N
Nicotinamide riboside, NR
Food & Supplements Program
Nicotinamide Riboside (NR) is a derivative of Niacin. Whether it has better or different benefits compared to niacin itself is unclear. It is clearly a more expensive product, with more profit for its sellers.
Nicotinamide Riboside—The Current State of Research and Therapeutic Uses.2020
Related Links
Nicotinamide adenine dinucleotide, NAD
Food & Supplements Program
NAD is an extremely important molecule for most cellular processes, involved in providing energy for those processes, as well as the ability to provide electrons to neutralize oxidizing agents coming from within and without.
Don’t forget that the N in NAD stands for niacin, and many of the benefits of NAD may come from niacin itself. If this is true, niacin would be preferred since it is far less expensive and supports several essential processes.
This may be true for all variants of niacin which include nicotinamide riboside and NADP.
Nicotinamide adenine dinucleotide – Wikipedia
The Role of NAD+ in Aging – Today’s Practitioner
NMN-nicotinamide mononucleotide-White-paper-LONGITY_WEB
Related Links
References
Vitamin B1: Thiamine and Benfotiamine
Vitamins
IMPORTANT NOTICE
This information is for educational purposes only, to facilitate quality conversations between patients and their personal physician(s). Several essential considerations are required to safely administer any protocol for an individual. This information is NOT intended to diagnose, treat or encourage self-treatment of any medical condition.
This page is under development. Working links will provide starting information. Please let us know about your interest in this page by emailing us here, and check back soon.
Conversations with Open AIÂ 10/7/2023
what is the relationship and relative potency of thiamine vs benfothiamine
ChatGPT
Thiamine (also known as vitamin B1) and benfotiamine are both forms of vitamin B1, but they have different properties and potencies when it comes to absorption and therapeutic effects.
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Thiamine:
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Thiamine is the naturally occurring form of vitamin B1 found in food sources like whole grains, nuts, and meats.
It is water-soluble and readily absorbed by the body.
Thiamine is essential for various biochemical processes in the body, including the conversion of carbohydrates into energy.
It is commonly used to treat and prevent thiamine deficiency, which can lead to conditions like beriberi and Wernicke-Korsakoff syndrome.
The recommended daily intake of thiamine for adults varies, but it is generally around 1.1 to 1.2 mg for men and 0.8 to 0.9 mg for women.
Benfotiamine:
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Benfotiamine is a synthetic, fat-soluble derivative of thiamine.
Unlike thiamine, benfotiamine is absorbed more efficiently by the body because it can pass through cell membranes more easily.
This enhanced absorption allows benfotiamine to reach higher levels in the blood and tissues compared to thiamine.
Benfotiamine is often used as a dietary supplement and is promoted for its potential to support nerve health and reduce the risk of complications associated with conditions like diabetes and neuropathy.
The recommended dosage of benfotiamine can vary but is typically in the range of 150-300 mg per day.
Relative Potency:
Benfotiamine is considered to be more potent than thiamine in terms of its bioavailability and ability to raise thiamine levels in the body. This is primarily because benfotiamine’s fat-solubility allows it to be better absorbed and retained in the tissues.
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However, it’s essential to note that while benfotiamine may have advantages in terms of absorption, thiamine remains the essential and natural form of vitamin B1 that the body requires for various physiological processes. In some cases, thiamine supplementation may be more appropriate, especially when treating specific thiamine deficiency-related conditions.
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The choice between thiamine and benfotiamine should be based on individual needs and health concerns, and it’s advisable to consult with a healthcare professional before starting any vitamin B1 supplementation regimen. Additionally, the relative potency and effectiveness of these forms of vitamin B1 may vary from person to person, depending on factors like metabolism and overall health.
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User
tell me about allithiamine and its potencyÂ
ChatGPT
Allithiamine is another derivative of vitamin B1 (thiamine) that is similar to benfotiamine. It is also known as “fat-soluble thiamine” and is a synthetic compound created by binding thiamine to a lipid (fat) molecule. This modification enhances its absorption and bioavailability in the body, making it more potent than regular thiamine.
Key points about allithiamine and its potency include:
Enhanced Absorption: Allithiamine, like benfotiamine, is fat-soluble, which means it can pass through cell membranes more easily than water-soluble thiamine. This enhanced absorption allows it to reach higher levels in the bloodstream and tissues.
Therapeutic Potential: Allithiamine is often used as a dietary supplement and is promoted for its potential to support various aspects of health, including nerve health and glucose metabolism. It is particularly popular in some alternative and complementary medicine practices.
Potential Benefits: Some studies and anecdotal reports suggest that allithiamine may be beneficial in managing conditions like diabetes, neuropathy (nerve damage), and other thiamine deficiency-related disorders. It is believed to have antioxidant properties and may help reduce oxidative stress.
Dosage: The recommended dosage of allithiamine can vary depending on the specific product and the intended use. Typical dosages range from 50 mg to 150 mg per day.
Consultation with a Healthcare Professional: As with any dietary supplement, it’s important to consult with a healthcare professional before starting allithiamine supplementation, especially if you have specific medical conditions or are taking other medications. They can provide guidance on the appropriate dosage and assess whether it is suitable for your individual needs.
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Relative Potency: Allithiamine, like benfotiamine, is generally considered to be more potent than traditional thiamine (vitamin B1) in terms of absorption and tissue retention. However, the specific potency may vary depending on the individual and their unique physiology.
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It’s worth noting that while allithiamine and benfotiamine are promoted for their potential benefits, more research is needed to establish their efficacy and safety conclusively. These modified forms of thiamine are often used as complementary or alternative treatments in addition to conventional medical approaches. As such, they should not be considered a replacement for medical advice and treatment when managing specific health conditions.
Conversation with Open AIÂ 10/7/2023
User: Can thiamine insufficiency cause intolerance of niacin or other nutrients?
ChatGPT
Thiamine (vitamin B1) insufficiency, often referred to as thiamine deficiency or beriberi, primarily affects the body’s ability to metabolize carbohydrates and generate energy from them. While thiamine deficiency itself may not directly cause intolerance of niacin (vitamin B3) or other nutrients, it can indirectly affect nutrient metabolism and lead to various health issues. Here’s how:
Impaired Energy Metabolism: Thiamine is essential for several enzymes involved in the breakdown of glucose (carbohydrates) and the production of ATP, which is the primary energy currency of cells. Thiamine deficiency can lead to reduced energy production and overall metabolic dysfunction.
Niacin Utilization: Niacin (B3) is involved in various metabolic pathways, including those related to energy production. In particular, niacin is a precursor for nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), coenzymes involved in redox reactions and energy metabolism.
Thiamine deficiency may indirectly impact niacin metabolism by reducing the overall efficiency of energy production. Since NAD and NADP are involved in redox reactions and electron transfer during energy metabolism, a lack of adequate energy production due to thiamine deficiency can affect the utilization of niacin.
General Malnutrition: Thiamine deficiency often occurs in the context of overall malnutrition, which can lead to deficiencies in multiple vitamins and minerals. These deficiencies can interact and exacerbate each other, potentially leading to broader nutritional issues and metabolic disturbances.
Symptoms and Health Effects: Thiamine deficiency itself can lead to various symptoms, such as fatigue, muscle weakness, and neurological problems. These symptoms may indirectly affect nutrient tolerance and absorption as the body’s overall health deteriorates.
In summary, while thiamine deficiency may not directly cause intolerance of niacin or other nutrients, it can have a cascading effect on overall nutrient metabolism and energy production. Thiamine is crucial for carbohydrate metabolism, and its deficiency can lead to a state of general metabolic dysfunction. Therefore, addressing thiamine deficiency is important not only for preventing specific thiamine-related symptoms but also for maintaining overall nutrient balance and metabolic health. If you suspect a thiamine deficiency or have concerns about nutrient intolerance, it is advisable to consult a healthcare professional for proper evaluation and treatment.
Conversation with Open AIÂ 10/7/2023
What is the metabolic connection between B1 thiamine and B3 niacin
ChatGPT
Thiamine (B1) and niacin (B3) are both essential B vitamins that play important roles in cellular metabolism, but they are not directly metabolically connected in terms of chemical reactions. However, they do interact indirectly through their involvement in various metabolic pathways.
Thiamine (B1):
Thiamine is essential for the conversion of carbohydrates into energy. It acts as a coenzyme in several key reactions within the citric acid cycle (also known as the Krebs cycle or TCA cycle) and the pentose phosphate pathway.
Thiamine pyrophosphate (TPP) is the active form of thiamine and is a cofactor for enzymes such as pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. These enzymes are involved in the breakdown of glucose and the production of ATP, the cell’s primary energy source.
Niacin (B3):
Niacin is important for the metabolism of carbohydrates, fats, and proteins. It serves as a precursor for two coenzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).
NAD and NADP play vital roles as electron carriers in various metabolic pathways, including glycolysis, the citric acid cycle, and oxidative phosphorylation. They are involved in redox reactions, where they accept and donate electrons during energy production.
Indirect Interaction:
While thiamine and niacin have distinct roles in cellular metabolism, they indirectly interact because they both contribute to the efficient utilization of nutrients for energy production. Thiamine is necessary for the initial steps of glucose metabolism, and niacin, as part of NAD and NADP, is involved in later steps that allow the transfer of energy-rich electrons for ATP production. Without adequate levels of both thiamine and niacin, cellular energy production can be impaired.
In summary, thiamine (B1) and niacin (B3) are not directly metabolically connected in terms of shared chemical reactions, but they are both essential for proper energy metabolism. Thiamine facilitates the initial steps of glucose breakdown, while niacin, through its role in NAD and NADP, participates in subsequent stages, contributing to the overall efficiency of cellular energy production.
User Go further and explain the relation to B2 riboflavin
ChatGPT
Riboflavin (B2), along with thiamine (B1) and niacin (B3), is another essential B vitamin involved in various metabolic processes. While B2, B1, and B3 each have specific roles, they are interconnected within cellular metabolism due to their roles as coenzymes or precursors for coenzymes.
Riboflavin (B2):
Riboflavin is a precursor for two coenzymes: flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These coenzymes are collectively referred to as flavins.
FMN and FAD are involved in a wide range of redox reactions in cells. They can accept and donate electrons during metabolic processes, making them critical for energy production.
Now, let’s explore the relationship between thiamine (B1), niacin (B3), and riboflavin (B2) in cellular metabolism:
Thiamine (B1):
Thiamine plays a crucial role in the metabolism of carbohydrates, as previously mentioned. It is involved in reactions that convert glucose into energy.
Thiamine pyrophosphate (TPP), the active form of B1, acts as a cofactor for enzymes such as pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase.
Niacin (B3):
Niacin is essential for the metabolism of carbohydrates, fats, and proteins. It serves as a precursor for the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP).
NAD and NADP are crucial coenzymes involved in redox reactions and electron transfer during various metabolic pathways, including glycolysis, the citric acid cycle, and oxidative phosphorylation.
The Connection:
Riboflavin (B2) is essential for the synthesis of the coenzymes FMN and FAD.
FMN and FAD are directly involved in redox reactions as electron carriers in many metabolic pathways, similar to NAD and NADP derived from niacin (B3).
Thiamine (B1) is necessary for the initial steps of glucose metabolism, which provides substrates for subsequent energy production processes.
In summary, while thiamine (B1), niacin (B3), and riboflavin (B2) have distinct roles within cellular metabolism, they are interconnected because they contribute to the overall efficiency of energy production. Thiamine is involved in the initial steps of glucose metabolism, riboflavin supports redox reactions through FMN and FAD, and niacin contributes to electron transfer through NAD and NADP. Together, these B vitamins ensure that the energy produced from nutrients is efficiently harnessed by the cell.
User Now connect thyroid hormone metabolism
ChatGPT
Thyroid hormone metabolism is intimately connected to the metabolism of various nutrients, including carbohydrates and fats, as well as the B vitamins thiamine (B1), riboflavin (B2), and niacin (B3). The thyroid gland produces two primary hormones: thyroxine (T4) and triiodothyronine (T3). These hormones play a central role in regulating metabolism throughout the body.
Here’s how thyroid hormone metabolism is interconnected with these B vitamins and nutrient metabolism:
Thiamine (B1):
Thiamine is essential for the proper functioning of enzymes involved in glucose metabolism. Thyroid hormones, especially T3, increase the rate of glucose absorption in the intestines and its utilization in cells.
Thyroid hormones enhance the activity of the sodium-potassium pump, which is essential for maintaining cellular membrane potential. Thiamine-dependent enzymes are involved in this process.
Riboflavin (B2):
Riboflavin is important for the synthesis of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are coenzymes involved in various redox reactions.
Thyroid hormones influence the metabolic rate, and redox reactions are fundamental to energy production. FMN and FAD participate in these reactions, ensuring efficient energy production in cells.
Niacin (B3):
Niacin is a precursor for nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), coenzymes that play essential roles in redox reactions and energy metabolism.
Thyroid hormones influence the metabolic rate, and NAD and NADP are integral to the transfer of electrons and the generation of ATP during energy production.
Nutrient Metabolism:
Thyroid hormones affect the metabolism of carbohydrates, proteins, and fats. They increase the rate at which these nutrients are broken down and utilized for energy.
The B vitamins (B1, B2, and B3) are coenzymes or precursors for coenzymes involved in the various metabolic pathways of these nutrients. For example, they participate in reactions that convert carbohydrates and fats into energy.
In summary, thyroid hormone metabolism is closely linked to nutrient metabolism and the activities of B vitamins, especially thiamine (B1), riboflavin (B2), and niacin (B3). Thyroid hormones play a central role in regulating metabolic processes, and these B vitamins are essential for the proper functioning of enzymes and coenzymes involved in these processes. The interplay between thyroid hormones and B vitamins ensures the efficient utilization of nutrients for energy production and overall metabolic balance in the body.
File Access
RDA: 1.2 mg
Most multi-B’s: 50-100 mg
High-Dose oral: 1-2000 mg 2x/day
High-Dose IM: 100 mg 2x/wk
Vitamin B2: Riboflavin
Vitamins
This page is under development. Working links will provide starting information. Please let us know about your interest in this page by emailing us here, and check back soon.
Trehalose
Food & Supplements Program
Trehalose is a naturally-occuring di-saccharide (two sugars) that can be broken down in the normal small intestine. It is used for dry eye and mucosal injuries. The Product Helios, for sore mouths, has trehalose, glutamine and arginine.
References
Lysosomes Dysfunction Causes Mitophagy Impairment in PBMCs of Sporadic ALS Patients.2021.pdf
Trehalose–an intriguing disaccharide with potential for medical application in ophthalmology.2011
Solubility
Solubility in water
68.9 g per 100 g at
20 °C
Soluble in ethanol
Trehalose sweetness and other trivia
File Access
SUGARS
Neutropenia
Immune, Allergy & Infection Program
Neutrophils are a type of white blood cells involved in immune system defense. When the blood test is high, it implies stimulation, usually with infection. Low neutrophils implies immune system supression, often from chemotherapy, but from other causes such as bone marrow dysfunction, toxicities, and other unknown causes.
An update on the diagnosis and treatment of chronic idiopathic neutropenia.2017
Evaluation and Management of Patients with Isolated Neutropenia.2013
Iron Deficiency Anemia-Induced Neutropenia in Adult Female.2020
ELANE Mutations in Cyclic and Severe Congenital Neutropenia—Genetics and Pathophysiology.2012
Serine, Phosphatidyl-Serine
This page is under development. Working links will provide starting information. Please let us know about your interest in this page by emailing us here, and check back soon.
File Access
Serine is an amino acid. Phosphatidyl-serine, a derivative, can help with adrenal balance, sleep and pain.
References
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From OpenAI 3/27/2023
how does serine blockage affect detoxification pathways
Serine metabolism plays an important role in detoxification pathways, particularly the detoxification of reactive oxygen species (ROS) that can damage cells and contribute to the development of various diseases. Serine is a precursor for the synthesis of glutathione, which is an important antioxidant that plays a key role in detoxification. Glutathione contains a thiol (-SH) group that can bind to and neutralize ROS, thereby protecting cells from oxidative damage.
Blockage of serine metabolism can impair the synthesis of glutathione, leading to decreased levels of this important antioxidant. This can lead to increased oxidative stress and damage to cells, tissues, and organs. For example, studies have shown that inhibition of serine hydroxymethyltransferase, an enzyme involved in serine metabolism, leads to decreased glutathione synthesis and increased oxidative stress in liver cells.
Furthermore, certain genetic disorders that affect serine metabolism, such as serine deficiency disorders and glycine encephalopathy, can cause severe neurological symptoms due to impaired detoxification pathways. These disorders are characterized by decreased levels of serine and glycine, and reduced synthesis of glutathione, which can lead to oxidative damage and neurological dysfunction.
In summary, blockage of serine metabolism can impair detoxification pathways, particularly the synthesis of glutathione, leading to increased oxidative stress and damage to cells and tissues.
provide citations
Fernández-Fernández S, Almeida A, Bolaños JP. Antioxidant and bioenergetic coupling between neurons and astrocytes. Biochem J. 2012 Jun 1;443(2):3-11. doi: 10.1042/BJ20120193. PMID: 22646003.
Owen OE, Kalhan SC, Hanson RW. The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem. 2002 Aug 30;277(35):30409-12. doi: 10.1074/jbc.R200006200. PMID: 12089146.
Höring S, Radloff M, Stüve B, et al. Inhibition of serine hydroxymethyltransferase 2 impairs glutathione synthesis and redox homeostasis in human hepatocytes but not in immortalized hepatocyte-like cells. Redox Biol. 2020 Apr;31:101442. doi: 10.1016/j.redox.2019.101442. Epub 2019 Dec 7. PMID: 31838456.
Item CB, Stöckler-Ipsiroglu S, Stromberger C, et al. Arginine:glycine amidinotransferase deficiency: the third inborn error of creatine metabolism in humans. Am J Hum Genet. 2001 Apr;68(4):839-47. doi: 10.1086/319522. Epub 2001 Mar 5. PMID: 11231901.
Varga M, Berenyi E, Kosztolanyi G, et al. Hypophosphatemic rickets, seizures, and mental retardation syndrome caused by a novel homozygous mutation in SLC20A2. Orphanet J Rare Dis. 2014 Oct 10;9:139. doi: 10.1186/s13023-014-0139-8. PMID: 25300976.
From OpenAI 3/27/2023
what minerals, vitamins, aminos and hormones are required for proper serine metabolism
Serine metabolism requires various minerals, vitamins, amino acids, and hormones to function properly. Some of the important ones are:
Vitamins:
a) Vitamin B6: Pyridoxal-5-phosphate (PLP), the active form of vitamin B6, is a cofactor for several enzymes involved in serine metabolism, including serine dehydratase, serine hydroxymethyltransferase, and phosphoserine aminotransferase.
b) Folate: 5,10-Methylene-tetrahydrofolate, a folate derivative, is required for the conversion of serine to glycine by the glycine cleavage system.
Minerals:
a) Magnesium: Magnesium is required as a cofactor for serine hydroxymethyltransferase, which converts serine to glycine.
b) Iron: Iron is required for the activity of serine dehydratase, which catalyzes the conversion of serine to pyruvate.
c) Zinc: Zinc is required for the activity of serine proteases, which are involved in the breakdown of proteins.
Amino acids:
a) Glycine: Serine can be converted to glycine via the glycine cleavage system.
b) Methionine: Methionine is required for the synthesis of S-adenosylmethionine (SAM), which is a methyl donor for the conversion of serine to glycine.
c) Cysteine: Cysteine is required for the synthesis of glutathione, which plays a role in the detoxification of reactive oxygen species generated during serine metabolism.
Hormones:
a) Insulin: Insulin stimulates the uptake of serine by cells and enhances the activity of serine hydroxymethyltransferase.
b) Glucagon: Glucagon stimulates the breakdown of glycogen to provide glucose for energy metabolism, which requires serine as a substrate.
Source:
Brosnan, J. T. (2003). Interorgan amino acid transport and its regulation. The Journal of nutrition, 133(6), 2068S-2072S.
Meinitzer, A., Puchinger, M., & Willeit, P. (2019). The role of the biomarker S-adenosylmethionine for the prediction of disease and mortality risk. Biomarkers in medicine, 13(6), 455-465.
Lu, S. C. (2009). Regulation of hepatic glutathione synthesis: current concepts and controversies. The FASEB journal, 23(2), 526-535.
Levene, A. P., Kudo, H., Armstrong, M. J., Thursz, M. R., Gedroyc, W., Anstee, Q. M., … & Goldin, R. D. (2019). Insulin resistance and diabetes increase fibrosis in the liver of patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis. Diabetologia, 62(10), 1692-1701.
From OpenAI 3/27/2023
describe serine metabolism and agents that might block its metabolism
Serine is an important amino acid that plays a role in a variety of biological processes, including protein synthesis, cell signaling, and the synthesis of other important biomolecules such as nucleotides and phospholipids.
Serine is synthesized in the body from 3-phosphoglycerate, a glycolytic intermediate, by the enzyme phosphoglycerate dehydrogenase. It can also be obtained from the diet by consuming foods rich in serine or its precursors.
Once serine is in the body, it can be converted into several other metabolites, including glycine, cysteine, and one-carbon units for nucleotide synthesis. Serine can also be converted into pyruvate through a series of enzymatic reactions known as serine catabolism.
Several agents have been identified that can block serine metabolism in various ways. For example, the drug 3-phosphoglycerate dehydrogenase inhibitors can block the first step of serine synthesis by inhibiting the enzyme that converts 3-phosphoglycerate to serine. Similarly, compounds such as hydroxypyruvate and hydroxypyruvate analogs can inhibit serine dehydratase, an enzyme involved in serine catabolism, thus preventing the breakdown of serine into pyruvate.
It is worth noting that blocking serine metabolism can have significant physiological consequences, as serine is an essential substrate for a number of cellular processes. For example, inhibiting serine synthesis can impair cell growth and division, while blocking serine catabolism can lead to the accumulation of toxic intermediates and cell death.
In summary, serine metabolism is a complex process that plays a critical role in many aspects of cellular physiology. While certain agents can block serine metabolism, such interventions should be carefully evaluated to avoid unintended consequences.
Mehta MM, Weinberg SE, Chandel NS. Mitochondrial control of immunity: beyond ATP. Nat Rev Immunol. 2017;17(10):608-620. doi: 10.1038/nri.2017.66
Snell K. Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul. 1984;22:325-400. doi: 10.1016/0065-2571(84)90014-7
Possemato R, Marks KM, Shaul YD, et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature. 2011;476(7360):346-350. doi: 10.1038/nature10350
Oldham WM, Clish CB, Yang Y, Loscalzo J. Hypoxia-mediated increases in L-2-hydroxyglutarate coordinate the metabolic response to reductive stress. Cell Metab. 2015;22(2):291-303. doi: 10.1016/j.cmet.2015.06.022
Labuschagne CF, van den Broek NJF, Mackay GM, Vousden KH, Maddocks ODK. Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Rep. 2014;7(4):1248-1258. doi: 10.1016/j.celrep.2014.04.045
