#Functions

[arcsin27]

if youre bisexual youre also insexual and sursexual

[fxwitches]

f(x) old piczzzzzz T-T

[alkistisnetwide]

People who self-type with rare and "coveted" labels, such as: INFJs, INTJs, 5s, 4s, IEIs, ILIs, Ns by extension

Let me ask, to what extent would your self-worth differ if you concluded you were mistyped?

To what extent would your self-worth change if you found typology to be a false idea?

Back when I believed socionics was the answer to everything at 15, I was negatively affected by that interest. I questioned things about myself because I seemed to have traits that didn't fit my EII (INFP,INFj) type, but I settled on it eitherway because of my focus on morality. It didn't help how little self esteem I had to be of the least impressive of the 4 "intelligent" types. Even worse, socionics changed how I saw others. I believed others lacked moral values and intelligence, thought in a manner inconceivable to me and would fundamentally be bad company for me

The enneagram had me constantly questioning every aspect of my behavior in order to affirm that I was indeed a 5w4

If you are invested in personality typing, I think you should consider the influence of your emotions on your investment and take a short break. People who are no longer certain about these systems, it might be useful to share your opinion of them in retrospect

[mingos-commodoreblog]

Commodore 64 Grund-Befehle

[morerichka8]

What are they growing this time? AI Fall, 2024 @morerichka

[wouldyoulikeafourleafclover]

Got my math test on functions back, just missed an A by about 3.5 marks so I am still on a B!

[evil-jennifer-hamilton-wb]

Y'all desmos has complex numbers now!!

(Complex numbers are just numbers to a girl like me, but big news for everybody else so I thought would disseminate.)

It was such a pain in the ass to do complex functions in desmos before, I have spent so many hours trying to get real number based desmos to do domain coloring with complex functions. I haven't actually had a chance to try it out yet so I don't know exactly how it's implemented.

(we did the same thing before they added 3D where you could use parametrics in 2D to graph any 3D explicit function, but it was a pain and took a long time to figure out how to graph 3d on a 2d space. (It took a while to engineer for me at least, idk if it was actually easy and I'm just stupid))

[courtneyslife]

Blooming Back into School

I live with my three friends two are in my sorority Phi Mu and one is not, but comes to all our events. This past Friday my sorority had a function called back in bloom so my roommates and I all went. When we all have a same event to go to our house turns into the best place to be. Our closets open up for all of us to look in and pick out dresses or accessories to wear and we blast music from our speaker downstairs so we can all hear it in our rooms. It is so run being able to run next door to my roommates room to have her help me do my hair or so borrow something. So we all got dolled up in floral and went out front to take pictures. The function was at Tin Roof and there was a live band playing which was so fun to go listen to the music and hang out with my roommates and our other friends all dressed up. The food was all so good and my favorite was the Mac n cheese balls or the mini chicken salad sandwich. After the function we all went back home and hung out and watched the new season of Emily in Paris. It was a very fun but also chill Friday with my friends.

[daily-public-domain]

Day 247: Riemann Zeta landscape

link

–This image is part of the public domain, meaning you can do anything you want with it! (you could even sell it as a shirt, poster or whatever, no need to credit it!)–

[hoe4kai]

The vibe i bring to the function

[nando161mando]

The function of private property under capitalism

[a-fox-studies]

August 9, 2023

Learning in the dark has a completely different vibe.

🎧 Sheltered - Cauzy

[lyssified]

Help

[thepersonalwords]

It is clear that the protective functions of workplace health and safety have transferred to the workers through the process of corporate government deregulation and reduced funding of relevant government departments.

Steven Magee

[jcmarchi]

Cellular traffic congestion in chronic diseases suggests new therapeutic targets

New Post has been published on https://thedigitalinsider.com/cellular-traffic-congestion-in-chronic-diseases-suggests-new-therapeutic-targets/

Cellular traffic congestion in chronic diseases suggests new therapeutic targets

Chronic diseases like Type 2 diabetes and inflammatory disorders have a huge impact on humanity. They are a leading cause of disease burden and deaths around the globe, are physically and economically taxing, and the number of people with such diseases is growing.

Treating chronic disease has proven difficult because there is not one simple cause, like a single gene mutation, that a treatment could target. At least, that’s how it has appeared to scientists. However, new research from MIT professor of biology and Whitehead Institute for Biomedical Research member Richard Young and colleagues, published in the journal Cell on Nov. 27, reveals that many chronic diseases have a common denominator that could be driving their dysfunction: reduced protein mobility. 

What this means is that around half of all proteins active in cells slow their movement when cells are in a chronic disease state, reducing the proteins’ functions. The researchers’ findings suggest that protein mobility may be a linchpin for decreased cellular function in chronic disease, making it a promising therapeutic target.

In their paper, Young and colleagues in his lab, including MIT postdoc Alessandra Dall’Agnese, graduate students Shannon Moreno and Ming Zheng, and Research Scientist Tong Ihn Lee, describe their discovery of this common mobility defect, which they call proteolethargy; explain what causes the defect and how it leads to dysfunction in cells; and propose a new therapeutic hypothesis for treating chronic diseases.

“I’m excited about what this work could mean for patients,” says Dall’Agnese. “My hope is that this will lead to a new class of drugs that restore protein mobility, which could help people with many different diseases that all have this mechanism as a common denominator.”

“This work was a collaborative, interdisciplinary effort that brought together biologists, physicists, chemists, computer scientists and physician-scientists,” Lee says. “Combining that expertise is a strength of the Young lab. Studying the problem from different viewpoints really helped us think about how this mechanism might work and how it could change our understanding of the pathology of chronic disease.”

Commuter delays cause work stoppages in the cell

How do proteins moving more slowly through a cell lead to widespread and significant cellular dysfunction? Dall’Agnese explains that every cell is like a tiny city, with proteins as the workers who keep everything running. Proteins have to commute in dense traffic in the cell, traveling from where they are created to where they work. The faster their commute, the more work they get done. Now, imagine a city that starts experiencing traffic jams along all the roads. Stores don’t open on time, groceries are stuck in transit, meetings are postponed. Essentially all operations in the city are slowed.

The slowdown of operations in cells experiencing reduced protein mobility follows a similar progression. Normally, most proteins zip around the cell bumping into other molecules until they locate the molecule they work with or act on. The slower a protein moves, the fewer other molecules it will reach, and so the less likely it will be able to do its job. Young and colleagues found that such protein slowdowns lead to measurable reductions in the functional output of the proteins. When many proteins fail to get their jobs done in time, cells begin to experience a variety of problems — as they are known to do in chronic diseases.

Discovering the protein mobility problem

Young and colleagues first suspected that cells affected in chronic disease might have a protein mobility problem after observing changes in the behavior of the insulin receptor, a signaling protein that reacts to the presence of insulin and causes cells to take in sugar from blood. In people with diabetes, cells become less responsive to insulin — a state called insulin resistance — causing too much sugar to remain in the blood. In research published on insulin receptors in Nature Communications in 2022, Young and colleagues reported that insulin receptor mobility might be relevant to diabetes.

Knowing that many cellular functions are altered in diabetes, the researchers considered the possibility that altered protein mobility might somehow affect many proteins in cells. To test this hypothesis, they studied proteins involved in a broad range of cellular functions, including MED1, a protein involved in gene expression; HP1α, a protein involved in gene silencing; FIB1, a protein involved in production of ribosomes; and SRSF2, a protein involved in splicing of messenger RNA. They used single-molecule tracking and other methods to measure how each of those proteins moves in healthy cells and in cells in disease states. All but one of the proteins showed reduced mobility (about 20-35 percent) in the disease cells. 

“I’m excited that we were able to transfer physics-based insight and methodology, which are commonly used to understand the single-molecule processes like gene transcription in normal cells, to a disease context and show that they can be used to uncover unexpected mechanisms of disease,” Zheng says. “This work shows how the random walk of proteins in cells is linked to disease pathology.”

Moreno concurs: “In school, we’re taught to consider changes in protein structure or DNA sequences when looking for causes of disease, but we’ve demonstrated that those are not the only contributing factors. If you only consider a static picture of a protein or a cell, you miss out on discovering these changes that only appear when molecules are in motion.”

Can’t commute across the cell, I’m all tied up right now

Next, the researchers needed to determine what was causing the proteins to slow down. They suspected that the defect had to do with an increase in cells of the level of reactive oxygen species (ROS), molecules that are highly prone to interfering with other molecules and their chemical reactions. Many types of chronic-disease-associated triggers, such as higher sugar or fat levels, certain toxins, and inflammatory signals, lead to an increase in ROS, also known as an increase in oxidative stress. The researchers measured the mobility of the proteins again, in cells that had high levels of ROS and were not otherwise in a disease state, and saw comparable mobility defects, suggesting that oxidative stress was to blame for the protein mobility defect.

The final part of the puzzle was why some, but not all, proteins slow down in the presence of ROS. SRSF2 was the only one of the proteins that was unaffected in the experiments, and it had one clear difference from the others: its surface did not contain any cysteines, an amino acid building block of many proteins. Cysteines are especially susceptible to interference from ROS because it will cause them to bond to other cysteines. When this bonding occurs between two protein molecules, it slows them down because the two proteins cannot move through the cell as quickly as either protein alone. 

About half of the proteins in our cells contain surface cysteines, so this single protein mobility defect can impact many different cellular pathways. This makes sense when one considers the diversity of dysfunctions that appear in cells of people with chronic diseases: dysfunctions in cell signaling, metabolic processes, gene expression and gene silencing, and more. All of these processes rely on the efficient functioning of proteins — including the diverse proteins studied by the researchers. Young and colleagues performed several experiments to confirm that decreased protein mobility does in fact decrease a protein’s function. For example, they found that when an insulin receptor experiences decreased mobility, it acts less efficiently on IRS1, a molecule to which it usually adds a phosphate group.

From understanding a mechanism to treating a disease

Discovering that decreased protein mobility in the presence of oxidative stress could be driving many of the symptoms of chronic disease provides opportunities to develop therapies to rescue protein mobility. In the course of their experiments, the researchers treated cells with an antioxidant drug — something that reduces ROS — called N-acetyl cysteine and saw that this partially restored protein mobility. 

The researchers are pursuing a variety of follow-ups to this work, including the search for drugs that safely and efficiently reduce ROS and restore protein mobility. They developed an assay that can be used to screen drugs to see if they restore protein mobility by comparing each drug’s effect on a simple biomarker with surface cysteines to one without. They are also looking into other diseases that may involve protein mobility, and are exploring the role of reduced protein mobility in aging.

“The complex biology of chronic diseases has made it challenging to come up with effective therapeutic hypotheses,” says Young. “The discovery that diverse disease-associated stimuli all induce a common feature, proteolethargy, and that this feature could contribute to much of the dysregulation that we see in chronic disease, is something that I hope will be a real game-changer for developing drugs that work across the spectrum of chronic diseases.”