3 ms·

Medicine isn't my field, but I wonder why the chirality, why gold, why microbiota as target, why those particular diseases? As in, I might be searching wrong,

by fer 3y ago

Medicine isn't my field, but I wonder why the chirality, why gold, why microbiota as target, why those particular diseases? As in, I might be searching wrong, but I can't find previous research that would hint in this particular direction, and I think it's reasonable to be skeptical about any "random button pushing"-looking research showing positive results.

epistasis 3y ago
Sometimes the only difference between random button pushing and science is if you write it down. Faff around and find out is the essence of the scientific method. That said, I never trust a paper that gets posted directly to HN much. But then, single papers are never to be trusted!
- Tagbert 3y ago
  A lot of biology is still a black box for us. You investigate a block box by pushing its buttons and recording the results. Hopefully, there are enough buttons and eventually response patterns begin to emerge. Or someone invents a way to open the box, just a little.
InSteady 3y ago
I can't speak to chiral gold, but as for exploring the connection between microbiota and neurodegenerative diseases, this is a hot area of study. Take a sentence from the abstract: >The gut–brain axis has emerged as a therapeutic target in neurodegenerative diseases by modulating metabolic activity, neuroimmune functions and sensory neuronal signaling. You can pretty much formulate a few dozen google searches from various keywords in that sentence + "microbiome," "microbiota," and/or "GI immune signaling," etc and come up with hundreds of papers. The GI tract is host to the majority of our immune system. Many of the molecules used for signaling (and all kinds of other tasks) come directly from the bacteria there, or else are dependent on bacterial metabolites as inputs. On a related note, I expect we will hear more about the metabolome in health and medicine research. As microbiome is the set of all microbes in the body, metabolome is the set of all metabolites (bacterial and endogenous) in the body. In this study, serum levels of an indole were found to be altered in Alzheimer's patients: >indole-3-acetic acid, which was lower in serum and cerebrospinal fluid of patients with AD compared with age-matched controls. In another study of MS patients, two other indoles, as well as butyrate, were found to be lower in serum concentration compared to healthy controls [1]: >Highlights - Gut microbiota and metabolites profiles of individuals with MS differ from healthy controls. Individuals with MS have reduced serum levels of indolepropionate. Individuals with MS have reduced serum levels of indolelactate and its producing bacteria. Individuals with MS have lower levels of species and genes involved in butyrate production. Indoles in particular may be an interesting avenue of research [2]: >What is the function of the indole in bacteria? Indole has recently been implicated as an important small molecule signal utilized by many bacteria to coordinate various forms of behavior. Indole plays a role in numerous bacterial processes, including: biofilm formation and maintenance, virulence factor production, antibiotic resistance and persister cell formation. [1] - https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00062-8.pdf https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21... [2] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175420/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175420/
arrosenberg 3y ago
Something of an educated guess, but microbiota because there are current hypotheses that rely on the gut-brain interaction, gold probably because its inert, and chirality is most likely because their target requires specific kinetics.
crdrost 3y ago
Alzheimer's is the most common form of dementia, affecting tens of millions of mostly elderly people, characterized by the brain getting “gummed up” by various mechanisms like reduced interconnectivity of your neurons, the formation of these plaques of a protein called amyloid beta on the brain tissue, tangles of a different protein called tau, and little “pearls” of a sort called vacuoles wrapping not sand grains but little lumps of hardened proteins. So there's a theme of proteins being where they're not supposed to be and misfolding and so on. There are several partial causes of these protein problems, including genetic factors, chronic high blood pressure, smoking history, depression history. One can alternatively characterize this as a sort of inflammatory response, which puts it in a bucket with Parkinson's and ALS and other things tied to oxidative stresses and long-term inflammation. I am not a physician but was trained as a physicist, part of where I know about this stuff comes from trying to research a speculative YouTube video that I never got around to making called “the biophysics of weight loss” where I would tell people that from a physics perspective, the scale in your bathroom lies, calories are necessary but not sufficient to understand the problem, feedback networks are complicated, and just in general tried to educate the public about basic physics from a direction that is not Newtonian mechanics. (So if you want to start with energy, what is the most frequent interaction with measured amounts of energy everyone has? It's either diet or the wattage ratings on electric bulbs, diet seemed more fun.) So where this gets interesting for me is, in trying to talk about the complex feedback loops and signaling and satiety around diet, diet and lifestyle factors do seem to affect these chronic levels of inflammation. Just a simple example, your blood has to maintain a strong homeostasis with respect to how much sugar is in there, too little and your cells don't have what they need, too much and bacteria could thrive inside of you. One mechanism the body uses is, if we detected the blood as too sugary, we dump this signaling molecule called insulin in there too. Muscle tissue will take up blood sugar without insulin, but fat cells need the insulin as a “key” to open a lock that lets sugar in for long-term storage as fat. But the fat cells have what we in computing would call backpressure—they don't just respond directly to insulin, they calibrate their response to what they can handle. If too much sugar is coming in and I can't store it, I reduce my sensitivity to the insulin, so that I take in less sugar for a given amount. If this happens chronically enough, you get a general insulin resistance, and that leads to high blood sugar, type-2 diabetes. Well, elevated blood sugar does something else that is linked to Alzheimer's: the Maillard reaction. This is the crusty delicious browning that happens when we sear a steak, or bake bread. The natural sugars in the muscle and natural proteins in the flour are enough in either case, the formula is sugar plus protein plus heat equals denatured brown crusty proteins. You are warm enough on the inside that this does “sous vide” your proteins very slowly, it is part of aging. So if your blood sugar is high, you age faster. The term in the literature is “advanced glycation” if you want to read more about this. I don't have diet recommendations, I am just interested because I can ask prospective students “if we turned you into a hot dog, how far would it stretch” and other silly things like that. I will say, keto was originally invented to help with epileptics, and it does that by moving the brain off of sugars and to a fuel that the brain “prefers” (in the sense of having fewer barriers to letting it in) called ketone bodies. Intermittent fasting also does this on shorter timescales. Anyway, the story about the gut microbiome maybe playing into this is even more complicated, some people talk about “leaky gut,” others say that that is crackpot, but the basic gist is that there is a theory that if you do not eat enough soluble and insoluble fiber, your gut microbiome (which needs to eat both to survive) essentially maybe eats you a little bit instead as it starves. And this causes you to be at war with your gut microbiome, and it means that the good bacteria that are not eating you are less able to crowd out the bad ones that want to eat you... And the claim is that this creates a constant chronic low-level inflammation, so there's that oxidative stress and early aging problem again, and so forth. I don't know that I believe this? But it does have me staying away from fruit juices, which are like fruit but you removed both the soluble and insoluble fiber.
thenerdhead 3y ago
Read Ed Yong's book "I Contain Multitudes". This area has been more/less blocked for many decades and with recent innovations and pipelines we may be able to start finding causal patterns.

by fer 3y ago

epistasis 3y ago

Sometimes the only difference between random button pushing and science is if you write it down. Faff around and find out is the essence of the scientific method. That said, I never trust a paper that gets posted directly to HN much. But then, single papers are never to be trusted!

Tagbert 3y ago
A lot of biology is still a black box for us. You investigate a block box by pushing its buttons and recording the results. Hopefully, there are enough buttons and eventually response patterns begin to emerge. Or someone invents a way to open the box, just a little.

InSteady 3y ago

I can't speak to chiral gold, but as for exploring the connection between microbiota and neurodegenerative diseases, this is a hot area of study. Take a sentence from the abstract: >The gut–brain axis has emerged as a therapeutic target in neurodegenerative diseases by modulating metabolic activity, neuroimmune functions and sensory neuronal signaling. You can pretty much formulate a few dozen google searches from various keywords in that sentence + "microbiome," "microbiota," and/or "GI immune signaling," etc and come up with hundreds of papers. The GI tract is host to the majority of our immune system. Many of the molecules used for signaling (and all kinds of other tasks) come directly from the bacteria there, or else are dependent on bacterial metabolites as inputs. On a related note, I expect we will hear more about the metabolome in health and medicine research. As microbiome is the set of all microbes in the body, metabolome is the set of all metabolites (bacterial and endogenous) in the body. In this study, serum levels of an indole were found to be altered in Alzheimer's patients: >indole-3-acetic acid, which was lower in serum and cerebrospinal fluid of patients with AD compared with age-matched controls. In another study of MS patients, two other indoles, as well as butyrate, were found to be lower in serum concentration compared to healthy controls [1]: >Highlights - Gut microbiota and metabolites profiles of individuals with MS differ from healthy controls. Individuals with MS have reduced serum levels of indolepropionate. Individuals with MS have reduced serum levels of indolelactate and its producing bacteria. Individuals with MS have lower levels of species and genes involved in butyrate production. Indoles in particular may be an interesting avenue of research [2]: >What is the function of the indole in bacteria? Indole has recently been implicated as an important small molecule signal utilized by many bacteria to coordinate various forms of behavior. Indole plays a role in numerous bacterial processes, including: biofilm formation and maintenance, virulence factor production, antibiotic resistance and persister cell formation. [1] - https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21)00062-8.pdf https://www.cell.com/cell-reports-medicine/pdf/S2666-3791(21... [2] - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175420/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175420/

arrosenberg 3y ago

Something of an educated guess, but microbiota because there are current hypotheses that rely on the gut-brain interaction, gold probably because its inert, and chirality is most likely because their target requires specific kinetics.

crdrost 3y ago

Alzheimer's is the most common form of dementia, affecting tens of millions of mostly elderly people, characterized by the brain getting “gummed up” by various mechanisms like reduced interconnectivity of your neurons, the formation of these plaques of a protein called amyloid beta on the brain tissue, tangles of a different protein called tau, and little “pearls” of a sort called vacuoles wrapping not sand grains but little lumps of hardened proteins. So there's a theme of proteins being where they're not supposed to be and misfolding and so on. There are several partial causes of these protein problems, including genetic factors, chronic high blood pressure, smoking history, depression history. One can alternatively characterize this as a sort of inflammatory response, which puts it in a bucket with Parkinson's and ALS and other things tied to oxidative stresses and long-term inflammation. I am not a physician but was trained as a physicist, part of where I know about this stuff comes from trying to research a speculative YouTube video that I never got around to making called “the biophysics of weight loss” where I would tell people that from a physics perspective, the scale in your bathroom lies, calories are necessary but not sufficient to understand the problem, feedback networks are complicated, and just in general tried to educate the public about basic physics from a direction that is not Newtonian mechanics. (So if you want to start with energy, what is the most frequent interaction with measured amounts of energy everyone has? It's either diet or the wattage ratings on electric bulbs, diet seemed more fun.) So where this gets interesting for me is, in trying to talk about the complex feedback loops and signaling and satiety around diet, diet and lifestyle factors do seem to affect these chronic levels of inflammation. Just a simple example, your blood has to maintain a strong homeostasis with respect to how much sugar is in there, too little and your cells don't have what they need, too much and bacteria could thrive inside of you. One mechanism the body uses is, if we detected the blood as too sugary, we dump this signaling molecule called insulin in there too. Muscle tissue will take up blood sugar without insulin, but fat cells need the insulin as a “key” to open a lock that lets sugar in for long-term storage as fat. But the fat cells have what we in computing would call backpressure—they don't just respond directly to insulin, they calibrate their response to what they can handle. If too much sugar is coming in and I can't store it, I reduce my sensitivity to the insulin, so that I take in less sugar for a given amount. If this happens chronically enough, you get a general insulin resistance, and that leads to high blood sugar, type-2 diabetes. Well, elevated blood sugar does something else that is linked to Alzheimer's: the Maillard reaction. This is the crusty delicious browning that happens when we sear a steak, or bake bread. The natural sugars in the muscle and natural proteins in the flour are enough in either case, the formula is sugar plus protein plus heat equals denatured brown crusty proteins. You are warm enough on the inside that this does “sous vide” your proteins very slowly, it is part of aging. So if your blood sugar is high, you age faster. The term in the literature is “advanced glycation” if you want to read more about this. I don't have diet recommendations, I am just interested because I can ask prospective students “if we turned you into a hot dog, how far would it stretch” and other silly things like that. I will say, keto was originally invented to help with epileptics, and it does that by moving the brain off of sugars and to a fuel that the brain “prefers” (in the sense of having fewer barriers to letting it in) called ketone bodies. Intermittent fasting also does this on shorter timescales. Anyway, the story about the gut microbiome maybe playing into this is even more complicated, some people talk about “leaky gut,” others say that that is crackpot, but the basic gist is that there is a theory that if you do not eat enough soluble and insoluble fiber, your gut microbiome (which needs to eat both to survive) essentially maybe eats you a little bit instead as it starves. And this causes you to be at war with your gut microbiome, and it means that the good bacteria that are not eating you are less able to crowd out the bad ones that want to eat you... And the claim is that this creates a constant chronic low-level inflammation, so there's that oxidative stress and early aging problem again, and so forth. I don't know that I believe this? But it does have me staying away from fruit juices, which are like fruit but you removed both the soluble and insoluble fiber.

thenerdhead 3y ago

Read Ed Yong's book "I Contain Multitudes". This area has been more/less blocked for many decades and with recent innovations and pipelines we may be able to start finding causal patterns.