DNA curving and bending in protein–DNA recognition

Most biological events are regulated at the molecular level by site-specific associations between specialized proteins and DNA. These associations may bring distal regions of the genome into functional contact or may lead to the formation of large multisubunit complexes capable of regulating highly site-specific transactional events. It is now believed that sequence-specific protein-DNA recognition and the ability of certain proteins to compete for multiple binding sites is regulated at several levels by the local structure and conformation of the binding partners. These encompass the microstructure of DNA, including its curvature, bending and flexing as well as conformational lability in the DNA-binding domains of the proteins. Possible mechanisms for binding specificity are discussed in the context of specific nucleoprotein systems with particular emphasis given to the roles of DNA conformations in these interactions.     

Cyclic AMP-Dependent Melatonin Production in Y79 Human Retinoblastoma Cells

Abstract: Melatonin is rhythmically synthesized in some vertebrate retinas and has been implicated in the regulation of key rhythmic events in the photoreceptor-pigment epithelial complex. In human retina, melatonin is present; however, no information exists on the cellular regulation of this hormone. We report here that the established human retinoblastoma cell line Y79 synthesizes and releases melatonin. Treatments that elevate cyclic AMP (cAMP) levels (forskolin, 8-Br-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1 -meth-ylxanthine) all stimulate melatonin release from static cultures of Y79 cells. Other 8-bromo nucleotide analogues (cyclic GMP, ATP, and AMP) are not effective. These results suggest that Y79 human retinoblastoma cells require a cAMP-dependent mechanism for melatonin biosynthesis similar to that described previously in other vertebrates. This is the first demonstration of melatonin release from a cultured human cell line. These results support the idea that human retinal cells share homologies with pineal cells, as suggested by the condition trilateral retinoblastoma.     

Responses of Lemur fulvus to Scents of Different Subspecies of L. fulvus and to Scents of Different Species of Lemuriformes

Captive Lemur fulvus were presented with scents of their own subspecies, scents of other subspecies of L. fulvus, and scents of other species of sympatric Lemuriformes. The results suggest that L. fulvus do not distinguish between scents of different subspecies of L. fulvus, and that they do distinguish between scents of their own species and other sympatric species of Lemuriformes.     

Redox reagents and divalent cations alter the kinetics of cystic fibrosis transmembrane conductance regulator channel gating.

Gating of the cystic fibrosis Cl(-) channel requires hydrolysis of ATP by its nucleotide binding folds, but how this process controls the kinetics of channel gating is poorly understood. In the present work we show that the kinetics of channel gating and presumably the rate of ATP hydrolysis depends on the species of divalent cation present and the oxidation state of the protein. With Ca(2+) as the dominant divalent cation instead of Mg(2+), the open burst duration of the channel is increased approximately 20-fold, and this change is reversible upon washout of Ca(2+). In contrast, "soft" divalent cations such as Cd(2+) interact covalently with cystic fibrosis transmembrane conductance regulator (CFTR). These metals decrease both opening and closing rates of the channel, and the effects are not reversed by washout. Oxidation of CFTR channels with a variety of oxidants resulted in a similar slowing of channel gating. In contrast, reducing agents had the opposite effect, increasing both opening and closing rates of the channel. In cell-attached patches, CFTR channels exhibit both oxidized and reduced types of gating, raising the possibility that regulation of the redox state of the channel may be a physiological mode of control of CFTR channel activity.     

Urea-induced structural changes in chromatin obtained by sedimentation.

Sedimentation coefficients have been determined for fractionated preparations of whole and stripped (depleted of very lysine-rich histones and non-histone proteins) chicken erythrocyte chromatin fragments in 0-10 M urea. Significant differences in urea effects are observed between these preparations; differences which can be interpreted structurally by use of Kirkwood's dynamical theory of the translational frictional coefficient. This type of analysis implies that urea-induced chain-swelling in stripped chromatin is due largely to the urea effect upon the constituent nu-bodies, whereas the much larger swelling observed in whole chromatin appears to involve also the effect of urea upon the region between adjacent nu-bodies.     

INTERDEPENDENT SUPERIORITY AND INFERIORITY FEELINGS

It is postulated that in neurotic persons who have unrealistic feelings of superiority and inferiority the two are interdependent. This is a departure from the concept of previous observers that either one or the other is primary and its opposite is overcompensation. The author postulates considerable parallelism, with equal importance for each. He submits that the neurotic person forms two logic-resistant compartments for the two opposed self-estimates and that treatment which makes inroads of logic upon one compartment, simultaneously does so upon the other. Two examples are briefly reported.The neurotic benefits sought in exaggeration of capability are the same as those sought in insistence upon inferiority: Presumption of superiority at once bids for approbation and delivers the subject from the need to prove himself worthy of it in dreaded competition; exaggeration of incapability baits sympathy and makes competition unnecessary because failure is conceded.Some of the characteristics of abnormal self-estimates that distinguish them from normal are: Preoccupation with self, resistance to logical explanation of personality problems, inconsistency in reasons for beliefs in adequacy on the one hand and inadequacy on the other, unreality, rationalization of faults, and difficulty and vacillation in the selection of adequate goals.