The insufficience of supervenient explanations of moral actions: Really taking Darwin and the naturalistic fallacy seriously

In a recent paper in this journal (Rottschaefer and Martinsen 1990) we have proposed a view of Darwinian evolutionary metaethics that we believe improves upon Michael Ruse's (e.g., Ruse 1986) proposals by claiming that there are evolutionary based objective moral values and that a Darwinian naturalistic account of the moral good in terms of human fitness can be given that avoids the naturalistic fallacy in both its definitional and derivational forms while providing genuine, even if limited, justifications for substantive ethical claims. Jonathan Barrett (this issue) has objected to our proposal contending that we cannot hold for the reality of supervenient moral properties without either falling foul of the naturalistic fallacy or suffering the consequences of postulating inexplicable moral properties. In reply, we show that Barrett's explicit arguments that we commit either the definitional or derivational form of the naturalistic fallacy fail and that his naturalistic intuitions that supervenience explanations of moral properties by nonmoral properties force us into what we call the explanatory form of the naturalistic fallacy also fail. Positively, his objections help us to clarify the nature of the naturalistic fallacy within an evolutionary based naturalistic ethics and to point out the proper role of both supervenience explanations and moral explanations in such an ethics.     

Brain serotonin and blood pressure regulation: studies using in vivo electrochemistry and direct tissue assay

Hypotensive responses to tryptophan and 5-hydroxytryptophan infusions were studied in normotensive male Sprague-Dawley rats. Results showed that 5-hydroxytryptophan but not tryptophan lowered pressure in a dose dependent way in direct relation to the production of brain serotonin and 5-HIAA. Intrinsic release of serotonin from brain was also studied during periods of induced hypertension and hypotension. Brain monoamine responses to blood pressure changes induced by intravenous phenylephrine and nitroprusside were measured in dorsal raphe nucleus and nucleus tractus solitarius by in vivo electrochemistry. Results showed that 5-HIAA was increased during drug induced hypertension and during reflex hypertension which followed a period of hypotension. These changes were blocked by sinoaortic denervation indicating that these central serotonergic neurons are responding to increased pressure sensed by baroreceptors. Therefore, serotonin has a role in blood pressure regulation as a pharmacologic agent and as a neurotransmitter in homeostatic control of pressure.     

Really taking Darwin and the naturalistic fallacy seriously: An objection to Rottschaefer and Martinsen

Out of a concern to respect the naturalistic fallacy, Ruse (1986) argues for the possibility of causal, but not justificatory, explanations of morality in terms of evolutionary processes. In a discussion of Ruse's work, Rottschaefer and Martinsen (1990) claim that he erroneously limits the explanatory scope of evolutionary concepts, because he fails to see that one can have objective moral properties without committing either of two forms of the naturalistic fallacy, if one holds that moral properties supervene on non-moral properties. In this short paper I argue that Rottschaefer and Martinsen's solution fails. If one takes moral properties to supervene on non-moral properties, then either one ends up committing one of the two forms of the naturalistic fallacy or else one is left postulating unbelievable brute metaphysical facts.     

Altered serotonin and norepinephrine metabolism in rat dorsal raphe nucleus after drug-induced hypertension

The effect of drug-induced hypertension on neurotransmitter release from dorsal raphe nucleus was studied by in vivo electrochemical electrodes in urethane anesthetized male Sprague-Dawley rats. Carbon paste electrodes were stereotaxically placed into dorsal raphe nucleus and neurotransmitter release was estimated electrochemically. Blood pressure was recorded from a femoral arterial catheter. Voltammograms taken from dorsal raphe nucleus showed two distinct peaks corresponding to norepinephrine and 5-hydroxyindole acetic acid (5-HIAA). After basal blood pressure and neurotransmitter release were monitored for 30 min, blood pressure was raised 50 mmHg by continuous intravenous infusion of L-phenylephrine hydrochloride. Drug infusion was discontinued after 50 min, but blood pressure and neurotransmitter release were measured for an additional 2 hr. Results showed that the 5-HIAA response increased immediately after the initiation of hypertension and remained elevated. By contrast, norepinephrine release initially decreased, then returned to the basal level and then rose in parallel with 5-HIAA to a level above baseline as drug-induced hypertension was discontinued. The same experimental protocol was used to study the electrochemical response to drug-induced hypotension. Blood pressure was lowered 20 mmHg by intravenous infusion of sodium nitroprusside dihydrate. During hypotension, no changes were seen in either transmitter response. However, as reflex hypertension appeared following discontinuation of the sodium nitroprusside infusion, the 5-HIAA response increased and the norepinephrine response decreased. These results show that drug-induced and reflex hypertension reduce norepinephrine release and increase serotonin turnover in dorsal raphe nucleus in anesthetized normotensive rats. These reciprocal changes appear to be a part of the neural response to hypertension.     

Explaining how and explaining why: developmental and evolutionary explanations of dominance

There have been two different schools of thought on the evolution of dominance. On the one hand, followers of Wright [Wright S. 1929. Am. Nat. 63: 274–279, Evolution: Selected Papers by Sewall Wright, University of Chicago Press, Chicago; 1934. Am. Nat. 68: 25–53, Evolution: Selected Papers by Sewall Wright, University of Chicago Press, Chicago; Haldane J.B.S. 1930. Am. Nat. 64: 87–90; 1939. J. Genet. 37: 365–374; Kacser H. and Burns J.A. 1981. Genetics 97: 639–666] have defended the view that dominance is a product of non-linearities in gene expression. On the other hand, followers of Fisher [Fisher R.A. 1928a. Am. Nat. 62: 15–126; 1928b. Am. Nat. 62: 571–574; Bürger R. 1983a. Math. Biosci. 67: 125–143; 1983b. J. Math. Biol. 16: 269–280; Wagner G. and Burger R. 1985. J. Theor. Biol. 113: 475–500; Mayo O. and Reinhard B. 1997. Biol. Rev. 72: 97–110] have argued that dominance evolved via selection on modifier genes. Some have called these “physiological” versus “selectionist,” or more recently [Falk R. 2001. Biol. Philos. 16: 285–323], “functional,” versus “structural” explanations of dominance. This paper argues, however, that one need not treat these explanations as exclusive. While one can disagree about the most likely evolutionary explanation of dominance, as Wright and Fisher did, offering a “physiological” or developmental explanation of dominance does not render dominance “epiphenomenal,” nor show that evolutionary considerations are irrelevant to the maintenance of dominance, as some [Kacser H. and Burns J.A. 1981. Genetics 97: 639–666] have argued. Recent work [Gilchrist M.A. and Nijhout H.F. 2001. Genetics 159: 423–432] illustrates how biological explanation is a multi-level task, requiring both a “top-down” approach to understanding how a pattern of inheritance or trait might be maintained in populations, as well as “bottom-up” modeling of the dynamics of gene expression.     

Catastrophe theory of dopaminergic transmission: a revised dopamine hypothesis of schizophrenia

Mathematical modeling of experimentally observed parameters of dopaminergic neuronal activity suggests the occurrence of multiple equilibrium states in neurons characterized by certain precisely defined properties of the tyrosine hydroxylating system. These equilibria may become unstable under certain conditions and transitions between multiple states are predicted. In addition, modeling of the spatial interactions of dopamine neurons within a neural net leads to domain wall soliton-like solutions of neuronal firing. In the discrete spatial case, these equations are isomorphic to those of the Ising model of phase transitions in lattice spins.The hypothesis is proposed that the occurrence of multiple stable equilibrium states rather than excessive dopaminergic transmission forms the pathophysiological basis of the schizophrenic thought disorder.The model is internally consistent with known clinical effects of drugs such as neuroleptics, reserpine and amphetamine. In agreement with postmortem and other studies, the theory predicts the lack of increased concentrations of dopamine or its major metabolite, homovanillic acid, in brain and cerebrospinal fluid of schizophrenics.The mathematical model is compatible with the theory that postulates an attention deficit as an underlying mechanism of schizophrenic psychosis and allows for a possible genetic heterogeneity of the disease.     

Flavonoids of Derris obtusa: Aurones and auronols

Heptacosanol and sitosterol, one chalcone, one flavone, one 3-O-methyl-flavonol, four aurones and two 3-O-methylauronols were isolated from the root bark of Derris obtusa. The latter compounds, called Derriobtusones A and B, are the first auronols found in nature. Structures were established through chemical and spectral means. Mass spectral fragmentation schemes are suggested for aurones and auronols.     

Bile acid and cholesterol excretion in the pregnant guinea pig: Studies on the hypercholesterolemia of pregnancy

The relationship of bile acid and cholesterol excretion to changes in plasma cholesterol during pregnancy were studied in guinea pigs. Plasma cholesterol level increased in the first trimester of pregnancy, reached to a peak during the second trimester and decreased in the third trimester reaching the lowest level at one week prior to parturition. Cholesterol level returned to the control level after parturition. Plasma triglyceride level followed a similar trend attaining peak values at second trimester and gradually returned to the control level at the third trimester of pregnancy. Bile acid and total sterol excretion were significantly higher in guinea pigs during the last phase of pregnancy while they remained unchanged during early stage of pregnancy.     

The discovery of the nature of ferredoxin in photosystems: A recollection

I describe here my recollection of the story of the discovery of the nature of ferredoxin in photosystems that began in 1965: this story involved the EPR measurements by a young physicist J.H.M. Thornley, using samples provided by J.F. Gibson and D. Hall, and in collaboration with F.R. Whatley.     

Differential regulation of high-affinity agonist binding to muscarinic sites in the rat heart, cerebellum, and cerebral cortex

The muscarinic agonist [3H]cismethyldioxolane ([3H]CD) was used to characterize the effects of regulators upon high-affinity agonist binding sites of the rat heart, cerebral cortex and cerebellum. Comparative studies with sodium ions (Na+), magnesium ions (Mg++), N-ethylmaleimide (NEM) and the guanine nucleotide Gpp(NH)p revealed tissue-specific effects. Mg++ preferentially enhanced while Gpp(NH)p and NEM reduced high-affinity [3H]CD binding in the heart and cerebellum. By comparison NEM enhanced high-affinity agonist binding in the cerebral cortex while Gpp(NH)p and Mg++ had little or no effect. Kinetic studies support an allosteric mechanism for these effects and provide further evidence for muscarinic receptor subtypes in mammalian tissues.     

Thromboxane and pulmonary hypertension following E. coli endotoxin infusion in sheep: Effect of an imidazole derivative

We assessed the effect of a specific thromboxane synthetase inhibitor (an imidazole derivative) on pulmonary hemodynamics and the concentrations of TxB₂ (TxA₂), 6-keto-PGF_1α (PGI₂), and PGF_2α in pulmonary lymph and transpulmonary blood samples following intravenous administration of E. coli endotoxin (1 μg/kg) in sheep. In control animals the rise in pulmonary artery pressure correlated with increases in plasma and lymph TxB₂ concentrations and large transpulmonary concentration gradients of this metabolite were measured. In imidazle treated animals both pulmonary hypertension as well as increases in plasma and lymph TxB₂ concentrations were substantially reduced. In contrast, peak concentrations of 6-keto-PGF_1α (PGI₂) and PGF_2α were severalfold higher than those measured in control animals. This suggests a shunting of endoperoxide metabolism towards prostacyclin and primary prostaglandins and documents the specificity of the thromboxane synthetase inhibitor. Out study provides evidence that endotoxin-induced pulmonary hypertension is mediated by pulmonary synthesis of TxA₂.     

Genetic evidence for the common identity of glucose-6-phosphatase,pyrophosphate-glucose phosphotransferase,carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase

We demonstrate that glucose-6-phosphatase, pyrophosphate-glucose phosphotransferase, carbamyl phosphate-glucose phosphotransferase and inorganic pyrophosphatase activities are deficient in livers of patients with type I glycogen storage disease. This provides strong genetic evidence that these enzymatic activities reside in a single protein or share a common polypeptide chain.     

Regulatory cells in human bone marrow: Suppression of an in vitro primary antibody response

Human bone marrow (BMC) contains regulatory cells that can suppress the in vitro primary PFC response of normal allogeneic spleen or tonsillar cells and autologous peripheral blood cells. Suppression is dependent upon the dose of BMC added, but is not due to cell crowding nor to excessive cytotoxicity, and requires the presence of viable, metabolically active BMC. BMC are maximally inhibitory when added during the first 24 hr of culture and do not cause an induced shift in the kinetics of the response. Thus, suppression reflects inhibition of early inductive events in the antibody response. The target of suppression is the non-T cell, with either polyclonal activator or Ag being required for maximal suppression. DNA synthesis of normal tonsillar cells is not inhibited by BMC. Characterization of the human bone marrow-suppressor cell has shown it to be radiosensitive, E-rosette negative, Fc receptor positive, and to reside in the large, weakly adherent cell population after velocity sedimentation and in the lymphocyte-depleted fraction after sucrose density gradient separation. Pretreatment of the bone marrow-suppressor cell with anti-human thymocyte serum does not abrogate suppression. We speculate on a possible physiologic role for this cell.     

On the integrated frameworks of species concepts: Mayden’s hierarchy of species concepts and de Queiroz’s unified concept of species

Richard L. Mayden and Kevin de Queiroz have devised and developed ‘a hierarchy of species concepts’ and ‘a unified species concept’, respectively. Although their integrated frameworks of species concepts are rather different as to how to integrate the diverse modern concepts of species, the end result is that they are likely to agree on species recognition in nature, because they virtually share the same major components (i.e. evolutionary or lineage concept of species; same way of delimiting species), and have the same important consequences. Both the hierarchical and unified frameworks, however, are interpreted to have shortcoming regarding the way of integrating the modern species concepts. I reformulate these ideas into a framework of species concepts as follows: It treats the idea of species as population‐level evolutionary lineages (sensu Wiley 1978 ) as the concept for species category, and it adopts the contingent biological properties of species (e.g. internal reproductive isolation, diagnosability, monophyly) as operational criteria in delimiting species. I also suggest that existing and revised versions of the integrated framework of species concepts all are not new species concepts, but versions of the evolutionary species concept, because they treat the evolutionary (or lineage) species concept as the concept for species category.     

Supraspinal influences on the penile reflexes of the male rat: a comparison of the effects of copulation, spinal transection, and cortical spreading depression.

The penile reflexes of the rat were observed on interruption of the copulatory behavior sequence after intromission and ejaculation in the initial ejaculatory series, after the penultimate series, during sexual exhaustion, and during recovery from sexual exhaustion 24 and 72 hr later. These were compared to the reflexes of the normal rat in control conditions, to those of the male rat after spinal transection, and to those of the sexually rested and sexually exhausted male rat under cortical spreading depression (CSD). It was concluded that (1) the stimuli associated with copulation evoke disinhibition of the penile reflexes, these showing the short reflex latencies observed in the spinal animal. The release of the spinal mechanisms is lost within 30 min of the last copulatory event. CSD further inhibits reflex responsivity. (2) Stimuli associated with intromission provoke acceleration of the normal rhythmic presentation of reflexes seen in the normal and spinal rat, resulting in a decrease in the duration of intervals between reflex clusters and an increase in reflex number. This excitation decays within about 15 min after intromission. (3) The increase in degree of penile extension and percentage of penile flips after spinal transection suggests tonic inhibition of reflex intensity in the normal rat. The decrease in capacity to attain full erection with the approach of sexual exhaustion suggests an increase in this inhibition. This does not recover during a rest period but instead intensifies. CSD effects did not mimic the effects of spinal transection but instead depressed reflex excitability. The relationship of these changes to the copulatory behavior pattern is discussed.     

Crystal structures of LacD from Staphylococcus aureus and LacD.1 from Streptococcus pyogenes: insights into substrate specificity and virulence gene regulation

Staphylococcus aureus LacD, a Class I tagatose-1,6-bisphosphate (TBP) aldolase, shows broadened substrate specificity by catalyzing the cleavage of 1,6-bisphosphate derivatives of d-tagatose, d-fructose, d-sorbose, and d-psicose. LacD.1 and LacD.2 are two closely-related Class I TBP aldolases in Streptococcus pyogenes. Here we have determined the crystal structures of S. aureus LacD and S. pyogenes LacD.1. Monomers of both enzymes are folded into a (β/α)₈ barrel and two monomers associate tightly to form a dimer in the crystals. The structures suggest that the residues E189 and S300 of rabbit muscle Class I fructose-1,6-bisphosphate (FBP) aldolase are important for substrate specificity. When we mutated the corresponding residues of S. aureus LacD, the mutants (L165E, L275S, and L165E/L275S) showed enhanced substrate specificity toward FBP.

Structured summary

lacDbinds to lacD by X-ray crystallography(View interaction)lacD1binds to lacD1 by X-ray crystallography(View interaction)     

Enhancement and suppression of immunoglobulin G-producing B cells in the presence of immune T cells.

Mice were immunized one to three times with sheep red blood cells. Four to seven days after the last immunization, the spleens were removed and the cells were cultured in vitro in the absence of antigen. Removal of most T cells by anti-θ serum treatment prior to culture could increase the number of IgG-producing B cells without affecting the number of specific or nonspecific IgM-producing B cells detected after 2 days of culture. Addition of graded numbers of immune cells to pure immune B cells enhanced the number of IgG-producing B cells, whereas addition or higher number of immune cells caused suppression. Since removal of T cells could also enhance the proliferation of IgG-producing B cells induced by lipopolysaccharide (LPS), a polyclonal B-cell activator, it is suggested that the suppressive effects of high numbers of immune T cells are exerted directly on the B cells.     

Photophosphorylation and the chemiosmotic perspective

Photophosphorylation was discovered in chloroplasts by D. Arnon and coworkers, and in bacterial ‘chromatophores’ (intercytoplasmic membranes) by A. Frenkel. Initial low rates were amplified by adding electron-carrying compounds such as FMN, later shown to support the ‘pseudocyclic’ electron flow. ATP synthesis, and coupling to electron flow, was detected accompanying linear electron flow from H₂O to either NADP⁺ or ferricyanide. Another pattern of electron flow supporting photophosphorylation was that of a cycle around Photosystem I (PS I). Isolation and analysis of the ATP synthase showed, as with mitochondrial and bacterial analogues, an intrinsic membrane complex (CF₀) and an extrinsic complex (CF₁). CF₁ is a latent ATPase, activated additively by the high-energy state of the thylakoids, and by reduction of a disulfide bond on the gamma subunit. Once reduced, ATP synthesis occurs at lower energy levels. The search for an ‘intermediate’ linking electron flow and ATP synthesis led to the discovery of post-illumination ATP synthesis by thylakoids, where turnover occurs in the dark. Once interpreted by P.Mitchell's chemiosmotic hypothesis, this led to the discovery of light-driven proton uptake into the thylakoid lumen, with accompanying Cl⁻ intake and Mg²⁺ and K⁺ output. Chemiosmosis was confirmed in several ways, including ATP synthesis in the dark due to an acid-to-base transition of thylakoids, and photophosphorylation accomplished in artificial lipid vesicles containing both the proton-pumping bacterial rhodopsin and a mitochondrial ATPase complex. The now generally accepted chemiosmotic interpretation is able to clarify some other aspects of photosynthesis as well. This revised version was published online in June 2006 with corrections to the Cover Date.     

Chlorophyll isolation,structure and function: major landmarks of the early history of research in the Russian Empire and the Soviet Union

This paper covers major events of the early history of chlorophyll research in the Russian Empire and the Soviet Union from 1771 until 1952, when the modern period of studies on photosynthesis began in full swing. Short biographical sketches of key scientists, reviews of their major research contributions and some selected photographs are included. This revised version was published online in August 2006 with corrections to the Cover Date.