A Sir2-Like Protein Participates in Mycobacterial NHEJ

In eukaryotic cells, repair of DNA double-strand breaks (DSBs) by the nonhomologous end-joining (NHEJ) pathway is critical for genome stability. In contrast to the complex eukaryotic repair system, bacterial NHEJ apparatus consists of only two proteins, Ku and a multifunctional DNA ligase (LigD), whose functional mechanism has not been fully clarified. We show here for the first time that Sir2 is involved in the mycobacterial NHEJ repair pathway. Here, using tandem affinity purification (TAP) screening, we have identified an NAD-dependent deacetylase in mycobacteria which is a homologue of the eukaryotic Sir2 protein and interacts directly with Ku. Results from an in vitro glutathione S-transferase (GST) pull-down assay suggest that Sir2 interacts directly with LigD. Plasmid-based end-joining assays revealed that the efficiency of DSB repair in a sir2 deletion mutant was reduced 2-fold. Moreover, the Δsir2 strain was about 10-fold more sensitive to ionizing radiation (IR) in the stationary phase than the wild-type. Our results suggest that Sir2 may function closely together with Ku and LigD in the nonhomologous end-joining pathway in mycobacteria

The effects of object size on spatial orientation: an eye movement study

IntroductionThe processing of visual information in the human brain is divided into two streams, namely, the dorsal and ventral streams, object identification is related to the ventral stream and motion processing is related to the dorsal stream. Object identification is interconnected with motion processing, object size was found to affect the information processing of motion characteristics in uniform linear motion. However, whether the object size affects the spatial orientation is still unknown.MethodsThirty-eight college students were recruited to participate in an experiment based on the spatial visualization dynamic test. Eyelink 1,000 Plus was used to collect eye movement data. The final direction difference (the difference between the final moving direction of the target and the final direction of the moving target pointing to the destination point), rotation angle (the rotation angle of the knob from the start of the target movement to the moment of key pressing) and eye movement indices under conditions of different object sizes and motion velocities were compared.ResultsThe final direction difference and rotation angle under the condition of a 2.29°-diameter moving target and a 0.76°-diameter destination point were significantly smaller than those under the other conditions (a 0.76°-diameter moving target and a 0.76°-diameter destination point; a 0.76°-diameter moving target and a 2.29°-diameter destination point). The average pupil size under the condition of a 2.29°-diameter moving target and a 0.76°-diameter destination point was significantly larger than the average pupil size under other conditions (a 0.76°-diameter moving target and a 0.76°-diameter destination point; a 0.76°-diameter moving target and a 2.29°-diameter destination point).DiscussionA relatively large moving target can resist the landmark attraction effect in spatial orientation, and the influence of object size on spatial orientation may originate from differences in cognitive resource consumption. The present study enriches the interaction theory of the processing of object characteristics and motion characteristics and provides new ideas for the application of eye movement technology in the examination of spatial orientation ability

Zipf's Law in Importance of Genes for Cancer Classification Using Microarray Data

Microarray data consists of mRNA expression levels of thousands of genes under certain conditions. A difference in the expression level of a gene at two different conditions/phenotypes, such as cancerous versus non-cancerous, one subtype of cancer versus another, before versus after a drug treatment, is indicative of the relevance of that gene to the difference of the high-level phenotype. Each gene can be ranked by its ability to distinguish the two conditions. We study how the single-gene classification ability decreases with its rank (a Zipf's plot). Power-law function in the Zipf's plot is observed for the four microarray datasets obtained from various cancer studies. This power-law behavior in the Zipf's plot is reminiscent of similar power-law curves in other natural and social phenomena (Zipf's law). However, due to our choice of the measure of importance in classification ability, i.e., the maximized likelihood in a logistic regression, the exponent of the power-law function is a function of the sample size, instead of a fixed value close to 1 for a typical example of Zipf's law. The presence of this power-law behavior is important for deciding the number of genes to be used for a discriminant microarray data analysis.Comment: 11 pages, 5 figures. submitte

Friendly P2P: Application-level Congestion Control for Peer-to-Peer Applications

International audiencePeer-to-Peer (P2P) file sharing applications use multiple TCP connections between peers to transfer data. The aggressiveness and robustness of P2P technology remarkably improve transfer efficiency and network bandwidth utilization. However, while the network bottleneck link is congested, P2P applications tend to unfairly steal bandwidth from other traditional Internet applications (Client/Server mode), which deteriorates the performance of traditional Internet applications. The paper proposes a friendlyP2P system with new application-level approaches for congestion detection and avoidance to keep fairness between P2P traffic and traditional Internet traffic. friendlyP2P, which is friendly to ISPs, namely to Internet networks and traditional Internet traffic, detects network congestion via throughput measurements and alleviates network congestion by optimization of the number of P2P connections from the viewpoint of P2P users. friendlyP2P system requires neither network node support nor TCP modification, which makes it easy to deploy. Simulation experiments demonstrate that fairness and congestion avoidance can be achieved in presence of congestion, and network bandwidth can be effectively utilized in absence of congestion with friendlyP2P technology

Cytotoxic and antibacterial polyketide-indole hybrids synthesized from indole-3-carbinol by Daldinia eschscholzii

Two skeletally undescribed polyketide-indole hybrids (PIHs), named indolchromins A and B, were generated from indole-3-carbinol (I3C) in the fungal culture (Daldinia eschscholzii). The indolchromin structures were elucidated mainly by their 1D and 2D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism (CD) spectra with the electronic CD (ECD) curves computed for all optional stereoisomers. Furthermore, the indolchromin construction pathways in fungal culture were clarified through enzyme inhibition, precursor feeding experiment, and energy calculation. The cascade reactions, including decarboxylative Claisen condensation catalyzed by 8-amino-7-oxononanoate synthase (AONS), C(sp3)-H activation, double bond migration, and Michael addition, all undergone compatibly during the fungal cultivation. In an MIC range of 1.3–8.6 μmol/L, (2S,4R)- and (2R,4S)-indolchromin A and (2R,4S)-indolchromin B are inhibitory against Clostridium perfringens, Clostridium difficile, Veillonella sp., Bacteroides fragilis, and Streptococcus pyogenes. (2R,4S)-Indolchromin A and (2S,4S)-indolchromin B were cytotoxic against the human breast cancer cell line MDA-MB-231 with IC50 values of 27.9 and 131.2 nmol/L, respectively, with the former additionally active against another human breast cancer cell line MCF-7 (IC50 94.4 nmol/L). KEY WORDS: Polyketide-indole hybrids, Indole-3-carbinol, Daldinia eschscholzii, 8-Amino-7-oxononanoate synthase, Decarboxylative Claisen condensation, Antibacterial, Anticance