Akt Activation Emulates Chk1 Inhibition and Bcl2 Overexpression and Abrogates G2 Cell Cycle Checkpoint by Inhibiting BRCA1 Foci

Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage.     

Three-dimensional structure of unstained, frozen-hydrated extended tails of bacteriophage T4

Unsupported, unstained frozen-hydrated extended tails of bacteriophage T4 have been studied by cryo-electron microscopy. Their three-dimensional structure has been reconstructed after correlation and averaging of the information from different particles. While the reconstructions of hydrated tails show all the features found by conventional electron microscopy, they are characterized by an open structure. Individual subunits constituting the axial repeat cannot be outlined unambiguously, as the density connectivity is sensitive to the phase-contrast transfer function effects. In order to minimize these effects, we found that the best data set for three-dimensional reconstruction is composed of layer-lines corrected for the phase-contrast transfer function and an uncorrected equator.     

THE HORMONAL INTEGRATION OF SEXUAL REPRODUCTION IN OEDOGONIUM

Rawitscher -Kunkel , Erika , and L. Machlis . (U. California, Berkeley.) The hormonal integration of sexual reproduction in Oedogonium. Amer. Jour. Bot. 49 (2) : 177–183. Illus. 1962.—Sexual reproduction in a heterothallic, nannandrous species of Oedogonium was investigated cytologically and physiologically. Several new observations are reported. Oogonial mother cells release a substance which attracts androspores to them. The androspores, when attached to the oogonial mother cells, grow in well-defined directions apparently in response to a hormone originating in the oogonial mother cells. An oogonial mother cell divides into an oogonium and a suffultory cell only after the attached androspores complete their development into dwarf males, each bearing an antheridium. Presumably the developing dwarf males provide a chemical stimulus for the division of the oogonial mother cell. During development, the oogonia become enveloped in a massive gel which also encases the antheridia cut off at the apical ends of the dwarf male plants. The gel appears to function as a sperm trap, preventing the dissemination of the sperm into the surrounding liquid. The sperm are attracted to the protoplasmic papilla which briefly protrudes through the oogonial pore indicating the operation of a second chemotactic agent.     

Understanding Performance Degradation in Cation‐Disordered Rock‐Salt Oxide Cathodes

The collective redox activities of transition‐metal (TM) cations and oxygen anions have been shown to increase charge storage capacity in both Li‐rich layered and cation‐disordered rock‐salt cathodes. Repeated cycling involving anionic redox is known to trigger TM migration and phase transformation in layered Li‐ and Mn‐rich (LMR) oxides, however, detailed mechanistic understanding on the recently discovered Li‐rich rock‐salt cathodes is largely missing. The present study systematically investigates the effect of oxygen redox on a Li_1.3Nb_0.3Mn_0.4O₂ cathode and demonstrates that performance deterioration is directly correlated to the extent of oxygen redox. It is shown that voltage fade and hysteresis begin only after initiating anionic redox at high voltages, which grows progressively with either deeper oxidation of oxygen at higher potential or extended cycling. In contrast to what is reported on layered LMR oxides, extensive TM reduction is observed but phase transition is not detected in the cycled oxide. A densification/degradation mechanism is proposed accordingly which elucidates how a unique combination of extensive chemical reduction of TM and reduced quality of the Li percolation network in cation‐disordered rock‐salts can lead to performance degradation in these newer cathodes with 3D Li migration pathways. Design strategies to achieve balanced capacity and stability are also discussed.     

Testing for Validity and Reliability in Cross-Cultural Research

A set of procedures is offered for assessing interraler reliability and certain aspects of validity of codes in cross-cultural studies. The method assumes that at least two independent raters have coded more than one trait. Each trait coded by one rater is correlated with each trait coded by a second, and all the codings by a single rater are intercorrelated with each other. The results are presented in a multitrait-multi-rater matrix. From this matrix it is possible to determine the interrater reliability and discriminant validity of trails in addition to a higher order concept based on pairs of traits.     

A severe autosomal recessive acromesomelic dysplasia,the Hunter-Thompson type,and comparison with the Grebe type

Summary Two siblings with a short-limb dwarfing condition which we call acromesomelic dysplasia, Hunter-Thompson type are reported. Abnormalities are limited to the limbs and limb joints in this severe form of dwarfism. The middle and distal segments of the limbs are most affected. The lower limbs are more affected than the upper. We are aware of one previously published case of this entity reported by A. G. W. Hunter and M. W. Thompson in 1976. Dislocations of the elbows and ankles were present in all three patients and dislocations of the hips and knees in two. One of the siblings who did not have hip and knee dislocations clinically resembled Grebe chondrodysplasia, another severe acromesomelic dwarfing condition. However, radiological analysis suggests that while acromesomelic dysplasia, Hunter-Thompson type and Grebe chondrodysplasia are related, they are not identical. Grebe chondrodysplasia has been established as an autosomal recessive trait. It appears probable that the entity we describe has the same mode of genetic transmission.