The role of neuropeptides in adverse myocardial remodeling and heart failure

In addition to traditional neurotransmitters of the sympathetic and parasympathetic nervous systems, the heart also contains numerous neuropeptides. These neuropeptides not only modulate the effects of neurotransmitters, but also have independent effects on cardiac function. While in most cases the physiological actions of these neuropeptides are well defined, their contributions to cardiac pathology are less appreciated. Some neuropeptides are cardioprotective, some promote adverse cardiac remodeling and heart failure, and in the case of others their functions are unclear. Some have both cardioprotective and adverse effects depending on the specific cardiac pathology and progression of that pathology. In this review, we briefly describe the actions of several neuropeptides on normal cardiac physiology, before describing in more detail their role in adverse cardiac remodeling and heart failure. It is our goal to bring more focus toward understanding the contribution of neuropeptides to the pathogenesis of heart failure, and to consider them as potential therapeutic targets.     

The role of the pentose-phosphate pathway in adjustment of the heart to a high load and the development of myocardial hypertrophy

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Key role of ERK1/2 molecular scaffolds in heart pathology

The ability of cardiomyocytes to detect mechanical and humoral stimuli is critical for adaptation of the myocardium in response to new conditions and for sustaining the increased workload during stress. While certain stimuli mediate a beneficial adaptation to stress conditions, others result in maladaptive remodelling, ultimately leading to heart failure. Specific signalling pathways activating either adaptive or maladaptive cardiac remodelling have been identified. Paradoxically, however, in a number of cases, the transduction pathways involved in such opposing responses engage the same signalling proteins. A notable example is the Raf–MEK1/2–ERK1/2 signalling pathway that can control both adaptive and maladaptive remodelling. ERK1/2 signalling requires a signalosome complex where a scaffold protein drives the assembly of these three kinases into a linear pathway to facilitate their sequential phosphorylation, ultimately targeting specific effector molecules. Interestingly, a number of different Raf–MEK1/2–ERK1/2 scaffold proteins have been identified, and their role in determining the adaptive or maladaptive cardiac remodelling is a promising field of investigation for the development of therapeutic strategies capable of selectively potentiating the adaptive response.     

Marking out a disciplinary common ground: The role of chemical pedagogy in establishing the doctrine of affinity at the heart of British chemistry

This paper presents a case study that contributes to the current debate among historians of chemistry concerning the role and influence of pedagogy in science. Recently, Bernadette Bensaude-Vincent and her colleagues concluded that in nineteenth-century France, ‘textbooks played an important role in discipline building and in creating theories’.1 ¹A. Garcia-Belmar, B. Bensaude-Vincent and J.R. Bertomeu-Sánchez, ‘The Power of Didactic Writings: French Chemistry Textbooks of the Nineteenth Century’, in Pedagogy and the Practice of Science: Historical and Contemporary Perspectives, edited by D. Kaiser (Cambridge, MA, 2005), 243. Developing this idea further, this paper examines the dissemination of knowledge through face-to-face chemical lectures, showing that the influence of pedagogical strategy on theoretical content of the science is far from negligible. The pedagogy of William Cullen was essentially responsible for the prevalence of the doctrine of affinity in British chemistry from the 1760s onwards. Cullen used his affinity theory as a pedagogical tool that to a large extent defined his discipline, and the pedagogical pyramid that he headed similarly ensured that the doctrine would remain at the heart of British chemistry. From a pedagogical tool, the doctrine of affinity was transformed over time into a chemical tool, offering British chemists a disciplinary common ground that both set and reinforced the boundaries to their discipline.     

The role of the Matthew effect in science

Robert Merton observed that better known scientists tend to get more credit than less well known scientists for the same achievements; he called this the Matthew effect. Scientists themselves, even those eminent researchers who enjoy its benefits, regard the effect as a pathology: it results, they believe, in a misallocation of credit. If so, why do scientists continue to bestow credit in the manner described by the effect? This paper advocates an explanation of the effect on which it turns out to allocate credit fairly after all, while at the same time making sense of scientists’ opinions to the contrary.     

The role of crustecdysone in the moulting crayfish

Résumé La crustecdysone injectée dans l'écrevisse,Procambarus sinulans ne cause pas la mue chez l'animal intact mais l'accélère après ablation des pédoncules oculaires.     

The role of the thymus in antinuclear autoimmunization

Résumé La thymectomie chez des souris CF1 âgées de 1 mois est suivie comme dans le cas de la thymectomie néonatale de l'apparition d'anticorps antinucléaires. Le transfert adoptif de l'autoimmunité antinucléaire apparu chez des animaux thymectomisés à la naissance n'est possible que si les animaux receveurs sont eux-mêmes thymectomisés. Ces constatations mettent en évidence un rôle possible de contrôle des réactions autoimmunes par le thymus.     

The role of glycine in the biosynthesis of steroids

Zusammenfassung Während der Biosynthese von Cholesterol mit homogenisierter Rattenleber wird [2-¹⁴C] des Glycins viel besser eingebaut als [1-¹⁴C].Saccharomyces cerevisiae produziert radioaktives Squelen (ausser Ergosterol mit Radioaktivität des Ringsystems) mit [2-¹⁴C] Glycin und mit [3-¹⁴C] Serin, aber nicht mit [1-¹⁴C] Glycin.

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Studies on Biosynthesis. Part VI. For Part V, seeA. K. Bose, K. S. Khanchandani andB. L. Hungund, Experientia,27, 1403 (1971). b) Presented at the 164th National Meeting of the American Chemical Society, New York, August, 1972.

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The support of this research by Stevens Institute of Technology and Sandoz Foundation is gratefully acknowledged. We wish to thank Drs.P. T. Funke, M. S. Manhas, P. K. Bhattacharyya, M. Anchel andH. Levey for valuable discussions and help with some of the experiments.     

The intercalated disc of the goldfish heart

Résumé L'examen au microscope électronique de coupes minces du cur de cyprin doré révèle la présence de disques intercalaires de forme soit simple, soit complexe, semblables aux disques des vertébrés supérieurs. De plus, les barres intercellulaires sont présentes. La structure et les rapports des disques et des barres avec la bande Z de la myofibrille suggèrent leur proche similarité.

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This study was aided by a grant from the National Heart Institute, of the National Institutes of Health, Department of Health, Education, and Welfare; Bethesda, Maryland.     

The role of the kidney in gastrin metabolism in the rat

Résumé Les taux moyens de sécrétion d'acide gastrique due à l'injection par voie i.v. du SHGI et de gastrine bovine brute ont été sensiblement plus élevées et les périodes de réaction plus longues chez les rats testés que chez les rats de contrôle. Aucune différences significative n'a été observée ni dans le taux moyen de sécrétion acide ni dans la période de réaction chez les deux types de rats, après injection d'histamine dihydrochloride.

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The authors are grateful to M.R.C. London for the SHGI sent to M.O.O. The work has been made possible by a fund from the University of Ibadan Senate Research Grant given to M.O.O.