A data driven approach to landslide susceptibility mapping in Great Britain

Landslides are a geo-hazard which can have significant societal impacts including loss of human life, physical damage to infrastructure and financial loss. The ability to assess where landslides will occur is therefore of great interest for the public good and can be approached both theoretically and empirically. With the ever increasing availability of spatial data, information on landslide events is now much more readily available ranging from initiation point coordinates to high (sub-metre) resolution topographic information and associated derivatives on affected (and unaffected) areas. Coupled with information on the geology of a region, it is possible to build up a detailed location specific profile of past events, all of which may prove useful for informing where future events may occur. We present preliminary results from an assessment of various data to reassess current British landslide susceptibility datasets. These could be used in future to provide additional information to support landslide forecasting. We define susceptibility as: The potential for the occurrence of a hazard within a specified area. This is currently provided for by the BGS GeoSure Landslides product [1] which classifies landslide prone areas on an A-E (low-high) basis, based on heuristics as well as consideration of lithology, discontinuities and slope angle. Data-driven analyses may provide further insights into where and why landslides occur. Using this knowledge, we hope to improve our current landslide susceptibility model. Consequently, this will enable us to be more confident in the identification of areas where landslides may occur in the future

Different expressions of trypsin and chymotrypsin in relation to growth in Atlantic salmon (Salmo salar L.)

The expressions of trypsin and chymotrypsin in the pyloric caeca of Atlantic salmon (Salmo salar L.) were studied in three experiments. Two internal (trypsin phenotypes, life stages) and three common external factors (starvation, feeding, temperatures) influencing growth rates were varied. Growth was stimulated by increased temperature and higher feeding rate, and it was depressed during starvation. The interaction between trypsin phenotype and start-feeding temperature affected specific activity of trypsin, but not of chymotrypsin. Trypsin specific activity and the activity ratio of trypsin to chymotrypsin (T/C ratio) increased when growth was promoted. Chymotrypsin specific activity, on the other hand, increased when there was a reduction in growth rate whereas fish with higher growth had higher chymotrypsin specific activity resulting in lower T/C ratio value. During a rapid growth phase, trypsin specific activity did not correlate with chymotrypsin specific activity. On the other hand, a relationship between specific activities of trypsin and chymotrypsin could be observed when growth declined, such as during food deprivation. Trypsin is the sensitive key protease under conditions favouring growth and genetically and environmentally affected, while chymotrypsin plays a major role when growth is limited or depressed. Trypsin specific activity and the T/C ratio value are shown to be important factors in the digestion process affecting growth rate, and could be applicable as indicators for growth studies of fish in captive cultures and in the wild, especially when food consumption rate cannot be measured

Long -term feeding with high plant protein based diets in gilthead seabream (Sparus aurata, L.) leads to changes in the inflammatory and immune related gene expression at intestinal level

[EN] Background: In order to ensure sustainability of aquaculture production of carnivourous fish species such as the gilthead seabream (Sparus aurata, L.), the impact of the inclusion of alternative protein sources to fishmeal, including plants, has been assessed. With the aim of evaluating long-term effects of vegetable diets on growth and intestinal status of the on-growing gilthead seabream (initial weight = 129 g), three experimental diets were tested: a strict plant protein-based diet (VM), a fishmeal based diet (FM) and a plant protein-based diet with 15% of marine ingredients (squid and krill meal) alternative to fishmeal (VM+). Intestines were sampled after 154 days. Besides studying growth parameters and survival, the gene expression related to inflammatory response, immune system, epithelia integrity and digestive process was analysed in the foregut and hindgut sections, as well as different histological parameters in the foregut. Results: There were no differences in growth performance (p = 0.2703) and feed utilization (p = 0.1536), although a greater fish mortality was recorded in the VM group (p = 0.0141). In addition, this group reported a lower expression in genes related to pro-inflammatory response, as Interleukine-1 beta (il1 beta, p = 0.0415), Interleukine-6 (il6, p = 0.0347) and cyclooxigenase-2 (cox2, p = 0.0014), immune-related genes as immunoglobulin M (igm, p = 0.0002) or bacterial defence genes as alkaline phosphatase (alp, p = 0.0069). In contrast, the VM+ group yielded similar survival rate to FM (p = 0.0141) and the gene expression patterns indicated a greater induction of the inflammatory and immune markers (il1 beta, cox2 and igm). However, major histological changes in gut were not detected. Conclusions: Using plants as the unique source of protein on a long term basis, replacing fishmeal in aqua feeds for gilthead seabream, may have been the reason of a decrease in the level of different pro-inflammatory mediators (il1 beta, il6 and cox2) and immune-related molecules (igm and alp), which reflects a possible lack of local immune response at the intestinal mucosa, explaining the higher mortality observed. Krill and squid meal inclusion in vegetable diets, even at low concentrations, provided an improvement in nutrition and survival parameters compared to strictly plant protein based diets as VM, maybe explained by the maintenance of an effective immune response throughout the assay.The research has been partially funded by Vicerrectorat d'Investigacio, Innovacio i Transferencia of the Universitat Politecnica de Valencia, which belongs to the project Aquaculture feed without fishmeal (SP20120603). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.Estruch-Cucarella, G.; Collado, MC.; Monge-Ortiz, R.; Tomas-Vidal, A.; Jover Cerdá, M.; Peñaranda, D.; Perez Martinez, G.... (2018). Long -term feeding with high plant protein based diets in gilthead seabream (Sparus aurata, L.) leads to changes in the inflammatory and immune related gene expression at intestinal level. BMC Veterinary Research. 14. https://doi.org/10.1186/s12917-018-1626-6S14Hardy RW. Utilization of plant proteins in fish diets: effects of global demand and supplies of fishmeal. Aquac Res. 2010;41:770–6.Martínez-Llorens S, Moñino AV, Vidal AT, Salvador VJM, Pla Torres M, Jover Cerdá M, et al. Soybean meal as a protein source in gilthead sea bream (Sparus aurata L.) diets: effects on growth and nutrient utilization. Aquac Res. 2007;38(1):82–90.Tacon AGJ, Metian M. Global overview on the use of fish meal and fish oil in industrially compounded aquafeeds: trends and future prospects. Aquaculture. 2008;285:146–58.Bonaldo A, Roem AJ, Fagioli P, Pecchini A, Cipollini I, Gatta PP. Influence of dietary levels of soybean meal on the performance and gut histology of gilthead sea bream (Sparus aurata L.) and European sea bass (Dicentrarchus labrax L.). Aquac Res. 2008;39(9):970–8.Kissil G, Lupatsch I. Successful replacement of fishmeal by plant proteins in diets for the gilthead seabream, Sparus Aurata L. Isr J Aquac – Bamidgeh. 2004;56(3):188–99.Monge-Ortíz R, Martínez-Llorens S, Márquez L, Moyano FJ, Jover-Cerdá M, Tomás-Vidal A. Potential use of high levels of vegetal proteins in diets for market-sized gilthead sea bream (Sparus aurata). Arch Anim Nutr. 2016;70(2):155–72.Santigosa E, Sánchez J, Médale F, Kaushik S, Pérez-Sánchez J, Gallardo MA. Modifications of digestive enzymes in trout (Oncorhynchus mykiss) and sea bream (Sparus aurata) in response to dietary fish meal replacement by plant protein sources. Aquaculture. 2008;282:68–74.Santigosa E, García-Meilán I, Valentin JM, Pérez-Sánchez J, Médale F, Kaushik S, et al. Modifications of intestinal nutrient absorption in response to dietary fish meal replacement by plant protein sources in sea bream (Sparus aurata) and rainbow trout (Onchorynchus mykiss). Aquaculture. 2011;317:146–54.Sitjá-Bobadilla A, Peña-Llopis S, Gómez-Requeni P, Médale F, Kaushik S, Pérez-Sánchez J. Effect of fish meal replacement by plant protein sources on non-specific defence mechanisms and oxidative stress in gilthead sea bream (Sparus aurata). Aquaculture. 2005;249:387–400.Martínez-Llorens S, Baeza-Ariño R, Nogales-Mérida S, Jover-Cerdá M, Tomás-Vidal A. Carob seed germ meal as a partial substitute in gilthead sea bream (Sparus aurata) diets: amino acid retention, digestibility, gut and liver histology. Aquaculture. 2012;338-341:124–33.Baeza-Ariño R, Martínez-Llorens S, Nogales-Mérida S, Jover-Cerda M, Tomás-Vidal A. Study of liver and gut alterations in sea bream, Sparus aurata L., fed a mixture of vegetable protein concentrates. Aquac Res. 2014;47(2):460–71.Estruch G, Collado MC, Peñaranda DS, Tomás Vidal A, Jover Cerdá M, Pérez Martínez G, et al. Impact of fishmeal replacement in diets for gilthead sea bream (Sparus aurata) on the gastrointestinal microbiota determined by pyrosequencing the 16S rRNA gene. PLoS One. 2015;10(8):e0136389. https://doi.org/10.1371/journal.pone.0136389 .Fekete SG, Kellems RO. Interrelationship of feeding with immunity and parasitic infection: a review. Vet Med. 2007;52(4):131–43.Kiron V. Fish immune system and its nutritional modulation for preventive health care. Anim Feed Sci Technol. 2012;173(1–2):111–33.Minghetti M, Drieschner C, Bramaz N, Schug H, Schirmer K. A fish intestinal epithelial barrier model established from the rainbow trout (Oncorhynchus mykiss) cell line, RTgutGC. Cell Biol Toxicol. 2017;33:539–55.Cerezuela R, Meseguer J, Esteban MÁ. Effects of dietary inulin, Bacillus subtilis and microalgae on intestinal gene expression in gilthead seabream (Sparus aurata L.). Fish Shellfish Immunol. 2013;34(3):843–8.Couto A, Kortner TM, Penn M, Bakke AM, Krogdahl O-TA, et al. Effects of dietary soy saponins and phytosterols on gilthead sea bream (Sparus aurata) during the on-growing period. Anim Feed Sci Technol. 2014;198:203–14.Estensoro I, Calduch-Giner JA, Kaushik S, Pérez-Sánchez J, Sitjá-Bobadilla A. Modulation of the IgM gene expression and IgM immunoreactive cell distribution by the nutritional background in gilthead sea bream (Sparus aurata) challenged with Enteromyxum leei (Myxozoa). Fish Shellfish Immunol. 2012;33(2):401–10.Pérez-Sánchez J, Estensoro I, Redondo MJ, Calduch-Giner JA, Kaushik S, Sitjà-Bobadilla A. Mucins as diagnostic and prognostic biomarkers in a fish-parasite model: transcriptional and functional analysis. PLoS One. 2013;8(6):e65457.Reyes-Becerril M, Guardiola F, Rojas M, Ascencio-Valle F, Esteban MÁ. Dietary administration of microalgae Navicula sp. affects immune status and gene expression of gilthead seabream (Sparus aurata). Fish Shellfish Immunol. 2013;35(3):883–9.Pérez-Sánchez J, Benedito-Palos L, Estensoro I, Petropoulos Y, Calduch-Giner JA, Browdy CL, et al. Effects of dietary NEXT ENHANCE ® 150 on growth performance and expression of immune and intestinal integrity related genes in gilthead sea bream (Sparus aurata L.). Fish Shellfish Immunol. 2015;44:117–28.Estensoro I, Ballester-Lozano G, Benedito-Palos L, Grammes F, Martos-Sitcha JA, Mydland L-T, et al. Dietary butyrate helps to restore the intestinal status of a marine teleost (Sparus aurata) fed extreme diets low in fish meal and fish oil. PLoS One. 2016;11(11):1–21.Torrecillas S, Caballero MJ, Mompel D, Montero D, Zamorano MJ, Robaina L, et al. Disease resistance and response against Vibrio anguillarum intestinal infection in European seabass (Dicentrarchus labrax) fed low fish meal and fish oil diets. Fish Shellfish Immunol. 2017;67:302–11.Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;3(6):1101–8.Omnes MH, Silva FCP, Moriceau J, Aguirre P, Kaushik S, Gatesoupe F-J. Influence of lupin and rapeseed meals on the integrity of digestive tract and organs in gilthead seabream (Sparus aurata L.) and goldfish (Carassius auratus L.) juveniles. Aquac Nutr. 2015;21:223–33.Francis G, Makkar HPS, Becker K. Antinutritional factors present in plant-derived alternate fish feed ingredients and their effects in fish. Aquaculture. 2001;199:197–227.Gatlin DM III, Barrows FT, Brown P, Dabrowski K, Gaylord TG, Hardy RW, et al. Expanding the utilization of sustainable plant products in aquafeeds: a review. Aquac Res. 2007;38:551–79.Kader MA, Bulbul M, Koshio S, Ishikawa M, Yokoyama S, Nguyen BT, et al. Effect of complete replacement of fishmeal by dehulled soybean meal with crude attractants supplementation in diets for red sea bream, Pagrus major. Aquaculture. 2012;350-353:109–16.Gómez-Requeni P, Mingarro M, Calduch-Giner JA, Médale F, Martin SAM, Houlihan DF, et al. Protein growth performance, amino acid utilisation and somatotropic axis responsiveness to fish meal replacement by plant protein sources in gilthead sea bream (Sparus aurata). Aquaculture. 2004;232(1–4):493–510.Kader MA, Koshio S, Ishikawa M, Yokoyama S, Bulbul M. Supplemental effects of some crude ingredients in improving nutritive values of low fishmeal diets for red sea bream, Pagrus major. Aquaculture. 2010;308(3–4):136–44.Mai K, Li H, Ai Q, Duan Q, Xu W, Zhang C, et al. Effects of dietary squid viscera meal on growth and cadmium accumulation in tissues of Japanese seabass, Lateolabrax japonicus (Cuvier 1828). Aquac Res. 2006;37(11):1063–9.Peres H, Oliva-Teles A. The optimum dietary essential amino acid profile for gilthead seabream (Sparus aurata) juveniles. Aquaculture. 2009;296(1–2):81–6.Cho CY, Slinger SJ, Bayley HS. Bioenergetics of salmonid fishes: energy intake, expenditure and productivity. Comp Biochem Physiol Part B. 1982;73(1):25–41.Venou B, Alexis MN, Fountoulaki E, Haralabous J. Effects of extrusion and inclusion level of soybean meal on diet digestibility , performance and nutrient utilization of gilthead sea bream ( Sparus aurata ). Aquaculture. 2006;261:343–56.Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP. Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper-excel-based tool using pair-wise correlations. Biotechnol Lett. 2004;26:509–15.Terova G, Robaina L, Izquierdo M, Cattaneo A, Molinari S, Bernardini G, et al. PepT1 mRNA expression levels in sea bream (Sparus aurata) fed different plant protein sources. Springerplus. 2013;2:17.Bates JM, Akerlund J, Mittge E, Guillemin K. Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe. 2007;2(6):371–82.Adamidou S, Nengas I, Henry M, Grigorakis K, Rigos G, Nikolopoulou D, et al. Growth, feed utilization, health and organoleptic characteristics of European seabass (Dicentrarchus labrax) fed extruded diets including low and high levels of three different legumes. Aquaculture. 2009;293(3–4):263–71.Daprà F, Gai F, Costanzo MT, Maricchiolo G, Micale V, Sicuro B, et al. Rice protein-concentrate meal as a potential dietary ingredient in practical diets for blackspot seabream Pagellus bogaraveo: a histological and enzymatic investigation. J Fish Biol. 2009;74(4):773–89.Overland M, Sorensen M, Storebakken T, Penn M, Krogdahl A, Skrede A. Pea protein concentrate substituting fish meal or soybean meal in diets for Atlantic salmon (Salmo salar)-effect on growth performance, nutrient digestibility, carcass composition, gut health, and physical feed quality. Aquaculture. 2009;288(3–4):305–11.Penn MH, Bendiksen EA, Campbell P, Krogdahl AS. High level of dietary pea protein concentrate induces enteropathy in Atlantic salmon (Salmo salar L.). Aquaculture. 2011;310(3–4):267–73.Hedrera MI, Galdames JA, Jimenez-Reyes MF, Reyes AE, Avendaño-Herrera R, Romero J, et al. Soybean meal induces intestinal inflammation in zebrafish larvae. PLoS One. 2013;8(7):1–10.Kokou F, Sarropoulou E, Cotou E, Rigos G, Henry M, Alexis M. Effects of fish meal replacement by a soybean protein on growth, histology, selected immune and oxidative status markers of Gilthead Sea bream, Sparus aurata. J World Aquac Soc. 2015;46(2):115–28.Kokou F, Sarropoulou E, Cotou E, Kentouri M, Alexis M, Rigos G. Effects of graded dietary levels of soy protein concentrate supplemented with methionine and phosphate on the immune and antioxidant responses of gilthead sea bream (Sparus aurata L.). Fish Shellfish Immunol. 2017;64:111–21.Calduch-Giner JA, Sitjà-Bobadilla A, Davey GC, Cairns MT, Kaushik S, Pérez-Sánchez J. Dietary vegetable oils do not alter the intestine transcriptome of gilthead sea bream (Sparus aurata), but modulate the transcriptomic response to infection with Enteromyxum leei. BMC Genomics. 2012;13(1):470.Piazzon MC, Galindo-Villegas J, Pereiro P, Estensoro I, Calduch-Giner JA, Gómez-Casado E, et al. Differential modulation of IgT and IgM upon parasitic, bacterial, viral, and dietary challenges in a perciform fish. Front Immunol. 2016;7. Article 637. https://doi.org/10.3389/fimmu.2016.00637 .Salinas I, Zhang Y, Sunyer JO. Mucosal immunoglobulins and B cells of teleost fish. Dev Comp Immunol. 2011;35(12):1346–65.Krogdahl A, Bakke-McKellep AM, Roed KH, Baeverfjord G. Feeding Atlantic salmon Salmo salar L. soybean products: effects on disease resistance (furunculosis), and lysozyme and IgM levels in the intestinal mucosa. Aquac Nutr. 2000;6:77–84.Chasiotis H, Effendi JC, Kelly SP. Occludin expression in goldfish held in ion-poor water. J Comp Physiol B Biochem Syst Environ Physiol. 2009;179(2):145–54.Chen KT, Malo MS, Beasley-Topliffe LK, Poelstra K, Millan JL, Mostafa G, et al. A role for intestinal alkaline phosphatase in the maintenance of local gut immunity. Dig Dis Sci. 2011;56(4):1020–7.Vaishnava S, Hooper LV. Alkaline phosphatase: keeping the peace at the gut epithelial surface. Cell Host Microbe. 2007;2(6):365–7.Tort L. Stress and immune modulation in fish. Dev Comp Immunol [internet]. Elsevier Ltd. 2011;35(12):1366–75.Martin SAM, Król E. Nutrigenomics and immune function in fish: new insights from omics technologies. Dev Comp Immunol. 2017;75:86–98.Burrells C, Williams PD, Southgate PJ, Crampton VO. Immunological , physiological and pathological responses of rainbow trout (Oncorhynchus mykiss) to increasing dietary concentrations of soybean proteins. Vet Immunol Immunopathol. 1999;72:277–88.Sahlmann C, Sutherland BJG, Kortner TM, Koop BF, Krogdahl Å, Bakke AM. Early response of gene expression in the distal intestine of Atlantic salmon (Salmo salar L.) during the development of soybean meal induced enteritis. Fish Shellfish Immunol. 2013;34(2):599–609.Esteban MÁ, Cuesta A, Ortuño J, Meseguer J. Immunomodulatory effects of dietary intake of chitin on gilthead seabream ( Sparus aurata L .) innate immune system. Fish Shellfish Immunol. 2001;11:303–15.Storebakken T, Kvien IS, Shearer KD, Grisdale-Helland B, Helland SJ. Estimation of gastrointestinal evacuation rate in Atlantic salmon (Salmo salar) using inert markers and collection of faeces by sieving: evacuation of diets with fish meal, soybean meal or bacterial meal. Aquaculture. 1999;172(3–4):291–9.Olsen RE, Myklebust R, Ringø E, Mayhew TM. The influences of dietary linseed oil and saturated fatty acids on caecal enterocytes in Arctic char (Salvelinus alpinus L.): a quantitative ultrastructural study. Fish Physiol Biochem. 2000;22(3):207–16.Heikkinen J, Vielma J, Kemiläinen O, Tiirola M, Eskelinen P, Kiuru T, et al. Effects of soybean meal based diet on growth performance, gut histopathology and intestinal microbiota of juvenile rainbow trout (Oncorhynchus mykiss). Aquaculture. 2006;261(1):259–68.Krogdahl A, Bakke-McKellep AM, Baeverfjord G. Effects of graded levels of standard soybean meal on intestinal structure, mucosal enzyme activities, and pancreatic response in Atlantic salmon (Salmo salar L.). Aquac Nutr. 2003;9:361–71.Cerezuela R, Fumanal M, Tapia-Paniagua ST, Meseguer J, Moriñigo MA, Esteban MA. Changes in intestinal morphology and microbiota caused by dietary administration of inulin and Bacillus subtilis in gilthead sea bream (Sparus aurata L.) specimens. Fish Shellfish Immunol. 2013;34(5):1063–70.Cerezuela R, Fumanal M, Tapia-Paniagua ST, Meseguer J, Moriñigo MÁ, Esteban MÁ. Histological alterations and microbial ecology of the intestine in gilthead seabream (Sparus aurata L.) fed dietary probiotics and microalgae. Cell Tissue Res. 2012;350(3):477–89.Deplancke B, Gaskins HR. Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. Am J Clin Nutr. 2001;73(suppl):1131S–41S.Kokou F, Rigos G, Henry M, Kentouri M, Alexis M. Growth performance, feed utilization and non-specific immune response of gilthead sea bream (Sparus aurata L.) fed graded levels of a bioprocessed soybean meal. Aquaculture. 2012;364-365:74–81

Challenges and Opportunities in Finfish Nutrition

Much of the criticism leveled at aquaculture (e.g., dependency on animal-derived feedstuffs, nutrient-laden effluent discharges, and increased organic contamination in edible products) can be traced to the feeds in use. Accordingly, finfish nutritionists are being challenged to formulate feeds that not only meet the nutritional requirements of livestock but also minimize production costs, limit environmental impacts, and enhance product quality. These challenges not only add considerable complexity to finfish nutrition but also afford opportunities to avoid some of the mistakes made by other industries in the past. From a review of the current status of finfish nutrition with respect to major nutrient classes, we comment on future opportunities and promising avenues of research. Alternative protein sources, specifically those derived from marine bycatch, plants, and microbes, are discussed, as well as methods to facilitate their implementation in finfish feeds. Dietary lipid, its role in fish bioenergetics and physiology, and quality of aquaculture products is reviewed with special emphasis on alternative lipid sources and finishing diets. Carbohydrates and fiber are discussed in terms of nutrient-sparing, least-cost diet formulation and digestive physiology. Micronutrients are reviewed in terms of current knowledge of requirements and, along with other dietary immunostimulants, are given further consideration in a review of nutriceuticals and application in finfish feeds. The status of nutritional research in new aquaculture species is also outlined. By integrating classical approaches with emerging technologies, dietary formulations, and species, finfish nutritionists may identify means to increase production efficiency and sustainability and provide for the continued success of aquaculture

MicroRNA Alterations and Associated Aberrant DNA Methylation Patterns across Multiple Sample Types in Oral Squamous Cell Carcinoma

Background: MicroRNA (miRNA) expression is broadly altered in cancer, but few studies have investigated miRNA deregulation in oral squamous cell carcinoma (OSCC). Epigenetic mechanisms are involved in the regulation of .30 miRNA genes in a range of tissues, and we aimed to investigate this further in OSCC. Methods: TaqManH qRT-PCR arrays and individual assays were used to profile miRNA expression in a panel of 25 tumors with matched adjacent tissues from patients with OSCC, and 8 control paired oral stroma and epithelium from healthy volunteers. Associated DNA methylation changes of candidate epigenetically deregulated miRNA genes were measured in the same samples using the MassArrayH mass spectrometry platform. MiRNA expression and DNA methylation changes were also investigated in FACS sorted CD44high oral cancer stem cells from primary tumor samples (CSCs), and in oral rinse and saliva from 15 OSCC patients and 7 healthy volunteers. Results: MiRNA expression patterns were consistent in healthy oral epithelium and stroma, but broadly altered in both tumor and adjacent tissue from OSCC patients. MiR-375 is repressed and miR-127 activated in OSCC, and we confirm previous reports of miR-137 hypermethylation in oral cancer. The miR-200 s/miR-205 were epigenetically activated in tumors vs normal tissues, but repressed in the absence of DNA hypermethylation specifically in CD44high oral CSCs. Aberrant miR-375 and miR-200a expression and miR-200c-141 methylation could be detected in and distinguish OSCC patient oral rinse and saliva from healthy volunteers, suggesting a potential clinical application for OSCC specific miRNA signatures in oral fluids. Conclusions: MiRNA expression and DNA methylation changes are a common event in OSCC, and we suggest miR-375, miR- 127, miR-137, the miR-200 family and miR-205 as promising candidates for future investigations. Although overall activated in OSCC, miR-200/miR-205 suppression in oral CSCs indicate that cell specific silencing of these miRNAs may drive tumor expansion and progression