Govindjee,an institution,at his 80th (really 81st) birthday in Třeboň in October, 2013: a pictorial essay

Govindjee (one name only), who himself is an institution, has been recognized and honored by many in the past for he is a true ambassador of “Photosynthesis Research” to the World. He has been called “Mr. Photosynthesis”, and compared to the Great Wall of China. To us in T?eboň, he has been a great research collaborator in our understanding of chlorophyll a fluorescence in algae and in cyanobacteria, and more than that a friend of the Czech “Photosynthesis” group, from the time of Ivan ?etlík (1928–2009) and of Zdeněk ?esták (1932–2008). Govindjee’s 80th (really 81st) birthday was celebrated by the Institute of Microbiology, Laboratory of Photosynthesis, by toasting him with an appropriate drink of a suspension of green algae grown at the institute itself. After my presentation, on October 23, 2013, of Govindjee’s contributions to photosynthesis, and his intimate association with the photosynthetikers (in Jack Myers’s words) of the Czech Republic, Govindjee gave us his story of how he began research in photosynthesis in the late 1950s. This was followed by a talk on October 25 by him on “Photosynthesis: Stories of the Past.” Everyone enjoyed his animated talk—it was full of life and enjoyment. Here, I present a brief pictorial essay on Govindjee at his 80th (really 81st) birthday in T?eboň during October 23–25, 2013.     

Leeuwenhoek as a founder of animal demography

Summary and conclusions Leeuwenhoek's observations relating to animal population, though scattered through many letters written during a period of over forty years, when seen in toto, were important contributions to the subject now known as animal demography. He maintained enough contact with other scientists to have received encouragement and some helpful suggestions, but the language barrier and the novelty of doing microscopic work forced him to be resourceful, inventive, and original. His multifarious investigations impinged upon population biology before he discovered a direct interest in it. He devised methods for estimating numbers of animalcules, and then he went on to estimate the population of the world. His interest in reproduction was an important avenue by which he approached the subject of reproductive capacity. Other important approaches were his studies of growth, longevity, and life histories. He discovered relationships between aspects of the life history, longevity, and reproductive capacity of several species of insects, notably calanders, scavenger flies, crane flies, aphids, and lice. An important feature of these investigations were the arithmetical calculations which he made of reproductive potentials. In spite of several limitations, these calculations were an important innovation to the study of animal population. In his later years, his investigations came more and more within the sphere of ecology. He made the first significant observations on food chains. It is especially interesting that fish were the subject of these observations, because it was not until the latter half of the nineteenth century that scientists realized that fish ultimately depend upon phytoplankton.These accomplishments did not pass unnoticed. Although Leeuwenhoek never synthesized his scattered observations concerning population, his originality and perception were appreciated by outstanding biologists of the eighteenth century. The important discussions of population biology by Réaumur, Buffon, and Bonnet all derived inspiration and assistance from the writings of Leeuwenhoek.⁷³ This ingenious Fellow of the Royal Society, by detecting through diligent application and scrutiny the mysteries of Nature and the secrets of natural philosophy,⁷⁴ became one of the founders of animal demography.     

Donald J. Reis, MD: Research Mentor Extraordinaire

Donald J. Reis, M.D., the late internationally reknowned neuroscientist, had a special talent for mentoring researchers early in their academic careers. His hands-on approach to laboratory investigation, his extraoridinary patience with novice researchers, his commitment to the scientific method, and his enthusiastic approach to the art of neuroscience all combined to make him the ideal mentor for many budding academics over the past four decades. The beauty of his scientific legacy is that he loved to each research. The following tribute is personal from one whose career was changed by a great mentor.     

Dan Salah Tawfik (1955‐2021)—A giant of protein evolution

It was with great sorrow that we have learned of the untimely death of our friend, mentor, collaborator, and hero, Dan Tawfik. Danny was a true legend in the field of protein function and evolution. He had an incredibly creative mind and a breadth of knowledge—his interests spanned chemistry and engineering to genetics and evolution—that allowed him to see connections that the rest of us could not. More importantly, he made solving biochemical mysteries fun: He was passionate about his work, and his face lit up with joy whenever he talked about scientific topics that excited him (of which there were a lot). Conversations with Danny made us all smarter by osmosis.Danny’s own evolution in science began with physical organic chemistry and biochemistry. His PhD at the Weizmann Institute of Science, awarded in 1995, was on catalytic antibodies under the supervision of Zelig Eshhar and Michael Sela. It was followed by a highly productive period at the University of Cambridge’s Centre for Protein Engineering, first as a postdoctoral fellow with Alan Fersht and Tony Kirby, and then as a senior researcher. Among his many achievements during his time in Cambridge was the demonstration that off‐the‐shelf proteins—the serum albumins—could rival the best catalytic antibodies in accelerating the Kemp elimination reaction due to non‐specific medium effects. This work was an early example of unexpected catalytic promiscuity, and it sowed the seed for Danny’s later fascination with “esoteric, niche enzymology” that went far beyond convenient model systems.It was also in Cambridge where Danny first realized the power of the then new field of directed evolution, both for biotechnology and for elucidating evolutionary processes. He and Andrew Griffiths pioneered emulsion‐based in vitro compartmentalization. The idea of controlling biochemical reactions in separate aqueous droplets inspired emulsion PCR and next‐generation sequencing technologies, whereas Danny used it to solve a long‐standing problem in directed evolution; in vitro selection techniques had always been good at identifying ligand‐binding proteins, but compartmentalization finally enabled the directed evolution of ultra‐fast catalysts.Danny returned to Israel in 2001 to join the faculty of the Weizmann Institute of Science where his scientific trajectory further evolved, diverged, and even “drifted”. He developed new methods for enzyme engineering and applied his evolutionary insights into de novo protein design efforts. In this context, Danny’s interest was always focused on how proteins evolve, particularly the connection between promiscuity, conformational diversity, and evolvability. His depth of understanding underpinned both applied research, such as engineering enzymes to detoxify nerve agents, and fundamental research, such as the evolution of enzymes from non‐catalytic scaffolds.Through it all, Danny retained his sense of joy and wonder at the “beautiful aspects of Nature’s chemistry”. This includes his discovery of an exquisite molecular specificity mechanism mediated by a single, short H‐bond that enables microbes to scavenge phosphate in arsenate‐rich environments. In recent years, he deciphered the biosynthetic mechanism of dimethyl sulfide, “the smell of the sea”, and homed in on the interplay between the evolution of an enzyme, its host organism, and environmental complexity. His insights into how the first proteins emerged caused tremendous excitement in the field. He established the roots of two common enzyme lineages, the Rossmann and P‐loop NTPases, as simple polypeptides, and suggested ornithine as the first cationic amino acid. Prior to his death, he published the results of another tour de force: evidence that the first organisms to utilize oxygen may have appeared much earlier than thought.His work impacted many research fields, and he won many significant awards. Most recently, Danny was awarded the EMET Prize for Art, Science and Culture (2020), informally dubbed “Israel’s Nobel Prize”. He was an active and valued member of the EMBO community, having been elected in 2009, and, until his passing, served on the Editorial Advisory Board of EMBO Reports.Danny was also a superb science communicator. Both his research articles and reviews are a joy to read. What stood out just as much as his brilliance was his personality, as he embodied the Yiddish concept of being a true “mensch”. Danny was humble, was down‐to‐earth, and treated all his colleagues—including the most junior members of our research teams—as equals. He championed the careers of others, both those who worked directly for him and those who were lucky enough to be “just” his friends and collaborators. He believed in us even when we did not believe in ourselves, and he was always there to answer questions both scientific and professional. While he loved to share his own ideas, he would be just as excited about ours. Despite his own busy schedule, he always found the time to help others. He was also excellent company, with a great, very dry, sense of humor, and endless interesting stories, including from his own colorful life. In the days after his untimely death, an often‐repeated phrase was “he was my best friend”. Danny’s former group members have gone on to be highly successful in both industry and academia, including more than 15 former doctoral and postdoctoral researchers who are now faculty. The network of researchers Danny has trained, mentored, or influenced is broad, and this legacy is testament to his qualities as both a scientist and a person.Danny was born in Jerusalem to an Iraqi Jewish family, and his Arabic Jewish identity was important to him. He believed strongly in coexistence and peace, and very much valued the Arabic part of his heritage. In his own words: “I am an Israeli, a Jew, an Arab, but first and foremost a human being”. He would often speak of the achievements of his children with immense pride. Danny also had a passion for being outdoors, especially climbing and hiking—when the best discussions were often to be had (Fig ​(Fig1).1). One of the easiest ways to persuade him to come for a seminar, a collaborative visit, or a conference was to have access to high‐quality climbing in the area. He passed away in a tragic rock‐climbing accident, doing what he loved most outside of science. Our thoughts are with his partner Ita and his children, and we join the much broader community of friends, collaborators, and colleagues whose hearts are broken by his sudden loss.Open in a separate windowFigure 1Dan Salah Tawfik (1955–2021)Photo courtesy of Prof. Joel Mackay, The University of Sydney.     

Caspar Bauhin (1560-1624)

The paper describes the life and scientific work of Caspar Bauhin, whose 425th anniversary of his birth is in 1985. He is well-known in anatomy and botany and some species of plants are called after him. In anatomy his name is linked with the ileocaecal valve, though he apparently did not discover it. Especially Bauhin was engaged in improvement of anatomical and botanical nomenclature.     

Energy and QoS Aware Routing in Wireless Sensor Networks

Many new routing protocols have been proposed for wireless sensor networks in recent years. Almost all of the routing protocols considered energy efficiency as the ultimate objective since energy is a very scarce resource for sensor nodes. However, the introduction imaging sensors has posed additional challenges. Transmission of imaging data requires both energy and QoS aware routing in order to ensure efficient usage of the sensors and effective access to the gathered measurements. In this paper, we propose an energy-aware QoS routing protocol for sensor networks which can also run efficiently with best-effort traffic. The protocol finds a least-cost, delay-constrained path for real-time data in terms of link cost that captures nodes energy reserve, transmission energy, error rate and other communication parameters. Moreover, the throughput for non-real-time data is maximized by adjusting the service rate for both real-time and non-real-time data at the sensor nodes. Such adjustment of service rate is done by using two different mechanisms. Simulation results have demonstrated the effectiveness of our approach for different metrics with respect to the baseline approach where same link cost function is used without any service differentiation mechanism.Kemal Akkaya received his B.S. degree in Computer Science from Bilkent University, Ankara, Turkey in 1997 and MS degree in Computer Science from Ortadogu Technical University (ODTU), Ankara, Turkey in 1999. He worked as a software developer at an automation project of Siemens and World Bank in Ankara, Turkey in 2000. He is currently a Ph.D. candidate at University of Maryland, Baltimore County (UMBC), Baltimore, MD. His research interests include energy aware routing, security and quality of service issues in ad hoc wireless networks.Mohamed F. Younis received B.S. degree in computer science and M.S. in engineering mathematics from Alexandria University in Egypt in 1987 and 1992, respectively. In 1996, he received his Ph.D. in computer science from New Jersey Institute of Technology. He is currently an assistant professor in the department of computer science and electrical engineering at the university of Maryland Baltimore County (UMBC). Before joining UMBC, he was with the Advanced Systems Technology Group, an Aerospace Electronic Systems R&D organization of Honeywell International Inc. While at Honeywell he led multiple projects for building integrated fault tolerant avionics, in which a novel architecture and an operating system were developed. This new technology has been incorporated by Honeywell in multiple products and has received worldwide recognition by both the research and the engineering communities. He also participated in the development the Redundancy Management System, which is a key component of the Vehicle and Mission Computer for NASAs X-33 space launch vehicle. Dr. Younis technical interest includes network architectures and protocols, embedded systems, fault tolerant computing and distributed real-time systems. Dr. Younis has four granted and three pending patents. He served on multiple technical committees and published over 40 technical papers in refereed conferences and journals.     

Effects of tumor necrosis factor α, interferon α and interferon γ on non-lymphoid leukemia cell lines: Growth inhibition,differentiation induction and drug sensitivity modulation

Summary The potential role of tumor necrosis factor (TNF), interferon (IFN) and interferon (IFN) in the therapy of non-lymphoid leukemia was studied in ten non-lymphoid leukemia cell lines. All three cytokines tested inhibited the growth of the cell lines. However, a high degree of variability in susceptibility to cytotoxic/cytostatic effect of the cytokines was found among individual cell lines. Some cell lines were sensitive to the antiproliferative action of only one of the cytokines tested, but were resistant to the others. Combinations of two cytokines had additive or synergistic effects and inhibited cell growth to a greater extent than did the individual cytokines alone. In addition to the growth-inhibitory effect, the cytokines induced an apparent cell differentiation. The differentiation of the two most sensitive cell lines, EoL-1 and PL-21, was confirmed using the nitroblue tetrazolium reduction test, by changes in cell morphology, immunophenotype marker profiles and by changes in c-myb expression. Furthermore, we showed that even in the cell lines relatively resistant to the antiproliferative effect of cytokines, such as cell line KCL-22, the inhibition of cell growth could be markedly increased with the DNA-topoisomerase-II-targeted drug, doxorubicin. Our data thus suggest that TNF, IFN and IFN together have a potential role in the immunotherapy of non-lymphoid leukemia in terms of their antiproliferative action, and their ability to induce differentiation and to modulate drug sensitivity.Supported in part by Special Coordination Funds from the Science and Technology Agency of the Japanese Government, and by the Hayashibara International Cancer Research Fellowship Program     

Stereospecificity and electrogenicity of amino acid transport in Riccia fluitans

In the aquatic liverwort Riccia fluitans, membrane depolarization (_m), change in membrane conductance (g_m), and current-voltage (I-V) characteristics in the presence of different amino acids as well as the uptake of ¹⁴C-labeled amino acids were measured. L-isomers of the tested amino acids generate larger electrical effects (_m, g_m) than D-isomers, and the I-V characteristics show that the positive electrical inward-current of 20 mA m^-2 generated by 0.5 mM D-serine is only about 50% of the current generated by adding 0.5 mM L-serine. Whereas - and -amino acids rapidly depolarize the membrane to the same extend, with -aminobutyric acid (-AB) and dipeptides no significant electrical effects have been measured. The uptake kinetics of ¹⁴C-labeled amino acids display three components: (I) A saturable high-affinity component with K_s-values of 48 M D-alanine, 12 M -aminoisobutyric acid (AIB), 9 M L-alanine, 8 M L-proline, and 6 M L-serine, respectively; (2) an apparently linear low-affinity component, and (3) an also linear but unspecific component at concentrations >20 times the given K_s-value. Uptake of ¹⁴C-labeled AIB can be inhibited competitively by all tested neutral amino acids, the L-isomers being more effective than the D-isomers, as well as by ammonium or methylamine. Vice versa, AIB competitively inhibits uptake of L-serine and L-alanine. It is concluded that an uncharged stereospecific carrier for the investigated amino acids exists in the plasmalemma of Riccia fluitans. Accumulation ratios of about 50 suggest secondary active transport driven by a transmembrane electro-chemical gradient (mainly _m) which is generated by the electrogenic proton pump. It is suggested that this carrier binds to the amino group forming either a charged binary complex with positively charged amines (Felle 1980), or an uncharged complex with -AB or dipeptides, whereas electrogenic transport of - and -amino acids is mediated by a ternary carrier complex, probably charged by a proton.Symbols and Abbreviations _m membrane potential (mV) - E_co equilibrium potential (mV) of the transport system - g_m membrane (slope) conductance (Sm^-2) - g_m change in g_m - I-V curve current-voltage curve - AIB -aminoisobutytric acid - -AB -aminobutyric acid     

Intravenously administered cloxacillin-induced neutropenia with eosinophilia in a patient with infective endocarditis: a case report

Background

Bacteremia following Staphylococcus aureus is a serious clinical condition which is often associated with distant metastatic infections. One of the most dreaded complications of Staphylococcus aureus bacteremia is infective endocarditis. Cloxacillin is a common antibiotic prescribed for suspected staphylococcal infections and confirmed methicillin-sensitive Staphylococcus aureus infections. Prolonged use of cloxacillin may lead to neutropenia.

Case presentation

A 38-year-old Sinhalese man presented to Teaching Hospital Kurunegala, Sri Lanka, complaining of a 3-week history of fever; he was found to have a pansystolic murmur over the apex of his heart. He had leukocytosis with predominant neutrocytosis. His C-reactive protein was 231?mg/l and erythrocyte sedimentation rate was 100?mm/first hour. Transthoracic two-dimensional echocardiography revealed prolapsed mitral valve with 7?×?13?mm vegetation over the posterior mitral valve. On the following day, three blood cultures became positive and were subsequently identified as Staphylococcus aureus. Intravenously administered cloxacillin 3?g 6 hourly was started. Following day 24 of intravenously administered cloxacillin, our patient developed high spike fever. His total white blood cells were: 990/mm³ with 34% neutrophils and 22% eosinophils. His hemoglobin concentration was 9.5?g/dL and platelet count remained normal (202?×?10⁶/mm³). His C-reactive protein was 78?mg/l, erythrocyte sedimentation rate was 95?mm/first hour, and he was otherwise comfortable, showing no signs of sepsis beside the high grade fever. His serum was negative for filarial and Toxoplasma antibodies while stool was negative for oocytes and amoebic cysts. Further, his serum was negative for dengue virus, Epstein–Barr virus, cytomegalovirus, and hepatitis B antibodies. He was clinically well on day 6 after stopping cloxacillin with 44% neutrophils and 18% eosinophils. His C-reactive protein and erythrocyte sedimentation rate became normal, and there was no further plan for cardiothoracic intervention or administration of antimicrobials. He was discharged from hospital and remained well 6?months later.

Conclusion

This case report signifies the potential fatal adverse effect of cloxacillin in methicillin-sensitive Staphylococcus aureus infections. Leukopenia is associated with prolonged use of high doses of cloxacillin. In addition to transthoracic two-dimensional echocardiography and inflammatory markers, sequential white blood cells and differential counts would help clinicians to assess the prognosis of patients with infective endocarditis.

     

The Prebiotic Leslie Orgel: Some of His Contributions to Our Understanding of the Origins of Life

In the previous recollection Jack Dunitz presented a delightful account of Leslie's pre-prebiotic life as a theoretical inorganic chemist. In this account I will present my recollections of his contributions, as a chemist-molecular biologist, to the field of origins of life.Leslie officially started his prebiotic research upon arrival at the Salk Institute in September 1964. Anna Beck and I, who arrived there at that time and Rolf Lohrmann and Robert Sanchez who joined the group within first year, were the vanguard of the large group of postdoctorals and graduate students that have spent time in Leslie's laboratory. John Sulston and Carl Woese were among the notables that spent time in Leslie's lab during his initial years at Salk.Leslie's emphasis on the new and different, which was described by Jack Dunitz, continued at Salk. He would greet me each day with well Jim, what's new! Or he would come upon an unusual reaction from the organic chemistry literature and ask me to explain it. Occasionally something new would occur in the lab and we would discuss its ramifications at great length throughout the day. He would often come up with a key suggestion on how this new finding should be extended to provide insight into an entirely different area. On other occasions he would suggest an empirical approach, such as setting up a series of reaction mixtures putting one of each of the metal salts in the lab inventory into each reaction, to determine if it was catalyzed by metal ions. This latter approach always seemed to me to be inconsistent with his background as a theoretician since I have yet to find a theoretician who would follow such a blatantly empirical approach to the discovery of new chemical reactions.Leslie claims to have no competence in the laboratory but he certainly understands what is required to obtain meaningful experimental data. First, he can often see through a forest of data and suggest a pivotal simple experiment to prove or disprove a hypothesis. Second, he has demanding standards for quality experimental design and execution. I have heard him on many occasions patiently (occasionally impatiently if it was a repeat offender) chastising a researcher in his laboratory ... for not performing the proper controls... to establish the validity of their experimental findings.Leslie started working on the prebiotic synthesis of nucleic acids and their replication when he came to Salk and was extremely successful in both studies. He improved the Oro synthesis of adenine (Oro, 1960) by extending it to dilute solutions of HCN (Ferris and Orgel, 1966) and to a general prebiotic synthesis of purines (Sanchez et al., 1966a). He also recognized that cyanoacetylene contained the carbon backbone of the pyrimidine ring and used it as a starting material for the prebiotic synthesis of pyrimidines (Sanchez et al., 1996b). Approaches to the prebiotic syntheses of nucleosides and nucleotides flowed logically from these studies (Beck et al., 1967; Lohrmann and Orgel, 1968, 1971; Fuller et al., 1972).Leslie conducted research on the nonenzymatic template-directed synthesis of RNA concurrently with studies on prebiotic synthesis. This research was initiated by the important discovery that the carbodiimide-driven condensation of A with pA gives higher yields of A²pA in the presence of poly(U) than in its absence (Sulston et al., 1968). Some minor reaction products included A³pA, A⁵pA and trimers. This discovery was followed by the substitution of an imidazole activated pA (ImpA) for the carbodiimide and pA in the reaction with A on a poly(U) template which gave much better yields of dimers and trimers (Weimann et al., 1968). In the following year this reaction was extended to the synthesis of oligo(G)s on a poly(C) template (Sulston et al., 1969), the system that was eventually shown to be optimal for probing the scope of nonenzymatic template-directed syntheses. The development of the RPC-5 column for the analysis of the oligonucleotides formed by template-directed synthesis was pivotal in characterizing the length and the regioselectivity of the phosphodiester bonds formed in these reactions (Lohrmann et al., 1980). A further advance was the development of the 2-methylimidazole activating group which resulted in the formation of oligo(G)s by template-directed synthesis that contain predominantly 3', 5'-linked phosphodiester bonds. This reaction proceeds in the solution phase (Inoue and Orgel, 1981) in contrast to the Zn²⁺- and Pb²⁺-catalyzed reactions which, while regioselective for the formation of the 3', 5'- and 2', 5'-linked phosphodiester bonds respectively, proceed via an insoluble metal complex (Lohrmann et al., 1980). Thus the 2-methylimidazole activating group made it possible to explore the efficiency of template-directed synthesis using templates containing different bases.The first self-replicating system, that was based on template-directed synthesis, was prepared by Günter von Kiedrowski in Leslie's laboratory in 1986 (von Kiedrowski, 1986). Leslie devised a replicater, which exhibited autocatalytic kinetics, that was also based on a templating reaction (Zielinski and Orgel, 1987).While prebiotic peptide synthesis was not a dominant theme in his laboratory Leslie did make important contributions to this field of work. He investigated the mechanism of peptide synthesis in aqueous solution using carbonyl diimidazole as the condensing agent (Ehler and Orgel, 1976) and he was able to make polypeptides containing 55 mers on mineral surfaces (Ferris et al., 1996). He proposed that the condensation of amino acids on the primitive Earth could have resulted in short polypeptides with alternating structures that would have formed small -sheets (Brack and Orgel, 1975). Subsequent studies have shown that some -sheets catalyze the hydrolysis of RNA (Barbier and Brack, 1992).Leslie, collaboratively with Francis Crick, has also published some theoretical papers dealing with the origin of life. The most perceptive was their anticipation of the RNA world before the name was coined by Gilbert (1986). In companion papers (Crick, 1968; Orgel, 1968), they suggested that RNA could have catalytic activity in addition to its ability to store genetic information, so that it could have been the basis for the first life. They noted that life based on protein was less likely because of its inability to preserve its sequence information by replication. In another very provocative paper they proposed that life on Earth may have been seeded here by intelligent aliens in a process they call Directed Panspermia (Crick and Orgel, 1973). They reckoned that the seeds of life might not survive the trip through open space but these initial microorganisms could have survived a trip through space if properly shielded in a spacecraft. In this scenario the Earth is a giant Petri dish and these aliens have performed an experiment using it. I have always felt that this paper had a major tongue-in-cheek component but it is often seriously mentioned as one possible explanation for the presence of life on Earth.In addition to his search for the novel and unusual Leslie also finds it challenging to search for the practical (again, not the usual practice of a theoretician!). He has the remarkable ability to appreciate the practical applications of his research and I know of at least two ideas that resulted in useful patents. (Some of the income from these patents is used to finance group parties at first rate restaurants.) One patent stemmed from the research on the prebiotic synthesis of pyrimidine nucleosides which Bob Sanchez developed into a an efficient preparation of the antileukemia agent cytosine arabinoside from cyanoacetylene, cyanamide and arabinose (Sanchez and Orgel, 1970). This successful patent is an excellent example of how the so called esoteric work in prebiotic chemistry led to a simple and new route to the synthesis of drugs or other useful materials. Another valuable patent came from the work of Barbara Chu which has been developed into a test for the genes from pathogens. She found that it was possible to prepare the 5'-imidazolides of high molecular weight QB RNA without affecting its autocatalytic replicating ability. This made it possible to attach cleavable reporter groups such as biotin or DNA probes to QB via the imidazolide intermediate, the selected DNA-QB probe could then be amplified by QB replicase, and easily detected after amplification (Chu et al., 1986).The search for useful therapeutic agents continues. In 1997 Leslie identified yet another possible application of Barbara's work. She made use of results from prebiotic chemistry showing that oligomers of glutamic acid bind irreversibly to hydroxylapatite, the predominant mineral in bone. She then attached potential therapeutic agents to the amino acid oligomers and demonstrated that they bound to the hydroxylapatite. This approach may be used to bind potential therapeutic agents to hydroxylapatite with the possibility that this might be a way to bring these agents to particular target site in bones (Chu and Orgel, 1997).The honors and awards that Leslie has received underline the high esteem in which he is held by his fellow scientists. He was recognized as a brilliant scientist by the British colleagues when he was awarded the Harrison prize of the Royal Society of Chemistry at the tender age of 30. Only five years later was he elected to the Royal Society. Among the awards he has received in the US are his election to the American Academy of Arts and Sciences in 1985, the National Academy of Sciences in 1990 and the Harold C. Urey medal of the International Society for the Study of the Origins of life in 1993. We in the field of the origins of life have not only benefitted from his major contributions to this field but the reputation of the field has also benefitted from having such a distinguished scientist as one of our own.Happy 70th birthday, Leslie! I thank you for baptizing me with HCN and sending me forth into the prebiotic world. It has been great fun as well as rewarding for me and I look forward to continuing our discussions of the origins of life for many years to come.     

Prophet in his own country: Carlos Chagas and the Nobel Prize

In 1909, Carlos Chagas (1878-1934) discovered a new protozoon, Trypanosoma cruzi, and the (previously unknown) disease that it causes. Within a few months, virtually single-handed, he described the pathogen, its vector, and the clinical features of American trypanosomiasis (Chagas disease), a feat unique in medical history. He headed the Oswaldo Cruz Institute after the death of its founder (1917) until his own death; and from 1920 until 1926 he also directed the Brazilian Department of Public Health. His discovery brought him worldwide acclaim, but at home antagonism against Chagas, muted for years, finally flared up in a campaign that was acted out in the 1921-22 plenary sessions of the National Academy of Medicine. Chagas's name was repeatedly proposed for the Nobel Prize but he never received it; this hostile campaign may have been instrumental in costing him the award.     

The role of routine serum testosterone testing: routine hormone analysis is not indicated as an initial screening test in the evaluation of erectile dysfunction

A 60-year-old male physician is self-referred to your office for evaluation of his erectile dysfunction, which has been worsening for 5 years. He reports his erections rarely achieve fullness for penetration, and he is unable to ejaculate. He has tried sildenafil citrate (Viagra(R); Pfizer Inc, New York, NY) with mild success in the past. He has a strong libido and feels healthy. He rarely exercises, but is on his feet most of the day at work. He has been healthy his whole life and never seeks a doctor's attention. He has no other medical problems. His only medication is a baby aspirin once a day. His physical examination, including genitalia, is normal. As part of his initial visit, should his serum testosterone level be checked by his urologist?     

Uncertain legislator: Georges Cuvier's laws of nature in their intellectual context

Conclusion We should now be able to come to some general conclusions about the main lines of Cuvier's development as a naturalist after his departure from Normandy. We have seen that Cuvier arrived in Paris aware of the importance of physiology in classification, yet without a fully worked out idea of how such an approach could organize a whole natural order. He was freshly receptive to the ideas of the new physiology developed by Xavier Bichat.Cuvier arrived in a Paris also torn by many overlapping debates on the nature of classification, and in particular that between the natural and artificial systems. The very validity of the enterprise of classification was questioned in many quarters. Cuvier's achievement on his entry into the Parisian world of science was not simply to establish himself as a highly competent anatomist: far more important, he also began to use ideas from many different specialties to change completely the notion of what was involved in natural history.¹²⁴ At the same time that he himself swung away from the guiding image of the field naturalist as the ideal of the specialty, he took ideas from the new physiology to answer questions about the order of the animal world, and from comparative anatomy to resurrect extinct creation — and to come to conclusions from that creation about the history of the forms of life and the manner of their succession. He showed himself able to alter the relationships between natural history and many other fields of study in a way that implied, rightly or wrongly, his own complete mastery over such a movement. Partly he was able to do this because the ideas he borrowed were not themselves logically articulated and thus could be easily adapted and refocused for many different specific purposes. The value of the heuristic possibilities inherent in the idea of life, for example, far outweighed its inability to generate full systems of classification. Cuvier also consistently refused to consider in science matters relating to the first causes of events. Freed from the consideration of first-order phenomena, he was able to use second-order explanations across a far wider field of applicability. Personal doubts about the validity of a theology that had used science in order to bolster its own claims were combined here with the strong influence of the Kantian critique of the limits of human reason.¹²⁵ Cuvier's characteristic mode of procedure was that of intellectual appropriation and a bold capacity for altering the relationships between different fields of knowledge, rather than, with the exception of taxonomy, the technique of expanding their subject matter. His claims to originality came, first, from this reappropriation and reorientation and, second, from the sheer scope of his work, which aimed at nothing less than the cataloging and classification of all animate objects.¹²⁶ They rested also on his acute use of his assertion of a certain relationship with the past of his subject. Very often he would present this history in such a way as to obscure his own intellectual genealogy, and often too he would give differing accounts of the priority of use of an idea in order to distract attention from the questionable exactitude of his own claims to originality. Cuvier came to Paris at precisely the time when society and institutions were most profitably malleable for a newcomer; it was also a time when many scientific disciplines had reached a stage advanced in terms of their factual content, yet relatively inadequate in conceptual organization. They were ripe for takeover by large-scale organizing ideas such as the animal economy and the subordination of characteristics. Paleontology is a particularly good example of a specialty in this particular form of underdevelopment in 1795.Cuvier paid a high price for his initial success. His electic applications of large-scale organizing ideas tended to mean that little of his own work had complete coherence at all levels. Ideas, as we have seen, that proved capable of providing a complete reform of the larger groups of the animal kingdom were incapable of producing its detailed working-out in the taxonomy of smaller groups, which had to be supplied from observed analogical correlations. Further, his physiological approach to classification involved the breakdown of strict correspondence between organs and functions, which left the way open for workers such as Geoffroy St. Hilaire gradually to tilt the balance away from the study of the correlations of hierarchies of functions, and toward morphology as the basis of the order of nature. Cuvier's brilliant appropriations from physiology from the beginning, therefore, contained the seeds of conflict with Geoffroy.Cuvier's eclectic approach made it very nearly impossible for him to present a clear idea of the ways in which the life sciences could be said to be lawful. In spite of his efforts to assimilate them to the position of the physical sciences in this respect, he was forced in the end to accord only an ambiguous status as laws to observational correlations. From this area of failure came much of the attempt to give his own two laws — the correlation of parts and the subordination of characteristics — predictive qualities, particularly in relation to paleontological research.It is not surprising that Cuvier's title as the legislator of natural history should represent more a claim than a reality. How, then, was he able to emerge as the leading French naturalist of his day? First of all must be adduced the sheer scale of his undertakings. Then comes his expertise as a practical anatomist, and the range of different topics toward which he turned his interest. His collaborators cannot be given credit for his output nor, as we have seen, for slavish adherence to his ideas. Cuvier was able to successfully claim to have dominated the underdeveloped specialties, such as paleontology, and turned them into a major heuristic input into both geology and comparative anatomy; but in other fields, such as physiology, he appropriated concepts and encouraged research but made little impact on the field himself. His attempts in 1812 to head off, or neutralize and absorb the growth of morphological studies landed him in a dangerously rigid position, which despite his encouragement of the new physiological research under the Restoration made further elaboration of his own conceptual underpinnings almost impossible.Cuvier's authority in the scientific world would in any case have been great because of his substantive achievement in taxonomy, but the rest of his work had enough ambiguities and dislocations for it to need the support of his political and social power. Cuvier's detractors seized on a vital fragment of the truth when they accused him of finding the political dimension all-important: it obscured the disjunctions in his theories and at the same time gave him the authority to make new claims for the status of the observational sciences - and for their relations of power with their surrounding specialties. Cuvier's science both thrived on and was halted by the power games of intellectual appropriation, manipulation of the past to confirm the present, and continual claims for hegemony.     

Organ-specific modulation of gene expression in transgenic plants using antisene RNA

We have shown leaf-specific inhibition GUS gene expression in transgenic Nicotiana plants using an antisense RNA with a 41-base homology spanning the translation start codon of the gene. GUS was expressed from the nominally constitutive 35S promoter and the antisense RNA was expressed from the light-regulated ca/b promoter of Arabidopsis thaliana. A range of GUS inhibition from 0 to 100% was obtained by screening a small population of transgenic plants and the specific levels of inhibition observed were stably inherited in two generations. An antiGUS gene dosage effect was observed in plants which were homozygous for antiGUS. RNA detection results suggest that duplex formation with the 41 base pair antiGUS RNA destabilized the GUS mRNA and that an excess of antisense. RNA was not required. Our results demonstrate the potential of antisense RNA as a strategy for obtaining plant mutants, especially down mutations in essential genes where only a short 5 sequence of the mRNA is required. They also suggest that the position effect on gene expression could be used in conjunction with an antisense RNA strategy to provide a versatile approach for crop improvement.     

Ecology and evolutionary biology in the war and postwar years: Questions and comments

Conclusion: Scientists qua engineers Of all the scientists discussed by Mitman, Keller, and Taylor, Odum stands out most as the technocrat, the social engineer. But less obvious candidates, like Allee, also fancied themselves in this capacity: Our task as biologists and as citizens of a civilized country, is a practical engineering job. Allee had in mind the establishment of an international cooperative order based on his biological principles. He apparently did not recognize the extent to which his principles were themselves an engineering feat: he had already constructed a world in which eternal peace and order were possible.To an engineer in the traditional sense, the world is changeable, but not in all respects; there are constraints, and these constraints are taken very seriously. Scientists acting as engineers, in the traditional sense, must also pay attention to constraints. But scientists sometimes also take the option of engineering the very constraints, intellectually reconstructing the world so that it can (supposedly) be physically manipulated in the desired direction. There seems to be a lot of engineering, in the extended sense, going on in the very interesting stories that Mitman, Keller, and Taylor tell.     

Bringing inorganic chemistry to life with inspiration from R. J. P. Williams

Our appreciation of the scholarly ideas and thinking of Bob Williams is illustrated here by a few of the areas in which he inspired us. His journey to bring inorganic chemistry to life began with an early interest in analytical chemistry, rationalising the relative stabilities of metal coordination complexes (The Irving-Williams Series), and elucidating the organometallic redox chemistry of vitamin B₁₂. He (and Vallee) recognised that metal ions are in energised (entatic) states in proteins and enzymes, which themselves are dynamic structures of rods and springs. He played a key role in helping Rosenberg to pave the road toward the clinic for the anticancer drug cisplatin. He believed that evolution is not just dependent on DNA, but also on the metallome. Organisms and the environment are one system: does DNA code directly for all the essential elements of life?     

Itinerary of Truman G. Yuncker’s expeditions

Many of the systematically and historically valuable collections in the DePauw University Herbarium (DPU), Greencastle, Indiana, were made by Truman G. Yuncker during his numerous expeditions. He collected in large, and until then unexplored, areas of Honduras, and undertook several expeditions to islands in the South Pacific (Manua, Niue, and Tonga) and Hawaii. In his late years he collected in the West Indies and in Brazil. His extensive collections ofCuscuta (Cuscutaceae) and Piperaceae each became among the largest in the world. In this article an itinerary of his expeditions is presented.