Just a warning that all the clinical evidence provided in that review was done by (or funded by) companies using their own products. It's a major issue in a lot of dermatological research as noted by this article from Harvard (https://www.hsph.harvard.edu/nutritionsource/collagen/).

It's worth noting that the American Academy of Dermatology has no recommendations regarding dietary collagen but does have evidenced backed advice for those looking to maintain healthy skin:

https://www.aad.org/public/cosmetic/younger-looking/firm-sagging-skin

https://www.aad.org/public/everyday-care/skin-care-secrets/anti-aging/reduce-premature-aging-skin

We think of walking as a rather simple task that the majority of the population does everyday without thinking. In reality, its actually quite a complex process that requires numerous brain areas as well as your senses constantly providing feedback.

The main motor system consists of your motor cortex with upper motor neurons (in the brain), your spinal cord with lower motor neurons, and the muscles they innervate. All those need to be firing in a complex pattern (tense the quad of one leg and release the hamstrings while doing the opposite on the other leg for example).

We also need to maintain balance. We do that by taking in 3 sensory inputs: the feel of the ground beneath our feet, the orientation of our environment with our eyes, and the placement of the fluid within our vestibular organs in our ears. All of those systems combine within the basal ganglia (like the thalamus) and the cerebellum to drive changes in our gait that allow us to stay upright even on uneven ground.

Walking is also a rhythmic motor movement so we need to maintain an even pace for each step. You can imagine how difficult it'd be to walk if every step went a different distance or your speed constantly increased or decreased. The cerebellum also is in charge of that and modifies our gait to maintain a certain pace.

All that is required just to walk on a treadmill. If we're also in a complex environment, let's say a sidewalk, we're also going to need to use our prefrontal and premotor cortices for planning future movements. If someone is walking in front of us, we'll need to plan a route around them and maybe speed up a little to pace them. If you see someone start to cross the street and they may intersect our path, we now need to calculate how fast they're going, the most probable path they'll take, and how we can change our own gait to prevent collision. Of course nearly all of this is done unconsciously without you even realizing it but it all needs to happen to successfully navigate just a sidewalk.

All of this is to say when people can't walk, there could be a multitude of problems and all these pathways contain millions if not hundreds of millions of connections. So there isn't a simple solution of reconnecting the pathways since its incredibly complex. Spinal cord injuries, uncontrolled diabetes, strokes, Parkinson's disease, amyotrophic lateral sclerosis, cancer, vertigo, etc are all disease that make it hard to walk but they affect different pathways.

Pyramidal system (motor cortex) - https://www.ncbi.nlm.nih.gov/books/NBK540976/

Extrapyramidal (everything else) system - https://www.ncbi.nlm.nih.gov/books/NBK554542/

FFI is caused by a mutation in the PrP gene that predisposes it to misfolding causing disease. If this DNA mutation is not passed down to the fetus, then it won't get the disease even if the mother has FFI. The misfolded protein itself will not be passed from mother to fetus.

www.science.org/doi/abs/10.1126/science.1439789

I'm pretty sure that antboyee. I see that around the skate park in north point park a lot.

Nope. The biggest difference is that male brains tend to be a little larger than female brains (which tracks with body size). Aside from that, there are essentially no differences between male and female brains. It's also important to note that brain size has a very weak correlation to intelligence so its not possible to make any claims based on size alone.

Human brains are not dimorphic - www.sciencedirect.com/science/article/pii/S0149763421000804

Brain mass and intelligence - www.scientificamerican.com/article/does-brain-size-matter1

Most of the responses here have already hit on the important parts so I'll just add a little extra.

When you sense touch, that signal is sent back to the spinal cord and then up to the brain. That signal is interpreted by your sensory cortex which has a map of your entire body called the homunculus. So when your shoulder is touched, the some of the neurons in the shoulder part of the sensory homunculus get activated which your brain can then interpret as a touch on the shoulder. Scientists have seen that the distribution of neurons is not equal to the surface area of your body parts. Just because you have more shoulders than hands doesn't mean you have more neurons dedicated to sensation for your shoulders than hands. In fact, its quite the opposite. Your hands, particularly the fingers, have a high density of sensory neuron endings making them exquisitely sensitive to touch. Your shoulder (and most other skin) has much fewer nerve endings and is less sensitive and thus takes up less of the sensory homunculus. This is why you can feel fine details with your finger tips but not with your shoulders or even the back of your hand.

Pain is interesting since there are pain sensing neurons in for both your somatic nervous system (skin, muscle, things under conscious control) and autonomic nervous system (stomach, heart, things under unconscious control). We are not very good at localizing pain coming from our autonomic nervous system which is why, for example, stomach aches often feel like a more generalized pain/unease. This phenomenon is also why appendicitis will first present like a stomach ache or cramp (autonomic pain) before eventually becoming sharp/burning pain in the lower right quadrant as the inflamed organ begins to irritate the skin above it (somatic pain).

Sensory homunculus - https://www.ncbi.nlm.nih.gov/books/NBK549841/

Somatic vs autonomic pain - https://journals.physiology.org/doi/full/10.1152/ajpgi.2000.279.1.G1

100% correct!

And since carbonic acid/bicarb is the main buffer in blood, we regulate that by regulating our breathing. CO2 is converted into carbonic acid so by holding our breath (or breathing slower), we retain CO2 and decrease blood pH. Inversely, by breathing faster we blow out more CO2 and increase our blood pH.

Decreased blood pH is one of the main drivers for breathing. When you're swimming underwater and you start to feel the urge to breathe, it isn't lack of oxygen but rather the decreased blood pH from retained CO2 that your brain is sensing.

As a short aside, it's really bad for your blood to be more acidic OR more basic than ~7.4 pH. So when you see products claiming to "alkalinize" your body/blood for health, it's complete BS. Acids and bases are not inherently bad or good just like how hot and cold things are not inherently bad or good. I see these ads pop up pretty frequently, especially in fitness related settings and it drives me nuts.

As far as I am aware there is no such molecule. Opioids, like many ligands, bind receptors in a dynamic equilibrium meaning they are constantly binding and dissociating. Some are 'stickier' than others but none of them require enzymatic removal. The life cycle of the drug starts with high concentrations in your blood soon after taking it. It then diffuses down its concentration gradient into various tissues including the CNS where it binds mu opioid receptors to create an analgesic effect. As the liver removes it from the blood, the concentration gradient gets reversed with higher concentrations in the tissues and lower in the blood. So it once again diffuses down the concentration gradient back into the blood system where it gets removed.

Receptors may get endocytosed by neurons to prevent continued activation, but this doesn't necessarily remove the opioid from the receptor, it just prevents downstream signaling.

Dissociation of opioids from receptors (computation modeling)

https://pubs.acs.org/doi/10.1021/jacsau.1c00341

Endocytosis of opioid receptors after activation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683597/

The name amino acid refers to the amine group (NH2-R) and the carboxylic acid group (COOH-R) that make up the backbone of amino acids. The amine group can be a proton acceptor while the carboxylic group can be a proton donator so most amino acids are neutral. Some amino acids have acidic R groups (gutamate/asparatate) which makes them acidic, while others have basic R groups (lysine, histidine, arginine) which makes them basic.

In reality, since proteins are made up of 100's or 1000's of amino acids, they act as buffers, accepting and donating protons as needed in the blood. However, protein isn't the main buffer used to maintain the blood pH. Our bodies need blood to be kept at ~7.4 pH in order to function and if that changes too much we can get really sick. Our blood uses carbonic acid/bicarbonate as its main buffer which provides stability to the blood pH.

It's very rare but possible. The majority of peripheral dopamine comes from peripheral sympathetic nerves which in part use dopamine to communicate. Some of this dopamine is taken up in the blood stream. Interestingly, there's almost as much dopamine in your blood as adrenaline though what it's doing there is not really known.

https://academic.oup.com/endo/article/151/12/5570/2456083?login=true

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373991/

This is a really interesting question but not one that has been addressed yet. In part because the use of the internet for socializing is fairly recent (IE in the last decade or two) and measuring the effects on long-term isolation in humans requires...decades of research. Using animal models would be faster but as far as I am aware we have no animal models of online social networks.

What we do know is that the use of the internet for socializing affects our loneliness and quality of life. This research is still fairly new since social media is fairly new and involves very quickly. Our current understanding is that socializing online enhances relationships and quality of life but cannot replace in-person connections. A study in Israel found that using the internet increased people's quality of life if they saw their family regularly (a proxy measurement of in-person interaction) but had no affect on those who did not.

Additionally, the way internet use affects us is often different depending on your age. For adolescents, the more time spent online was correlated with higher loneliness while in older adults the opposite was true. This may be do to the differences in how people from different age groups use the internet: older adults tend to go online more often to communicate compared with adolescents.

It's hard to make any concrete statements at this point since we just don't have the data yet. From the information we do have, I think it's reasonable to hypothesize that using the internet to socialize can help reduce the negative affects of isolation but are not a good replacement for offline relationships.

Loneliness and social media (Israeli study): https://journals.sagepub.com/doi/full/10.1177/1745691617713052

Loneliness and social media (review):

https://journals.sagepub.com/doi/full/10.1177/1745691617713052

The cells resume their cell functions almost immediately after thawing. You'll hear the term "media" a lot when talking about cell culture. Media is a general term for liquid food for cells. It contains macronutrients (carbs like sugar, protein usually in the form of amino acids, and fats), micronutrients (vitamins/minerals), some other components (hormones/growth factors), and a buffer to maintain a physiological pH.

There are a ton of different types of media for different cells but the most commonly used is DMEM (Dulbecco's modified Eagle's medium) supplemented with 2-10% fetal bovine serum (FBS) for additional nutrients. Often researchers will also add antibiotics such as penicillin and streptomycin to prevent bacterial growth.

The media provides the fuel while atmospheric dissolved oxygen provides oxygen. Once the cells return to 37C, they spend a little time recovering as generally cells undergoing stress such as temperature changes and exposure to organic solvents like DMSO will stop dividing. This recovery period can take between 2-48 hours depending on cell type. For commonly grown cells like HeLa (from Henrietta Lacks) or HEK293, they take about 6 hours to recover and begin dividing.

Depends on the size of the sample. Cells are really small so the volume they are frozen in can be very small too. I work with cells (stem cells, neurons, and others) and cryopreserve them regularly often at 100,000 cells in 500 microliters (0.017 fl ounces) using DMSO as a cryopreservent. When I thaw them, I'll place the vial in a 37C water bath which will thaw them in about 30 - 45 seconds. Then the cells are quickly diluted in media without DMSO to reduce the concentration. The solution is spun so the cells all pellet in the bottom of the tube, the media with DMSO is removed and replaced with fresh media for plating.

Larger volumes are generally not used precisely for the reason that they do not freeze and thaw evenly (IE the interior freezes/thaws slower than the outside). It can be done with special plasticware that increases the surface area but I've never seen it done in routine tissue culture as there is no need.

Great question. This is a special case since the hemophilia A gene is only on the X chromosome and not on the Y chromosome. Since XY males will only have one copy of the X chromosome, they only need to inherit one mutant allele to develop disease. The Y chromosome doesn't have a copy of that gene to make up for the mutant one. In XX females, they have two copies of the gene and thus will need two copies of the recessive disease allele to develop disease (just like genes on any other chromosome).

All chromosomes except sex chromosomes are symmetrical so this is a special case that makes XY males more susceptible to certain genetic diseases.

Dominant alleles are alleles that overtake the other one in their function. The body doesn't know which is which, its an inherent trait to the gene.

Nearly all genes come as pairs, and if one of the pair can outperform the other, then its considered dominant. There are many different ways this can happen both normally and in disease. Here are some examples:

Blood type - In the ABO blood type group there are three alleles, A, B and O. A and B are dominant over O in that if you are AO or BO then your blood type is A or B. On a cellular level, the ABO locus encodes a glycoprotein. A and B alleles will express this glycoprotein (although slightly differently) while O will express no glycoprotein. Thus if you have an A or B allele, it will dominant over the O allele.

Eye color - The OCA2 gene has a large role in eye color determination. The brown eye allele will cause the cells in your iris to produce melanin and turn your irises brown while the blue eye allele will produce much less melanin. Thus if you have one brown eye allele, it will dominant over the blue eye allele by producing a lot of melanin.

Alzheimer's disease - The protein APP is involved in forming amyloid plaques seen in patients with Alzheimer's. In some families, this protein is mutated such that it forms these plaques much faster than normal. Faster plaque formation means faster disease onset and progression. Since only one allele is needed to be mutated to cause disease (it doesn't matter there's a normal one), this mutation is considered to be dominant.

Like others have mentioned, there is a tendency for dominant alleles to be "gain-of-function" which means these mutations (or normal variations) cause a new function. In ABO alleles, its production of a glycoprotein. In eye color, its production of melanin in the iris. In APP, it's the increased tendency to aggregate into plaques. This tendency is because of the redundancy of having two copies of your genes. If one loses its function, you already have another copy to take its place. Thus loss-of-function mutations are less likely to cause disease. But this isn't always the case.

Hemophilia A - This clotting disorder is caused by a mutation in the factor VIII gene. This gene is located on the X chromosome the mutation is considered recessive. If you have at least one copy of the normal factor VIII gene, you won't develop disease. However, if you have only one copy of the X chromosome (IE males) and you have the factor VIII mutation, then you will develop the disease as you only have one copy of those genes.

Cancer - The protein p53 is an important cancer preventing gene in your body. It's involved in making sure your cells are dividing at an appropriate time and rate. It functions by oligomerizing (four of the proteins get together). If there is a mutation in p53, then the mutant form will poison the complex and prevent its function. IE if one of the four proteins that get together to form the complex is mutant, the whole complex won't function. Thus having a normal allele will not prevent disease.

ABO blood group - https://www.ncbi.nlm.nih.gov/books/NBK2267/

Eye color - https://www.sciencedirect.com/science/article/pii/S0002929707626822

Alzheimer's genetics - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453386/

Hemophilia A - https://medlineplus.gov/ency/article/000538.htm

p53 mutations - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135636/

I would absolutely consider maturation and aging as two separate processes. Maturation can be seen as a physiological process (IE normal) while aging can be thought of as pathological (IE bad). Both progress at different rates for different systems and are enormously influenced by environmental factors.

Sexual development, for example, begins during puberty (~ages 9-11) and lasts for 2-4 years. Increased body fat can cause early puberty while decreased body fat can delay it. Contrast that to brain maturation which begins at birth (or at conception, some may argue) and continues through the age of 25. Around this age is when most people considered humans "fully developed" biologically.

Aging can "begin" at nearly any time depending on many factors including diet, exercise, sleep, stress, etc. In fact, risk of disease and/or death is better predicted by using calculations of biological age (IE how well does your body function) than chronological age.

Muscle loss is often seen in the elderly often thought to begin in middle age and continually progress. However, a strength building exercise program can often halt this loss or even reverse it.

Cognitive decline is often seen as an inescapable feature of aging. However, multiple studies have shown that diet, exercise, sleep, and stress management (IE lifestyle interventions) can reduce risk for Alzheimer's by nearly 60%. In fact, in a clinical trial for lifestyle interventions to prevent dementia, they found that those that adhered to the protocol actually improved cognitive performance over 2 years.

Metabolism is often blamed for weight gain as we age. A large study of over 6000 participants found that there is no change in metabolism from age 20-60. They did find a strong correlation to increased metabolism with increased lean mass (fat-free mass).

That isn't to say we can become immortal by doing push ups and having a kale salad now and again. As we live longer, we accumulate risk for disease. It can be thought of as rolling the dice the over and over again and eventually something will happen. Since aging is inevitable (at least for now), starting good habits young will help make sure that each time those dice are rolled, the risk for disease is as low as possible. This is often called "healthy aging".

Human development - https://www.britannica.com/science/human-development

Body fat and sexual development - https://www.nature.com/articles/nrendo.2011.241

Brain maturation in humans - www.ncbi.nlm.nih.gov/pmc/articles/PMC3621648

Biological age is a better predictor of mortality than chronological age - academic.oup.com/biomedgerontology/article/72/7/877/2629918

Preventing age-related muscle loss - www.ncbi.nlm.nih.gov/pmc/articles/PMC2804956/

Lifestyle interventions prevent AD by up to 60% - lifestylemedicine.org/wp-content/uploads/2022/08/ACLM-Article-Lifestyle-Intervention-Alzheimers.pdf

Lifestyle interventions improve cognition in those at risk for dementia - alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12492

Metabolism is stable between 20-60 (editorial) - www.health.harvard.edu/blog/surprising-findings-about-metabolism-and-age-202110082613

Metabolism is stable between 20-60 (scientific article) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370708/

Healthy aging via lifestyle changes - www.sciencedirect.com/science/article/pii/S0304416509000208

You're absolutely correct. I mistyped electrons instead of protons. I've edited my original comment!

I think you may have the first 4 complexes of the ETC and ATP synthase mixed up (though ATP synthase is sometimes consider complex V). The ETC pumps protons** across the inner mitochondrial membrane from the matrix to the intermembrane space to create the proton gradient. The protons then flow down their gradient across the membrane (IMS to matrix) via ATP synthase which generates ATP in the process.

The first diagram from the Khan academy article about oxphos does a great job at showing how the protons flow and how each complex contributes. https://www.khanacademy.org/science/ap-biology/cellular-energetics/cellular-respiration-ap/a/oxidative-phosphorylation-etc

EDIT: electrons -> protons

Like nearly everything in biology, water exists in a dynamic equilibrium. Constantly shifting between H2O and H+ & OH-. The mitochondrial matrix is an aqueous environment (IE watery) so there is a constant supply of H+ and OH-. The electron transport chain scoops these protons and sends them across the inner mitochondrial membrane to create the proton gradient.

Additional protons are also provided by the oxidation of NADH to NAD+ & H+.

That's a little like asking how does a taco truck know that its a taco truck. The truck itself doesn't know what it does, but inside it has the ingredients for tacos, a taco chef, and all the signage on the outside of the truck indicating its a taco truck.

The same works in cells. The golgi apparatus is essentially just a collection of membranes but its the proteins within the membranes that give it the function. And if you took out all those proteins and swapped in endoplasmic reticulum proteins, then it'd be the ER (just like if you swapped out taco ingredients for ice cream in your food truck). The proteins within organelles gather together through inter-molecular interactions. There are multiple proteins whose role it is to gather all the golgi components and keep them together (NSF and p97 for example).

Something else to consider is how do we define organelles? While in textbooks the organelles look quite distinct from one another, they actually exist on a spectrum. For example, it was thought each cell had a single golgi apparatus housed within the cell body. Recent research has shown that there are actually other golgi-like organelles ("golgi outposts") positioned far from the cell body (like in axons of neurons) that perform some functions of the golgi but not others.

Another example would be lysosomes (a round, acidic compartment used in autophagy). The lysosomal associated membrane protein 1 (LAMP1) was considered the marker for lysosomes for a long time. However, there have been multiple studies showing that there vesicles with LAMP1 on them that are not acidified which calls into question their identity. Another marker that researchers use is a protein called spinster which, in muscle cells, localizes to a tubular network rather than vesicles. Are these networks lysosomes? Are non-acidified LAMP1 compartments lysosomes? These questions are still being debated.

Going back to the original question, how does an organelle define its function? By the proteins associated with it. And these proteins assemble using a large assortment of chaperones that collect the protein components, bring them to their destination, and assist in forming complexes. And while we talk about organelles as distinct parts that have distinct functions, they exist on a spectrum.

Assembly of the golgi: www.ncbi.nlm.nih.gov/pmc/articles/PMC5710388

Golgi outposts: www.cell.com/trends/cell-biology/fulltext/S0962-8924(20)30145-8

Heterogeneity of LAMP1 vesicles: https://pubmed.ncbi.nlm.nih.gov/29940787/, www.ncbi.nlm.nih.gov/pmc/articles/PMC6123004/

Tubular lysosomes: https://pubmed.ncbi.nlm.nih.gov/35646899/

Pain is complex experience that doesn't necessarily involve a physical stimulus. It's kind of like asking if we can measure objective happiness.

We do have tests like the ice water paradigm you mentioned but they are limited as people may withdraw their hands at different pain thresholds (eg if one subject is apathetic about the study they might withdraw their hand sooner than another who is invested and is willing to withstand more pain). There have been more recent attempts at measuring pain perception in the brain. Currently there is research into identifying which regions of the brain activate in response to pain and seeing if we can predict the amount of pain someone is experiencing based on their brain activity in those regions. But generally this requires EEG or MRI which can be expensive and time consuming.

Advances in pain assessment: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979466/

Phantom pain: www.mayoclinic.org/diseases-conditions/phantom-pain/symptoms-causes/syc-20376272

The answer to your question really depends on the type of exercise you are doing. If you are doing steady state cardio (IE your heart rate remains constant), your calories burnt will also remain constant. You may increase energy expenditure slightly as you fatigue as your movement efficiency will decrease.

If your heart rate is NOT constant, your energy expenditure will change similarly. Between your resting heart rate and 90% of your HR max, calorie usage and HR increase linearly. As your HR exceeds 90% of the max, energy expenditure increases much faster. Though most experts recommend against training at 90+% of your HR max as you risk injury and often requires extended recovery time limiting your fitness improvement as well as overall calories burned (IE going for 1 run at 95% instead of 3 runs at 70% in a week burns fewer calories and takes the same recovery time, approximately).

HR and calories burned: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005766/
Running efficiency and fatigue: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722636/
Metabolism during different exercises: https://www.nature.com/articles/s42255-020-0251-4

There are actually quite a few types of antibiotics. Most people don't hear about most of them because they're reserved for specific infections (oral vancomycin for c difficile, isoniazid/rifampin for tuberculosis, linezolid for MRSA, and carbapenems as a last resort). Most common bacterial infections are treated with common antibiotics to limit bacterial resistance.

If a bacterial infection is resistant to treatment, additional antibiotics will be added in combination. Investigational antibiotics may also be used if the benefit outweighs the risk. Currently there are studies being performed to try and identify antibiotic (or other drug) combinations that more effectively kill bacteria. Some drugs work together synergistically (IE they're better together than expected) while others antagonistically (IE they work against each other) and it's not clear why.

Treatment options for multi-drug resistant bacteria - www.frontiersin.org/articles/10.3389/fmicb.2019.00080

Assessment of drug interactions - https://www.science.org/doi/10.1126/sciadv.1701881

There are several classes of drugs that are known to have depressive side effects (including some heart medications that affect ion channels, and some medications that affect hormones). Usually these are quite minor as a medication would not be approved by the FDA if depression was a major side effect.

Currently the FDA has a black box warning for suicidal ideation for SSRI's (an anti-depressant). Generally the increase in suicidal ideation occurs within a month or so of initiating treatment before the risk begins to reduce to that of someone without depression. The mechanism for this is unknown although its been proposed that there is a brief phase where the treatment increases motivation/energy before mood. There have been several critiques of the link between suicide and SSRI's with the main points being that the link exists in adolescents and children but not adults. Thus pooled analyses lose this distinction.

Suicidal ideation following anti-depressant initiation - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178080/

Critique on the link between suicide and anti-depressant-
https://pubmed.ncbi.nlm.nih.gov/31130881/

Medications with depressive side effects - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2729620/

For those seeking help regarding suicide -
https://988lifeline.org/

Yes! But the response doesn't necessarily have to reach the level of cytokine storm for anti-inflammatories to be helpful.