2,2-dipyridyl binding to metal substituted horse liver alcohol dehydrogenase

The binding of 2,2-dipyridyl to metal substituted horse liver alcohol dehydrogenase was measured by spectrophotometric titrations. Large changes in the visible absorption spectra were seen for the Co2+, Cu2+ and Ni2+ hybrids upon coordination of 2,2-dipyridyl, due to a change in coordination number. The formation constants for binding to the Co2+ and Cd2+ hybrids are of the order 10(6) M-1, which means that these hybrids have a 500-fold higher affinity for 2,2-dipyridyl than the native Zn2+ enzyme. 2,2-dipyridyl has a 100-fold higher affinity for enzyme bound Cd2+ than for aqueous Cd2+ ions, while for Cu2+ and Zn2+ the opposite is the case. None of the substituted metal ions were removed from the active site during titration with the chelator 2,2-dipyridyl.     

An aryl hydrocarbon hydroxylating hepatic cytochrome P-450 from the marine fish Stenotomus chrysops

Hepatic microsomal cytochrome P-450 from the untreated coastal marine fish scup, Stenotomus chrysops, was solubilized and resolved into five fractions by ion-exchange chromatography. The major fraction, cytochrome P-450E (M_r = 54,300), was further purified to a specific content of 11.7 nmol heme/mg protein and contained a chromophore absorbing at 447 nm in the CO-ligated, reduced difference spectrum. NH₂-terminal sequence analysis of cytochrome P-450E by Edman degradation revealed no homology with any known cytochrome P-450 isozyme in the first nine residues. S. chrysops liver NADPH-cytochrome P-450 reductase, purified 225-fold (M_r = 82,600), had a specific activity of 45–60 U/mg with cytochrome c, contained both FAD and FMN, and was isolated as the one-electron reduced semiquinone.Purified cytochrome P-450E metabolized several substrates including 7-ethoxycoumarin, acetanilide, and benzo[a]pyrene when reconstituted with lipid and hepatic NADPH-cytochrome P-450 reductase from either S. chrysops or rat. The purified, reconstituted monooxygenase system was sensitive to inhibition by 100 μM 7,8-benzoflavone, and analysis of products in reconstitutions with purified rat epoxide hydrolase indicated a preference for oxidation on the benzo-ring of benzo[a]pyrene consistent with the primary features of benzo[a]pyrene metabolism in microsomes. Cytochrome P-450E is identical to the major microsomal aromatic hydrocarbon-inducible cytochrome P-450 by the criteria of molecular weight, optical properties, and catalytic profile. It is suggested that substantial quantities of this aromatic hydrocarbon-inducible isozyme exist in the hepatic microsomes of some untreated S. chrysops. The characterization of this aryl hydrocarbon hydroxylase extends our understanding of the metabolism patterns observed in hepatic microsomes isolated from untreated fish.     

Limb outgrowth in the chick embryo induced by dissociated and reaggregated cells of the apical ectodermal ridge.

Mesodermal cores of the stage 19 chick leg bud were capped with an intact apical ectodermal ridge (AER) or with strips cut from centrifugal pellets formed from Pronase-dissociated AERs. They were then covered with embryonic back-skin ectoderm and grown as grafts to the somite region of a host embryo. Control mesoderms were capped with centrifugal aggregates of nonridge limb ectoderm or similarly treated back-skin ectoderm, with ethanol-killed AERs or with no ectodermal cells other than the enveloping back-skin ectoderm.Controls were vascularized slowly and atypically and showed little outgrowth, forming only proximal skeletal structures. Recombinants equipped with AER cells were vascularized more fully and promptly and began vigorous growth after brief delay, forming legs with all skeletal segments represented, including claw-tipped toes. The latter were arranged in anteroposterior order corresponding to the original polarity of the mesoderm.Histological sections of recombinants made with cytologically distinctive quail AERs reveal that the cap of ridge cells, whether initially intact or reaggregated beneath the back-skin envelope, undergo a period of reorganization, forming a typical AER at the apex of the chimeric appendage after 48 hr. Meanwhile vigorous growth of the recombinant continues.These results show that the AER can cooperate with nonlimb ectoderm in promoting the morphogenesis of successively more distal levels of the limb skeleton. They also show that dissociated ridge cells can reorganize a typical AER at the apex of the limb mesoblast, meanwhile exercising their inductive effect on it.     

Stephen Jay Gould,Jack Sepkoski,and the ‘Quantitative Revolution’ in American Paleobiology

During the 1970s, a “revolution” in American paleobiology took place. It came about in part because a group of mostly young, ambitious paleontologists adapted many of the quantitative methodologies and techniques developed in fields including biology and ecology over the previous several decades to their own discipline. Stephen Jay Gould, who was then just beginning his career, joined others in articulating a singular vision for transforming paleontology from an isolated and often ignored science to a “nomothetic discipline” that could sit at evolution’s “high table.” Over the course of a single decade, between 1970 and 1980, this transformation had in large part been accomplished. Among those most centrally involved in this process were Gould, Thomas Schopf, David Raup, and Gould’s graduate student Jack Sepkoski, all of whom made major contributions in theoretical and quantitative analysis of the fossil record and evolutionary history. Recognizing that an ideological agenda was not enough, Gould and others developed and promoted new outlets, technologies, and pedagogical strategies to nurture their new discipline. This paper describes this process of transformation, and presents Sepkoski’s education and participation as exemplary of the “new model paleontologist”, which Gould hoped to produce.     

Plastoquinone redox control of chloroplast thylakoid protein phosphorylation and distribution of excitation energy between photosystems: discovery,background, implications

Chloroplast thylakoid protein phosphorylation was discovered, and the most conspicuous phosphoproteins identified, by John Bennett at Warwick University. His initial findings were published in 1977. The phosphoproteins included apoproteins of chloroplast light harvesting complex II. Thylakoid protein phosphorylation was shown to influence distribution of excitation energy between Photosystems I and II in 1979, during a visit by Bennett to the laboratory of Charles J. Arntzen at the University of Illinois at Urbana-Champaign. That work was published by Bennett, Katherine E. Steinback and Arntzen in 1980. Control of both protein phosphorylation and excitation energy distribution by the redox state of the plastoquinone pool was first established in 1980 during the author's visit to Arntzen's laboratory. The experiments were prompted by the realization that coupling between redox state of an inter-photosystem electron carrier and excitation energy distribution provides a concrete mechanism for adaptations known as state transitions. This work was published by Allen, Bennett, Steinback, and Arntzen in 1981. This discovery and its background are discussed, together with some implications for photosynthesis and for research generally. This minireview is a personal account of the Urbana-Warwick and related collaborations in 1979–83: it includes impressions, conjectures, and acknowledgements for which the author is solely responsible. This revised version was published online in June 2006 with corrections to the Cover Date.     

The problematic unity of biometrics

The word "biometry" may be less than 200 years old, but it can be argued that work we would now consider biometric dates back even to the pre-Christian era. The unity of biometry is attested through examples spanning two millennia, and a lesson from Francis Galton is recalled from a century ago.     

The priority dispute over the function of the lymphatic system and Glisson's ghost (the 18th-century Hunter-Monro Feud)

Basic Immunology has had only two significant public priority disputes. The first began in the late 1650s and concerned the recognition of the peripheral network of vessels which collects lymph throughout the body. The publication of this major anatomical discovery prompted a priority feud discussed in a previous paper. The subject of this essay is the second dispute which occurred a century later in the late 1750s. It focused on the function of the lymphatic system and precipitated a heated war of words between a young Scotch medical graduate (Alexander Monro) and a noted London anatomist (William Hunter). Their published charges and responses ranged from feigned respect to ad hominen invectives. But in retrospect, the priority claims of both were precluded by the observations and speculations of an Englishman (Francis Glisson) a full century before. The several editions of his work were unknown to Hunter and Monro at the inception of their feud.     

John Harris' argument for a duty to research

John Harris suggests that partcipation in or support research, particularly medical research, is a moral duty. One kind of defence of this position rests on an appeal to the past, and produces two arguments. The first of these arguments is that it is unfair to accept the benefits of research without contributing something back in the form of support for, or participation in, research. A second argument is that we have a social duty to maintain those practices and institutions that sustain us, such as those which contribute to medical knowledge. This argument is related to the first, but it does not rely so heavily on fairness. Another kind of defence of the duty to research rests on an appeal to the future benefits of research: research is an effective way to discharge a duty to rescue others from serious illness or death, therefore we have a duty to research. I suggest that all three of Harris' lines fail to provide a compelling duty to research and spell out why. Moreover, not only do the lines of argument fail in their own terms: in combination, they turn out to be antagonistic to the very position that Harris wants to defend. While it is not my intention here to deny that there might be a duty to research, I claim that Harris' argument for the existence of such a duty is not the best way to establish it.     

Harris lines: A study of age-associated bias in countingand interpretation

Harris lines are regularly used in paleopathology as indicators of episodic nonspecific stress, but the methodology for their use has not been clearly established. We studied radiographs of the distal shaft of the tibia in 82 immature and 49 mature subjects from a medieval burial site and compared the number of Harris lines and observer error according to age categories. We found statistically significant differences in both line counts and in observer error by age groups. In conclusion, studies of Harris lines must take into account age variation in order to be validated. Am J Phys Anthropol 103: 209–217, 1997. © 1997 Wiley-Liss, Inc.     

Ambiguities and Asymmetries in Consent and Refusal: Reply to Manson

John Harris claims that is it ‘palpable nonsense’ to suggest that ‘a child (or anyone) might competently consent to a treatment but not be competent to refuse it.’ In ‘Transitional Paternalism: How Shared Normative Powers Give Rise to the Asymmetry of Adolescent Consent and Refusal’ Neil Manson aims to explain away the apparent oddness of this asymmetry of consent and refusal, by appealing to the idea of shared normative powers, presenting joint bank accounts as an example. In this article, I will argue that Manson's account fails to explain away the oddness. Rather, I will argue that there are ambiguities to which Manson has not paid sufficient attention. In fact, as odd as it may sound, I argue that Manson actually agrees with Harris (at least in relation to the asymmetry of competence). He fails to recognize that he agrees with Harris because he is not careful enough to distinguish between different asymmetries, which I have labelled the asymmetries of choice, permissibility and competence.