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.     

PROTEINS OF AXONAL TRANSPORT: INTERACTION OF RAPIDLY TRANSPORTED PROTEINS WITH LECTINS

Rapidly transported fucose-labelled glycoproteins from the optic system of the rabbit were solubilised with the non-ionic detergent Berol 172. The major labelled components were bound to wheat germ agglutinin or Concanavalin A coupled to Sepharose but not to other lectins or glycoproteins. It was concluded that rapidly transported proteins contain exposed N-acetyl-D-glucosamine     

A note on antibiotic-resistant Escherichia coli in adult man, raw sewage and sewage-polluted River Tigris in Mosul, Nineva

A total of 600 isolates of Escherichia coli were isolated, over a 9 month period during 1984, from healthy human adults, raw sewage and the sewage-polluted River Tigris in Nineva. Over 90% of these organisms were E. coli type 1, but only 8.3% could be serogrouped as enteropathogenic E. coli . Resistance of these organisms to 11 antimicrobial drugs was assessed. Over 40% were antibiotic-resistant and of these 77.1% were resistant to more than one antibiotic. The minimal inhibitory concentration of ampicillin for 193 selected strains from the various sources was determined and ranged from <0.625- > 160 μg/ml. The high incidence of antibiotic-resistant E. coli in this locality and the possible implications to human health are discussed.     

Urine selenium level in healthy adult population

The level of urine selenium in healthy adult population, 230 persons, was examined. Persons were selected regarding sex, ages, and smoking habits. No differences versus these observations have been found. For a total, group values are 16.96 Se nmol/creatinine mmol, SD=5.44. It is possible from a single-void specimen to express daily excretion of selenium.     

Purification and characterization of aquacobalamin reductase (NADPH) from Euglena gracilis

Euglena aquacobalamin reductase (NADPH: EC 1.6.99.-) was purified, and its subcellular distribution was studied to elucidate the mechanism of the conversion of hydroxocobalamin to 5'-deoxyadenosylcobalamin. The enzyme was found in the mitochondria. It was purified about 150-fold over the Euglena mitochondrial extract in a yield of 38%. The purified enzyme was homogeneous in polyacrylamide gel electrophoresis. Spectra of the purified enzyme showed that it was a flavoprotein. The molecular weight of the enzyme was calculated to be 66,000 by Sephadex G-100 gel filtration and 65,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was specific to NADPH with an apparent Km of 43 microM and to hydroxocobalamin with an apparent Km of 55 microM. The enzyme did not require FAD or FMN as a cofactor. The optimum pH and temperature were 7.0 and 40 degrees C, respectively.     

Assignment of the prealbumin (PALB) gene (familial amyloidotic polyneuropathy) to human chromosome region 18q11.2–q12.1

Summary The assignment of the human prealbumin (PALB) gene to chromosome region 18q11–q12.1 has been achieved using a human genomic probe in the study of human-mouse somatic cell hybrids and by in situ hybridization. Because familial amyloidotic polyneuropathy was reported previously to be due to a mutation in prealbumin, it can be inferred that the gene for this disorder also maps to 18q11.2–q12.1.     

The temporal region and the supramastoid ridge in mesolithic skulls from Padina in the Iron Gate Gorge of the Danube

Studies of the morphological features of the temporal region of mesolithic skulls from Padina in the Iron Gate Gorge of the Danube revealed a very prominent and large supramastoid ridge which is the most striking feature in skulls of both sexes. Mastoid processes were larger in male skulls, but in 25% of the cases there was an overlap between the size of the processes in male and female specimens. The mastoid ridge was prominent in both sexes. The digastric fossa was always well defined in both sexes and in the two thirds of the skull specimens it was deep. The posterior root of the zygoma was prominent in all the skulls, but it was better developed in the male specimens. The parietotemporal suture in both sexes rises above the level of the pterion. There were no morphological or anthropometrical differences between the left and the right side of individual skulls outside the limits of natural asymmetry. All these morphological characteristics of the temporal region may help in racial and sexual diagnosis of the Mesolithic skulls from the Iron Gate Gorge.     

Sex differences in the response of rats to drugs affecting GABAergic transmission

The administration of diazepam 1.0 mg/kg decreased the level of plasma corticosterone in female but not in male Wistar rats. Picrotoxin, another drug affecting GABAergic transmission, also brought about an increase of plasma corticosterone in both sexes. However, in order to achieve a plasma corticosterone increase of similar magnitude (more than 500%) a threefold higher dose of picrotoxin had to be given to males. When the convulsive properties of picrotoxin were tested, it became evident that the dose of picrotoxin (2.5 mg/kg) which was subconvulsive in male was almost 100% convulsive in female rats. The existing sex differences in the response of rats to drugs affecting GABAergic transmission might have possible implications in the treatment of GABA system dysfunction.