An assessment of histone-modification antibody quality

We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibodies, more than 20% failed in chromatin immunoprecipitation experiments. We advise rigorous testing of histone-modification antibodies before use, and we provide a website for posting new test results (http://compbio.med.harvard.edu/antibodies/)

An assessment of histone-modification antibody quality

We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibodies, more than 20% failed in chromatin immunoprecipitation experiments. We advise rigorous testing of histone-modification antibodies before use, and we provide a website for posting new test results (http://compbio.med.harvard.edu/antibodies/)

Optimization of Energy-Consuming Pathways towards Rapid Growth in HPV-Transformed Cells

Cancer is a complex, multi-step process characterized by misregulated signal transduction and altered metabolism. Cancer cells divide faster than normal cells and their growth rates have been reported to correlate with increased metabolic flux during cell transformation. Here we report on progressive changes in essential elements of the biochemical network, in an in vitro model of transformation, consisting of primary human keratinocytes, human keratinocytes immortalized by human papillomavirus 16 (HPV16) and passaged repeatedly in vitro, and the extensively-passaged cells subsequently treated with the carcinogen benzo[a]pyrene. We monitored changes in cell growth, cell size and energy metabolism. The more transformed cells were smaller and divided faster, but the cellular energy flux was unchanged. During cell transformation the protein synthesis network contracted, as shown by the reduction in key cap-dependent translation factors. Moreover, there was a progressive shift towards internal ribosome entry site (IRES)-dependent translation. The switch from cap to IRES-dependent translation correlated with progressive activation of c-Src, an activator of AMP-activated protein kinase (AMPK), which controls energy-consuming processes, including protein translation. As cellular protein synthesis is a major energy-consuming process, we propose that the reduction in cell size and protein amount provide energy required for cell survival and proliferation. The cap to IRES-dependent switch seems to be part of a gradual optimization of energy-consuming mechanisms that redirects cellular processes to enhance cell growth, in the course of transformation

Transcriptome-wide discovery of circular RNAs in Archaea

Circular RNA forms had been described in all domains of life. Such RNAs were shown to have diverse biological functions, including roles in the life cycle of viral and viroid genomes, and in maturation of permuted tRNA genes. Despite their potentially important biological roles, discovery of circular RNAs has so far been mostly serendipitous. We have developed circRNA-seq, a combined experimental/computational approach that enriches for circular RNAs and allows profiling their prevalence in a whole-genome, unbiased manner. Application of this approach to the archaeon Sulfolobus solfataricus P2 revealed multiple circular transcripts, a subset of which was further validated independently. The identified circular RNAs included expected forms, such as excised tRNA introns and rRNA processing intermediates, but were also enriched with non-coding RNAs, including C/D box RNAs and RNase P, as well as circular RNAs of unknown function. Many of the identified circles were conserved in Sulfolobus acidocaldarius, further supporting their functional significance. Our results suggest that circular RNAs, and particularly circular non-coding RNAs, are more prevalent in archaea than previously recognized, and might have yet unidentified biological roles. Our study establishes a specific and sensitive approach for identification of circular RNAs using RNA-seq, and can readily be applied to other organisms

Negotiation On Data Allocation in Multi-Agent Environments

We propose a strategic negotiation model that takes into account the passage of time during the negotiation process itself in order to solve the problem of data allocation in environments with self-motivated servers which have no common interest and no central controller. The model considers situations characterized by complete, as well as incomplete, information. Using this negotiation mechanism, the servers have simple and stable negotiation strategies that result in efficient agreements without delays. We provide heuristics for finding the details of the strategies which depend on the specific settings of the environment, and demonstrate the quality of the heuristics, using simulations. We prove that our methods yield better results than the static allocation policy currently used for data allocation for servers in distributed systems. Negotiation is proposed in Distributed Artificial Intelligence (DAI) as a means for agents to communicate and compromise to reach mutually beneficia..

Bidding Mechanisms for Data Allocation in Multi-Agent Environments

. We propose a bidding mechanism for data allocation in environments of self-motivated data servers with no common preferences and no central controller. The model considers situations where each server is concerned with the data stored locally, but does not have preferences concerning the exact storage location of data stored in remote servers. We considered situations of complete, as well as incomplete, information, and formally proved that our method is stable and yields honest bids. In the case of complete information, we also proved that the results obtained by the bidding approach are always better than the results obtained by the static allocation policy currently used for data allocation for servers in distributed systems. In the case of incomplete information, we demonstrated, using simulations, that the quality of the bidding mechanism is, on average, better than that of the static policy. 1 Introduction In this paper, we consider the problem of determining the location of d..

Stable repeated strategies for information exchange between two autonomous agents

AbstractThis paper deals with the problem of designing a strategy profile which will enable collaborative interaction between agents. In particular, we consider the problem of information sharing among agents. Providing information in a single interaction as a response to queries is often nonbeneficial. But there are stable strategy profiles that make sharing information beneficial in the long run. This paper presents these types of mechanisms and specifies under which conditions it is beneficial to the agents to answer queries. We analyze a model of repeated encounters in which two agents ask each other queries over time. We present different strategies that enable information exchange, and compare them according to the expected utility for the agents, and the conditions required for the cooperative equilibrium to exist