Tackling America's Eating Habits, One Store at a Time

http://dx.doi.org/10.1126/science.337.6101.147

A rewiring model of intratumoral interaction networks.

Intratumoral heterogeneity (ITH) has been regarded as a key cause of the failure and resistance of cancer therapy, but how it behaves and functions remains unclear. Advances in single-cell analysis have facilitated the collection of a massive amount of data about genetic and molecular states of individual cancer cells, providing a fuel to dissect the mechanistic organization of ITH at the molecular, metabolic and positional level. Taking advantage of these data, we propose a computational model to rewire up a topological network of cell-cell interdependences and interactions that operate within a tumor mass. The model is grounded on the premise of game theory that each interactive cell (player) strives to maximize its fitness by pursuing a rational self-interest strategy, war or peace, in a way that senses and alters other cells to respond properly. By integrating this idea with genome-wide association studies for intratumoral cells, the model is equipped with a capacity to visualize, annotate and quantify how somatic mutations mediate ITH and the network of intratumoral interactions. Taken together, the model provides a topological flow by which cancer cells within a tumor cooperate or compete with each other to downstream pathogenesis. This topological flow can be potentially used as a blueprint for genetically intervening the pattern and strength of cell-cell interactions towards cancer control

Attitudes of referees in a multidisciplinary journal: An empirical analysis

This paper looks at 10 years of reviews in a multidisciplinary journal, The Journal of Artificial Societies and Social Simulation (JASSS), which is the flagship journal of social simulation. We measured referee behavior and referees' agreement. We found that the disciplinary background and the academic status of the referee have an influence on the report time, the type of recommendation and the acceptance of the reviewing task. Referees from the humanities tend to be more generous in their recommendations than other referees, especially economists and environmental scientists. Second, we found that senior researchers are harsher in their judgments than junior researchers, and the latter accept requests to review more often and are faster in reporting. Finally, we found that articles that had been refereed and recommended for publication by a multidisciplinary set of referees were subsequently more likely to receive citations than those that had been reviewed by referees from the same discipline. Our results show that common standards of evaluation can be established even in multidisciplinary communities

Unforeseen Costs of Cutting Mosquito Surveillance Budgets

A budget proposal to stop the U.S. Centers for Disease Control and Prevention (CDC) funding in surveillance and research for mosquito-borne diseases such as dengue and West Nile virus has the potential to leave the country ill-prepared to handle new emerging diseases and manage existing ones. In order to demonstrate the consequences of such a measure, if implemented, we evaluated the impact of delayed control responses to dengue epidemics (a likely scenario emerging from the proposed CDC budget cut) in an economically developed urban environment. We used a mathematical model to generate hypothetical scenarios of delayed response to a dengue introduction (a consequence of halted mosquito surveillance) in the City of Cairns, Queensland, Australia. We then coupled the results of such a model with mosquito surveillance and case management costs to estimate the cumulative costs of each response scenario. Our study shows that halting mosquito surveillance can increase the management costs of epidemics by up to an order of magnitude in comparison to a strategy with sustained surveillance and early case detection. Our analysis shows that the total costs of preparedness through surveillance are far lower than the ones needed to respond to the introduction of vector-borne pathogens, even without consideration of the cost in human lives and well-being. More specifically, our findings provide a science-based justification for the re-assessment of the current proposal to slash the budget of the CDC vector-borne diseases program, and emphasize the need for improved and sustainable systems for vector-borne disease surveillance

Tumors attenuating the mitochondrial activity in T cells escape from PD-1 blockade therapy

PD-1 blockade therapy has revolutionized cancer treatments. However, a substantial population of patients is unresponsive. To rescue unresponsive patients, the mechanism of unresponsiveness to PD-1 blockade therapy must be elucidated. Using a ‘bilateral tumor model’ where responsive and unresponsive tumors were inoculated into different sides of the mouse belly, we demonstrated that unresponsive tumors can be categorized into two groups: with and without systemic immunosuppressive property (SIP). The SIP-positive tumors released uncharacterized, non-proteinaceous small molecules that inhibited mitochondrial activation and T cell proliferation. By contrast, the SIP-negative B16 tumor escaped from immunity by losing MHC class I expression. Unresponsiveness of SIP-positive tumors was partially overcome by improving the mitochondrial function with a mitochondrial activator; this was not successful for B16, which employs immune ignorance. These results demonstrated that the ‘bilateral tumor model’ was useful for stratifying tumors to investigate the mechanism of unresponsiveness and develop a strategy for proper combination therapy

Systematic Characterizations of Text Similarity in Full Text Biomedical Publications

Computational methods have been used to find duplicate biomedical publications in MEDLINE. Full text articles are becoming increasingly available, yet the similarities among them have not been systematically studied. Here, we quantitatively investigated the full text similarity of biomedical publications in PubMed Central.72,011 full text articles from PubMed Central (PMC) were parsed to generate three different datasets: full texts, sections, and paragraphs. Text similarity comparisons were performed on these datasets using the text similarity algorithm eTBLAST. We measured the frequency of similar text pairs and compared it among different datasets. We found that high abstract similarity can be used to predict high full text similarity with a specificity of 20.1% (95% CI [17.3%, 23.1%]) and sensitivity of 99.999%. Abstract similarity and full text similarity have a moderate correlation (Pearson correlation coefficient: -0.423) when the similarity ratio is above 0.4. Among pairs of articles in PMC, method sections are found to be the most repetitive (frequency of similar pairs, methods: 0.029, introduction: 0.0076, results: 0.0043). In contrast, among a set of manually verified duplicate articles, results are the most repetitive sections (frequency of similar pairs, results: 0.94, methods: 0.89, introduction: 0.82). Repetition of introduction and methods sections is more likely to be committed by the same authors (odds of a highly similar pair having at least one shared author, introduction: 2.31, methods: 1.83, results: 1.03). There is also significantly more similarity in pairs of review articles than in pairs containing one review and one nonreview paper (frequency of similar pairs: 0.0167 and 0.0023, respectively).While quantifying abstract similarity is an effective approach for finding duplicate citations, a comprehensive full text analysis is necessary to uncover all potential duplicate citations in the scientific literature and is helpful when establishing ethical guidelines for scientific publications

Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells

Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets

The Effectiveness of RNAi in Caenorhabditis elegans Is Maintained during Spaceflight

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Overcoming spaceflight-induced (patho)physiologic adaptations is a major challenge preventing long-term deep space exploration. RNA interference (RNAi) has emerged as a promising therapeutic for combating diseases on Earth; however the efficacy of RNAi in space is currently unknown. METHODS: Caenorhabditis elegans were prepared in liquid media on Earth using standard techniques and treated acutely with RNAi or a vector control upon arrival in Low Earth Orbit. After culturing during 4 and 8 d spaceflight, experiments were stopped by freezing at -80°C until analysis by mRNA and microRNA array chips, microscopy and Western blot on return to Earth. Ground controls (GC) on Earth were simultaneously grown under identical conditions. RESULTS: After 8 d spaceflight, mRNA expression levels of components of the RNAi machinery were not different from that in GC (e.g., Dicer, Argonaute, Piwi; P>0.05). The expression of 228 microRNAs, of the 232 analysed, were also unaffected during 4 and 8 d spaceflight (P>0.05). In spaceflight, RNAi against green fluorescent protein (gfp) reduced chromosomal gfp expression in gonad tissue, which was not different from GC. RNAi against rbx-1 also induced abnormal chromosome segregation in the gonad during spaceflight as on Earth. Finally, culture in RNAi against lysosomal cathepsins prevented degradation of the muscle-specific α-actin protein in both spaceflight and GC conditions. CONCLUSIONS: Treatment with RNAi works as effectively in the space environment as on Earth within multiple tissues, suggesting RNAi may provide an effective tool for combating spaceflight-induced pathologies aboard future long-duration space missions. Furthermore, this is the first demonstration that RNAi can be utilised to block muscle protein degradation, both on Earth and in space.This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Japan Society for the Promotion of Science, and “Ground-Based Research Announcement for Space Utilization” promoted by the Japan Space Forum. TE was supported by the Medical Research Council UK (G0801271). NJS was supported by the National Institutes of Health (NIH NIAMS ARO54342). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript