Why linguistics needs the cognitive scientist.
Explore the source record for details and available documents.
Anthropology, Cultural↗
Biomedical subjects
S R Anderson
Publications and source records attributed to S R Anderson.
Discography.
Discography is a diagnostic tool that has been used for many years. Although controversial, it provides a physiologic test for evaluation of a disc with a volumetric, manometric, radiographic, and pain-provocative challenge. Although it has a controversial past, when the anatomy and pathophysiology are considered particularly in relation to intradiscal pressure and applied loads (that correlate with daily activities of the patient), the interpretation of the results of discography become more objective and reproducible. As with any procedure, indications for patient selection are an important step in successful outcomes. The equipment and technique used for performing discography using a manometry system are described in this article, as are a review of complications and outcomes. Discography is a safe, accurate, reproducible, objective diagnostic tool when tested for volume, pressure, fluoroscopic changes, and pain provocation.
Fluoroscopy↗
A rationale for the treatment algorithm of failed back surgery syndrome.
Failed back surgery syndrome is continued low back pain with or without radicular pain after lumber surgery. The syndrome is difficult to treat due to the variability of pain generators. By examining the anatomy and pathophysiology of the pain mechanisms, a logical progression for an algorithm for treatment is presented.
Algorithms↗
The human language faculty as an organ.
Developments in the study of language and cognition give increasing credibility to the view that human knowledge of natural language results from--and is made possible by--a biologically determined capacity specific both to this domain and to our species. The functional properties of this capacity develop along a regular maturational path, such that it seems more appropriate to speak of knowledge of our own language as growing rather than as being learned. That our learning of language results from a specific innate capacity rather than by general mechanisms of induction is supported by the extent to which we can be shown to know things that we could not have learned from observation of any plausible available teaching. The domain-specificity of the language faculty is supported by the many dissociations that can be observed between control of language structure and other cognitive functions. Finally, the species-specificity of the human language faculty is supported by the observation that (absent severe pathology) every human child exposed in even limited ways to the triggering experience of linguistic data develops a full, rich capacity that is essentially homogeneous with that of the surrounding community. Efforts to teach human language to other species, however, have uniformly failed. These considerations make it plausible that human language arises in biologically based ways that are quite comparable to those directing other aspects of the structure of the organism. The language organ, in this sense, can be interpreted in a functional sense, and not as implying an anatomical location comparable to that of, say, the kidney.
Brain↗
Implications of the Relenza ruling.
Explore the source record for details and available documents.
Antiviral Agents↗
Expedition health and safety: a risk assessment.
Little has been published on the risks of participating in an expedition. A questionnaire survey was conducted to quantify those risks and to determine how expedition organizers plan for medical mishaps. 246 expeditions, taking 2381 participants to more than one hundred countries, were studied retrospectively. 65 expeditions (26%) reported no medical incidents; the remaining 181 reported 835 in 130,000 man-days (6.4 per 1000 man-days). 59% of the medical incidents seen on expeditions were preventable, one-third of these being due to gastrointestinal upsets. 78% of medical incidents were classified as minor and only 5% (40) as serious. There was no excess of serious incidents in any particular organizational group or environment. The findings of this survey suggest that the health risks of participating in a well-planned expedition are similar to those encountered during normal active life.
Adolescent↗
Binding of 9-anthroylcholine monitors the interactions of adenosine cyclic 3',5'-phosphate-dependent protein kinase with MgATP, substrates, and regulatory subunits.
The isolated catalytic subunit of cAMP-dependent protein kinase and smooth muscle myosin light chain kinase undergo interactions with the fluorescent dye 9-anthroylcholine (9AC) that are responsive to the two enzymes' associations with substrates and effectors. Additionally, the binding of 9AC is highly sensitive to subtle structural or functional differences among closely related protein kinases. Skeletal muscle myosin light chain kinase and the catalytically active chymotryptic fragment of the gamma-subunit of phosphorylase kinase do not associate with 9AC. The 1:1 fluorescent complex of the isolated catalytic subunit of cAMP-dependent protein kinase with 9AC exhibits a dissociation constant of 21 microM. The association of the catalytic subunit with either of the regulatory subunits, RI and RII, results in decreases in the observed 9AC fluorescence that are reversed upon the addition of cAMP. The effects of MgATP and of polypeptide substrates (Kemptide, troponin I, protamine) on the 9AC-catalytic subunit complex are consistent with a general noncompetitive model in which the interactions of 9AC and the other ligands with the enzyme are mutually antagonistic but not purely competitive.
Adenosine Triphosphate↗
Flexibility involving the intermolecular dityrosyl cross-links of enzymatically polymerized calmodulin.
The role of dityrosine as a fluorescent crossbridge between adjacent calmodulin molecules within the high molecular mass polymers that are generated by Arthromyces peroxidase-catalyzed cross-linking [Malencik, D. A., and Anderson, S. R. (1996) Biochemistry 35, 4375] has been examined in frequency domain fluorescence anisotropy studies. Measurements on a polymer fraction possessing a range of molecular masses > 96 000 in NaDodSO4 polyacrylamide gel electrophoresis demonstrate predominating fast local rotations involving the dityrosyl moieties. Normal distribution analyses of the results show peak rotational correlation times of 0.6 ns (zero Ca2+) and 1.2 ns (+Ca2+), values that are smaller than the principal correlation times determined for the global rotation of the free calmodulin monomer in either the presence or absence of Ca2+. The intermolecularly cross-linked segments of the polymers retain a degree of the mobility that is characteristic of the tyrosine-containing sequences of native calmodulin. The half-widths of the normal distribution curves range from 13 ns (zero Ca2+) to approximately 90 ns (5 mM Ca2+), thus encompassing varying rates of segmental motion within the polymers. When Ca2+ is present, possible contributions from the global rotations of polymer molecules are detected near the operating limits of the method. Experiments with the intramolecularly cross-linked calmodulin monomer give global rotational correlation times of 7.9 ns (zero Ca2+) and 11.4 ns (+Ca2+), which compare to values of 7.2 ns and 9.9 ns found previously in time domain measurements [Small, E. W., and Anderson, S. R. (1988) Biochemistry 27, 419]. Rotations of apparent phi2 = 0.2 to 0.3 ns also are detected, accounting for 31% (-Ca2+) to 23% (+Ca2+) of the anisotropy.
Animals↗
Identification of a new phosphorylation site in cardiac muscle phosphofructokinase.
The novel phosphorylation site (Ser376) that we discovered during in vitro studies of the troponin C- or calmodulin-induced phosphorylation of rabbit muscle phosphofructokinase [Zhao, Z., Malencik, D.A., and Anderson, S. R. (1991) Biochemistry 30, 2204] also undergoes phosphorylation in the epinephrine-stimulated rabbit heart. Reversed-phase HPLC and/or iron chelate affinity chromatography performed on CNBr digests of phosphofructokinase that had been isolated from epinephrine-treated hearts yields a largely phosphorylated peptide corresponding to amino acid residues 371-378 of the enzyme. Mass spectrometry, gas phase sequencing, and amino acid analyses establish the structure and phosphorylation state of the peptide.
Animals↗
Dityrosine: preparation, isolation, and analysis.
This article describes chromatographic and spectroscopic techniques that have multiple applications in the preparation, isolation, and analysis of dityrosine. A three-step chromatographic procedure facilitates the preparation of 120 mg or more (yield > 26% of theoretical maximum) of dityrosine from the enzyme-catalyzed oxidation of tyrosine. DEAE-cellulose chromatography performed in a boric acid-sodium borate buffer removes most of the contaminating pigments. Two-dimensional pH-dependent chromatography on BioGel P-2 separates dityrosine from tyrosine, residual pigments, salts, etc. Elemental analysis indicates that the purified product is approximately 92% dityrosine by weight. Fast atom bombardment mass spectrometry and two types of reverse-phase high-performance liquid chromatography (HPLC), monitored in fluorescence and absorbance measurements, verify the purity of the dityrosine. The distinctive pH-dependent chromatography of dityrosine on BioGel P-2, with reversible adsorption to the matrix occurring at pH values less than 3, is useful for the isolation of varying quantities of dityrosine and for analysis per se. Affinity chromatography on immobilized phenyl boronate (Matrex Gel PBA-60) is an alternate method for the isolation and determination of dityrosine, which undergoes specific interactions with the boronate moiety and possible hydrophobic association with the phenyl group. Two new reverse-phase HPLC techniques expedite the analysis of picomole quantities of dityrosine. One employs isocratic elution (92% H2O, 8% acetonitrile, and 0.1% trifluoroacetic acid) of an ODS II Spherisorb column, with both fluorometric and spectrophotometric detection. The other procedure may be performed in conjunction with total amino acid analysis. A rapid gradient program, developed with a Phenomenex Ultracarb 20 column, clearly separates dabsylated dityrosine and tyrosine from other dabsylated amino acids. It is especially useful when dityrosine is a trace component.
Boronic Acids↗
Rabbit liver phosphofructokinase: rapid purification and phosphorylation site identification.
Liver phosphofructokinase can be selectively precipitated by the addition of protamine sulfate to a heat-treated crude extract and redissolved, giving nearly full recovery of catalytic activity in combination with a 67-fold increase in specific activity. We have incorporated protamine sulfate precipitation into a five step purification procedure that can be completed in one day--giving 47% recovery of electrophoretically homogeneous liver phosphofructokinase having a specific activity of 50 units/mg. The radio-labeled fragment isolated from a CNBr digest of liver phosphofructokinase that has undergone in vitro phosphorylation catalyzed by the cAMP-dependent protein kinase has the sequence AEYVSGELEHVTRRSLS.
Adenosine Triphosphate↗
Dityrosine formation in calmodulin: cross-linking and polymerization catalyzed by Arthromyces peroxidase.
We employ bovine brain calmodulin, a protein that is subject to photoactivated dityrosine formation [Malencik, D. A., & Anderson, S. R. (1987) Biochemistry 26, 695; (1994) Biochemistry 33, 13363], as a model for the development of an efficient enzyme-catalyzed protein cross-linking technique. Key steps in the elaboration of the procedure are (1) identification of a peroxidase, from Arthromyces ramosus, that catalyzes dityrosine production in proteins that are not acted on by other common peroxidases, (2) monitoring of the intrinsic fluorescence of dityrosine to determine optimum reaction conditions, achieved with calmodulin in solutions containing boric acid-sodium borate (concentration > or = 0.2 M), approximately pH 8.3, approximately 40 degrees C, and (3) quenching of the reaction with reduced glutathione. Arthromyces peroxidase is the only common peroxidase able to catalyze significant dityrosine production in calmodulin, through a reaction that is largely intermolecular. Gel filtration yields fractions (accounting for approximately 40% of the initial calmodulin) that represent differing mobility ranges in NaDodSO4 polyacrylamide gel electrophoresis and contain close to the maximum possible amounts of dityrosine. The various fractions undergo Ca2+-dependent conformational changes detected in sedimentation velocity and/or fluorescence anisotropy measurements. Most of the samples stimulate the Ca2+-dependent activity of smooth muscle myosin light chain kinase. In catalytic assays utilizing the synthetic phosphatic acceptor peptide, the average activities range from 50 to 100% of that determined for native calmodulin. However, only the least polymerized fraction and the photogenerated calmodulin dimers significantly enhance the p-nitrophenylphosphatase activity of calcineurin. The ability to prepare soluble calmodulin polymers that retain a substantial degree of biological activity and exhibit the intense visible fluorescence of dityrosine illustrates the potential usefulness of Arthromyces peroxidase in the zero-length cross-linking of proteins.
Animals↗
Dityrosine formation in calmodulin: conditions for intermolecular cross-linking.
The pattern and extent of photoactivated dityrosine formation in bovine brain calmodulin are strongly affected by the presence of superoxide dismutase during UV irradiation. The addition of the enzyme to Ca(2+)-containing solutions of calmodulin results in an altered distribution of the dityrosine-containing photoproducts, from a predominance of cross-linked monomer to a mixture of products with inter- and intramolecular cross-linking. When Ca2+ is absent, significant dityrosine formation occurs only in the presence of superoxide dismutase. Fractionation of the latter reaction mixture yields a dimer of calmodulin, corresponding to a single component in sedimentation equilibrium, a smaller amount of a more highly polymerized material, and virtually no cross-linked monomer--as was found in the absence of the enzyme [Malencik, D.A., & Anderson, S.R. (1987) Biochemistry 26, 695]. Although it is homogeneous in terms of molecular weight, the purified dimer contains three electrophoretic components. Chemical characterization demonstrates intermolecular cross-linking of Tyr-99 to Tyr-138 and probably of Tyr-99 to Tyr-99. On the average, 85-90% of the dimeric calmodulin molecules bind two molecules of smooth muscle myosin light chain kinase. Catalytic activity determinations with this enzyme detect no difference between the dimer and the native protein. Fluorescence anisotropy measurements of Ca2+ binding give a Hill coefficient of < or = 0.73 and a free Ca2+ concentration of approximately 11 microM at 50% saturation. The average pKa of the dityrosine cross-link in the dimeric calmodulin is 8.5-8.6 (+/- Ca2+). Sedimentation velocity experiments show that the average Ca(2+)-liganded dimer has an elongated structure, with a relative frictional ratio approximately 30% greater than that of the native monomer. In terms of functional properties, the dimeric calmodulin preparation is more like the native protein than it is like the previously reported cross-linked monomer.
Amino Acids↗
Primary and secondary kinetic isotope effects as probes of the mechanism of yeast enolase.
Enolase catalyzes the interconversion of 2-phosphoglycerate and phosphoenolpyruvate. Kinetic isotope effects have been used to determine whether abstraction of the proton from C-2 and loss of hydroxide from C-3 of 2-phosphoglycerate occur in a concerted reaction or as sequential processes and whether these steps are kinetically significant for the enolase-catalyzed reaction. Enolase exhibits a significant primary deuterium isotope effect, as well as catalyzing the relatively rapid exchange of the C-2 proton with solvent water. Secondary C-3 deuterium isotope effects are also reported, both when the C-2 carbon carries a hydrogen and when this center is deuterated. These results provide information about the kinetic significance and timing of the transition state(s) associated with the loss of H+ and OH-. Strong evidence has been presented for a stepwise mechanism where both the rate of proton abstraction and one or both of the later transition states, i.e., those associated with hydroxide loss and product release, limit the overall reaction rate. If a concerted reaction were to be invoked, the presence of a small secondary 2H isotope effect in combination with the observed rate of exchange of the C-2 proton require the intrinsic secondary 2H kinetic isotope effect to be effectively unity. For the concerted mechanism, an intrinsic effect of unity would be consistent only with an extremely asymmetric transition state that is dominated by C-H bond cleavage.
Deuterium↗
Racemization and oxidation studies of hair protein in the Homo tirolensis.
Amino acids contained in fossil materials show an increasing extent of racemization with age, postulating time and temperature as the two major variables. The recent discovery of the Homo tirolensis made possible a comparison between racemization rates of the amino acids found in hair at identical ages (5200 years of age) but at different diagenetic temperatures ("Ginger," found in the hot, dry sand of Egypt; H. tirolensis, found on a glacier of the Otztaler Alps). The rate of racemization was higher in the H. tirolensis, which is surprising and in contrast to current concepts. Ortho-tyrosine and di-tyrosine, parameters for OH-radical attack, were also higher in the H. tirolensis, suggesting a role for free OH-radical involvement in the racemization process.
Amino Acids↗
Preparation and functional characterization of a catalytically active fragment of phosphorylase kinase.
Limited proteolysis of rabbit muscle phosphorylase kinase catalyzed by chymotrypsin generates a 33 kD product whose kinase activity is independent of both calcium and pH over the range of 6.8 to 8.3 (Malencik, D.A. & Fischer, E.H. Calcium and Cell Function III: 161-188, 1982). This active preparation consists of three related species containing residues 1-290, 1-296, and 1-298 of the 44.7 kD gamma-subunit of phosphorylase kinase (Harris, W.R., Malencik, D.A., Johnson, C.M., Carr, S.A., Roberts, G.D., Byles, C.E., Anderson, S.R., Heilmeyer, L.M.G., Fischer, E.H. & Crabb, J.W.J. Biol. Chem. 265:11740-11745, 1991). Good recoveries of catalytic activity--with varying degrees of calcium dependence--result upon the digestion of phosphorylase kinase with assorted proteases. However, especially high yields of the chymotryptic fragment are obtainable, with purification on an Ultrogel-34 column and a DEAE Sepharose CL-6B column giving 23% of the maximum possible protein. Physical characterization shows that the 33 kD chymotryptic fragment is globular, with S20,w = 2.9S, and that it has an isoelectric point of 5.3. Our continuous catalytic assay, based on differences in the binding of the fluorescent dye 1-anilinonaphthalene-8-sulfonate by phosphorylase a and b, shows that, on a molar basis, the activity of the fragment is 2.8 fold greater than that of phosphorylase kinase (Malencik, D.A., Zhao, Z. and Anderson, S.R. Biochem. Biophys. Res. Comm. 174: 344-350, 1991). The active fragment also undergoes autophosphorylation. Incubation with Mg[gamma-P32] ATP results in the reaction of 0.7 mol 32P/mol fragment. When the catalytic subunit of the cAMP-dependent protein kinase is also present, the amount of 32P incorporated increases to 1.1 mol/mol. In the former case, phosphorylation occurs primarily at Ser30 while in the latter an additional reaction takes place at Ser81. The phosphopeptides correspond to sequences occurring in the gamma-subunit of phosphorylase kinase.
Amino Acid Sequence↗
Continuous spectrophotometric assay of protein tyrosine phosphatase using phosphotyrosine.
A continuous activity assay for protein tyrosine phosphatases (PTPs), employing phosphotyrosine (P-Tyr) as a substrate, has been developed and applied to measure the activities of two purified enzymes, namely, the full length T-cell protein tyrosine phosphatase (TC PTP) and its truncated form (TC delta C11 PTP). The reaction was followed by changes in ultraviolet absorption and fluorescence resulting from the dephosphorylation of P-Tyr. Both enzymes obey Michaelis-Menten kinetics, with Km = 304 microM, Vmax = 62,000 units/mg for TC PTP and Km = 194 microM, Vmax = 73,000 units/mg for TC delta C11 PTP. The D- and L-forms of P-Tyr are equally effective as substrates. The optimum pH for both enzymes is 4.75. The known effectors of PTPs have the predicted effects on catalytic activity.
Hydrogen-Ion Concentration↗
Development of a continuum of services for children and adults with autism and other severe behavior disorders.
The development of a 12-step continuum of services for individuals with autism is described. The operation and funding of outreach parent training; homebased early intervention; preschool, vocational, and adult intermediate care; and school consultation programs are outlined. The use and importance of evaluative data on both treatment outcome and staff skills are emphasized.
Activities of Daily Living↗