Current Issues in Molecular Biology

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Factors That Affect the Horizontal Transfer of Transposable Elements

by Joana C. Silva, Elgion L. Loreto and Jonathan B. Clark

Curr. Issues Mol. Biol. 2004, 6(1), 57-72; https://0-doi-org.brum.beds.ac.uk/10.21775/cimb.006.057 - 25 Nov 2003

Cited by 1 | Viewed by 706

Transposable elements are characterized by their ability to spread within a host genome. Many are also capable of crossing species boundaries to enter new genomes, a process known as horizontal transfer. Focusing mostly on animal transposable elements, we review the occurrence of horizontal [...] Read more.

Transposable elements are characterized by their ability to spread within a host genome. Many are also capable of crossing species boundaries to enter new genomes, a process known as horizontal transfer. Focusing mostly on animal transposable elements, we review the occurrence of horizontal transfer and examine the methods used to detect such transfers. We then discuss factors that affect the frequency of horizontal transfer, with emphasis on the mechanism and regulation of transposition. An intriguing feature of horizontal transfer is that its frequency differs among transposable element families. Evidence summarized in this review indicates that this pattern is due to fundamental differences between Class I and Class II elements. There appears to be a gradient in the incidence of horizontal transfer that reflects the presence of DNA intermediates during transposition. Furthermore, horizontal transfer seems to predominate among families for which copy number is controlled predominantly by self-regulatory mechanisms that limit transposition. We contend that these differences play a major role in the observed predominance of horizontal transfer among Class II transposable elements. Full article

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The Sleeping Beauty Transposable Element: Evolution, Regulation and Genetic Applications

by Zoltán Ivics, Christopher D. Kaufman, Hatem Zayed, Csaba Miskey, Oliver Walisko and Zsuzsanna Izsvák

Curr. Issues Mol. Biol. 2004, 6(1), 43-56; https://0-doi-org.brum.beds.ac.uk/10.21775/cimb.006.043 - 25 Nov 2003

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Abstract

Members of the Tc1/mariner superfamily of transposable elements isolated from vertebrate species are inactive due to the accumulation of mutations. A representative of a subfamily of fish elements estimated to be last active >10 million years ago has been reconstructed, and named [...] Read more.

Members of the Tc1/mariner superfamily of transposable elements isolated from vertebrate species are inactive due to the accumulation of mutations. A representative of a subfamily of fish elements estimated to be last active >10 million years ago has been reconstructed, and named Sleeping Beauty (SB). This element opened up new avenues for studies on DNA transposition in vertebrates, and for the development of transposon tools for genetic manipulation in important model species and in humans. Multiple transposase binding sites within the terminal inverted repeats, a transpositional enhancer sequence, unequal affinity of the transposase to the binding sites and the activity of the cellular HMGB1 protein all contribute to a highly regulated assembly of SB synaptic complexes, which is likely a requirement for the subsequent catalytic steps. Host proteins involved in double-strand DNA break repair are limiting factors of SB transposition in mammalian cells, underscoring evolutionary, structural and functional links between DNA transposition, retroviral integration and V(D)J recombination. SB catalyzes efficient cut-and-paste transposition in a wide range of vertebrate cells in tissue culture, and in somatic tissues as well as the germline of the mouse and zebrafish in vivo, indicating its usefulness as a vector for transgenesis and insertional mutagenesis. Full article

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The ER Glycoprotein Quality Control System

by Selma Dejgaard, Johan Nicolay, Maryam Taheri, David Y. Thomas and John J.M. Bergeron

Curr. Issues Mol. Biol. 2004, 6(1), 29-42; https://0-doi-org.brum.beds.ac.uk/10.21775/cimb.006.029 - 25 Nov 2003

Cited by 1 | Viewed by 549

Abstract

The endoplasmic reticulum (ER) is the major site for folding and sorting of newly synthesized secretory cargo proteins. One central regulator of this process is the quality control machinery, which retains and ultimately disposes of misfolded secretory proteins before they can exit the [...] Read more.

The endoplasmic reticulum (ER) is the major site for folding and sorting of newly synthesized secretory cargo proteins. One central regulator of this process is the quality control machinery, which retains and ultimately disposes of misfolded secretory proteins before they can exit the ER. The ER quality control process is highly effective and mutations in cargo molecules are linked to a variety of diseases. In mammalian cells, a large number of secretory proteins, whether membrane bound or soluble, are asparagine (N)-glycosylated. Recent attention has focused on a sugar transferase, UDP-Glucose: glycoprotein glucosyl transferase (UGGT), which is now recognized as a constituent of the ER quality control machinery. UGGT is capable of sensing the folding state of glycoproteins and attaches a single glucose residue to the Man₉GlcNAc₂ glycan of incompletely folded or misfolded glycoproteins. This enables misfolded glycoproteins to rebind calnexin and reenter productive folding cycles. Prolonging the time of glucose addition on misfolded glycoproteins ultimately results in either the proper folding of the glycoprotein or its presentation to an ER associated degradation machinery. Full article

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The Genome Revolution in Vaccine Research

by Barbara Capecchi, Davide Serruto, Jeannette Adu-Bobie, Rino Rappuoli and Mariagrazia Pizza

Curr. Issues Mol. Biol. 2004, 6(1), 17-28; https://0-doi-org.brum.beds.ac.uk/10.21775/cimb.006.017 - 25 Nov 2003

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Abstract

The conventional approach to vaccine development is based on dissection of the pathogen using biochemical, immunological and microbiological methods. Although successful in several cases, this approach has failed to provide a solution to prevent several major bacterial infections. The availability of complete genome [...] Read more.

The conventional approach to vaccine development is based on dissection of the pathogen using biochemical, immunological and microbiological methods. Although successful in several cases, this approach has failed to provide a solution to prevent several major bacterial infections. The availability of complete genome sequences in combination with novel advanced technologies, such as bioinformatics, microarrays and proteomics, have revolutionized the approach to vaccine development and provided a new impulse to microbial research. The genomic revolution allows the design of vaccines starting from the prediction of all antigens in silico, independently of their abundance and without the need to grow the pathogen in vitro. This new genome-based approach, which we have named "Reverse Vaccinology", has been successfully applied for Neisseria meningitidis serogroup B for which conventional strategies have failed to provide an efficacious vaccine. The concept of "Reverse Vaccinology" can be easily applied to all the pathogens for which vaccines are not yet available and can be extended to parasites and viruses. Full article

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Signal Transduction in T Helper Cells: CD4 Coreceptors Exert Complex Regulatory Effects on T Cell Activation and Function

by Rolf König and Wenhong Zhou

Curr. Issues Mol. Biol. 2004, 6(1), 1-16; https://0-doi-org.brum.beds.ac.uk/10.21775/cimb.006.001 - 25 Nov 2003

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Abstract

The immune system provides a highly sophisticated surveillance mechanism to detect diverse antigens and protect the host organism from invading pathogens and altered cells (e.g., virus-infected and tumor cells). Adaptive immune responses depend on the recognition of antigen by specific antigen receptors that [...] Read more.

The immune system provides a highly sophisticated surveillance mechanism to detect diverse antigens and protect the host organism from invading pathogens and altered cells (e.g., virus-infected and tumor cells). Adaptive immune responses depend on the recognition of antigen by specific antigen receptors that are expressed on the surface of T and B lymphocytes. Helper T cells provide regulatory functions and direct the adaptive immune system to respond appropriately to a particular antigen (i.e., cytotoxic T cell responses against viral infections and tumor cells, humoral responses against extracellular bacteria and parasitic worms). Helper T cells express CD4 co-receptors, which recognize conserved domains on MHC class II proteins, the same proteins that present antigen to the T cell receptor. Recent progress in T cell biology has identified multiple regulatory functions of the CD4 coreceptor during thymocyte development and antigen stimulation of mature T helper cells. These regulatory functions of CD4 depend on T cell receptor-independent signal transduction. In this review, I discuss the regulation of T cell signaling and emphasize the functional consequences of proper and improper CD4 coreceptor signaling. Full article

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Curr. Issues Mol. Biol., Volume 6, Issue 1 (January 2004) – 5 articles

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