A Mechanistic Investigation of the Relationship Between Extramural Vascular Invasion (EMVI) and CpG Island Methylator Phenotype (CIMP) in Rectal Cancer

Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer death worldwide. Each year, one million people will develop CRC, and 40-50% will die within five years. Furthermore, rectal and distal sigmoid cancers are known to present at a later stage and have a poorer prognosis than other colonic cancers. Rectal cancers that demonstrate pathological extramural vascular invasion (EMVI-positive) are known to have a poorer prognosis than those that do not (EMIV-negative), and EMVI has is acknowledged as an important risk factor for systemic recurrence, local recurrence and death. Additionally, EMVI status influences the need for pre- and post-operative chemoradiation (CRT); which may influence survival outcomes. Aberrant DNA methylation is emerging as a carcinogenic mechanism and potential biomarker in colorectal cancer. This study investigates the association between hypermethylation and EMVI in vivo and in vitro. Firstly, the in vivo associations between hypermethylation, EMVI, and clinical and histopathological outcomes are examined. Secondly, an investigation of the effects of demethylation on invasive colorectal cell lines in vitro aims to illuminate the genetic and cellular mechanisms that underlie methylation-dependent pathological cellular behaviour. Finally, highlighted biologic mechanisms are investigated in vivo to discover if there is an association with EMVI and survival outcomes. By these means the axis of association between hypermethylation, EMVI, and clinical outcomes is investigated. The investigation is conducted within the framework of consensus molecular subtyping in colorectal cancer, and in concordance with current methodologies of assessing DNA methylation status. The primary findings demonstrate that EMVI is associated with hypermethylation in vivo, but that there is no direct correlation between hypermethylation and disease-free (DFS) or overall survival (OS). In vitro, demethylation of hypermethylated colorectal cancer cells, by means of established demethylating agent 5-azacytidine and putative demethylator RRx-001, reduces their propensity to migrate and invade. Demethylation in vitro is also associated with changes in the expression of the metalloproteinases involved in the metabolism of the basement membrane and the epithelial-to-mesenchymal transition and tumour metastasis, notably MMP2 and TIMP2. Changes in expression were confirmed at transcriptomal and proteomic levels in response to demethylation. In vivo, MMP2 expression was shown to be statistically significantly associated with EMVI, DFS, and OS, and was also independently predictive of EMVI, raising the possibility that it could act as a diagnostic and predictive biomarker in rectal cancers. These findings indicate a mechanistic association between hypermethylation and EMVI, mediated by methylation-dependent expression of metalloproteinases. Metalloproteinase expression, specifically MMP2, may act as a potential biomarker for EMVI and correlates to survival outcomes in rectal cancer

Physics of breadmaking

Bread dough is a foam and the stability of the gas bubbles towards disproportionation and coalescence during the breadmaking process determines for a large part the final appearance of the baked bread with respect to crumb structure and loaf volume. Gas bubble behaviour in bread dough is determined by both surface and bulk rheological properties of dough (components). These properties were studied and their relevance to breadmaking was established.Surface dilational moduli of different dough components were determined. It appears that wheat lipids and added surfactants as SSL and DATEM can retard disproportionation to a large extent if these components are present in the right concentration and modification. Wheat proteins will hardly retard this foam instability mechanism.Dynamic measurements and biaxial extension tests on wheat and rye flour as well as wheat gluten doughs were performed. Both flour and gluten doughs show strain hardening at 20 and at 55°C. Wheat cultivars with good breadmaking performance exhibit stronger strain hardening properties than poor baking ones and rye. Next to strain hardening, biaxial stress and extensibility are important parameters determining bread quality.During mixing both the surface tension and the viscosity of the dough determine the (minimum) radii of the entrapped gas bubbles. Directly after mixing surface properties dominate primarily gas bubble behaviour by retarding disproportionation, especially if surfactants like SSL or DATEM are added. Already during first proof bulk properties, especially biaxial stress, extensibility and strain hardening, start to dominate gas bubble stability and this remains as such during almost the remainder of the breadmaking process. In the final stage of oven rise surface properties may contribute to the stability of some dough films that have become very thin

Rainfall-induced volcanic activity on Montserrat

Dome-forming volcanic eruptions cyclically extrude bodies of lava over several months, which then become gravitationally unstable and collapse, generating pyroclastic flows. On 29 July 2001 extreme rainfall over Montserrat coincided with a major collapse of the Soufriere Hills lava dome. We present rainfall and seismic records that demonstrate, for the first time, a relationship between intense rainfall and lava dome collapse, with associated pyroclastic flow generation. After seven months of little rain and a period of sustained dome growth, the onset of intense rain was followed within hours by dome collapse and pyroclastic flows. The large-scale weather system responsible for the rain was identifiable in satellite images and predicted by meteorological forecasts issued 60 hours prior to the volcanic activity. It is suggested that weather prediction of intense rainfall be incorporated with existing geophysical and geochemical measurements to improve warnings of these hazardous events

Growth and mass wasting of volcanic centers in the northern South Sandwich arc, South Atlantic, revealed by new multibeam mapping

New multibeam (swath) bathymetric sonar data acquired using an EM120 system on the RRS James Clark Ross, supplemented by sub-bottom profiling, reveals the underwater morphology of a not, vert, similar 12,000 km2 area in the northern part of the mainly submarine South Sandwich volcanic arc. The new data extend between 55° 45′S and 57° 20′S and include Protector Shoal and the areas around Zavodovski, Visokoi and the Candlemas islands groups. Each of these areas is a discrete volcanic center. The entirely submarine Protector Shoal area, close to the northern limit of the arc, forms a 55 km long east–west-trending seamount chain that is at least partly of silicic composition. The seamounts are comparable to small subaerial stratovolcanoes in size, with volumes up to 83 km3, indicating that they are the product of multiple eruptions over extended periods. Zavodovski, Visokoi and the Candlemas island group are the summits of three 3–3.5 km high volcanic edifices. The bathymetric data show evidence for relationships between constructional volcanic features, including migrating volcanic centers, structurally controlled constructional ridges, satellite lava flows and domes, and mass wasting of the edifices. Mass wasting takes place mainly by strong erosion at sea level, and dispersal of this material along chutes, probably as turbidity currents and other mass flows that deposit in extensive sediment wave fields. Large scale mass wasting structures include movement of unconsolidated debris in slides, slumps and debris avalanches. Volcanism is migrating westward relative to the underlying plate and major volcanoes are asymmetrical, being steep with abundant recent volcanism on their western flanks, and gently sloping with extinct, eroded volcanic sequences to their east. This is consistent with the calculated rate of subduction erosion of the fore-arc

The kinematics of bidisperse granular roll waves

Small perturbations to a steady uniform granular chute flow can grow as the material moves downslope and develop into a series of surface waves that travel faster than the bulk flow. This roll wave instability has important implications for the mitigation of hazards due to geophysical mass flows, such as snow avalanches, debris flows and landslides, because the resulting waves tend to merge and become much deeper and more destructive than the uniform flow from which they form. Natural flows are usually highly polydisperse and their dynamics is significantly complicated by the particle size segregation that occurs within them. This study investigates the kinematics of such flows theoretically and through small-scale experiments that use a mixture of large and small glass spheres. It is shown that large particles, which segregate to the surface of the flow, are always concentrated near the crests of roll waves. There are different mechanisms for this depending on the relative speed of the waves, compared to the speed of particles at the free surface, as well as on the particle concentration. If all particles at the surface travel more slowly than the waves, the large particles become concentrated as the shock-like wavefronts pass them. This is due to a concertina-like effect in the frame of the moving wave, in which large particles move slowly backwards through the crest, but travel quickly in the troughs between the crests. If, instead, some particles on the surface travel more quickly than the wave and some move slower, then, at low concentrations, large particles can move towards the wave crest from both the forward and rearward sides. This results in isolated regions of large particles that are trapped at the crest of each wave, separated by regions where the flow is thinner and free of large particles. There is also a third regime arising when all surface particles travel faster than the waves, which has large particles present everywhere but with a sharp increase in their concentration towards the wave fronts. In all cases, the significantly enhanced large particle concentration at wave crests means that such flows in nature can be especially destructive and thus particularly hazardous

Understanding the effect of emulsifiers on bread aeration during breadmaking

[EN] BACKGROUNDMuch research has been done to explain the action of emulsifiers during breadmaking, but there is still plenty unknown to elucidate their functionality despite their diverse chemical structure. The aim of the present study was to provide some light on the role of emulsifiers on air incorporation into the dough and gas bubbles progress during baking and their relationship with bread features. Emulsifiers like diacetyl tartaric acid ester of monoglycerides (DATEM), sodium stearoyl lactylate (SSL), distilled monoglyceride (DMG-45 and DMG-75), lecithin and polyglycerol esters of fatty acids (PGEF) were tested in very hydrated doughs. RESULTSEmulsifiers increase the maximum dough volume during proofing. Emulsifiers increase the number of bubbles incorporated during mixing, observing higher number of bubbles, particularly with PGEF. Major changes in dough occurred at 70K when bubble size augmented, becoming more heterogeneous. DMG-75 produced the biggest bubbles. As a consequence, emulsifiers tend to increase the number of gas cells with lower size in the bread crumb, but led to greater crumb firmness, which suggested different interactions between emulsifiers and gluten, affecting protein polymerization during baking. CONCLUSIONThe progress of the bubbles during baking allowed the differentiation of emulsifiers, which could explain their performance in breadmaking. (c) 2018 Society of Chemical IndustryAuthors acknowledge the financial support of the Spanish Ministry of Economy and Competitiveness (Project AGL2014-52928-C2-1-R), the European Regional Development Fund (FEDER) and Generalitat Valenciana (Project Prometeo 2017/189).Garzon, R.; Hernando Hernando, MI.; Llorca Martínez, ME.; Molina Rosell, MC. (2018). Understanding the effect of emulsifiers on bread aeration during breadmaking. Journal of the Science of Food and Agriculture. 98(14):5494-5502. https://doi.org/10.1002/jsfa.9094S549455029814Rosell, C. M., & Garzon, R. (2015). 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