Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells

Here we investigated the potential role of bone-resorbing osteoclasts in homeostasis and stress-induced mobilization of hematopoietic progenitors. Different stress situations induced activity of osteoclasts (OCLs) along the stem cell-rich endosteum region of bone, secretion of proteolytic enzymes and mobilization of progenitors. Specific stimulation of OCLs with RANKL recruited mainly immature progenitors to the circulation in a CXCR4- and MMP-9-dependent manner; however, RANKL did not induce mobilization in young female PTPepsilon-knockout mice with defective OCL bone adhesion and resorption. Inhibition of OCLs with calcitonin reduced progenitor egress in homeostasis, G-CSF mobilization and stress situations. RANKL-stimulated bone-resorbing OCLs also reduced the stem cell niche components SDF-1, stem cell factor (SCF) and osteopontin along the endosteum, which was associated with progenitor mobilization. Finally, the major bone-resorbing proteinase, cathepsin K, also cleaved SDF-1 and SCF. Our findings indicate involvement of OCLs in selective progenitor recruitment as part of homeostasis and host defense, linking bone remodeling with regulation of hematopoiesis.     

Biology of Tetrastichus howardi (Olliff) (Hymenoptera: Eulophidae): A facultative Hyperparasitoid of stem borers

The biology of the parasitoid Tetrastichus howardi, which was introduced from the Philippines into South Africa for the biological control of the stem borer Chilo partellus, was studied in the laboratory. On average, a T. howardi female produced 101 progeny (92% females) which developed in 4.3 hosts. The upper threshold temperature for development was around 33°C, the minimum threshold was calculated as 12.8°C and the thermal constant as 239.8 day‐degrees. With hosts, females lived 23.6 and males 16.7 days. T. howardi was found to be a facultative hyperparasitoid with a very wide host range. As a primary parasitoid, it developed in pupae of various Lepidoptera as well as Coleoptera and Hymenoptera and as a hyperparasitoid in dipteran and hymenopteran parasitoids. A linear relation was found between the number of emergent parasitoids and the volume of the host from which they emerged. Preference tests indicated that T. howardi preferred to parasitize the phytophagous insects C. partellus and Heliothis armigera, over their parasitoids Xanthopimpla stemmator and Palexorista laxa. The host selection of inexperienced T. howardi females was different from the experienced parasitoids. When given a choice, females showed preference for the host species they were allowed to parasitize previously and the host species from which they had been reared. The use of facultative hyperparasitoids in biological control in general and against stem borers in South Africa in particular is discussed.     

A novel postpriming regulatory check point of effector/memory T cells dictated through antigen density threshold-dependent anergy

CTLs act as the effector arm of the cell-mediated immune system to kill undesirable cells. Two processes regulate these effector cells to prevent self reactivity: a thymic selection process that eliminates autoreactive clones and a multistage activation or priming process that endows them with a license to kill cognate target cells. Hitherto no subsequent regulatory restrictions have been ascribed for properly primed and activated CTLs that are licensed to kill. In this study we show that CTLs possess a novel postpriming regulatory mechanism(s) that influences the outcome of their encounter with cognate target cells. This mechanism gauges the degree of Ag density, whereupon reaching a certain threshold significant changes occur that induce anergy in the effector T cells. The biological consequences of this Ag-induced postpriming control includes alterations in the expression of cell surface molecules that control immunological synapse activity and cytokine profiles and induce retarded cell proliferation. Most profound is genome-wide microarray analysis that demonstrates changes in the expression of genes related to membrane potential, TCR signal transduction, energy metabolism, and cell cycle control. Thus, a discernible and unique gene expression signature for anergy as a response to high Ag density has been observed. Consequently, activated T cells possess properties of a self-referential sensory organ. These studies identify a new postpriming control mechanism of CTL with anergenic-like properties. This mechanism extends our understanding of the control of immune function and regulation such as peripheral tolerance, viral infections, antitumor immune responses, hypersensitivity, and autoimmunity.     

A Tradeoff in the Neural Code across Regions and Species

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Ce-emerin and LEM-2: essential roles in Caenorhabditis elegans development, muscle function, and mitosis

Emerin and LEM2 are ubiquitous inner nuclear membrane proteins conserved from humans to Caenorhabditis elegans. Loss of human emerin causes Emery-Dreifuss muscular dystrophy (EDMD). To test the roles of emerin and LEM2 in somatic cells, we used null alleles of both genes to generate C. elegans animals that were either hypomorphic (LEM-2-null and heterozygous for Ce-emerin) or null for both proteins. Single-null and hypomorphic animals were viable and fertile. Double-null animals used the maternal pool of Ce-emerin to develop to the larval L2 stage, then arrested. Nondividing somatic cell nuclei appeared normal, whereas dividing cells had abnormal nuclear envelope and chromatin organization and severe defects in postembryonic cell divisions, including the mesodermal lineage. Life span was unaffected by loss of Ce-emerin alone but was significantly reduced in LEM-2-null animals, and double-null animals had an even shorter life span. In addition to striated muscle defects, double-null animals and LEM-2-null animals showed unexpected defects in smooth muscle activity. These findings implicate human LEM2 mutations as a potential cause of EDMD and further suggest human LEM2 mutations might cause distinct disorders of greater severity, since C. elegans lacking only LEM-2 had significantly reduced life span and smooth muscle activity.     

Parasites of the spotted stalk borer,Chilo partellus [Lepidoptera: Pyralidae] in South Africa

One egg parasite, 7 larval parasites, 2 pupal parasites and 3 larval hyperparasites were recorded parasitizing the spotted stalk borer,Chilo partellus (Swinhoe) on maize and grain sorghum in South Africa.Trichogrammatoidea lutea Girault [Trichogrammatidae] parasitized eggs ofC. partellus mainly in mid-summer. The larval parasites were active throughout the season with occasional peaks of up to 75% parasitism.Apanteles sesamiae Cameron [Braconidae], proved to be the most abundant larval parasite. It was recorded fromca. 93% of parasitized larvae but its efficiency was reduced by the hyperparasite,Aphanogmus fijiensis (Ferriére) [Ceraphronidae], which reached sometimes up to 100% parasitism on cocoons ofA. sesamiae. The efficiency ofIphiaulax sp. [Braconidae], the 2^nd most abundant larval parasite, was also hindered by the hyperparasite,Eurytoma sp. [Eurytomidae] Pupal parasites were sometimes very abundant reaching up to 100% parasitism without any interference by hyperparasites. The most abundant pupal parasites wereDentichasmias busseolae Heinrich [Ichneumonidae] andPediobius furvus (Gahan) [Eulophidae].      

An improved method for mass rearing Paratheresia claripalpis for biological control of lepidopteran stalk borers

An improved method for mass rearing Paratheresia claripalpis Van der Wulp (Diptera: Tachinidae), for biological control of lepidopteran stalk borers is described and compared to the commonly used method. The improved method was found to be superior by being less labour intensive and by producing 2.25 times more parasites from the same number of hosts.

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Amélioration de la technique d'élevage de masse de Paratheresia claripalpis pour la lutte biologique contre Diatraea saccharalis

Résumé Une technique d'élevage de massa de la tachinaire, P. claripalpis Van der Wulp, est décrite et comparée à la technique classique. Cette technique correspond à une amélioration puisqu'elle demande moins de travail et produit 2.25 fois plus de parasites pour le même nombre d'hôtes.

     

Antibody-mediated targeting of human single-chain class I MHC with covalently linked peptides induces efficient killing of tumor cells by tumor or viral-specific cytotoxic T lymphocytes

Soluble forms of human MHC class I HLA-A2 were produced in which the peptide binding groove was uniformly occupied by a single tumor or viral-derived peptides attached via a covalent flexible peptide linker to the N terminus of a single-chain -2-microglobulin-HLA-A2 heavy chain fusion protein. A tetravalent version of this molecule with various peptides was found to be functional. It could stimulate T cells specifically as well as bind them with high avidity. The covalently linked single chain peptide-HLA-A2 construct was next fused at its C-terminal end to a scFv antibody fragment derived from the variable domains of an anti-IL-2R subunit-specific humanized antibody, anti-Tac. The scFv–MHC fusion was thus encoded by a single gene and produced in E. coli as a single polypeptide chain. Binding studies revealed its ability to decorate Ag-positive human tumor cells with covalent peptide single-chain HLA-A2 (scHLA-A2) molecules in a manner that was entirely dependent upon the specificity of the targeting Antibody fragment. Most importantly, the covalent scHLA-A2 molecule, when bound to the target tumor cells, could induce efficient and specific HLA-A2-restricted, peptide-specific CTL-mediated lysis. These results demonstrate the ability to generate soluble, stable, and functional single-chain HLA-A2 molecules with covalently linked peptides, which when fused to targeting antibodies, potentiate CTL killing. This new approach may open the way for the development of new immunotherapeutic strategies based on antibody targeting of natural cognate MHC ligands and CTL-based cytotoxic mechanisms.Kfir Oved and Avital Lev contributed equally to this work     

Hibernation by the lepidopteran stalk borers, Busseola fusca and Chilo partellus on grain sorghum

The lepidopteran stalk borers, the indigenous Busseola fusca (Fuller) (Noctuidae), and the exotic Chilo partellus (Swinhoe) (Pyralidae), were studied in grain sorghum fields, Sorghum bicolor (L.) Moench (cultivar SSK-52), in the dry season of 1986 (April–October) at Delmas and Brits, Transvaal, South Africa. More than 90% of plants at both sites were infested, but as winter progressed, the proportion of plants infested and the level of infestation dropped gradually. The borer larvae hibernated inside the dry stalks, but the location differed: 65% of B. fusca were in the lower third and 30% in the middle third, whereas for C. partellus it was 45 and 50% respectively. Both borers overwintered as larvae in either of the last three instars, but the proportions of larval instars were different. About 82% of B. fusca hibernated as 6th and 16% as 5th larval instars whereas with C. partellus it was 40 and 45% respectively. C. partellus started to emerge from diapause in the second part of August and it lasted until the first week of November, a period of 12 weeks, but with B. fusca on the other hand pupation lasted only 3 weeks during October–November. Parasitism was low on both species, but higher on B. fusca. Three parasites, Chelonus curvinaculatus Cameron, Chelonus sp. and Pristomerus sp. hibernated in the borers, one parasite Iphiaulax sp., hibernated in its cocoon inside the stalks, and two parasites Apanteles sesamiae Cameron and Bracon sp. were active in winter. Two ants, Pheidole megacephala Febricius, and Dorylus helvolus (L.), preyed on the borer larvae in winter.

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Hibernation des chenilles de deux espèces de mineuses, Busseola fusca et Chilo partellu dans les tiges de Sorghum bicolor

Résumé Deux chenilles mineuses de tiges, B. fusca, Noctuidae indigène, et C. partellus, Pyralidae exotique, ont été étudiées dans des champs de S. bicolor (cultivar SSK-52), pendant la saison sèche de 1986 (Avril–Octobre) à Delmas et Brits, au Transvaal en Afrique du Sud. Plus de 90% des pieds des deux stations étaient infestés, mais plus l'hiver avançait, plus la proportion de plantes in festées et le taux d'infestation diminuaient. Les chenilles ont hiverné dans les tiges sèches, mais leurs positions étaient différentes: 65% des B. fusca étaient dans le tiers inférieur et 30% dans le tiers médian, tandis que pour C. partellus, il s'agissait respectivement de 45 et 50%. Les duex chenilles hivernaient à l'un des 3 derniers stades larvaires, mais les proportions étaient différentes. Pour B. fusca environ 82% hivernaient au 6ème stade et 16% au 5ème stade, tandis que pour C. partellus c'étaient 40 et 45% respectivement. C. partellus a commencé à sortir de diapause pendant la seconde moitié d'Août et a continué jusqu'à la première semaine de Novembre, soit durant une période de 12 semaines, mais avec B. fusca la nymphose a duré seulement 3 semaines en Octobre–Novembre. Le parasitisme des deux espèces a été faible, mais plus important chez B. fusca. Trois parasites, Chelonus curvimaculatus Cameron, Chelonus sp. et Pristomerus sp. ont hiverné dans leurs cocons à l'intérieur des tiges, et deux parasites, Apanteles sesamiae Cameron et Bracon sp. étaient actifs en hiver. Deux fourmis, Pheidole megacephala Fabricius et Dorylus helvolus L. capturaient des chenilles de ces mineuses pendant l'hiver.