Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field

Building the process-drug–side effect network to discover the relationship between biological Processes and side effects

<p>Abstract</p> <p>Background</p> <p>Side effects are unwanted responses to drug treatment and are important resources for human phenotype information. The recent development of a database on side effects, the side effect resource (SIDER), is a first step in documenting the relationship between drugs and their side effects. It is, however, insufficient to simply find the association of drugs with biological processes; that relationship is crucial because drugs that influence biological processes can have an impact on phenotype. Therefore, knowing which processes respond to drugs that influence the phenotype will enable more effective and systematic study of the effect of drugs on phenotype. To the best of our knowledge, the relationship between biological processes and side effects of drugs has not yet been systematically researched.</p> <p>Methods</p> <p>We propose 3 steps for systematically searching relationships between drugs and biological processes: enrichment scores (ES) calculations, t-score calculation, and threshold-based filtering. Subsequently, the side effect-related biological processes are found by merging the drug-biological process network and the drug-side effect network. Evaluation is conducted in 2 ways: first, by discerning the number of biological processes discovered by our method that co-occur with Gene Ontology (GO) terms in relation to effects extracted from PubMed records using a text-mining technique and second, determining whether there is improvement in performance by limiting response processes by drugs sharing the same side effect to frequent ones alone.</p> <p>Results</p> <p>The multi-level network (the process-drug-side effect network) was built by merging the drug-biological process network and the drug-side effect network. We generated a network of 74 drugs-168 side effects-2209 biological process relation resources. The preliminary results showed that the process-drug-side effect network was able to find meaningful relationships between biological processes and side effects in an efficient manner.</p> <p>Conclusions</p> <p>We propose a novel process-drug-side effect network for discovering the relationship between biological processes and side effects. By exploring the relationship between drugs and phenotypes through a multi-level network, the mechanisms underlying the effect of specific drugs on the human body may be understood.</p

Fluphenazine-induced acute and tardive dyskinesias in monkeys

Five Cebus apella monkeys were treated with biweekly injections of fluphenazine enanthate (0.1–3.2 mg/kg IM). Three of these completed 1 full year of treatment, one injured its leg after 6 months of treatment and was killed, and another died of unknown causes after 9 months of treatment. All monkeys displayed abnormal movements corresponding to the early appearing extrapyramidal symptoms of neuroleptic-treated patients. These consisted initially of slowing or absence of volitional movement, trembling of the hands, trembling of the entire body, and general drowsy behavior. As treatment progessed, a variety of abnormal postures and movements appeared after each injection that were not exacerbated by drug withdrawal and, as tested at the end of the year, could be abolished or prevented with benztropine mesylate (0.2–0.5 mg/kg IM). The three monkeys that completed 1 year of treatment with fluphenazine were then withdrawn from the drug. After withdrawal, all three developed movements similar in appearance to those of patients with tardive dyskinesia (TD). Reinstitution of fluphenazine treatment, as tested in one monkey, abolished all movements resembling TD.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46432/1/213_2004_Article_BF00555204.pd

Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field