Different roles of the human Orc6 protein in the replication initiation process

In eukaryotes, binding of the six-subunit origin recognition complex (ORC) to DNA provides an interactive platform for the sequential assembly of pre-replicative complexes. This process licenses replication origins competent for the subsequent initiation step. Here, we analyze the contribution of human Orc6, the smallest subunit of ORC, to DNA binding and pre-replicative complex formation. We show that Orc6 not only interacts with Orc1–Orc5 but also with the initiation factor Cdc6. Biochemical and imaging experiments reveal that this interaction is required for licensing DNA replication competent. Furthermore, we demonstrate that Orc6 contributes to the interaction of ORC with the chaperone protein HMGA1a (high mobility group protein A1a). Binding of human ORC to replication origins is not specified at the level of DNA sequence and the functional organization of origins is poorly understood. We have identified HMGA1a as one factor that might direct ORC to AT-rich heterochromatic regions. The systematic analysis of the interaction between ORC and HMGA1a revealed that Orc6 interacts with the acidic C-terminus of HMGA1a and also with its AT-hooks. Both domains support autonomous replication if targeted to DNA templates. As such, Orc6 functions at different stages of the replication initiation process. Orc6 can interact with ORC chaperone proteins such as HMGA1a to facilitate chromatin binding of ORC and is also an essential factor for pre-RC formation.     

Predictability of Plastic Parts Behaviour Made from Rapid Manufacturing

One of the most important issues to resolve in parts manufactured from rapid manufacturing (RM) technologies is to know their behavior working under real conditions. Total quality manufacturing (TQM) is only possible if mechanical properties are well known in the design stage depending on the processing parameters. This work is mainly focused on testing of several samples made with different selective laser sintering (SLS) parameters and technologies. This procedure is the starting point to establish a basis for designing for RM and the standardization of RM testing. The experiments and the analysis of variance (ANOVA) analyzed the effects of several factors on mechanical properties. The SLS technologies were 3DSystem and EOS. The results show which factor has a large effect on the variables and the interaction between them. The conclusions are very useful for developing rules for designing (designing for RM) and creating new standard rules (ISO, AISI, and DIN) for RM materials and parts testing. The ANOVA gives a better knowledge of the effects of these factors and eliminates unimportant parameters.     

Structure specificity of some immunoadjuvant synthetic glycopeptides.

The immunoadjuvant activity of muramyl dipeptide seems to be critically dependent on the type of substitution of the gamma-carboxyl group of the D-isoglutamine residue. Moreover the nonapeptide L-Ala-D-isoGlu-L-lys-D-Ala-(Gly)5-OME also shows a definite effect.     

Effect of glucose administration on bilirubin excretion in the rabbit

Summary The effect of i.v. infusion of glucose on the hepatic handling of bilirubin was examined in rabbits. A significant increase in the excretion of conjugated bilirubin into the bile was observed, accompanied by a decrease in bilirubinemia. Hepatic bilirubin concentrations were lowered and the UDP-glucose concentrations and liver UDP-glucuronosyl and UDP-glucosyl transferase activities increased.     

Accumulation of drastic mutants in selection lines for resistance to the insecticides dichlorvos and malathion inDrosophila melanogaster

Summary Viability tests were performed on second and third chromosomes from lines ofDrosophila melanogaster selected for increased resistance to the organophosphorus insecticides dichlorvos and malathion, in order to evaluate the accumulation of drastic alleles. Our results show that malathion reduces significantly the relative viability of chromosome 3 and also increases the frequency of drastic alleles in this chromosome, while dichlorvos increases significnatly the frequency of drastic alleles in chromosome 2.Work supported in part by the Spanish Ministry of Education and Science (Grant No. 0577/84 CAICYT).—We are grateful to Productos Cruz Verde S.A. and Agrocrós S.A. for generously supplying the insecticides dichlorvos and malathion, respectively.     

Photoperiodic summation is temperature-dependent inPyrrhocoris apterus (L.) (Heteroptera)

Summary InPyrrhocoris apterus, a low temperature, 15°C, prevented the termination of diapause by long days and, unexpectedly, also the induction of diapause by short days. Both responses were enabled at a higher temperature, 26°C. In contrast to current concepts, it was proved that the summation of photoperiodic signals was temperature-dependent, since the morphogenetic development was prevented by starvation.     

Empirical factors and structure transference: Returning to the London account

We offer a framework to represent the roles of empirical and theoretical factors in theory construction, and examine a case study to illustrate how the framework can be used to illuminate central features of scientific reasoning. The case study provides an extension of French and Ladyman's (1997) analysis of Fritz and Heinz London's model of superconductivity to accommodate the role of the analogy between superconductivity and diamagnetic phenomena in the development of the model between 1935 and 1937. We focus on this case since it allows us to separate the roles of empirical and theoretical factors, and so provides an example of the utility of the approach that we have adopted. We conclude the paper by drawing on the particular framework here developed to address a range of concerns.     

Corticosteroidogenesis by isolated human adrenal cells: effect of serotonin and serotonin antagonists.

The direct effect of serotonin and antiserotonin agents on adrenal steroid biosynthesis was studied in isolated adrenal cells derived from patients with Cushing's syndrome. The results indicate that serotonin increases corticosterone production, while the serotonin antagonists cyproheptadine and methysergide depress adrenal steroid - particularly cortisol and aldosterone - biosynthesis.     

The use of dipeptide-p-nitranilides for the study of aminopeptidase specificity.

The use of dipeptide-p-nitranilides for the study of 2 placental aminopeptidases separated on Sephadex G200 helped in establishing some regular features of their specifities. The high-molecular (320,000 daltons) one prefers Phe in position P'1 to Leu, whereas the lower-molecular aminopeptidase (145,000 daltons) prefers Leu. The high-molecular aminopeptidase splits very slowly the N-terminal Leu when Gly is in adjacent position. Leu-Gly-p-NA is therefore an inhibitor of this AP.