EK
Date-November 3, 2014
Source-Federation of American Societies for Experimental Biology
Almost everyone knows that improving your eating habits will most likely improve your health. What most people may not know, however, is that the effects of poor eating habits persist long after dietary habits are improved. In a new report appearing in the November 2014 issue of the Journal of Leukocyte Biology, scientists use mice to show that even after successful treatment of atherosclerosis (including lowering of blood cholesterol and a change in dietary habits) the effects of an unhealthy lifestyle still affect the way the immune system functions. This change in function occurs largely because poor eating habits alter the way genes express themselves, including genes related to immunity. This change in gene expression (epigenetics) ultimately keeps the risk of cardiovascular disorders higher than it would be had there been no exposure to unhealthy foods in the first place.–“I hope that this study demonstrates the importance of diet-induced changes in the epigenome and encourages further research into the interaction between dietary patterns, DNA methylation and disease,” said Erik van Kampen, a researcher involved in the work from the Division of Biopharmaceutics at the Leiden Academic Centre for Drug Research at Leiden University in Leiden, The Netherlands.–To make their discovery, scientists used two groups of mice that had an altered gene making them more susceptible to developing high blood cholesterol and atherosclerosis. These mice were either fed a high-fat, high-cholesterol diet (Western-type diet, WTD) or a normal diet (chow). After a long period of feeding, bone marrow was isolated from the mice and transplanted into mice with a similar genetic background that had their own bone marrow destroyed. The recipient mice were left on chow diet for several months, after which the development of atherosclerosis in the heart was measured. The number and status of immune cells throughout the body and epigenetic markings on the DNA in the bone marrow also were examined. They found that DNA methylation, an epigenetic signature, in the bone marrow was different in mice that received bone marrow from the WTD-fed donors compared to the mice receiving bone marrow from chow-fed donors. Furthermore, these mice had large differences in their immune system and increased atherosclerosis.–“We’ve long known that lifestyle and nutrition could affect immune system function,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “The ability of nutritional history to have durable affects on immune cells demonstrated in this new report could have profound implications for treatment of diseases with immune underpinnings. The length of such effects will be critical to determine and it will be interesting to examine the effects of drugs that can modify epigenetics.”–Story Source-The above story is based on materials provided by Federation of American Societies for Experimental Biology. Note: Materials may be edited for content and length.—Journal Reference-E. van Kampen, A. Jaminon, T. J. C. van Berkel, M. Van Eck. Diet-induced (epigenetic) changes in bone marrow augment atherosclerosis. Journal of Leukocyte Biology, 2014; 96 (5): 833 DOI: 10.1189/jlb.1A0114-017R
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Alzheimer’s Disease and Parkinson’s Disease. A Dietary Connection
By Fred Kummerow, Ph.D.
For the past 70 years I have been researching lipids (fats) and their relationship to heart disease. I found that patients who ate an overabundance of deep fat fried foods and too much polyunsaturated fatty acids (PUFAs) produced a chemical change in the composition of their arteries. –When I analyzed the blood of these patients I found that their arteries had an increase of calcification. If these patients continue to eat these oxidized fats, the calcification will completely block their arteries. Heart disease can be prevented if these foods are not consumed. —-The oils generally used in deep fat frying, like soybean oil (and other vegetable oils) are readily oxidized because they contain linoleic and linolenic acids. These acids are easily oxidized. Prolonged exposure to air causes them to pick up oxygen and become oxidized. Repeated use just creates more oxidation.—In my laboratory we have fed weanling rats oils that had been heated at various temperatures. The rats that were fed the high temperature fats (365°F / 180°C) had lower growth rates than the rats that were fed lower temperature fats. Any foods that have been deep fried should be avoided, including potato chips and fried food from fast-food restaurants. Oils that are high in linoleic acid and linolenic acid should be avoided. —-The current research is on Alzheimer’s disease (AD) and Parkinson’s disease (PD.—AD is the most common cause of dementia. During the course of the disease, the chemistry and structure of the brain changes, leading to the death of brain cells. The challenges in AD research today include discovering methods to diagnose patients in an earlier stage and to find new treatments to prevent or cure the disease.–The brain is 81% lipids and over half of these lipids are phospholipids (fatlike, phosphorus-containing substances). PUFAs, which are easily oxidized (combined with oxygen), attach to the phospholipid molecule creating oxidative stress. The damaging consequences of oxidative stress have been implicated in a variety of very different human disorders including arteriosclerosis and diseases of the nervous system. Oxidative stress is an important pathogenic factor in AD. –I believe, just like heart disease patients, people with AD are eating too many polyunsaturated fatty acids (PUFAs) and deep fried foods. The American Heart Association and the National Institute of Health have recommended increasing PUFA consumption and decreasing saturated fat intake. Doing this increases free radicals when it is not offset with enough antioxidant rich fruits and vegetables. —Free radical damage accumulates with age. They may cause cells to function poorly or even die. When free radicals overwhelm the body’s ability to regulate them, oxidative stress occurs. An excess of oxidative stress can lead to the oxidation of lipids and proteins.
The research on preventing heart disease can also be used to prevent brain diseases. Tissue from the brain of someone who had AD is receptive to dyes that do not stain normal tissue suggesting that a chemical change occurred. –I suspect this chemical change occurs during oxidation of PUFAs. Discoverying that PUFAs are easily oxidized in the arterial cells and this could also be a factor in brain cells. The fact that AD is steadily increasing is alerting to the fact that –there is something wrong in the diet of these patients. –The Idea that AD and PD can be alleviated by monitoring the diets of patients with these diseases. A recent study at UCLA has shown that cognitive decline can be reversed by controlling the diet.–Patients eliminated simple carbohydrates and processed food from their diets. They increased their consumption of vegetables and fruits and limited their consumption of fish to non-farmed. The patients increased their sleep to almost 8 hours nightly, exercised 4-5 times per week and reduced their stress with meditation and relaxation.[F3] These patients also fasted three hours between meals and 12 hours between dinner and breakfast[F4]. The personalized therapeutic program was used based on the underlying pathogenesis of AD. Nine out of ten showed improvement and improvements have been sustained after two and one half years. This shows that more extensive therapeutic trials are needed. –The aim of my research is to find a way to prevent AD by analyzing the lipid plasma for two oxysterols. These two oxysterols were present in the plasma of the patients who needed bypass operations and are present in the food supply as frying fats and powdered egg yolk. My hypothesis is based on my studies of preventing calcification of the coronary arteries. I want to show that these two components are in the blood of patients with AD. — Controlling the amount of oxidation and consuming a healthy balanced diet the body can rid itself of the oxidized polyunsaturated fat. If this is the cause of Alzheimer’s disease, proper nutrition will end this terrible disease.[F5]–The diet plan that I would suggest would be to eat three balanced meals a day. Including 3 serving of protein, 5 -8 servings of fruits and vegetables, 3 servings of whole dairy products, at least one egg daily and eliminating simple carbohydrates and processed foods. Adequate amounts of sleep and exercise would also be encouraged. I then hope to continue this research with Parkinson’s disease patients. –.
Fred A. Kummerow, Ph.D.
Adjunct professor in biochemistry at the University of Illinois
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Biological fat with a sugar attached essential to maintaining brain’s supply of stem cells
Date-November 3, 2014
Source-Medical College of Georgia at Georgia Regents University
Dr. Robert Yu, MCG neuroscientist and corresponding author of the study in The Journal of Neuroscience and Dr. Jing Wang, MCG postdoctoral fellow and the study’s first author.
Fat and sugar aren’t usually considered healthy staples, but scientists have found that a biological fat with a sugar attached is essential for maintaining the brain’s store of stem cells.–Neural stem cells help the brain develop initially, then repopulate brain cells lost to usual cell turnover as well as to a trauma or malady, such as a head injury or stroke.–While the cell population and activity decrease as a natural part of aging, scientists at the Medical College of Georgia at Georgia Regents University are studying how neural stem cells are normally maintained with the long-term goal of helping the supply stay robust despite aging as well as infirmity.–They have discovered that in mice missing the sugar containing lipid ganglioside GD3, neural stem cells have a dramatically impaired ability to self-renew, said Dr. Robert K. Yu, MCG neuroscientist and corresponding author of the study in The Journal of Neuroscience.–The scientists focused on brain areas with typically the largest supply of neural stem cells: an area just below several midbrain cavities filled with cerebrospinal fluid, called the subventricular zone, as well as the hippocampus, a major center for learning and memory.–Mice missing ganglioside GD3 on the membranes of neural stem cells had much smaller supplies of the cells in these key areas throughout life and expressed signs of lost hope with behaviors such as not actively seeking dry land when placed in water, Yu said. Additionally, the mice had impaired maintenance of the area of the brain involved in the sense of smell as well as the portion of the hippocampus that enables formation of new memories.–The changes, which correlate with aging or illness, were corrected when GD3 was restored.–“If GD3 is missing, we found these neural stem cells cannot be maintained throughout life; they are reduced by a big percentage even in a one-month-old mouse,” said Dr. Jing Wang, MCG postdoctoral fellow and the study’s first author. In fact, by one month of life, there was about a 60 percent reduction in the supply and by six months, which is considered aged in a mouse, there were only a handful of neural stem cells remaining, Wang said.–The scientists note that in healthy young mice, GD3 is abundant but seems to naturally decrease with age.–A Yu and Wang paper published in the journal PNAS in 2013 showed that GD3 is the predominant ganglioside in mouse neural stem cells where it interacts with epidermal growth factor receptors, also found on the cell surface. GD3 plays an important role in growth factor signaling, which, in turn, tells neural stem cells to proliferate or die.–“In a normal situation, that growth factor enables the neural stem cells to reproduce more stem cells,” Wang said. “This gives us a better idea about how our neural stem cell population is maintained over our life. Our long-term goal is to use endogenous neural stem cells for repair of brain or spinal cord damage, so we need to learn how they proliferate, how to keep them inside the brain.”–The two are optimistic that one day manipulating levels of growth factors and sugar-containing lipids will enable a more steadfast supply of neural stem cells throughout life, although getting the substances into the brain is a challenge. It’s already known that, at least in rats, exercise can also help.–Neural stem cells are able to self-renew, in theory at least, forever. Their ability to maintain a steady supply of themselves and to differentiate into different types of brain cells are their most important properties, Yu said.–Next steps include examining the role of other growth factors and gangliosides.–Yu is the Georgia Research Alliance Eminent Scholar Chair in Molecular and Cellular Neurobiology. The studies were funded by the National Institutes of Health and the Veterans Administration.-Story Source-The above story is based on materials provided by Medical College of Georgia at Georgia Regents University. Note: Materials may be edited for content and length.–Journal Reference-J. Wang, A. Cheng, C. Wakade, R. K. Yu. Ganglioside GD3 Is Required for Neurogenesis and Long-Term Maintenance of Neural Stem Cells in the Postnatal Mouse Brain. Journal of Neuroscience, 2014; 34 (41): 13790 DOI: 10.1523/JNEUROSCI.2275-14.2014
Suggestions to consider—MCT Oils- Glycerol—Octacosanol—ATP—Ribose—Saturated Fats—these are components that activate the body on several fronts and support immune functions—regeneration—immune protecting—
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Show of the Month November 15 2014
This Drug Has Sickened Thousands of Animals – Will It Be At Your Holiday Feast?
Startling decline in European birds- Majority of losses from most common species
Ignoring This will cost You
37 Million Bees Found Dead In Ontario, Canada After Planting Large GMO Corn Field
Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines- Glyphosate-based herbicides toxicity
Time- and dose-dependent effects of roundup on human embryonic and placental cells – Glyphosate inhibits beneficial gut bacteria
HOW WELL DO FLU VACCINES WORK
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This Drug Has Sickened Thousands of Animals – Will It Be At Your Holiday Feast?
I have been to countless holiday meals when I had no control over the ingredients. Of course, I ate what was offered and was polite but knowing what I know now about what’s really in food – it’s hard for me to just shut up and take it. The more we shut up and take it, the more disgusting things like what I am about to share with you continue to happen. That’s why I am sharing these important facts about how to avoid drugged up turkeys this holiday season.
I know it’s tempting this time of year when you get coupons from the grocery store offering a whole turkey for FREE in exchange for shopping in their store. These “FREE” store-brand turkeys generally aren’t free of antibiotics and are raised on a diet of GMOs. Most conventionally raised (non-organic) turkeys are pumped full of antibiotics, and this overuse of antibiotics is creating a major human health issue.. There is another drug that is permitted to be fed to turkeys in the U.S. that is banned in dozens of countries due to health issues. You won’t find it on the label, it’s been shown to leave residues in the meat, and the meat companies are not required to tell you whether they use it.—–I’m talking about Topmax (otherwise known as Ractopamine).-Ractopamine is a growth enhancing drug that’s fed to some turkeys to increase their muscle mass. Basically, it’s used to make big turkeys look perfect for a big Holiday feast. We’ve been conditioned to think that “bigger is better” – but when it comes to turkey, its not! This drug has been shown to cause horrible health problems (and even the death of) animals, as can be witnessed by it’s rampant use on pigs during the last decade. As reported by NBC News, “Since it was introduced, ractopamine had sickened or killed more than 218,000 pigs as of March 2011, more than any other animal drug on the market, a review of FDA veterinary records shows. Pigs suffered from hyperactivity, trembling, broken limbs, inability to walk and death, according to FDA reports released under a Freedom of Information Act request.”–It’s fed to some conventional turkeys, and we might be eating it too.-Residues of ractopamine have been found in meat samples tested by the USDA and Consumer Reports. This is because there’s no mandatory withdrawal period for the drug, which can be fed to turkeys right up until the day they are slaughtered. The FDA established some “safe maximum residue limits” (MRLs) for ractopamine residue, so they are allowing some of this residue to remain in the meat sold at the store. Most meat is never tested for ractopamine residues, so it’s anyone’s guess how much we are really eating. That’s frightening, considering that ractopamine carries a bold warning label that states:
“NOT FOR HUMAN USE”
Label for TopmaxWhy is this permitted?
The FDA has allowed widespread use of ractopamine in turkey feed since its approval in 2008. This led the Animal Legal Defense Fund and the Center For Food Safety to file a legal petition with FDA demanding that they conduct comprehensive scientific studies that document the risks of ractopamine to human and animal health – because clearly more needed to be done before it gained FDA approval. The FDA approved ractopamine based on safety studies submitted by the company that makes it (Elanco), which is standard for most food and drugs on the market, and have reportedly refused to share their records. To date, ractopamine is still allowed to be fed to turkeys, cows, and pigs (up to 80% of pigs eat ractopamine-laced feed).
Other countries don’t take the use of ractopamine so lightly. For instance, China and Taiwan prohibit any traces of ractopamine residue in meat, and have rejected some U.S. exports. Also any meat exported to the European Union needs to be certified as ractopamine-free or it will be rejected.
Jennie-O’s customer service agent told us that it’s not routinely used and only used on a limited basis if necessary — whatever that means, because ractopamine is not a “necessary” drug used to treat disease. Jennie-O indicated that there would be no way of knowing at the store if their turkeys were fed ractopamine because it’s not labeled or otherwise indicated.
According to Safeway Grocery Stores – “Ractopamine is a growth promotant that can be feed to turkeys so our Safeway Farms turkey may or may not have the promotant in their feed. To guarantee that growth promotant was not part of the diet, please choose our Open Nature or O Organics brands which do not allow growth promotants.”
As these companies aren’t required to disclose whether ractopamine is used, and their claims are not third-party certified, it’s difficult to confirm its use. Even turkeys that are labeled “No Hormones Added” or “Raised Without Hormones” may have still been fed ractopamine to promote growth (because it is not a hormone), so don’t be fooled by this label. Growth hormones aren’t allowed to be used in raising poultry, so this label is meaningless and used as a marketing trick when labeled on turkeys (such as Butterball).
BREAKING NEWS UPDATE!
I just found out that two lawsuits were filed against the FDA yesterday (11/6/14), as reported in the Wall Street Journal, “In two different lawsuits filed on Thursday…groups including the Center for Food Safety, the Humane Society of the United States and United Farm Workers of America argue that in approving drugs like Topmax, a medicated feed additive used to produce lean muscle instead of fat, the FDA failed to adequately consider the drugs’ collective effects on animal welfare, worker safety, wildlife and U.S. waterways”. Both of these lawsuits are asking the Court to set aside FDA’s unlawful approval of these drugs until the FDA issues a more thorough environmental analyses. You can read these Complaints here and here.
From Humane Society, et al:
“FDA approved Ractopamine for use in pigs in 1999 under the brand name Paylean, and subsequently approved Ractopamine for cattle and turkeys under the brand names Optaflexx and Topmax, respectively. Since its initial approval as Paylean, Ractopamine use has increased significantly in the pork, beef, and turkey industries”–“Today, Ractopamine is fed to approximately 60% to 80% of pigs, cattle, and turkeys raised in the United States”–“The FDA also apparently failed to provide for any public or expert comment on its NEPA analysis for Topmax”.
From The Center for Food Safety, et al:
“FDA does not require any withdrawal period for ractopamine before slaughter. A 2006 scientific study concluded “there is a possibility that adulteration of feed with ractopamine could result in residues in animal tissues and lead to human poisoning.” A 2013 Consumer Reports test of 240 U.S. pork products found that about one in five tested positive for ractopamine residues”
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Startling decline in European birds- Majority of losses from most common species
Date:
November 2, 2014 Source:University of Exeter
Around 90 percent of these losses were from the 36 most common and widespread species, including house sparrows, skylarks, grey partridges and starlings.–Bird populations across Europe have experienced sharp declines over the past 30 years, with the majority of losses from the most common species, say the University of Exeter, the RSPB and the Pan-European Common Bird Monitoring Scheme (PECBMS) in a new study. However numbers of some less common birds have risen.-The study, published today in the journal Ecology Letters, reveals a decrease of 421 million individual birds over 30 years. Around 90 percent of these losses were from the 36 most common and widespread species, including house sparrows, skylarks, grey partridges and starlings, highlighting the need for greater efforts to halt the continent-wide declines of our most familiar countryside birds.–Richard Inger from the University of Exeter said: “It is very worrying that the most common species of bird are declining rapidly because it is this group of birds that people benefit from the most.”–“It is becoming increasingly clear that interaction with the natural world and wildlife is central to human wellbeing and significant loss of common birds could be quite detrimental to human society.”–Birds provide multiple benefits to society. They help to control agricultural pests, are important dispersers of seeds, and scavenging species play a key role in the removal of carcasses from the environment. In addition, for many people birds are the primary way in which they interact with wildlife, through listening to bird song, enjoying the sight of birds in their local environment, feeding garden birds and through the hobby of bird watching.–The majority of the declines can be attributed to considerable losses from relatively few common birds, but not all common species are declining. Numbers of great tits, robins, blue tits and blackbirds were all shown to be increasing. Populations of rarer species, including marsh harriers, ravens, buzzards and stone curlews have also shown increases in recent years: this is likely to be the result of direct conservation action and legal protection in Europe.–Head of Species Monitoring and Research at the RSPB’s Centre for Conservation Science Richard Gregory said: “The rarer birds in this study, whose populations are increasing, have benefited from protection across Europe. For example, white storks and marsh harriers receive among the highest level of protection in the EU — this is why their numbers have increased. The conservation and legal protection of all birds and their habitats in tandem are essential to reverse declines.–“This is a warning from birds throughout Europe. It is clear that the way we are managing the environment is unsustainable for many of our most familiar species.”–Petr Vorisek from the PECBMS said: “The study brings a very important message to conservation practice in Europe. This would not have been possible without thousands of skilled volunteer fieldworkers who count birds according to high scientific standards and contribute their data to the national monitoring schemes.”–Conservation efforts tend to be focused on rarer species but the research suggests that conservationists should also address issues affecting common birds, for example those traditionally associated with farmland. The decline in bird populations can be linked to modern farming methods, deterioration of the quality of the environment and habitat fragmentation, although the relative importance of these pressures remains unclear.–The study brought together data on 144 species of European bird from many thousands of individual surveys in 25 different countries, highlighting the value of the different national monitoring schemes increasingly working together. The researchers suggest that greater conservation funding and effort should be directed to wider scale environmental improvement programmes. These could include urban green space projects, and effective agri-environment schemes, which, informed by lessons learned from past schemes, should aim to deliver real outcomes for declining bird species whether they are rare or common.–Story Source-The above story is based on materials provided by University of Exeter.-Journal Reference-Richard Inger, Richard Gregory, James P. Duffy, Iain Stott, Petr Voříšek, Kevin J. Gaston. Common European birds are declining rapidly while less abundant species’ numbers are rising. Ecology Letters, 2014; DOI: 10.1111/ele.12387
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Ignoring This will cost You
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37 Million Bees Found Dead In Ontario, Canada After Planting Large GMO Corn Field
Millions of bees dropped dead after GMO corn was planted few weeks ago in Ontario, Canada. The local bee keeper, Dave Schuit who produces honey in Elmwood lost about 37 million bees which are about 600 hives.–“Once the corn started to get planted our bees died by the millions,” Schuit said. While many bee keepers blame neonicotinoids, or “neonics.” for colony collapse of bees and many countries in EU have banned neonicotinoid class of pesticides, the US Department of Agriculture fails to ban insecticides known as neonicotinoids, manufactured by Bayer CropScience Inc.–Two of Bayer’s best-selling pesticides, Imidacloprid and Clothianidin, are known to get into pollen and nectar, and can damage beneficial insects such as bees. The marketing of these drugs also coincided with the occurrence of large-scale bee deaths in many European countries and the United States.–Nathan Carey another local farmer says that this spring he noticed that there were not enough bees on his farm and he believes that there is a strong correlation between the disappearance of bees and insecticide use.–In the past, many scientists have struggled to find the exact cause of the massive die-offs, a phenomenon they refer to as “colony collapse disorder” (CCD). In the United States, for seven consecutive years, honeybees are in terminal decline.–US scientists have found 121 different pesticides in samples of bees, wax and pollen, lending credence to the notion that pesticides are a key problem. “We believe that some subtle interactions between nutrition, pesticide exposure and other stressors are converging to kill colonies,” said Jeffery Pettis, of the ARS’s bee research laboratory.-The collapse in the global honeybee population is a major threat to crops. It is estimated that a third of everything we eat depends upon honeybee pollination, which means that bees contribute over 30 billion to the global economy.–A new study published in the Journal Proceedings of the National Academy of Sciences revealed that neonicotinoid pesticides kill honeybees by damaging their immune system and making them unable to fight diseases and bacteria.–After reporting large losses of bees after exposure to Imidacloprid, banned it for use on corn and sunflowers, despite protests by Bayer. In another smart move, France also rejected Bayer’s application for Clothianidin, and other countries, such as Italy, have banned certain neonicotinoids as well.–After record-breaking honeybee deaths in the UK, the European Union has banned multiple pesticides, including neonicotinoid pesticides.
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Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines
Glyphosate-based herbicides are the most widely used across the world; they are commercialized in different formulations. Their residues are frequent pollutants in the environment. In addition, these herbicides are spread on most eaten transgenic plants, modified to tolerate high levels of these compounds in their cells. Up to 400 ppm of their residues are accepted in some feed. We exposed human liver HepG2 cells, a well-known model to study xenobiotic toxicity, to four different formulations and to glyphosate, which is usually tested alone in chronic in vivo regulatory studies. We measured cytotoxicity with three assays (Alamar Blue®, MTT, ToxiLight®), plus genotoxicity (comet assay), anti-estrogenic (on ERα, ERβ) and anti-androgenic effects (on AR) using gene reporter tests. We also checked androgen to estrogen conversion by aromatase activity and mRNA. All parameters were disrupted at sub-agricultural doses with all formulations within 24 h. These effects were more dependent on the formulation than on the glyphosate concentration. First, we observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor [F6]in MDA-MB453-kb2 cells for the most active formulation (R400), then from 2 ppm the transcriptional activities on both estrogen receptors were also inhibited on HepG2[F7]. Aromatase transcription and activity were disrupted from 10 ppm. Cytotoxic effects started at 10 ppm with Alamar Blue assay (the most sensitive), and DNA damages at 5 ppm. A real cell impact of glyphosate-based herbicides residues in food, feed or in the environment has thus to be considered, and their classifications as carcinogens/mutagens/reprotoxics is discussed.
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Glyphosate-based herbicides toxicity
Roundup (R) was highly toxic on human cells, from 10-20 ppm, far below agricultural dilutions. This occurred on hepatic (HepG2, Hep3B and embryonic (HEK293) as well on placental (JEG3) cell lines, but also on human placental extracts, primary umbilical cord cells (HUVEC) and freshly isolated testicular cells (Richard et al. 2005; Benachour et al. 2007; Benachour & Seralini 2009; Gasnier et al. 2010; Clair et al. 2012). All formulations cause total cell death within 24 h, through an inhibition of the mitochondrial succinate dehydrogenase activity, and necrosis, through the release of cytosolic adenylate kinase measuring membrane damage. They also induced apoptosis through the activation of enzymatic caspases 3 / 7 activities. Most importantly, the R commercialized formulation is always more toxic than the active principle alone, the glyphosate (G). These effects were more dependent on the formulation and thus adjuvants content than on the G concentration. We recently measured compositions and effects of 9 Gbased formulations and identified ethoxylated adjuvants (commonly called POEA) asthe active principle of cytotoxicity (Messnage et al. 2012a). However, these are considered as inert diluents in international regulations and are not taken into account for chronic effects which are insufficiently tested, and only with G in pre-commercial testing. We previously underlined this loophole (Mesnage 2010). Long term feeding and reproductive trials with pesticides are the only tests long enough to reveal a potential endocrine disruption which was consequently never studied for R until recently (Seralini et al. 2012), however it was for G by itself. We investigated it by measuring androgen to estrogen conversion by aromatase activity and mRNA on placental human cells and showed that G interacts with the active site of the purifed enzyme (Richard et al. 2005). Both parameters were disrupted at subagricultural doses within 24 h. We also observed a human cell endocrine disruption from 0.5 ppm on the androgen receptor in transfected cells, and then from 2 ppm the transcriptional activities on both estrogen receptors which were also inhibited (Gasnier et al. 2009). Aromatase transcription and activity were disrupted from 10 ppm on
HepG2. On freshly isolated rat testicular cells, low non-toxic concentrations of R and G (1 ppm) induced a testosterone decrease by 35 % (Clair et al. 2012). This is expected to occur in human cells which are fitted with the same steroidogenic equipment. G-based formulations are claimed to have been extensively studied by industry and regulatory agencies and are considered as one of the safest pesticides (Williams et al.2000). This allowed the establishment of high maximum residue limits (MRL) for GM food / feed (up to 400 ppm). For instance, 20 ppm of G are authorized in GM soy and this MRL is in the range of concentrations typically found in a GM soy harvest. In the light of our results, the safety of these thresholds is clearly challenged.
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Time- and dose-dependent effects of roundup on human embryonic and placental cells.
Benachour N1, Sipahutar H, Moslemi S, Gasnier C, Travert C, Séralini GE.
Author information
Abstract
Roundup is the major herbicide used worldwide, in particular on genetically modified plants that have been designed to tolerate it. We have tested the toxicity and endocrine disruption potential of Roundup (Bioforce on human embryonic 293 and placental-derived JEG3 cells, but also on normal human placenta and equine testis. The cell lines have proven to be suitable to estimate hormonal activity and toxicity of pollutants. The median lethal dose (LD(50)) of Roundup with embryonic cells is 0.3% within 1 h in serum-free medium, and it decreases to reach 0.06% (containing among other compounds 1.27 mM glyphosate) after 72 h in the presence of serum. In these conditions, the embryonic cells appear to be 2-4 times more sensitive than the placental ones. In all instances, Roundup (generally used in agriculture at 1-2%, i.e., with 21-42 mM glyphosate) is more efficient than its active ingredient, glyphosate, suggesting a synergistic effect provoked by the adjuvants present in Roundup. We demonstrated that serum-free cultures, even on a short-term basis (1 h), reveal the xenobiotic impacts that are visible 1-2 days later in serum. We also document at lower non-overtly toxic doses, from 0.01% (with 210 microM glyphosate) in 24 h, that Roundup is an aromatase disruptor. The direct inhibition is temperature-dependent and is confirmed in different tissues and species (cell lines from placenta or embryonic kidney, equine testicular, or human fresh placental extracts). Furthermore, glyphosate acts directly as a partial inactivator on microsomal aromatase, independently of its acidity, and in a dose-dependent manner. The cytotoxic, and potentially endocrine-disrupting effects of Roundup are thus amplified with time. Taken together, these data suggest that Roundup exposure may affect human reproduction and fetal development in case of contamination. Chemical mixtures in formulations appear to be underestimated regarding their toxic or hormonal impact.
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Glyphosate inhibits beneficial gut bacteria
Tuesday, Jan. 8, 2013 – A new study published in the journal Current Microbiology describes the harmful effect of glyphosate on intestinal bacteria in poultry. The evidence is that glyphosate is toxic to beneficial bacteria such as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lactobacillus spp, while pathogenic bacteria such as Salmonella Entritidis, Salmonella Gallinarum, Salmonella Typhimurium, Clostridium perfringens and Clostridium botulinum are highly resistant to glyphosate.–A reduction of beneficial bacteria in the gastrointestinal tract disturbs the normal gut bacterial community and allows salmonella and clostridia species to grow unchecked thus increasing the incidence of these two diseases.–The researchers pointed out that glyphosate also has the potential to induce genetic mutations within bacteria, making it possible for a new level of pathogenicity to emerge following chronic exposure to this chemical.- Oral bioavailability of glyphosate: studies using two intestinal cell lines.
Vasiluk L1, Pinto LJ, Moore MM.–Author information –Abstract
Glyphosate is a commonly used nonselective herbicide that inhibits plant growth through interference with the production of essential aromatic amino acids. In vivo studies in mammals with radiolabeled glyphosate have shown that 34% of radioactivity was associated with intestinal tissue 2 h after oral administration. The aim of our research was to investigate the transport, binding, and toxicity of glyphosate to the cultured human intestinal epithelial cell line, Caco-2, and the rat small intestinal crypt-derived cell line, ileum epithelial cells-18 (IEC-18). An in vitro analysis of the transport kinetics of [14C]-glyphosate showed that 4 h after exposure, approximately 8% of radiolabeled glyphosate moved through the Caco-2 monolayer in a dose-dependent manner. Binding of glyphosate to cells was saturable and approximately 4 x 10(11) binding sites/cell were estimated from bound [14C]. Exposure of Caco-2 cells to > or =10 mg/ml glyphosate reduced transmembrane electrical resistance (TEER) by 82 to 96% and increased permeability to [3H]-mannitol, indicating that paracellular permeability increased in glyphosate-treated cells. At 10-mg/ml glyphosate, both IEC-18 and Caco-2 cells showed disruption in the actin cytoskeleton. In Caco-2 cells, significant lactate dehydrogenase leakage was observed when cells were exposed to 15 mg/ml of glyphosate. These data indicate that at doses >10 mg/ml, glyphosate significantly disrupts the barrier properties of cultured intestinal cells
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HOW WELL DO FLU VACCINES WORK? FALL CAMPAIGN IS IN FULLSWING
One easily gets the impression that the answer is very well indeed. Get your shot and you will be protected. Flu vaccination has become mandatory in many health care institutions. No shot and either wear a mask or quit. One would expect that most would be protected. The efficacy (relative risk reduction in controlled trials) is typically 50-60 % and can go higher, especially for children. Vaccine Manufacturers and promoters would of course like it close to 100% which would justify the claim if one gets their shot, they won’t get the flu. If one took an exit poll was taken from a vaccination clinic at a local mall, probably a surprising number would say just that. Thus it is of interest to look at two recent meta-analyses and examine the other side of the coin, the absolute benefits, a taboo subject in this field. International Health News November 2014 Page 7 –Recently, Ossterholm et al16 examined the efficacy of influenza vaccination as indicated by studies that were randomized, placebo controlled and where the cases were laboratory verified as viral influenza. It was required that vaccine efficacy be reported for all circulating influenza strains. Meta analyses of qualifying trials were conducted separately for adults and children or just adults A second recent study by Tricco et al17 compared the efficacy of influenza vaccines depending on whether or not they were matched to at least one of the strains circulating that year. Both matched and unmatched randomized controlled trials involving either trivalent inactivated vaccine (TIV) or nasal spray containing live attenuated influenza vaccine (LAIV) were analyzed. All the meta analyses had a mixture of studies involving children and adults in varying proportions, but more than half of the studies using LAIV involved children. The results of these two studies are given in the table below. Both papers provided enough information to calculate absolute results, actually by two methods which gave very close to identical results. The published papers ignored absolute results.
VACCINE EFFICACY IN RECENT META -ANALYSES
Study STUDIES Age NNT RRR No Benefit Vaccine
Osterholm16 8 18-64 64 60% 98.4% TIV
Osterholm 16 7 0.5-7 8 84% 87.3% LAIV
Trico17 12 A&C 93 62% 98.9% TIV-Matched
Tricco17 11 A&C 204 51% 99.5% TIV-Mismatched
Tricco17 15 A&C 18 77% 94.4% LAIV-Matched
Tricco17 15 A&C 48 60% 97.9% LAIV-Mismatched
TIV—Trivalent inactivated vaccine. LAIV—Live attenuated influenza vaccine.
NNT—Number needed to treat. RRR—Relative risk reduction. A&C—adults and children. Note that most of the relative risk reductions (RRR) are impressive. Those who do not understand relative risk reduction will assume that for example, a RRR of 60% means that 60% of those vaccinated will not get the flu. However, only 1.6% will actually benefit whereas 98.4 will not. The magnitude of the relativemrisk reduction is related to the absolute risk reduction divided by the absolute risk in the control group, and thus can be very large for small absolute benefits in the case of disorders or diseases that have a low population incidence, which is the case with the flu in adults. Children have a higher untreated population risk, but it is still only generally only a few percentage points. Risk reductions are generally adjusted for confounding, and but these can be used to calculate the adjusted absolute risk reduction and number needed to treat. Note also that the RRR correlate rather poorly with the NNT, something at the very heart of the problem of using the RRR. The above table suggests that independent of the type of the vaccine or how well it matches the strains during a given year, most vaccinated individuals do not benefit but must simply hope they are lucky. For TIV, a very common vaccine, mismatching does not seem to make much difference. However, the benefit for children from the LAIV is quite strong, as seen in the analysis involving LAIV by Osterholm et al and in the two by Tricco et al involving both LAIV which had heavy representation of children in the studies included, since it is the popular vaccine type for children. While numbers needed to treat of 8 are not common in clinical trials or their pooled analyses, it is unfortunately still true, as shown in the table, that even with such a low number, most do not benefit. There is very little data for those over 65 of age. The analysis by Osterholm et al prompted a number of comments in the literature. It is interesting in these comments that the focus was universally on relative risk reduction, never on the percentage treated that do or do not benefit, i.e. the absolute results. This appears to be a taboo point of view. Commentators worried that the “modest” relative risk reductions in the 50% range would be used by critics to discourage vaccination, but if this is the case, the more realistic view based on absolute benefit would rightly terrify proponents of this popular public health intervention and the related desire to develop herd immunity. Furthermore, there is always the worrisome problem that adverse effects have been suppressed by the industry, certainly far from an unheard of approach to doing business; therefore one cannot do a risk/benefit analysis.-The above results are a nice example of how a given set of trial results can be presented in different ways (another term is spin) that either accentuate the positive or provide a more realistic view. For those who find this hard to believe, an appendix at the end of this issue is included which gives a sample calculation. The potential for creating unrealistic expectations is obviously great and an almost universally used approach. It seems worth mentioning in passing that pregnant women, if they decide to get a flu shots, should demand the mercury free one which generally comes in a single dose vial not a septum capped little bottle. Live attenuated influenza vaccine which is delivered as a nasal spray, in generally mercury free. However, given that the vaccine preparation may have other dangers to the fetus aside from mercury toxicity which may be unknown or suppressed, perhaps the dismal percentage of adults benefiting should be given considerable weight by this special group. What should one do? There do not appear to be studies that have provided strong evidence concerning actions found to dramatically reduce the risk of the flu. Mainstream medicine regards the problem solved with vaccination. While maintaining a vitamin D status that is sufficient or more than just sufficient can be justified from a number of studies and is easy and inexpensive to accomplish and justified for a large number of other reasons, definitive studies have yet to appear. The subject of maintaining a high level of immune response will have to wait for a future issue of IHN.
CDC REPORTS INFLUENZA OUTBREAK IN A VACCINATED POPULATION
On October 24, 2014 the Centers for Disease Cont rol in its Morbidity and Mortality Report described a flu outbreak among the crew of a navy ship moored in San Diego. In February of 2014, 25 cases of influenza, of which 20 were influenza A, occurred over a short period among a crew of 102. Ninety-nine percent of the crew had been vaccinated with a vaccine very well matched with the flu viruses circulating in 2013-14. The fact that it was influenza was documented by laboratory tests. The headline in the New England Journal of Medicine’s daily online Journal Watch of October 24 read as follows: Flu Outbreak Aboard Navy Ship Highlights Possibility of Illness in Vaccinated Populations. The interesting word is “possibility.” Reference to the above table indicates that 94.4% to 98.9% of vaccinated populations are not protected with a matched vaccine, depending on the type of vaccine, and the 94.4% is due in part to heavy weighting from children. These results apply to large pooled populations and studies covered a number of years. Of the 25 flu cases, 16 received the TIV form, 8 the LAIV and one was unvaccinated. Using the term “possibly” seems rather an understatement. According to the CDC report, Tamiflu was given to the crew to “reduce the impact and spread of the disease.” This is the same antiviral that has been discredited and found virtually useless after huge amounts of government funds throughout the world were spend stockpiling it. See the February 2013 issue of IHN for the full story of the shocking Tamiflu saga.
Reference List
1. Robertson RP. Red wine and diabetes health: getting skin in the game. Diabetes. 2014;63:31-38.
2. Cullmann M, Hilding A, Ostenson CG. Alcohol consumption and risk of pre-diabetes and type 2 diabetes
development in a Swedish population. Diabet Med. 2012;29:441-452.
3. Marfella R, Cacciapuoti F, Siniscalchi M et al. Effect of moderate red wine intake on cardiac prognosis after
recent acute myocardial infarction of subjects with Type 2 diabetes mellitus. Diabet Med. 2006;23:974-981.
4. Knoops KT, de Groot LC, Kromhout D et al. Mediterranean diet, lifestyle factors, and 10-year mortality in
elderly European men and women: the HALE project. JAMA. 2004;292:1433-1439.
5. Blomster JI, Zoungas S, Chalmers J et al. The relationship between alcohol consumption and vascular
complications and mortality in individuals with type 2 diabetes. Diabetes Care. 2014;37:1353-1359.
6. Karatzi K, Karatzis E, Papamichael C, Lekakis J, Zampelas A. Effects of red wine on endothelial function:
postprandial studies vs clinical trials. Nutr Metab Cardiovasc Dis. 2009;19:744-750.
7. Karatzi K, Papamichael C, Karatzis E et al. Postprandial improvement of endothelial function by red wine and
olive oil antioxidants: a synergistic effect of components of the Mediterranean diet. J Am Coll Nutr.
2008;27:448-453.
8. Natella F, Macone A, Ramberti A et al. Red wine prevents the postprandial increase in plasma cholesterol
oxidation products: a pilot study. Br J Nutr. 2011;105:1718-1723.
9. Natella F, Ghiselli A, Guidi A, Ursini F, Scaccini C. Red wine mitigates the postprandial increase of LDL
susceptibility to oxidation. Free Radic Biol Med. 2001;30:1036-1044.
10. Wu Y, Ding Y, Tanaka Y, Zhang W. Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the
Treatment and Prevention. Int J Med Sci. 2014;11:1185-1200.
11. Li G, Zhang P, Wang J et al. The long-term effect of lifestyle interventions to prevent diabetes in the China Da
Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet. 2008;371:1783-1789.
12. Wilson PW, Meigs JB, Sullivan L, Fox CS, Nathan DM, D’Agostino RB, Sr. Prediction of incident diabetes
mellitus in middle-aged adults: the Framingham Offspring Study. Arch Intern Med. 2007;167:1068-1074.
13. Taylor R. Type 2 diabetes: etiology and reversibility. Diabetes Care. 2013;36:1047-1055.
14. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes:
normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol.
Diabetologia. 2011;54:2506-2514.
15. Yamaoka K, Tango T. Effects of lifestyle modification on metabolic syndrome: a systematic review and metaanalysis.
BMC Med. 2012;10:138.
16. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: a
systematic review and meta-analysis. Lancet Infect Dis. 2012;12:36-44.
17. Tricco AC, Chit A, Soobiah C et al. Comparing influenza vaccine efficacy against mismatched and matched
strains: a systematic review and meta-analysis. BMC Med. 2013;11:153.
APPENDIX
Pooled data from 8 studies, adults 18-64 years of age, given trivalent inactivated influenza vaccine compared to unvaccinated controls. Cases laboratory -validated as viral influenza. Taken from Figure 2.16
THE RAW DATA
Vaccinated Control
Cases of flu 221 357
Total in group 18,797 13,095
CALCULATIONS
Flu Case %: (221/18,797) X 100 = 1.118%, No Flu % (357/13,095) X 100 = 2.730%,
Percentage who benefited: 2.730% — 1.118% = 1.55% or 1.55 per 100
Percentage with no benefit: 100% – 1.55% = 98.4%
The absolute risk reduction produced by vaccination was the percentage that benefited, 1.55% is the difference between the flu rates in the two groups, expressed as a percentage rather than probability, i.e. 0.0155. If 1.55/100 had benefit, how many must be vaccinated for one to benefit? It is calculated from 1.55/100 = 1/x and thus x = 64. This number needed to treat for one individual to benefit, i.e. not get the viral flu, and is the NNT. Put another way, it is the reciprocal of the absolute risk reduction expresses as a probability (range 1.0 to 0), not a percentage, i.e. NNT = 1/0.0155. The time interval is approximately the flu season. The unadjusted risk ratio 0.4 is obtained from the ratio 1.118/ 2.730 = 0.4 and the relative risk reduction (RRR) was 1 — 0.4 = 0.60 or as a percentage 60%. Why is this true? Details. Risk ratio = (case % in treated group)/(case % in untreated group) = T/U. But 1 = (T/U) = (U – T)/U = RRR, the relative risk reduction obtained comparing the % of cases prevented to the case % in the untreated (control) group. The same calculation can be done without expressing the numbers as percentages, since the 100 cancels out. Thus the four numbers, i.e. the cases and size of the groups, constitute the input data that produce these various final results used to express how well the treatment works. The 60% RRR looks great, the number who do not benefit looks terrible. Same data, just different presentations, both correct. Some think that by getting the vaccination they will not get the flu, some think that their risk is reduced by 60%, but interpret this by thinking that if a group of 100 are vaccinated, 60 will not get the flu. In fact, if 100 are vaccinated, between 1 and 2 individuals will be protected and 98% to 99% will not be protected. This is what the critics of the use of relative risk reductions are talking about, but no one is listening. Why spoil a nice picture based on a perfectly valid calculation. It is also noteworthy that when a disease or disorder has a very small population prevalence reflected by the percentage of cases in the control group, this forces the NNT and the percentage that do not benefit into the range seen in this example. This is the consequence of treating a group where the vast majority will not become cases, treatment or no treatment. One can argue that treatment is still desirable, but one must not have unrealistic expectations, and now the risk of adverse side effects becomes a major issue. Small absolute benefits and large NNT should stimulate research to find something better. Instead the RRR becomes a powerful marketing and public health tool.
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Show of the Month November 22 2014
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
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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