Synthesizing, acetylating and separating using column chromatography was actually very interesting. Remaking the point in history when the first “sandwich” compound was discovered in 1951, a very cool structure to a molecule that has proven itself to be very useful through the ages.
Everyone on a steady low carb diet had, sooner or later, to start researching about reasons behind things like dry eyes, bruises, muscle cramps, constipation, energy levels and such. These is what I take daily and why and in most cases (except Alpha Lipoic Acid) I take these supplements in the morning before/during breakfast. Feel free to add up and let me know what you need and use.
Magnesium: 400mg x 4 pills turns out to be the ideal amount for me to keep cramps (especially leg cramps which used to wake me up in the middle of the night) at bay, along with managing bowel movements and general lack of energy/keto flu symptoms, which are usually due to lack of electrolytes. Some take Milk of Magnesia for the latter but I personally can’t stand the taste (it literally makes me puke), so I find magnesium caps to make up perfectly for it.
L-Carnitine: 588mg x 4 pills. the New Atkins book is the first source where Ilearned about Carnitine. It is an amino acid that helps metabolising fat, basically transporting the fat out of the fat cells. Everyone in a state of ketosis could use more of this. It also apparently helps a lot with brain activity and energy, especially the Acetyl l-carnitine version, though the L-Carnitine tartarate seems to be the preferred version for fat loss. In my case I have had Acetyl-l-carnitine in the last 6/8 months and I can tell given equal inputs in terms of food and water I do see a difference when I take 2400mg of carnitine per day.
CoQ10: 200mg x 2. Suggested by the Atkins book as well as a fat transporter just like l-carnitine. CoQ10 can have a balancing effect on blood sugars and insulin, and may be helpful for reducing insulin resistance which ultimately can boost fat-burning. Dr Atkins tells of a study which showed improved fat-burning and weight loss when persons who were previously deficient in CoQ10 were given the supplement. Apparently the best form to consume as supplement is Ubiquinol, which is the synthesised version of the CoQ10 our body actually uses. Although in Ubiquinol form the cost is unsustainable to me, even though it’s told to be so much more concentrated than the simple CoQ10 pills. For economical reasons though I am still personally on the simple CoQ10, 200mg. If you’re under 25 years old, your body is capable of converting CoQ10 to the reduced Ubiquinol form fairly well and the additional expense of purchasing the reduced form is unnecessary. However, if you’re older, your body becomes increasingly challenged to convert the oxidized CoQ10 to ubiquinol.
Choline: 500mg x 1. I’ve just recently come around this as it’s supposed to support the L-Carnitine function and metabolisation of fat, though it’s supposed to be taken around meals and I haven’t quite done that yet.
Omega-3: 1400mg x1 (EPA 647mg + DHA 253mg) evn though I should get to 2. Besides the general appreciation for omega 3 oils they support increased absorption of L-Carnitine as well as helping the ones suffering from hypothyroidsm. What’s important and defines the quality in Omega-3 pills is the actual EPA & DHA content, which for low carbers is suggested to be around EPA 1,500 mg / DHA 750 mg daily. Should be taken with Choline just before meals.
Alpha Lipoic Acid/R-Lipoic Acid: 1200mg ad hoc before sleep or before uncontrollable carb-y meals. ALA reduces blood sugar by pushing glucose into the muscle for use rather than toward conversion for fat deposits. it basically flips a “switch” that causes increase in the amount of energy to go towards building muscle and decrease in the amount of energy used to go towards adding fat, Usually when my carbs intake is worryingly close or maybe even over 20g per day I usually take 1200 to 2400mg and if it doesn’t prevent me from slipping out of ketosis it certainly helps me to go back into it sooner. Be careful though to have it really just when you have had carbs and you actually have glucose to push into muscles, cause if taken when eating super low carb, even just 1200mg can send you into hypoglycaemia and knock you down for an entire day. Believe me, it happened twice to me and once you’re there you just need to wear it off, even eating sugar won’t help. Beside this keto-help effect though it is known to be a quite potent anti radicals.
On these I can comment myself, although usually there are some more supplements considered default for low-carb diets/keto people, so for reference here they come:
Vitamin K2 complex: if you have noticed extra-bruising occurring since eating low carb, you might be lacking vitamin K.
Iodine/Selenium/Vitamin D3: help with thyroid functions, especially against hypothyroidism. Vitamin D3 is also suspected to be connected with the “killing” of fat cells rather than just the shrinking, it is suggested in quantities up to 10000 IU per day.
Alpha GPC: This nootropic boostsawareness&cognitivecapacity * The significance of choline for yourcreation of attention and memoryraising acetyl choline is efficientlydocumented. It can beguaranteed by a range ofclinical studiesmilligrams - More Information: ThoroughWearing down (with study) And Wikipedia.org/wiki/Alpha-GPC
Huperzine A: Raisesintellectualfunctionality, and possesses neuroprotective outcomes. A studyobtainedresults that proven 58Per cent of patientsaddressed with Huperzine-A hadalterations in cognition, and conduct functionsMore Info: DetailedBreak down (with reports) And Wikipedia.org/wiki/Huperzine_A
Hericium Erinaceus (Lion’s Mane): Improvememory and awareness, improveneurologicalupkeep, detoxes liver, stop alzheimer’s, normalizebloodstreamsugar and cholesteroldiplomas. In just adual sightless, placebo controlledexamine, revealed that Hericium Erinaceus(Lion’s Mane) is effectiveformodest cognitivemilligrams - Much More Information: CompleteFail to function properly (with scientific research) And
Boostsemphasis, restduring the night, safeguardcomponents And blood pressurelevelsmanagement. L-Theanine is becomingstudiedfor theability toreducestress, improve cognition and boost yourmindset. In a 1999 components ofpaperpublished by Food itemsTechnology and
Science, L-Theanine was provided tofolks in dosenumbers of 50 - 200 mgs. It wasbasicallyobserved that L-Theanine straightimpactedthe production of Alpha Surfinside aexcellentstrategy. Alpha waveswould be thequiethowevertellbrainissueneeded to concentrationmg - Much More Information: In depthFail to function properly (with studies) And Wikipedia.org/wiki/Theanine
Caffeinated drinksintake: Boostemphasis, booststorage, raiseenergy, detoxes liver organ, wards far from alzheimer’s, increaseenergy, alleviate despression signs or symptoms, and so forth. According to a new study in Japan, scientists found out that just as
muscle cells are stimulated by caffeine, brain cells in the hippocampus are
stimulated to increase calcium concentration. This raises thecellular materialindicateactivityconsequentlyimprovingstorage. Caffeine intake intakemg - More Details: ThoroughWearing down (with research studies) & Wikipedia.org/wiki/Caffeine intake
Bacopa: Enhancesbrainmemory and function. Bacopa monnieri is extensivelytested and provenas being amemory and concentrationincreaser. Outcomes ofstudyjust recentlyshown that Bacopa decreasedsome timethought it wasnecessary toresearcha freshmethod by virtuallyone half! Memberstaking Bacopa increased the work outin as little as 6 timesin comparison toten daysfor yourmanage teammilligrams - More Information: ThoroughBreaking down (with scientific tests) &
Pterostilbene: Combatsaway from and reverses mentaltumble, it reducesblood circulation lipids and cholestrerol degrees. According to dog reports it can be shown to demonstrate
anti–cancers, contra–hypercholesterolemia, anti–hypertriglyceridemia
qualities.It can bebelieved the substancealso offersanti-diabeticcharacteristics as wellmg - Additional Information: DetailedBreak down (with reports) And Wikipedia.org/wiki/Pterostilbene
Mucuna Pruriens: Raiseenergy, concentration and focus. Mucuna capabilitiesregular dopamine, among the mostvital neurotranmitters, that has aaspect in peoplecapability tocompletely focusamongstall sorts ofother activities. Furthermore, it is actuallymostlyliable for regulating sexuality and frame of mind as wellmilligrams - More Details: ThoroughMalfunction (with analysis) And
GABA: Stimulatesrobustcalmness, relaxation and sleep lucid dreaming, And
decreasesnervousness. Gaba is a vital&popular inhibitory neurotransmitter inside themind, GABA really helps toimprovemaking alpha brainsearch, proven toincreaseclarity and focus. That are connected to anxiety and anxietymg - More Details, as well
it lessens beta brain waves:DetailedMalfunction (with reports) And Wikipedia.org/wiki/Gamma-Aminobutyric_acidanswer
Nutritional supplement B6: Higherenergy, regulatesensing And appropriatehuman braindevelopment, Scientistsfound out thatNutritionalhealth supplement B6 functionsan important role in the creation of serotonin and dopamine, which can benecessary forneurologicaldialogueVitamin supplement supplementmg - Additional Information: DetailedDeteriorating (with records) & Wikipedia.org/wiki/Vitamin_B6
B Nutritional-12: Decreasesfatigue, betterelectrical energy, decrease instress. B Vitamin-12 is a crucialmethod to obtainnourishmentrequired forevery person. Latestresearch indicatesadequatemeasure of B-12 can quitintellectualdecline. Industry expertsdiscovered thatfolkssuffering fromstoragechallenges, when resolved with B12, lots ofsigns or symptomsfaded in half a yearlinked tomodifications inintellectualtop quality&completely focus. B VitaminMore Information and facts: In depthBreak down (with scientific tests) And Wikipedia.org/wiki/Nutritious_B12
ACETYL L CARNITINE
Carnitine HCL: Effectivecontra--oxidant, also lowerslowenergy. Acetylcarnitine & carnitine performvitalfunctionswithin your body. These vitamins and minerals shuttle acetyl-businesses And essential fatty acids into mitochondria for strength-manufacturing. It may wellwork as astrengthtank of acetyl groupings and similarlynutritionenhancepotentialproducing.
A new study begins to clarify how brain structure and chemistry give
rise to specific aspects of “fluid intelligence,” the ability to adapt
to new situations and solve problems one has never encountered before.
The study, reported in the journal NeuroImage, links higher
concentrations of a marker of energy production in the brain with an
improved ability to solve verbal and spatial problems. It also finds an
association between brain size and number-related problem-solving.
The analysis involved 211 research subjects, making it the largest
study to date linking brain chemistry and intelligence in living humans,
said University of Illinois postdoctoral researcher Erick Paul, who led the work with research scientist Ryan Larsen and Illinois neuroscience professor Aron Barbey. The work was conducted in the Decision Neuroscience Laboratory at the Beckman Institute for Advanced Science and Technology. More studies will be needed to confirm and extend the findings, the researchers said.
“In our data, we observed two facets of fluid intelligence – one that
involves quantitative or numeric reasoning, and another that involves
verbal or spatial reasoning,” Paul said. “A similar separation of
reasoning abilities has been demonstrated in previous studies.”
The researchers conducted magnetic resonance spectroscopy to analyze
brain concentrations of a compound called NAA (N-acetyl aspartate), a
byproduct of glucose metabolism and a marker of energy production. They
measured brain volume in all subjects using magnetic resonance imaging.
“We found that the quantitative reasoning component of intelligence
correlated with brain volume, but not with the concentration of NAA in
the brain,” Paul said. “And the verbal and spatial components of
intelligence correlated with NAA, but not with brain volume.”
The team observed the same basic relationships when analyzing males and females separately.
The findings add to the evidence that fluid intelligence involves distinct yet interrelated processes in the brain, Paul said.
“Surely there are many things about the brain that determine a
person’s intelligence, and the goal is to try to tease apart that
puzzle,” he said. “These two brain biomarkers, brain volume and NAA, are
each giving us independent information about fluid intelligence. There
are different properties of the brain that we can measure, and these
different properties go with these different facets of fluid
“Our findings contribute to a growing body of evidence to suggest
that intelligence reflects multiple levels of organization in the brain –
spanning neuroanatomy, for example brain size, and neurophysiology,
such as brain metabolism – and that specific properties of the brain
provide a powerful lens to investigate and understand the nature of
specific intellectual abilities,” Barbey said.
ASA / Aspirin : inhibits the synthesis of thromboxane A2 ( thromboxane A2 is an arachidonate product that causes platelets to change shape, release their granules, and aggregate) by irreversible acetylation of the enzyme cyclooxygenase
Clopidogrel & Ticlopidine : reduce platelet aggregation by inhibiting the ADP pathway of platelets. These drugs are thienopyridine derivatives that achieve their antiplatelet effects by irreversibly blocking the ADP receptor on platelets.
Abciximab, Eptifibatide & Tirofiban : target the platelet IIb/IIIa receptor complex. The IIb/IIIa complex functions as a receptor mainly for fibrinogen and vitronectin but also for fibronectin and von Willebrand factor. Activation of this receptor complex is the “final common pathway” for platelet aggregation.
Dipyridamole : vasodilator that inhibits platelet function by inhibiting adenosine uptake and cyclic GMP phosphodiesterase activity.
with both rare and common types of autism spectrum disorder share a
similar set of epigenetic modifications in the brain, according to a
study published November 17 in Cell. More than 68% of
individuals with different types of autism spectrum disorder show
evidence of the same pattern of histone acetylation–a chemical
modification of the protein scaffold around which DNA wraps. The
findings suggest that a single global epigenetic pattern affecting
shared molecular pathways in the brain could underlie diverse
manifestations of this psychiatric disease.
“We find epigenetic changes that are present in most patients with
autism spectrum disorder, or ASD,” says co-senior study author Shyam
Prabhakar of the Genome Institute of Singapore. “This suggests that,
despite tremendous heterogeneity in the primary causes of autism, such
as DNA mutations and environmental perturbations during development, ASD
has molecular features that are commonly shared. It is encouraging that
ASD has common molecular changes, because this opens up the possibility
of designing drugs to correct these changes.”
Association Study of Autism Spectrum Disorder” by Wenjie Sun, Jeremie
Poschmann, Ricardo Cruz-Herrera del Rosario, Neelroop N. Parikshak,
Hajira Shreen Hajan, Vibhor Kumar, Ramalakshmi Ramasamy, T. Grant
Belgard, Bavani Elanggovan, Chloe Chung Yi Wong, Jonathan Mill, Daniel
H. Geschwind, Shyam Prabhakar, in Journal of the American Geriatrics Society. Published online November 17 2016 doi:10.1016/j.cell.2016.10.031
N6-methyladenine: A Newly Discovered Epigenetic Modification
The majority of cellular functions are carried out by proteins encoded by specific genes present in cellular DNA. Genes are first transcribed to RNA which is then translated to proteins. The regulation of this process is important for maintaining correct cellular function. One of the ways that cells regulate gene expression is by epigenetic modifications to chromatin. The term “epigenetics” refers to reversible chemical modifications of DNA and histone proteins (DNA in the nucleus of eukaryotes is wrapped around histones) that affect the transcriptional status of genes. A number of histone modifications such as methylation and acetylation of lysine residues have already been discovered and characterized. Until recently; however, methylation of the 5 position of cytosine was the only known epigenetic DNA modification (A). Methylation of cytosine by DNA methyltransferases is associated with transcriptional silencing, while the removal of these methyl groups by TET enzymes is associated with transcriptional re-activation (B and C). In addition to controlling gene silencing, cytosine methylation also silences retrotransposons, a class of mobile genetic elements. If left unregulated, transposons can insert themselves into important regions of the genome and lead to mutagenesis.
Recently, N6-methyladenine, a new epigenetic modification, was discovered in mammalian cells. N6-mA had previously been discovered in prokaryotes and simple eukaryotes and was shown to function as a transcriptional activator. By contrast, a recent report published in Nature, has shown that N6-mA functions as a transcriptional silencer in mammalian cells, specifically in mouse embryonic stem cells. N6-mA primarily acts to silence the LINE-1 family of retrotransposons during early embryogenesis, which prevents genomic instability. The authors identified N6-mA by using a modified single molecule DNA sequencing technique. DNA bound to a specific modified histone protein was immunoprecipitated using an antibody against a specific histone modification (H2A.X), sequenced, and analyzed by mass spectrometry (D). This identified and determined the position of N6-mA. The authors then generated knockouts of the enzyme Alkbh1, which they believed may function as a demethylase for N6-mA. When Alkbh1 was absent from cells, they found an increase in the levels of N6-mA, showing that Alkbh1 functions as an N6-mA demethylase in vivo. This is important because epigenetic modifications are reversible. Genes can be turned off by methylation and then turned back on by removing the methyl group, so determining the enzyme responsible for the removal of N6-mA supports its role as an epigenetic modification.
In healthy cells, the tau protein helps to stabilise microtubules that act as rails for transporting materials around the cell. In people with Alzheimer’s, these proteins become toxic, but an important unanswered question is what forms of tau are toxic: the tangles may not be the whole story.
In the new study, Li Gan and her colleagues at the Gladstone Institute of Neurological Disease in San Francisco found that the brains of those with Alzheimer’s have high levels of tau with a particular modification, called acetylated tau.
They then looked at what acetylated tau does in a mouse model of Alzheimer’s, finding that it accumulates at synapses – the connections between neurons.
When we form memories, synapses become strengthened through extra receptors inserted into the cell membranes, and this heightens their response. But acetylated tau depletes another protein called KIBRA, which is essential for this synapse-strengthening mechanism.
“We’re excited because we think we now have a handle on the link between tau and memory,” says Gan. “We’re also cautious because we know this may not be the only link. It’s still early days in understanding the mechanism.”
In cultured neurons, restoring levels of KIBRA reversed the effects of acetylated tau, restoring their ability to strengthen connections. This offers a strategy for therapies, Gan says. “If we provide neurons with more of this protein, we can repair the lost synaptic strengthening that we usually observe.”
If synapses can’t become strengthened, the connections between neurons – and the memories they encode – may be lost. These lost synapses correlate more closely with cognitive decline than any other feature.
“It turns out that they’re very important – not just markers of cognitive change, but they may actually be driving the disease process in several ways,” says Tara Spires-Jones at the University of Edinburgh Medical School, a member of the grant review board at Alzheimer’s Research UK.
Spires-Jones cautions that findings in mouse studies have not always translated well to Alzheimer’s in humans. “I am really excited about this paper, and I think it is a good step in terms of knowing which the toxic forms of tau are and giving us new targets to follow up, but it is a long way from people.”
Urtica dioica or commonly called Stinging Nettle is a diverse herb with known medical attributes dating back to as early as around 100 AD. The stinging sensation this plant can give off comes from small glass like hairs on the leaves, that when broken release a stinging liquid made up of formic acid, histamine, acetyl-choline and serotonin. However, fear not because the juice made from grinding the leaves of this plant can be used to treat its sting.
Nettle can used to treat hay fever, asthma, itchy skin, insect bites, and most importantly treat acute allergy symptoms. (After trying this brew I did notice a significant decrease in my seasonal allergy symptoms.) In addition nettle can boost the production of breast milk, cleanse urine, treat enlarged prostates, work as an anti-arthritic, and slow bleeding. If you’re on any sort of medication for depression, diabetes, high blood pressure, or sedatives nettle can cause a moderate reaction.
The tea has a light grassy smell and mild taste of spinach. Honey is a great addition to this tea.
“Immunostaining of planktonic Cnidaria. Acetylated tubulin (green), myosin (red), nuclei (blue). Image taken with ZEISS Lightsheet Z.1 during the EMBO course on Marine Animal Models in Evolution & Development, Sweden 2013. www.zeiss.com/lightsheet Sample courtesy of Helena Parra, Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona.”
The association of autism spectrum disorders with oxidative stress, redox imbalance, and mitochondrial dysfunction has become increasingly recognized. In this study, extracellular flux analysis was used to compare mitochondrial respiration in lymphoblastoid cell lines (LCLs) from individuals with autism and unaffected controls exposed to ethylmercury, an environmental toxin known to deplete glutathione and induce oxidative stress and mitochondrial dysfunction. We also tested whether pretreating the autism LCLs with N-acetyl cysteine (NAC) to increase glutathione concentrations conferred protection from ethylmercury. Examination of 16 autism/control LCL pairs revealed that a subgroup (31%) of autism LCLs exhibited a greater reduction in ATP-linked respiration, maximal respiratory capacity, and reserve capacity when exposed to ethylmercury, compared to control LCLs. These respiratory parameters were significantly elevated at baseline in the ethylmercury-sensitive autism subgroup as compared to control LCLs. NAC pretreatment of the sensitive subgroup reduced (normalized) baseline respiratory parameters and blunted the exaggerated ethylmercury-induced reserve capacity depletion. These findings suggest that the epidemiological link between environmental mercury exposure and an increased risk of developing autism may be mediated through mitochondrial dysfunction and support the notion that a subset of individuals with autism may be vulnerable to environmental influences with detrimental effects on development through mitochondrial dysfunction.
To celebrate my finally finishing the semester, I thought I would dish out another OB Science Time, this time in my own fascinating field of epigenetics, and how this relates to the clones of Orphan Black! YAY!!
So what exactly is epigenetics? Epigenetics refers to the heritable alterations in phenotype without changes to genotype, as well as the modifications of gene activity that are not based on alterations of DNA sequence. In other words, there is a heritable and a non-heritable side to the study of epigenetics.
I’ll make this a tad simpler. Almost every cell in your body contains a nucleus that contains all the DNA in your genome. Brain cells, heart cells, skin cells, kidney cells - they all have the exact same DNA. But then why are some genes only expressed in certain cells, causing every cell type to have different functions? Chromosomal modifications. Certain additions to the chromosome (methyl groups, acetyl groups, ubiquitin, etc.) will cause changes in expression of the genes on that part of the chromosome.
Now some of this is inherited from the parents. When mitosis occurs and the DNA is duplicated, the chromosomal modifications are duplicated to ensure that the expression patterns of the genes is maintained. The same happens in the gametes when meiosis occurs, so the epigenetics of the parents is passed down to the child.
But you can also acquire new epigenetic modifications. Cellular interactions, foreign materials, the microenvironment of the cell, the activities of the person, and many other things can cause alterations in the epigenome of a person. The womb is considered to be an important influence on the epigenome, right down to the minute microenvironments, which is why even identical twins can have epigenetic differences because they are experiencing different microenvironments.
So this is an extremely fascinating field, but what does it mean for twins, or even, say, a whole bunch of clones in some great experimental conspiracy on a certain Canadian sci-fi show? Well, it basically means that, even though all the Leda clones have the exact same genome, they can have many differences in their epigenomes, causing all the differences we see between them.
But epigenetics is specifically interesting when it comes to the clone disease! We know that Sarah and Helena are both fertile, meaning they do not express the synthetic infertility sequence that Ethan created. Now this could be due to a mutation in their sequence, or a complete absence of the sequence from their genome. But then why couldn’t Cosima just use Sarah’s bone marrow for the transplant, because she wouldn’t have the same sequence.
Now, if Sarah and Helena both had the exact same sequence, but had epigenetic modifications that were silencing the synthetic sequence, that would explain why their own cells are not an option. Giving Cosima a transplant from Sarah could maybe have a chance of working, but most likely, the environment of Cosima’s body would maintain the epigenetic patterns that were already present, and would remove the modifications silencing Sarah’s gene, making the whole transplant moot (hehe). And Sarah’s genetics would be no assistance in gene therapy, because gene therapy involves the injection of a single naked gene, without any modifications, so the epigenetic modifications would be removed before the injection.
So, basically, not only is epigenetics a completely fascinating field in reality, it can help explain some of what we have seen in Orphan Black!!
As always, if you have any questions, comments, concerns, don’t be afraid to hit me up so we can discuss all the science!!! And for more OB Science Time click here :D
“Immunostaining of planktonic Cnidaria. Acetylated tubulin (green), myosin (red), nuclei (blue). Image taken with ZEISS Lightsheet Z.1 during the EMBO course on Marine Animal Models in Evolution & Development, Sweden 2013. www.zeiss.com/lightsheet Sample courtesy of Helena Parra, Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona. Part of the Life:Magnified exhibit at Washington Dulles Airport, 2014″
Yesterday I purified a larger amount on slightly decomposed 1,1′-diacetylferrocene by sublimation/distillation at reduced pressure. After the purification, these crystals were left in the still pot.
1,1′-diacetylferrocene is an orange to red crystalline solid, with a melting point
122-128 °C. It is an organoiron compound with the formula Fe(C5H4COMe)2, it consists of ferrocene substituted by two acetyl group on each of the cyclopentadienyl rings. It is an air-stable solid that is soluble in organic solvents and as seen it forms beautiful crystals.
Cnidaria, MultiView Light Sheet Microscopy (4 of 4)
Immunostaining of planktonic Cnidaria. Acetylated tubulin (green), myosin (red), nuclei (blue). Image taken with ZEISS Lightsheet Z.1 during the EMBO course on Marine Animal Models in Evolution & Development, Sweden 2013. www.zeiss.com/lightsheet Sample courtesy of Helena Parra, Institut de Biologia Evolutiva (CSIC-Universitat Pompeu Fabra), Barcelona.