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Redeker, K. R.

Publications and source records attributed to Redeker, K. R..

3 recordsLinked to original sources

Breast cancer cohort study identifies an effective, non-invasive, breath-based diagnostic linked to cellular environment-dependent, novel methylation metabolisms

Volatile organic compounds (VOCs) demonstrate promise as non-invasive diagnostic tools. However, lack of mechanistically linked VOCs with biomarker discovery platforms limit delivery to the clinic. In this cohort-based study, we observed significant alterations of chloride-containing volatile fluxes, inclusive of methyl chloride (MeCl), in the breath of cancer patients that are consistent with our newly described metabolic model, derived through in vitro cellular assays and in vivo mice models. The diagnostic accuracy of this cohort study (60 patients) is equivalent to mammogram approaches. This newly identified and novel metabolism along with associated diagnostic biomarkers were initially identified through headspace studies of breast cancer cell lines which were deprived of serum, glucose or oxygen, similar to cellular conditions in tumors. In these cellular assays MeCl was consistently informative of cellular stress. Under resource limited conditions cellular production of MeCl was significantly reduced, and in several cases, cellular metabolism shifted to consumption. We present a new "push-pull" model in which cellular production of MeCl is linked to cellular methylation potential and methyl-transferase activity while consumption of MeCl is associated with methionine generation. Neither consumption nor production metabolisms have been described or quantified in humans or human tissues previously. The cellular headspace-derived model was tested using xenograft tumour bearing mice, which demonstrated reduced MeCl production, consistent with this model This work therefore presents a potentially powerful breath biomarker for cancer that translates from cellular and mice models through to human subjects. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/726956v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@71fcdeorg.highwire.dtl.DTLVardef@1905726org.highwire.dtl.DTLVardef@149bb10org.highwire.dtl.DTLVardef@1981c33_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LI(Poly)chloromethane compounds, including methyl chloride and chloroform, are indicative of cancer status in breath sampled from breast cancer clinic patients C_LIO_LIGlucose, serum and oxygen starvation induce significant changes in cellular metabolic fluxes C_LIO_LIReduced methyl chloride production is indicative of cellular stress in vitro C_LIO_LIMethyl chloride production is linked to cellular methylation activity C_LIO_LIMethyl chloride consumption is linked to methionine synthesis, cellular enrichment in chloride concentration, and enhanced chloroform fluxes C_LIO_LIMethyl chloride fluxes in in vitro cell cultures under pathophysiologically relevant conditions translate to the breath of tumour bearing mice C_LI

molecular biology↗

Wood ants on the edge: how do thecharacteristics of linear edges affect thepopulation dynamics of an edgespecialist?

Landscape structure modulates species dispersal by presenting barriers or opportunities. Slow-dispersing edge specialists, e.g. the northern hairy wood ant (Formica lugubris), are likely to be most affected by topography and land management practices, because they require adjacent contrasting habitats, e.g. to access both food and sunlight. In managed forests, canopy gaps are often linear and anthropogenic, such as paths, firebreaks, and roads (collectively rides), and their orientation determines shade distribution. Using data spanning 10 years, we ask how ride orientation and width affect the distribution and dispersal of three F. lugubris populations in the North York Moors, UK. Ride orientation clearly affected nest abundance, with a higher nest density on rides oriented north-south (N-S) or east-west (E-W) (cardinal directions) than on those oriented NE-SW or NW-SE (intercardinal directions). Conforming to predictions based on sunlight availability, N-S oriented rides were occupied more symmetrically than E-W ones, where the north side was used predominantly. Nests were generally larger on narrower rides. Ride orientation also clearly affected dispersal: wood ants dispersed c15 m/year along rides oriented in cardinal directions, compared with only c5 m/year on rides oriented intercardinally. Our results show that ride characteristics (width, orientation), resulting directly from forestry practices, influence the distribution and dispersal of an ecosystem engineer woodland species; this may also apply to other forest-edge specialists. As wood ants can suppress defoliating pests, these findings could benefit forest management; forest planners could encourage wood ant colonisation of plantation forest by ensuring linear features contribute to north-south and east-west connectivity.

ecology↗

Non-destructive chemical sensing within bulk soil using 1000 biosensors per gram of matrix

Gene expression can be monitored in hard-to-image environmental materials using gas-reporting biosensors, but these outputs have only been applied in autoclaved matrices that are hydrated with rich medium. To better understand the compatibility of indicator gas reporting with environmental samples, we evaluated how matrix hydration affects the gas signal of an engineered microbe added to a sieved soil. A gas-reporting microbe presented a gas signal in a forest soil (Alfisol) when hydrated to an environmentally-relevant osmotic pressure. When the gas signal was concentrated prior to analysis, a biosensor titer of 103 cells/gram soil produced a significant signal when soil was supplemented with halides. A signal was also observed without halide amendment, but a higher cell titer (106 cells/gram soil) was required. A sugar-regulated gas biosensor was able to report with a similar level of sensitivity when added to an unsterilized soil matrix, illustrating how gas concentration enables biosensing within a soil containing environmental microbes. These results establish conditions where engineered microbes can report on gene expression in living environmental matrices with minimal perturbation, using biosensor titers that are orders of magnitude lower than the number of cells typically observed in a gram of soil.

synthetic biology↗