Clinical,Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis

BACKGROUND: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.     

Plant communities and landscape diversity along a Canadian Arctic river

Abstract. We analysed the structure and diversity of the vegetation along an Arctic river to determine the relationship between species richness and plant community structure. We examined whether variation in species richness along the corridor is structured as (1) an increase in the number of communities due to increasing landscape heterogeneity, (2) an increase in the floristic distinctiveness (β-diversity) of communities, or (3) an increase in within-community richness (α-diversity) as species-poor communities are replaced by species-rich communities. We described 24 community types and analysed the relationship between site vascular species richness (γ-diversity) and β-diversity, α-diversity, site environmental heterogeneity, and the number of distinct plant communities. We also measured diversity patterns of vascular, bryophyte, and lichen species within communities and examined their relationship to community-level estimates of environmental factors. We found that an increase in site species richness correlated with an increase in the number of communities (r²= 0.323, P= 0.0173) and β-diversity (r²= 0.388, P= 0.0075), rather than an increase in the α-diversity of individual communities. Moisture and pH controlled most of the differences in composition between communities. Measures of species richness and correlations with moisture and pH within communities differed among vascular, bryophyte, and lichen species. Bryophyte richness was positively correlated with moisture (r²= 0.862, P= 0.0010) and lichen richness was negatively correlated with moisture (r²= 0.809, P= 0.0031). Vascular plants had a peak in richness at pH 6.5 (r²= 0.214, P < 0.0001). We conclude that site variation in vascular richness in this region is controlled by landscape heterogeneity, and structured as variation in the number and distinctiveness of recognizable plant communities.     

Conservation of bog plant species assemblages: Assessing the role of natural remnants in mined sites

Abstract. Bogs, economically valuable wetlands, are subjected to exploitation in southern Canada. We addressed plant conservation within bogs mined for peat, in which small undisturbed remnants are left, mostly at the margins of the mined areas. The main goal of the study was to test whether these remnants act as refuges for plants which could recolonize areas that are planned for restoration after mining is completed. Mosses, lichens and vascular plants were sampled in remnants of 24 mined bogs in southeastern Canada during the summer of 1997. The vegetation was also sampled at the margins and centres of 24 nearby natural bogs in plots similar in size to these remnants. Using similarity analysis and ordination techniques, we found that plant species assemblages in remnants of mined bogs differ from those near the margins of natural bogs, and that certain species are associated with the centre of natural bogs, due to the presence of pools. We also showed that water conditions of remnants are affected by drainage due to peat mining. Sphagnum moss showed itself to be a key indicator of mining effects on vegetation. Implications for peat resource management and bog conservation are discussed.     

Characterization of the sperm receptor on the surface of eggs of Strongylocentrotus purpuratus

Eggs of the sea urchins Strongylocentrotus purpuratus and Arbacia punctulata bind sperm with a high degree of species specificity. By use of an in vitro assay that utilizes bindin (the protein from sperm that mediates sperm-egg binding) egg surface-derived glycoconjugates that function as receptors in this adhesion process have been identified and purified. These glycoconjugates are of extraordinarily high molecular weight and exhibit some properties expected for a proteoglycan. The isolated receptors from both species bind to sperm and inhibit fertilization species specifically. Both receptors contain active carbohydrate-rich fragments that can be liberated by proteolytic digestion. The carbohydrate-rich receptor fragment from S. purpuratus is a very high-molecular-weight (>10⁶), negatively charged glycosaminoglycan-like polymer containing fucose, galactosamine, iduronic acid, and sulfate esters. By contrast, the carbohydrate-rich fragment derived from the A. punctulata receptor is of defined molecular weight (6000) and has no net charge. Incubation of acrosome-reacted sperm with nanomolar amounts of the carbohydrate-rich fragments from either species results in inhibition of fertilization, indicating that these receptor fragments retain sperm binding activity. However, studies utilizing heterologous gametes show that the carbohydrate-rich receptor fragments are not species specific in binding. Thus, it appears that although the carbohydrate chains of the receptor are an adhesive element of the receptor, the intact glycoconjugate is required for species-specific binding.     

A long-term study of Pinus banksiana population dynamics

Abstract. The long-term population dynamics of a pure, naturally-established stand of Pinus banksiana (jack pine) in southeastern Manitoba, Canada is described. The study was initiated at stand age 15, when all 468 trees in a plot were mapped and their trunk diameter at breast height (DBH) measured. The plot was remeasured eight times — every five years (six years in one case) — and mortality and DBH changes recorded. Total mortality over the 41-yr study period was ca. 84 %. Mortality was initially very low, increased once the stand entered the self-thinning stage from ages 25–46, and declined at ages 46–56. Mortality was restricted to the smallest size classes throughout. The stand reached the self-thinning line at ca. age 30. The self-thinning slope was significantly less steep than the theoretically expected value of ?0.5. The distribution of DBH values was initially symmetric, showed increasing positive skewness during the period of highest mortality, and became symmetric again at later stages. Size (DBH) inequality was highest just prior to the onset of density-dependent mortality, and subsequently declined. Tree DBH values were positively autocorrelated both initially and at later stages of stand development, but were spatially independent during the period of highest density-dependent mortality. The stand initially had a strongly clumped pattern at all spatial scales. Patterns of mortality were non-random during stand development, however, resulting in increased spatial regularity over time. Mortality was initially restricted to high density patches of the stand, but occurred throughout the plot once the self-thinning line was reached. Mortality during the self-thinning stage deviated from random expectation at local spatial scales (1–2m radius), suggesting that individuals were competing with their immediate neighbours. It is argued that an integrated approach, incorporating both population size and spatial structures, is essential in improving our understanding of long-term plant population dynamics.     

Photoinhibition – a historical perspective

Photoinhibition is a state of physiological stress that occurs in all oxygen evolving photosynthetic organisms exposed to light. The primary damage occurs within the reaction center of Photosystem II (PS II). While irreversible photoinduced damage to PS II occurs at all light intensities, the efficiency of photosynthetic electron transfer decreases markedly only when the rate of damage exceeds the rate of its repair, which requires de novo PS II protein synthesis. Photoinhibition has been studied for over a century using a large variety of biochemical, biophysical and genetic methodologies. The discovery of the light induced turnover of a protein, encoded by the plastid psbA gene (the D1 protein), later identified as one of the photochemical reaction center II proteins, has led to the elucidation of the underlying mechanism of photoinhibition and to a deeper understanding of the PS II `life cycle.' This revised version was published online in August 2006 with corrections to the Cover Date.     

A comparative study of the bactericidal activity of horseshoe crab (Limulus polyphemus) hemolymph and vertebrate serum

This paper describes a partially heat-labile, naturally occurring bactericidal factor in cell-free hemolymph preparations obtained from Limulus polyphemus. This bactericidal activity has been shown to be directed against two Gram-negative bacteria, Escherichia coli and Klebsiella pneumoniae, whereas it had no effect on the Gram-positive bacteria tested, Micrococcus lysodeikticus and Staphylococcus aureus. Maximal bactericidal activity of this factor was observed at 30°C and pH 6.0. Since complement and antibody are required for antimicrobial activity in vertebrate sera, the activity of this factor in the presence of various complement inhibitors was assayed. The bactericidal activity of Limulus hemolymph is abolished by treatment with endotoxin; however, other anticomplementary substances were without effect. Limulus amebocyte lysate is known to contain protein which may be precipitated by endotoxin; it is possible that the reduction of bactericidal activity produced by endotoxin treatment may be caused by the denaturation of a bactericidal protein moiety produced by the hemocytes.     

Discussion on “Instrumented difference-in-differences” by Ting Ye,Ashkan Ertefaie,James Flory,Sean Hennessy & Dylan S. Small

We reinterpret the instrumented difference-in-differences (iDID) under a linear instrumental variables (IV) model. Under the linear IV model, we show why iDID is a clear improvement over two existing methods, difference-in-differences (DID) and a cross-sectional, IV analysis. We also re-express some of the assumptions of iDID using familiar, regression-based identification assumptions. We conclude with a method inspired by the linear IV model that can potentially remedy the weak identification problem in iDID.     

His Own Synthesis: Corn, Edgar Anderson, and Evolutionary Theory in the 1940s

Tracing the contributions of Edgar Anderson (1897--1969) of the Missouri Botanical Garden to the important discussions in evolutionary biology in the 1940s, this paper argues that Anderson turned to corn research rather than play a more prominent role in what is now known as the Evolutionary Synthesis. His biosystematic studies of Iris and Tradescantia in the 1930s reflected such Synthesis concerns as the species question and population thinking. He shared the 1941 Jesup Lectures with Ernst Mayr. But rather than preparing his lectures as a potentially key text in the Synthesis, Anderson began researching Zea mays -- its taxonomy, its origin, and its agronomic role. In this study, Anderson drew on the disciplines of taxonomy, morphology, genetics, geography, anthropology, archaeology, and agronomy among others in his own creative synthesis. Though his maize research in the 1940s represented the most sustained work of his career, Anderson was also drawn in many directions during his professional life. For example, he enjoyed teaching, working with amateurs, and popular writing. This revised version was published online in July 2006 with corrections to the Cover Date.