Plant mitochondrial carriers: an overview

In the two last decades, biochemical studies using mitochondrial swelling experiments or direct solute uptake in isolated mitochondria have lead to the identification of different transport systems at the level of the plant mitochondrial inner membrane. Although most of them have been found to have similar features to those identified in animal mitochondria, some differences have been observed between plant and animal transporters. More recently, molecular biology studies have revealed that most of the mitochondrial exchanges are performed by nuclear encoded proteins, which form a superfamily. Members of this family have been reported in animals, yeast as well as plants. This review attempts to give an overview of the present knowledge concerning the biochemical and molecular characterisation of plant members of the mitochondrial carrier family and, when possible, a comparison with carriers from other organisms.     

Purification and study of equine infectious anemia virus antigens, produced in vivo or in cultured cells]

The G and C antigens of equine infectious anemia virus have been produced in vivo and in infected cell culture, then they have been purified. Their physico-chemical properties have been determined, particularly their molecular weight, their sedimentation coefficient, their density and the iso electric point.     

Therapeutic Protein Kinase Inhibitors

Protein kinase inhibitors represent an important and still emerging class of targeted therapeutic agents. Drug discovery and development strategies have explored numerous approaches to target the inhibition of protein kinase signaling. This review will highlight some of the strategies that have led to the successful clinical development of therapeutic protein kinase inhibitors, particularly as anticancer drugs. Some notable advances have been made in the development of novel protein and oligonucleotide-based biologics that target growth factor or receptor tyrosine kinases. Also, advances have been made in the rational design of small-molecule inhibitors that target unique kinase conformational forms and binding sites, and have specific kinase selectivity profiles. A review will also be given of some of the potential clinical toxicities and adverse side-effects associated with these kinase-targeted drugs. Therapeutic protein kinase inhibitors have been highly beneficial to cancer patients and offer the promise of future therapies for other diseases as well. Received 02 September 2008; received after revision 13 October 2008; accepted 15 October 2008     

Molecular parasitology: progress towards the development of vaccines for malaria, filariasis, and schistosomiasis

Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages of Plasmodium and Schistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed.     

No-go theorems: What are they good for?

No-go theorems have played an important role in the development and assessment of scientific theories. They have stopped whole research programmes and have given rise to strong ontological commitments. Given the importance they obviously have had in physics and philosophy of physics and the huge amount of literature on the consequences of specific no-go theorems, there has been relatively little attention to the more abstract assessment of no-go theorems as a tool in theory development. We will here provide this abstract assessment of no-go theorems and conclude that the methodological implications one may draw from no-go theorems are in disagreement with the implications that have often been drawn from them in the history of science.     

Mitochondrial defects and hearing loss

The techniques of human molecular genetics have been rapidly applied to the study of hearing loss. These studies have implicated more than 60 loci as causes of nonsyndromic hearing loss. Mutations at more than a dozen nuclear genes have been demonstrated to cause hearing loss, and these have been covered in recent reviews. However, a perhaps unexpected feature of the molecular characterization of human hearing loss has been the occurrence of mutations in the mitochondrial DNA (mtDNA). The importance of mitochondrial function in hearing is emphasized by the recent discovery of mutations in a nuclear-encoded mitochondrial protein which results in hearing loss. This article reviews the current status of our knowledge of mtDNA mutations that have been shown to cause hearing loss, and the suggestion of potential molecular, cellular and tissue-specific pathophysiological mechanisms by which dysfunction of mitochondria may lead to a loss of hearing.     

The naturalism of the sciences

The sciences are characterized by what is sometimes called a “methodological naturalism,” which disregards talk of divine agency. In response to those who argue that this reflects a dogmatic materialism, a number of philosophers have offered a pragmatic defense. The naturalism of the sciences, they argue, is provisional and defeasible: it is justified by the fact that unsuccessful theistic explanations have been superseded by successful natural ones. But this defense is inconsistent with the history of the sciences. The sciences have always exhibited what we call a domain naturalism. They have never invoked divine agency, but have always focused on the causal structure of the natural world. It is not the case, therefore, that the sciences once employed theistic explanations and then abandoned them. The naturalism of the sciences is as old as science itself.     

Animal models in interferon research: Some current trends

Conclusions Concepts about interferon have changed dramatically over the years. Initially it was considered to be an antiviral protein which selectively inhibited the replication of viruses²⁴. Over the years we have discovered an increasing number of interferons and many different biological activities. Other regulatory proteins have been detected and the interferons have become part of an interacting family of biological response-modifying proteins. Because of the complexity of these systems, animal experiments are the only way to assess the clinical potential of interferons (and interferon-like molecules). It is important that the animal experiments should not be too restricted in scope, because interferon has now proved to have activity in conditions other than viral infections, for example against tumors and infections other than those caused by viruses.     

Time series forecasting using robust regression

The method of ordinary least squares (OLS) and generalizations of it have been the mainstay of most forecasting methodologies for many years. It is well-known, however, that outliers or unusual values can have a large influence on least-squares estimators. Users of automatic forecasting packages, in particular, need to be aware of the influence that outlying data values can have on statistical analyses and forecasting results. Robust methods are available to modify least-squares procedures so that outliers have much less influence on the final estimates; yet these formal methods have not found their way into general forecasting procedures. This paper provides a case study in which classical least-square-estimation procedures are complemented with a robust alternative to enhance statistical fit criteria and improve forecasting performance. The study suggests that much can be gained in understanding the nature of outliers and their influence on forecasting performance by performing a robust regression in addition to OLS.     

The presence of an endogenous peroxidase activity in hairy cell leukemia cells]

Mononuclear cells from hairy cell leukemia have been studied in three cases by ultrastructural immunocytochemistry. Cells have fairly detectable surface immunoglobulins, without monoclonal distribution however. In addition these cells have a peroxidatic activity which is revealed in the perinuclear space and strands of endoplasmic reticulum.     

Molecular parasitology: Progress towards the development of vaccines for malaria,filariasis, and schistosomiasis

Summary Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages ofPlasmodium andSchistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed.     

Periostin in fibrillogenesis for tissue regeneration: periostin actions inside and outside the cell

More than 10 years have passed since the naming of periostin derived from its expression sites in the periosteum and periodontal ligament. Following this finding, we have accumulated more data on the expression patterns of periostin, and, finally, with the generation of periostin-deficient mice, have revealed functions of periostin in the regeneration of tissues in bone, tooth, heart, and skin, and its action in cancer invasion. Since periostin is a matricellular protein, the first investigation of periostin function showed its enhancement of cell migration by acting outside the cell. On the other hand, recent observations have demonstrated that periostin functions in fibrillogenesis in association with extracellular matrix molecules inside the cell.     

Deoxyribozymes: useful DNA catalysts in vitro and in vivo

Deoxyribozymes (DNA enzymes; DNAzymes) are catalytic DNA sequences. Using the technique of in vitro selection, individual deoxyribozymes have been identified that catalyze RNA cleavage, RNA ligation, and a growing range of other chemical reactions. DNA enzymes have been used in vitro for applications such as biochemical RNA manipulation and analytical assays for metal ions, small organic compounds, oligonucleotides, and proteins. Deoxyribozymes have also been utilized as in vivo therapeutic agents to destroy specific mRNA targets. Although many conceptual and practical challenges remain to be addressed, deoxyribozymes have substantial promise to contribute meaningfully for applications both in vitro and in vivo.     

Untersuchungen über einen mikrobiologisch feststellbaren Serumfaktor nach Gelbsucht

Summary The germination of spores and pollen grains is often inhibited by the serum of subjects who have once suffered from a jaundice. Experiments have been done with spores ofHelminthosporium sativum andAlternaria tenuis and with pollen grains of short style and long style plants ofPrimula obconica. 36 samples of a series of 50 persons, who have suffered from a jaundice, showed the inhibition of germination. 5 samples with positive reaction have been found in a second series of 344 sera of subjects who have never suffered from a jaundice. We observed positive reaction withHepatitis epidemica acuta (6 samples); all other kind of diseases so far tested did not show any similar reaction.     

They give you the keys and say ‘drive it!’ Managers, referred expertise, and other expertises

On the face of it, the directors of new large scientific projects have an impossible task. They have to make technical decisions about sciences in which they have never made a research contribution—sciences in which they have no contributory expertise. Furthermore, these decisions must be accepted and respected by the scientists who are making research contributions. The problem is discussed in two interviews conducted with two directors of large scientific projects. The paradox is resolved for the managers by their use of interactional and referred expertise. The same analysis might be applicable to management in general. An Appendix, co-authored with Jeff Shrager, compares the notion of referred expertise with contributory expertise.     

Logic of discovery and justification in regulatory genetics

In the above pages I have sketched a history of the genesis and comparative evaluation of the repressor model of genetic regulation of enzyme induction. I have not attempted in this article to carry out an analysis of the more scientifically interesting fully developed Jacob-Monod operon theory of genetic regulations but such an analysis of the operon theory would not, I believe, involve any additional logical or epistemological features than have been discussed above.I have argued that the above account of the development of a theory of enzyme induction involved inferential moves and well-characterized desiderata, of both empirical and non-empirical character, in the genesis and evaluation of new hypotheses and theories. I have also contended that the reasoning displayed in the genesis of a theory is in a large measure identical to that utilized in evaluating a theory. Both of these conclusions are at variance with the views of philosophers such as H. Reichenbach, Sir Karl Popper, and C.G. Hempel who have argued that the genesis of new hypotheses is primarily an irrational affair and that only the context of justification is susceptible of rational reconstruction. In the alternative view presented here, scientific discovery and scientific justification represent the application in contexts, which are primarily telically distinguishable, of a fundamentally unitary logic of scientific inquiry.     

History of science and its utopian reconstructions

In recent years explicitly utopian visions have reappeared across the political spectrum. To a surprising degree these visions have drawn on histories and science and technology. What should scholars of Science and Technology Studies (STS) and History and Philosophy of Science (HPS) make of these developments? The concept of utopia has often been treated with considerable distrust in these fields, as an indication of closed end-directed blueprints, or as an indication of fantasies of limitless technological improvement and purification of categories. Alongside this uneasiness, however, HPS and STS scholars have also projected transformative ambitions, seeking to recover from the past different ways of knowing and relating to the human and non-human world. By engaging with critiques of utopia from thinkers including Karl Popper, Otto Neurath, Bruno Latour, Isabelle Stengers and Donna Haraway, and exploring some of the utopian strands which have recurred in studies of science and technology—including the longing for integration, the association of science with planning, and the ways in which feminist scholars have envisaged alternative forms of science—we can understand the ongoing, and often unrecognised, utopian dimensions of HPS and STS.     

Changes in the plasma membrane surface of lymphocytes stimulated in vivo with DNCB.

Stereological principles have been used to evaluate ultrastructural changes which accompany the transformation of lymphocytes stimulated in vivo with dinitrochlorobenzene (DNCB). Whereas unstimulated lymphocytes and blast cells have slightly more than the minimal containing plasmalemmal surface for their volume, stimulated (blast-derived) lymphocytes have an excess surface area in the order of 30%. This observation is discussed in the context of altered cell function and the biosynthesis of additional membrane components.     

Visiting Newton's atelier before the Principia, 1679–1684

The worksheets that presumably contained Newton's early development of the fundamental concepts in his Principia have been lost. A plausible reconstruction of this development is presented based on Newton's exchange of letters with Robert Hooke in 1679, with Edmund Halley in 1686, and on some clues in the diagram associated with Proposition 1 in Book 1 of the Principia that have been ignored in the past. A graphical construction associated with this proposition leads to a rapidly convergent method to obtain orbits for central forces, which elucidates how Newton may have have been led to formulate some of his most fundamental propositions in the Principia.