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PubMed1995

[The history of tomography].

It is easily forgotten that not yet a hundred years ago the only way to look into the patients' body was via invasive procedures. Within the year of the discovery of X-rays by Conrad Röntgen the need for three dimensional imaging had been voiced. The driving force behind this development was undoubtedly clinical motivation. Planar X-radiographs were not satisfactory to the clinicians who urged the radiologists to provide them with tomographic images. Between 1910 and 1940, classical tomography has been the product of individuals rather than collective groups. It is only in the mid thirties that scientists found out about each other and started to correspond vigorously. Mayer was the first to suggest in 1914 the idea of tomography. Bocage, Grossman and Vallebona all developed the idea further and built their own equipment. In 1931 Ziedses des Plantes published the most extensive and thorough study on tomography. In the forties and fifties a stagnation is noticed, only further refinements to the existing equipment are carried out. Although Frank and Takahashi published the basic principles of axial tomography in the mid forties, we had to wait for the necessary developments in electronics before Hounsfield was able to develop and commercialize the first axial computer tomography in 1972 (EMI-Scanner). At the time all the big radiology companies rushed into the field and soon, second, third and fourth generation CT scanners became available. Only a few years later a new way of generating images without using ionizing radiation was introduced. Lauterbur and Damadian produced the first low quality images with magnetic resonance, a technique called zeugmatography by its inventors. In 1974 the first images of a living subject were published and initial scepticism was replaced by euphoria. This resulted in the spectacular evolution in Magnetic Resonance that we are now observing. While it is impossible to predict the future, the development of networks, the increase in data acquisition and storage will spread a new light on our specialty. A closer cooperation between radiologists, pathologists and clinicians will undoubtedly be necessary, as well as a partial redefinition of the radiologists task.

History, 20th Century↗
PubMed2006

The DnaA homolog of the hyperthermophilic eubacterium Thermotoga maritima forms an open complex with a minimal 149-bp origin region in an ATP-dependent manner.

In Escherichia coli, ATP-DnaA, but not ADP-DnaA, forms an initiation complex that undergoes site-specific duplex DNA unwinding, open complex formation. However, it remains unclear how highly the ATP-dependent activation of the initiation factor is conserved in evolution. The hyperthermophile Thermotoga maritima is one of the most ancient eubacteria in evolution. Here, we show that the DnaA homolog (tmaDnaA) of this bacterium forms open complexes with the predicted origin region (tma-oriC) in vitro. TmaDnaA has a strong and specific affinity for ATP/ADP as well as for 12-mer repeating sequences within the tma-oriC. Unlike ADP-tmaDnaA, ATP-tmaDnaA is highly cooperative in DNA binding and forms open complexes in a manner that depends on temperature and the superhelical tension of the tma-oriC-bearing plasmid. The minimal tma-oriC required for unwinding is a 149-bp region containing five repeats of the 12-mer sequence and two AT-rich 9-mer repeats. TmaDnaA-binding to the 12-mer motif provokes DNA bending. The 9-mer region is the duplex-unwinding site. The tmaDnaA-binding and unwinding motifs of tma-oriC share sequence homology with corresponding archaeal and eukaryotic sequences. These findings suggest that the ATP-dependent molecular switch of the initiator and the mechanisms in the replication initiation complex are highly conserved in eubacterial evolution.

Adenosine Triphosphate↗
PubMed2004

Alteration of product specificity of Aeropyrum pernix farnesylgeranyl diphosphate synthase (Fgs) by directed evolution.

Directed evolution of the C25 farnesylgeranyl diphosphate synthase of Aeropyrum pernix (Fgs) was carried out by error-prone PCR with an in vivo color complementation screen utilizing carotenoid biosynthetic pathway enzymes. Screening yielded 12 evolved clones with C20 geranylgeranyl diphosphate synthase activity which were isolated and characterized in order to understand better the chain elongation mechanism of this enzyme. Analysis of these mutants revealed three different mechanisms of product chain length specificity. Two mutants (A64T and A64V) have a single mutation at the 8th amino acid upstream of a conserved first aspartate-rich motif (FARM), which is involved in the mechanism for chain elongation reaction of all prenyl diphosphate synthases. One mutant (A135T) carries a single mutation at the 7th amino acid upstream of another conserved region (141GQ142), which was recently found to be another important region controlling chain elongation of a type III C20 geranylgeranyl diphosphate synthase and Escherichia coli C15 farnesyl diphosphate synthase. Finally, one mutant carrying four mutations (V84I, H88R, I177 M and M191V) is of interest. Molecular modeling, site-directed mutagenesis and in vitro assays of this mutant suggest that product chain-length distribution can be also controlled by a structural change provoked by a cooperative interaction of amino acids.

Aeropyrum↗
PubMed2006

Evolving public perceptions and stability in vaccine uptake.

Recent vaccine scares and sudden spikes in vaccine demand remind us that the effectiveness of mass vaccination programs is governed by the public perception of vaccination. Previous work has shown that the tendency of individuals to optimize self-interest can lead to vaccination levels that are suboptimal for a community. We use game theory to relate population-level demand for vaccines to decision-making by individuals with varied beliefs about the costs of infection and vaccination. In contrast to previous work proposing that universal vaccination is impossible in a game theoretic context, we show that optimal individual behavior can vary between universal vaccination and no vaccination, depending on the relative costs and benefits to individuals. By coupling game models and epidemic models, we demonstrate that the pursuit of self-interest often leads to stable dynamics but can lead to oscillations in vaccine uptake over time. The instability is exacerbated in populations that are more homogeneous with respect to their perceptions of vaccine and infection risks. This research illustrates the importance of applying temporal models to an inherently temporal situation, namely, the time evolution of vaccine coverage in an informed population with a voluntary vaccination policy.

Algorithms↗
PubMedDate not supplied

Nurse practitioners - or advanced clinical nurses?

This article reviews a specific finding from a research project that examined the experiences of students, teachers and clinicians involved in a nurse practitioner degree programme. The development of advanced clinical nursing roles has presented challenges to the professional structure of nursing, particularly in the area of the unregulated and confusing array of titles adopted by nurses that infer advanced clinical practice. Over a 2-year period, practitioner ethnography was used to examine a sample of 10 student nurse practitioners who were undertaking a clinical degree programme (BSc (Hons) Nurse Practitioner). Data were also collected from 11 other individuals involved in the degree programme: teachers, medical mentors and senior academics. The data were systematically analysed and structured, leading to the inductive identification of themes and frameworks. The sample's experience of the development of advanced clinical nursing roles led to consideration of the evolution of new career structures and identities associated with advanced nursing practice. This evidence enabled a view of advanced clinical nursing roles within a framework of advanced nursing practice. The development of advanced clinical nursing is dependent on the cooperation of clinical nurses, educators, managers, doctors and politicians. Nevertheless, that development can only succeed if strategic policy is backed by the development of a professional clinical nursing career framework that enables the process.

Anthropology, Cultural↗
PubMed2006

Evolutionary fate of duplicate genes encoding aspartic proteinases. Nothepsin case study.

Gene duplication is considered an important evolutionary mechanism leading to new gene functions. According to the classical model, one gene copy arising from gene duplication retains the ancestral function, whilst the other becomes subject to directional selection for some novel functions. Hence, according to this model, long-term persistence of two paralogous genes is possible only with the acquisition of functional innovation. In the absence of neofunctionalization, one of the duplicate genes may be lost following accumulation of deleterious mutations, ultimately leading to the loss of function. Recently, new mechanisms have been proposed according to which both paralogs are maintained without apparent neofunctionalization. In this paper we describe the molecular evolution of the aspartic proteinase gene family, with particular regard for the nothepsin gene, a sex- and tissue-specific form of aspartic proteinase active in fish. The finding of nothepsin in a reptile is indicative of the presence of this gene in organisms other than fish. However, the failure to find any nothepsin-like gene in avian, murine and human genome suggests that the gene has been lost in certain lineages during evolution. At variance with piscine nothepsin expressed exclusively in female liver under the estrogens action, the reptilian counterpart lacks both tissue and sex specificity, as it is constitutively expressed in different tissues of male and female specimens. The expression of the nothepsin gene in fish and lizard is accompanied by the expression of a paralogous gene encoding for cathepsin D. Functional divergence analysis indicates that cathepsin D accumulated amino acid substitutions, whereas nothepsin retained most of the ancestral functions. Phylogenetic analysis shows a preponderance of replacement substitutions compared to silent substitutions in the branch leading to the cathepsin D clade, whilst nothepsin evolves under negative selection. To explain the loss of the nothepsin gene in certain lineages, we propose a model that takes into account the complementary degenerative mutations occurring in regulatory elements of the promoter regions of the two genes. According to this model, gene loss occurs whenever the two genes acquire the same expression pattern. The coexistence of cathepsin D and nothepsin is explained in terms of metabolic cooperation of the two enzymes.

Amino Acid Sequence↗
PubMed1994

Conserved cut repeats in the human cut homeodomain protein function as DNA binding domains.

Homeodomain-containing proteins are believed to function as sequence-specific DNA binding proteins, regulating gene expression. Specificity of sequence recognition is conferred by the homeodomain acting either alone or in conjunction with other conserved DNA binding domains as is the case for Pou domain and Paired domain proteins. The recent isolation of cDNAs encoding mammalian homologues of the Drosophila Cut homeodomain protein has revealed that the 72-amino acid Cut Repeats are conserved in evolution. We have investigated the biochemical activity of human Cut Repeats by expressing fusion proteins containing glutathione S-transferase linked to various combinations of Cut Repeats and Cut homeodomain. We show by gel retardation and DNase footprinting assays that Cut Repeats can function as DNA binding domains, either independently or in cooperation with the homeodomain. The binding affinity (KD) to a specific recognition site was estimated to be 8 x 10(-9) M for Cut Repeat 3 and 4 x 10(-10) M for Cut Repeat 1. When both Cut Repeat 3 and the Cut homeodomain were present in the fusion protein, the binding affinity was increased to 4 x 10(-11) M. These results define a novel class of proteins that contain in addition to the homeodomain a second conserved protein domain, the Cut Repeats, that also function as a DNA binding domain.

Animals↗
PubMed1998

GABA transporters in Drosophila melanogaster: molecular cloning, behavior, and physiology.

Molecular cloning of GABA transporter-homologous cDNAs from a Drosophila melanogaster head-specific library was accomplished using a conserved oligomer from a highly conserved domain within the mammalian GABA transporters. Partial DNA sequencing of these cDNAs demonstrated homology with the mammalian transporters, indicating these are ancient, evolutionarily conserved molecules. Although the Drosophila cDNAs had distinct restriction enzyme patterns, they recognized the same locus in Drosophila genomic DNA, suggesting that the multiple isoforms might arise via alternative splicing. Antibodies specific for the mammalian GABA transporters GAT 1, GAT 2 and GAT 3 recognized non-overlapping and developmentally distinct patterns of expression in Drosophila neuronal tissues. Treatment of larval instars with nipecotic acid, a generalized GABA reuptake inhibitor, revealed specific, dose-dependent alterations in behavior consistent with the presence of multiple transporter molecules with differing affinities for this drug. Synaptic current recordings revealed that nipecotic acid treated larvae have an increase in latency jitter of evoked quantal release, resulting in a broader average excitatory junctional current which was manifested in a broader EJP. These results imply that alterations in the development of the CNS occur if GABAergic neurotransmission is potentiated during development. The data suggest that, as in mammals, there are multiple GABA transporters in Drosophila whose expression is differentially regulated.

Amino Acid Sequence↗
PubMed2005

The second wave of evolutionary economics in biology.

Several core issues in economics and biology overlap substantially. At the theoretical level, these include analogies and differences among rational choice, learning, genetic evolution and cultural evolution. At the empirical level, they include the structure of decision making, its neural basis and, more generally, human nature. We illustrate here the increasingly important collaboration between economics and biology with several characteristic examples, including signaling, markets, statistical reasoning, cooperation, punishment, reputation and social norms. In contrast to the mutual borrowing of ideas during the 1970s and 1980s, we now see the joint exploration of empirical and theoretical issues by biologists and economists that constitutes a second wave of interactions between the two disciplines.

Journal Article↗
PubMed1992

Independent origins of New Zealand moas and kiwis.

Two groups of flightless ratite birds existed in New Zealand during the Pleistocene: the kiwis and the moas. The latter are now extinct but formerly included 11 species. We have enzymatically amplified and sequenced approximately 400 base pairs of the mitochondrial 12S rRNA gene from bones and soft tissue remains of four species of moas as well as eight other species of ratite birds and a tinamou. Contrary to expectation, the phylogenetic analysis shows that the kiwis are more closely related to Australian and African ratities than to the moas. Thus, New Zealand probably was colonized twice by ancestors of ratite birds.

Animals↗
PubMed1977

Evaluation of transbronchial biopsy of the lung.

Transbronchial biopsy of the lung through the fiberoptic bronchoscope is becoming a widely utilized clinical diagnostic technic. The authors reviewed the histologic features of 109 consecutive cases. The primary problem is the small size of the pulmonary tissue samples obtained, which is further compounded by an apparent mechanical inability to enter the biopsy forceps into dense nodules of neoplastic tissue. The diagnosis of carcinoma can best be made by examining the periphery of the cancer for microscopic extension into adjacent pulmonary parenchyma; however, multiple levels of the tissue block are needed to find such foci. A second problem reflects the use of transbronchial biopsy in the early clinical evolution of various infectious diseases in which pulmonary tissue may contain organisms without a fully developed inflammatory response, which would ordinarily provide the clue to the infective agent. The latter problem appears in cases of infections by Pneumocystis carinii. Close cooperation between the clinician and the pathologist is particularly important in all of these clinical situations.

Biopsy↗
PubMed1983

Species adaptation in a protein molecule.

The allosteric properties of hemoglobins, especially their responses to ligands other than oxygen, vary widely in different classes of vertebrates. Knowing the stereochemistry of the cooperative effects in human hemoglobin, one can infer the stereochemical basis of these variations from the changes in amino acid sequence. The results indicate that the tertiary and quaternary structures of deoxy- and oxyhemoglobin have remained almost invariant during vertebrate evolution and that most of the amino acid replacements between species are functionally neutral. Adaptations leading to responses to new chemical stimuli have evolved by only a few (one to five) amino acid substitutions in key positions. Once such a response has become superfluous, it may be inactivated, not necessarily by a reversal of one of the original substitutions but by any other that happens to inhibit it.

Adaptation, Physiological↗
PubMed2003

Stable equidistant step trains during crystallization of insulin.

Bunching of growth steps plagues layerwise crystallization of materials in laboratory, industrial, and geological environments, and theory predicts that equidistant step trains are unstable under a variety of conditions. Searching for an example of stable equidistant step trains, we monitored the generation and spatiotemporal evolution of step trains on length scales from 100 nm to 1 mm during the crystallization of insulin, using atomic force microscopy and phase-shifting interferometry. We show that near-equidistant step trains are generated by single and cooperating screw dislocation. The lack of step-step interaction and the overall transport-controlled growth regime further regularize the step train and ensure the stability of the obtained equidistant arrangement.

Crystallization↗
PubMed2000

B-1 cells: the lineage question revisited.

The origins and functions of B-1 cells have sparked a good deal of controversy, largely centered on whether these B cells are developmentally distinct from the principal B cell populations (B-2) found in peripheral lymphoid organs. However, the prime criteria for assigning B-1 and B-2 cells to separate developmental lineages are satisfied by studies published some time ago that 1) identify distinct sources of progenitors for B-1 and B-2 cells; 2) show that these progenitors express their inherent commitment developing under the same conditions in co-transfer recipients; and, 3) have distinctive developmental patterns revealed by analysis of cells at various stages along the B-cell development pathway. I review these developmental studies here both to clarify the issue and to set the stage for presentation of evidence from more recent studies, which further define the functional differences between B-1 and B-2 cells and reveal intriguing complexities in the selective and other mechanisms that control the V(H) composition of the B-1 antibody repertoire.

Animals↗
PubMed1994

[Value and future of electron beam computed tomography].

Mecanic computed tomography would probably never reach the acquisition brevity obtained by EBT. This machine is the best for exploration of cardiovascular diseases, and non cooperative patients, and for cine and flow studies. Morever, there are never tube cooling delays or interruptions in any procedures. Its disadvantages are the price, the impossibility to tilt the gantry, and the computer which are to be improved. With "Evolution", Siemens proposes now improvements with the CVS mode and a computer release without increasing of the price.

Evaluation Studies as Topic↗