Minimal Resection Takes Place during Break-Induced Replication Repair of Collapsed Replication Forks and Is Controlled by Strand Invasion

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Characterization of the iron-sulfur protein of the mitochondrial outer membrane partially purified from beef kidney cortex

The iron-sulfur protein present in the mitochondrial outer membrane has been partially purified from beef kidney cortex mitochondria be means of selective solubilization followed by DEAE-cellulose chromatography. The EPR spectrum of the iron-sulfur protein with g-values at 2.01, 1.94 and 1.89 was well resolved up to 200 K which is unusual for an iron-sulfur protein. Analyses confirmed a center with two iron and two labile sulfur atoms in the protein. By measuring the effect of oxidation-reduction potential on the EPR signal amplitude, midpoint potentials at pH 7.2 were determined both for the purified ironsulfur protein, +75 (±5) mV, and in prepared mitochondrial outer membrane, +62 (±6) mV. At pH 8.2 slightly lower values were indicated, +62 and 52 mV, respectively. The oxidation-reduction equilibrium involved a one electron transfer. A functional relationship to the rotenone-insensitive NADH-cytochrome c oxidoreductase in the mitochondrial outer membrane is suggested. Both this activity and the iron-sulfur center were sensitive to acidities slightly below pH 7 in contrast to the iron-sulfur centers of the inner membrane.     

Traveling Companions Add Complexity and Hinder Performance in the Spatial Behavior of Rats

We sought to uncover the impact of the social environment on the spatial behavior of rats. Food-deprived rats were trained in a spatial task of collecting food items from 16 equispaced objects. Following training, they were tested, first alone and then with a similarly-trained cage-mate. It was found that the presence of another rat substantially altered the rats'' spatial behavior. Lone rats collected the food items faster while traveling a shorter distance, reflecting a higher efficiency of task completion. When accompanied by a partner, however, the rats traveled together, visiting the same set of objects in each trip with one of them leading. Whether alone or with a partner, rats continued to revisit the same objects; however, more such revisits occurred with a partner. We argue that revisiting objects is not necessarily an error, since returning to past places is an important aspect of rats’ natural behavior. Revisiting an object following food depletion implies that searching for food was not the main driving force in the rats'' spatial behavior. Specifically, despite food deprivation, rats were more attentive to one another than to the food. This could be adaptive, since foraging and feeding in groups is a way of poison avoidance in wild rats. Finally, the addition of a social component added complexity to the environment since the rats organized their spatial behavior in reference to one another in addition to their organization in the physical surrounding. Consequently, when tested with a partner, spatial behavior was less structured, less predictable and more chaotic.     

Fatty acid starvation activates RelA by depleting lysine precursor pyruvate

Bacteria undergoing nutrient starvation induce the ubiquitous stringent response, resulting in gross physiological changes that reprograms cell metabolism from fast to slow growth. The stringent response is mediated by the secondary messengers pppGpp and ppGpp collectively referred to as (p)ppGpp or ‘alarmone’. In Escherichia coli, two paralogs, RelA and SpoT, synthesize (p)ppGpp. RelA is activated by amino acid starvation, whereas SpoT, which can also degrade (p)ppGpp, responds to fatty acid (FA), carbon and phosphate starvation. Here, we discover that FA starvation leads to rapid activation of RelA and reveal the underlying mechanism. We show that FA starvation leads to depletion of lysine that, in turn, leads to the accumulation of uncharged tRNA^Lys and activation of RelA. SpoT was also activated by FA starvation but to a lower level and with a delayed kinetics. Next, we discovered that pyruvate, a precursor of lysine, is depleted by FA starvation. We also propose a mechanism that explains how FA starvation leads to pyruvate depletion. Together our results raise the possibility that RelA may be a major player under many starvation conditions previously thought to depend principally on SpoT. Interestingly, FA starvation provoked a ~100‐fold increase in relA dependent ampicillin tolerance.     

Amino acid content of leguminous proteins as affected by genetic and nutritional factors. I.

Summary Tetraploid and diploid red clover have been cultivated in greenhouse under aseptic conditions. The plant cultures were given only one source of nitrogen: either they were given nitrate in the nutrient solution or they were inoculated withRhizobium for establishing symbiotic fixation.The amino acid composition of protein from the different series and from different parts of the plants was analysed by paper chromatography.There was a clear arginine reaction from the tetraploid clover material but no arginine at all was found in the diploid clover material.Plants fed on nitrate and those fed on symbiotically fixed nitrogen showed the same amino acid pattern as far as can be judged from the chromatograms. The hydrolysates from inoculated plants showed usually more intense ninhydrine reaction on the chromatograms than hydrolysates from not inoculated plants, although diluted to the same nitrogen content. For this fact we have so far no explanation.     

Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans

Aims

A study of 222 candidate genes in type 2 diabetes reported association of variants in RAPGEF1, ENPP1, TP53, NRF1, SLC2A2, SLC2A4 and FOXC2 with type 2 diabetes in 4,805 Finnish individuals. We aimed to replicate these associations in a Danish case-control study and to substantiate any replicated associations in meta-analyses. Furthermore, we evaluated the impact on diabetes-related intermediate traits in a population-based sample of middle-aged Danes.

Methods

We genotyped nine lead variants in the seven genes in 4,973 glucose-tolerant and 3,612 type 2 diabetes Danish individuals. In meta-analyses we combined case-control data from the DIAGRAM+ Consortium (n = 47,117) and the present genotyping results. The quantitative trait studies involved 5,882 treatment-naive individuals from the Danish Inter99 study.

Results

None of the nine investigated variants were significantly associated with type 2 diabetes in the Danish samples. However, for all nine variants the estimate of increase in type 2 diabetes risk was observed for the same allele as previously reported. In a meta-analysis of published and online data including 55,521 Europeans the G-allele of rs1042522 in TP53 showed significant association with type 2 diabetes (OR = 1.06 95% CI 1.02–1.11, p = 0.0032). No substantial associations with diabetes-related intermediary phenotypes were found.

Conclusion

The G-allele of TP53 rs1042522 is associated with an increased prevalence of type 2 diabetes in a combined analysis of 55,521 Europeans.