slouchingtoepiphany t1_je5if97 wrote

If you're uncomfortable about making the decision, place your car in storage for 3 months somewhere cheap (outside of Boston). At the end of those three months, you can decide whether you can live without it or not (or sooner, if you find that you really need it).


slouchingtoepiphany t1_je5evn4 wrote

Here are a couple of links to articles that you might find interesting. Reference #1 posits that the evolutionary precusor to crystallins (a transparent protein that comprises the lens) occurred in sea squirts (Ciona). Reference #2 provides a review of how the crystallins evolved into two super families are kinds that we see today.


slouchingtoepiphany t1_jdxp0yl wrote

Cheers for all those mentioned. My daughter graduated from A-B but while she was a student she participated in HS, Open Door, and Theatre III productions. And I, as a devoted Dad, worked on the props and scenery for everything that she was in. All these organizations provide great experiences for kids (and their parents).


slouchingtoepiphany t1_jdcw57d wrote

FYI, several years ago, I had to send in a check to the RMV to renew my license and the renewal never came, even though they cashed the check (you can get photos of the cashed check either on the RMV web site or your bank's web site). I tried to call the RMV multiple times which was utterly pointless, so I went to one of their locations and showed them printouts of my payment after which they gave me my new license on the spot.


slouchingtoepiphany t1_jd8fo7h wrote

You're asking a good question. When a cell dies, it's because it loses the ability to make ATP, the product of oxidative metabolism and glycolysis and is sometimes called the "universal currency" for cellular reactions. The lack of ATP results in many things going wrong, including the cell's ability to maintain the integrity of its membranes, but many other reactions that are deleterious to the cell also take place. The cells that are most vulnerable to this are those that are the most metabolically active, which include the brain and heart. When these fail, many of the body's systems also fail and death may be declared when an individual has lost circulatory, respiratory, or CNS (brain) function.


slouchingtoepiphany t1_jbytf32 wrote

I'm sorry for what you're going through, but your depiction of your treatment over 3 years is spectacular! Seriously, I work in clinical research and it's very hard to depict multiple lines of therapy over a long period of time. Very nice!


slouchingtoepiphany t1_jbsuh8z wrote

Actually, when you're at the scale of these molecular interactions, the concepts of rigidity hold up pretty nicely. (BTW, the broadest term for these kinds of interactions can be called "ligand-receptor binding", and the "lock-and-key" model works well for describing it. The ligand (or soluble protein) binds specifically to its receptor with high affinity. The subsequent steps are analogous to the mechanism within a lock when the key is turned. The altered structure of the receptor causes a change in another molecule (e.g., a "kinase" enzyme), which in turn induces a conformation change in another molecule. Subsequent interactions can result in a cascade of changes that result in the cell changing in some way (e.g., secreting a hormone or altering the voltage potential across its membrane).


slouchingtoepiphany t1_j331d9p wrote

It's funny because I intended to provide some of the information that u/masklinn (in much less detail, of course), but saw that he/she had already done a superb job. Still, I want to say something, so I'll mention that the particular, slime like feel of the mucins derives from the heterogeneous, O-linked glycoproteins (i.e., carbohydrate chains linked through an oxygen atom to a protein). These carb moieties have a negative charge on them that causes water molecules to be electrostatically attracted to them, making them very "wet" and slippery.

PS: The UN u/Snule is perfect for this conversation. :)


slouchingtoepiphany t1_j26a2kc wrote

>bizarre experience

That's a good summary of an SY performance, bizarre. I saw one a few years ago in Providence, RI. It included an Asian performer singing opera in Italian, a strange mix of traditional Chinese dance and modern electronics about the Monkey King, and political theater that amounted to a litany of cusses about the PRC. I don't know what this says about the residents of Providence (I live outside of Boston).


slouchingtoepiphany t1_izsjas2 wrote

Years ago, I helped write a study protocol and grant proposal for using hyperpolarized, Noble gas MRI to diagnose early-stage autism, but the fundamental approach was so flawed that I wanted no part of it. Indeed, it's hard to develop noninvasive, objective ways to diagnose disorder like these because (a) the changes that occur are not uniform among all people and (b) the means for following possible markers are not well developed.


slouchingtoepiphany t1_izshje6 wrote

I just looked it up, apparently there are two forms of Fatal Insomnia, one of them is inherited (autosomal dominant) and the other is caused by a prion (I didn't know that). There's a little more info available here:

However, it's known that, during sleep, the extent for gene expression in the brain rises and it's believed that the resulting proteins partially underlie the anatomical basis for memory and other developmental changes in the brain.


slouchingtoepiphany t1_iz319ug wrote

The recipient should receive Type A blood, but you wouldn't know that from the information that you were given. People with Type A blood (30%) are more common than people with Type B (11%), so it the donation should be the based on availability of donor blood. However, physiologically, it would make no difference.


slouchingtoepiphany t1_ix3qkyh wrote

This is a great answer and I might add an increase in the number of dendrites at the synapse as well. These physical changes are thought to result in electrophysiological changes in the post-synaptic neuron, such as long-term potentiation (LTP). But u/chazwomaq, is correct in that nobody knows how these changes underlie the formation of memories.


slouchingtoepiphany t1_iupb48g wrote

Thanks for providing these links. I'm hopeful that ongoing research in data analysis someday providing more theories on how life may have originated and when/how different forms of life emerged. If I were young enough to start over in another field, this is where I would go.


slouchingtoepiphany t1_itvaxls wrote

You're asking a very good question and we understand some aspects of it, but not all of them, nor is there a single comprehensive theory that fully explains all aspects of memory storage and retrieval. But first, one point of clarification, most neurons are not replaced during life. Except for sensory neurons in the olfactory bulb and a sub-set of neurons in the hippocampus, the neurons we have in our brains are the same throughout our lives.

Just to get encoding/decoding out of the way, information the obtain through our sensory receptors is parceled out (primarily through the thalamus and related ganglia) to different regions of our cerebral cortex: vision (occipital lobe), somatosensory (parietal lobe), auditory (temporal lobe), higher cognitive function (frontal lobe), and movement and motor skills (cerebellum). For movement or behavior in general, the individual draws from information saved in these areas.

Now to address your question. In the cortical areas mentioned above, neurons contact other neurons at synapses (the places where neurotransmitters are released from one neuron to another to either increase (excitatory) or decrease (inhibitory) the potential of the second neuron firing. And thus it continues from neuron to neuron. When neurotransmitters repeatedly act in synapse, in addition to causing the post-synaptic neuron to fire, they elicit subtle changes both pre- and post-synaptically. Pre-synaptically, these changes include increases in the number of NT-containing vesicles formed along with enzymatic modifications to increase how much NT is released. Post-synaptically, the numbers of NT receptors increase, as do the numbers of dendrites, and other changes referred to collectively as "post-synaptic densities." Over time and many thousands of times fired, the synapse becomes "stronger" or more able to fire (a model for this is calls it long-term potentiation or LTP).

This is what happens at a single neuronal synapse and it's the fundamental "unit" of memory, however note that each neuron receives input from about 1,000 neurons and provides output to another 1,000 neurons, and there are many, many neurons in the cortices (I don't recall how many, but there's an estimate for the entire brain of 10 to the 11th power that's sometimes mentioned.

Somehow, all of these individual synaptic changes give rise to memories and learned behaviors, but alas, we don't understand the full sequence of how this processing occurs.


slouchingtoepiphany t1_itrs4u1 wrote

There are numerous regulatory, clinical, legal, and ethical processes and procedures in place to ensure that the potential risk to someone who agrees to participate is minimized. In fact, there's too much for me to easily summarize, so I'll just mention a few of the protections that exist:

  • Pre-clinical Testing: Before a drug can be tested in humans, it must undergo rigorous testing in vitro and in animals to identify any risks that might exist. Then regulatory agencies (e.g., FDA and EMA) review the data and either allow or deny test in humans.
  • Clinical Trials: There are 3 phases of trials, beginning with small trials with healthy subjects and eventually larger trials involving numerous patients with the disease in question. At every step, safety and efficacy results are analyzed for potential risks and, if necessary, studies are terminated.
  • Communication of Risk: Physician investigators and potential subjects are given detailed information about the drug, including risks and benefits, if any. For physicians, this is in the "Investigator's Brochure" and for subjects it's in the "Informed Consent" form. In both cases, the documents must be read, understood, and signed.
  • Safety Monitoring: This is an onging process throughout clinical trials during which information about any and all adverse events is continually collected and evaluated for any signs issues.
  • Study Design: This is the area that may address your question more specifically because depending on the disease being studied, trials may differ. For cancer trials specifically, placebos are typically not used unless they are given in addition to the best available therapy that exists. Results are then analyzed to determine if there is an additional benefit to the drug beyond what the current treatment alternatives are, and there is no (or very little) additional risk to the patient. Results are also analyzed during the trial (i.e., an interim analysis) to ensure that patients are experiencing some benefit (or the study is terminated due to lack of efficacy) and not experiencing unacceptable adverse events (or the study is terminated for safety).

There are still more safeguards in place, but I hopefully this provides the gist.