Modulation of globin gene expression by a tumor promoter during induced differentiation of Friend erythroleukemic cells

Friend erythroleukemic cells were induced to differentiate by dimethylsulfoxide (Me2SO) in the absence or presence of the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate. The effects of the latter on the molecular parameters related to globin mRNA metabolism were examined. When differentiation was scored by benzidine staining, it had an inhibitory effect on Me2SO-treated cells. On the other hand, when differentiation was followed by determination of globin mRNA accumulation, it had a pleiotropic effect on Me2SO-treated cells. At the early phase of differentiation (2--3 days) the rate of globin mRNA accumulation was higher in the promoter-treated cells than in the control. This unexpectedly high level of accumulation was followed by a sharp reduction and most of the globin RNA sequences disappeared at later stages of differentiation (days 4--5). The reduction can be related to the effect of the promoter on the stability of globin RNA in the cytoplasm which was reduced from a half-life of 16 h to that of 8 h only. Other parameters, such as the rate of globin mRNA synthesis and its capability to serve as a template for cell-free protein synthesis were not affected by treatment with the promoter throughout the differentiation process.     

View from the top: hierarchies and reverse hierarchies in the visual system

We propose that explicit vision advances in reverse hierarchical direction, as shown for perceptual learning. Processing along the feedforward hierarchy of areas, leading to increasingly complex representations, is automatic and implicit, while conscious perception begins at the hierarchy's top, gradually returning downward as needed. Thus, our initial conscious percept--vision at a glance--matches a high-level, generalized, categorical scene interpretation, identifying "forest before trees." For later vision with scrutiny, reverse hierarchy routines focus attention to specific, active, low-level units, incorporating into conscious perception detailed information available there. Reverse Hierarchy Theory dissociates between early explicit perception and implicit low-level vision, explaining a variety of phenomena. Feature search "pop-out" is attributed to high areas, where large receptive fields underlie spread attention detecting categorical differences. Search for conjunctions or fine discriminations depends on reentry to low-level specific receptive fields using serial focused attention, consistent with recently reported primary visual cortex effects.     

Zero-crossing detectors in primary visual cortex?

David Marr and others have hypothesized that the visual system processes complex scene information in stages, the first of which involves the detection of light intensity edges or zero-crossings (Marr, 1982). Ideal zero-crossing detector mechanisms have been described and modeled in terms of their possible physiological implementation (Marr and Hildreth, 1980; Poggio, 1983). We now present evidence of visual cortical receptive fields which resemble in spatial organizational terms the requirements of zero-crossing analysis. The linear and nonlinear summation within and between the receptive field subunits are described and compared with predicted processes. The relative subunit sizes and separations are analyzed in these terms. Our findings support the notion that receptive fields may correspond with zero-crossing filters rather than zero-crossing detector gates.     

Effects of cyclic GMP on the kinetics of the photocurrent in rods and in detached rod outer segments

We investigated the effects of high concentrations of cytoplasmic cyclic GMP on the photocurrent kinetics and light sensitivity of the tiger salamander rod both in intact cells and in detached outer segments. Photoreceptors were internally perfused with cGMP by applying patch pipettes containing cGMP to the inner or outer segment. Large increases in the concentration of cGMP in the outer segment cytoplasm were achieved only when the patch pipette was applied directly to the outer segment. The dark-current amplitude increased with increasing cGMP concentrations up to approximately 1,400 pA. Internal perfusion with 5.0 mM cGMP introduced a delay of 1-3 s in the photocurrent. The magnitude of the delay was inversely proportional to the light intensity. In addition, the photocurrent time course was slowed down and the light sensitivity, measured 1 s after the flash, was decreased approximately 100-fold when compared with that of the intact cell. The observed effects of cGMP were compared with those predicted by a model that assumes that the initial photocurrent time course is determined by the kinetics of the light-activated phosphodiesterase (PDE) and the cGMP dependence of the light-sensitive channels. At high concentrations of cGMP, the experimental data were similar to those predicted by the model and based on the known biochemical properties of the light-activated PDE and cGMP-activated channels.     

Drosophila EGFR signalling is modulated by differential compartmentalization of Rhomboid intramembrane proteases

We explore the role of differential compartmentalization of Rhomboid (Rho) proteases that process the Drosophila EGF receptor ligands, in modulating the amount of secreted ligand and consequently the level of EGF receptor (EGFR) activation. The mSpitz ligand precursor is retained in the ER, and is trafficked by the chaperone Star to a late compartment of the secretory pathway, where Rho-1 resides. This work demonstrates that two other Rho proteins, Rho-2 and Rho-3, which are expressed in the germ line and in the developing eye, respectively, cleave the Spitz precursor and Star already in the ER, in addition to their activity in the late compartment. This property attenuates EGFR activation, primarily by compromising the amount of chaperone that can productively traffic the ligand precursor to the late compartment, where cleavage and subsequent secretion take place. These observations identify changes in intracellular compartment localization of Rho proteins as a basis for signal attenuation, in tissues where EGFR activation must be highly restricted in space and time.