Transthyretin: a review from a structural perspective

Transthyretin (formerly called prealbumin) plays important physiological roles as a transporter of thyroxine and retinol-binding protein. X-ray structural studies have provided information on the active conformation of the protein and the site of binding of both ligands. Transthyretin is also one of the precursor proteins commonly found in amyloid deposits. Both wild-type and single-amino-acid-substituted variants have been identified in amyloid deposits, the variants being more amyloidogenic. Sequencing of the gene and the resulting production of a transgenic mouse model have resulted in progress toward solving the mechanism of amyloid formation and detecting the variant gene in individuals at risk. Received 23 January 2001; received after revision 4 April 2001; accepted 30 April 2001     

Of the morphogenes that make a ring, a rod and a sphere in Escherichia coli

In 1993, William Donachie wrote "The success of molecular genetics in the study of bacterial cell division has been so great that we find ourselves, armed with much greater knowledge of detail, confronted once again with the same naive questions that we set to answer in the first place". Indeed, attempts to answer the apparently simple question of how a bacterial cell divides have led to a wealth of new knowledge, in particular over the past decade and a half. And while some questions have been answered to a great extent since the early reports of isolation of division mutants of Escherichia coli, some key pieces of the puzzle remain elusive. In addition to it being a fundamental process in bacteria that merits investigation in its own right, studying the process of cell division offers an abundance of new targets for the development of new antibacterial compounds that act directly against key division proteins and other components of the cytoskeleton, which are encoded by the morphogenes of E. coli. This review aims to present the reader with a snapshot summary of the key players in E. coli morphogenesis with emphasis on cell division and the rod to sphere transition.     

The melatonin rhythm: both a clock and a calendar

The paper briefly reviews the data which shows that the circadian production and secretion of melatonin by the pineal gland can impart both daily, i.e., clock, and seasonal, i.e., calendar, information to the organism. The paper summarizes the 3 patterns of nocturnal melatonin production that have been described. Clearly, regardless of the pattern of nocturnal melatonin production a particular species normally displays, the duration of nightime elevated melatonin is proportional to the duration of the night length. Since daylength under natural conditions changes daily the melatonin rhythm, which adjusts to the photoperiod sends time of year information to the organism. The melatonin receptors which subserve the clock message sent by the pineal gland in the form of a melatonin cycle may reside in the biological clock itself, namely, the suprachiasmatic nuclei (SCN). The melatonin receptors that mediate seasonal changes in reproductive physiology are presumably those that are located on the pars tuberalis cells of the anterior pituitary gland. Besides these receptors which likely mediate clock and calendar information, melatonin receptors have been described in other organs. Interestingly, the distribution of melatonin receptors is highly species-specific. Whereas the clock and calendar information that the melatonin cycle imparts to the organism relies on cell membrane receptors, a fact that is of some interest considering the high lipophilicity of melatonin, recent studies indicate that other functions of melatonin may require no receptor whatsoever.     

Palinurin,a new linear sesterterpene from a marine sponge

Summary The structure of a new linear sesterterpene, palinurin (1), obtained from the marine spongeIrcinia variabilis, was determined by spectral and chemical means.This work was carried out at the Progetto Finalizzato Oceanografia e Fondi Marini, C.N.R., Roma. We thank Professor M. Sarà (University of Genova) for the identification of the sponge, Mr C. Di Pinto for¹H-and¹³C-NMR, Mr G. Scognamiglio for technical assistance.     

Nifurpipone,a new nitrofuran with a large antimicrobial spectrum

Riassunto Il nifurpipone (5-nitro-2-furaldeide N'-metil-N-piperazino-acetidrazone) è un nuovo nitrofuranico a largo spettro antibatterico, escreto con le urine e quindi potenzialmente indicato nelle infezioni delle vie urinarie.     

Cyanovirin-N: a sugar-binding antiviral protein with a new twist

Cyanovirin-N (CV-N), an 11-kDa protein from the cyanobacterium Nostoc ellipsosporum, is a highly potent virucidal agent that has generated interest as a lead natural product for the prevention and chemotherapy of human immunodeficiency virus infection. The antiviral activity of CV-N is mediated through specific, high-affinity interactions with the viral surface envelope glycoproteins. A number of structures of wild-type, mutant and sequence-shuffled CV-N have been solved by nuclear magnetic resonance and crystallography, showing that the protein exists as either a quasi-symmetric two-domain monomer or a domain-swapped dimer. Structures of several complexes of CV-N with oligosaccharides help in explaining the unique mode of high-affinity binding of these molecules to both forms of CV-N. RID="*" ID="*"Corresponding author.     

On a rabbit hyperlipemia induced by a fungic galactomannane peptide

Summary I.v. injection into rabbits of a fungic galactomannane peptide isolated from the culture medium ofAspergillus oryzae induced the apparition, 20 h later, of an hypertriglyceridemia, with a concomittant decrease of about 70% of the post-heparin lipoprotein lipase activity. The same effect had been obtained earlier with a carbohydrate-rich fraction purified from a crude papain preparation. The 2 fractions are compared.     

Furospongolide,a new C21 furanoterpene from a marine organism

Summary The structure of a new linear C₂₁ furanoterpene, furospongolide (1), obtained from the marine spongeDysidea herbacea, was determined by spectral means.We thank Professor J. Vacelet for the identification and Dr Loya and Mr Benayahu for the collection of the sponge.     

Immunological response between protozoa symbiotic to a roach and a termite

Résumé L'analyse des responsabilités immunologiques après immunisation d'animaux expérimentaux avec les protozoaires symbiotiques du roach,Cryptocercus et du termiteZootermopsis indique une étroite affinité chimique entre les protozoas de ces hôtes. Les résultats semblent confirmer indirectement la taxonomic morphologique courante des hôtes.     

Fine structure of a neurosecretory axon in a crustacean skeletal muscle

Résumé Un axone neuro-sécréteur à extrémités localisées dans le muscle squelettique du craneCarcinus est décrit. Ces extrémités contiennent 6 sortes de vésicules ayant les diamètres de 1300 a 3700 . Il est suggéré que es petites vésicules correspondent à la phase de rétablisement de la membrane, pendant la décharge des granules euro-sécréteurs. On suppose aussi que cet axone peutêtre l'intermédiaire d'une influence trophique du nerf sur le muscle.

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I am most grateful to Mr.K. Oates and Mr.G. R. Abram for excellent technical assistance.

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Supported by a Research Studentship from the Science Research Council.     

Immunotherapy against antigenic tumors: a game with a lot of players

Our understanding of how immune responses are generated and regulated drives the design of possible immunotherapies for cancer patients. For that reason, we first describe briefly the actual immunological theories and their common perspectives about cancer vaccine development. Second, we describe cancer vaccines that are able to induce tumor-specific immune responses in cancer patients. However, these responses are not always followed by tumor rejection. At the end of the review, we discuss two possible reasons that might explain this dichotomy of cancer immunology. First, the immune response generated, although detectable, may not be quantitatively sufficient to reject the tumor. Second, the tumor microenvironment may modulate tumor cell susceptibility to the systemic immune response induced by the immunization. Finally, we discuss what, in our opinion, might be the best way to improve cancer vaccine strategies and how the relationship between the tumor and its surroundings might be studied in more details. Received 21 June 2001; received after revision 15 August 2001; accepted 15 August 2001     

Osmotic behaviour of isolated axons of a euryhaline and a stenohaline crustacean

Résumé Les axones isolés du crustacé euryhalinEriocheir sinensis sont capables d'effectuer une régularisation de volume lorsqu'ils sont soumis à des chocs hypo-osmotiques. Les mécanismes pouvant être impliqués dans ce processus sont discutés.

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Chercheur qualifié du Fonds National de la Recherche Scientifique.