Studies on chlorophyll biosynthesis and other things

Our research on chlorophyll biosynthesis, over a period of approximately twenty years, has been described, emphasizing those areas in which our laboratory made significant and timely contributions. References to some of our most important articles are included. Portions of the chlorophyll biosynthetic pathway, in which our own laboratory was not involved, for example, the reduction of protochlorophyllide to chlorophyllide and the phytylation of the latter to yield chlorophyll a, have not been covered in this article. Those events which preceded my involvement with chlorophyll biosynthesis, but which contributed to the formation of my own scientific personality, are mentioned briefly in the Introduction. My non-scientific avocations have been included at the request of the reviewers and Govindjee.     

Elevated plasma vasopressin in cardiomyopathic hamsters

Hamsters of the BIO 14.6 strain characteristically develop cardiomyopathy as they age, and hamsters of this strain have overt signs of heart failure by 11 months of age. Plasma levels of the posterior pituitary hormone arginine-vasopressin (AVP) were found to be elevated (approximately 2-fold) in 11 month old BIO 14.6 hamsters, compared to age-matched hamsters of a control strain. AVP appeared inappropriately elevated in these animals, since they were neither hyperosmotic nor markedly hypotensive. The elevated levels of AVP observed in these animals appears to contribute to vasomotor tone, since intravenous adminstration of a specific antagonist of the vasoconstrictor action of AVP [d(CH₂)₅Ome(TYR)AVP] elicited a fall in arterial pressure (9±2 mm Hg, n=6, p<0.05). The AVP antagonist had no effect on arterial pressure in hamsters of a control strain, and vehicle administration had no effect on arterial pressure in either strain. These data indicate that inappropriately elevated levels of AVP contribute to the cardiovascular state of myopathic hamsters. Since elevated plasma AVP has been noted in human congestive heart failure, these results suggest that AVP may contribute to the cardiovascular status during congestive heart failure.     

A Turing test for collective motion

A widespread problem in biological research is assessing whether a model adequately describes some real-world data. But even if a model captures the large-scale statistical properties of the data, should we be satisfied with it? We developed a method, inspired by Alan Turing, to assess the effectiveness of model fitting. We first built a self-propelled particle model whose properties (order and cohesion) statistically matched those of real fish schools. We then asked members of the public to play an online game (a modified Turing test) in which they attempted to distinguish between the movements of real fish schools or those generated by the model. Even though the statistical properties of the real data and the model were consistent with each other, the public could still distinguish between the two, highlighting the need for model refinement. Our results demonstrate that we can use ‘citizen science’ to cross-validate and improve model fitting not only in the field of collective behaviour, but also across a broad range of biological systems.     

Role of angiotensin II in oral contraceptive hypertension in anesthetized rats

Rats fed a diet containing an oral contraceptive estrogen-progestogen mixture (Enovid) for 26 weeks developed a significant (P<0.01) elevation in mean arterial pressure (145 ± 6 mm Hg) when compared to a control group of rats fed the same diet without oral contraceptive steroids (mean arterial pressure averaged 117 ± 6 mm Hg). Infusion of [Sar¹, Ala⁸] angiotensin II, a competitive antagonist of angiotensin II, reduced the mean arterial pressure (P<0.01) in the oral contraceptive-treated rats to 117 ± 9 mm Hg, while infusion of this angiotensin II analogue into the control rats did not lower the arterial pressure. These studies provided evidence that angiotensin II may be involved in the hypertension produced by Enovid treatment in rats.     

Surviving an identity crisis: A revised view of chromatin insulators in the genomics era

The control of complex, developmentally regulated loci and partitioning of the genome into active and silent domains is in part accomplished through the activity of DNA-protein complexes termed chromatin insulators. Together, the multiple, well-studied classes of insulators in Drosophila melanogaster appear to be generally functionally conserved. In this review, we discuss recent genomic-scale experiments and attempt to reconcile these newer findings in the context of previously defined insulator characteristics based on classical genetic analyses and transgenic approaches. Finally, we discuss the emerging understanding of mechanisms of chromatin insulator regulation. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development.     

The bicarbonate effect,oxygen evolution,and the shadow of Otto Warburg

A short list of the twentieth century's dominant figures in photosynthesis would unquestionably include Otto Warburg. One of his many discoveries, the `bicarbonate effect' remains a lasting puzzle to his heirs in the field. Recent developments in this area of research have renewed interest and call for a re-examination of the ideas surrounding this controversial topic. Focus here will be on hypotheses developed by a small number of researchers who proposed that bicarbonate may be involved in oxygen evolution. The effect of bicarbonate on the acceptor side of Photosystem II (PS II) is discussed by Jack van Rensen (in this issue). This revised version was published online in June 2006 with corrections to the Cover Date.     

Pulmonary microembolism: Attenuated pulmonary vasoconstriction with prostaglandin inhibitors and antihistamines

The mechanism(s) involved in the pulmonary vascular and airway responses to pulmonary microembolism have not been clearly defined. Therefore, we determined the effects of specific prostaglandin and histamine blockade on the hemodynamic and arterial blood gas tension responses to particulate microembolism (200 μ glass beads) in intact anesthetized dogs. The marked increases in pulmonary arterial pressure and pulmonary vascular resistance observed in the untreated dogs were attenuated, but not abolished, following both prostaglandin blockade (with either meclofenamate or polyphloretin phosphate) and histamine blockade (with chlorpheniramine and metiamide) at 5 minutes, and were still attenuated 30 minutes post embolization. Combined prostaglandin and histamine blockade further attenuated, but again did not abolish, the pulmonary vascular responses. Cardiac outputs and systemic arterial pressures were unchanged from control by embolism. The alveolar hypoventilation (decreased arterial oxygen tension and increased carbon dioxide tension) observed in the untreated embolized dogs was prevented only with the prostaglandin inhibitors. Pulmonary microembolism in intact dogs, therefore, appears to induce vasoconstriction mediated partially by prostaglandin and histamine action, and alveolar hypoventilation mediated by prostaglandin, but not histamine, action.     

Integrated But Not Whole? Applying an Ontological Account of Human Organismal Unity to the Brain Death Debate

As is clear in the 2008 report of the President's Council on Bioethics, the brain death debate is plagued by ambiguity in the use of such key terms as ‘integration’ and ‘wholeness’. Addressing this problem, I offer a plausible ontological account of organismal unity drawing on the work of Hoffman and Rosenkrantz, and then apply that account to the case of brain death, concluding that a brain dead body lacks the unity proper to a human organism, and has therefore undergone a substantial change. I also show how my view can explain hard cases better than one in which biological integration (as understood by Alan Shewmon and the President's Council) is taken to imply ontological wholeness or unity.     

Unresponsiveness of GH cells to cyclo(histidyl-proline), a metabolite of thyrotropin releasing hormone

Cyclo(Histidyl-Proline) is a metabolite of thyrotropin-releasing hormone. It has been suggested that this peptide plays a role in regulating prolactin secretion in GH cells. An investigation of the effect of cyclo(His-Pro) on GH cells indicated that it does not affect basal prolactin release or accumulation or the levels stimulated by TRH. cAMP levels in GH cells are elevated by TRH or VIP, but not influenced by cyclo(His-Pro). cGMP levels in GH cells are not affected by either TRH or cyclo(His-Pro). While there is specific binding of TRH to receptors in GH cells, no such receptors for cyclo(His-Pro) are detectable. It is suggested that GH cells are unresponsive to cyclo(His-Pro).