Human UBIAD1 localizes to mitochondria and converts vitamin K(1) to vitamin K(2). Vitamin K(2) is best known as a cofactor in blood coagulation, but in bacteria it is a membrane-bound electron carrier. Whether vitamin K(2) exerts a similar carrier function in eukaryotic cells is unknown. We identified Drosophila UBIAD1/Heix as a modifier of pink1, a gene mutated in Parkinson's disease that affects mitochondrial function. We found that vitamin K(2) was necessary and sufficient to transfer electrons in Drosophila mitochondria. Heix mutants showed severe mitochondrial defects that were rescued by vitamin K(2), and, similar to ubiquinone, vitamin K(2) transferred electrons in Drosophila mitochondria, resulting in more efficient adenosine triphosphate (ATP) production. Thus, mitochondrial dysfunction was rescued by vitamin K(2) that serves as a mitochondrial electron carrier, helping to maintain normal ATP production.
I have started to fallow TULIP with great results. You are my hero for puting this thread together heh. and of course thanks for everyone else who have contributed. I have tried some nootropics without big success before. Piracetam gave me depression, noopept made me less social and less creative, but from button to top approach (improve mitochondria energy) have worked better.
I am using co10 200 mg a day, pqq 20 mg, pregnenolone 50 mg a day + cheap lasers for 30s per region every other day for 2 weeks. Coffee and l-carnitine titrate (I wasn't able to get ALCAR in local shop) sometimes as well.
Sometimes when I take this stack I feel tingling feeling in back of my head and I like it. It seems I have better verbal flow and thinking.
I'm pretty happy with results. I am more energetic, more social and brain fog has disappeared. I have finally started to work on projects which I delayed for a year. Depression is almost gone.
Baseline energy have improved, but at this point its not enough and I want to push this further.
I was wondering if there is something complimentary to this stack you recommend to test?
I read that you were also including artichoke in your stack. Do you still recommend it?
Have you experimented with anything else with good results?
I have started to fallow TULIP with great results. You are my hero for puting this thread together heh. and of course thanks for everyone else who have contributed. I have tried some nootropics without big success before. Piracetam gave me depression, noopept made me less social and less creative, but from button to top approach (improve mitochondria energy) have worked better.
I was wondering if there is something complimentary to this stack you recommend to test?
I read that you were also including artichoke in your stack. Do you still recommend it?
Have you experimented with anything else with good results?
Hey raimis100, that's awesome that TULIP is working so well for you! I'm a pretty big fan of the bottom up approach myself. =)
I have tried a huge number of things over the past couple of years...some with good results and some with not so good results. I'm currently working through all of the recent research on mitochondrial function and I should be able to answer your questions better in the coming weeks.
I only included artichoke extract occasionally in the past but I did notice a nice boost when I did. It was almost a bit too much though...not sure if I 'recommend it' per se, but I don't think it would hurt if you wanted to experiment with it on occasion.
For recent experiments just go back over the most recent four or five pages in this thread. I've discussed noradrenaline enhancers, ampakines, PDE5 inhibitors, etc. Sorry, I know this thread isn't the most organized. =)
And...since we're on the topic of PDE5 inhibitors I thought it apropos to mention this recent rodent study with one of my other favorite topics...HDACi. Apparently, vorinistat + tadalafil, "alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons." Pretty cool.
Clin Epigenetics. 2015 Oct 8;7:108. doi: 10.1186/s13148-015-0142-9. eCollection 2015.
Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.
Given the implication of histone acetylation in memory processes, histone deacetylase inhibitors (HDACIs) have been postulated as potential modulators of cognitive impairment in Alzheimer's disease (AD). However, dose-dependent side effects have been described in patients with the currently available broad-spectrum HDACIs, explaining why their therapeutic potential has not been realized for chronic diseases. Here, by simultaneously targeting two independent enzyme activities, histone deacetylase (HDAC) and phosphodiesterase-5 (PDE5), we propose a novel mode of inhibitory action that might increase the therapeutic specificity of HDACIs.
RESULTS:
The combination of vorinostat, a pan-HDACI, and tadalafil, a PDE5 inhibitor, rescued the long-term potentiation impaired in slices from APP/PS1 mice. When administered in vivo, the combination of these drugs alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons. Significantly, the combination of vorinostat and tadalafil was more effective than each drug alone, both against the symptoms and in terms of disease modification, and importantly, these effects persisted after a 4-week washout period.
CONCLUSIONS:
The results highlight the pharmacological potential of a combination of molecules that inhibit HDAC and PDE5 as a therapeutic approach for AD treatment.
And...since we're on the topic of PDE5 inhibitors I thought it apropos to mention this recent rodent study with one of my other favorite topics...HDACi. Apparently, vorinistat + tadalafil, "alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons." Pretty cool.
Clin Epigenetics. 2015 Oct 8;7:108. doi: 10.1186/s13148-015-0142-9. eCollection 2015.
Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.
Given the implication of histone acetylation in memory processes, histone deacetylase inhibitors (HDACIs) have been postulated as potential modulators of cognitive impairment in Alzheimer's disease (AD). However, dose-dependent side effects have been described in patients with the currently available broad-spectrum HDACIs, explaining why their therapeutic potential has not been realized for chronic diseases. Here, by simultaneously targeting two independent enzyme activities, histone deacetylase (HDAC) and phosphodiesterase-5 (PDE5), we propose a novel mode of inhibitory action that might increase the therapeutic specificity of HDACIs.
RESULTS:
The combination of vorinostat, a pan-HDACI, and tadalafil, a PDE5 inhibitor, rescued the long-term potentiation impaired in slices from APP/PS1 mice. When administered in vivo, the combination of these drugs alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons. Significantly, the combination of vorinostat and tadalafil was more effective than each drug alone, both against the symptoms and in terms of disease modification, and importantly, these effects persisted after a 4-week washout period.
CONCLUSIONS:
The results highlight the pharmacological potential of a combination of molecules that inhibit HDAC and PDE5 as a therapeutic approach for AD treatment.
This is very cool science, but how could we apply it in practice? Yes, tadalafil is cheap and abdundant at the 15 mg/kg rodent dose. But vorinostat is prohibitively expensive at 50 mg/kg.
The cheapest HDAC inhibitor I can think of is thymoquinone (economically derived from Nigella sativa). At 10 mg/kg (intraperitoneal -- d'oh!) it revved up neurogenesis in the dentate gyrus by about 25%. Given that Nigella sativa is about 1/3 oil by mass, and the oil in turn yields about 4 mg thymoquinone per 1 g of oil with SC-CO2 extraction (or, presumably, digestive extraction), an 80 kg adult human would need to eat about 600 g of Nigella sativa (or 200 g of oil) per day, which would be indigestible in practice, to say nothing of the cost. Granted, some antidepressive effects were obtained at lower doses, but no mention was made of neurogenesis in that case; maybe the required dose is massively overestimated, but I have no evidence for that.
I'm hoping someone will point me to a cheaper HDAC inhibitor or a lower neurogenesis threshold of thymoquinone. ("Cheap" essentially means dollars per neuron created.) Anyone? [EDIT: Maybe trichostatin A, which is now really cheap from a variety of dodgy vendors on Alibaba; at least one could run a mass spectrometry analysis to verify. Or maybe sodium butyrate?]
Edited by resveratrol_guy, 16 October 2015 - 12:57 AM.
This is very cool science, but how could we apply it in practice? Yes, tadalafil is cheap and abdundant at the 15 mg/kg rodent dose. But vorinostat is prohibitively expensive at 50 mg/kg.
Hey, what's up resveratrol_guy?
Sorry man, I posted that study as just interesting science for the time being. I wouldn't recommend attempting to replicate it at this time. I am a big fan of tadalafil/PDE5i though.
I have started to fallow TULIP with great results. You are my hero for puting this thread together heh. and of course thanks for everyone else who have contributed. I have tried some nootropics without big success before. Piracetam gave me depression, noopept made me less social and less creative, but from button to top approach (improve mitochondria energy) have worked better.
I am using co10 200 mg a day, pqq 20 mg, pregnenolone 50 mg a day + cheap lasers for 30s per region every other day for 2 weeks. Coffee and l-carnitine titrate (I wasn't able to get ALCAR in local shop) sometimes as well.
Sometimes when I take this stack I feel tingling feeling in back of my head and I like it. It seems I have better verbal flow and thinking.
I'm pretty happy with results. I am more energetic, more social and brain fog has disappeared. I have finally started to work on projects which I delayed for a year. Depression is almost gone.
Baseline energy have improved, but at this point its not enough and I want to push this further.
I was wondering if there is something complimentary to this stack you recommend to test?
I read that you were also including artichoke in your stack. Do you still recommend it?
Have you experimented with anything else with good results?
Google ASMR for the tingling. Have you had this ever happen prior?
I googled ASMR. Maybe this feeling could be categorized as ASMR, maybe not. I have had this experience before, but never from sounds as far as I have noticed. I had the tingling feeling first few times I used co10 and then first few days I added PQQ to this stack. These effects have disappeared, but I am still trying to chase this feeling. It's euphoric.
Someone who isn't me had similar feeling when I tried amphetamine for this firs time as well. So maybe thats just from dopamine rush.
Have you looked into PDE5i for mitochondrial function and biogenesis? This is just a rodent study...but interesting nonetheless.
"...chronic treatment with tadalafil activates NO-induced SIRT1-PGC-1α signaling and attenuates mitochondrial dysfunction in type 2 diabetic hearts."
"Treatment of diabetic mice with tadalafil protected oxidative phosphorylation with an improved rates of oxidative phosphorylation through complex I..."
"Taken together, our results provide an interesting paradigm where tadalafil enhances mitochondrial function via activation of AMPK and SIRT1 and their downstream targets, including PGC-1α in the heart."
"Remarkably, the increased production of ROS from complex 1 in diabetic mice was decreased by tadalafil treatment."
"Tadalafil treatment in db/db mice attenuated ROS generation and preserved the loss of mitochondrial membrane potential in cardiomyocytes following simulated ischemia-reoxygenation injury in vitro and attenuated myocardial oxidative stress including in vivo lipid per oxidation."
"Since activation of SIRT1 decreases oxidative stress via its regulatory effects on mitochondrial function (1), we further determined mitochondrial function as well as the regulation of downstream signaling proteins that might play a role in tadalafil-induced NO-SIRT1 signaling in the heart following tadalafil treatment in db/db mice."
"...tadalafil treatment improved bioavailability of NO as evidenced by enhanced circulating NOx levels (Fig. 2C) and improved cardiac function in diabetic mice."
"Enhanced nitric oxide (NO) production is known to activate silent information regulator 1 (SIRT1), which is a histone deacetylase that regulates PGC-1α, a regulator of mitochondrial biogenesis and coactivator of transcription factors impacting energy homeostasis."
"Moreover, the favorable effects on metabolic status of db/db mice such as a trend toward decreased body weights, blood glucose, and significant improvement in hyperinsulinemia and hypertriglyceridemia suggest possible use of tadalafil in diabetes-induced cardiovascular abnormalities."
"The chronic treatment with tadalafil ameliorated circulating inflammatory cytokines and chemokines while improving fasting glucose levels and reducing infarct size following ischemia-reperfusion injury in diabetic hearts."
"Importantly, this complex I-based defect in integrated respiration in the total mitochondrial population was abrogated by tadalafil treatment."
"In the present study, forward flow through complex I also increased production of H2O2 in mitochondria from db/db mice that was markedly attenuated by treatment with tadalafil."
"... the capacity for mitochondrial production of ATP is clearly improved by tadalafil."
"PDE-5 inhibitors, which could act as SIRT1 activators, represent a highly safe and attractive class of compounds that are already Food and Drug Administration approved for erectile dysfunction and pulmonary hypertension."
Chronic inhibition of phosphodiesterase 5 with tadalafil attenuates mitochondrial dysfunction in type 2 diabetic hearts: potential role of NO/SIRT1/PGC-1α signaling.
Enhanced nitric oxide (NO) production is known to activate silent information regulator 1 (SIRT1), which is a histone deacetylase that regulates PGC-1α, a regulator of mitochondrial biogenesis and coactivator of transcription factors impacting energy homeostasis. Since phosphodiesterase-5 inhibitors potentiate NO signaling, we hypothesized that chronic treatment with phosphodiesterase-5 inhibitor tadalafil would activate SIRT1-PGC-1α signaling and protect against metabolic stress-induced mitochondrial dysfunction in diabetic hearts. Diabetic db/db mice (n = 32/group; 40 wk old) were randomized to receive DMSO (10%, 0.2 ml ip) or tadalafil (1 mg/kg ip in 10% DMSO) for 8 wk. Wild-type C57BL mice served as nondiabetic controls. The hearts were excised and homogenized to study SIRT1 activity and downstream protein targets. Mitochondrial function was determined by measuring oxidative phosphorylation (OXPHOS), and reactive oxygen species generation was studied in isolated mitochondria. Tadalafil-treated diabetic mice demonstrated significantly improved left ventricular function, which is associated with increased cardiac SIRT1 activity. Tadalafil also enhanced plasma NO oxidation levels, myocardial SIRT1, PGC-1α expression, and phosphorylation of eNOS, Akt, and AMPK in the diabetic hearts. OXPHOS with the complex I substrate glutamate was decreased by 50% in diabetic hearts compared with the nondiabetic controls. Tadalafil protected OXPHOS with an improved glutamate state 3 respiration rates. The increased reactive oxygen species production from complex I was significantly decreased by tadalafil treatment. In conclusion, chronic treatment with tadalafil activates NO-induced SIRT1-PGC-1α signaling and attenuates mitochondrial dysfunction in type 2 diabetic hearts.
Recent studies demonstrate that mitochondrial dysfunction is a mediator of acute kidney injury (AKI). Consequently, restoration of mitochondrial function after AKI may be key to the recovery of renal function. Mitochondrial function can be restored through the generation of new, functional mitochondria in a process called mitochondrial biogenesis (MB). Despite its potential therapeutic significance, very few pharmacological agents have been identified to induce MB. To examine the efficacy of phosphodiesterase (PDE) inhibitors (PDE3: cAMP and cGMP activity; and PDE4: cAMP activity) in stimulating MB, primary cultures of renal proximal tubular cells (RPTCs) were treated with a panel of inhibitors for 24 hours. PDE3, but not PDE4, inhibitors increased the FCCP-uncoupled oxygen consumption rate (OCR), a marker of MB. Exposure of RPTCs to the PDE3 inhibitors, cilostamide and trequinsin, for 24 hours increased peroxisome proliferator-activated receptor γ coactivator-1α, and multiple mitochondrial electron transport chain genes. Cilostamide and trequinsin also increased mRNA expression of mitochondrial genes and mitochondrial DNA copy number in mice renal cortex. Consistent with these experiments, 8-Br-cGMP increased FCCP-uncoupled OCR and mitochondrial gene expression, whereas 8-Br-cAMP had no effect. The cGMP-specific PDE5 inhibitor sildenafil also induced MB in RPTCs and in vivo in mouse renal cortex. Treatment of mice with sildenafil after folic acid-induced AKI promoted restoration of MB and renal recovery. These data provide strong evidence that specific PDE inhibitors that increase cGMP are inducers of MB in vitro and in vivo, and suggest their potential efficacy in AKI and other diseases characterized by mitochondrial dysfunction and suppressed MB.
A) Fill glass with water, add MB drops, add Vit C. and wait 3 hours for it to turn clear?
B) No need to wait
C) Ingest Vit. C a few hours before taking MB solution?
What's up, Groundhog Day?
I took 1000mg of Vitamin C right around the same time I took MB (before or after didn't seem to matter...just relatively close to the same time). Worked like a charm.
"This process is achieved with the activation of mTOR dependent translation of preexisting RNA granules (red) allowing for the transition from short-term plasticity to the initial phase of long-term plasticity. Simultaneously, the cAMP→PKA→ERK pathway induces the synthesis and activation of chromatin remodeling proteins including PARP-1. PARP-1 allows chromatin relaxation and the transcription of immediate early genes (e.g. c-fos and c-jun) and late-phase genes require for long-term plasticity. An essential component of late-phase activity-dependent gene expression is rRNA biosynthesis, the rate-limiting step in the production of new ribosomes. Ribosomal biogenesis requires both Pol I driven transcription and the efficient processing of nascent rRNA transcripts—two processes now shown to be regulated by PAR. In this model, new and qualitatively different ribosomes become assembled into new RNA granules (green) that are shipped to activated synapses in order to maintain, through local protein synthesis, the long-lasting changes required to consolidate memory."
Long-term memory (LTM) formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose) polymerase-1 (PARP-1), are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP) in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosyl)ation (PAR) dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP) ribose molecules (pADPr) after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA) and extracellular signal-regulated kinase (ERK)--two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I), responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components)--hence, new ribosomes and nucleoli integrity--are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation.
Widely thought to be a housekeeping process, the regulation and synthesis of rRNA emerges as a potentially central mechanism for the maintenance of synaptic plasticity and memory. We have recently shown that an essential component of late-phase synaptic plasticity is rRNA biosynthesis - the rate-limiting step in the production of new ribosomes. We hypothesize that a particular population of ribosomes is generated upon learning-associated neural activity to alter the rate of synthesis of plasticity factors at tagged synapses that will support the maintenance of synaptic plasticity and memory.
A) Fill glass with water, add MB drops, add Vit C. and wait 3 hours for it to turn clear?
B) No need to wait
C) Ingest Vit. C a few hours before taking MB solution?
What's up, Groundhog Day?
I took 1000mg of Vitamin C right around the same time I took MB (before or after didn't seem to matter...just relatively close to the same time). Worked like a charm.
Do you take regular Vit C or ester C? How often do you take MB?
Do you take regular Vit C or ester C? How often do you take MB?
I just took regular Vit C.
I tested 3 droppers of MB from bluebrainboost over the course of approx. 2 months. Nothing huge to report. I'm thinking my mitochondria are probably in pretty good shape already. Moving on to other experiments for the time being.
I've been looking back over the research on the inner mitochondrial membrane (phosphatidylethanolamine, phosphatidylcholine, cardiolipin, etc.). It's still all over the place. DHA will look good in study A and then study B will show that it's detrimental. Such is the nature of science. ha
The studies (not of the highest quality) actually claim to increase memory, reaction time, and IQ in healthy humans! Pretty bold claims. I'm skeptical but $20 seemed like a reasonable amount for a quick trial.
In previous studies, we have shown that phosphodiesterase type 5 inhibitors (PDE5-Is) can improve early consolidation of object memory. These conclusions were based on the timing of drug administration relative to the learning trial (i.e. before or after). However, there are very little pharmacological data available about the pharmacokinetic profile of orally administered PDE5-Is in the rat. Furthermore, there is still debate whether these effects are achieved via central or peripheral mechanisms and if acquisition processes are improved. In the current study, we tested the effects of the PDE5-I vardenafil in a cholinergic-deficit model and compared the effects after intracerebroventricular (ICV) versus oral (PO) administration. We found that PO vardenafil restored a scopolamine-induced memory impairment when dosed within 2 min after the learning trial while ICV vardenafil was able to restore memory when injected within 4 min after learning. Because the test trial was within 10 min after the learning trial, this suggests that these effects on object memory are related to acquisition processes that may still be ongoing in a time window after the learning trial. To further elucidate the extent of this acquisition window, we investigated the pharmacokinetic profile of vardenafil after PO administration where it was detected within 4 min post-dose. Taken together, our data suggest that PDE5 is involved in acquisition processes, which may linger for at least 4-6 min after learning. Further studies are needed to exclude that these effects could also be explained on basis of an effect on early consolidation processes. Additionally, the effectiveness of ICV-administered vardenafil provides further experimental evidence that PDE5-Is improve memory via a central mechanism.
The studies (not of the highest quality) actually claim to increase memory, reaction time, and IQ in healthy humans! Pretty bold claims. I'm skeptical but $20 seemed like a reasonable amount for a quick trial.
Wow, that's interesting. I wonder how much is the increase in IQ.....please keep us informed
Association between Cerebral Blood Flow and Cognitive Improvement Effect by B. mori Extracted Component [n.d.]
Lee, S.H.;Kim, Y.S.(Seoul National University, Seoul, Republic of Korea) Kim, S.S.;Kang, Y.K.;Lee, M.Y.;Lee, W.B.;Kim, D.K.(Chung-Ang University, Seoul, Republic of Korea)E-mail:dkkim@cau.ac.kr Lee, K.G.;Yeo, J.H.(National Institute of Agricultural Science and Technology, RDA, Suwon, Republic of Korea)E-mail:y610525@rda.go.kr
Abstract:
To investigate whether BF-7, extracted from Bombyx mori, improved learning and memory of ordinary people, K-WAIS (Korean version of Wechsler adult intelligence scale) was performed in 4 normal students. Treatment with 400 mg of BF-7 increased mean IQ from 103 to 114. To know how BF-7 plays such a positive role, we measured the blood flow to brain, especially for the area concerned with learning and memory, with Single Photon Emission Computed Tomography(SPECT).
In this study they claim that BF-7 enhanced the learning, memory, attention, and mathematical ability of 30 healthy university students. It increased accuracy in the Gronwall version of the PASAT by 3.5-fold and in the Levin version of the PASAT by 3.7-fold. There don't appear to be any controls in this study though. Just before and after scores for the 30 students.
Here's another free full text study with a control group in which they claim BF-7 enhances learning and memory in healthy volunteers between the ages of 19 and 64. There were 99 total participants in the study.
Extended quotes:
"BF-7 Enhanced Memory Quotient BF-7
The memory quotient (MQ), is the most direct index reflecting memorizing ability. The average MQ of all 98 volunteers was around 105. Interestingly, the average MQ was significantly increased to about 126.6 after receiving of BF-7 for 3 weeks, but not in the placebo group (Fig. 3). To determine whether BF- 7 can enhance memorizing ability, we analyzed im- proved MQ score differences. The increased MQ score increased significantly from 3.1 to 20.6 in a dose-dependent manner (Fig. 3). These results sug- gest that BF-7 enhances memorizing ability."
"BF-7 Increased Memory Recall Efficiency
Memory recall efficiency indicates how much and how precisely individual recall preserved memory. A higher percentage score represents bet- ter efficiency. As shown in Fig. 4, the memory re- call efficiency score was significantly increased from 31 to 58.9% and from 41.5 to 66.5% in the BF-7 200 mg/day and BF-7 400 mg/day for 3 weeks group, respectively, but not in the placebo group. The results indicate that the memory recall efficiency was improved by BF-7."
Neuroprotection and Enhancement of Learning and Memory by BF-7
Dae Kyong Kim,a Yong Koo Kang,b Moo Yeol Lee,c Kwang-Gill Lee,d Joo-Hong Yeo,d Won Bok Lee,b Yong Sik Kim,e and Sung Su Kim*, b
aDepartment of Pharmacy, College of Pharmacy, bDepartment of Anatomy, cDepartment of Physiology, College of Medicine, Chung- Ang University, 221 Huksuk-dong, Dongjak-gu, Seoul 156–756, Korea, dApplied Entomology Division, Department of Sericulture and Entomology, National Institute of Agriculture Science Technology, 249 Seodun-dong, Kwonsun-gu, Suwon 441–707, Korea, and eDepartment of Pharmacology, College of Medicine, Seoul National University, 28 Yongun-dong, Chongno-gu, Seoul 110–799, Korea
(Received January 11, 2005; Accepted February 2, 2005)
To investigate whether BF-7 improves the learning and memory of normal people, the Rey-Kim Memory Test was performed in a placebo group (32 persons), BF-7 200 mg group (33 persons), and BF-7 400 mg group (34 per- sons). BF-7 significantly enhanced learning and memory function in a dose-dependent manner. Our results show that BF-7 protects neurons from amyloid beta (Aβ) toxicity and reduces oxidative stress. We measured the levels of acetylcholine in the brain in a memory impairment animal model. Administration of BF-7 significantly increased acetylcholine levels. It is assumed that the protection of neurons and maintaining the appropriate acetylcholine levels are mechanisms by which BF-7 improves brain function. The results suggest that BF-7 is effective in improv- ing learning and memory ability.
The shortest time any of the studies mentioned was 3 weeks before they measured effects so I'm not expecting anything any time soon. I'm gonna do most of my posting on BF-7 over in rikelme's thread since I found out about it through him (and I like to give props to people who help me out). Check it out if you're interested in seeing more of the research and following my 4 week and his 16 week trial. http://www.longecity...s-a-nootropic/
One of the simplest, most straightforward introductions to Bayesian thinking that I've found on the net. Please watch if you have time! Understanding prior probabilities and base rate neglect are probably two of the most important thinking skills one can acquire.
What is a human mostly made of? Bacteria? Water? Carbon?
In this video Dawkins discusses 'middle world'...or the sizes and speeds and temperatures in which our human senses were designed to intuitively function. Take special note of his statement about rocks...rocks are made of atoms and atoms are made of mostly...empty space. Now, replace 'rocks' with 'humans'...humans are made of atoms and atoms are made mostly of, you guessed it, empty space. Therefore, humans are made mostly of empty space.
Let's take this one step further. Einstein unified space and time into four dimensional spacetime. Therefore, humans are made mostly of spacetime.
The only further thing I would add is that in atoms spacetime is imbued with fields. The strong nuclear force is mediated by the gluon field (which holds the quarks in protons and neutrons together and which holds protons and neutrons together) and the electromagnetic field holds electrons in their orbitals (probability clouds) around the nucleus (protons/neutrons).
Thus, humans are made mostly of spacetime imbued with fields. The world truly is "queer" to our senses...or to my senses, at least.
• Methylene blue (MB) transiently increases the ratios NAD/NADH and pAMPK/AMPK.
• MB induces PGC1α, SURF1, and complex IV biogenesis.
• Oxidants production as well as telomere erosion decreases in MB-treated cells.
• MB activates the metabolic pathways of cell defense and energy metabolism.
• MB, a potent anti-senescence agent in vitro, maybe also effective in vivo.
Abstract
Methylene blue (MB) delays cellular senescence, induces complex-IV, and activates Keap1/Nrf2; however, the molecular link of these effects to MB is unclear. Since MB is redox-active, we investigated its effect on the NAD/NADH ratio in IMR90 cells. The transient increase in NAD/NADH observed in MB-treated cells triggered an investigation of the energy regulator AMPK. MB induced AMPK phosphorylation in a transient pattern, which was followed by the induction of PGC1α and SURF1: both are inducers of mitochondrial and complex-IV biogenesis. Subsequently MB-treated cells exhibited >100% increase in complex-IV activity and a 28% decline in cellular oxidants. The telomeres erosion rate was also significantly lower in MB-treated cells. A previous research suggested that the pattern of AMPK activation (i.e., chronic or transient) determines the AMPK effect on cell senescence. We identified that the anti-senescence activity of MB (transient activator) was 8-times higher than that of AICAR (chronic activator). Since MB lacked an effect on cell cycle, an MB-dependent change to cell cycle is unlikely to contribute to the anti-senescence activity. The current findings in conjunction with the activation of Keap1/Nrf2 suggest a synchronized activation of the energy and cellular defense pathways as a possible key factor in MB's potent anti-senescence activity.
Edited by pleiotropic, 29 October 2015 - 06:22 AM.
It has been said of this problem that "... no other statistical puzzle comes so close to fooling all the people all the time" and "that even Nobel physicists systematically give the wrong answer, and that they insist on it, and they are ready to berate in print those who propose the right answer". https://en.wikipedia...ty_Hall_problem
Give this video a look and I'll explain why I actually think the problem is quite intuitive if you just simplify it a little and look at it in the right way.
Many people complain that the Monty Hall problem is not intuitive. I disagree. It's completely intuitive if you think about it in the right way. All you have to do is think about the number of possible outcomes AND the probability of each outcome. Ask yourself...how many possible outcomes are there? How many ways are there to win? How many ways are there to lose? I'll simplify the problem by limiting our discussion to just Door1. Remember, at the start the car is behind one of the doors...so, if the car is behind Door1, how many possible ways are there to win? If the car is behind Door1, how many possible ways are there to lose? Let's take a look...
If the car is behind Door1 AND you pick Door1 AND you stay, you win.
If the car is behind Door1 AND you pick Door2 AND you stay, you lose.
If the car is behind Door1 AND you pick Door3 AND you stay, you lose.
Therefore, your initial pick was right 1/3 of the time.
Therefore, if you stay you win 1/3 of the time.
Therefore, your initial pick was wrong 2/3 of the time.
Therefore, if you stay you lose 2/3 of the time.
Now let's take a look at what happens if you switch...
If the car is behind Door1 AND you pick Door1 AND you switch, you lose.
If the car is behind Door1 AND you pick Door2 AND you switch, you win.
If the car is behind Door1 AND you pick Door3 AND you switch, you win.
Therefore, your initial pick was wrong 2/3 of the time.
Therefore, if you switch you win 2/3 of the time.
Therefore, your initial pick was right 1/3 of the time.
Therefore, if you switch you lose 1/3 of the time.
That's it. There are only six possible scenarios if the car is behind Door1! The reason that there are more wins if you switch is that you are more likely to pick a goat first (2/3 lose) than a car (1/3 win). If you pick a goat first AND switch then you win (this would happen 2/3 of the time). If you pick a goat first AND stay then you lose. Therefore, you should switch.
The reason (I think) so many people have trouble with the problem is that they don't think about the probability of 'what'. It's the probability of a certain outcome. What are the total possible outcomes? Six (if limited to car behind Door1). What is my probability of a win if I stay? 1/3. What is my probability of a win if I switch? 2/3.
You can do this for Door2 and Door3 if you like but the result is the same. (I'll do it below just for completeness =))
As you can see, the way in which we think about a problem can make it more or less intuitive. All we had to do was simplify our thinking a bit (focus on 'car behind Door1' scenarios) AND switch our thinking to the probability of outcomes and it actually becomes quite intuitive. We just have to approach the problem in a new way and the solution will often present itself to us.
Door2
If the car is behind Door2 AND you pick Door1 AND you stay, you lose.
If the car is behind Door2 AND you pick Door2 AND you stay, you win.
If the car is behind Door2 AND you pick Door3 AND you stay, you lose.
If the car is behind Door2 AND you pick Door1 AND you switch, you win.
If the car is behind Door2 AND you pick Door2 AND you switch, you lose.
If the car is behind Door2 AND you pick Door3 AND you switch, you win.
Door3
If the car is behind Door3 AND you pick Door1 AND you stay, you lose.
If the car is behind Door3 AND you pick Door2 AND you stay, you lose.
If the car is behind Door3 AND you pick Door3 AND you stay, you win.
If the car is behind Door3 AND you pick Door1 AND you switch, you win.
If the car is behind Door3 AND you pick Door2 AND you switch, you win.
If the car is behind Door3 AND you pick Door3 AND you switch, you lose.
So after starting to supplement with BF-7 you are more interested in math problems?
haha Good question. =)
I know you're just playing around but the semi-serious answer is that I've written about biases and heuristics a fair amount over the years and I figured since I was writing more about supplements over in rikelme's thread it was a good time to bring some of that stuff up again. =)
I think Brain Health is about having the best hardware AND the best software we can and I am continually amazed at how my brain plays tricks on me. It takes some active effort (for me, at least) to become aware of inbuilt biases/tendencies and attempt to overcome them when they are not useful. I know that I didn't naturally take prior probabilities into account until I was taught the concept.
Seriously, lostfalco, it appears that your cognitive abstraction level has ascended several notches, inasmuch as I understand your point about having the best software in addition to the best hardware. But what's more atypical with regards to your posts above is their tenuous relevance to the topic of your own thread here. Granted, while I disagree with whoever labelled them as pointless and timewasting, it seems to me that perceiving such distant connections might equally be associated with enhanced mental function, as schizophrenia.
To cut to the chase, are you OK? I second raimis100 in inquiring as to any connection with BF-7, or some other recent change.
A few posts about heuristic thinking/techniques and one gets labeled as schizophrenic? Going through the 86 pages of this thread, one would see that Falco has posted a lot of studies, articles, and presentations about models of thinking, neuroscientific research in regards to sensory substitution, and I believe even some math/physics related stuff (he's at least sent me some math/physics related ideas in the past).
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