Atypical E2Fs either Counteract or Cooperate with RB during Tumorigenesis Depending on Tissue Context

Simple Summary In virtually all human malignancies, the CDK-RB-E2F pathway is dysregulated resulting in the activation of the E2F transcriptional network. Rb and atypical E2Fs are the most important negative regulators of E2F-dependent transcription during tumorigenesis. However, it is unknown whether they cooporate or act independently in tumor development. Here we show that combined loss of RB and atypical E2Fs in mice enhances tumorigenesis in the liver, while in the pituitary gland, we observe inhibition of tumorigenesis. These findings suggest that the interaction between RB and atypical E2Fs in controlling tumorigenesis occurs in a tissue cell-type specific manner. E2F-transcription factors activate many genes involved in cell cycle progression, DNA repair, and apoptosis. Hence, E2F-dependent transcription must be tightly regulated to prevent tumorigenesis, and therefore metazoan cells possess multiple E2F regulation mechanisms. The best-known is the Retinoblastoma protein (RB), which is mutated in many cancers. Atypical E2Fs (E2F7 and -8) can repress E2F-target gene expression independently of RB and are rarely mutated in cancer. Therefore, they may act as emergency brakes in RB-mutated cells to suppress tumor growth. Currently, it is unknown if and how RB and atypical E2Fs functionally interact in vivo. Here, we demonstrate that mice with liver-specific combinatorial deletion of Rb and E2f7/8 have reduced life-spans compared to E2f7/8 or Rb deletion alone. This was associated with increased proliferation and enhanced malignant progression of liver tumors. Hence, atypical repressor E2Fs and RB cooperatively act as tumor suppressors in hepatocytes. In contrast, loss of either E2f7 or E2f8 largely prevented the formation of pituitary tumors in Rb+/- mice. To test whether atypical E2Fs can also function as oncogenes independent of RB loss, we induced long-term overexpression of E2f7 or E2f8 in mice. E2F7 and -8 overexpression increased the incidence of tumors in the lungs, but not in other tissues. Collectively, these data show that atypical E2Fs can promote but also inhibit tumorigenesis depending on tissue type and RB status. We propose that the complex interactions between atypical E2Fs and RB on maintenance of genetic stability underlie this context-dependency

The Community Ecology of Herbivore Regulation in an Agroecosystem: Lessons from Complex Systems

AbstractWhether an ecological community is controlled from above or below remains a popular framework that continues generating interesting research questions and takes on especially important meaning in agroecosystems. We describe the regulation from above of three coffee herbivores, a leaf herbivore (the green coffee scale, Coccus viridis), a seed predator (the coffee berry borer, Hypothenemus hampei), and a plant pathogen (the coffee rust disease, caused by Hemelia vastatrix) by various natural enemies, emphasizing the remarkable complexity involved. We emphasize the intersection of this classical question of ecology with the burgeoning field of complex systems, including references to chaos, critical transitions, hysteresis, basin or boundary collision, and spatial self-organization, all aimed at the applied question of pest control in the coffee agroecosystem

The Core Human Microbiome: Does It Exist and How Can We Find It? A Critical Review of the Concept

The core microbiome, which refers to a set of consistent microbial features across populations, is of major interest in microbiome research and has been addressed by numerous studies. Understanding the core microbiome can help identify elements that lead to dysbiosis, and lead to treatments for microbiome-related health states. However, defining the core microbiome is a complex task at several levels. In this review, we consider the current state of core human microbiome research. We consider the knowledge that has been gained, the factors limiting our ability to achieve a reliable description of the core human microbiome, and the fields most likely to improve that ability. DNA sequencing technologies and the methods for analyzing metagenomics and amplicon data will most likely facilitate higher accuracy and resolution in describing the microbiome. However, more effort should be invested in characterizing the microbiome’s interactions with its human host, including the immune system and nutrition. Other components of this holobiontic system should also be emphasized, such as fungi, protists, lower eukaryotes, viruses, and phages. Most importantly, a collaborative effort of experts in microbiology, nutrition, immunology, medicine, systems biology, bioinformatics, and machine learning is probably required to identify the traits of the core human microbiome

Machine Learning in Automated Text Categorization

The automated categorization (or classification) of texts into predefined categories has witnessed a booming interest in the last ten years, due to the increased availability of documents in digital form and the ensuing need to organize them. In the research community the dominant approach to this problem is based on machine learning techniques: a general inductive process automatically builds a classifier by learning, from a set of preclassified documents, the characteristics of the categories. The advantages of this approach over the knowledge engineering approach (consisting in the manual definition of a classifier by domain experts) are a very good effectiveness, considerable savings in terms of expert manpower, and straightforward portability to different domains. This survey discusses the main approaches to text categorization that fall within the machine learning paradigm. We will discuss in detail issues pertaining to three different problems, namely document representation, classifier construction, and classifier evaluation.Comment: Accepted for publication on ACM Computing Survey

Complex chloroplast RNA metabolism: just debugging the genetic programme?

<p>Abstract</p> <p>Background</p> <p>The gene expression system of chloroplasts is far more complex than that of their cyanobacterial progenitor. This gain in complexity affects in particular RNA metabolism, specifically the transcription and maturation of RNA. Mature chloroplast RNA is generated by a plethora of nuclear-encoded proteins acquired or recruited during plant evolution, comprising additional RNA polymerases and sigma factors, and sequence-specific RNA maturation factors promoting RNA splicing, editing, end formation and translatability. Despite years of intensive research, we still lack a comprehensive explanation for this complexity.</p> <p>Results</p> <p>We inspected the available literature and genome databases for information on components of RNA metabolism in land plant chloroplasts. In particular, new inventions of chloroplast-specific mechanisms and the expansion of some gene/protein families detected in land plants lead us to suggest that the primary function of the additional nuclear-encoded components found in chloroplasts is the transgenomic suppression of point mutations, fixation of which occurred due to an enhanced genetic drift exhibited by chloroplast genomes. We further speculate that a fast evolution of transgenomic suppressors occurred after the water-to-land transition of plants.</p> <p>Conclusion</p> <p>Our inspections indicate that several chloroplast-specific mechanisms evolved in land plants to remedy point mutations that occurred after the water-to-land transition. Thus, the complexity of chloroplast gene expression evolved to guarantee the functionality of chloroplast genetic information and may not, with some exceptions, be involved in regulatory functions.</p

Validity and reproducibility of an interviewer-administered food frequency questionnaire for healthy French-Canadian men and women

OBJECTIVE: To evaluate the validity (study 1) and the reproducibility (study 2) of an interviewer-administered food frequency questionnaire (FFQ). METHOD: The FFQ was designed at Laval University and contains 91 items and 33 subquestions. Study 1: The FFQ was compared against a 3-day food record (2 week-days and 1 weekend-day), at week 0, 6 and 12 of a nutritional intervention. Study 2: In order to evaluate the reproducibility of the FFQ, 2 registered dietitians administered the FFQ 4-weeks apart among subjects who were not part of the nutritional intervention. RESULTS: Study 1: Mean values for intake of most nutrients assessed by the FFQ and by the 3-day food record were not statistically different. Energy-adjusted correlation coefficients for major macronutrients ranged from 0.36 for proteins to 0.60 for carbohydrates (p ≤ 0.01). Agreement analysis revealed that on average, 35% of the subjects were classified in the same quartile when nutrients were assessed by either the 3-day food record or the FFQ. Study 2: Significant associations were observed between dietary measurements derived from the two FFQs administered 4 weeks apart. Correlation coefficients for the reproducibility of macronutrients ranged from 0.66 for carbohydrates to 0.83 for lipids after energy adjustment. On average, 46% of the subjects were classified in the same quartile when nutrient intakes were assessed by either FFQ. CONCLUSION: These data indicated that the FFQ developed has a good validity and is reproducible

Reproducibility and Relative Validity of a Food Frequency Questionnaire Developed for Female Adolescents in Suihua, North China

BACKGROUND: This study aims to evaluate the reproducibility and validity of a food frequency questionnaire (FFQ) developed for female adolescents in the Suihua area of North China. The FFQ was evaluated against the average of 24-hour dietary recalls (24-HRs). METHODOLOGY/PRINCIPAL FINDINGS: A total of 168 female adolescents aged 12 to 18 completed nine three consecutive 24-HRs (one three consecutive 24 HRs per month) and two FFQs over nine months. The reproducibility of the FFQ was estimated using intraclass correlation coefficients (ICCs), and its relative validity was assessed by comparing it with the 24-HRs. The mean values of the 24-HRs were lower than those of the FFQs, except for protein (in FFQ1) and iron (in FFQ2). The ICCs for all nutrients and food groups in FFQ1 and FFQ2 were moderately correlated (0.4-0.8). However, all the ICCs decreased after adjusting for energy. The weighted κ statistic showed moderate agreement (0.40-0.6) for all nutrients and food groups, except for niacin and calcium, which showed poor agreement (0.35). The relative validity results indicate that the crude Spearman's correlation coefficients of FFQ1 and the 24-HRs ranged from 0.41 (for Vitamin C) to 0.65 (for fruit). The coefficients of each nutrient and food group in FFQ2 and the 24-HRs were higher than those in FFQ1 and the 24-HRs, indicating good correlation. Although all energy-adjusted Spearman's correlation coefficients were lower than the crude coefficients, de-attenuation to correct for intra-individual variability improved the correlation coefficients. The weighted κ coefficients of nutrients and food groups ranged from 0.32 for beans to 0.52 for riboflavin in FFQ1 and the 24-HRs, and 0.32 for Vitamin C to 0.54 for riboflavin in FFQ2 and the 24-HRs. CONCLUSION: The FFQ developed for female adolescents in the Suihua area is a reliable and valid instrument for ranking individuals within this study