Direct demonstration of production of transforming growth factor activity by embryonic chick tissue

Summary The presence of transforming growth factor activity in early chick embryos was directly demonstrated by the ability of limb and tail buds to induce anchorage independent division in NRK 49f cells. Colony number increased with limb bud number and developmental stage. Medium conditioned by tail buds contained some stimulating effect, and strongly promoted the action of other transforming growth factors.     

Direct demonstration of production of transforming growth factor activity by embryonic chick tissue

The presence of transforming growth factor activity in early chick embryos was directly demonstrated by the ability of limb and tail buds to induce anchorage independent division in NRK 49 f cells. Colony number increased with limb bud number and developmental stage. Medium conditioned by tail buds contained some stimulating effect, and strongly promoted the action of other transforming growth factors.     

Protecting DNA from errors and damage: an overview of DNA repair mechanisms in plants compared to mammals

The genome integrity of all organisms is constantly threatened by replication errors and DNA damage arising from endogenous and exogenous sources. Such base pair anomalies must be accurately repaired to prevent mutagenesis and/or lethality. Thus, it is not surprising that cells have evolved multiple and partially overlapping DNA repair pathways to correct specific types of DNA errors and lesions. Great progress in unraveling these repair mechanisms at the molecular level has been made by several talented researchers, among them Tomas Lindahl, Aziz Sancar, and Paul Modrich, all three Nobel laureates in Chemistry for 2015. Much of this knowledge comes from studies performed in bacteria, yeast, and mammals and has impacted research in plant systems. Two plant features should be mentioned. Plants differ from higher eukaryotes in that they lack a reserve germline and cannot avoid environmental stresses. Therefore, plants have evolved different strategies to sustain genome fidelity through generations and continuous exposure to genotoxic stresses. These strategies include the presence of unique or multiple paralogous genes with partially overlapping DNA repair activities. Yet, in spite (or because) of these differences, plants, especially Arabidopsis thaliana, can be used as a model organism for functional studies. Some advantages of this model system are worth mentioning: short life cycle, availability of both homozygous and heterozygous lines for many genes, plant transformation techniques, tissue culture methods and reporter systems for gene expression and function studies. Here, I provide a current understanding of DNA repair genes in plants, with a special focus on A. thaliana. It is expected that this review will be a valuable resource for future functional studies in the DNA repair field, both in plants and animals.     

Effect of the pentosanpolysulfate SP 54 on the collagen of embryonic limb buds cultured in vitro

Summary After addition of SP 54 to limb buds from 11-day-old mouse embryos in tissue culture, collagen with an altered structure is produced.Durchgeführt mit Unterstützung durch die DFG (SFB 29).     

Effect of sublethal concentrations of sumithion on limb regeneration of fresh water field crab Oziotelphusa senex senex

The initiation and progress of regeneration following the removal of the left 4th walking leg were altered in the crab (Oziotelphusa senex senex) by exposure to sumithion. Depending on the concentration used, sumithion caused a complete inhibition of regeneration, a delay of initiation of limb bud development or a reduction of limb bud growth rate. Crustacean limb regeneration can also be used as a sensitive bioassay for studying the effects of environmental pollutants.     

Molecular pathogenesis of virus infections

Although a very wide range of viral diseases exists in vertebrates, certain generalizations can be made regarding pathogenetic pathways on the molecular level. The presentation will focus on interactions of virions and their components with target cells. Using coronaviruses as examples the changes in virulence have been traced back to single mutational events; recombination, however, is likely to be an alternative mechanism by which virus-host interactions (e.g. the cell-, organ- or animal species-spectrum) can dramatically change. Receptor molecules are essential for the early interactions during infection and some of these have been identified. Events in the target cell and the host organism are discussed, and wherever possible, aspects of virus evolution and cooperation between infectious agents are highlighted.     

The role of ras and other low molecular weight guanine nucleotide (GTP)-binding proteins during hematopoietic cell differentiation

Recent progress in the understanding of signal transduction and gene regulation in hematopoietic cells has shown that many intracellular signalling pathways are modulated by low molecular weight guanine nucleotide (GTP)-binding proteins (LMWGs). LMWGs act as molecular switches for regulating a wide range of signal-transduction pathways in virtually all cells. In hematopoietic cells, LMWGs have been shown to participate in essential functions such as growth control, differentiation, cytoskeletal organization, cytokine and chemoattractant-induced signalling events, reduced nicotinamide adenine dinucleotide phosphate oxidase activity, intracellular vesicle transport and secretion. In human leukemias, myelodysplastic syndromes and myeloproliferative disorders, Ras activation occurs by point mutations, overexpression or by alteration of NF-1 Ras-GTPase activating protein (GAP). These are postinitiation events in leukemia but may modulate growth-factor-dependent and independent leukemic growth. Two animal models of mutated N-ras expression resulting in myelodysplastic and myeloproliferative features are discussed. The role of Ras in organ development is discussed in the context of transgenic knockout mice. More LMWG functions will certainly be identified as we gain a better understanding of regulatory pathways modulating myeloid signal transduction. This review will summarize our current understanding of this rapidly advancing area of research.     

Effect of testosterone and 17-beta estradiol on limb regeneration in the newt, Notophthalmus viridescens

Gonadectomy, or injections of testosterone or 17-beta estradiol, had no apparent effect on the rate of regeneration or histological appearance of limb regenerates in the newt, Notophthalmus viridescens. Neither promotion, nor inhibition of limb regeneration was observed.     

Transglutaminase induction by various cell death and apoptosis pathways

Clarification of the molecular details of forms of natural cell death, including apoptosis, has become one of the most challenging issues of contemporary biomedical sciences. One of the effector elements of various cell death pathways is the covalent cross-linking of cellular proteins by transglutaminases. This review will discuss the accumulating data related to the induction and regulation of these enzymes, particularly of tissue type transglutaminase, in the molecular program of cell death. A wide range of signalling pathways can lead to the parallel induction of apoptosis and transglutaminase, providing a handle for better understanding the exact molecular interactions responsible for the mechanism of regulated cell death.     

Molecular and Cellular Basis of Regeneration and Tissue Repair

Upon amputation of the urodele limb, the epidermal cells surrounding the amputation plane migrate to heal the wound. The resulting wound epidermis (WE) induces the regeneration process, resulting in blastema formation, cell division, and ultimately repatterning into a new limb. Despite its central role in the initiation of limb regeneration, little is known about how the WE forms. Here we discuss various models of WE formation and the experimental data in support of each.     

Muscle development, regeneration and laminopathies: how lamins or lamina-associated proteins can contribute to muscle development, regeneration and disease

The aim of this review article is to evaluate the current knowledge on associations between muscle formation and regeneration and components of the nuclear lamina. Lamins and their partners have become particularly intriguing objects of scientific interest since it has been observed that mutations in genes coding for these proteins lead to a wide range of diseases called laminopathies. For over the last 10 years, various laboratories worldwide have tried to explain the pathogenesis of these rare disorders. Analyses of the distinct aspects of laminopathies resulted in formulation of different hypotheses regarding the mechanisms of the development of these diseases. In the light of recent discoveries, A-type lamins—the main building blocks of the nuclear lamina—together with other key elements, such as emerin, LAP2α and nesprins, seem to be of great importance in the modulation of various signaling pathways responsible for cellular differentiation and proliferation.     

Development and differentiation of the intestinal epithelium

The gastrointestinal tract develops from a simple tube to a complex organ with patterns of differentiation along four axes of asymmetry. The organ is composed of all three germ layers signaling to each other during development to form the adult structure. The gut epithelium is a constitutively developing tissue, constantly differentiating from a stem cell in a progenitor pool throughout the life of the organism. Signals from the adjacent mesoderm and between epithelial cells are required for normal orderly development/differentiation, homeostasis, and apoptosis. Embryonically important patterning factors are used during adult stages for these processes. Such critical pathways as the hedgehog, bone morphogenetic protein, Notch, Sox, and Wnt systems are used both in embryologic and adult times of gut development. We focus on and review the roles of these factors in gut epithelial cell development and differentiation.Received 18 October 2002; received after revision 18 December 2002; accepted 18 December 2002     

Metabolic engineering of Saccharomyces cerevisiae: a key cell factory platform for future biorefineries

Metabolic engineering is the enabling science of development of efficient cell factories for the production of fuels, chemicals, pharmaceuticals, and food ingredients through microbial fermentations. The yeast Saccharomyces cerevisiae is a key cell factory already used for the production of a wide range of industrial products, and here we review ongoing work, particularly in industry, on using this organism for the production of butanol, which can be used as biofuel, and isoprenoids, which can find a wide range of applications including as pharmaceuticals and as biodiesel. We also look into how engineering of yeast can lead to improved uptake of sugars that are present in biomass hydrolyzates, and hereby allow for utilization of biomass as feedstock in the production of fuels and chemicals employing S. cerevisiae. Finally, we discuss the perspectives of how technologies from systems biology and synthetic biology can be used to advance metabolic engineering of yeast.     

The chordate amphioxus: an emerging model organism for developmental biology

The cephalochordate amphioxus is the closest living invertebrate relative of the vertebrates. It is vertebrate-like in having a dorsal, hollow nerve cord, notochord, segmental muscles, pharyngeal gill slits and a post-anal tail that develops from a tail bud. However, amphioxus is less complex than vertebrates, lacking neural crest and having little or no mesenchyme. The genetic programs patterning the amphioxus embryo are also similar to those patterning vertebrate embryos, although the amphioxus genome lacks the extensive gene duplications characteristic of vertebrates. This relative structural and genomic simplicity in a vertebrate-like organism makes amphioxus ideal as a model organism for understanding mechanisms of vertebrate development.Received 18 February 2004; received after revision 9 April 2004; accepted 19 April 2004     

Emery-Dreifuss muscular dystrophy at the nuclear envelope: 10 years on

Emery-Dreifuss muscular dystrophy (EDMD) is a neuromuscular degenerative condition with an associated dilated cardiomyopathy and cardiac conduction defect. It can be inherited in either an X-linked or autosomal manner by mutations in the nuclear proteins emerin and lamin A/C, respectively. Traditionally muscular dystrophies were associated with defects in sarcolemma-associated proteins and, therefore, a nuclear connection suggested the existence of novel signalling pathways associated with this group of diseases. Subsequently, other mutations in the lamin A/C gene were attributed to a range of tissue-specific degenerative conditions, collectively known as the ‘laminopathies’. Therefore, any proposed hypothesis underlying the molecular mechanism of EDMD needs to include this anomaly. As we celebrate the 10th anniversary of the identification of emerin as a component of the nuclear envelope, I discuss here the available evidence that currently implicates EDMD as arising from perturbations in myogenic regulatory pathways, causing temporal delays in both cell cycle progression and muscle regeneration. Received 25 May 2006; received after revision 22 June 2006; accepted 22 August 2006     

Electron microscopic study of the penetration and distribution of somitic cells in the mesoblast of the limb buds of reptiles (Anguis fragilis and Lacerta viridis)]

Based on characteristics of mitochondria and on the amount of lipid inclusions, a distinction between somitic cells and mesoblastic somatopleural cells is possible, at the early stages of the development of the limb bud in Reptiles (Anguis fragilis and Lacerta viridis). The dislocation of the ventral processes of the somites and the localisation of the somitic cells in the mesoblast of the anterior limb buds could be studied.     

Adducin: structure, function and regulation

Adducin is a ubiquitously expressed membrane-skeletal protein localized at spectrin-actin junctions that binds calmodulin and is an in vivo substrate for protein kinase C (PKC) and Rho-associated kinase. Adducin is a tetramer comprised of either alpha/beta or alpha/gamma heterodimers. Adducin subunits are related in sequence and all contain an N-terminal globular head domain, a neck domain and a C-terminal protease-sensitive tail domain. The tail domains of all adducin subunits end with a highly conserved 22-residue myristoylated alanine-rich C kinase substrate (MARCKS)-related domain that has homology to MARCKS protein. Adducin caps the fast-growing ends of actin filaments and also preferentially recruits spectrin to the ends of filaments. Both the neck and the MARCKS-related domains are required for these activities. The neck domain self-associates to form oligomers. The MARCKS-related domain binds calmodulin and contains the major phosphorylation site for PKC. Calmodulin, gelsolin and phosphorylation by the kinase inhibit in vitro activities of adducin involving actin and spectrin. Recent observations suggest a role for adducin in cell motility, and as a target for regulation by Rho-dependent and Ca2+-dependent pathways. Prominent physiological sites of regulation of adducin include dendritic spines of hippocampal neurons, platelets and growth cones of axons.     

Tracking prions: the neurografting approach

The physical nature of the agent that causes transmissible spongiform encephalopathies (the 'prion'), is the subject of passionate controversy. Investigation of it has benefited tremendously from the use of transgenic and knockout technologies. However, prion diseases present several other enigmas, including the mechanism of brain damage and how the affinity of the agent for the central nervous system is controlled. Here we show that such questions can be effectively addressed in transgenic and knockout systems, and that pathogenesis may be clarified even before we can be certain about the nature of the infectious agent. Availability of mice overexpressing the Prnp gene (which encodes the normal prion protein) and Prnp knockout mice allows for selective reconstitution experiments aimed at expressing PrP in specific portions of the brain or in selected populations of hemato- and lymphopoietic origin. We summarize how such studies can offer insights into how prions administered to peripheral sites can gain access to central nervous tissue, and into the molecular requirements for spongiform brain damage.     

Zur entwicklungsphysiologischen Wirkungsanalyse von antimitotischen Stoffen

Summary The cleavage mitoses of eggs of the fresh-water oligochete Tubifex may be irreversibly blocked, if treated during a relatively short time by solutions of certain antimitotic substances (benzoquinone, naphthoquinone or colchicine). It is also possible to inhibit tail regeneration in tadpoles of Rana or Xenopus by a single colchicine treatment during only 30 to 60 minutes. It is discussed whether this is due to irreversible loss of regeneration capacity or simply to an inhibition of the first regeneration processes.     

Multiple roles of class I HDACs in proliferation, differentiation, and development

Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future.