Targeting Homologous Recombination in Notch-Driven C. elegans Stem Cell and Human Tumors

Mammalian NOTCH1-4 receptors are all associated with human malignancy, although exact roles remain enigmatic. Here we employ glp-1(ar202), a temperature-sensitive gain-of-function C. elegans NOTCH mutant, to delineate NOTCH-driven tumor responses to radiotherapy. At ≤20°C, glp-1(ar202) is wild-type, whereas at 25°C it forms a germline stem cell⁄progenitor cell tumor reminiscent of human cancer. We identify a NOTCH tumor phenotype in which all tumor cells traffic rapidly to G2⁄M post-irradiation, attempt to repair DNA strand breaks exclusively via homology-driven repair, and when this fails die by mitotic death. Homology-driven repair inactivation is dramatically radiosensitizing. We show that these concepts translate directly to human cancer models.     

Biomarker profiles in serum and saliva of experimental Sj?gren's syndrome: associations with specific autoimmune manifestations

Introduction  

Sj?gren's syndrome (SS) is a systemic autoimmune disease that mainly targets the exocrine glands. The aim of this study was to investigate the involvement of 87 proteins measured in serum and 75 proteins analyzed in saliva in spontaneous experimental SS. In addition, we intended to compute a model of the immunological situation representing the overt disease stage of SS.     

Unsaturated oligogalacturonic acids are generated by in vitro treatment of pectin with human faecal flora.

Pectins with a degree of esterification (DE) of 95, 66, 34 and 0%, respectively, were incubated in vitro with human faecal flora (pH 7.8). The concentration and composition of oligogalacturonic acids (oligoGalA) generated were determined using high-performance thin-layer chromatography (HPTLC) with UV and colorimetric detection. In the first period of the anaerobic degradation, the pectin macromolecules were fragmented into unsaturated oligoGalA as intermediate products by the action of bacterial pectate lyases. Depending on the incubation time and the DE of pectin, the amount of unsaturated oligoGalA having different degrees of polymerization changed continuously. These oligoGalA were present in the cultures for some hours. Mixtures of unsaturated di-, tri- and tetraGalA were the end products of a pectate lyase action. Later, the oligoGalA disappear as a result of their further fermentation by the gastrointestinal microflora under formation of short-chain fatty acids (SCFA). Low-esterified pectins were depolymerized and fermented faster than the highly esterified by the human faecal flora in vitro. Furthermore, a mixture of unsaturated oligoGalA prepared from pectic acid by the action of pectate lyase from Erwinia carotovora was completely fermented by human faecal flora.     

Structural analysis of 5S rRNA, 5S rRNA-protein complexes and ribosomes employing RNase H and d(GTTCGG)

The hybridization of d(GTTCGG) to eubacterial 5S rRNAs, 5S rRNA-protein complexes, 70S ribosomes and 50S and 30S ribosomal subunits was investigated. This oligonucleotide, which may be considered to be an analogue of the T psi CG loop of tRNAs, was chosen in order to investigate a possible interaction between tRNAs with ribosomal components during protein synthesis. The hybridization was analysed by RNase H hydrolysis studies and, in the case of the ribosomes and ribosomal subunits, in addition with the radioactively labelled oligodeoxyribonucleotide in binding studies. The results obtained lead to the conclusion that nucleotides in loop c, i.e. positions 42-47, are available for oligonucleotide interaction in free Escherichia coli and Bacillus stearothermophilus 5S rRNAs and not available in the corresponding 5S rRNA-protein complexes. The 70S ribosomes and ribosomal subunits did not interact with the oligonucleotide. Under the assumption that d(GTTCGG) is an analogue of the T psi CG loop of tRNAs and in view of the results obtained, we conclude that in the unprogrammed ribosomes the T psi CG loop of tRNAs does not interact via standard Watson-Crick base pairs with the ribosomal 5S, 16S or 23S RNAs.     

Elucidation of the antigenic determinant in lipotropin for two monoclonal antibodies

Two monoclonal antibodies were found to give enhanced affinity for β-lipotropin when mixed, as evidenced by competitive radioimmunoassay. Both monoclonals were found to react with a pentapeptide Ala-Glu-Leu-Glu-Tyr, which is a sequence of high local hydrophilicity within the N-terminal section of β-lipotropin.     

Die Ausdrucksbewegungen der Sichelente,Anas falcata L.

Zusammenfassung Die Ausdrucksbewegungen der Sichelente,Anas (Eunetta) falcata Georgi, werden beschrieben, soweit möglich vorläufig analysiert und mit denen nächstverwandter Arten, vor allem denen vonAnas (Nettium) crecca crecca L.,Anas (Chaulelasmus) strepera L. undAnas (Mareca) penelope L. verglichen. Dieser Vergleich ergibt, genau wie der morphologischer Merkmale des Gefieders und der Knochentrommel, eine systematische Stellung vonfalcata genau zwischen den drei genannten Arten, näher den beiden erstgenannten als der dritten. Die Verteilung der Merkmal-Gemeinsamkeiten einerseits mitcrecca, andererseits mitstrepera, läßt den Schluß zu, daß die drei Arten divergent aus einer gemeinsamen Ahnenform entstanden seien. Keine gemeinsamen Merkmale, die bei anderen Arten fehlen, verbinden die drei genannten Formen zu einer Gruppe.Beim Gesellschaftsspiel der Sichelerpel sind, im Gegensatz zu dem aller anderen bisher daraufhin untersuchten Schwimmentenarten, alle beteiligten Bewegungsweisen, einschließlich des einleitenden Schüttelns, zur Ente hin orientiert, die hier, wie beicrecca undstrepera, am Spiel der Erpel sehr regen Anteil nimmt. Dagegen fehlen solche Bewegungen, die durch Ritualisierung aus Angriffsverhalten entstanden sind, beim Gesellschaftsspiel völlig, spielen aber eine große Rolle, analog dem Triumphgeschrei der Gänse und Tadorninen, beim Zusammenhalt der bereits verpaarten Tiere.     

Some effects of air ions on the activity of rats

A duct system was arranged through which flowed air of controlled ion concentration. In series was a chamber with a flexible dielectric floor which made possible electrical detection of activity.Exposure to various ion concentrations of either polarity produced pronounced effects.In addition to gross motor activity six other behavioural parameters were recorded. The lowest ion concentration were most effective. In addition to presenting a controlled ambient ion concertration the ion current drawn by the animal was measured. This varied markedly from rat to rat.

---

Zusammenfassung Ein Kanalsystem zum Durchfluss von Luft bekannter Ionenkonzentration wurde eingerichtet. Angeschlossen war eine Kammer mit einem beweglichen dielektrischen Boden, der die Registrierung der Aktivität von Ratten ermöglichte. Neben der motorischen Aktivität wurden 6 andere Verhaltensformen der Tiere registriert.Die niedrigste Ionenkonzentration war am wirksamsten zur Anregung der Aktivität. Neben der Ionenkonzentration in der Kammer wurde der von den Tieren eingeatmete Ionenstrom gemessen; er variierte stark von Tier zu Tier.

---

Resume On a construit un canal dans lequel il est possible de faire circuler de l'air dont la concentration en ions est contrôlable. On y a adjoint une cellule dont le sol est constitué par un diélectrique flexible permettant de déceler électriquement l'activité de petits animaux.En exposant des rats à des concentrations ioniques variables et de polarité différente, on peut constater des effets prononcés sur le comportement des animaux. En effet, en plus de l'activité motrice, on a enregistré six autres formes de ce comportement. Ce sont les plus faibles concentrations qui produisent le plus d'effets. A part la concentration en ions à l'intérieur de la cellule, on a également mesuré la quantité d'ions absorbés par les bêtes par voie respiratoire. Cette quantité varie fortement d'un individu à l'autre.

---

---

This work was supported by Public Health Service Research Grant #AP00305-02 from the Division of Air Pollution, Bureau of State Services and also by a grant from the Atmospheric Science Research Center of the State University of New York.