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Metals can be extremely difcult to remove medicine rock generic zofran 4mg, and sometimes their presence can- not be easily determined by testing medicine queen mary buy cheap zofran. One reason this occurs is that some metals symptoms ear infection cheap zofran 4 mg visa, like mercury medications safe during breastfeeding buy generic zofran 8mg, can be hard to detect as they may be tightly associated with virus or bacteria in your body. This is another example of the interaction of two ac- Autism: Pathways to Recovery 35 cidents on the highway—metals and microbes (viruses and/or bacteria). Alone, each can be an issue, but together they may have an additive efect, just as two accidents on the same roadway can have a greater impact on trafc fow than two individual accidents on diferent highways. If, due to improper methylation, this situation does occur, then metals and microbes can inhabit your cells together, and the former may not be easy to detect. However, using the approach outlined in this book, when we frst support the methylation cycle and next address in- fections, we often see an excretion of metals as well, traceable through standard biochemical testing. Tat is why some doctors treat autism through metal chelation (binding) and detoxifcation, and as a result of these treatments we often see improvements in cognitive function, speech, and other areas of functioning. Because of this empirical confrmation, detoxifcation has become a major focus in the holistic approach to autism and other disorders. However, not all physicians are well versed in the rationale and methods of de- toxifcation, and not everyone can accept the image of the body’s being full of toxins. Let me assure you, we are exposed to them, and they remain unless we successfully detoxify. A growing body of genetic research clearly shows that a variety of genes serve a detoxifca- tion function and that specifc genetic impairments in those genes may increase the risk of disease. Garlic is well known as an antiviral, antifungal, antibacterial nutritional supplement. Glutathione is one of the body’s most important defense mechanisms against viruses. Nutrigenomics and the Methylation Cycle It is possible that all of these chelating agents act to both chelate heavy metals as well as to trigger the removal of chronic virus-containing metals from the body. The “detox rash” with which most parents of children with autism are familiar may in some cases be a viral rash, as chronic virus is eliminated from the body along with the excretion of toxic metals. To use the example again of automobile accidents tying up trafc, this would be like removing two disabled vehicles at one time, and letting through the fow of cars. Methylation and Detoxifcation As I just mentioned, one common method for removing metals used by some doctors is a process called chelation. But some of these toxic metals are so bound up and sequestered in the body that traditional chelators cannot get to them. An important part of the protocol presented in this book is a proprietary approach to metal detoxifcation that allows us to target these sequestered metals, along with microbes in the body. The success that this new approach is providing is seen in clinical improvements, along with signifcant increases in urine and/ or fecal excretion of toxic metals. Tese results suggest that these chronic infec- tions efciently bind toxic metals in the body where no chelating agent seems to be able to efectively remove them. Tese results are observed even with patients who, it was thought, did not have signifcant levels of mercury. Yet, in these patients, there is a substantial release of mercury and other toxic metals as the viral and bacterial load is reduced, and patients’ symptoms improve dramatically. One major reason that we need a well-functioning methylation cycle is that the methyl groups the cycle produces can help in the removal of these metals. For example, with arsenic, methyl groups do this by directly combining with these sequestered toxins and removing them. Overall, having a functional methylation cycle can also help to reduce the bacterial or viral load, indirectly aiding in toxin excretion. However, with mutations in this pathway, the body may have difculty address- ing toxin excretion, which is why testing and supplementing for genetic weak- nesses on the pathway can be so important. On the other hand, the fact that methylation is so necessary for detoxifcation but environmental toxins can disrupt methylation creates a toxic catch-22. For example, cadmium inhibits the methylation of phospholipids, which afects your cellular membrane function. Genetic testing reveals that some people Autism: Pathways to Recovery 37 have a tendency to produce insufcient numbers of methyl groups. Obviously, this factor alone reveals why a one-size-fts-all treatment approach is not helpful. Researchers have found that many children with autism do not make enough of the antioxidant glutathione, which is also crucial to removing toxins from the body. When the methylation pathway is dysfunctional, the body can’t produce sufcient glutathione. Further, if the cellular mitochondria are dysfunctional— as they are in some children with autism—they will produce more free radicals as a byproduct and deplete the body’s glutathione. Toxic metals such as aluminum can decrease mitochondrial energy, contributing to mitochondrial dysfunction. So, frst, aluminum and bacteria can interact to decrease mitochondrial function; impaired mitochondria create a greater need for the anti-oxidant glutathione; however due to impaired methylation the body can’t produce the glutathione it needs—another example of the multifactorial, multilayered nature of this condi- tion. Tere is a re- ciprocal relationship between methylation and infammation, almost as if they were on a seesaw: increased infammation will tend to decrease methylation and vice versa. Under-methylation contributes to several kinds of infammation in your body: • Heart and vascular infammation • Autoimmune disorders • Neurological infammation Heart and Vascular Infammation Proteins, especially meats and dairy, contain the amino acid methionine. Nutrigenomics and the Methylation Cycle supposing there are too few methyl groups and homocysteine can’t covert back to methionine In that case, homocysteine levels build up in the body, produc- ing infammation, heart disease, poor circulation, degenerative and other health conditions. Clinically, CoQ10 has been used in the treatment of angina, heart failure, and after coronary artery bypass and cardiomyopathy—infammation and weaken- ing of the heart muscle. Autoimmune Disorders Arthritis, Lupus, Diabetes Part of what I believe often occurs with autism is too much emphasis on the B-cell immune response, which is mediated by antibodies, relative to the cell- mediated response, which is mediated by the T cells. This may be due (at least in part) to the fact that the methylation cycle is needed to make new T cells. Unlike B cell clones, which are “set for life” so to speak, T cell clones need to expand “on demand. A prevalence of immature T cells increases the infammatory response if not properly regulated. This disregulation commonly occurs when there are adequate helper T cells to aid in the antibody response but a lack of enough suppressor T cells to control that response—resulting in autoimmune disorders like lupus, rheumatoid arthritis and type-1 diabetes. Allergic Reactions Histamines, as I mentioned earlier, cause allergic reactions when they are re- leased in response to antigens. Histamine levels in your body are dependent on the methylation cycle because histamines are broken down, or deactivated, by receiving a methyl group. Impaired methylation therefore leads to abnormally high levels of histamine and increased allergic sensitivity, something we often see in children with autism. Chronic infam- mation creates an undesirable feedback loop: improper functioning of the meth- ylation cycle produces infammation, while infammation worsens the ability to methylate properly. Autism: Pathways to Recovery 39 Neurological Infammation Excitotoxins are a signifcant contributor to neurological infammation. Tese chemicals do just what they say—they excite the neurons to fre and ultimately lead to nerve cell death. This can occur over many years—by the time an indi- vidual experiences symptoms, the damage has been done. Excitotoxins occur naturally in the body, but they have also been added to our food supply in huge quantities in the last ffty years. Monosodium glutamate, aspartame, hydrolyzed vegetable protein, and other additives—all these excito- toxins stimulate your taste buds and mask the real taste of food. Commonly, they are added to enhance the favor of artifcial and processed foods, which wouldn’t taste very palatable without them; natural foods, in addition to their higher nu- tritional value, don’t require this form of favor enhancement. Excitotoxins in food overexcite the neurons to the point where they become infamed and begin fring so rapidly they become completely exhausted or die. Tat is misleading, since you must take into account that, in the body, glutamate exists only in very, very small concentra- tions. When the concentration rises above this very minute level, your neurons can become overexcited and fail to fre normally. Further, a wide variety of nutritional supplements contain glutamine or gluta- mate, while many consumers and practitioners remain unaware of its potential for harm in genetically susceptible individuals.
Defects of biopterin metabolism and biogenic amine biosynthesis: Clinical medications migraine headaches purchase zofran 8 mg with amex, diagnostic and therapeutic aspects medicine 027 purchase zofran uk. Antioxidant activity of carotenoids: An electron-spin resonance study on beta-carotene and lutein interactions with spin radicals generated in a chemical system medicine 7 discount zofran amex. Lecithinization of superoxide dismutase potentiates its protective effect against Forssman antiserum-induced elevation in guinea pig airway resistance medications list template order zofran line. Lecithinized superoxide dismutase enhances its pharmacologic potency by increasing its cell membrane affinity. Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Effect of 5,6,7,8-tetrahydroneopterin on oxidative modification of low- density lipoprotein, and its uptake in the macrophage-like cell line J774. A novel fluorogenic reagent for thiols: Ammonium 7-fluorobenzo-2-oxa- 1,3-diazole-4-sulfonate. Direct demonstration of a physiological role for carbon monoxide in olfactory receptor neurons. Immunoelectron microscopic localization of catalase in human eosinophilic leukocytes. Liquid chromatographic determination of glutathione with electrochemically pretreated glassy carbon electrode. Simultaneous determination of uric and ascorbic acids in human serum by reversed-phase high-performance liquid chromatography with electrochemical detection. Determination of phylloquinone and menaquinone in human milk using high performance liquid chromatography. Microanalysis of eumelanin and pheomelanin in hair and melanomas by chemical degradation and liquid chromatography. Detection of some retinoid radicals using high-performance liquid chromatography with electron spin resonance spectroscopy or electrochemical detection. A simple, rapid and sensitive method for the determination of rat serum uric acid by reversed-phase high-performance liquid chromatography with electrochemical detection. Effect of hemodialysis on total antioxidant capacity of serum antioxidants in patients with chronic renal failure. Cancer chemopreventative activity of resveratrol, a natural product derived from grapes. Characterization of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs. Non-selenium-dependent glutathione peroxidase activity in rat lung: Association with lung glutathione S-transferase activity and the effects of hypoxia. Antioxidant effects of ubiquinones in microsomes and mitochondria are mediated by tocopherol recycling. Antioxidant action of ubiquinol homologues with different isoprenoid chain length in biomembranes. Dihydrolipoic acid - universal antioxidant both in the membrane and in the aqueous phase: reduction of peroxyl, ascorbyl and chromanoxyl radicals. High-performance liquid chromatography with electrochemical detection for the determination of thioctic and thioctic acid amide. Toxicology, carcinogenicity, and teratogenicity of some orally administered retinoids. In vitro study of antioxidant potential of various drugs used in the perioperative period. Characterization of a mammalian peroxiredoxin that contains one conserved cysteine. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. Urinary excretion measurement of cysteine and homocysteine in the form of their S-pyridinium derivatives by high-performance liquid chromatography with ultraviolet detection. Simultaneous, high-performance liquid chromatographic analysis of retinol, tocopherols, lycopene and and carotene in serum and plasma. Reference ranges for retinol, tocopherols, lycopene and alpha- and beta-carotene in plasma by simultaneous high-performance liquid chromatographic analysis. High-performance liquid chromatographic post-column reaction system for the electrochemical detection of ascorbic acid and dehydroascorbic acid. Biotransformation of the naturally occurring isothiocyanate sulforaphane in the rat: Identification of phase 1 metabolites and glutathione conjugates. The role of cellular antioxidants and of administered coenzyme Q10 in oxidative cellular damage - experimental liver ischemia and endotoxenia. Low dose alpha tocopherol improves and high dose alpha tocopherol worsens endothelial vasodilator function in cholesterol-fed rabbits. Doxorubicin (adriamycin): A critical review of free radical-dependent mechanisms of cytotoxicity. Picomole analysis of glutathione, glutathione disulfide, glutathione S-sulfonate, and cysteine S-sulfonate by high-performance liquid chromatography. Separation and identification of carotenoids and their oxidation products in the extracts of human plasma. Inactivation of tryptophan hydroxylase by nitric oxide: Enhancement by tetrahydrobiopterin. Involvement of the N-methyl-d-aspartate receptor and free radical in homocysteine mediated toxicity on rat cerebella granule cells in culture. Uric acid substantially enhances the free radical-induced inactivation of alcohol dehydrogenase. A comparative study of the concentrations of hypoxanthine, xanthine, uric acid and allantoin in the peripheral blood of normals and patients with acute myocardial infarction and other ischemic diseases. Antioxidant action of neuromelanin: Mechanism of inhibitory effect on lipid peroxidation. Electrochemical determination of femtomole amounts of free reduced and oxidized glutathione. Measurement of biological thiols and disulfides by high-performance liquid chromatography and electrochemical detection of silver mercaptide formation. Effect of 5,6,7,8- tetrahydroneopterin on the bovine endothelial cell injury induced by cumene hydroperoxide. Parinaric acid as a sensitive fluorescent probe for the determination of lipid peroxidation. Protective effects of estrogens and catecholestrogens against peroxidative membrane damage in vitro. Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress. Validated high-performance liquid chromatography-electrochemical method for determination of glutathione and glutathione disulfide in small tissue samples. Incorporation of ubiquinones into lipid vesicles and inhibition of lipid peroxidation. Inhibition of auto-oxidation of egg yolk lecithin in solvent solution and liposomes by oxidized and reduced coenzyme Q. Quantitative determination of vitamin E and oxidized and reduced coenzyme Q by high- performance liquid chromatography. Simultaneous determination of tocopherols, ubiquinols, and ubiquinones in blood, plasma, tissue homogenates, and subcellular fractions. Exercise training effects on mitochondrial enzyme activity, ubiquinone and vitamin E. Simultaneous determination of tocopherols, ubiquinols and ubiquinones in blood plasma, tissue homogenates, and subcellular fractions. Quantitative determination of vitamin E and oxidized and reduced coenzyme Q by high- performance liquid chromatography. Improved method for the determination of vitamin K1 epoxide in human plasma with electrofluorometric reaction detection. Determination of (endogenous) vitamin K1 in human plasma by reversed- phase high-performance liquid chromatography using fluorometric detection after post-column electrochemical reduction. Reduced free-radical-trapping capacity and altered plasma antioxidant status in cystic fibrosis. Comparisons of coenzyme Q bound to mitochondrial membrane proteins among different mammalian species. Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary additives.
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Schistosomes Itchy papular rash 20 medications that cause memory loss buy discount zofran online, other symptoms depend on the organ that the organism resides in treatment for vertigo purchase zofran 8mg with amex. The sequelae symptoms may be completely different from the symptoms of the acute illness and may occur even if the immune system successfully manages to eliminate the primary infection symptoms 4dpo buy zofran american express. The action of the immune system may initiate the condition as a result of an autoimmune response (Archer and Young 1988; Bunning 1994; Bunning et al symptoms viral meningitis discount 8mg zofran mastercard. However, it is also possible that the initial infection may not have passed when the secondary symptoms appear. For the purposes of this review, sequelae which may last less than three months are also included and, therefore, according to Parkin’s definition (Parkin 2000) are not chronic. The evidence that micro-organisms or their products are directly or indirectly associated with sequelae ranges from convincing to circumstantial, due to the fact that it is unlikely that such complications are identified or epidemiologically linked to the initial illness because the data are not systematically collected. In addition, host symptoms caused by a specific pathogen or product of a pathogen are often wide-ranging and difficult to link with a specific incident, particularly as the time of onset of sequelae may vary. However, sequelae such as hypertension and renal failure may not manifest themselves until 15 years later (Loirat 2001). Leptospires, the bacteria causing leptospirosis, may persist in the brain — in one report, 4 out of 11 patients had persistent headaches for between 6 and 34 years post-infection; ophthalmic involvement with blurred vision has been reported to persist for decades following acute infection (Shpilberg et al. Where there is a long time-period between the initial symptoms and the sequelae, it becomes more difficult to prove an association between the initial disease and the delayed sequelae. It is stressed that the development of a sequela is incidental to exposure to recreational water, i. Lindsay (1997) raises a further issue which is not widely discussed in the literature: the effect of chronic disease on human personality factors as a result of symptoms such as continual pain from arthritis, irritable bowel or other conditions such as chronic diarrhoea. Host factors can influence both the severity of the acute symptoms and the propensity to develop sequelae (Reynolds 2003). The population of immunocompromised individuals is growing (Soldatou and Davies 2003). This population is more susceptible to waterborne infections and tend to experience more severe outcomes (e. People with reduced immune function due to cancer treatment have been shown to have a case-fatality rate for adenovirus infection of 53% (Hierholzer 1992). People with liver diseases are at particularly high risk of fatal septicaemia after ingestion of, or percutaneous exposure to, Vibrio vulnificus (Levine and Griffin 1993). The management interventions that may be required to ensure a safe recreational water environment are outside the scope of this publication but include compliance and enforcement measures, water quality monitoring, sanitary surveys, animal waste control measures, wastewater treatment, risk communication and information dissemination to increase public awareness. The difficulties associated with attributing an infection to recreational water use are numerous and the majority of research in this field has focussed on infections associated with the use of recreational waters resulting in minor, self-limiting symptoms. However, it is plausible that more serious illnesses could result from the recreational use of water and this association has not yet been investigated to any great extent. It is also increasingly apparent that a number of micro-organisms or their products are directly or indirectly associated with secondary health outcomes or sequelae and a number of these sequelae may result from waterborne infections. The 14 Water Recreation and Disease acute diseases attributable to waterborne pathogens and their epidemiology have been well described, but the sequelae that can result from these diseases have not. Assessing potential sequelae of waterborne infections is a critical part of microbial risk assessment and the formulation of public policy. Chapter 2 looks at hazard identification and quantification in recreational waters. Chapter 3 develops a framework for associating disease outcomes with recreational water exposures and presents a systematic method for ranking severity. Chapters 4–6 describe information on specific bacterial, protozoan, trematode and viral pathogens and uses the criteria outlined in Chapter 3 to establish the credibility of association for transmission of each pathogen through recreational water use. Environment Agency, England and Wales (2002) Recreational water quality objectives and standards: Phase 1 – data collection, presentation and recommendations. A report from the control of infection unit, Bristol and Weston Health Authority, to the Bristol City Docks Water Quality Study Group. Cryptosporidiosis-associated mortality following a massive waterborne outbreak in Milwaukee, Wisconsin. Proceedings of 18 Water Recreation and Disease the Annual Conference of the New Zealand Water and Waste Association. Microbes and Infection, 4(4), 399–403 National Centre for Social Research (1998) Leisure day visits. New Jersey Department of Health (1989) A study of the relationship between illness and ocean beach water quality. Public Health Laboratory Service (1959) Sewage contamination of coastal bathing waters in England and Wales: a bacteriological and epidemiological study. Final report on project on epidemiological study on bathers from selected beaches in Malaga, Spain (1988–1989), Athens, Greece. Risk assessment approaches are increasingly being used as a scientific rationale for risk management. This chapter describes the various methods used for identification and quantification of hazards in recreational water risk assessment. Plausibility of Associated Infections: Acute Effects, Sequelae and Mortality by Kathy Pond. The risk of harm occurring is defined as the probability that it will occur as a result of exposure to a defined quantum of hazard (Lacey and Pike 1989). Epidemiological studies are central to the assessment of risk by providing estimates of risk and data for risk assessment models. The aim of descriptive epidemiological investigations is to identify who was ill, the timing of the illness and the location. It is then possible to identify whether the same cases have been exposed to the same source. Confounding factors such as food consumption, age or gender should then be investigated and eliminated since they may bias the interpretation of the results of the study. These investigations will not confirm the route of transmission but may help to build a hypothesis about the cause of the illness which can then be further tested by an observational study. The main types of epidemiological studies used to evaluate the health effects from bathing water pollution are cohort studies and randomised controlled trials. Cohort studies consider a group of people (the cohort), initially free of disease, who are classified into subgroups according to exposure to a potential cause of disease or outcome. Variables of interest are specified and measured and the whole cohort is followed up to see how the disease or outcome of interest differs between the groups with and without exposure. The data is collected at different points in time – prospective cohort studies are capable of estimating the associations of interest, but there may be variation in the composition of different exposure groups, there may be significant loss of follow-up subjects, and in some cases, the studies measure perception rather than the actual clinical incidence. In retrospective cohort studies the estimation of exposure can be significantly inaccurate because water quality can vary to a large degree both temporally and spatially (Kay and Dufour 2000). In randomised controlled trials, subjects in a population are randomly allocated to groups – the control group and the treatment group, and the results of exposure are assessed by comparing the outcome in the two groups (see Box 2. Randomised controlled trials allow the accurate estimation of exposure to water, as well as water-quality assessments (Kay and Dufour 2000). However, these studies are costly and there are ethical problems relating to the need to ask volunteers to swim in contaminated waters. A summary of major epidemiological studies undertaken in relation to illness associated with the use of recreational water and their findings are given in Hazard Identification and Factors Related to Infection and Disease 23 section 1. After initial interviews and medical checks, volunteers reported to the specified bathing location on the trial day where they were randomised into bather and non-bather groups. Bathers entered the water at specified locations where intensive water quality monitoring was taking place. The locations and times of exposure were known for each bather and, thus, a precise estimate of "exposure". A control group of non-bathers came to the beach and had a picnic of identical type to that provided for all volunteers. One week after exposure all volunteers returned for further interviews and medical examinations and later they completed a final postal questionnaire, three weeks after exposure. Samples were collected synchronously at locations 20 m apart every 30 minutes and at three depths. The analysis of the data centred on the links between water quality and gastroenteritis (see Fleisher et al. The data were analysed for relationships between water quality, as indexed by any of the five bacterial indicators measured at any of the three depths and gastroenteritis. Only faecal streptococci, measured at chest depth, provided a statistically significant relationship between water quality and the risk of gastroenteritis. In addition, the results apply only to healthy adult volunteers, and may not be applicable directly to infants or chronically sick people or specialist user groups such as surfers.
Department of Microbiology and Biochemistry symptoms 5 days after iui order zofran once a day, Hochschule Geisenheim 20 University medicine you can order online zofran 4mg lowest price, Von-Lade-Stra e 1 medicine 8 discogs purchase zofran 8 mg overnight delivery, 65366 Geisenheim sewage treatment generic zofran 4 mg on line, Germany. Department of Agriculture, Food and Environment Sciences, University of Foggia, 22 Foggia, Italy. In the present study we have spotted two groups of genetically close –yet 42 distinct– strains from Burgundy wines, one adapted to red wines of and the other 43 white wines. We shed a new light on the existence of ‘virtuous’ bacterial component 44 associated with given ‘terroirs’, and on the possible repercussions of the highlighted 45 microbial genomic diversity on the typical quality traits of regional wines. The integrated analysis of genomic and 50 metabolomic data indicate that the adaptation of each genetic group to their respective 51 niches impacts on the contribution to the volatile fraction of wines. All these results 52 are promising for the innovation of rational selection of malolactic starters. It has been observed that the biogeography of microorganisms 58 is influenced by human practices, as microorganisms have been domesticated to 59 different food matrices that are produced in different regions (Legras et al. Even for products that are made (almost) 61 worldwide such as bread and wine, in which species are not always specific to a 62 region or product, local variations in the biogeography of microorganisms have been 63 observed in the form of genomic traces (Legras et al. This leads to a discussion about the possible 68 existence/dimension on the so-called ‘microbial terroir’ (Gilbert et al. These recent findings tip the balance towards the possibility to 73 talk about microbial terroir of wines. This adaptation is visible at the 80 genomic level, either by the presence/absence of genes, by the presence of specific 81 mutations, or by the genomic signatures (Borneman et al. A large-scale study, analysing a collection of 514 strains isolated from 83 different regions and products, shows that the distribution of O. These 98 compounds can modify the fruity, vegetal or smoked aromas (Antalick et al. Several studies have 100 been made regarding the genetic and genomic variability of O. Here, we have analysed these strains at the genomic and 109 metabolomic levels in order to elucidate the molecular bases of their specific 110 adaptation to each type of wine, and their possible contribution to wine quality. Each genome was assembled either 150 from the clean reads, either from the clean and extended reads, with kmer lengths of 151 25, 37 and 49, giving a total of 6 independent assemblies per genome. Assembly 152 statistics were calculated using homemade programs, and the best of the six 153 assemblies for each genome was kept based on their assembly statistics. The specific mutations 172 of each group of strains were analysed for enrichment with GeneAnswers R package 173 (Feng et al. A matrix containing the quantity of features falling into each subsystem 187 category was built for each strain. For cluster analysis, the matrix was normalised 188 with the formula log1p(x-min(x)), where x represents the number of features. The 189 clusterisation was performed using Canberra distances and Ward clustering method 190 using pheatmap R package. Since Canberra distances computation does not admit 191 vectors composed of only 0’s, the normalised categories composed of only 0’s were 192 replaced by 1’s; it doesn’t have any effect in the clusterisation given that they 193 represent non-informative categories. The unique genes were searched by 199 mutually subtracting the core-genomes and pan-genomes of the two groups of strains. Ethyl butyrate-4,4,4-d3 (>99%), ethyl 209 hexanoate-d11 (>98%), ethyl octanoate-d15 (>98%) and ethyl trans-cinnamate-d5 210 (phenyl-d5) (>99%) were obtained from Cluzeau (Sainte Foy la Grande, France). Sodium sulphate anhydrous 213 (99%) was supplied from Scharlau Chemie (Sentmenat, Spain). The 224 oven temperature was programmed at 40°C for 5 min then raised to 200 °C at 4 225 °C/min. Compounds were quantitated by extrapolating from a calibration curve made 226 on 12% hydroalcoholic solution. According to this method, 1 mL of 231 wine was spiked with 50 µL of internal standard solution (octan-3-ol at 412. The 236 oven temperature was programmed at 80°C for 5 min then raised to 200°C at 237 3°C/min, and then held at that temperature for 15 min. Compounds were quantitated 238 by extrapolating from a calibration curve made on 12% hydroalcoholic solution. A 245 mixture of ethyl butyrate-4,4,4-d3, ethyl hexanoate-d11, ethyl octanoate-d15 and ethyl 246 trans-cinnamate-d5 (phenyl-d5) at about 200 mg/L in ethanol was used as internal 247 standard. In accordance with this method, 5 µL of internal standard solution was 248 added to 5 mL of wine then introduced into a 20 mL standard headspace vial filled 249 with 3. The solution was homogenized with a vortex shaker 250 and then loaded onto a Gerstel autosampling device. The program consisted of 251 swirling the vial at 500 rpm for 2 min at 40 °C, then inserting the fibre into the 252 headspace for 30 min at 40 °C as the solution was swirled again, then transferring the 253 fibre to the injector for desorption at 250°C for 15 min. The oven temperature was 262 programmed at 40 °C for 5 min then raised to 220 °C at 3 °C/min, and then held at 263 that temperature for 30 min. Compounds were quantitated by extrapolating 266 from a calibration curve made on Chardonnay white wine. According to this method, 10 mL 274 of wine were spiked with 5 µL of internal standard solution (octan-3-ol at 1. The mixture was successively extracted with 8 mL and twice with 4 mL of 276 dichloromethane. The organic phases were blended, dried over sodium sulfate, and 277 concentrated under nitrogen flow (100 mL/min) to obtain 250 µL of wine extract. One microliter of organic extract was injected in splitless mode 281 (injector temperature, 250°C; splitless time, 0. The oven was programmed at 40°C for the first minute, raised to 220°C at 3 284 °C/min, and then held at that temperature for 20 min. Compounds were quantitated by extrapolating from a 287 calibration curve made on Chardonnay white wines. Prior to the mathematical 298 transformations useless parts of the chromatogram at the beginning and at the end 299 were removed. They were sequenced by the Illumina method and assembled to produce 101 328 drafts of 127 to 287 contigs (table 1). To ascertain their phylogenetic distribution, a 335 phylogenomic tree was reconstructed with these 14 newly sequenced genomes and 50 336 additional ones reported in previous works (Borneman et al, 2012, Campbell-Sills et 337 al, 2015). Figure 1 shows that all the new strains belong to the 339 genetic group A reported previously (Bilhere et al. The tree also revealed that the 14 new genomes 343 are closely related and that are more distant from all other genomes, suggesting that 344 strains of subgroups A2. More in depth, the cluster analysis 364 revealed that genes of the ‘monosaccharides’ subcategory are overrepresented in all 365 ‘Champagne’/white wine strains. A preliminary analysis of the roles present in this 366 subcategory indicated that these genes belong to fructose utilisation functions. In 367 exchange, genes of the ‘sugar alcohols’, ‘oxidative stress’ and ‘periplasmic stress’ 368 subcategories are more abundant in red wine strains. A preliminary analysis of the 369 roles in the sugar alcohols subcategory shows that the genes correspond to mannitol 370 and glucoside utilisation functions; among the roles of genes of the periplasmic and 371 oxidation stress are an intramembrane protease RasP/YluC, an organic hydroperoxide 372 resistance, a ferroxidase and an iron-binding ferritin-like antioxidant protein. A search for unique roles in this subcategory showed that all 379 the Burgundy strains lost two genes related to the phytoene metabolism: the phytoene 380 synthase and phytoene dehydrogenase. A local Tblastn search for the sequences of the 381 enzymes encoded by these genes against the 50 strains reported in Campbell-Sills et 382 al (2015) shows that nearly half of the strains carry the genes. Their absence in all the 383 Burgundy strains seems to be a characteristic of this group. The pan- and core- 397 genomes were also calculated separately for the strains coming from red wines and 398 ‘Champagne’/white wines. It revealed that the strains coming from red wines have a set of 408 32 orthogroups that are not present in any strain coming from ‘Champagne’ and white 409 wines; on the opposite, the strains coming from ‘Champagne’ and white wine have all 410 in common 63 orthogroups that are not present in any strain from red wine (table S2). These results are congruent with the observations of the 425 subsystems cluster analysis, clarifying differences in the content of sugar metabolism 426 genes between both groups of strains. A local Tblastn search for one the 105 427 glycosyltransferases that are unique to white wine strains against all the strains 428 reported in Campbell-Sills et al. A 437 search for unique mutations revealed that 1,552 of them are exclusive to ‘red wine 438 strain’s, while 1,780 are present only in white wine strains. This confirms recent 443 observations reported for ‘Champagne’ strains (Campbell-Sills et al.