Lilian Vaughan Morgan (1870-1952): Her Life and Work

Lilian Vaughan Morgan was an important geneticist of the firstpart of the 20th century. She discovered both the attached-Xand closed-X chromosomes as part of her extensive research onthe X chromosome of Drosophila. She received A.B and M.S. degreesin Biology from Bryn Mawr College and became an independentinvestigator in the 1890s at the Marine Biological Laboratory,Woods Hole, Massachusetts. Although her research at the turnof the century was in embryology, she made the successful transitionto genetics. In 1904 she married T. H. Morgan, raised four children,managed the Morgan household, and when the children were grownresumed full time research. She always worked independently,and in her lifetime published 16 single author papers.     

Inbreeding,eugenics, and Helen Dean King (1869–1955)

Helen Dean King’s scientific work focused on inbreeding using experimental data collected from standardized laboratory rats to elucidate problems in human heredity. The meticulous care with which she carried on her inbreeding experiments assured that her results were dependable and her theoretical explanations credible. By using her nearly homozygous rats as desired commodities, she also was granted access to venues and people otherwise unavailable to her as a woman. King’s scientific career was made possible through her life experiences. She earned a doctorate from Bryn Mawr College under Thomas Hunt Morgan and spent a productive career at the Wistar Institute of Anatomy and Biology in Philadelphia where she had access to the experimental subjects which made her career possible. In this paper I examine King’s work on inbreeding, her participation in the debates over eugenics, her position at the Wistar Institute, her status as a woman working with mostly male scientists, and her involvement with popular science.     

Profiles of Pioneer Women Scientists: Katherine Esau

“Profiles of Pioneer Women Scientists: Katherine Esau” tells the story of a noted botanist, plant anatomist, and electron microscopist who was born in the Russian Ukraine (in 1898), forced to flee the Bolshevik Revolution with her family—her father a mayor of Ekaterinoslav under the Czar—to Germany, where she received a bachelor’s degree in agriculture, education she put to good use in America. Beginning in a sugarbeet field in Salinas, California, she progressed through the doctoral degree at the University of California at Davis (UC Davis) and there began her exceptional research on plant anatomy and plant viral diseases. Her textbookPlant Anatomy became known among college students as “Aunt Kitty’s Bible,” and all of her textbooks have gone into second, and some to third, editions. Transferring to the University of California at Santa Barbara (with its new Chancellor, V. I. Cheadle) only two years before retirement, she blossomed anew, producing some of her best work there and obtaining National Science Foundation support for a new electron microscope and other research funds through her 89th year. Katherine Esau started accruing awards and honors at a relatively early age (Faculty Research Lecturer at age 50, election to the National Academy of Sciences at 59) and has never stopped (the President’s Medal of Science at age 91, a UC Santa Barbara building named for her at age 93). It has been her good fortune to live to enjoy these honors. The short autobiography of her father, a truly enterprising engineer, is included here, as are the recollections of Celeste Turner Wright. Celeste, who arrived at UC Davis the same year as Katherine Esau, became an acclaimed poet, and chaired the English Department for many years. She has added a lively reminiscence of the days she and Katherine spent at UC Davis. The introduction to the book by one of Esau’s former graduate students, Ray Franklin Evert, himself a renowned plant pathologist, provides a heartfelt tribute to his greatly admired professor.     

Anna Fraentzel Celli (1878-1958)

This paper provides a short history of Anna Fraentzel Celli life, from her arrival in Italy in 1898 to her death in 1958, reviewing available documents and written testimonies. Anna Fraentzel was born in Berlin in 1878, third of four daughters from a bourgeois family; her maternal grandfather, Luigi Traube, was a very well known physician, as well as her father Oscar, and she developed an early interest in medicine that she couldn't fulfill: actually after her father's death she was forced to shorten her education, she couldn't enter the medical school, as she would have liked to, and she attended the nursing school, instead, displaying a lot of good practical sense. As a nurse in Hamburg in 1896 she met Prof. Angelo Celli, who was there on a professional visit, and who assisted the young nurse in finding a job at the city hospital. She was much younger than him, who was already a middle aged respected scientist; anyhow, even after his departure, they kept in touch and eventually fell in love. They married in 1899 and she moved to Rome to work at the S. Spirito Hospital joining a brilliant group of physicians and researchers as Tommasi-Crudeli, Marchiafava, Bignami, Bastianelli, Dionisi, Grassi, and her husband Angelo. They had long been studying the mode of transmission of the malaria infection and in 1898 they had identified the mosquito Anopheles as the vector of the malaria parasite. She got enthusiastically involved both in the scientific work and in the antimalarial campaign which Celli promoted in the Agro Romano. The strong personality of Anna Celli, her active involvement in social problems, her passionate dedication to her work, her peculiar way of being feminist, expressed fully her commitment to the struggle against malaria and illiteracy in the Agro Romano and in the Paludi Pontine at the beginning of the twentieth century. She must be credited as a major force in the creation and functioning of the Peasant Schools, as well as in the organisation of the experimental antimalarial health clinics. After her husband's death in 1914 she continued as a promoter of the antimalarial campaign, co-operating with the Red Cross and other institutions. Moreover, she edited the scientific and historical papers which Angelo Celli had collected and written during his life. She was also a prolific writer and lecturer on these issues and gained widespread appreciation both in Italy and in Germany. Toward the end of her life she retired to a nursing home in Rome where she died almost alone in 1958.     

Nora Volkow: motivated neuroscientist

Nora Volkow claims to have always been curious about the workings of the human brain. Even as a medical student in her native Mexico, she investigated animal behavior with the ultimate goal of understanding human motivation. Upon completing her medical studies, in the early 80s, she moved to the U.S. to take advantage of emerging neuroimaging technologies, first during her psychiatry residency at New York University and Brookhaven National Laboratory, and then as a faculty member at the University of Texas in Houston. In Houston, Volkow embarked on seminal studies into human drug use and the functioning brain, which she continued to pursue, again at Brookhaven, during the subsequent two decades. Volkow established herself as an eminent researcher and proponent of neuroscience, and her insights into the brain have greatly advanced our appreciation of human behavior and motivation. In 2003, she took up her present position as Director of the National Institute on Drug Abuse.     

BOOK REVIEW

Books Reviewed in this Article:
Ricketts, E. F. and J. Calvin. 1968. Between Pacific Tides . 4th Ed. Revised by J. W. Hedgpeth. Stanford University Press, Stanford, California, U.S.A. $10.00.     

Foreseeing fates: a commentary on Manton (1928) ‘On the embryology of a mysid crustacean,Hemimysis lamornae’

Sidnie Manton became best known for her work on arthropod locomotion, and for proposing radical views on the evolution of arthropods that were accepted for a generation. However, her early training was as an embryologist, and the work that she carried out at the beginning of her career still stands as one of the major twentieth century contributions to the study of crustacean embryology. Here, I review her first major paper, largely completed while she was a graduate student, describing embryonic development in Hemimysis lamornae, a small shrimp-like animal found in the seas around the UK. The clarity of her writing and the quality of her figures set a standard that laid the basis for subsequent work, and although not all of her conclusions have stood the test of time, they remain a standard reference for work today. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.     

Recombinational history and molecular evolution of western equine encephalomyelitis complex alphaviruses.

Western equine encephalomyelitis (WEE) virus (Togaviridae: Alphavirus) was shown previously to have arisen by recombination between eastern equine encephalomyelitis (EEE)- and Sindbis-like viruses (C. S. Hahn, S. Lustig, E. G. Strauss, and J. H. Strauss, Proc. Natl. Acad. Sci. USA 85:5997-6001, 1988). We have now examined the recombinational history and evolution of all viruses belonging to the WEE antigenic complex, including the Buggy Creek, Fort Morgan, Highlands J, Sindbis, Babanki, Ockelbo, Kyzylagach, Whataroa, and Aura viruses, using nucleotide sequences derived from representative strains. Two regions of the genome were examined: sequences of 477 nucleotides from the C terminus of the E1 envelope glycoprotein gene which in WEE virus was derived from the Sindbis-like virus parent, and 517 nucleotide sequences at the C terminus of the nsP4 gene which in WEE virus was derived from the EEE-like virus parent. Trees based on the E1 region indicated that all members of the WEE virus complex comprise a monophyletic group. Most closely related to WEE viruses are other New World members of the complex: the Highlands J, Buggy Creek, and Fort Morgan viruses. More distantly related WEE complex viruses included the Old World Sindbis, Babanki, Ockelbo, Kyzylagach, and Whataroa viruses, as well as the New World Aura virus. Detailed analyses of 38 strains of WEE virus revealed at least 4 major lineages; two were represented by isolates from Argentina, one was from Brazil, and a fourth contained isolates from many locations in South and North America as well as Cuba. Trees based on the nsP4 gene indicated that all New World WEE complex viruses except Aura virus are recombinants derived from EEE- and Sindbis-like virus ancestors. In contrast, the Old World members of the WEE complex, as well as Aura virus, did not appear to have recombinant genomes. Using an evolutionary rate estimate (2.8 x 10(-4) substitutions per nucleotide per year) obtained from E1-3' sequences of WEE viruses, we estimated that the recombination event occurred in the New World 1,300 to 1,900 years ago. This suggests that the alphaviruses originated in the New World a few thousand years ago.     

引进巨胚稻与普通稻的米质和营养成分分析比较

对引进的巨胚稻进行引种栽培并对其米质和营养成分进行全面分析.结果表明,巨胚稻的胚重是普通水稻胚重的3～5倍,多项营养成分如蛋白质、钙、磷、钾、钠、锰、VE、VB6和膳食纤维等的含量比普通稻米要高得多,这个结果表明巨胚稻是加工婴幼儿食品非常好的原料.     

Louisa May Alcott: her mysterious illness

Louisa May Alcott (1832-1888), famous in her own time and immortalized in ours as a major figure of the "American Renaissance," died at the age of 55 after intermittent suffering over 20 years. Her illnesses evoked intense interest in her time and in ours. Alcott tracked her signs and symptoms (in letters and journal entries), which included headaches and vertigo, rheumatism, musculo-skeletal pain, and skin rashes; in her final years she recorded severe dyspepsia with symptoms of obstruction, and headaches compatible with severe hypertension. Her death came suddenly with a stroke. Standard biographies propose that her illnesses were due to acute mercury poisoning from inorganic mercury medication she received for a bout of typhoid in 1863, a cause she herself believed. We have reviewed Alcott's observations, as well as those of others, and have determined that acute mercury poisoning could not have caused her long-term complaints. We propose instead that Alcott suffered a multi-system disease, possibly originating from effects of mercury on the immune system. A portrait of Alcott raises the possibility that she had systemic lupus erythematosus (SLE).     

Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption

It is generally believed that vitamin E is absorbed along with chylomicrons. However, we previously reported that human colon carcinoma Caco-2 cells use dual pathways, apolipoprotein B (apoB)-lipoproteins and HDLs, to transport vitamin E. Here, we used primary enterocytes and rodents to identify in vivo vitamin E absorption pathways. Uptake of [(3)H]alpha-tocopherol by primary rat and mouse enterocytes increased with time and reached a maximum at 1 h. In the absence of exogenous lipid supply, these cells secreted vitamin E with HDL. Lipids induced the secretion of vitamin E with intermediate density lipoproteins, and enterocytes supplemented with lipids and oleic acid secreted vitamin E with chylomicrons. The secretion of vitamin E with HDL was not affected by lipid supply but was enhanced when incubated with HDL. Microsomal triglyceride transfer protein inhibition reduced vitamin E secretion with chylomicrons without affecting its secretion with HDL. Enterocytes from Mttp-deficient mice also secreted less vitamin E with chylomicrons. In vivo absorption of [(3)H]alpha-tocopherol by mice after poloxamer 407 injection to inhibit lipoprotein lipase revealed that vitamin E was associated with triglyceride-rich lipoproteins and small HDLs containing apoB-48 and apoA-I. These studies indicate that enterocytes use two pathways for vitamin E absorption. Absorption with chylomicrons is the major pathway of vitamin E absorption. The HDL pathway may be important when chylomicron assembly is defective and can be exploited to deliver vitamin E without increasing fat consumption.     

Isolation of glycosaminoglycans and variation with age in the feline brain

M any laboratories have reported the presence of glycosaminoglycans (GAG) in the brains of a variety of species, including monkey, man, cat, pig, rabbit, sheep, rat and chicken (C handrasekaran and B achhawat , 1969; C lausen and H ansen , 1963; C lausen and R osenkast , 1962; C ustod and Y oung , 1968; M argolis , 1967; O nodera , H irona , H oriuchi and K ashimura , 1966; S aigo and E gami , 1970; S ingh and B achhawat , 1965 , 1968; S ingh , C handrasekaran , C herian and B achhawat , 1969). Because of the interest of our laboratory in the GAG of the cat brain (C ustod and Y oung , 1968; Y oung , 1963), we initiated the present studies to quantify these various brain polysaccharides and to investigate their changes as a function of postnatal age.     

Nettie Maria Stevens (1861-1912)

Nettie M. Stevens is one of the first women who contributed to genetic research. She discovered the role of sex chromosomes in sex determination during the first decade of the twentieth century. However, her discovery has rarely been recognized, and her scientific reputation was eclipsed by that of T.H. Morgan, who was credited for the establishment of modern genetics. Her name is absent from most biology and genetic texts. It is now time to recognize her valuable contribution with this short biography.     

A woman with thyrotoxicosis- and hyperemesis gravidarum-associated Wernicke's encephalopathy

Although hyperthyroidism arising from primary thyroid disease is rare in pregnancy, transient gestational hyperthyroidism is not uncommon. This condition can be associated with hyperemesis gravidarum (HG), and Wernicke's encephalopathy. We present the case of a woman with toxic nodular goiter complicating HG-associated Wernicke's encephalopathy. A 38-year-old Caucasian woman, who had received a diagnosis of hyperthyroidism and HG early in her pregnancy, had intrauterine fetal death at Week 16 of gestation. One day after undergoing therapeutic abortion, she was admitted to our clinic with persistent thyrotoxicosis, nausea, and vomiting. A toxic thyroid nodule was detected. She was given antithyroid medication, total parenteral nutrition. On Day 10 of hospitalization, she developed ataxia, aphasia, and somnolence. Cranial magnetic resonance imaging showed increased bilateral thalamic signalization. She was given a diagnosis of Wernicke's metabolic encephalopathy, for which she received thiamine and multivitamin preparations. She responded dramatically on the second day of thiamine therapy. Her consciousness improved rapidly and she began to speak. Her muscle tone was slightly weak and she had paresthesias in both legs. Absorption of thiamine may be particularly impaired in pregnant women with hyperemesis and hyperthyroid disease. Wernicke's encephalopathy should be considered in hyperthyroid women with HG who develop neurological abnormalities.     

Effect of hypervitaminosis A on hemolysis and lipid peroxidation in the rat

Erythrocytes from rats fed large doses of Vitamin A alone, or large doses of vitamin A and vitamin E or diphenyl-p-phenylene diamine (DPPD) were studied for H2O2-induced hemolysis. The vitamin A-dosed rats were more susceptible than normal rats to H2O2-induced hemolysis. Hemolysis was not accompanied by lipid peroxidation. Nevertheless, the antioxidants vitamin E and DPPD inhibited hemolysis in erythrocytes from vitamin A-dosed rats. These antioxidants had the same inhibitory effect when they were included in the diet or added to erythrocyte suspensions in vitro. Erythrocytes from vitamin A-dosed rats with or without added vitamin E or DPPD were less susceptible than the erythrocytes from normal rats to osmotic challenge, showing that vitamin A was present in levels sufficient to alter the structure of the erythrocyte membrane. These studies show that oxidative hemolysis occurs when the erythrocyte membrane is modified. Furthermore, this oxidative hemolysis is unrelated to lipid peroxidation.     

Clonidine in spinal cord injury.

A 16-year-old girl, one of dizygotic twins, presented in 1976 complaining of a 1-year history of a lack of coordination and an inability to run. The results of biochemical tests confirmed the diagnosis of classic abetalipoproteinemia. In addition to the recognized neurologic features of this disorder, she had a reduced evoked motor unit potential and markedly elevated serum levels of muscle enzymes, which suggested myositis. The serum vitamin E level was markedly decreased. Oral therapy with vitamin E, 800 mg daily, was begun, and in 1981 the dosage was increased to 3200 mg daily. Over the 7 years of follow-up she improved clinically, there was an increase in the evoked motor unit potential, the serum levels of some of the muscle enzymes decreased to normal, and the serum and tissue vitamin E levels increased significantly. It was concluded that treatment with high doses of vitamin E was responsible for the arrest of the usually progressive neuropathy and myopathy.     

50 years ago The cautious recognition of the protein nature of some hormones

Professor Dorothea Raacke, Boston University, is well known for her research on protein hormones and on protein synthesis, starting at the University of California, Berkeley. She pioneered in studies of the function of ribosomes. More recently she has written extensively in the history of biology, and the lives of biologists.     

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.