The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus.

Mutations at the steel locus (Sl) of the mouse affect the same cellular targets as mutations at the white spotting locus (W), which is allelic with the c-kit proto-oncogene. We show that KL, a hematopoietic growth factor obtained from conditioned medium of BALB/c 3T3 fibroblasts that stimulates the proliferation of mast cells and early erythroid progenitors, specifically binds to the c-kit receptor. The predicted amino acid sequence of isolated KL-specific cDNA clones suggests that KL is synthesized as an integral transmembrane protein. Linkage analysis maps the KL gene to the Sl locus on mouse chromosome 10, and KL sequences are deleted in the genome of the Sl mouse. These results indicate that the Sl locus encodes the ligand of the c-kit receptor, KL.     

Eusynaptomyces benjaminii,spec. nova, (Ascomycetes,Laboulbeniales) und seine Anpassungen an das Fortpflanzungsverhalten seines WirtesEnochrus testaceus (Coleoptera,Hydrophilidae)

Eusynaptomyces benjaminii is described as a new species of the ectoparasiticLaboulbeniales (Ascomycetes). It exists only on two very restricted areas of the body (= position specifity) of its hostEnochrus testaceus (F.) (Coleoptera, Hydrophilidae): on the claws of the right fore-leg and on the lower side of the frontal border of the pronotum. In these two habitatsEu. benjaminii develops two extremely different growth-forms. Male and female hosts are parasitized on somewhat different parts of their body. This can be explained by their mating behaviour. The growth-forms ofEu. benjaminii are so different that one ignorant of the biology of hosts and parasites, might regard them as members of different species or even genera. They are to be interpreted as adaptations of one species to growth positions and mating behaviour of the host. There is no sex-of-host specifity as assumed by certain authors for several species of theLaboulbeniales.

     

Life cycle assessment of contaminated sites remediation

For the federal state of Baden-Wiirttemberg, Germany, the decision tool “Umweltbilanz von Altlastensanierungsverfahren” has been developed and found suitable for the quantification and evaluation of environmental impacts caused by remediation of contaminated sites. The developed tool complements the remediation toolbox of Baden-Wiirttemberg. The tool includes a streamlined life cycle assessment (LCA) and a synopsis of the LCA results with the results of a risk assessment of the contaminated site. The risk assessment tool is not explained here. The data base for the life cycle inventory includes several techniques used in remedial actions. The life cycle impact assessment utilises 14 impact categories. The method allows comparisons between remedial options for specific contaminated sites. A software tool has been developed to be available in 1999.     

Development of a neuromedin U–human serum albumin conjugate as a long‐acting candidate for the treatment of obesity and diabetes. Comparison with the PEGylated peptide

Neuromedin U (NMU) is an endogenous peptide implicated in the regulation of feeding, energy homeostasis, and glycemic control, which is being considered for the therapy of obesity and diabetes. A key liability of NMU as a therapeutic is its very short half‐life in vivo. We show here that conjugation of NMU to human serum albumin (HSA) yields a compound with long circulatory half‐life, which maintains full potency at both the peripheral and central NMU receptors. Initial attempts to conjugate NMU via the prevalent strategy of reacting a maleimide derivative of the peptide with the free thiol of Cys34 of HSA met with limited success, because the resulting conjugate was unstable in vivo. Use of a haloacetyl derivative of the peptide led instead to the formation of a metabolically stable conjugate. HSA–NMU displayed long‐lasting, potent anorectic, and glucose‐normalizing activity. When compared side by side with a previously described PEG conjugate, HSA–NMU proved superior on a molar basis. Collectively, our results reinforce the notion that NMU‐based therapeutics are promising candidates for the treatment of obesity and diabetes. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Comparison of two chickpea varieties regarding their responses to direct and induced Fe deficiency

The effects of Fe deficiency (whether direct or bicarbonate-induced) on plant morphology, growth parameters, photosynthesis-related pigment contents, gas exchange, and water relations were addressed in two contrasting chickpea varieties (INRAT88 and Chetoui, respectively tolerant and sensitive to Fe deficiency). A marked decrease in the whole plant Fe content was observed in the Fe deprived plants of both varieties, especially the bicarbonate-treated ones, which showed a slower growth development and water deficit stress symptoms (increased leaf tissue osmolality associated with decreased shoot height, increased leaf mass to area ratio, and decreased water content). Both Fe shortage and bicarbonate addition resulted in both varieties in the decline of the photosynthetic pigment contents, contributing to lower photosynthetic efficiency (φ_c) and lower net photosynthesis (A). Fe deficiency reduced the water use efficiency and physiological availability of water too. However, INRAT88 was more tolerant to Fe deficiency than Chetoui, by maintaining a higher growth rate associated with lower respiration rate (R_D), higher chlorophyll a and b concentrations, higher A, lower transpiration rate (E) and a higher water use efficiency (A/E). The present data suggest that the efficient utilisation of Fe for the synthesis of chlorophyll together with the effective control of electron-transport chains at chloroplasts (high A) and mitochondria (low R_D) may account for the higher tolerance of INRAT88 to direct Fe deficiency. Further investigations with respect to oxidative stress and ROS generation, or about photorespiration would be helpful for a better understanding of their interaction with Fe deficiency in this grain legume.     

Epithelial–mesenchymal transition in rhesus monkey embryonic stem cell colonies: the role of culturing conditions

Colonies of rhesus monkey embryonic stem cells (rhESC; cell line R366.4) have been described before to show a spatially ordered process of epithelial–mesenchymal transition in vitro. In the present investigations, we have studied variables of culturing conditions which influence the reproducibility of the formation of crater-like ingression centers in the colonies. Critical parameters are found to be age and density of mouse embryonic fibroblast (MEF) feeder cell layers, the mode of mitotic inactivation of the MEFs (mitomycin C, or irradiation), and the mode of rhESC isolation during subculturing (enzymatic/mechanical cell cluster isolation; type of enzyme). The described culturing system appears to offer a reproducible in vitro model potentially useful for studies on cellular processes involved in gastrulation in the primate.     

DNA damage-induced expression of p53 suppresses mitotic checkpoint kinase hMps1: the lack of this suppression in p53MUT cells contributes to apoptosis

DNA damage induced by the topoisomerase I inhibitor irinotecan (CPT-11) triggers in p53(WT) colorectal carcinoma cells a long term cell cycle arrest and in p53MUT cells a transient arrest followed by apoptosis (Magrini, R., Bhonde, M. R., Hanski, M. L., Notter, M., Scherübl, H., Boland, C. R., Zeitz, M., and Hanski, C. (2002) Int. J. Cancer 101, 23-31; Bhonde, M. R., Hanski, M. L., Notter, M., Gillissen, B. F., Daniel, P. T., Zeitz, M., and Hanski, C. (2006) Oncogene 25, 165-175). The mechanism of the p53-independent apoptosis still remains largely unclear. Here we used five p53WT and five p53MUT established colon carcinoma cell lines to identify gene expression alterations associated with apoptosis in p53MUT cells after treatment with SN-38, the irinotecan metabolite. After treatment, 16 mitosis-related genes were found to be expressed at least 2-fold stronger in the apoptosis-executing p53MUT cells than in the cell cycle-arrested p53WT cells by oligonucleotide microarray analysis. One of the genes whose strong post-treatment expression was associated with apoptosis was the mitotic checkpoint kinase hMps1 (human ortholog of the yeast monopolar spindle 1 kinase). hMps1 mRNA and protein expression were suppressed by the treatment-induced and by the exogenous adenovirus-coded p53 protein. The direct suppression of hMps1 on RNA level or inhibition of its activity by a dominant-negative hMps1 partly suppressed apoptosis. Together, these data indicate that the high expression of mitotic genes in p53MUT cells after SN-38 treatment contributes to DNA damage-induced apoptosis, whereas their suppression in p53WT cells acts as a safeguard mechanism preventing mitosis initiation and the subsequent apoptosis. hMps1 kinase is one of the mitotic checkpoint proteins whose expression after DNA damage in p53MUT cells activates the checkpoint and contributes to apoptosis.     

A T-cell HCV vaccine eliciting effective immunity against heterologous virus challenge in chimpanzees

Three percent of the world's population is chronically infected with the hepatitis C virus (HCV) and at risk of developing liver cancer. Effective cellular immune responses are deemed essential for spontaneous resolution of acute hepatitis C and long-term protection. Here we describe a new T-cell HCV genetic vaccine capable of protecting chimpanzees from acute hepatitis induced by challenge with heterologous virus. Suppression of acute viremia in vaccinated chimpanzees occurred as a result of massive expansion of peripheral and intrahepatic HCV-specific CD8(+) T lymphocytes that cross-reacted with vaccine and virus epitopes. These findings show that it is possible to elicit effective immunity against heterologous HCV strains by stimulating only the cellular arm of the immune system, and suggest a path for new immunotherapy against highly variable human pathogens like HCV, HIV or malaria, which can evade humoral responses.