From Bretonneau to therapeutic antibodies,from specificity to specific remedies,Saint-Cyr-Sur-Loire,France, November 19, 2012

Held on November 19, 2012 in Saint-Cyr-sur-Loire, France, the symposium “From Bretonneau to therapeutic antibodies, from specificity to specific remedies” focused on the historical development of antibodies as therapeutics, with an emphasis on the seminal work of the French physician Pierre-Fidèle Bretonneau (1778–1862). The morning session was devoted to discussion of the evolution of the concept of specificity in medicine, which started with an epistemological definition. The contributions of Bretonneau to the emergence of the concept of specificity, notably with his studies on diphtheria, and the subsequent development of antidiphtheric serotherapy in Europe during the period 1894–1898 were then presented in detail. The afternoon session began with a presentation on the role of French physiologists during the years 1860–1890 in establishing the basic concepts of specific immunity and the principles of serotherapy. The history of antivenom serotherapy, particularly its discovery by Césaire Phisalix, and the development of antilymphocyte globulins as successful transplantation drugs were then discussed. The symposium ended with the inauguration of a stele representing Bretonneau, who lived in Saint-Cyr-sur-Loire and died 150 y ago.     

Protein tyrosine phosphatases: from genes, to function, to disease

The protein tyrosine phosphatase (PTP) superfamily of enzymes functions in a coordinated manner with protein tyrosine kinases to control signalling pathways that underlie a broad spectrum of fundamental physiological processes. In this review, I describe recent breakthroughs in our understanding of the role of the PTPs in the regulation of signal transduction and the aetiology of human disease.     

Stream ecosystem response to, and recovery from, experimental exposure to selenium

The effects of selenium on streamecosystems were studied in outdoor,experimental stream mesocosms during a dosingperiod in which sodium selenite was added atnominal concentrations of 30 µg/L,10 µg/L, and 2.5 µg/L. The durationof the high, medium, and low treatments were573 d, 972 d, and 311 d, respectively. Apost-dosing period of three years (hightreatment) and two years (medium, lowtreatments) also was studied. Seleniumconcentrations in water, sediment, plants, andmacroinvertebrates were measured throughoutthe dosing and recovery periods. Fatheadminnows and bluegill sunfish were periodicallyheld in the streams to measure seleniumaccumulation and its effects on fish survivaland reproduction. Quantitative samples ofmacroinvertebrates were collected to assessselenium effects on macroinvertebratecommunities.Mean selenium concentration inwater was quite close to the nominalconcentration. Selenium accumulated in thesediment in all three treated streams, but notin the control streams. Sediment seleniumdecreased slowly after dosing ceased, but wasstill significantly higher than in controlstreams three years (high treatment) and twoyears (medium treatment) later.Macrophytetissue selenium concentrations weresignificantly greater in all three treatmentsthan those in the control streams duringdosing. Macrophyte selenium bioaccumulationfactors (BAFs) ranged from about 300 to 1900. Tissue selenium decreased rapidly in all threetreatments after dosing ended.During dosing,selenium concentrations in animals from allthree treatments were significantly higherthan in those from control streams. The BAFsfor macroinvertebrates ranged from 1100 to2000. Isopods accumulated more, and amphipodsless, selenium than other invertebrates. Therewere no significant effects of selenium onmacroinvertebrate abundance, richness ordiversity. Several macroinvertebrates werenot affected by exposure to selenium, butisopod and Tubifex populations weredramatically reduced in the high and mediumtreatments. After dosing, mean seleniumconcentration in macroinvertebrates decreasedslowly.Bluegill sunfish accumulated seleniumduring dosing and after selenium additionsceased. Tissue selenium was highest in theliver, followed by the gonads, skeletalmuscle, and whole body. Tissue seleniumconcentrations one (high, medium) and two(high) years after dosing were lower thanduring dosing, but whole body, skeletal muscleand liver concentrations were high enough tobe considered potentially toxic.Recovery ofselenium contaminated streams includes bothreduction of tissue selenium concentration tonon-toxic levels in fish and their foodorganisms and recovery of populations of taxadeleteriously affected by selenium exposure. Our results suggest that when selenium iseliminated from the water in streams, seleniumconcentrations in sediment, plants,macroinvertebrates, and fishes will decreaseto levels that approach concentrationsconsidered to be non-toxic to fish andwildlife and that affected populations willrecover within several years. Based onselenium accumulation in the food chain andthe presence of real, but not statisticallysignificant, effects on fish mortality andreproduction in the low treatment streams, wesupport a selenium water quality criterion forthe protection of fishes and sensitiveinvertebrates of 2 µg/L or less.     

Plant metabolomics: from holistic hope, to hype, to hot topic

In a short time, plant metabolomics has gone from being just an ambitious concept to being a rapidly growing, valuable technology applied in the stride to gain a more global picture of the molecular organization of multicellular organisms. The combination of improved analytical capabilities with newly designed, dedicated statistical, bioinformatics and data mining strategies, is beginning to broaden the horizons of our understanding of how plants are organized and how metabolism is both controlled but highly flexible. Metabolomics is predicted to play a significant, if not indispensable role in bridging the phenotype-genotype gap and thus in assisting us in our desire for full genome sequence annotation as part of the quest to link gene to function. Plants are a fabulously rich source of diverse functional biochemicals and metabolomics is also already proving valuable in an applied context. By creating unique opportunities for us to interrogate plant systems and characterize their biochemical composition, metabolomics will greatly assist in identifying and defining much of the still unexploited biodiversity available today.     

Introduction to an International Guide to Stratigraphic Classification,Terminology, and Usage

International Subcommission on Stratigraphic Classification [Report No. 7a; editor H. D. Hedberg]: Introduction to an International Guide to Stratigraphic Classification, Terminology, and Usage. Lethaia, Vol 5, pp. 283–295. Oslo, July 15th, 1972. The International Subcommission on Stratigraphic Classification (ISSC), a subcommission of the IUGS Commission on Stratigraphy, has been working for the last 15–20 years towards the preparation of an International Guide to Stratigraphic Classification, Terminology, and Usage. The purpose of the Guide is to promote international agreement on principles of stratigraphic classification and to establish internationally acceptable stratigraphic terminology and rules of stratigraphic procedure. The Introduction explains the background of its preparation.     

Fluorocholesterols, in contrast to hydroxycholesterols, exhibit interfacial properties similar to cholesterol

We used an automated Langmuir-Pockels surface balance to characterize the air-water interfacial properties of cholesterol (CH) and its derivatives with hydrophilic OH and F substitutions at isologous sites on the sterol body or side chain. We studied 6-fluorocholesterol, 25-fluorocholesterol, 25,26,26,26,27,27,27-heptafluorocholesterol, 7alpha-hydroxycholesterol, 7beta-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, alone and in mixtures with 1-palmitoyl-2-oleoyl-sn-3-glycero-phosphocholine (POPC). Pressure;-area isotherms of the fluorocholesterols were essentially indistinguishable from CH and all condensed POPC monomolecular layers (monolayers) to variable degrees. Both nucleus-substituted hydroxycholesterols formed expanded monolayers, with lift-offs from baseline 22-26 A(2)/molecule larger than CH, suggesting interfacial tilting; furthermore, in binary mixtures, they condensed POPC monolayers less than CH. In contrast, the side chain hydroxylated CHs were oriented horizontally in the interface at large molecular areas, and became vertical below 140 A(2)/molecule with the side chain-OH rather than 3-OH group anchored in the subphase, as evidenced by low collapse pressures and smaller molecular areas than CH. Both side chain hydroxycholesterols expanded POPC monolayers at molar ratios <30%, but induced condensation with higher ratios, suggesting that OH-acyl chain (POPC) repulsion is superceded at higher mole fractions by lateral phase separation and intersteroidal H-bonding. These studies predict that fluorocholesterols should exhibit intramembrane spatial occupancy nearly identical to CH, whereas nucleus and especially side chain hydroxycholesterols will perturb membrane lipid packing notably.     

The RCC1 superfamily: from genes, to function, to disease

The Regulator of Chromosome Condensation 1 (RCC1) was identified over 20 years ago as a critical cell cycle regulator. By analyzing its amino acid sequence, RCC1 was found to consist of seven homologous repeats of 51-68 amino acid residues, which were later shown to adopt a seven-bladed beta-propeller fold. Since the initial identification of RCC1, a number of proteins have been discovered that contain one or more RCC1-like domains (RLDs). As we show here, these RCC1 superfamily proteins can be subdivided in five subgroups based on structural criteria. In recent years, a number of studies have been published regarding the functions of RCC1 superfamily proteins. From these studies, the emerging picture is that the RLD is a versatile domain which may perform many different functions, including guanine nucleotide exchange on small GTP-binding proteins, enzyme inhibition or interaction with proteins and lipids. Here, we review the available structural and functional data on RCC1 superfamily members, paying special attention to the human proteins and their involvement in disease.     

Somatic cell mutants resistant to ricin, diphtheria toxin, and to immunotoxins

The human B-cell line Namalwa expresses the common acute lymphoblastic leukemia antigen (CALLA). Frame-shift mutants in Namalwa cell cultures were generated with ICR-191, and mutants were then selected for resistance to ricin or resistance to a conjugate of ricin with the anti-CALLA antibody J5 in the presence of lactose. Three mutants were found that were resistant to ricin and were in addition shown to be resistant to diphtheria toxin, to a J5-ricin conjugate, and to a conjugate between ricin B-chain and gelonin. The mutants, however, were sensitive to a J5-gelonin conjugate. These mutants expressed high levels of CALLA and/or receptors for ricin, and their cell-free translation systems appeared to be as sensitive to the inhibitory action of ricin A-chain and of gelonin as the translation system of wild-type Namalwa cells. The behavior of these mutants was consistent with the hypothesis that these cells possess an alteration of their surface that impedes the passage of ricin and diphtheria toxin across the plasma membrane. A fourth mutant was found to bind reduced quantities of ricin and was resistant to ricin but was sensitive to J5-ricin. The properties of this cell line provide evidence that the binding of antibody-ricin conjugates to cells via the ricin moiety may be prevented without impeding the cytotoxicity of the conjugates.     

Response of an aphid parasitoid, Aphelinus asychis to its host, plant, host-plant complex, and to malathion

Aphelinus asychis (Walker) can be valuable as a biocontrol agent of the aphid, Schizaphis graminum (Rondani), a major pest on grain crops in the United States. This study reports the wind tunnel, and olfactometric responses of this parasitoid to the host (aphid), plant (sorghum), and host-plant complex (aphid-infested sorghum). In addition, the parasitoids' response to malathion-treated plants is also presented. The goal of the present study was to test the hypothesis that volatiles associated with the host attract natural enemies, as reported in cases of many hymenopterous parasitoids, and also to learn about the effects of insecticides on these parasitoids. In wind tunnel studies, these parasitoids moved upwind in the direction of the host-infested plant. There was no direct flight observed, however, these parasitoids were observed to hop and jump, and sometimes walk to their host. In the olfactometer experiments, we found that A. asychis is attracted to host-plant complex. The parasitoids' response to malathion in the olfactometer suggested that a malathion formulation when applied to plants can lure these beneficials, thus providing new insight into the ongoing task of integrating chemical and biological control of insect pests.