Symmetry and Asymmetry Models for Rectangular Tables

The models of complete, quasi and conditional symmetry as well as marginal homogeneity and diagonal asymmetry, applicable to square contingency tables are extended to non-square ones. Several properties of the models are investigated and estimation and test theory is presented. The utility of the new proposed models is discussed and illustrated by reanalyzing classical data sets.     

Encapsulation of the peptide Ac-Glu-Thr-Lys-Thr-Tyr-Phe-Trp-Lys-NH2 into polyvinyl alcohol biodegradable formulations—Effect of calcium alginate

It has been recently reported that the peptide Ac-Glu-Thr-Lys-Thr-Tyr-Phe-Trp-Lys-NH₂, analogue of the Glu1811-Lys1818 region of A3 light chain of blood coagulation factor VIII, presents in vitro significant anticoagulant activity. The encapsulation of this peptide into different polyvinyl alcohol formulations is examined here. The formulations were prepared using polyvinyl alcohol cross-linked with either boric acid or glutaraldehyde, giving a series of twelve different hydrogels. In case of PVA-boric acid method, a small percentage of sodium alginate was used in order to avoid bead's agglomeration. In that case, the most efficient encapsulation of the octapeptide (74%) was achieved with 0.2% (w/w) sodium alginate. It was also observed that the increase in sodium alginate percentage leads to beads with increased peptide release time, ranging from 60 to 90 min at 0.02% and 1% (w/w) sodium alginate respectively. The water holding of the PVA gels was estimated to be 27% regardless of the cross-linking reagent used, while it was increased with increasing sodium alginate concentration and reached about 60% for 1% sodium alginate. The longer octapeptide release, at 120 min, was observed with PVA-glutaraldehyde hydrogel, with encapsulation efficiency comparable to those obtained with boric acid, indicating that this hydrogel may be further used in drug delivery systems.     

生物传感器在食源性致病菌大肠杆菌O157∶H7检测中的应用进展

食源性致病菌是引发食物中毒的主要微生物，对人类的健康构成了重要威胁，也逐渐发展为公共卫生、食品工业部门高度重视的一个问题。近年来，因食源性致病菌产生的疾病在世界各地蔓延，其中，大肠杆菌O157∶H7是食源性致病菌种类中造成病死率较高的一种细菌，其感染剂量低、致病性强等特点引起研究人员和世界各国卫生组织的广泛关注。基于此，对大肠杆菌O157∶H7的检测方法及其演变进行了梳理和比较分析，并着重综述了生物传感器（biosensor）在其检测中的应用进展，以期为大肠杆菌O157∶H7快速、准确和可商业化的检测方法的研发提供参考。     

Computational study of the activity,dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26

Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues—three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor—using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1) hyperinsulinemia may be due to the drastically reduced activity (and binding affinity) of the mutant insulins. 2) Y26_BS and Y26_BE are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.     

An analysis of Ca2+ release by DGEA: mobilization of two functionally distinct internal stores in Saos-2 cells

Osteoblasts can be activated by their collagen matrix and inparticular the DGEA peptide motif. We have reported that DGEA is ableto activate Ca²⁺ signalingpathways in the human osteoblast-like cell line, Saos-2, by a tyrosinekinase-dependent pathway (T. J. McCann, W. T. Mason, M. C. Meikle, andF. McDonald. Matrix Biol. 16:271-280, 1997). In the present study, we show that this activityis due to coupling of the signal to intracellularCa²⁺ stores, since the DGEA actionis not blocked by La³⁺ but is lostwhen Ca²⁺ stores are depleted with2 µM and blocked by 10 µM ryanodine. The activated stores alsodiffer functionally from those activated by thrombin, as blockade withU-73122 obstructs only thrombin-activated Ca²⁺ release. We have shown thatthe DGEA activity was not due to its high-charge density, since the twoacidic residues can be substituted with their uncharged homologues(asparagine and glutamine) without significant loss of activity. Thiswas in turn measured by an adhesion assay that also demonstrated thislevel of specificity. Furthermore, by constructing DGEA bound to FITC,we have shown that DGEA binding was dependent on divalent cations. Wehave also demonstrated that an intact actin cytoskeleton is notrequired for Ca²⁺ activation byinhibiting actin polymerization with the addition of cytochalasin B. These data strengthen the argument that collagen has a significant rolein regulating osteoblast function via this peptide motif.

     

The circadian system of c-fos deficient mice

We examined the role of c-fos in the synchronization of circadian rhythms to environmental light cycles using a line of gene-targeted mice carrying a null mutation at this locus. Circadian locomotor rhythms in mutants had similar periods as wild-type controls but took significantly longer than controls to entrain to 12:12 light-dark cycles. Light-induced phase shifts of rhythms in constant dark were attenuated in mutants although the circadian timing of phase delays and advances was not changed. A functional retinohypothalamic projection was indicated from behavioral results and light-induced jun-B expression in the SCN. The results indicate that while c-fos activation is not an absolute requirement for rhythm generation nor photic responses, it is required for normal entrainment of the mammalian biological clock.Abbreviations SCN suprachiasmatic nucleus - RHT retinohypothalamic tract - IEG immediate early genes - NGF nerve growth factor - VIP vasoactive intestinal polypeptide - DD constant darkness - CT circadian time     

Effects of chimaerism for two T/t complex mutations on sperm function

Mouse chimaeras produced by aggregation of embryos heterozygous for two different recessive mutations at the T/t complex have been analyzed by breeding to explore the basis for the phenomena of male transmission ratio distortion and sterility associated with these genes. Whereas males of genotype t^w2/t^w5 are always sterile, male chimaeras of the type +/t^w2 ? +/t^w5 are normally fertile; furthermore, they transmit each t mutation to the same very high extent seen in ordinary (+/t) heterozygotes. Since spermatogenic cells derived from either the +/t^w2 and +/t^w5 genotypes thus function quite independently of one another in mosaic testes, it can be concluded that sterility, and presumably distorted transmission ratio as well, depends on specific interactions between T/t alleles in diploid spermatogenic cells or their individual meiotic descendants.