Plectasin is a peptide antibiotic with therapeutic potential from a saprophytic fungus

Animals and higher plants express endogenous peptide antibiotics called defensins. These small cysteine-rich peptides are active against bacteria, fungi and viruses. Here we describe plectasin-the first defensin to be isolated from a fungus, the saprophytic ascomycete Pseudoplectania nigrella. Plectasin has primary, secondary and tertiary structures that closely resemble those of defensins found in spiders, scorpions, dragonflies and mussels. Recombinant plectasin was produced at a very high, and commercially viable, yield and purity. In vitro, the recombinant peptide was especially active against Streptococcus pneumoniae, including strains resistant to conventional antibiotics. Plectasin showed extremely low toxicity in mice, and cured them of experimental peritonitis and pneumonia caused by S. pneumoniae as efficaciously as vancomycin and penicillin. These findings identify fungi as a novel source of antimicrobial defensins, and show the therapeutic potential of plectasin. They also suggest that the defensins of insects, molluscs and fungi arose from a common ancestral gene.     

Licensing of natural killer cells by host major histocompatibility complex class I molecules

Self versus non-self discrimination is a central theme in biology from plants to vertebrates, and is particularly relevant for lymphocytes that express receptors capable of recognizing self-tissues and foreign invaders. Comprising the third largest lymphocyte population, natural killer (NK) cells recognize and kill cellular targets and produce pro-inflammatory cytokines. These potentially self-destructive effector functions can be controlled by inhibitory receptors for the polymorphic major histocompatibility complex (MHC) class I molecules that are ubiquitously expressed on target cells. However, inhibitory receptors are not uniformly expressed on NK cells, and are germline-encoded by a set of polymorphic genes that segregate independently from MHC genes. Therefore, how NK-cell self-tolerance arises in vivo is poorly understood. Here we demonstrate that NK cells acquire functional competence through 'licensing' by self-MHC molecules. Licensing involves a positive role for MHC-specific inhibitory receptors and requires the cytoplasmic inhibitory motif originally identified in effector responses. This process results in two types of self-tolerant NK cells--licensed or unlicensed--and may provide new insights for exploiting NK cells in immunotherapy. This self-tolerance mechanism may be more broadly applicable within the vertebrate immune system because related germline-encoded inhibitory receptors are widely expressed on other immune cells.     

Yeast extract as a supplement to chemically defined medium for axenic culture ofCaenorhabditis briggsae

Zusammenfassung Es wird der Nachweis erbracht, dass Hefenextrakte die Neubildung derC. briggsae in bakterienfreien (axenischen) Kulturen fördern. Durch Zufügung dieser Extrakte in einen chemisch definierten Nährboden werden grössere Nematodenpopulationen erzielt. Die biologische Aktivität wird durch Dialyse, Ammoniumsulfatniederschlag oder durch leichtes Erwärmen verstärkt.     

Does ammonium uptake influence xylem sap composition inPhaseolus vulgaris L. andGlycine max (L.) Merill?

The question of whether ammonium uptake influences the occurrence of ureides in legumes has been addressed in this study by investigating threeP. vulgaris genotypes as well as one cultivar ofGlycine max. All plants were raised in sand culture during the dry season in northern Thailand and irrigated daily with nitrogen-free nutrient solution, or the same solution containing 12 mol m^–3 nitrogen in the form of (NH₄)₂SO₄ or KNO₃, each treatment consisting of different proportions of either compound. Regression analyses of xylem sap composition relative to ammonium vs. nitrate supply of plants harvested at V4, R1 and R6 indicated close positive correlations of xylem amino nitrogen content and negative correlations with xylem nitrate content and ammonium supply. Statistically significant correlations between relative xylem ureide content and ammonium availability could be established for theP. vulgaris cultivar Brilliant up to stage R1, but not for the other plants investigated. It was concluded that at least for some genotypes of common bean a relationship exists between ureide production and ammonium uptake by the root system. Since the extent to which ureide production is stimulated remains quite small, its relevance to the xylem solute technique for measurement of N₂ fixation may be limited. Nevertheless, due to the possibility of large genotypic differences in the impact of ammonium on ureide production, this factor must be considered in calculations if N₂ fixation is to be determined in soils containing significant amounts of ammonium, e.g. in paddy fields.     

Minimum sum of diameters clustering

The problem of determining a partition of a given set ofN entities intoM clusters such that the sum of the diameters of these clusters is minimum has been studied by Brucker (1978). He proved that it is NP-complete forM3 and mentioned that its complexity was unknown forM=2. We provide anO(N ³ logN) algorithm for this latter case. Moreover, we show that determining a partition into two clusters which minimizes any given function of the diameters can be done inO(N ⁵) time.Acknowledgments: This research was supported by the Air Force Office of Scientific Research Grant AFOSR 0271 to Rutgers University. We are grateful to Yves Crama for several insightful remarks and to an anonymous referee for detailed comments.     

Maximum sum-of-splits clustering

ConsiderN entities to be classified, and a matrix of dissimilarities between pairs of them. The split of a cluster is the smallest dissimilarity between an entity of this cluster and an entity outside it. The single-linkage algorithm provides partitions intoM clusters for which the smallest split is maximum. We study here the average split of the clusters or, equivalently, the sum of splits. A (N ²) algorithm is provided to determine maximum sum-of-splits partitions intoM clusters for allM betweenN – 1 and 2, using the dual graph of the single-linkage dendrogram.

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Résumé SoientN objets à classifier et une matrice de dissimilarit és entre paires de ces objets. L'écart d'une classe est la plus petite dissimilarité entre un objet de cette classe et un objet en dehors d'elle. L'algorithme du lien simple fournit des partitions enM classes dont le plus petit écart est maximum. On étudie l'écart moyen des classes, ou, ce qui est équivalent, la somme des écarts. On propose un algorithme en (N ²) pour déterminer des partitions enM classes dont la somme des écarts est maximum pourM allant deN – 1 à 2, basé sur le graphe dual du dendrogramme de la méthode du lien simple.

     

Espaliers: A generalization of dendrograms

Dendrograms are widely used to represent graphically the clusters and partitions obtained with hierarchical clustering schemes. Espaliers are generalized dendrograms in which the length of horizontal lines is used in addition to their level in order to display the values of two characteristics of each cluster (e.g., the split and the diameter) instead of only one. An algorithm is first presented to transform a dendrogram into an espalier without rotation of any part of the former. This is done by stretching some of the horizontal lines to obtain a diagram with vertical and horizontal lines only, the cutting off by diagonal lines the parts of the horizontal lines exceeding their prescribed length. The problem of finding if, allowing rotations, no diagonal lines are needed is solved by anO(N ²) algorithm whereN is the number of entities to be classified. This algorithm is the generalized to obtain espaliers with minimum width and, possibly, some diagonal lines.Work of the first and second authors has been supported by FCAR (Fonds pour la Formation de Chercheurs et l'Aide à la Recherche) grant 92EQ1048, and grant N00014-92-J-1194 from the Office of Naval Research. Work of the first author has also been supported by NSERC (Natural Sciences and Engineering Research Council of Canada) grant to École des Hautes Études Commerciales, Montréal and by NSERC grant GP0105574. Work of the second author has been supported by NSERC grant GP0036426, by FCAR grant 90NC0305, and by an NSF Professorship for Women in Science at Princeton University from September 1990 until December 1991. Work of the third author was done in part during a visit to GERAD, Montréal.     

Efficient algorithms for divisive hierarchical clustering with the diameter criterion

Divisive hierarchical clustering algorithms with the diameter criterion proceed by recursively selecting the cluster with largest diameter and partitioning it into two clusters whose largest diameter is smallest possible. We provide two such algorithms with complexitiesO( N ²) andO(N ²logN) respectively, where denotes the maximum number of clusters in a partition andN the number of entities to be clustered. The former algorithm, an efficient implementation of an algorithm of Hubert, allows to find all partitions into at most clusters and is inO(N ²) for fixed . Moreover, if in each partitioning the size of the largest cluster is bounded byp times the number of entities in the set to be partitioned, with 1/2<=p<1, it provides a complete hierarchy of partitionsO(N ² logN) time. The latter algorithm, a refinement of an algorithm of Rao allows to build a complete hierarchy of partitions inO(N ² logN) time without any restriction. Comparative computational experiments with both algorithms and with an agglomerative hierarchical algorithm of Benzécri are reported.

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Résumé Les algorithmes de classification hiérarchique descendante utilisant le critère du diamètre, sélectionnent récursivement la classe de plus grand diamètre et la partitionnent en deux classes, dont le plus grand diamètre est le plus, petit possible. Nous proposons deux tels algorithmes, avec des complexités enO ( N²) etO(N ² logN) respectivement, où désigne le nombre maximum de classes d'une partition etN le nombre d'objets à classifier. Le premier algorithme, une implantation d'un algorithme de Hubert, permet de construire des partitions avec au plus classes et est enO(N ²) pour fixé. De plus, si dans chaque bipartition le nombre d'objets de la plus grande classe, est borné parp fois le nombre d'objets de l'ensemble à partitionner, où 1/2≤p<1, cet algorithme permet de construire une hiérarchie complète de partitions en tempsO(N ² logN). Le second algorithme, un raffinement d'un algorithme de Rao, permet de construire une hiérarchie complète de partitions en tempsO(N ² logN) sans aucune restriction On présente également des résultats de calcul comparatifs pour les deux algorithmes et pour l'algorithme de classification hiérarchique ascendante de Benzécri.

     

Evolution of species interactions in a biofilm community

Biofilms are spatially structured communities of microbes whose function is dependent on a complex web of symbiotic interactions. Localized interactions within these assemblages are predicted to affect the coexistence of the component species, community structure and function, but there have been few explicit empirical analyses of the evolution of interactions. Here we show, with the use of a two-species community, that selection in a spatially structured environment leads to the evolution of an exploitative interaction. Simple mutations in the genome of one species caused it to adapt to the presence of the other, forming an intimate and specialized association. The derived community was more stable and more productive than the ancestral community. Our results show that evolution in a spatially structured environment can stabilize interactions between species, provoke marked changes in their symbiotic nature and affect community function.