Q & A. [interview

Elaine and Gary Ostrander spent their youth in New Jersey and New York before heading to Nebraska for their teen years and eventually Washington State for High School and college, as their father moved around in library administration. Elaine was an undergraduate at the University of Washington, a graduate student at the Oregon Health Sciences University and a postdoc with James Wang at Harvard, studying DNA supercoiling. She next went to Berkeley, where she began the canine genome project, initiating the meiotic linkage map and working on human chromosome 21 at the Lawrence Berkeley National Labs. In 1993 she moved to the Fred Hutchinson Cancer Research Center where she is now a Member of the Divisions of Clinical Research and Human Biology. She is also an Affiliate Professor of Genome Sciences and Biology at the University of Washington, and heads the Program in Genetics at the Hutchinson Center. Gary completed his undergraduate degree in Biology at Seattle University, a M.S. degree at Illinois State University and a Ph.D at the University of Washington in Ocean and Fisheries Science. He went on to be a postdoc in the Department of Pathology at the University of Washington Medical School while being mentored by Senitroh Hakomori of the Fred Hutchinson Cancer Research Center and Eric Holmes of the Pacific Northwest Research Foundation. His work focused on using novel aspects of the biology of fishes to address fundamental questions about cancer. He subsequently held both faculty and administrative positions at Oklahoma State University. Since 1996, he has been at the Johns Hopkins University, where he currently holds academic appointments in the Departments of Biology and Comparative Medicine and is the Associate Provost for Research.     

Atul Butte discusses the divide between bioinformatics and the clinic

Atul Butte is an Assistant in Endocrinology and Informatics and Attending Physician at Children's Hospital, Boston, USA (http://www.chip.org), and is an Instructor in Paediatrics at Harvard Medical School (http://www.harvard.edu). He received his undergraduate degree in Computer Science from Brown University in 1991, and worked in several stints as a software engineer at Apple Computer and Microsoft Corporation. He graduated from the Brown University School of Medicine in 1995, during which he worked as a research fellow at National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; http://www.niddk.nih.gov) through the Howard Hughes/NIH Research Scholars Program. He completed his residency in Paediatrics and Fellowship in Paediatric Endocrinology in 2001, both at Children's Hospital. During his research under Isaac Kohane (at Children's Hospital) he developed a novel methodology for analyzing large data sets of RNA expression, called Relevance Networks. His recent awards include the 2003 Emory University School of Medicine, Pathology Residents’ Choice Award, 2002 American Association for Clinical Chemistry Outstanding Speaker Award, 2002 Endocrine Society Travel Award based on presentation merit, 2001 American Association for Cancer Research Scholar-In-Training Award and the 2001 Lawson Wilkins Paediatric Endocrine Society Clinical Scholar Award.     

Homology, female orgasm and the forgotten argument of Donald Symons

The ‘byproduct account’ of female orgasm, a subject of renewed debate since Lloyd (The case of the female orgasm, Harvard University Press, Cambridge, 2005), is universally attributed to Symons (The evolution of human sexuality, Oxford University Press, Oxford, 1979). While this is correct to the extent that he linked it to the adaptive value of male orgasm, I argue that the attribution of the theory as we understand it to Symons is based on a serious and hitherto unrecognised misinterpretation. Symons had a different explanation of why women can orgasm, and beneath this explanation lies an obscure line of argument, including a particularly obscure use of the word ‘homologous’.     

Photosynthetic activity of isolated chloroplasts from Euglena gracilis

Functional chloroplasts from photoheterotrophic Euglena gracilis can be isolated in isoosmotic gradients of 10–80% Percoll. The chloroplasts display rates of CO₂ dependent O₂ evolution and CO₂ fixation of 30–50 mol mg^-1 chlorophyll h^-1 or 25–35% of the net O₂ evolution by the whole cells and appear to be strikingly different from spinach chloroplasts in several respects: 1. tolerance to high concentration of orthophosphate in the assay medium; 2. inability to support oxaloacetate-dependent O₂ evolution; 3. ability to support only low to moderate rates of 3-phosphoglycerate-dependent O₂ evolution; 4. an apparent absence of a phosphate translocator in the terms described by Heldt and Rapley ([1970] FEBS Lett. 10, 143–148).University of California, Dept. of Plant and Soil Biology, 108 Hilgard Hall, Berkeley, CA 94720 USA     

Childbirth and Authoritative Knowledge: Cross-Cultural Perspectives; African American Midwifery in the South: Dialogues of Birth, Race, and Memory; Reading Birth and Death: A History of Obstetric Thinking

Childbirth and Authoritative Knowledge: Cross-Cultural Perspectives. Robbie E. Davis-Floyd and Carolyn Sargent. eds. Berkeley, CA: University of California Press, 1997. xii. 510pp.
African American Midwifery in the South: Dialogues of Birth, Race, and Memory. Gertrude Jacinta Fraser. Cambridge, MA: Harvard University Press, 1998. xii. 287 pp.
Reading Birth and Death:. History of Obstetric Thinking. Jo Murphy-Lawless. Bloomington: Indiana University Press, 1998. viii. 343pp.     

Representations of Art and Arts of Representation

The Traffic in Culture: Refiguring Art and Anthropology. George E. Marcus and Fred R. Myers. eds. Berkeley: University of California Press, 1995. 380 pp.
The Death of Authentic Primitive Art and Other Tales of Progress. Shelly Errington. Berkeley: University of California Press, 1998. 309 pp.     

The Parasites of Homo sapiens by R.W. Ashford and W. Crewe

Liverpool School of Tropical Medicine, 1998. £10.00 (viii + 128 pages)ISBN 0 9508756 9 4     

Mercury detoxification and natural product synthesis: the work of Christopher T. Walsh

Mercuric Reductase. Purification and Characterization of a Transposon-encoded Flavoprotein Containing an Oxidation-Reduction-active Disulfide (Fox, B., and Walsh, C. T. (1982) J. Biol. Chem. 257, 2498–2503)Cloning, Overproduction, and Characterization of the Escherichia coli Holo-acyl Carrier Protein Synthase (Lambalot, R. H., and Walsh, C. T. (1995) J. Biol. Chem. 270, 24658–24661)Christopher Thomas Walsh was born in 1944 in Boston, Massachusetts. He attended Harvard University, where he did undergraduate research with E. O. Wilson, publishing a first author paper on the composition of fire ant trail substance in Nature (1). He earned his A.B. in biology in 1965. Walsh then went to Rockefeller University to work with Leonard B. Spector, publishing six first author papers and earning a Ph.D. in 1970 with a dissertation titled “The Mechanism of Action of the Citrate Cleavage Enzyme.”Open in a separate windowChristopher T. WalshWalsh did a 2-year postdoctoral fellowship with Robert H. Abeles at Brandeis University before joining the faculty of the Massachusetts Institute of Technology (MIT) in 1972 as an assistant professor. He eventually became the Karl Taylor Compton Professor and chairman of the chemistry department there.Walsh''s initial research at MIT centered on studies of a class of enzyme inhibitors called “suicide substrates,” compounds that were not toxic to cells but resembled normal metabolites so closely that they underwent metabolic transformation to form products that were inhibitory. Walsh also started to explore novel chemical transformations in biology, which led to his elucidation of the process by which bacteria detoxify mercury-containing molecules in the environment by cleaving carbon-mercury bonds and then reducing the mercuric salt to elemental mercury. An enzyme that is central to this process is a flavoprotein called mercuric reductase. The enzyme catalyzes two-electron reduction of mercuric ions to elemental mercury using NADPH as an electron donor. The elemental mercury is volatile and is thus nonenzymatically removed from the environment.In the first Journal of Biological Chemistry (JBC) Classic reprinted here, Walsh and Barbara Fox describe the purification of mercuric reductase from Pseudomonas aeruginosa. To their surprise, they discovered that the enzyme had a high degree of similarity to lipoamide dehydrogenase and glutathione reductase, flavoenzymes that catalyze the transfer of electrons between pyridine nucleotides and disulfides. This paper initiated a series of studies investigating how the inorganic Hg²⁺ substrate is bound to two pairs of thiols, one in the active site and one as an exit site, and how electrons flow from NADPH through the FAD to the bound Hg²⁺.In 1987, Walsh moved to Harvard Medical School to learn more biology and medicine and to become chairman of the department of biological chemistry and molecular pharmacology. He continued to study biocatalysts and began exploring antibiotic and antitumor agents as well. One of his first major findings at Harvard explained the mechanism by which resistance develops to the antibiotic vancomycin (2), work that provided the foundation to create new antibiotics.Walsh also is widely recognized for spurring a renaissance in natural product biosynthesis. This started with his investigation of holo-acyl carrier protein synthase (ACPS), a phosphopantetheinyltransferase (PPTase) that transfers the 4′-phosphopantetheine (4′-PP) moiety from coenzyme A to Ser-36 of acyl carrier protein (ACP) in E. coli. Walsh and Ralph H. Lambalot purified ACPS to near homogeneity by exploiting the fact that ACPS could be refolded and reconstituted after elution from an apo-ACP affinity column under denaturing conditions. As reported in the second JBC Classic reprinted here, Walsh and Lambalot used N-terminal sequencing of ACPS to determine that dpj, an essential gene of previously unknown function, was the structural gene for ACPS. These studies led to the identification of other PPTase genes and enzymes involved in the conversion of apo forms of acyl and peptidyl carrier proteins in polyketide and nonribosomal peptide synthases/synthetases. This, in turn, allowed posttranslational activation of these multimodular enzymes when heterologously expressed in E. coli, which started Walsh on a 10-year, 200-paper focus on the characterization of the many enzymatic steps in assembly line biosynthesis of natural products.Currently, Walsh is the Hamilton Kuhn Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. He also was president of the Dana Farber Cancer Institute from 1992 to 1995. Walsh has received many honors and awards for his contributions to science. These include the Eli Lilly Award in Biochemistry (1979), the American Chemical Society (ACS) Arthur C. Cope Scholar Award in Organic Chemistry (1998), the ACS Repligen Award for Chemistry of Life Processes (1999), the ACS Alfred Bader Award for Bioorganic Chemistry (2003), the American Society for Microbiology Promega Biotechnology Research Award (2004), the American Society for Biochemistry and Molecular Biology Fritz Lipmann Award (2005), the ACS Murray Goodman Award (2007), and the Stanford University School of Medicine Pauling Medal and Lecture (2010). Walsh also was elected to the American Academy of Arts and Sciences (1988), the National Academy of Sciences (1989), and the American Philosophical Society (2003). He served on the JBC editorial board from 1978 to1980.¹     

Q & A. Philip Ingham

Philip Ingham grew up in Liverpool and graduated from Cambridge University in 1977. He did his D.Phil in Developmental Genetics at Sussex University and postdoctoral work in Strasbourg, France before joining the laboratory of David Ish-Horowicz at the ICRF Mill Hill Laboratories. Here he applied the emerging technique of tissue in situ hybridisation to the analysis of the Drosophila segmentation genes. After a short spell at the MRC Laboratory of Molecular Biology in Cambridge, he rejoined the ICRF as a Research Scientist at the Developmental Biology Unit in Oxford. His group pioneered the analysis of the Hedgehog signalling pathway in Drosophila and in collaboration with the labs of Andy McMahon and Cliff Tabin at Harvard University, discovered the Hedgehog gene family in vertebrates. In 1996 he was appointed Professor of Developmental Genetics at the University of Sheffield where he has established the Centre for Developmental Genetics.     

Charles Stacy French: A tribute

Charles Stacy French, one of the great men of photosynthesis research, died on 13 October 1995. He received his PhD at Harvard University where he associated with William Arnold, Caryl Haskins, later president of the Carnegie Institution of Washington, and Pei-Sung Tang. He did early work on the photosynthesis of photosynthetic bacteria with Robert Emerson and later with Otto Warburg. French worked for three years with James Franck in Chicago. His associates there included Hans Gaffron, Robert Livingston, Warren Butler and Roderick Clayton. After spending three years at the University of Minnesota he became the director of the Department of Plant Biology of the Carnegie Institution of Washington and remained there until he retired in 1973. French's research career at the Carnegie Institution was marked by the development of novel and ingenious pieces of equipment such as the French pressure cell used to prepare chloroplast particles to measure partial reactions of photosynthesis. He developed the first recording fluorescence spectrophotometer and demonstrated efficient energy transfer between certain photosynthetically-active pigments, a spectrophotometer that measured the first derivative of absorbance, as well as a novel analog computer to show that complex absorption curves in living plants are produced by a number of distinct forms of chlorophyll occurring in vivo. French used the Blinks rate-measuring oxygen electrode to measure action spectra of oxygen evolution by photosynthesis automatically. He and Jack Myers did some of the pioneering work on the Emerson effect showing the necessary cooperation of two photosystems in photosynthesis. French used the Carnegie Institution's fellowship program to bring large numbers of scientists from around the world to his laboratory. When Stacy French died in 1995, the field of photosynthesis lost one of its great and early pioneers.This is CIW/DPB publication No. 1314.     

Colin Hill discusses in silico modeling of human cells

Colin Hill is the founder of Gene Network Sciences (GNS; http://www.gnsbiotech.com) and serves as President and Chief Executive Officer. He has extensive scientific experience in the areas of gene network modeling, pioneering the application of methods based in statistical physics and non-linear dynamics to the stochastic dynamics of gene expression. He is the co-founder of a multidisciplinary research effort at Cornell University dedicated to combining computational and experimental approaches to the study of signal transduction pathways. Hill is the co-creator of the Digital Cell™ software environment for the modeling of complex gene networks and biochemical pathways. He earned his BS degree in Physics from Virginia Polytechnic and State University and his MS degrees in Physics from McGill University and Cornell University.     

An Ancestral Recombination Graph for Diploid Populations with Skewed Offspring Distribution

A large offspring-number diploid biparental multilocus population model of Moran type is our object of study. At each time step, a pair of diploid individuals drawn uniformly at random contributes offspring to the population. The number of offspring can be large relative to the total population size. Similar “heavily skewed” reproduction mechanisms have been recently considered by various authors (cf. e.g., Eldon and Wakeley 2006, 2008) and reviewed by Hedgecock and Pudovkin (2011). Each diploid parental individual contributes exactly one chromosome to each diploid offspring, and hence ancestral lineages can coalesce only when in distinct individuals. A separation-of-timescales phenomenon is thus observed. A result of Möhle (1998) is extended to obtain convergence of the ancestral process to an ancestral recombination graph necessarily admitting simultaneous multiple mergers of ancestral lineages. The usual ancestral recombination graph is obtained as a special case of our model when the parents contribute only one offspring to the population each time. Due to diploidy and large offspring numbers, novel effects appear. For example, the marginal genealogy at each locus admits simultaneous multiple mergers in up to four groups, and different loci remain substantially correlated even as the recombination rate grows large. Thus, genealogies for loci far apart on the same chromosome remain correlated. Correlation in coalescence times for two loci is derived and shown to be a function of the coalescence parameters of our model. Extending the observations by Eldon and Wakeley (2008), predictions of linkage disequilibrium are shown to be functions of the reproduction parameters of our model, in addition to the recombination rate. Correlations in ratios of coalescence times between loci can be high, even when the recombination rate is high and sample size is large, in large offspring-number populations, as suggested by simulations, hinting at how to distinguish between different population models.     

The Mechanism of Amino Acid Activation: the Work of Mahlon Hoagland

Enzymatic Carboxyl Activation of Amino Acids(Hoagland, M. B., Keller, E. B., and Zamecnik, P. C. (1956) J. Biol. Chem. 218, 345–358)Mahlon Bush Hoagland was born in Boston, Massachusetts in 1921. He attended Harvard University and graduated in 1943. Knowing that he wanted to be a surgeon, Hoagland then enrolled at Harvard Medical School. However, he was diagnosed with tuberculosis, and his poor health prevented him from becoming a surgeon when he received his M.D. in 1948. Instead, he accepted a research position at Massachusetts General Hospital. In 1953, he became a postdoctoral fellow with Journal of Biological Chemistry (JBC) Classic author Fritz Lipmann (1) at Huntington Laboratories (also at Massachusetts General Hospital), and a year later, he moved to an adjoining laboratory to work on protein synthesis with JBC Classic author Paul Zamecnik (2).Open in a separate windowMahlon HoaglandInspired by Lipmann''s insights into acyl activation mechanisms, Hoagland used a cell-free system created by Zamecnik that carried out net peptide bond formation using ¹⁴C-amino acids (3) to uncover the mechanism of amino acid activation. As reported in the JBC Classic reprinted here, he isolated an enzyme fraction that, in the presence of ATP and amino acids, catalyzed the first step in protein synthesis: the formation of aminoacyl adenylates or activated amino acids. Using data from analysis of this fraction, Hoagland presented a scheme for amino acid activation in his Classic paper.A few years later, Zamecnik and Hoagland discovered a molecule that is essential for protein synthesis: tRNA. This discovery is the subject of the Zamecnik Classic (2).After the discovery of tRNA, Hoagland spent the next year (1957–1958) at Cambridge University''s Cavendish laboratories working with Francis Crick. During that year he traveled to France to visit the Institute Pasteur in Paris. Experiments begun at the Institute would, by 1960, lead to the discovery of messenger RNA (mRNA).When he returned to the United States, Hoagland was appointed associate professor of microbiology at Harvard Medical School. He remained there until 1967 when he accepted a position as professor at Dartmouth Medical School. In 1970, he became the director of the Worcester Foundation for Experimental Biology, a Massachusetts research institute founded by his father. He retired in 1985 and currently lives in Thetford, Vermont.Hoagland has received several awards and honors in recognition of his contributions to science. These include the 1976 Franklin Medal, the 1982 and 1996 Book Awards from the American Medical Writers Association, and membership in the American Academy of Arts and Sciences and the National Academy of Sciences.     

The Use of Isotope Effects to Study Dopamine ��-Monooxygenase Catalysis: the Work of Judith P. Klinman

Deduction of the Kinetic Mechanism in Multisubstrate Enzyme Reactions from Tritium Isotope Effects. Application to Dopamine β-Hydroxylase(Klinman, J. P., Humphries, H., and Voet, J. G. (1980) J. Biol. Chem. 255, 11648–11651)Use of Isotope Effects to Characterize Intermediates in the Mechanism-based Inactivation of Dopamine β-Monooxygenase by β-Chlorophenethylamine(Bossard, M. J., and Klinman, J. P. (1990) J. Biol. Chem. 265, 5640–5647)Judith Klinman was born Judith Pollock in 1941 in Philadelphia, Pennsylvania. Early on, she realized she was interested in science and decided to go to the University of Pennsylvania to study chemistry. However, her parents wanted her to become a medical technologist and forget about science. She eventually got them to agree to let her go if she got a scholarship; she graduated in 1962 with an A.B. She then decided to go to graduate school at New York University, but moved back to Penn after a year. Working with Edward R. Thornton, she completed her Ph.D. in 3 years, publishing a thesis titled “A Kinetic Study of the Hydrolysis and Imidazole-catalyzed Hydrolysis of Substituted Benzoyl Imidazole in Light and Heavy Water.”Open in a separate windowJudith P. KlinmanAfter graduating in 1966, Klinman first carried out postdoctoral research with David Samuel at the Weizmann Institute of Science in Israel and later with Journal of Biological Chemistry (JBC) Classic author Irwin Rose (1) at the Institute for Cancer Research in Philadelphia. Returning to the United States in 1968, she joined the Institute for Cancer Research in Philadelphia, where she was a research scientist for 10 years. In 1978 she became the first woman professor in the chemistry department of the University of California, Berkeley, where she continues to do research today as Professor of Chemistry and Molecular and Cell Biology in the Department of Chemistry.Throughout her research career, Klinman has contributed extensively to the understanding of the fundamental properties that underlie enzyme catalysis. Early in her career, she developed the application of kinetic isotope effects to the study of enzyme catalysis, showing how these probes can be used to uncover chemical steps, to determine kinetic order, and to obtain substrate dissociation constants. The two JBC Classics reprinted here stem from her use of isotope effects to isolate the chemical steps involved in the dopamine β-monooxygenase-catalyzed conversion of dopamine and oxygen to norepinephrine and water.In 1965, JBC Classic author Seymour Kaufman (2) suggested that oxygen binding precedes the addition of substrate in dopamine β-hydroxylase (now called dopamine β-monooxygenase) (3). However, confirmation of this hypothesis was hard to do using classical methods such as product and dead-end inhibition studies and equilibrium exchange techniques because of the apparent reversibility of the chemical step and the fact that one of the reaction products was water. In the first Classic, Klinman was able to disprove this hypothesis and use the sensitivity of kinetic tritium isotope effects to changes in oxygen concentrations in the reaction to provide unequivocal evidence for a random order of addition of dopamine and oxygen to dopamine β-hydroxylase.In the second Classic, Klinman uses isotope effects to study the inhibition of dopamine β-monooxygenase by β-chlorophenethylamine. Previously, she had postulated an inhibition mechanism in which bound α-aminoacetophenone was generated followed by an intramolecular redox reaction to yield a ketone-derived radical cation as the inhibitory species (4). However, she was unable to determine whether inhibition by α-aminoacetophenone occurred at the reductant- or substrate-binding site and was unable to provide evidence of keto-enol tautomerization of α-aminoacetophenone at the active site. Both of these questions were addressed using kinetic isotope effects. As reported in the JBC Classic, she showed that α-aminoacetophenone acts at the substrate-binding site and that there are two isotope-sensitive steps in β-chlorophenethylamine inactivation, with the second step attributed to an isotope-sensitive partitioning of the bound enol of α-aminoacetophenone between reketonization and oxidation.Over the years, Klinman continued her investigations into enzyme catalysis. In 1990 she demonstrated the presence of the neurotoxin, 6-hydroxydopaquinone (TPQ), at the active site of a copper-containing amine oxidase from bovine plasma, overcoming years of incorrect speculation regarding the nature of the active site structure and opening up the currently active field of protein-derived cofactors. Subsequent work from her group showed that the extracellular protein lysyl oxidase, responsible for collagen and elastin cross-linking, contains a lysine cross-linked variant of TPQ. Since the 1990s, Klinman''s kinetic studies of enzyme reactions have demonstrated anomalies that implicate quantum mechanical hydrogen tunneling in enzyme-catalyzed hydrogen activation reactions. In recent years she has developed a unique set of experimental probes for determining the mechanism of oxygen activation. These probes are beginning to shed light on how proteins can reductively activate O₂ to free radical intermediates, while avoiding oxidative damage to themselves.In addition to being the first woman faculty member in the physical sciences at the University of California, Berkeley, Klinman was the first woman Chair of the Department of Chemistry from 2000 to 2003. During her tenure at Berkeley she has been a Chancellor''s Professor, Guggenheim Fellow, and Miller Fellow. She was elected to the National Academy of Sciences (1994), the American Academy of Arts and Sciences (1993), and the American Philosophical Society (2001) and has received the Repligen Award (1994) and the Remsen Award (2005) from the American Chemical Society and the Merck Award from the American Society for Biochemistry and Molecular Biology (2007). Klinman was also President of the American Society for Biochemistry and Molecular Biology in 1998 and served on the editorial board of the Journal of Biological Chemistry from 1979 to 1984.     

Structure-Function Relationships in Ribonuclease S: the Work of Frederic M. Richards

The Preparation of Subtilisin-modified Ribonuclease and the Separation of the Peptide and Protein Components(Richards, F. M., and Vithayathil, P. (1959) J. Biol. Chem. 234, 1459–1465)The Three-dimensional Structure of Ribonuclease-S. Interpretation of an Electron Density Map at a Nominal Resolution of 2 Å(Wyckoff, H. W., Tsernoglou, D., Hanson, A. W., Knox, J. R., Lee, B., and Richards, F. M. (1970) J. Biol. Chem. 245, 305–328)Frederic Middlebrook Richards (1925–2009) was born in New York City. He attended the Massachusetts Institute of Technology and, after a brief stint in the military, received his B.S. in 1948. Richards then enrolled in graduate school at Harvard Medical School, where he worked with Barbara Low and received his Ph.D. in 1952. After graduating he remained at Harvard for another year as a research fellow with Edwin Joseph Cohn, who was featured in a previous Journal of Biological Chemistry (JBC) Classic (1). Richards then moved to the Carlsberg Laboratory in Denmark where, with Kaj Linderstrøm-Lang and others, he began working on ribonuclease.Open in a separate windowFrederic M. RichardsAfter a short stint as a postdoctoral fellow at Cambridge University, Richards joined the faculty of the Department of Biochemistry at Yale University in 1955 as an assistant professor. He rose rapidly through the ranks, becoming professor in 1963. That year, Richards was also appointed chairman of the Department of Molecular Biology and Biophysics at Yale, which entailed a move from the Medical School to the Yale College campus. Following a sabbatical at Oxford University in 1967–1968, for which Richards and his wife Sally sailed their own boat with a small crew across the Atlantic Ocean, Yale merged the Medical School Department of Biochemistry and the Yale College Department of Molecular Biology and Biophysics to form a new university-wide Department of Molecular Biophysics & Biochemistry (MB&B) with Richards as its founding chair (1969–1973). Richards remained at Yale for his entire research career, eventually becoming Sterling Professor of Molecular Biophysics and Biochemistry.Much of Richard''s early research centered on bovine pancreatic ribonuclease (RNase). During his time at the Carlsberg laboratory, he showed that cleavage of RNase by the protease subtilisin produces a modified RNase (RNase S) that is still active (2). After starting his own lab at Yale, Richards was able to separate RNase S into a 20-residue S-peptide and a 102-residue S-protein, both of which lacked enzymatic activity. However, when the peptide and protein were recombined, the activity was recovered. Richards published an initial paper on this finding in 1958 (3). He followed this up with a more extensive article in the JBC, which is reprinted here as the first JBC Classic. In this paper, Richards and co-workers purified and characterized RNase S, separated it into S-peptide and S-protein, showed that almost all enzymatic activity is recovered when the two components are recombined, and also reported that the only observed change in covalent structure during the conversion of RNase A to RNase S is the hydrolysis of the peptide bond between residues 20 and 21.The demonstration that two separate, inactive fragments of the enzyme RNase A could be reconstituted to form an active enzyme provided the first experimental evidence that the ability of a protein to form a three-dimensional structure is an intrinsic property of its amino acid sequence. This work also foreshadowed the extensive RNase A refolding studies performed by Nobel laureate Christian Anfinsen, as discussed in a previous JBC Classic (4).In the 1960s Richards teamed up with Harold Wyckoff to solve the three-dimensional structure of RNase S. Initially, in 1967, they produced a 3.5 Å electron density map (5), which they used to determine the approximate conformation of the peptide chain. Three years later, they collected data to 2 Å, as reported in the second JBC Classic reprinted here. Using these data, Richards, Wyckoff, and colleagues produced an electron density map, which they used to determine the complete three-dimensional structure of RNase S. This structure tied with three others for the third protein structure ever solved to atomic resolution. Richards also showed that RNase S was enzymatically active in crystal form, putting to rest the widely held view at that time that protein crystal structures were irrelevant to the conformation and behavior of enzymes in solution.Richards received many honors and awards for his scientific achievements, including the Pfizer-Paul Lewis Award in Enzyme Chemistry (1965), election as Fellow of the American Academy of Arts and Sciences (1968), election to the National Academy of Sciences (1971), the Kai Linderstrøm-Lang Prize in Protein Chemistry (1978), the American Society for Biochemistry and Molecular Biology Merck Award (1988), the Stein and Moore Award of the Protein Society (1988), and the State of Connecticut Medal of Science (1995). He was also president of ASBMB (1979) and the Biophysical Society (1972–1973).     

The BPP (protein biochemistry and proteomics) two-dimensional electrophoresis database

The BPP (protein biochemistry and proteomics) two-dimensional electrophoresis (2-DE) database (http://www-smbh.univ-paris13.fr/lbtp/Biochemistry/Biochimie/bque.htm) was established in 1998. The current release contains 11 reference maps from human hematopoietic and lymphoid cell line samples. These reference maps have now 255 identified spots, corresponding to 84 protein entries. The World Wide Web (WWW) presentation is designed to allow public access to the available 2-DE data together with logical connections to databases providing complementary information.     

The Reincarnation of Khensur Rinpoche: The Trials of Telo Rinpoche: A Stranger in My Native Land

The Reincarnation of Khensur Rinpoche. 1991. 55 minutes. color. video by Tenzing Sonam and Ritu Sarin. For more information, contact University of California Extension. Center Media and Independent Learning, 2000 Center Street. Suite 400. Berkeley, CA 94704.
The Trials of Telo Rinpoche. 1994. 50 minutes, color. video by Tenzing Sonam and Ritu Sarin. For more information, contact University of California Extension. Center Media and Independent Learning, 2000 Center Street. Suite 400. Berkeley, CA 94704.
Stranger in My Native Land. 1998. 30 minutes, color. video by Tenzing Sonam and Ritu Sarin. For more information, contact University of California Extension. Center Media and Independent Learning, 2000 Center Street. Suite 400. Berkeley, CA 94704.     

Characterization of low-molecular-weight-glutenin subunit genes from the D-genome of Triticum aestivum,Aegilops crassa,Ae. cylindrica and Ae. tauschii

Twenty low-molecular-weight-glutenin subunit (LMW-GS) gene sequences from the D-genome from Aegilops crassa (2n = 4x = 28), Ae. cylindrica (2n = 4x = 28), Ae. tauschii (2n = 2x = 14) and Triticum aestivum (2n = 6x = 42) were obtained using five sets of specific allele primer pairs. Only the sequences of the first primer pair were complete coding sequences (cds) of LMW-GS, and had 305, 304, 306 and 305 LMW-m amino acid residues in Ae. crassa, Ae. cylindrica, Ae. tauschii and T. aestivum, respectively. The repetitive domain and repeat motif numbers of all LMW glutenin subunits showed eight conserved cysteine residues that lead to the same functional activity in different genome. Based on DNA and predicted protein sequences, phylogenetic trees for all sets of sequences were drawn. At the DNA level, the species closest to T. aestivum for the second, third, fourth and fifth set of sequences were Ae. cylindrica, Ae. tauschii and Ae. crassa, respectively. At the protein level, the species closest to T. aestivum based on the first, second and fifth set of sequences were Ae. cylindrica, Ae. crassa and Ae. crassa, respectively. For other sets of sequences, bread wheat proved to be a distinct species. The LMW-GS gene sequences have been recorded in the GenBank with accession numbers JQ726549–JQ726568JQ726549JQ726550JQ726551JQ726552JQ726553JQ726554JQ726555JQ726556JQ726557JQ726558JQ726559JQ726560JQ726561JQ726562JQ726563JQ726564JQ726565JQ726566JQ726567JQ726568.     

One million sensors sold

A significant milestone has been reached by silicon fingerprint sensor provider AuthenTec as it announced the shipment of its one millionth sensor — the first in the industry to do so, the supplier claims. The sensor was shipped to Targus Group International, a provider of mobile lifestyle solutions, and will be embedded into its DEFCON Authenticator suite of notebook security products.This is a short news story only. Visit www.compseconline.com for the latest computer security industry news.