The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.     

Identification of an Arabidopsis thaliana mutation (vsm1) that restricts systemic movement of tobamoviruses

Following inoculation, many plant viruses spread locally from cell to cell until they reach the vascular system, through which they then move to other parts of the plant, resulting in systemic infection. To isolate host genes involved in systemic transport of plant viruses, ethyl methanesulfonate-mutagenized Arabidopsis thaliana plants were screened for significant delays in the systemic movement of turnip vein clearing virus (TCVC). One such mutant, designated vsm1 (virus systemic movement), was identified. Unlike the wild-type plants, vsm1 did not develop viral disease and did not allow the systemic spread of the virus. The local viral movement within the inoculated vsm1 leaves, however, was not affected. TVCV systemic movement within the vsm1 plants was likely blocked at the step of viral entry into the host plant vasculature from the infected leaf tissue. vsm1 plants also restricted the systemic movement of another tobamovirus but not of an unrelated carmovirus.     

Synthesis of 9-deoxo-4'-deoxy-6,9-epoxyerythromycin derivatives: novel and acid-stable motilides

In our quest toward the discovery of highly potent and acid-stable motilides, novel 4"-deoxy derivatives of 9-deoxo-6, 9-epoxyerythromycin were designed, synthesized, and evaluated for their gastrointestinal prokinetic activities. These compounds, in their 9R configuration, were more potent than their 6,9-enol ether homologues in inducing well-coordinated smooth muscle contractions in an in vitro rabbit duodenal assay: e.g., (9R), (8S)-9-deoxo-4"-deoxy-3'-N-desmethyl-3'-N-ethyl-6, 9-epoxyerythromycin A (10) and (9R), (8S)-9-deoxo-4"-deoxy-3'-N-desmethyl-3'-N-ethanol-6, 9-epoxyerythromycin A (15) had a pED50 of 8.54 and 8.11 compared to a pED50 of 7.22 for compound 2 (ABT-229). Reduction of the 6,9-enol ether, which was aimed at improving the acid stability, afforded the most stable motilides to date with t1/2 of 5.5 h for 10 and 15. Compounds 10 and 15 bind specifically to rabbit antral smooth muscle motilin receptors with pIC50 values of 8.52 and 8.70.     

Cyanide Contents of Leaves of Commonly Consumed Cassava Varieties from Three Geographical Regions of Ghana

Consuming a cyanogenic plant is an etiological factor to the persistence of iodine deficiency in the post salt iodization phase. Ghana, notably the Northern belt, still reports of iodine deficiency after 14 years of mandatory consumption of iodized salt by an Act of Parliament. The study aimed at determining the cyanide contents of leaves of commonly consumed cassava varieties in Ghana and investigating the effects of some environmental factors on cyanide content. Three communities each from Southern, Middle and Northern Ghana served as the study sites from where young, non-diseased and fully-spread cassava leaves were sampled from plants of commonly consumed cassava varieties. Cyanide was analyzed by the standard color~metric method based on the chloramine-T/pyridine-barbituric acid protocol （4500-CN E）. Cassava leaves from Northern Ghana had significantly higher mean cyanide content （177.22 ± 20.82 ppm） than those from Middle （130.83± 33.00 ppm） and Southern Ghana （127.24 ± 37.54 ppm） （P 〈 0.001）. Two-factor ANOVA showed significantly higher adverse environmental effects on cyanide contents of leaves of unimproved cassava varieties than improved ones （R2 = 0.627, P = 0.023）. From multiple regression analysis, temperature was the most significant environmental factor explaining 33% of the variability in cyanide content （R2 = 0.331, P = 0.002）, followed by altitude （R2 = 0.106, P = 0.049） and rainfall （R2 = 0.084, P = 0.062）. The high cyanide contents of cassava leaves from Northern Ghana, due principally to the high atmospheric temperature, may be a contributory factor to the high prevalence of goiter and the persistence of iodine deficiency in that geographic region.     

The Influence of Common Chlorides on the Adsorption of SBX on Chalcopyrite Surface during Flotation Process

Chalcopyrite flotability were investigated in four common chloride salts. The results indicated that NaCl, KCl, CaCl₂ increased chalcopyrite recovery while MgCl₂ decreased its recovery. The monovalent salts played an insignificant role while divalent salts apparently decreased the contact angle of chalcopyrite, regardless of the presence of collectors. Furthermore, the zeta potential was increased in divalent salts and even changed from negative to positive values in MgCl₂, highly due to Mg(OH)₂ precipitation on chalcopyrite surface. In addition, molecular dynamics simulation indicated that Mg(OH)₂ precipitates on chalcopyrite (112) surface stabilized the liquid layer and formed a hydrophilic barrier to inhibit SBX adsorption.     

Electrolytic Generation “In-Situ” of Sodium Hypochlorite

In-situ production of sodium hypochlorite is one of the oldest electrochemical processes of the chemical industry. During the past twenty years a new “in-situ” hypochlorite industry has developed. Construction and performance of present-day cells are considered in detail. Modern cells are fed with seawater or similar weak brines and yield solutions suitable for disinfection, e. g. in breweries, laundries, etc., or for treatment of municipal sewage. Particular importance attaches to units for chlorination of cooling water for power stations or on board ships, thus hindering growth of organisms leading to operating failures. The article closes by considering development trends.     

Dryland soil nitrogen cycling influenced by tillage, crop rotation, and cultural practice

Management practices may influence dryland soil N cycling. We evaluated the effects of tillage, crop rotation, and cultural practice on dryland crop biomass (stems and leaves) N, surface residue N, and soil N fractions at the 0?C20?cm depth in a Williams loam from 2004 to 2008 in eastern Montana, USA. Treatments were two tillage practices (no-tillage [NT] and conventional tillage [CT]), two crop rotations (continuous spring wheat [Triticum aestivum L.] [CW] and spring wheat-barley [Hordeum vulgaris L.] hay-corn [Zea mays L.]-pea [Pisum sativum L.] [W-B-C-P]), and two cultural practices (regular [conventional seed rates and plant spacing, conventional planting date, broadcast N fertilization, and reduced stubble height] and ecological [variable seed rates and plant spacing, delayed planting, banded N fertilization, and increased stubble height]). Nitrogen fractions were soil total N (STN), particulate organic N (PON), microbial biomass N (MBN), potential N mineralization (PNM), NH₄?CN, and NO₃?CN. Crop biomass N was 30?% greater in W-B-C-P than in CW in 2005. Surface residue N was 30?C34?% greater in NT with the regular and ecological practices than in CT with the regular practice. The STN, PON, and MBN at 10?C20 and 0?C20?cm were 5?C41?% greater in NT or CW with the regular practice than in CT or CW with the ecological practice. The PNM at 5?C10?cm was 22?% greater in the regular than in the ecological practice. The NH₄?CN and NO₃?CN contents at 10?C20 and 0?C20?cm were greater in CT with W-B-C-P and the regular practice than with most other treatments in 2007. Surface residue and soil N fractions, except PNM and NO₃?CN, declined from autumn 2007 to spring 2008. In 2008, NT with W-B-C-P and the regular practice gained 400?kg?N?ha^?1 compared with a loss of 221?kg?N?ha^?1 to a gain of 219?kg?N?ha^?1 in other treatments. No-tillage with the regular cultural practice increased surface residue and soil N storage but conventional tillage with diversified crop rotation and the regular practice increased soil N availability. Because of continuous N mineralization, surface residue and soil N storage decreased without influencing N availability from autumn to the following spring.     

Tobamovirus evolution: gene overlaps, recombination, and taxonomic implications

Tobamoviruses, mostly isolated from solanaceous plants, may represent ancient virus lineages that have codiverged with their hosts. Recently completed nucleotide sequences of six nonsolanaceous tobamoviruses allowed assessment of the codivergence hypothesis and support a third subgroup within tobamoviruses. The genomic sequences of 12 tobamoviruses and the partial sequences of 11 others have been analyzed. Comparisons of the predicted protein sequences revealed three clusters of tobamoviruses, corresponding to those infecting solanaceous species (subgroup 1), those infecting cucurbits and legumes (subgroup 2), and those infecting crucifers. The orchid-infecting odontoglossum ringspot tobamovirus was associated with subgroup 1 genomes by its coat and movement protein sequences, but with the crucifer-pathogenic tobamoviruses by the remainder of its genome, suggesting that it is the progeny of a recombinant. For four of five genomic regions, subgroup 1 and 3 genomes were equidistant from a subgroup 2 genome chosen for comparison, suggesting uniform rates of evolution. A phylogenetic tree of plant families based on the tobamoviruses they harbor was congruent with that based on rubisco sequences but had a different root, suggesting that codivergence was tempered by rare events of viruses of one family colonizing another family. The proposed subgroup 3 viruses probably have an origin of virion assembly in the movement protein gene, a large (25-codon) overlap of movement and coat protein open reading frames, and a comparably shorter genome. Codon-position-dependent base compositions and codon prevalences suggested that the coat protein frame of the overlap region was ancestral. Bootstrapped parsimony analysis of the nucleotides in the overlap region and of the sequences translated from the -1 frame (the subgroup 3 movement protein frame) of this region produced trees inconsistent with those deduced from other regions. The results are consistent with a model in which a no or short overlap organization was ancestral. Despite encoding of subgroup 2 and 3 movement protein C-termini by nonhomologous nucleotides, weak similarities between their amino acid sequences suggested convergent sequence evolution.