Colon cancer stemness as a reversible epigenetic state: Implications for anticancer therapies

The recent discovery of cancer cell plasticity, i.e. their ability to reprogram into cancer stem cells (CSCs) either naturally or under chemotherapy and/or radiotherapy, has changed, once again, the way we consider cancer treatment. If cancer stemness is a reversible epigenetic state rather than a genetic identity, opportunities will arise for therapeutic strategies that remodel epigenetic landscapes of CSCs. However, the systematic use of DNA methyltransferase and histone deacetylase inhibitors, alone or in combination, in advanced solid tumors including colorectal cancers, regardless of their molecular subtypes, does not seem to be the best strategy. In this review, we first summarize the knowledge researchers have gathered on the epigenetic signatures of CSCs with the difficulty of isolating rare populations of cells. We raise questions about the relevant use of currently available epigenetic inhibitors (epidrugs) while the expression of numerous cancer stem cell markers are often repressed by epigenetic mechanisms. These markers include the three cluster of differentiation CD133, CD44 and CD166 that have been extensively used for the isolation of colon CSCs.and . Finally, we describe current treatment strategies using epidrugs, and we hypothesize that, using correlation tools comparing associations of relevant CSC markers with chromatin modifier expression, we could identify better candidates for epienzyme targeting.     

Lime treatment and its effects on the chemistry and biota of hardwater eutrophic lakes

1. The main focus of this study was to investigate the effects of single and multiple moderate doses of lime (slaked lime, Ca(OH)₂, and/or calcite, CaCO₃) on eutrophic hardwater lakes. This information would contribute to strategies to manage phytoplankton and macrophyte biomass in eutrophic lakes.
2. Water chemistry and biota were monitored for up to 7 years after initial lime treatment and results were compared with reference systems.
3. Complementary studies investigated the effect of lime on macrophytes in ponds, irrigation canals and microcosm experiments.
4. When water pH was kept within its natural range (≤ 10), single and multiple lime applications to lakes and ponds controlled macrophyte biomass, without negatively affecting invertebrate communities.
5. Single lime treatments at moderate dosages of lakes and ponds resulted in variable and mostly temporary changes in chlorophyll a (chl a ) and phosphorus (P) concentration. Although sediment P release was reduced in single-dose lakes during the first winter following treatment, reductions appeared temporary.
6. Multiple treatments of lakes and ponds were effective at reducing both chl a and P concentrations over longer periods. Mean winter P release rate was also reduced after initial treatment.
7. In laboratory studies, sediment cores were incubated with eight different treatments to assess P release. Redox-sensitive treatments were no more effective at lowering total P concentration in overlying water than some redox-insensitive treatments. Lime reduced total P concentrations, but was not as effective as treatments with alum.
8. The use of lime in managing macrophyte and phytoplankton biomass in shallow, hardwater lakes and ponds may be preferable over other treatments, because lime is economical and non-toxic as long as pH is kept within a natural range.     

Diel vertical and horizontal distribution of crustacean zooplankton and young of the year fish in a sub-alpine lake: an approach based on high frequency sampling

Understanding the spatial dynamics of predators and their preyis one of the most important goals in aquatic ecology. We studiedspatial and temporal onshore–offshore distribution patternsin young of the year (YOY) Eurasian perch (Perca fluviatilis)and crustacean zooplankton (Daphnia hyalina, Cyclops prealpinus)along a transect in Lake Annecy (France). Our study representsa first attempt at coupling hydroacoustic fish survey and highfrequency zooplankton recording to assess simultaneously thelarge-scale distribution patterns of YOY fish and their zooplanktonprey over a diel cycle (day, dusk and night sampling). We hypothesizedthat the spatial distribution of zooplankton could be shapedby both anti-predator behaviour (horizontal and vertical migrations)and predation losses. Fish biomass, size structure and dietwere assessed from split-beam echosounding and net trawlingsamples, whereas crustacean abundances were estimated with asmall modified Longhurst–Hardy continuous plankton recorder.We evaluated the diel changes in the spatial distribution patternsof fish and zooplankton and determined the overlap between theirdistributions. Fish biomass was dominated by YOY perch in upperwarmer layers and salmonids (Coregonus lavaretus and Salvelinusalpinus) in the colder and oxygenated deep layers. YOY perchwere aggregated in dense schools in the epilimnion during theday and dispersed at night. Fish biomass was distributed alonga strong increasing onshore–offshore gradient at night,whereas crustacean prey showed a decreasing gradient. This onshore–offshorenegative gradient in crustacean distribution, expressed on ashorter scale during the day, shifted toward the surface watersat night. A distinct kinetic of diel vertical migration (DVM)patterns was exhibited by daphnid and cyclopoid populationsand resulted in distinct vulnerability to perch predation. Spatio-temporaldistribution of crustaceans in Lake Annecy during the diel cyclestudy was probably shaped both by predation loss to YOY perchand by anti-predator behaviour (DVM, DHM) by zooplankton. Theimplications for fine-scale studies of fish-zooplankton interactionsare discussed.     

Effects of experimentally induced cyanobacterial blooms on crustacean zooplankton communities

SUMMARY 1. Large in situ enclosures were used to study the effects of experimentally induced cyanobacterial blooms on zooplankton communities. A combination of N and P was added to shallow (2 m) and deep enclosures (5 m) with the goal of reducing the TN : TP ratio to a low level (∼5 : 1) to promote cyanobacterial growth. After nutrient additions, high biomass of cyanobacteria developed rapidly in shallow enclosures reaching levels only observed during bloom events in eutrophic lakes.
2. In the shallow enclosures, particulate phosphorus (PP) was on average 35% higher in comparison with deep enclosures, suggesting that depth plays a key role in P uptake by algae. Phytoplankton communities in both deep and shallow enclosures were dominated by three cyanobacteria species – Aphanizomenon flos-aquae , Anabaena flos-aquae and Microcystis aeruginosa – which accounted for up to 70% of total phytoplankton biomass. However, the absolute biomass of the three species was much higher in shallow enclosures, especially Aphanizomenon flos-aquae . The three cyanobacteria species responded in contrasting ways to nutrient manipulation because of their different physiology.
3. Standardised concentrations of the hepatotoxic microcystin-LR increased as a result of nutrient manipulations by a factor of four in the treated enclosures. Increased biomass of inedible and toxin producing cyanobacteria was associated with a decline in Daphnia pulicaria biomass caused by a reduction in the number of individuals with a body length of >1 mm. Zooplankton biomass did not decline at moderate cyanobacteria biomass, but when cyanobacteria reached high biomass large cladocerans were reduced.
4. Our results demonstrate that zooplankton communities can be negatively affected by cyanobacterial blooms and therefore the potential to use herbivory to reduce algal blooms in such eutrophic lakes appears limited.     

Sapwood hydraulic conductivity and leaf area – sapwood area relationships following thinning of a Eucalyptus nitens plantation

This study tested the hypothesis that the relationship between leaf area (projected, or one‐sided) and sapwood area in Eucalyptus nitens (Deane and Maiden) Maiden is affected by thinning treatment. However, no difference in the relationship between leaf area and sapwood area was found 8 years after thinning. This result suggests that a single regression equation can be used to predict the leaf area of trees in thinned and unthinned stands. The relationship was non‐linear, implying a causal relationship between growth rate and the ratio of leaf area to sapwood area (A_l : A_s). Sapwood hydraulic conductivity increased by approximately 100% from breast height to crown base, whereas sapwood area decreased by 19%. This implies that the efficiency of water transport through the sapwood increased by 60% along this length. This conclusion is supported by the A_l : A_s relationships which showed that the sapwood area at crown base supported, on average, close to 60% more leaf area than a similar amount of sapwood area at breast height. That large trees in this study had greater hydraulic conductivity and higher A_l : A_s lends support to the argument that resource capture, and hence growth rate, influence sapwood hydraulic conductivity.     

Rapid purification of 2,4-dichlorophenol hydroxylase by biospecific desorption from 10-carboxydecylamino-sepharose

10-Carboxydecylamino-Sepharose, which bears a mixture of ionic and aliphatic substituent groups, adsorbs 2,4-dichlorophenol hydroxylase from Acinetobacter in a non-biospecific manner. The enzyme has been specifically desorbed by its substrate, 2,4-dichlorophenol, giving a 42-fold purification (to greater than 90% purity) in a single step. The enzyme contained 3.1 moles of FAD per mole and displayed a catalytic constant of 14.7 s(-1). Mixed-function adsorbents probably have wide applicability for biospecific desorption of proteins. The present report indicates that they may be useful in the purification of aromatic hydroxylases bearing flavin prosthetic groups that readily dissociate in conventional purification procedures employing conditions of high ionic strength.     

Permeabilization of Drosophila eggs

Vitelline membrane of Drosophila eggs were permeabilized by a brief immersion in octane. The treatment made the eggs very sensitive to desiccation and to the tonicity and the composition of the incubation medium. Permeabilized eggs were able to absorb cytological stains, metabolites, alkaloids, and antibiotics.     

One falls,we all fall: How boys of color develop close peer mentoring relationships

The aim of this study was to investigate the processes involved in developing close peer mentoring relationships among African American and Latino male adolescents in a school-based, group peer mentoring program. Qualitative one-on-one in-depth interviews were conducted with six school staff members, who administer the program, and 26 program participants about their experiences in the mentoring program. Data analysis revealed five program processes that led to close mentoring relationships: (a) rapport-building activities, (b) safe space, (c) mutual support, (d) group identity, and (e) trust. These processes ultimately led to bonding and friendship among program members, which further solidified the previous processes. Implications and future directions are discussed.