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The Rybp protein has been promoted as a Polycomb group (PcG)-associated protein, but its molecular function has remained elusive. Here we show that Rybp is a novel ubiquitin binding protein and is itself ubiquitinated. The Rybp interacting PcG protein Ring1B, a known ubiquitin E3 ligase, promotes Rybp ubiquitination. Moreover, one target of Rybp’s ubiquitin binding domain appears to be ubiquitinated histone H2A; this histone is a substrate for Ring1B’s E3 ligase activity in association with gene silencing processes. These findings on Rybp provide a further link between the ubiquitination system and PcG transcriptional repressors.

The Ccr4-Not complex is a highly conserved regulator of mRNA metabolism. The transcription regulatory function of this complex in higher eukaryotes, however, is largely unexplored. Here we report that CNOT1, the large human subunit, represses the ligand-dependent transcriptional activation function of oestrogen receptor (ER) alpha. Promoter recruitment assays indicate that CNOT1 contains an intrinsic ability to mediate transcriptional repression. Furthermore, CNOT1 can interact with the ligand-binding domain of ERalpha in a hormone-dependent fashion and is recruited with other Ccr4-Not subunits to endogenous oestrogen-regulated promoters dependent on the presence of ligand. In addition, siRNA-mediated depletion of endogenous CNOT1 or other Ccr4-Not subunits in breast cancer cells results in deregulation of ERalpha target genes. Finally, CNOT1 interacts in a ligand-dependent manner with RXR and represses transcription mediated by several RXR heterodimers. These findings define a function for the human Ccr4-Not complex as a transcriptional repressor of nuclear receptor signalling that is relevant for the understanding of molecular pathways involved in cancer.

The effects of ligands on the irreversible inhibition of the NAD+-dependent isocitrate dehydrogenase from ox brain were studied. Isocitrate in the presence of Mg2+ ions was found to protect against denaturation at 40 degrees C and this protection was enhanced by ADP which also protected on its own. None of the substrates or the activator ADP afforded protection against inhibition by diethylpyrocarbonate. Inactivation by this compound and by elevated temperatures did not obey first-order kinetics with respect to time. Inhibition by iodoacetate appeared to obey first-order kinetics both with respect to time and to inhibitor concentration. Protection against inhibition was afforded by isocitrate, NAD+ and ADP. The dependence of the extent of protection on the concentration of the magnesium-isocitrate complex was sigmoid at both pH 6.5 and pH 7.5 indicating the apparent homotropic cooperativity seen in initial-rate kinetic experiments to be a reflection of cooperative binding of this substrate. ADP reduced the affinity of the enzyme for this substrate without affecting the degree of this cooperativity. The dependence of the extent of protection by ADP upon its concentration obeyed Michaelis-Menten kinetics. The significance of these observations in terms of the kinetic and allosteric mechanism followed by this enzyme is discussed in the light of previous kinetic studies.

Item does not contain fulltext Research on the role of the nucleus accumbens in behaviour has been largely focused on the functions of this structure in conditioning to appetitive stimuli. It has been suggested that a network comprising the nucleus accumbens and its convergent inputs might mediate dissociable functions in the acquisition, the consolidation and the retrieval of information. However, findings related to a role of this structure in aversive conditioning are somewhat contradictory, and its involvement in this form of learning is still under debate. Moreover, very little evidence is available on the step of information processing mediated by the accumbens. Thus the purpose of this study was to investigate the effects of the blockade of the AMPA and NMDA glutamate receptors, which have been suggested to mediate the transmission of information from the limbic system to this structure, on a classical aversive conditioning task - the one-trial step through inhibitory avoidance paradigm (24 h interval between training and testing). Intra-accumbens focal injections of AP-5 and DNQX (NMDA and AMPA antagonists, respectively) were performed immediately after training, before training and before testing in mice. The NMDA antagonist (37.5, 75 and 150 ng per side) impaired animal performance only if administered immediately after but not before training or before testing. Conversely, DNQX (0.5, 1.0 and 5.0 ng per side) reduced the step through latencies when administered before training and before testing. These findings suggest that NMDA receptor activation within the accumbens is necessary in formation but not expression of memory for inhibitory avoidance. AMPA receptors, instead, are necessary for the acquisition and the expression but not consolidation of inhibitory avoidance memory.

This investigation focuses on cultural differences in the relationship between maternal sen- sitivity, emotional expression, and control strategies during the first year of life and infant attachment outcomes at 12 months. Participants were middle-class Puerto Rican and Anglo mother-infant pairs . Ratings of physical control, emotional expression, and maternal sensitivity during mother- (N 60) infant interactions in five everyday home settings, videotaped when the infants were 4, 8, and 12 months old, were examined in combination with 12-month Strange Situation classifications. Results suggest that physical control shows a different pattern of relatedness to maternal sensitivity, emotional expression, and attachment outcomes among the Puerto Rican compared to the Anglo mothers in this study. These findings have implications for practitioners and researchers interested in normative parenting among diverse cultural groups. RESUMEN: Esta investigacion se enfoca en las diferencias culturales en la relacion entre la sensibilidad materna, la expresion emocional y las estrategias de control durante el primer ano de vida y los resultados de la afectividad del infante a los 12 meses. En el estudio participaron 60 pares de madres-infantes de origen puertorriqueno y anglosajon. Los puntajes de control fisico, expresion emocional y sensibilidad materna, durante las interacciones entre la madre y su infante en cinco situaciones caseras de cada dia, grabadas en video cuando los infantes tenian 4, 8y1 2meses de nacidos, fueron examinados en combinacion con las clasificaciones de la "Situacion Extrana" a los doce meses. Los resultados indican que el control fisico muestra un patron diferente de relacion en cuanto a la sensibilidad materna, a la expresion emocional, y

Both internal and external factors help to determine the personality of the African American family. Personality traits of the African American family include adherence to historical values, diversity in family structure, and family communication. A review of the history of the African American family from its African roots to contemporary America is presented here.

This article presents a study on the formation of anisometric, ellipsoidal supraparticles by evaporation-induced self-assembly from multicomponent colloidal dispersion droplets deposited on a superhydrophobic surface. Performing the formation process on bent surface substrates grants precise control on the shape and spatial orientation of the final dried supraparticles. Due to the V-shaped surfaces providing interfacial blockage, anisotropic evaporation rates occur with respect to the direction of the bending channel. This proportionally leads to inhomogeneous accumulation of fumed silica (FS), used as structure guiding component. Thus, upon the increase of FS-particle interaction via ionic strength (NaCl), this so-formed shell provides enough anisotropic stiffness resulting in predictable droplet deformation with the elongation orientation being perpendicular to the bending axis. The anisotropic evaporation rates were monitored and quantified using an established, empiric kinetic model and taking into account surface geometry. Employing this reliable control of elongation direction and using additional Fe3O4@SiO2 core–shell nanoparticles, anisometric magnetic Janus supraparticles with defined patch position were prepared, which are not accessible on flat surfaces. The results can find application in the controlled, easy to scale up, nanofabrication process of patchy anisometric supraparticles.

Infusion of the abdominal aorta with pancreatic elastase induces aneurysms in a rat model (Anidjar/Dobrin). Because elastolysis liberates elastin degradation products (EDPs), the present experiment was carried out to test the hypothesis that an EDP alone could induce features of aneurysm disease.The EDP val/gly/val/ala/pro/gly (VGVAPG), elastase, or saline solution was infused into infrarenal aorta (n = 4/group). After 1 week aortic diameters were measured, and the tissues were prepared for histologic examination. Adventitial capillaries (vessels per high-power field) were counted over a standardized preparation of aorta. Wall thickness was measured by means of computer-aided planimetry.There was an increase of greater than 100-fold in mean vessels per high-power field in aortas receiving VGVAPG or elastase versus saline controls (4.10 +/- 0.68 SEM or 4.48 +/- 0.49 SEM versus 0.03 +/- 0.03 SEM, respectively, p0.05). The VGVAPG-perfused group had a 26% +/- 4% SEM increase in diameter from baseline that was statistically significant (p0.01), but the aortas did not reach aneurysmal dimensions.Although no aneurysms occurred at 1 week after the infusion of EDP, the results demonstrate that the EDP VGVAPG can induce a characteristic feature of aneurysm disease. The model permits study of the earliest stages of experimental aneurysm formation and raises interesting questions regarding the role of the vasa vasorum in this pathologic process.

A new, high throughput, low cost process for the manufacture of PDP barrier ribs — Foam Glass Barrier™ — is described. The new barrier rib is a vitreous glass containing a uniform distribution of small, closed bubbles which chemically etches at high rates anisotropically, has high strength and does not outgas.

The sigmoid dependence of the initial rate of the reaction catalysed by NAD+-dependent isocitrate dehydrogenase on the concentration of isocitrate is greatly reduced as the pH is decreased. The apparent pK for this process is 7.3. At pH values of 6.0 and 6.5 the enzyme exhibits hyperbolic kinetics with respect to isocitrate at relatively high concentrations of NAD+, but the dependence becomes sigmoid at lower NAD+ concentrations. The allosteric activators ADP and citrate have only small effects on the activity of the enzyme at pH 6.5 but in the latter case the effects are increased by decreasing the concentration of NAD+. The dependence of initial velocity on the NAD+ concentration is hyperbolic at all pH values in the pH range 6--8.5. NADH is a competitive inhibitor of enzyme activity with respect to NAD+, and its presence induces a sigmoid dependence of initial velocity on isocitrate concentration at pH 6.5 and in the presence of high concentrations of NAD+. Kinetic studies at pH 6.5 indicate that the apparent maximum velocity of the reaction with respect to NAD+ is insensitive to changes in the isocitrate concentration and that with isocitrate as the substrate is relatively insensitive to changes in the NAD+ concentration under conditions where the behaviour appears to be hyperbolic. threo-Ds-Isocitrate is the true substrate for the enzyme and the corresponding Ls isomer is neither a substrate nor an inhibitor.

Venison from feral red deer has been exported from New Zealand for many years but the farming of red deer as a commercial enterprise is a recent development. Two independent evaluations, one at the Invermay Agricultural Research Centre and the other at the Meat Industry Research Institute of New Zealand, were carried out to compare the eating qualities of venison from the two sources. Venison from young male red deer raised in three environments (feral, grassfed and feedlot) was analysed for palatability differences. A significant variation (P

Summary Material from kudu shot on tsetse control was studied for information on breeding and feeding habits. A number of animals was measured and weighed, illustrating that males were bigger than females. Field observations and stomach contents showed that the species is mainly a browser eating a wide variety of plants. A marked peak of calving was observed and this coincided with the tall grass season (January-April), when the newly-born young are apparently hidden. Kudu in the area studied may be solitary but are generally associated in small groups of about four, although as many as eleven have been seen together in the study area.

This paper reviews reports of windigo psychosis, in particular those cases that are “cured” before they are “full-blown,” with a view to studying evidence of an organic factor related to the development of the illness. Knowledge of biological factors related to ritual behavior in different cultures is reviewed in this context, together with examples of windigo cases and relevant information about nutrition. It is indicated that the traditional “cure” of windigo symptoms, which frequently includes the ingestion of fatty meat, particularly bear meat, indicates a positively reinforced—due to beneficial effect—curing method for this condition. Thus, such an investigation of a widespread way of curing windigo psychosis supplements our analysis of culture with an additional — extracultural — dimension.