Wednesday, October 28, 2009

Meabolomics.. coming of age?

According to Oliver et al. 1998 and Tweeddale et al. 1998, metabolomics is the
study of all of an organism’s low-molecular-weight molecules or metabolites. It is also defined (although sometimes under a slightly different name of metabonomics)as ‘the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modification’(Nicholson et al. 1999, 2002).

After more than a decade (Oliver et al., 1998), metabolomics has begun to acquire some credence in the scientific community and is finally coming of age, although its acceptance cannot be compared with that of its forerunners,

Metabolic network showing the links between en...Image via Wikipedia


genomics and proteomics.

The legitimization of metabolomics as a valid scientific entity depends on the size of the research community it influences (Arita, 2009). By far the most effective medium for inoculation is the web infrastructure: public servers that accommodate experimental data, simple formats and guidelines for their interpretation, and connectivity between data and tools for analysis. When these elements satisfy the condition to initiate a social epidemic, metabolomics will be accepted as a fundamental data-driven science that can unite hitherto independently conducted research disciplines.

At present, both technologies are applied not only to traditional biology but also to metagenomics and environmental sciences, such as the monitoring of microbial dynamics in different environments [Fan at el., 2009; Wikoff et al. 2009].

Still, enthusiasm for metabolomics continues to be lukewarm. Although the name ‘metabolomics’ suggests comprehensive detection, the number of identifiable metabolites is currently limited even if multiple measurement technologies are combined [Fernie, 2007]

The trade-off between coverage(physicochemical variations of metabolites that can be detected by the same method) and/or sensitivity (the lowest detectable metabolite concentration), and precision (accuracy of detected masses or signals) is a severe hurdle this emerging technology has yet to overcome, and the identifiable number of metabolites has not increased
much

In their seminal paper, Fiehn et al. used gas chromatography/ mass spectrometry (GC/MS) and reported the peak assignment of 164 metabolites (101 polar and 63 lipophilic)
in Arabidopsis thaliana [Fiehn et al, 2007]. After nearly a decade, using the same analytical platform, the number of metabolites identifiable at top research institutes was even
lower; this may be attributable to higher measurement accuracy [14,15]. In 2003, Soga et al. reported the detection of 1692 ionic metabolite peaks from Bacillus subtilis by capillary electrophoresis/mass spectrometry (CE/MS) [16].

Another important factor is the intelligibility of data. In biology, the readability of raw data affects popularity. In fact, metabolism, the primary research topic in metabolomics, is notorious for its incomprehensibility and many researchers stayed away from metabolic networks containing lengthy structural and stoichiometric information. The KEGG database gained popularity for its oversimplified representation of metabolic networks: each metabolite is represented as a node without structure, and each reaction as a binary relationship without stoichiometry [34].

In metabolomics we confront many ambiguous data such as metabolite IDs and mass spectral tags (MSTs), that is, repeatedly detected but unidentified mass signals that account for more than half of the detected spectral peaks [50].

Metabolon has recently got 6 millions in serises C financing
Metabolon offers global biochemical profiling (metabolomic) services to researchers working in drug safety and toxicology, bioprocess optimization, consumer products and other areas which benefit from insight into complex biochemical processes and how they change in response to experimental variables.

The company’s technology has been used to identify biochemical biomarkers useful for the development of a wide range of diagnostics. These markers are being applied to the development of its own proprietary diagnostic tools for prostate cancer and insulin resistance.

http://www.metabolon.com/news/index.php
METABOLON CLOSES ADDITIONAL FINANCING
Series C Round Now Closed with a Total of $12.3 Million in Additional Capital



Ellis DI, Dunn WB, Griffin JL, Allwood JW, Goodacre R: Metabolic
fingerprinting as a diagnostic tool. Pharmacogenomics 2007,
8:1243-1266.

Walsh MC, Nugent A, Brennan L, Gibney MJ: Understanding the
metabolome — challenges for metabolomics. Nutr Bull 2009,
33:316-323.

Scalbert A, Brennan L, Fiehn O, Hankemeier T, Kristal BS, van
Ommen B, Pujos-Guillot E, Verheij E, Wishart D, Wopereis S:
Mass-spectrometry-based metabolomics: limitations and
recommendations for future progress with particular focus on
nutrition research. Metabolomics 2009. (Epub ahead of print).
Presented by eminent scientists in metabolomics research, this review
spans topics from the technological foundation of metabolomics to its
future challenges. It is highly recommended as an overview of the
research trend.


14. Kusano M, Fukushima A, Arita M, Jonsson P, Moritz T,
Kobayashi M, Hayashi N, Tohge T, Saito K: Unbiased
characterization of genotype-dependent metabolic
regulations by metabolomic approach in Arabidopsis thaliana.
BMC Syst Biol 2007, 1:53.
15. Lytovchenko A, Beleggia R, Schauer N, Isaacson T, Leuendorf JE,
Hellmann H, Rose JK, Fernie AR: Application of GC–MS for the
detection of lipophilic compounds in diverse plant tissues.
Plant Methods 2009, 5:4
16. Soga T, Ohashi Y, Ueno Y, Naraoka H, Tomita M, Nishioka T:
Quantitative metabolome analysis using capillary
electrophoresis mass spectrometry. J Proteome Res 2003,
2:488-494.
17. van der Werf MJ, Overkamp KM, Muilwijk B, Coulier L,
Hankemeier T: Microbial metabolomics: toward a platform
with full metabolome coverage
. Anal Biochem 2007,
370:17-25.
TNO Quality of Life, 3700 AJ Zeist, The Netherlands. mariet.vanderwerf@tno.nl

18. Gladwell M: The Tipping Point: How Little Things Can Make a Big
DifferenceLittle, Brown and Company; 2000.
19. Liolios K, Mavromatis K, Tavernarakis N, Kyrpides NC: The
Genomes On Line Database (GOLD) in 2007: status of genomic
and metagenomic projects and their asso

34. Okuda S, Yamada T, Hamajima M, Itoh M, Katayama T, Bork P,
Goto S, Kanehisa M: KEGG Atlas mapping for global
analysis of metabolic pathways. Nucleic Acids Res 2008,
36:W423-426.
35. Arita M: The metabolic world of Escherichia coli is not small.
Proc Natl Acad Sci U S A 2004, 101:1543-1547.
50. Kopka J, Schauer N, Krueger S, Birkemeyer C, Usadel B,
Bergmu¨ ller E, Do¨ rmann P, Weckwerth W, Gibon Y, Stitt M et al.:
GMD@CSB.DB: the Golm Metabolome Database.
Bioinformatics 2005, 21:1635-1638.
51. Horai H, Arita M, Nishioka T: Comparison of ESI-MS Spectra in
MassBank Database. In Proceedings of the First International
Conference on BioMedical Engineering and Informatics (BMEI), vol
2; Sanya, China: 2008:853-857.
52. Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B,
Hau DD, Psychogios N, Dong E, Bouatra S et al.: HMDB: a
knowledgebase for the human metabolome. Nucleic Acids Res
2009, 37:D603-610.

53. Kind T, Scholz M, Fiehn O: How large is the metabolome? A
critical analysis of data exchange practices in chemistry. PLoS
One 2009, 4:e5440.


Arita M. What can metabolomics learn from genomics and proteomics? Curr Opin Biotechnol. 2009 Dec;20(6):610-5. Epub 2009 Oct 21.
Metabolomics review (see pubmed abstract and the full article in pdf format)

Fan WMT, Bird JA, Brodie EL, Lane AN: 13C-isotopomer-based
metabolomics of microbial groups isolated from two forest
soils. Metabolomics 2009, 5:108-122.

Fernie AR: The future of metabolic phytochemistry: larger
numbers of metabolites, higher resolution, greater
understanding. Phytochemistry 2007, 68:2861-2880.

Fiehn O, Kopka J, Do¨ rmann P, Altmann T, Trethewey RN,
Willmitzer L: Metabolite profiling for plant functional genomics.
Nat Biotechnol 2000, 18:1157-1161.

Nicholson JK, Lindon JC, Holmes E (1999) ‘Metabonomics’:
understanding the metabolic responses of living systems to
pathophysiological stimuli via multivariate statistical
analysis of biological NMR spectroscopic data. Xenobiotica 29: 1181–1189

Nicholson JK, Connelly J, Lindon JC, Holmes E (2002) Metabonomics: a platform for studying drug toxicity and gene function. Nat Rev Drug Discov 1: 153–161

Oliver SG, Winson MK, Kell DB, Baganz F. 1998. Systematic functional analysis of the yeast genome. Trends in Biotechnology 16: 373-378.

Tweeddale H, Notley-McRobb L, Ferenci T (1998) Effect of slow growth on metabolism of Escherichia coli, as revealed by global metabolite pool (‘‘metabolome’’) analysis.
J Bacteriol 180: 5109–5116


Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC,
Siuzdak G: Metabolomics analysis reveals large effects of gut
microflora on mammalian blood metabolites. Proc Natl Acad
Sci U S A 2009, 106:3698-3703.

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Tuesday, October 27, 2009

Most Marketed Foods are Least Healthy

The typical box cover of Lucky CharmsImage via Wikipedia

New report on marketing spending and nutrient content of cereals confirms once again that the most marketed foods are among the worst for health.

This report has spurred numerous blogs (by Marion Nestle, ABC News, etc) and a lot of debate.
Many think that eating healthy food is solely our own responsibility and the industry should not be blamed. Is it really so?

Eating used to be just a biological function based on energetic needs until food industry had discovered that it could be transformed into addiction. Combining fat, salt and sugar with flavors, textures and visual appeal can make us crave, stimulate our brains to want more, and wire us to overeat. Our bodies are not supposed to crave for unhealthy ingredients, researchers have shown that we are happy to eat non-sweetened food without unneeded additives.

Indeed, we just need "to understand why we eat what we eat", says Dr. David Kessler, the former commissioner of the U.S. Food and Drug Administration and former dean of the Yale School of Medicine. But it may not be easy for most of us - without health-warning labels and regulations. Taste, preferences acquired during childhood and adolescence, friends & family, and media have more influence on what we eat than our understanding of what is healthy and what is not. In 1997, food manufacturers spent 44.4% of their advertising budget on prepared convenience foods, confectionery, snacks, bakery goods compared with only 2.2% on fruits, vegetables, grains and beans. Yale report finds that of the 19 brands marketed in 2008 through early 2009, only Kellogg Mini-Wheats received a healthy nutrition rating. The six worst brands belong to General Mills: Lucky Charms, Cinnamon Toast Crunch, Honey Nut Cheerios, Trix, Reeses’s Puffs and Cocoa Puffs. Post follows with their Fruity and Cocoa Pebbles brand. Finally, Kellogg Frosted Flakes, Corn Pops and Froot Loops complete the worst offenders list. These cereals with the lowest nutrition quality were marketed directly to children in high volumes on television, the internet and in the supermarket.

Aurametrix supports Dr. Kessler's call for action asking for:
  1. All restaurants to list calorie counts for all their dishes;
  2. All food products to carry labels revealing added sugars, refined carbs and fats;
  3. Better public education about food, nutrition and addiction
  4. AND food marketing to be monitored and exposed

We might even need cigarette-like health-warning labels... as in video-games.



Aurametrix is working on tools to help you evaluate your personal health risks and benefits and make the right health & food choices.
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Thursday, October 22, 2009

Healthy and Tasty Halloween

Here are some of the healthiest Halloween treats. Which one is your favorite? Vote for the best and worst treats below.

  1. Fresh fruit - although apples were listed as of the most disappointing treats since it was given to Snow White, it can still be a treat. And what about caramel honey apples, bananas and tangerines?

    Miniature Food Fruit PlateImage by PetitPlat by sk_ via Flickr


  2. Raisins, other dried fruit, nuts or treats like raisinets: dietary fiber and other essential vitamins and minerals. This is another disappointing treat according to Ed Levin though
  3. Lollipops: It takes a while to eat them and they have less calories, some varieties are also free of artificial glavors and colors and can be safe for kids with food allergies. Ed Levin does not consider them to be a treat though, especially dum dum varieties - not even if "they were breaded and deep-fried and served at a fair".
  4. Popcorn balls - especially the spooky type, or Sugarless gum.
  5. Pretzels or crackers
  6. Non-food options: Every kid loves little gifts. School supplies, inexpensive toys, mechanical pencils, colored pencils, balloons, crayons, small craft kits, party favor style toys, and even a toothbrush.





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Thursday, October 15, 2009

The Mechanics of Digestion

Once we swallow a bite of food, a pill, or slurp a smoothie, the ride begins - as food has to travel down the 30 feet (9 meters) pathway before all is said and done. Fortunately, muscle tone in our organs shortens that length by about half.

Digestion begins in the brain that sends messages to a system of salivary glands. Mechanical digestion
starts in the mouth: My Pink Elephant Still Smells Like Rotten Apples. Starting from Mouth to Pharynz to Esophagus to Stomach to Small Intestine to Large Intestine to Rectum to Anus.

The first part of swallowing is a
flinging back of the food into the upper part of the esophagus by a backward movement of the tongue. This powerful motion is followed by wave-like movements in the distal segments of the gullet, which empty remaining bits of food into the stomach. Mechanical movements of the esophagus, stomach, and intestine keep food passing through the digestive system. The normal movements of the small intestine are rhythmical segmentation, or swaying and pendular, or a peristaltic rush. In the stomach the movement is also peristaltic, kneading and mixing take place only in the strong-muscled pars pylorica. The pylorus does not wait to open until the food is digested. Fluids run out as soon as they are drunk, but solids are being held back until the stomach has a chance to liquefy them. The colon is a sluggish organ with few and slow movements, but a few times a day there are mass movements which carry material usually from the transverse colon over into the sigmoid. These movements may give rise to the final act of digestion, letting organisms eliminate waste from the GI tract.

Healthy peristalsis will let you drink a glass of water while standing on your head, although if not skilled enough it could come out of your nose. Astronauts claim that they do not have any problems digesting food with zero gravity.
The mechanics of the digestive tract can, indeed, be affected by the accessory organs - salivatory glands, pancreas, liver, and gallbladder, enzymes and small molecules helping to digest food.
Reverse peristalsis, vomiting, constipation, delay in absorption, leaky gut, intestinal gases caused by fermentation and by irritating foods, may all upset the gradient.

If you tend to have digestive problems, you may need to lie down at least two hours after you finish a meal, this seems to help some people. It does not work for many others though.
In general, your best bet for maximum digestive efficiency seems to be sitting upright. The Mayo Clinic also suggests that you make sure you're relaxed while you're eating, so that your digestive muscles contract normally.

Digestion time also varies depending on the individual and the type of meal. For healthy adults, it's usually between 24 and 72 hours. After you eat, it takes about six to eight hours for food to pass through your stomach and small intestine. Food then enters your large intestine (colon) for further digestion and absorption of water. Elimination of undigested food residue through the large intestine usually begins after 24 hours. Complete elimination from the body may take several days.
Heartburn - a feeling that food is stack in the throat - is one of digestive problems that is usually made worse by lying down or bending over while eating. It gets better if you sit or stand up.

This happens when food and stomach juices go back into the esophagus. Common causes of this (gastroesophageal reflux or GERD) include:

  • Anatomical abnormalities such as

o incomplete closing of the valve (the lower esophageal sphincter, or LES) between the esophagus and the stomach,
o
hiatal hernia, which occurs when a small portion of the stomach pushes upward through the diaphragm, which is the muscle that separates the lungs from the abdomen.

  • Pressure on the stomach caused by obesity, frequent bending over and lifting, tight clothes, straining with bowel movements, vigorous exercise, and pregnancy.
  • Smoking
  • Stress, which can increase the amount of acid your stomach makes and cause your stomach to empty more slowly.

Common foods that can worsen reflux symptoms include

  • Citrus fruits
  • Chocolate
  • Drinks with caffeine or alcohol
  • Fatty and fried foods
  • Garlic and onions
  • Mint flavorings
  • Spicy foods
  • Tomato-based foods, like spaghetti sauce, salsa, chili, and pizza

Use of prescription and nonprescription medicines, such as aspirin, ibuprofen, prednisone, iron, potassium, antihistamines, or sleeping pills is also one of common causes.




Aurametrix is developing decision support systems to help you manage your health - estimate cost/benefits of performing diagnostic tests, therapies and life style modifications. Better tools for a healthier world.

Monday, October 12, 2009

ALT and AST

ALT (ALanine Aminotransferase) test is one of the most common tests used to detect liver damage. ALT values are usually compared to the levels of other enzymes, such as aspartate aminotransferase (AST), to help determine which form of liver disease is present.

Here are a few values reported by the Internet users on various medical forums, blogs and microblogging sites:

Normal Moderately Elevated High
ALT 0-55
40 50 59 66 70 92 109 119 214 227 227 258 434 533 670
AST 0-40
37 43 132 106 90 212 122 281 34 131 288 34 72 114 217

According to different sources, normal values are supposed to be between:
4–36 units per liter (U/L) or 0.07–0.62 microKat/L for ALT and 8–35 units per liter (U/L) or 0.14–0.58 microKat/L for AST; 8-20 for both ALT and AST, 0-40/0-45 IU/L for ALT and AST respectively. Lab Corp considers 0-55 IU/L as normal values for ALT, while Covance lists 6-43 U/L.
Some sources list separate references for males and females.

Higher AST were observed for women with a family history of diabetes, when adjusted for age and BMI.

In acute liver injury, such as viral hepatitis, the ALT and AST may be as high as 1000U/L. In chronic hepatitis or cirrhosis of the liver, ALT and AST may be 10 to 100 times their normal values.

Besides severe liver damage, lead poisoning, exposure to carbon tetrachloride, severe drug reactions, necrosis of large tumors and shock, elevated levels of ALT may be caused by:
  • Alcohol abuse.
  • Celiac disease
  • Fatty deposits in the liver
  • Long-term (chronic) diseases that affect the liver, such as Cirrhosis
  • Medicines, such as statins, antibiotics, chemotherapy, aspirin, narcotics, and barbiturates. People who take acetaminophen (such as Tylenol) can have high ALT blood levels.
  • Mononucleosis
  • Hepatitis (viral, autoimmune) /ALT can be 20x normal value/
  • Hereditary hemochromatosis
  • Liver ischemia (blood flow deficiency to the liver)
  • Liver tumor
  • Quickly growing young children
  • Use of drugs that are poisonous to the liver

ALT test is a part of a liver panel, also known as liver function tests or LFT, is used to detect, evaluate, and monitor liver disease or damage. It usually consists of seven tests that are run at the same time on a blood sample.

ALT -
ALanine Aminotransferase, also known as Glutamate-pyruvate transaminase (EC 2.6.1.2), catalyzes the reversible conversion of L-alanine and alpha-ketoglutarate to L-glutamate and pyruvate. It has 2 distinct molecular and genetic forms: one cytoplasmic (soluble) (GPT1) and one mitochondrial (GPT2; MIM 138210).
AST - ASpartate Aminotransferase, also known as Glutamic-oxaloacetic transaminase is a pyridoxal phosphate-dependent enzyme which exists in cytoplasmic and mitochondrial forms, GOT1 and GOT2, respectively. GOT plays a role in amino acid metabolism and the urea and tricarboxylic acid cycles. See also HPRD:00687; MIM:138180; HPRD:00684; MIM:138150


Aurametrix is developing decision support systems to help you evaluate personal health risks, decide on preventative measures, estimate cost/benefits of performing diagnostic tests. Better tools for a healthier world.
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Wednesday, October 7, 2009

Brain is Lazy but Hackable

Your brain is lazy, shallow, and easily distracted.. but ultimately hackable.

Maximal working memory load is 4-5 things (Cowan 2001) - Even the best students can remember only 6-7 themes out of a possible 30.

We process visual and auditory information separately - bullet-point slides make us read words and listen, overloading of the language areas and leaving the visual cortex absolutely bored, with almost nothing to do. Sparse text with pictures is the best way to present information.

So, don's say much, split the load, and make the brains work - for example, by adding pictures that are not easily linked to the words.


Chris Atherton, a cognitive psychologist (on twitter as @finiteattention, recently delivered this presentation at the Technical Communication UK Conference,