What constitutes a network in the acinar cells of amphibian and mammalian pancreas?

Résumé Il a été montré que l'appareil réticulaire classique de Golgi dans les cellules pancréatiques des amphibies et des mammifères est un produit artificiel. Un certain nombre de raisons sont proposées pour expliquer ce fait.     

Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage.     

Alsatian chemists in Paris in the 19th century: a network, a school?

During the nineteenth century French chemistry was marked by an outstanding number of Alsatian chemists whose scientific contributions cannot be ignored. Especially following the Franco-Prussian War, their regional origin was given a particular importance as a means of affirming their singularity on the French scientific scene. However, some questions may be raised: can we distinguish the Alsatians from other French chemists before 1870? Were they a homogeneous group sharing a common origin? The aim of this article therefore, is, to show that by their theoretical options within chemistry, their personal and professional relationships, as well as by their participation in various common initiatives, they organized themselves both formally and informally within the Parisian scientific community. Amongst these forms of organization the research school of Charles Adolphe Wurtz (1817-84) emerges as the nucleus of what we may envisage as a network of Alsatian chemists working in Paris, in the second half of the nineteenth century.     

Wnt and lithium: a common destiny in the therapy of nervous system pathologies?

Wnt signaling is required for neurogenesis, the fate of neural progenitors, the formation of neuronal circuits during development, neuron positioning and polarization, axon and dendrite development and finally for synaptogenesis. This signaling pathway is also implicated in the generation and differentiation of glial cells. In this review, we describe the mechanisms of action of Wnt signaling pathways and their implication in the development and correct functioning of the nervous system. We also illustrate how a dysregulated Wnt pathway could lead to psychiatric, neurodegenerative and demyelinating pathologies. Lithium, used for the treatment of bipolar disease, inhibits GSK3β, a central enzyme of the Wnt/β-catenin pathway. Thus, lithium could, to some extent, mimic Wnt pathway. We highlight the possible dialogue between lithium therapy and modulation of Wnt pathway in the treatment of the diseases of the nervous system.     

Cerivastatin: a cellular and molecular drug for the future?

The 'statin story' began in 1987 when the first-generation, fungal HMG-CoA reductase inhibitor lovastatin received FDA approval in the USA. Ten years later, the sixth compound of this class came onto the world market - the fully synthetic statin cerivastatin. A number of clinical studies had confirmed its high pharmacological efficacy, its excellent pharmacokinetic properties with fast and nearly complete absorption after oral uptake, a linear kinetic over a broad concentration range, and its favorable safety profile. The greatest advantages, of cerivastatin, however, are its lipophilicity, its high bioavailability of about 60% after oral application and its potency at 100-fold lower doses compared to other lipophilic statins. Nevertheless, the most exciting findings are certainly its non-lipid-related, pleiotropic effects at the cellular and molecular level. Statin therapy was also found to reduce mortality in cases where cholesterol levels or atherosclerotic plaque formation remained unaltered. However, cerivastatin improves endothelial dysfunction, possesses anti-inflammatory, antioxidant, anticoagulant, antithrombotic, antiproliferative, plaque-stabilizing, immunmodulatory, and angiogenic effects, and may even prevent tumor growth, Alzheimer's disease, and osteoporosis. Most of these effects seem to be based on the inhibition of isoprenoid synthesis. Although cerivastatin is no longer on the market because of some problematic side effects, it could be one of the most potent cellular and molecular drugs for the future. Received 29 May 2002; received after revision 23 August 2002; accepted 26 August 2002 RID="*" ID="*"Corresponding author.     

Problems and promises: How to tell the story of a Genome Wide Association Study?

The promise of treatments for common complex diseases (CCDs) is understood as an important force driving large scale genetics research over the last few decades. This paper considers the phenomenon of the Genome Wide Association Study (GWAS) via one high profile example, the Wellcome Trust Case Control Consortium (WTCCC). The WTCCC despite not fulfilling promises of new health interventions is still understood as an important step towards tackling CCDs clinically. The ‘sociology of expectations’ has considered many examples of failure to fulfil promises and the subsequent negative consequences including disillusionment, disappointment and disinvestment. In order to explore why some domains remain resilient in the face of apparent failure, I employ the concept of the ‘problematic’ found in the work of Giles Deleuze. This alternative theoretical framework challenges the idea that the failure to reach promised goals results in largely negative outcomes for a given field. I will argue that collective scientific action is motivated not only by hopes for the future but also by the drive to create solutions to the actual setbacks and successes which scientists encounter in their day-to-day work. I draw on eighteen interviews.     

Minkowski spacetime and Lorentz invariance: The cart and the horse or two sides of a single coin?

Michel Janssen and Harvey Brown have driven a prominent recent debate concerning the direction of an alleged arrow of explanation between Minkowski spacetime and Lorentz invariance of dynamical laws in special relativity. In this article, I critically assess this controversy with the aim of clarifying the explanatory foundations of the theory. First, I show that two assumptions shared by the parties—that the dispute is independent of issues concerning spacetime ontology, and that there is an urgent need for a constructive interpretation of special relativity—are problematic and negatively affect the debate. Second, I argue that the whole discussion relies on a misleading conception of the link between Minkowski spacetime structure and Lorentz invariance, a misconception that in turn sheds more shadows than light on our understanding of the explanatory nature and power of Einstein׳s theory. I state that the arrow connecting Lorentz invariance and Minkowski spacetime is not explanatory and unidirectional, but analytic and bidirectional, and that this analytic arrow grounds the chronogeometric explanations of physical phenomena that special relativity offers.     

C16-methyl derivatives of progesterone and 17α-acetoxyprogesterone: Preparation and biological activities

Zusammenfassung Mehrere Derivate des 16-Methyl-progesteron wurden synthetisiert und biologisch geprüft. Die Einführung einer C16-Methylgruppe ergab keine gesteigerte Progesteronaktivität in den getesteten Verbindungen.     

Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells

It is well documented that activation of calpain, a calcium-sensitive cysteine protease, marks the pathology of naturally and experimentally occuring neurodegenerative conditions. Calpain-mediated proteolysis of major membrane-skeletal protein, αII-spectrin, results in the appearance of two unique and highly stable breakdown products, which is an early event in neural cell pathology. This review focuses on spectrin degradation by calpain within neurons induced by diverse conditions, emphasizing a current picture of multi-pattern neuronal death and a recent success in the development of spectrin-based biomarkers. The issue is presented in the context of the major structural and functional properties of the two proteins.Received 7 March 2005; received after revision 22 April 2005; accepted 13 May 2005     

Early research on the biological effects of microwave radiation: 1940–1960

Two overriding considerations shaped the development of early research on the biological effects of microwave radiation—possible medical application (diathermy) and uncertainty about the hazards of exposure to radar. Reports in the late 1940s and early 1950s of hazards resulting from microwave exposure led to the near abandonment of medical research related to microwave diathermy at the same time that military and industrial concern over hazards grew, culminating in the massive research effort known as ‘the Tri-Service program’ (1957–1960). Both the early focus on medical application and the later search for hazards played important roles in dictating how this field of research developed as a science.     

Rationality and irrationality in the history of continental drift: Was the hypothesis of continental drift worthy of pursuit?

The revolution in geology, initiated with Alfred Wegener’s theory of continental drift, has been the subject of many philosophical discussions aiming at resolving the problem of rationality underlying this historical episode. Even though the debate included analyses in terms of scientific methodology, applications of concrete accounts of epistemic justification to this case study have been rare. In particular, the question as to whether Wegener’s theory was epistemically worthy of pursuit in the first half of the twentieth century, that is, in its early development, remained open or inadequately addressed. The aim of this paper is to offer an answer to this question. The evaluation of Drift will be done by means of an account of theory evaluation suitable for the context of pursuit, developed in ?e?elja and Straßer (accepted for publication). We will argue that pursuing the theory of continental drift was rational, i.e., that it was irrational to reject its pursuit as unworthy.     

On glioblastoma and the search for a cure: where do we stand?

Although brain tumours have been documented and recorded since the nineteenth century, 2016 marked 90 years since Percival Bailey and Harvey Cushing coined the term “glioblastoma multiforme”. Since that time, although extensive developments in diagnosis and treatment have been made, relatively little improvement on prognosis has been achieved. The resilience of GBM thus makes treating this tumour one of the biggest challenges currently faced by neuro-oncology. Aggressive and robust development, coupled with difficulties of complete resection, drug delivery and therapeutic resistance to treatment are some of the main issues that this nemesis presents today. Current treatments are far from satisfactory with poor prognosis, and focus on palliative management rather than curative intervention. However, therapeutic research leading to developments in novel treatment stratagems show promise in combating this disease. Here we present a review on GBM, looking at the history and advances which have shaped neurosurgery over the last century that cumulate to the present day management of GBM, while also exploring future perspectives in treatment options that could lead to new treatments on the road to a cure.     

Sirenids: a family of polyploid urodeles?

Riassunto I tre Sirenidi viventi hanno 46, 52 e 64 cromosomi; il corredo diS. lacertina sembra tetraploide (4n=52). Viene fatta l'ipotesi che anche i corredi delle altre due specie derivino per (allo-)poliploidia da corredi a minor numero cromosomico, come si ritrovano nelle famiglie superiori dell'Ordine.

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Research carried out through a contribution from the C.N.R.     

The epistemological virtues of assumptions: towards a coming of age of Boltzmann and Meinong’s objections to ‘the prejudice in favour of the actual’?

Two complementary debates of the turn of the nineteenth and twentieth century are examined here: the debate on the legitimacy of hypotheses in the natural sciences and the debate on intentionality and ‘representations without object’ in philosophy. Both are shown to rest on two core issues: the attitude of the subject and the mode of presentation chosen to display a domain of phenomena. An orientation other than the one which contributed to shape twentieth-century philosophy of science is explored through the analysis of the role given to assumptions in Boltzmann’s research strategy, where assumptions are contrasted to hypotheses, axioms, and principles, and in Meinong’s criticism of the privileged status attributed to representations in mental activities. Boltzmann’s computational style in mathematics and Meinong’s criticism of the confusion between representation and judgment give prominence to an indirect mode of presentation, adopted in a state of suspended belief which is characteristic of assumptions and which enables one to grasp objects that cannot be reached through direct representation or even analogies. The discussion shows how assumptions and the movement to fiction can be essential steps in the quest for objectivity. The conclusion restates the issues of the two debates in a contemporary perspective and shows how recent developments in philosophy of science and philosophy of language and mind can be brought together by arguing for a twofold conception of reference.     

Induction of IgG1 and IgE responses to protein-conjugated and unconjugated β-lactam antibiotics in the mouse-efficacy of Freund's complete adjuvant

Summary One or two injections two weeks apart of protein-conjugated penicillin G, cephalothin or cefmetazole emulsified with Freund's complete adjuvant were quite effective in producing anti-antibiotic antibodies of the IgE as well as of the IgG₁ class in mice. Long-lasting and boostable production of both antibody classes was also obtained against unconjugated cephalothin or cefmetazole, though the positivity depended on the mouse strain.     

Was Feyerabend a Popperian? Methodological issues in the History of the Philosophy of Science

For more than three decades, there has been significant debate about the relation between Feyerabend and Popper. The discussion has been nurtured and complicated by the rift that opened up between the two and by the later Feyerabend's controversial portrayal of his earlier self. The first part of the paper provides an overview of the accounts of the relation that have been proposed over the years, disentangles the problems they deal with, and analyses the evidence supporting their conclusions as well as the methodological approaches used to process that evidence. Rather than advancing a further speculative account of the relation based on Feyerabend's philosophical work or autobiographical recollections, the second part of the paper strives to clarify the problems at issue by making use of a wider range of evidence. It outlines a historical reconstruction of the social context within which Feyerabend's intellectual trajectory developed, putting a special emphasis on the interplay between the perceived intellectual identity of Feyerabend, Feyerabend's own intellectual self-concept, and the peculiar features of the evolving Popperian research group.     

Can postictal suppression of the perforant path-fascia dentata responses account for the ECS-induced anterograde amnesia in rats?

Summary Electroconvulsive shock (ECS) decreases fascia dentata responses to entorhinal stimulation by 50% in unanesthetized rats. Synaptic potentials and population spikes return to pre-ECS level during 1 h and 3 h, respectively. This recovery rate is compared with the dynamics of ECS-induced anterograde amnesia.     

History of science and science combined: solving a historical problem in optics—the case of Galileo and his telescope

Archive for History of Exact Sciences - The claim that Galileo Galilei (1564–1642) transformed the spyglass into an astronomical instrument has never been disputed and is considered a...