Gene-target recognition among members of the myc superfamily and implications for oncogenesis

Myc and Mad family proteins regulate multiple biological processes through their capacity to influence gene expression directly. Here we show that the basic regions of Myc and Mad proteins are not functionally equivalent in oncogenesis, have separable E-box-binding activities and engage both common and distinct gene targets. Our data support the view that the opposing biological actions of Myc and Mxi1 extend beyond reciprocal regulation of common gene targets. Identification of differentially regulated gene targets provides a framework for understanding the mechanism through which the Myc superfamily governs the growth, proliferation and survival of normal and neoplastic cells.     

Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation

X-linked forms of mental retardation (XLMR) include a variety of different disorders and may account for up to 25% of all inherited cases of mental retardation. So far, seven X-chromosomal genes mutated in nonspecific mental retardation (MRX) have been identified: FMR2, GDI1, RPS6KA3, IL1RAPL, TM4SF2, OPHN1 and PAK3 (refs 2-9). The products of the latter two have been implicated in regulation of neural plasticity by controlling the activity of small GTPases of the Rho family. Here we report the identification of a new MRX gene, ARHGEF6 (also known as alphaPIX or Cool-2), encoding a protein with homology to guanine nucleotide exchange factors for Rho GTPases (Rho GEF). Molecular analysis of a reciprocal X/21 translocation in a male with mental retardation showed that this gene in Xq26 was disrupted by the rearrangement. Mutation screening of 119 patients with nonspecific mental retardation revealed a mutation in the first intron of ARHGEF6 (IVS1-11T-->C) in all affected males in a large Dutch family. The mutation resulted in preferential skipping of exon 2, predicting a protein lacking 28 amino acids. ARHGEF6 is the eighth MRX gene identified so far and the third such gene to encode a protein that interacts with Rho GTPases.     

The SARD variety of multifractality of ventricular epicardial mapping during ischemia

Myocardial ischemia creates abnormal electro- physiological substrates that can result in life-threat- ening ventricular arrhythmias. In order to investigate the relation between ischemia and variability of multi- fractality, ventricular epicardial electr…     

Organizing for Research and Action: Implementing Action Researcher Networks

The article describes and analyzes the process by which action researchers transcend boundaries—including discipline and institutional boundaries, as well as those between academia and industry—to develop effective action researcher networks. The particular empirical setting explored is that defined by the CO-IMPROVE project, a European Union-funded project which addresses the facilitation of collaborative improvement of operations practice and performance in the extended manufacturing enterprise through collaborative action learning among both managers and researchers.     

The importance of the terminal hemi-acetal group for the ionophoric properties of nigericin

Opening of the terminal hemi-acetal in dihydronigericin drastically reduces the ionophoric properties of nigericin and dehydroxymethylnigericin with 6 intact heterocycles. This is shown by 2 complementary methods, first with a liquid membrane electrode system, secondly by testing their ionophoric activities in rat liver mitochondria.     

Asymmetry in the link between the yield spread and industrial production: threshold effects and forecasting

We analyse the nonlinear behaviour of the information content in the spread for future real economic activity. The spread linearly predicts one‐year‐ahead real growth in nine industrial production sectors of the USA and four of the UK over the last 40 years. However, recent investigations on the spread–real activity relation have questioned both its linear nature and its time‐invariant framework. Our in‐sample empirical evidence suggests that the spread–real activity relationship exhibits asymmetries that allow for different predictive power of the spread when past spread values were above or below some threshold value. We then measure the out‐of‐sample forecast performance of the nonlinear model using predictive accuracy tests. The results show that significant improvement in forecasting accuracy, at least for one‐step‐ahead forecasts, can be obtained over the linear model. Copyright © 2004 John Wiley & Sons, Ltd.     

Is the process of localized lysosomal exocytosis responsible for the cytolytic action of killer T-lymphocytes?]

In this paper, we formulate the hypothesis that in the process of target cell lysis a lysosomal enzyme regurgitation, performed by killer cells at the level of the target effector junction, accounts for the target lesion which precedes the lysis (lethal hit). This process of exocytosis, similar to the one described previously in polymorphonuclear neutrophils is supported by cytological studies performed directly on identified killers isolated by micromanipulation. Light and electron microscopy observations confirm a previous report which describes the effector cells rich in lysosomal bodies. In addition, when a killer cell is associated with a target cell to form a conjugate, lysosomes are concentrated near the cell junction and, after incubation at 37 degrees C, acid phosphatases may be detected at the junction. Lysosomal enzyme exocytosis explains why target lysis needs an effector target binding to occur and also the other conditions required for any exocytosis process such as Ca++ in the medium, integrity of the microtubular apparatus, a low level of cyclic AMP and energy dependancy.     

Odontogenesis, organogenetic model in teratomas: crown formation]

Using the technique of 3 dimensional reconstruction, the various steps involved in the formation and growth of the crown of a tooth primordium observed in a complex ovarian teratoma have been compared with that occurring in dermoid cysts and in the normal dental system. Inside dermoid cysts, the characteristic form of the tooth is established during the production of the dentine and enamel and the process is often similar to that occurring during normal tooth development. In teratomas, however, organogenesis and morphogenesis take place within a system undergoing multidirectional development. They are dissociated during both the embryonic stage and that of a structural formation. Morphogenesis is the most disturbed and the role of the environment is presumably therefore very important.