Thursday, December 17, 2020

Programmed Cell Death To Fight Infection

Just in time for cold and flu season, this article.  Abstract:

Eukaryotic cells can die from physical trauma, which results in necrosis. Alternatively, they can die through programmed cell death upon the stimulation of specific signalling pathways. In this Review, we discuss the role of different cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary 'arms race' with pathogens. Finally, we describe how the resulting cell corpses - apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) - promote the clearance of infection.

The human body has many defenses against infection and we should do what we can do help: healthy diet, adequate sleep, physical activity, and hand washing.

Friday, December 11, 2020

The Best Christmas Gift (Letters from My Friend)

 


Introduction

Hana was my best friend for seven years. The first five of these years were at the University, where we both studied and graduated with BS/MS in Biotechnology. Our graduation coincided with the explosion of a societal chaos. The chaos was fueled by the dying socialism and the newly-born capitalism. The nascent but deformed capitalism in Eastern Europe was the child of the former socialist leaders floating on the vast funds of their communist parties. 

There were no jobs for University graduates anymore. In the past, the communist party was handing job assignments to each graduate; however, at the the end of the eighties, the jobs and all socialist structures and enterprises collapsed.  I still carry the stigma of joining the unemployment line as soon as I was awarded my Master's degree.  Before even being employed for the first time in my life, I had to experience the feeling of being useless and unworthy. My solution was to start a PhD program in a pharmaceutical research institute. The position secured a small stipend; however, my mentor “disappeared”. This is another long story that is not worthy narrating.  Absurdities like this disappearance were abundant and we did not pay them any attention, for our focus was on mere survival.  Eventually, I learned English on my own, took the TOEFL and GRE exams required for applications to US graduate schools, and in two years after graduating with MS degree, I left for New York city and a PhD program there.  Hana stayed behind with her family and her job. She had always had an excellent command of English and she was able to find jobs requiring English in the mushrooming private enterprises.  Hana intended to join me in the USA once ready to switch to studying mode again.

I met Hana during lectures in our first college year. She was reticent and hesitant to talk to us, the other four girls in the student group. She was darker than all of us. She had darker skin color, dark and shiny long hair, exotic dark eyes. She carried the enigma of a foreigner. She also seemed depressed and even permanently offended by something.

Forward seven years. Hana and Joy were the two friends who sent me at the airport before my flight to New York city.  I was leaving for my PhD studies. My English was poor, and I relied on approximately $1,000 that my parents had borrowed from relatives.  My ticket was paid by a charity foundation. I was desperate to get out of the country.  After a heartfelt goodbye at the airport, I never saw Hana again.

During the seven years of our friendship, Hana proved to be the kindest, most sophisticated, knowledgeable and smart person I had ever met in my life. She could derive mathematical formulas, bake amazing cakes, cook delicious pasta, tailor jackets and pants, play the piano, sing, discuss all famous music bands, movies, singers and actors, and speak Farsi, English, Russian, German, and Bulgarian. She was also studying Norwegian. She was impeccable in all aspects and she was my inspiration to become better in everything I did.

During my first year in the USA, I received three letters from Hana and then the letters stopped; the news from and about her dried out. I asked my parents about Hanna, and they reluctantly said that she had been in a car accident. She was treated in a hospital, they added. This was the story that mom and dad kept repeating until I went back home for a visit after the first year of PhD studies. And then they told me the truth. Hana had passed away. She had died months before I got home. The car accident happened on an icy road, somewhere in the provinces. Everyone else in the car got out unscathed. Only the part of the overturned car where Hana was sitting was so badly crumpled that had to be cut by emergency workers. A small provincial hospital nearby took care of Hana. Her condition was stable at the beginning but deteriorated suddenly. The likely cause was a blood clot. There was no defibrillator, and a helicopter was sent to transfer Hana to the capital, but it was too late. 

People say that time heals. Time never healed my pain and never changed my refusal to accept the reality. No one can accept the death of a 25-year old smart and talented young woman. And probably because it was so painful, I avoided thinking about her until recently. 

It has been 27 years.

This past week before Christmas, I was looking for colored paper that I had boxed away, along with a bunch of letters from my mom and relatives. As I was going through the box, a small picture of Hana fell out of an envelope. The envelope also contained three letters from Hana. These are the only letters she wrote to me after I came to the US. The last letter was written two or three weeks before her death.  I must have hidden these letters from myself long time ago, because I did not want to cry anymore. I re-read the letters 27 years later. I did not remember even a word.

The three letters were the best Christmas gift I have ever received. I did cry again when I read them; however, for the first time I felt a newly-found appreciation for the gift of friendship in my early life.  Along with the sharp bitterness of the loss, for the first time, I felt gratitude of having had someone so special. Hana will be always in my thoughts as an inspiration to become better in everything I do.  This is the power of a great example. 

The three letters below do not reflect the true intellectual and emotional strength of Hana, for she always doubted herself and put herself down.

 

Letter #1

Dear Pari,

I am guilty. My conscience is uneasy and most of all, I feel guilty because of abandoning you. But you know me well – I cannot change, I keep postponing everything as if tomorrow I would do it in a better way. Since you left, I have been thinking about you and praying for you. I was aware of how much you expected a letter from me and despite of this, I did not sit down to write one. If I tell you that it was lack of time, you probably would not believe it and you would not be mistaken. When I read the first and last sentences of your letter, a sharp heartache impaled me! No, I am not the kindest person you have ever known, I am not even good, but I would like you to know that I miss you tremendously and I am miserable without you.  Please, do not conclude that I will not write to you! Maybe not as frequently as I wish, but I will try.

I am happy that all is well there. It is terribly interesting to read your letters - it is as if I am in New York city! You do not know, but at the beginning, I was very worried about you – being in a foreign country and all, but now I have been reassured. You are going to make it! I can hardly imagine myself in your shoes – to have lectures in English, to do homework and take tests with grades higher than 90% … All of this seems to me so impossible and unachievable. You are the best! I do not believe that your English has not improved, on the contrary! I wish I could let you listen now to Suzanne Vega… and I greatly envy you that you are so close to her (she lives in N.Y.). You did not write anything about your job – how is it? Do you get tired? Do you have enough money? And most importantly, are you coming home for a visit? I apologize, I am so nosy, right?

Maybe you would be more interested to find out something about me, despite that my life is not so exciting and bubbling with new experiences like yours.  I will start from the beginning. Soon after you left, I went to the resort of Basko with Sophia. I did not feel like going there; however, we happened to have a great time! Every morning we rose early and went to the mountains with the service bus for the personnel of the cable car line. This bus is not allowed to serve guests like us, but we begged since all other buses for the mountains were stopped. High in the mountains, we hiked for hours and at five o’clock in the afternoon, we again used the service bus to go back to the town. We spent a lot of money this week, but spoiled ourselves with everything – chocolate, ice cream, orange juice and even Irish Cream (but not the original, of course…). Admittedly, I had my brief depression episodes, but everything else was superb. By the time I got back home, I had taken a firm decision to sever relations with my “dear” boss and quit my job. I had to wait, however, till the beginning of September, when she was to return from her vacation. Till then, I decided to have a great life and frequently skipped on going to work. Moreover, during that time, the boss’s niece came to live in our office. The office is in fact the apartment of my boss’s brother, who is married and lives in Germany. Can you imagine that the niece was born on 09/03/1968!!! (yes, my birth date) and, of course, she was the cutest! Most of the time, we just talked over a cup of coffee and a coke. She even insisted on treating me because of our common birth date, so we went to a disco and a night club. I got back home at 4:00 AM. We had a great time, but at the end, my boss came back and on her first day in the office, I presented her my resignation (which to my surprise, was accepted well ... thank God!). I had to continue working there till the end of October since the company's policy calls for a 30-day advanced resignation. And this was the worst of times. The boss decided that I should finish the most difficult and least rewarding tasks; so, I ran like a Phoenician to do it all.

You cannot imagine the relief I felt the first day after I was done with that job. I woke up in the morning and realized I did not have to catch the bus to that office ever again! Took three days of “rest” (this is in quotation marks because I had to finish myriad of postponed tasks and obligations) and then I started the new job, which is highly satisfying. My starting salary will be 3,000 xxx (or higher) and the environment is incomparable. The colleagues are extremely nice and congenial. Although there is lots of work to be done, all is accomplished in a quiet manner, without stress and anxiety. There are always people around and I no longer feel like I am confined to a solitary prison cell like I experienced in my previous job. I work on a computer and translate directly from English; this experience would be of help for my future [studies]. After the torture with the nasty typewriter at my former office, the place here feels like a paradise. There are also games her!. Outside the job, life is more or less the same. I go to the movies, take music lessons (now I am studying harmony), and so on. It is not that interesting to describe.

I received a letter from my cousin in Connecticut, who on request by my father, paid my application fee to Boston University and Clarkson University. My cousin also asked me to send him all my documents and he will try to secure my admission in his university, which is unfortunately a private institution and I may not be able to afford the tuition. There is nothing else. I hope to be together with you next year.

This is all for now. I have not called Joy because I lost her phone number. I hope she remembers me and calls one of these days.

Pari, I miss you.

With lots of love,

Hana

 

PS Please, forgive my ugly handwriting.

 

Letter #2

Hello, dear Pari!

This time you have the right to be angry with me. I am a horrible person. I cannot stop procrastinating. I have been planning to write you a letter and I carry with me a pack of letter stationary all the time. And yet, I could not find the time to do it until now. Finally, here it is this blank page of paper that I started to fill with letters. It is a Sunday evening, and all is quiet!

Pari, forgive me that I do not write you on a regular basis. I do think about you frequently. Many things happened to me recently – they may seem strange to you, but believe me, they are not less strange to me. Do you remember when we talked about God? You said that everyone has their own God, and until recently I more or less thought the same. But something happened to me (not a miracle, but SOMETHING), which made me believe in the one and only God – the one who created all around us and who is above all. I cannot explain the change within myself, but I cannot deny that I had not expected this change. For a long time, I have been preparing for this and now, I know that there is nothing impossible for God, and all goes according to God’s plan.

I have always been looking for a meaning in everything, but I could never find the meaning anywhere. It is frightening to think that we live just like that, just because we were born (to overjoy our parents), to achieve something (if we could), to create children (who could give some meaning to our lives and then make them meaningless again), and to disappear into the nothingness. When I start reasoning like this, I do not want to live anymore. Now, however, I believe that there is something to live for, albeit, I have still not discovered what it is exactly.  Excuse me that I am bothering you with these thoughts, but this is what's on my mind lately.

Here, nothing is happening except for the prices steadily climbing up. Thank God, for now, I have not had financial problems. I am relatively well paid, but most importantly, I have amazing colleagues and every day go to work with pleasure. There is lots of work especially for me; I just finalized the translation of a magazine. In addition, there is always something new to do, there are lots of in-coming and out-going communications and faxes, etc. I do not event notice how the time flies; whereas, at my previous job, I could not wait for 6:00 PM to leave. The only thing that troubles me is that my eyes strain terribly. But obviously this is the inevitable evil when working on a computer. Besides work, I am quite busy – I go to church three times a week, twice a week I join the choir rehearsals, and take lessons in music harmony, etc. I go home only to take a shower and sleep. Our neighborhood just got central heating and it is a bliss!

I hope that you do not feel estranged and lonely anymore in NY.  You are going to make it. I am glad that you are there, where you deserve to be. How were your Christmas and New Year’s Eve? (all was normal for me). Excuse my belated postcard! 

Write me about your studies, it is so interesting!  I still do not have any news from Fordham University, but I have been accepted in Clarkson University (stipend?). Boston University acknowledged that my document package was complete, and the application was sent for a review. I am pretty sure that next year we will trod the same grounds.

This is all for now. I have many other things to share, but I can hardly keep my eyes open (my handwriting evidences this). I love you and I pray for you!

Hana

 

Letter #3

Dear Pari, 

Good Morning!

It is 21 minutes past midnight. You probably still have daylight. It is so strange that at the same time somewhere is night, and somewhere else is daylight… As in the song of Suzanne Vega, “…half the world in sweetness, the other in fear”. I received your letter a day ago, after finding my mailbox empty every day for a long time. I was overjoyed! 

The pictures are amazing – one of them (the one with you, of course) decorates my shelves now. You look great and your friends seem cute. Yale University is stunning; it is probably fantastic to study there (in all these buildings, architecture, etc.). I have no new pictures, so I cannot surprise you with anything. I have been thinking of buying a camera, but the film developing here is quite expensive.

This does not mean that I am frugal. My last acquisition is over 9,700 xxx – a CD player and a speaker. Finally, my dream is a reality! At the moment, I am writing and listening to the sounds of Tubular Bells II by Mike Oldfield.

Thank you so much for watching the interview with Suzanne Vega on my behalf! What would not I give just to be able to peek at her. 

Lately, I frequently catch myself thinking that I would like to go to the United States. This is strange, since until recently I perceived this possibility as a burden. Maybe I am changing – the mere fact that I am sitting down to reply to your letter in such a short time is very indicative. With the risk of being annoying, I will quote Suzanne Vague again, “I think it is called my destiny that I am changing…”.

I still have not received a notice from Fordham University about my application. I am accepted in NEU and Clarkson University; however, there is still no decision about a stipend. Boston University acknowledged that my application was complete, but they are still reviewing it.

Pari, I have this strange feeling that next year we will be together! I miss you very much, I need a close friend like you.

There is nothing interesting around me. I go to work, sing in the choir, hang around here and there… But it is TERRIBLY interesting to read about your American life, it is not the least boring or stupid as you qualify it!

My dear, my eyes are closing… Do not despair and do not fear, because “God has given us not a spirit of fear, but a spirit of strength, love, and self-control” (II Quran 1:7).

I love you!

Waiting for news,

Hana

 

 This is my real life, but all names of people and locations are changed.