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Domain organizations of modular extracellular matrix proteins and their evolution.

Multidomain proteins which are composed of modular units are a rather recent invention of evolution. Domains are defined as autonomously folding regions of a protein, and many of them are similar in sequence and structure, indicating common ancestry. Their modular nature is emphasized by frequent repetitions in identical or in different proteins and by a large number of different combinations with other domains. The extracellular matrix is perhaps the largest biological system composed of modular mosaic proteins, and its astonishing complexity and diversity are based on them. A cluster of minireviews on modular proteins is being published in Matrix Biology. These deal with the evolution of modular proteins, the three-dimensional structure of domains and the ways in which these interact in a multidomain protein. They discuss structure-function relationships in calcium binding domains, collagen helices, alpha-helical coiled-coil domains and C-lectins. The present minireview is focused on some general aspects and serves as an introduction to the cluster.

Animals↗

The role of laparoscopic surgery in gynaecological oncology.

Minimal access surgery is here to stay in gynaecological oncology. Within the last three years, rapid strides have been made in applying minimal access surgical techniques to a wide range of gynaecological oncology procedures. The re-assessment of radical vaginal surgery has come largely because of the ease of accessing the pelvic lymph nodes using retroperitoneal and intraperitoneal techniques. An ability to assess the lymph nodes of the pelvis and the para-aortic region prior to definitive therapy is making management of many oncological conditions more logical. Question marks still arise over the place of minimal access surgery in ovarian cancer. A recent study by Professor Gunther Kinderman (Munich) in which, following a postal questionnaire, he identified an unacceptably high rate of laparoscopic interventions in invasive cancer with a parallel unacceptably high rate of metastatic disease, particularly in the port sites, has demonstrated a need for constant vigilance and careful assessment of the application of minimal access surgery in certain areas of oncology. Even while this chapter was in press, Professor Daniel Dargent has shown the possibility of carrying out assessment laparoscopically of the groin lymph nodes using a combination of minimal access surgery and plastic surgical techniques to remove fat. This technique when applied to sentinel node identification may revolutionize our assessment of the groin. Clearly this is an exciting time in gynaecological oncology and many and new inventive applications are being visualized by surgeons throughout the world. When this chapter is rewritten in two years time, inevitably, a considerable part of it will be altered. A glimpse of the future has been seen and we await the full vision with bated breath.

Female↗

The versatile August Bier (1861-1949), father of spinal anesthesia.

"A professor is a gentleman with a different point of view." This characteristic and sarcastic statement was often recited by August Bier (1861-1949) and can also be aptly applied to him. As the father of spinal and intravenous regional neural blockade, Bier had a tremendous impact on surgery and anesthesia. It took him only two years to become a senior lecturer in surgery (so-called "Habilitation") under the guidance of Friedrich von Esmarch. In 1899, he was appointed chairman of the Department of Surgery at the University of Greifswald. From there, he moved to the University of Bonn in 1903 and then succeeded Ernst von Bergmann in Berlin in 1907. Bier's interest in the philosophical theories of Hippocrates and Heraclitus had a significant influence on his outlook on medical practice. His surgical colleagues disapproved of this and his interest in homeopathy. On the other hand, he earned much respect as the co-author of a surgical textbook, i.e., Chirurgische Operationslehre (Operative Surgery). He had a remarkable breadth of nonmedical interests, including philosophy and forestry, and the ideas he expressed are viable even today. His publications on philosophical subjects are as up to date as his concepts in forestry. In 1932, Bier finally decided to retire, although by then he was no longer operating. From that time on, he lived out his days at his estate in Sauen, and he died in 1949 at the age of 88. In this paper we describe some previously unknown aspects of Bier's work in both surgery and research; anesthesiologists and their patients are the beneficiaries of two other of his inventions, namely, spinal and IV local anesthesia. Unfortunately, it is not possible to acknowledge all the innovations of this ingenious surgeon, who truly deserved the description "A professor is a gentleman with a different point of view."

Anesthesia, Spinal↗

Supply and demand for alcohol in Australia: relationships between industry structures, regulation and the marketplace.

Aspects of alcohol supply and demand relationships are examined in relation to the two main beverage varieties in Australia, wine and beer. It is argued that this case study illustrates how the 'supply side' is able to create and protect demand for alcohol through both taking advantage of and influencing government regulation of the market for alcohol. In relation to low alcohol beer the impact on public health and safety has been extremely positive. In relation to the creation of cask wine in the late 1960s there have been demonstrably deleterious effects. Preferential taxation arrangements for the Australian wine industry have dramatically increased both exports and home consumption. One unintended consequence has been the creation of a major new market for cheap bulk wines that have had a devastating public health impact, particularly on Aboriginal communities, and also the invention of 'alco-pops'. Two-thirds of all table wine consumed in Australia now comes in a cask and 90% of this product is manufactured by three multi-national companies that wield enormous power and political influence to maintain the status quo. The Australian beer industry is well known internationally for its export of 'full strength' (around 5% by volume) beers. What is less well known is its commercial success in the development of low and mid-strength varieties for home consumption. In some States these now comprise 40% by volume of the beer market. This development can largely be attributed to State taxation arrangements, to drink-driving law enforcement, marketing strategies and to a decade of intense competition between several major brewers. This case study indicates how alcohol taxation policy can have major impacts on public health (both positive and negative) but that in a modern market economy it is difficult for governments to act in the public interest due to pressures from vested interest groups.

Journal Article↗

The theory of DNA separation by capillary electrophoresis.

The Human Genome has been sequenced in large part owing to the invention of capillary electrophoresis. Although this technology has matured enough to allow such amazing achievements, the physical mechanisms at play during separation have yet to be completely understood and optimized. Recently, new separation regimes and new physical mechanisms have been investigated. The use of free-flow electrophoresis and new modes of pulsed-field electrophoresis have been suggested, while we have observed a shift towards single nucleotide polymorphism analysis and microchip technologies. A strong theoretical basis remains essential for the efficient development of new methods.

Coated Materials, Biocompatible↗

Evolution of the diverse antifreeze proteins.

Different types of ice-growth-inhibiting antifreeze proteins, first recognized in fish, have now been isolated from insects and plants, and the list continues to expand. Their structures are amazingly diverse; how they attain the same function are subjects of intense research. Evolutionary precursors of several members have been identified - divergent proteins of apparently unrelated function. The hybridization of information from structural and molecular evolution studies of these molecules provides a forum in which issues of selection, gene genealogy, adaptive evolution, and invention of a novel function can be coherently addressed.

Amino Acid Sequence↗

Regulation of neural determination by evolutionarily conserved signals: anti-BMP factors and what next?

The evolutionary conservation of Chordin/bone morphogenetic protein (BMP) signaling supports the hypothesis of dorsal-ventral axis inversion of vertebrates and invertebrates, and implies that the invention of a central nervous system occurred only once during animal evolution. This hypothesis is further strengthened by recent findings of the conservation of downstream genes and modifier genes of neural induction. On the other hand, in contrast with such gross conservation, recent data suggest that the requirement for some signals in neural determination may differ even within the vertebrate subphylum.

Amphibians↗

Scanning force microscopy under aqueous solutions.

Merely ten years after its invention, the scanning force microscope is becoming a powerful method to investigate the structure and dynamics of biological molecules under aqueous environments. From the visualization of transcription in real time to the mechanical manipulation of individual proteins, the advances made during the past year open up a vast number of exciting applications of this technique in biology.

Connectin↗

Developmental evolution: Axial patterning in insects.

The Drosophila bicoid gene is well known for encoding a protein that forms a morphogenetic gradient with a key role in anterior patterning of the fruitfly embryo. Recent results suggest the evolution of bicoid might have involved dramatic changes in function - essentially the invention of a new regulatory protein.

Animals↗

Identification of caspases and apoptosis in the simple metazoan Hydra.

Apoptosis is a normal process by which cells die and are eliminated from tissue by phagocytosis [1]. It is involved in regulating cell numbers in adult tissues and in eliminating 'excess' cells during embryogenesis and development. Apoptosis is mediated by activation of caspases, which then cleave a variety of cellular substrates and thereby cause the characteristic morphology of apoptotic cells (rounded cells, condensed chromatin, susceptibility to phagocytosis) [2]. Although apoptosis has been well documented in nematodes, insects and mammals, it is not yet clear how early in evolution apoptosis or its component enzymes arose. In the simple metazoan Hydra vulgaris, cell death regulates cell numbers [3] [4] [5]. In starved animals, for example, epithelial cell proliferation continues at a nearly normal rate although the tissue does not increase in size; the excess cells produced are eliminated by phagocytosis. Cell death can also be induced in wild-type hydra by treatment with colchicine [6] or in a mutant strain (sf-1) by temperature shock [7]. Here, we show that cell death in hydra is morphologically indistinguishable from apoptosis in higher animals, that hydra polyps express two genes with strong homology to members of the caspase 3 family, and that caspase-3-specific enzyme activity accompanies apoptosis in hydra. The occurrence of apoptosis and caspases in a member of the ancient metazoan phylum Cnidaria supports the idea that the invention of apoptosis was an essential feature of the evolution of multicellular animals.

Animals↗

Metabolites: a helping hand for pathway evolution?

The evolution of enzymes and pathways is under debate. Recent studies show that recruitment of single enzymes from different pathways could be the driving force for pathway evolution. Other mechanisms of evolution, such as pathway duplication, enzyme specialization, de novo invention of pathways or retro-evolution of pathways, appear to be less abundant. Twenty percent of enzyme superfamilies are quite variable, not only in changing reaction chemistry or metabolite type but in changing both at the same time. These variable superfamilies account for nearly half of all known reactions. The most frequently occurring metabolites provide a helping hand for such changes because they can be accommodated by many enzyme superfamilies. Thus, a picture is emerging in which new pathways are evolving from central metabolites by preference, thereby keeping the overall topology of the metabolic network.

Animals↗

The evolution of ribonucleotide reduction.

Ribonucleotide reduction was essential for the transition from RNA to DNA by supplying deoxyribonucleotide precursors. The reaction requires free radical chemistry. Three quite different classes of ribonucleotide reductases are known today. All three are proteins containing a stable free radical amino acid, but each uses a different mechanism for its generation. Did they evolve from a common ancestor, with the arrival of atmospheric oxygen providing the driving force for their divergence, or was each a separate evolutionary invention?

Escherichia coli↗

Imaging and manipulation of biological structures with the AFM.

Many biologists have dreamt of physically touching and manipulating the biomolecules they were investigating. With the invention of the atomic force microscope (AFM), this dream has come true. Here, recent applications of the AFM to image and to manipulate biological systems at the nanometer scale are reviewed. Macromolecular biological assemblies as well as individual biomolecules can be subjected to controlled nanomanipulation. Examples of AFM application in imaging and nanomanipulation include the extraction of chromosomal DNA for genetic analysis, the disruption of antibody--antigen bonds, the dissection of biological membranes, the nanodissection of protein complexes, and the controlled modulation of protein conformations. Also reviewed is the novel combination of single molecule imaging and force spectroscopy which allows biomolecules to be imaged, and inter- and intramolecular forces to be measured. Future application of these nanotechniques will reveal new information on the structure, function and assembly of biomolecules.

Antigen-Antibody Complex↗

Experimental study of the effects of different stapling devices in healing of the mechanically sutured bronchial stump.

OBJECTIVE: The invention of the mechanical suture of the bronchial stump resulted in the significant decrease of the incidence of bronchial fistulas. Bronchial fistula constitutes the most dangerous complication of the pulmonary resection. In connection with some negative opinions in world literature regarding the safety of applying some types of mechanical suture, the multi-factor analysis of efficacy of bronchial stump closure following the total pneumonectomy by two different types of stapling devices was performed. METHODS: The experimental study was performed on 22 sheep. Each sheep underwent left pneumonectomy. In group I the bronchus was closed by the hinged-jaw stapling device (TA-Premium, Auto-Suture). In group II the bronchus was closed by the stapling device of parallel pattern (RLV 30 Ethicon). The macroscopic parameters (i.e. linear structure of staples, degree of staples closure, the symmetry of staples closure in the medial and lateral part of bronchial stump) as well as microscopic parameters (i.e. degree of inflammatory reaction, degree disorder in collagen fibers system, degree of disorders in cartilaginous system, degree of vascular proliferation and nervous regeneration) were evaluated. RESULTS: In three cases of group I the serious abnormalities in staples closure in the medial part of the bronchial stump were revealed. Abnormalities were found also in microscopic evaluation of the specimens. In the whole group the inflammatory reaction predominated in the medial part of bronchial stump near the hinge of the cartridge (P value <0.05). The disorder in the collagen fibers system as well as in the stratified structure of muscular fibers and cartilaginous system was proved. On the other hand, in group II all staples were properly closed in adequate linear structure, without any symmetry in both medial and lateral end of the bronchial stump. The microscopic findings were only the subtle inflammatory process and a slight disarrangement in muscular, collagen and cartilaginous systems. CONCLUSION: The listed abnormalities of mechanical, hinged-jaw suture of bronchial stump seem to be due to the inaccurate placement of staples, their incomplete closure, and excessive damage to the sutured tissues. We conclude that the application of the hinged-jaw mechanical suture of the bronchial stump might result in higher incidence of bronchial fistula after pneumonectomy.

Animals↗

Basic principles and equipment in neuroendoscopy.

In sum, understanding some of the basic principles of endoscopy and awareness of available resources can potentially be of considerable help to experienced neurosurgeons as well as beginners in selection of the most appropriate tools for different procedures and making cost-effective choices when browsing through multiple commercial advertisements and purchasing new equipment. Although numerous advantages in science and industry have made it possible to offer a wide variety of neuroendoscopes and tools, we believe the major achievements in this field are yet to occur. This particularly refers to the development of smaller fiberoptic scopes with better image quality and three-dimensional endoscopes and to the invention of more efficient tools for endoscopic tumor removal with the same degree of safety as in open surgery.

Central Nervous System Diseases↗

Ion trap mass spectrometry: a personal perspective.

This paper is a personal perspective of the commercial development of the three-dimensional quadrupole ion trap mass spectrometer. Early ion trap invention and development which dates back to 1953, is described. The development of the ion trap is traced through three ages with the last age being where commercial development takes place. Key technical breakthroughs in ion trap technology and commercialization are presented and described up to the present time.

Journal Article↗

Microplate array diagonal gel electrophoresis (MADGE), CpG-PCR and temporal thermal ramp-MADGE (Melt-MADGE) for single nucleotide analyses in populations.

Important requirements for molecular genetic epidemiological studies are economy, sample parallelism, convenience of setup and accessibility, goals inadequately met by existent approaches. We invented microplate array diagonal gel electrophoresis (MADGE) to gain simultaneously the advantages of simple setup, 96-well microplate compatibility, horizontal electrophoresis, and the resolution of polyacrylamide. At essentially no equipment cost (one simple plastic gel former), 10-100-fold savings on time for sample coding, liquid transfers, and data documentation, in addition to volume reductions and gel re-use, can be achieved. MADGE is compatible with ARMS, restriction analysis and other pattern analyses. CpG-PCR is a general PCR approach to CpG sites (10-20% of all human single base variation): both primers have 3' T, and are abutted to the CpG, forcing a TaqI restriction site if the CpG is intact. Typically, a 52 bp PCR product is then cut in half. CpG-PCR also illustrates that PAGE-MADGE readily permits analysis of 'ultrashort' PCRs. Melt-MADGE employs real-time-variable-temperature electrophoresis to examine duplex mobility during melting, achieving DGGE-like de novo, mutation scanning, but with the conveniences of arbitrary programmability, MADGE compatibility and short run time. This suite of methods enhances our capability to type or scan thousands of samples simultaneously, by 10-100-fold.

CpG Islands↗