Tony Pantalleresco Radio Show notes – November 22nd 2014

Tony Pantallaresco

Welcome to Tony Pantalleresco Radio Show notes – November 22nd 2014

topics in this show include:

Synthetic biology- First functional ‘designer’ chromosome in yeast synthesized by scientists–
Scientists ‘boot up’ a bacterial cell with a synthetic genome
Repeated Oral AdministrationHistopathological and ultra structural effects of nanoparticles on rat testis following 90 days
High-fat diet postpones brain aging in mice

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Synthetic biology– ‘Telomerator’ reshapes synthetic yeast chromosome into more flexible, realistic form, redefining what geneticists can build
Date:

November 3, 2014

Source:

NYU Langone Medical Center / New York University School of Medicine

The telomerator can reformat the “clockface” of a synthetic yeast chromosome into 12 unique linear “timelines,” or chromosomes of equal length.

Credit: Courtesy of NYU Langone.–NYU Langone yeast geneticists report they have developed a novel tool — dubbed “the telomerator” — that could redefine the limits of synthetic biology and advance how successfully living things can be engineered or constructed in the laboratory based on an organism’s genetic, chemical base-pair structure.–Synthetic biologists aim to use such “designer” microorganisms to produce novel medicines, nutrients, and biofuels[F8] .–In a report in the Proceedings of the National Academy of Sciences online Nov. 3, NYU Langone scientists say the telomerator should also improve study of yeast genetics, the model microorganism for human genetics, and help researchers determine how genes, as well as the chromosomes housing them, interact with each other.–The research team, led by Jef Boeke, PhD, a professor and director of NYU Langone’s Institute for Systems Genetics, built the telomerator to convert circular chromosomes into linear ones. Boeke says this better resembles the natural structure of more complex organisms, including humans. Comprising about 1,500 chemical base pairs linked together, the human-made piece of telomerator code can be inserted as a single unit at any position on circular DNA and almost anywhere among a chromosome’s other genes, whose base pairs can number into the hundreds of thousands.—“Our new telomerator resolves a serious and practical issue facing biologists everywhere by helping us experiment with synthetic genes in ways that are more realistic and more closely aligned to the biology of higher organisms, such as humans,” says Boeke. “Until now, we’ve relied on synthesizing functional and stable yeast chromosomes in a circular format — with their telomeres cut off — so they can be uniformly reproduced for easy experimentation within bacteria, whose chromosomes are circular in shape,” he says.–What makes the telomerator particularly effective, researchers say, is its precise capacity to add buffering chromosome endings, or telomeres, to newly linearized yeast chromosomes.–Moreover, the telomerator, which took Boeke and lead study investigator Leslie Mitchell, PhD, two years to construct and test, allows researchers to study how a gene’s position or placement on a chromosome affects the gene’s function.–The key components of the telomerator are its telomere seed sequences, which are exposed when the telomerator “cassette” — its packaged components — is activated.–To test the device, Mitchell inserted a telomerator cassette at 54 different locations on a circular synthetic yeast chromosome of about 90,000 base pairs and tested whether the chromosome could be segmented and straightened at each position. Researchers compared the process to a clock dial, in which they could insert the telomerator at any “hour” on the clock face to break the circle and yield 12 different timelines, but all of equal length. Colonies grew for 51 of the linear yeast chromosomes, failing only in chromosomes where essential genes were placed too close to the telomere ends.–Additional testing confirmed that the modified yeast chromosomes were in a linear format and of the precise length predicted by researchers.–Boeke’s research is part of an international effort to manufacture all the yeast chromosomes, threadlike structures that carry genes in the nucleus of all plant and animal cells, and move genetic research one step closer to constructing the organism’s entire functioning genome. Earlier this year, Boeke’s team reported building the first of the 16 yeast chromosomes, which they call synIII, and successfully incorporating it into brewer’s yeast, known scientifically as Saccharomyces cerevisiae.–Story Source-The above story is based on materials provided by NYU Langone Medical Center / New York University School of Medicine. Note: Materials may be edited for content and length.[F9]

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First functional ‘designer’ chromosome in yeast synthesized by scientists
Date-March 27, 2014 Source-NYU Langone Medical Center

Researchers have synthesized the first functional chromosome in yeast, an important step in the emerging field of synthetic biology, designing microorganisms to produce novel medicines, raw materials for food, and biofuels.–An international team of scientists led by Jef Boeke, PhD, director of NYU Langone Medical Center’s Institute for Systems Genetics, has synthesized the first functional chromosome in yeast, an important step in the emerging field of synthetic biology, designing microorganisms to produce novel medicines, raw materials for food, and biofuels.–Over the last five years, scientists have built bacterial chromosomes and viral DNA, but this is the first report of an entire eukaryotic chromosome, the threadlike structure that carries genes in the nucleus of all plant and animal cells, built from scratch. Researchers say their team’s global effort also marks one of the most significant advances in yeast genetics since 1996, when scientists initially mapped out yeast’s entire DNA code, or genetic blueprint.–“Our research moves the needle in synthetic biology from theory to reality,” says Dr. Boeke, a pioneer in synthetic biology who recently joined NYU Langone from Johns Hopkins University.–“This work represents the biggest step yet in an international effort to construct the full genome of synthetic yeast,” says Dr. Boeke. “It is the most extensively altered chromosome ever built. But the milestone that really counts is integrating it into a living yeast cell. We have shown that yeast cells carrying this synthetic chromosome are remarkably normal[F10] . They behave almost identically to wild yeast cells, only they now possess new capabilities and can do things that wild yeast cannot.”-In this week’s issue of Science online March 27, the team reports how, using computer-aided design, they built a fully functioning chromosome, which they call synIII, and successfully incorporated it into brewer’s yeast, known scientifically as Saccharomyces cerevisiae.–The seven-year effort to construct synIII tied together some 273, 871 base pairs of DNA, shorter than its native yeast counterpart, which has 316,667 base pairs. Dr. Boeke and his team made more than 500 alterations to its genetic base, removing repeating sections of some 47,841 DNA base pairs, deemed unnecessary to chromosome reproduction and growth. Also removed was what is popularly termed junk DNA, including base pairs known not to encode for any particular proteins, and “jumping gene” segments known to randomly move around and introduce mutations. Other sets of base pairs were added or altered to enable researchers to tag DNA as synthetic or native, and to delete or move genes on synIII.–“When you change the genome you’re gambling. One wrong change can kill the cell,” says Dr. Boeke. “We have made over 50,000 changes to the DNA code in the chromosome and our yeast still live. That is remarkable. It shows that our synthetic chromosome is hardy, and it endows the yeast with new properties[F11] .”–The Herculean effort was aided by some 60 undergraduate students enrolled in the “Build a Genome” project, founded by Dr. Boeke at Johns Hopkins. The students pieced together short snippets of the synthetic DNA into stretches of 750 to 1,000 base pairs or more, an effort led by Srinivasan Chandrasegaran, PhD, a professor at Johns Hopkins. Chandrasegaran is also the senior investigator of the team’s studies on synIII.–Student participation kicked off what has become an international effort, called Sc2.0 for short, in which several academic researchers have partnered to reconstruct the entire yeast genome, including collaborators at universities in China, Australia, Singapore, the United Kingdom, and elsewhere in the U.S.-Yeast chromosome III was selected for synthesis because it is among the smallest of the 16 yeast chromosomes and controls how yeast cells mate and undergo genetic change. DNA comprises four letter-designated base macromolecules strung together in matching sets, or base pairs, in a pattern of repeating letters. “A” stands for adenine, paired with “T” for thymine; and “C” represents cysteine, paired with “G” for guanine. When stacked, these base pairs form a helical structure of DNA resembling a twisted ladder.–Yeast shares roughly a third of its 6,000 genes — functional units of chromosomal DNA for encoding proteins — with humans. The team was able to manipulate large sections of yeast DNA without compromising chromosomal viability and function using a so-called scrambling technique that allowed the scientists to shuffle genes like a deck of cards, where each gene is a card. “We can pull together any group of cards, shuffle the order and make millions and millions of different decks, all in one small tube of yeast,” Dr. Boeke says. “Now that we can shuffle the genomic deck, it will allow us to ask, can we make a deck of cards with a better hand for making yeast survive under any of a multitude of conditions, such as tolerating higher alcohol levels.”–Using the scrambling technique, researchers say they will be able to more quickly develop synthetic strains of yeast that could be used in the manufacture of rare medicines, such as artemisinin for malaria, or in the production of certain vaccines, including the vaccine for hepatitis B, which is derived from yeast. Synthetic yeast, they say, could also be used to bolster development of more efficient biofuels, such as alcohol, butanol, and biodiesel[F12] .–The study will also likely spur laboratory investigations into specific gene function and interactions between genes, adds Dr. Boeke, in an effort to understand how whole networks of genes specify individual biological behaviors.–Their initial success rebuilding a functioning chromosome will likely lead to the construction of other yeast chromosomes (yeast has a total of 16 chromosomes, compared to humans’ 23 pairs), and move genetic research one step closer to constructing the organism’s entire functioning genome, says Dr. Boeke.–Dr. Boeke says the international team’s next steps involve synthesizing larger yeast chromosomes, faster and cheaper. His team, with further support from Build a Genome students, is already working on assembling base pairs in chunks of more than 10,000 base pairs. They also plan studies of synIII where they scramble the chromosome, removing, duplicating, or changing gene order.–Detailing the Landmark Research Process–Before testing the scrambling technique, researchers first assessed synIII’s reproductive fitness, comparing its growth and viability in its unscrambled from — from a single cell to a colony of many cells — with that of native yeast III. Yeast proliferation was gauged under 19 different environmental conditions, including changes in temperature, acidity, and hydrogen peroxide, a DNA-damaging chemical. Growth rates remained the same for all but one condition.–Further tests of unscrambled synIII, involving some 30 different colonies after 125 cell divisions, showed that its genetic structure remained intact as it reproduced. According to Dr. Boeke, individual chromosome loss of one in a million cell divisions is normal as cells divide. Chromosome loss rates for synIII were only marginally higher than for native yeast III.–To test the scrambling technique, researchers successfully converted a non-mating cell with synIII to a cell that could mate by eliminating the gene that prevented it from mating.–Story Source-The above story is based on materials provided by NYU Langone Medical Center. Note: Materials may be edited for content and length.-Journal Reference-N. Annaluru, H. Muller, L. A. Mitchell, S. Ramalingam, G. Stracquadanio, S. M. Richardson, J. S. Dymond, Z. Kuang, L. Z. Scheifele, E. M. Cooper, Y. Cai, K. Zeller, N. Agmon, J. S. Han, M. Hadjithomas, J. Tullman, K. Caravelli, K. Cirelli, Z. Guo, V. London, A. Yeluru, S. Murugan, K. Kandavelou, N. Agier, G. Fischer, K. Yang, J. A. Martin, M. Bilgel, P. Bohutski, K. M. Boulier, B. J. Capaldo, J. Chang, K. Charoen, W. J. Choi, P. Deng, J. E. DiCarlo, J. Doong, J. Dunn, J. I. Feinberg, C. Fernandez, C. E. Floria, D. Gladowski, P. Hadidi, I. Ishizuka, J. Jabbari, C. Y. L. Lau, P. A. Lee, S. Li, D. Lin, M. E. Linder, J. Ling, J. Liu, J. Liu, M. London, H. Ma, J. Mao, J. E. McDade, A. McMillan, A. M. Moore, W. C. Oh, Y. Ouyang, R. Patel, M. Paul, L. C. Paulsen, J. Qiu, A. Rhee, M. G. Rubashkin, I. Y. Soh, N. E. Sotuyo, V. Srinivas, A. Suarez, A. Wong, R. Wong, W. R. Xie, Y. Xu, A. T. Yu, R. Koszul, J. S. Bader, J. D. Boeke, S. Chandrasegaran. Total Synthesis of a Functional Designer Eukaryotic Chromosome. Science, 2014; DOI: 10.1126/science.1249252

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Scientists ‘boot up’ a bacterial cell with a synthetic genome
Date-May 20, 2010-Source-American Association for the Advancement of Science

Scanning electron micrographs of M. mycoides JCVI-syn1. Samples were post-fixed in osmium tetroxide, dehydrated and critical point dried with CO2 , then visualized using a Hitachi SU6600 scanning electron microscope at 2.0 keV.

Credit: Electron micrographs were provided by Tom Deerinck and Mark Ellisman of the National Center for Microscopy and Imaging Research at the University of California at San Diego–Scientists have developed the first cell controlled by a synthetic genome. They now hope to use this method to probe the basic machinery of life and to engineer bacteria specially designed to solve environmental or energy problems[F13] .–The study will be published online by the journal Science, at the Science Express website, on May 20.–The research team, led by Craig Venter of the J. Craig Venter Institute, has already chemically synthesized a bacterial genome, and it has transplanted the genome of one bacterium to another.[F14] Now, the scientists have put both methods together, to create what they call a “synthetic cell,” although only its genome is synthetic.–“This is the first synthetic cell that’s been made, and we call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer,” said Venter.–“This becomes a very powerful tool for trying to design what we want biology to do. We have a wide range of applications [in mind],” he said.–For example, the researchers are planning to design algae that can capture carbon dioxide and make new hydrocarbons that could go into refineries. They are also working on ways to speed up vaccine production. [F15] Making new chemicals or food ingredients and cleaning up water are other possible benefits, according to Venter.–In the Science study, the researchers synthesized the genome of the bacterium M. mycoides and added DNA sequences that “watermark” the genome to distinguish it from a natural one.–Because current machines can only assemble relatively short strings of DNA letters at a time, the researchers inserted the shorter sequences into yeast, whose DNA-repair enzymes linked the strings together. They then transferred the medium-sized strings into E. coli and back into yeast. After three rounds of assembly, the researchers had produced a genome over a million base pairs long.–The scientists then transplanted the synthetic M. mycoides genome into another type of bacteria, Mycoplasm capricolum.[F16] The new genome “booted up” the recipient cells. Although fourteen genes were deleted or disrupted in the transplant bacteria, they still looked like normal [F17] M. mycoides bacteria and produced only M. mycoides proteins, the authors report.–“This is an important step we think, both scientifically and philosophically. It’s certainly changed my views of the definitions of life and how life works,” Venter said.–Acknowledging the ethical discussion about synthetic biology research, Venter explained that his team asked for a bioethical review in the late 1990s and has participated in variety of discussions on the topic.–“I think this is the first incidence in science where the extensive bioethical review took place before the experiments were done. It’s part of an ongoing process that we’ve been driving, trying to make sure that the science proceeds in an ethical fashion, that we’re being thoughtful about what we do and looking forward to the implications to the future,” he said.–This research was funded by Synthetic Genomics, Inc. Three of the authors and the J. Craig Venter Institute hold Synthetic Genomics, Inc. stock. The J. Craig Venter Institute has filed patent applications on some of the techniques described in this paper.–More information can be found on the J. Craig Venter Institute web site at: http://www.jcvi.org/cms/research/projects/first-self-replicating-synthetic-bacterial-cell/—Story Source–The above story is based on materials provided by American Association for the Advancement of Science. Note: Materials may be edited for content and length.–Journal Reference–Daniel G. Gibson, John I. Glass, Carole Lartigue, Vladimir N. Noskov, Ray-Yuan Chuang, Mikkel A. Algire, Gwynedd A. Benders, Michael G. Montague, Li Ma, Monzia M. Moodie, Chuck Merryman, Sanjay Vashee, Radha Krishnakumar, Nacyra Assad-Garcia, Cynthia Andrews-Pfannkoch, Evgeniya A. Denisova, Lei Young, Zhi-Qing Qi, Thomas H. Segall-Shapiro, Christopher H. Calvey, Prashanth P. Parmar, Clyde A. Hutchison III, Hamilton O. Smith, and J. Craig Venter. Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome. Science, May 20, 2010 DOI: 10.1126/science.1190719

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Repeated Oral AdministrationHistopathological and ultra structural effects of nanoparticles on rat testis following 90 days (Chronic study)
Mansee Thakur, Himanshu Gupta, Dipty Singh, Ipseeta R Mohanty, Ujjwala Maheswari, Geeta Vangae, Arvind Joshi

[Hide abstract]
ABSTRACT: Background Nanoparticles (Ag NPs)[F18] have recently received much attention for their possible applications in biotechnology and biomedical. However, little is known about the toxicity in reproductive organs of animal model following exposure to Nanoparticles.Objective This study therefore, tried to examine the effects of Nanoparticles with a mean diameter of 5-20 nm range on the histology of the testis of wistar rats and correlate it with Transmission Electron Microscopy results.Materials and methods Sixteen wistar rats were randomly divided into two groups of 8 rats each. Each group received the following via gavage technique for 90 days: Control Group (Group-1)-tap water; Experimental group (Group 2) – Nanoparticles (20ug/kg/day). After ninety days (chronic study), rats were sacrificed and testis tissues was processed for histology and transmission electron microscopic study. There was significant difference between the observations of group-1 and group 2. The changes observed in the testis were disarray of the spermatogenic cells and disorientation of the testis. These changes were observed to have been disappearing from normal histological features. Detailed structural damages were observed with TEM analysis, such as depletion of germ cells, germinal cells necrosis, especially in spermatogonia and Leydig cells had an abnormal fibroblast-like appearance, abnormal space between neighboring sertoli cells, mitochondria, lost cristae and vacuolated (none energized) with those animals exposed to nanoparticles.Conclusion It seems that nanoparticles have acute and significant effects on spermatogenesis and number of spermatogenic cells. More experimental investigations are necessary to elucidate better conclusion regarding the safety of nanoparticles on male reproduction system.

Journal of nanobiotechnology. 10/2014; 12(1):42.

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High-fat diet postpones brain aging in mice
Date:

November 5, 2014

Source:

University of Copenhagen – The Faculty of Health and Medical Sciences

Coconut oil and fresh coconut The researchers see a particular positive effect when the mice are given the so-called medium chain fatty acids — e.g., from coconut oil.—New Danish-led research suggests that signs of brain aging can be postponed in mice if placed on a high-fat diet. In the long term, this opens the possibility of treatment of children suffering from premature aging and patients with Alzheimer’s and Parkinson’s disease. The research project is headed by the Center for Healthy Aging, University of Copenhagen and the National Institute of Health.–When we get older, defects begin to develop in our nervous system, our brain loses some of its intellectual capacity, and the risk of developing diseases such as Parkinson’s and Alzheimer’s increases. Alzheimer’s disease is currently the fastest-growing age-related disease.–Throughout our lives, it is important that our cells — to the extent possible — keep our DNA undamaged, and, therefore, the cells have a system that repairs the damage that occurs all the time. Humans age when the repair system ceases to function. In diseases such as Alzheimer’s, the researchers also see damage to the DNA–A new research project headed by the Center for Healthy Aging, University of Copenhagen and the National Institute of Health has studied mice having a defect in their DNA repair system. In humans, this defect causes the disorder Cockayne syndrome, where patients prematurely age as children and die at an age of 10-12 years. The study shows that placing a mouse model of Cockayne syndrome on a high-fat diet will postpone aging processes such as impaired hearing and weight loss.

Fat putting a stop to premature aging–“The study is good news for children with Cockayne syndrome, because we do not currently have an effective treatment. Our study suggests that a high-fat diet can postpone aging processes. A diet high in fat also seems to postpone the aging of the brain. The findings therefore potentially imply that patients with Alzheimer’s and Parkinson’s disease in the long term may benefit from the new knowledge,” says Professor Vilhelm Bohr from the Center for Healthy Aging, University of Copenhagen and the National Institute of Health, who has headed the study.–Our brain has a constant need for fuel in the form of either sugar or so-called ketones. Ketones are the brain’s fuel reserve, and, in particular, play an important role in periods of low blood sugar levels, e.g. if you are fasting[F19] . This is because the body breaks down fat if it needs sugar, and during this process it produces ketones. The researchers see a particular positive effect when the mice are given the so-called medium chain fatty acids — e.g. from coconut oil.[F20]

Brain cells need extra fuel

“In cells from children with Cockayne syndrome, we have previously demonstrated that aging is a result of the cell repair mechanism being constantly active. It eats into the resources and causes the cell to age very quickly. We therefore hope that a diet with a high content of coconut oil or similar fats will have a beneficial effect, because the brain cells are given extra fuel and thus the strength to repair the damage,” says postdoc Morten Scheibye-Knudsen from the National Institute of Health.–The study has just been published in the scientific journal Cell Metabolism.–Story Source-The above story is based on materials provided by University of Copenhagen – The Faculty of Health and Medical Sciences. Note: Materials may be edited for content and length.–Journal Reference-Morten Scheibye-Knudsen, Sarah J. Mitchell, Evandro F. Fang, Teruaki Iyama, Theresa Ward, James Wang, Christopher A. Dunn, Nagendra Singh, Sebastian Veith, Md Mahdi Hasan-Olive, Aswin Mangerich, Mark A. Wilson, Mark P. Mattson, Linda H. Bergersen, Victoria C. Cogger, Alessandra Warren, David G. Le Couteur, Ruin Moaddel, David M. Wilson, Deborah L. Croteau, Rafael de Cabo, Vilhelm A. Bohr. A High-Fat Diet and NAD Activate Sirt1 to Rescue Premature Aging in Cockayne Syndrome. Cell Metabolism, 2014; 20 (5): 840 DOI: 10.1016/j.cmet.2014.10.005

TOP C

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[F1]In other words the results will be reflective back the individual who is using the methods—proof is in the results

[F2]In other words —the glory was in the practice rather then the results

[F3]A process to alleviate and reverse the decline require habits and chemistry

[F4]Key point here —allowing the body to utilize and rest –so not to overload and over consume

[F5]At this point it is theoretical but anyone who makes the right changes to what they consume and eliminate things that cause organ or tissue failure or eliminate cellular damage will slow down or reverse negative implication causing health to become dysfunctional or debilitated

[F6]Male Hormone–

[F7]Female Hormones

[F8]This is utilizing things on a nanoscale—we are dealing here with creation with no restrictions—and with nanogenetics there is a real danger and a significant concern on what these things will assimilate with—what they can alter—disrupt or incorporate into there matrix or be incorporated—and it’s effect on NORMAL biological life and if once incorporated can it be removed and the original DNA or GENE be restored to it’s original design

[F9]This is a form of weaponizing the genes as a bionano weapon —which may have been already releases through chemtrails and other bioagents in the water supply and food chain—with this technology you could insert this sequence target a specific gene or gene type and activate or deactivate the signals or program that the gene des —disrupting any biology in the system —anything from heart rate to sugar regulation to immune response or non response—this is the real implication to this —another form of weaponizing ones own body against itself through genetic manipulation

[F10]Normal!!!— only they now possess new capabilities and can do things that wild yeast cannot—and this is called NORMAL

[F11]Now the question remains what are those new properties—what do they do —how do they work—what function do they fulfil

[F12]Will never happen unless the oil industry controls this technology—whenthey mention the benfits they forget to mention who will have this technology to produce these wonderful developments as well—when you are talking progress and development things like this are utilized more for war and control then benefit

[F13]That could be classified as anything—from human populations to environmental

[F14]Genetic Engineering–

[F15]Bio Manipulation and incorporating this with a nano delivery method—you will have genetic alterations with this in anything you inject this into–

[F16]Disease Creation??—pestilence—even an accidental release of this could wipe out –populations and set back people in evolution

[F17]But the alterations caused a different effect—what was that effect

[F18]Silver Nano Particles

[F19]palm kernel oil and coconut oil. Sources of MCT’s as well as horse fat–

[F20]

From a nutritional standpoint, saturated triglycerides with a medium (6 to 12) carbon chain length (MCT) have traditionally been regarded as biologically inert substances, merely serving as a source of fuel calories that is relatively easily accessible for metabolic breakdown compared with long chain triglycerides (LCT). This quality of MCT has been shown to offer both benefits and risks depending on the clinical situation, with potential positive effects on protein metabolism in some studies on one side, and an increased risk for ketogenesis and metabolic acidosis on the other. At another level, studies regarding lipid effects of MCT on the immune system, as with LCT, so far have yielded equivocal results, although there is a recent experimental evidence to suggest that MCT posses immune modulating properties and should in fact be regarded as bioactive mediators. Most of this information comes from studies where effects of MCT have been compared with those of LCT in lipid emulsions, as part of parenteral (intravenous) nutrition formulations. Unfortunately, the relevance of these observations for clinical practice remains largely unclear because adequately powered trials that clearly point out the position of MCT in relation to structurally different lipids have not been performed. In the present paper we review the experimental and clinical evidence for cellular and physiological effects of nutritional MCT. In addition, studies describing possible mechanisms behind the observed effects