126 research outputs found
Review of Benedict Anderson, 'Under Three Flags: Anarchism and the anti-colonial imagination' (London: Verso, 2005)
Modernizing the Manileña: Technologies of conspicuous consumption for the well-to-do woman, circa 1880s–1930s
The Effects of Ash and Black Carbon (Biochar) on Germination of Different Tree Species
Forest fires generate large amounts of ash and biochar, or black carbon (BC), that cover the soil surface, interacting with the soil’s constituents and its seedbank. This study concerns reproductive ecology assessments supported by molecular characterisation to improve our understanding of the effects of fire and fire residues on the germination behaviour of 12 arboreal species with a wide geographic distribution. For this purpose, we analysed the effects of three ash and one BC concentration on the germination of Acacia dealbata Link, A. longifolia (Andrews) Willd., A. mearnsii De Wild., A. melanoxylon R. Br., Pinus nigra Arnold, P. pinaster Aiton, P. radiata D. Don, P. sylvestris L., Quercus ilex L., Q. pyrenaica Willd., Q. robur L., and Q. rubra L. Each tree species was exposed to ash and BC created from its foliage or twigs (except for Q. rubra, which was exposed to ash and BC of Ulex europaeus L.). We monitored germination percentage, the T50 parameter, and tracked the development of germination over time (up to 1 yr). The BC of A. dealbata, P. pinaster, and Q. robur was analysed by pyrolysis-gas chromatography-mass spectrometry (PY-GC-MS) to assess the molecular composition. In six species, ash inhibited the germination, while in another five species, germination was not affected by ash or by BC. In Q. rubra, ash and BC stimulated its germination. This stimulating effect of the BC on Q. rubra is likely to be related to the chemical composition of the ash and BC obtained from Ulex feedstock. The BC of U. europaeus has a very different molecular composition than the other BC samples analysed, which, together with other factors, probably allowed for its germination stimulating effects.This study was carried out within the Project 10MDS200007PR, financed by the Xunta de Galicia; the Project AGL2013-48189-C2-2-R, financed by the Ministerio de Economía y Competitividad, Spain; and FEDERS
Relationship of Adiposity and Insulin Resistance Mediated by Inflammation in a Group of Overweight and Obese Chilean Adolescents
The mild chronic inflammatory state associated with obesity may be an important link between adiposity and insulin resistance (IR). In a sample of 137 overweight and obese Chilean adolescents, we assessed associations between high-sensitivity C-reactive protein (hs-CRP), IR and adiposity; explored sex differences; and evaluated whether hs-CRP mediated the relationship between adiposity and IR. Positive relationships between hs-CRP, IR and 2 measures of adiposity were found. Hs-CRP was associated with waist circumference (WC) in boys and fat mass index (FMI) in girls. Using path analysis, we found that hs-CRP mediated the relationship between adiposity (WC and FMI) and the homeostatic model assessment of insulin resistance (HOMA-IR) (p < 0.05) in both sexes. Our novel finding is that inflammation statistically mediated the well described link between increased adiposity and IR
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
Explaining Extreme Events of 2012 from a Climate Perspective
Attribution of extreme events is a challenging science and one that is currently undergoing considerable evolution. In this paper are 19 analyses by 18 different research groups, often using quite different methodologies, of 12 extreme events that occurred in 2012. In addition to investigating the causes of these extreme events, the multiple analyses of four of the events, the high temperatures in the United States, the record low levels of Arctic sea ice, and the heavy rain in northern Europe and eastern Australia, provide an opportunity to compare and contrast the strengths and weaknesses of the various methodologies. The differences also provide insights into the structural uncertainty of event attribution, that is, the uncertainty that arises directly from the differences in analysis methodology. In these cases, there was considerable agreement between the different assessments of the same event. However, different events had very different causes. Approximately half the analyses found some evidence that anthropogenically caused climate change was a contributing factor to the extreme event examined, though the effects of natural fluctuations of weather and climate on the evolution of many of the extreme events played key roles as well.Peer Reviewe
Pathway and network analysis of more than 2500 whole cancer genomes
The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments
Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study
Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection
Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study
Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life
- …