The influence of a new antitumor agent on hemopoietic colony forming cells

Summary The cytostatic and immunsuppressive agent N-methyl-N--chloroethylbenzaldehyde hydrazone (B1) in invitro experiments has a stimulating effect on colony-forming culture (CFUc) of bone marrow from C57BL mice. This unusual behaviour, which is in contrast to other cytostatics, could also be observed in vitro with CFUc obtained from mice treated with therapeutic doses of B1 for 2 weeks. This stimulation is not a particular effect of B1 alone but seems to depend on a synergistic effect of the combination of B1 and the colony-stimulating activity (CSA) present in the serum from endotoxin-treated mice (MP) in the testing system. The results suggest that the described effect of B1 is due to an interference at the cell membrane of CFUc or their precursor cells.     

The influence of N-methyl-N-β-chloroethyl hydrazines on the mitotic index of Ehrlich ascites tumor cells and the leukopoiesis of the mouse

Summary The cytostatic activity of N-methyl-N--chloroethylbenzaldehyd hydrazone, (B1) is at least equal to that of procarbazine when its effect is tested with the Ehrlich ascites tumor cells of the mouse and the Yoshida sarcoma of the rat. B1 causes a slighter decrease of mitotic cells and no shift from prophase to metaphase. These results suggest that the cytostatic effect of B1 is due to interference with cell metabolism or an effect at the cell membrane and not to an effect on cell proliferation. This assumption is supported by a considerable depression, of lymphocytes and a minor effect on granulopoiesis, which is especially sensitive towards proliferation toxins. All these findings suggest a different mechanism of action of B1 and procarbazine.     

DNA protection by stress-induced biocrystallization.

The crystalline state is considered to be incompatible with life. However, in living systems exposed to severe environmental assaults, the sequestration of vital macromolecules in intracellular crystalline assemblies may provide an efficient means for protection. Here we report a generic defence strategy found in Escherichia coli, involving co-crystallization of its DNA with the stress-induced protein Dps. We show that when purified Dps and DNA interact, extremely stable crystals form almost instantaneously, within which DNA is sequestered and effectively protected against varied assaults. Crystalline structures with similar lattice spacings are formed in E. coli in which Dps is slightly over expressed, as well as in starved wild-type bacteria. Hence, DNA-Dps co-crystallization is proposed to represent a binding mode that provides wide-range protection of DNA by sequestration. The rapid induction and large-scale production of Dps in response to stress, as well as the presence of Dps homologues in many distantly related bacteria, indicate that DNA protection by biocrystallization may be crucial and widespread in prokaryotes.     

Context generalization in Drosophila visual learning requires the mushroom bodies.

The world is permanently changing. Laboratory experiments on learning and memory normally minimize this feature of reality, keeping all conditions except the conditioned and unconditioned stimuli as constant as possible. In the real world, however, animals need to extract from the universe of sensory signals the actual predictors of salient events by separating them from non-predictive stimuli (context). In principle, this can be achieved if only those sensory inputs that resemble the reinforcer in their temporal structure are taken as predictors. Here we study visual learning in the fly Drosophila melanogaster, using a flight simulator, and show that memory retrieval is, indeed, partially context-independent. Moreover, we show that the mushroom bodies, which are required for olfactory but not visual or tactile learning, effectively support context generalization. In visual learning in Drosophila, it appears that a facilitating effect of context cues for memory retrieval is the default state, whereas making recall context-independent requires additional processing.     

Germline mutations in BAP1 predispose to melanocytic tumors

Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.     

Strong genetic differentiation among neighboring populations of a locally endemic primrose

Maguire primrose is a locally endemic plant of northern Utah, USA, with a total known range of less than 20 km 2 . A previous study found evidence for strong differentiation among local populations at 4 allozyme loci. Here we reexamined populations using 165 AFLP loci and found further evidence of unusually strong genetic structure. We also found an apparently fixed nucleotide difference between populations for a noncoding region of chloroplast DNA, mirroring the patterns seen for AFLP loci. Furthermore, we tested the hypothesis that the current population structure is the result of breeding barriers between plants from different populations. We made controlled hand-pollinated crosses and found that interpopulation crosses did not set significantly fewer seeds than intrapopulation crosses. Thus, we found no evidence of breeding barriers to explain these genetic patterns. However, we did note a relatively short overlap in flowering time, suggesting that phenology is a more feasible explanation for genetic differentiation than pollen-stigma incompatibility. Our study emphasizes that even locally endemic plants can house measurable genetic differences over a short geographic scale.     

The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome

Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder.