We have isolated mouse cDNA clones encoding a novel member of the TIMP family, designated TIMP-3. We have assigned the Timp-3 locus to the [C1-D1] region of mouse chromosome 10 using both genetic and cytogenetic methods. The conceptual translation product of the Timp-3 cDNA shows a high degree of similarity with ChIMP-3, a recently cloned chicken metalloproteinase inhibitor, as well as significant structural similarity with the amino acid sequences of the previously isolated members of this family, TIMP-1 and TIMP-2. The pattern of expression of Timp-3 in the developing mouse embryo is distinct from that previously reported for Timp-1. Timp-3 is expressed in cartilage and skeletal muscle, in myocardium, in the skin, oral and nasal epithelium, in the newborn mouse liver, in the epithelium of some tubular structures such as the developing bronchial tree, oesophagus, colon, urogenital sinus, bile duct, in the kidney, salivary glands, and in the choroid plexus of the brain. The patterns of Timp-3 expression in surface epithelia and in the epithelial lining of many tubular organs suggests that TIMP-3 may be involved in regulating ECM remodeling during the folding of epithelia and during the formation, branching, and expansion of epithelial tubes. In the mouse placenta, expression is seen in the trophoblast, raising the possibility that TIMP-3 may be involved in regulating trophoblastic invasion of the uterus. We propose a role for TIMP-3 in musculoskeletal and cardiac development, in the morphogenesis of certain epithelial structures, and placental implantation. © 1994 Wiley-Liss, Inc.
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