Wednesday, October 9, 2013

The Nobel Prize in Physiology or Medicine 2013

The Nobel Prize in Physiology or Medicine 2013

The Nobel Prize in Physiology or Medicine 2013 was awarded jointly to James E. Rothman, Randy W. Schekman and Thomas C. Südhof "for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells".



A Presentation to summerize the discovery




Summary of the Press Release by the Nobel Foundation


Summary

The 2013 Nobel Prize honours three scientists who have solved the mystery of how the cell organizes its transport system. Each cell is a factory that produces and exports molecules. For instance, insulin is manufactured and released into the blood and chemical signals called neurotransmitters are sent from one nerve cell to another. These molecules are transported around the cell in small packages called vesicles. The three Nobel Laureates have discovered the molecular principles that govern how this cargo is delivered to the right place at the right time in the cell.
Randy Schekman discovered a set of genes that were required for vesicle traffic. James Rothman  unravelled protein machinery that allows vesicles to fuse with their targets to permit transfer of cargo. Thomas Südhof revealed how signals instruct vesicles to release their cargo with precision.
Through their discoveries, Rothman, Schekman and Südhof have revealed the exquisitely precise control system for the transport and delivery of cellular cargo. Disturbances in this system have deleterious effects and contribute to conditions such as neurological diseases, diabetes, and immunological disorders.

How cargo is transported in the cell

In a large and busy port, systems are required to ensure that the correct cargo is shipped to the correct destination at the right time. The cell, with its different compartments called organelles, faces a similar problem: cells produce molecules such as hormones, neurotransmitters, cytokines and enzymes that have to be delivered to other places inside the cell, or exported out of the cell, at exactly the right moment. Timing and location are everything. Miniature bubble-like vesicles, surrounded by membranes, shuttle the cargo between organelles or fuse with the outer membrane of the cell and release their cargo to the outside. This is of major importance, as it triggers nerve activation in the case of transmitter substances, or controls metabolism in the case of hormones. How do these vesicles know where and when to deliver their cargo?

Traffic congestion reveals genetic controllers

Randy Schekman was fascinated by how the cell organizes its transport system and in the 1970s decided to study its genetic basis by using yeast as a model system. In a genetic screen, he identified yeast cells with defective transport machinery, giving rise to a situation resembling a poorly planned public transport system. Vesicles piled up in certain parts of the cell. He found that the cause of this congestion was genetic and went on to identify the mutated genes. Schekman identified three classes of genes that control different facets of the cell´s transport system, thereby providing new insights into the tightly regulated machinery that mediates vesicle transport in the cell.

Docking with precision

James Rothman was also intrigued by the nature of the cell´s transport system. When studying vesicle transport in mammalian cells in the 1980s and 1990s, Rothman discovered that a protein complex enables vesicles to dock and fuse with their target membranes. In the fusion process, proteins on the vesicles and target membranes bind to each other like the two sides of a zipper. The fact that there are many such proteins and that they bind only in specific combinations ensures that cargo is delivered to a precise location. The same principle operates inside the cell and when a vesicle binds to the cell´s outer membrane to release its contents.
It turned out that some of the genes Schekman had discovered in yeast coded for proteins corresponding to those Rothman identified in mammals, revealing an ancient evolutionary origin of the transport system. Collectively, they mapped critical components of the cell´s transport machinery.

Timing is everything

Thomas Südhof was interested in how nerve cells communicate with one another in the brain. The signalling molecules, neurotransmitters, are released from vesicles that fuse with the outer membrane of nerve cells by using the machinery discovered by Rothman and Schekman. But these vesicles are only allowed to release their contents when the nerve cell signals to its neighbours. How is this release controlled in such a precise manner? Calcium ions were known to be involved in this process and in the 1990s, Südhof searched for calcium sensitive proteins in nerve cells. He identified molecular machinery that responds to an influx of calcium ions and directs neighbour proteins rapidly to bind vesicles to the outer membrane of the nerve cell. The zipper opens up and signal substances are released. Südhof´s discovery explained how temporal precision is achieved and how vesicles´ contents can be released on command.

Vesicle transport gives insight into disease processes

The three Nobel Laureates have discovered a fundamental process in cell physiology. These discoveries have had a major impact on our understanding of how cargo is delivered with timing and precision within and outside the cell.  Vesicle transport and fusion operate, with the same general principles, in organisms as different as yeast and man. The system is critical for a variety of physiological processes in which vesicle fusion must be controlled, ranging from signalling in the brain to release of hormones and immune cytokines. Defective vesicle transport occurs in a variety of diseases including a number of neurological and immunological disorders, as well as in diabetes. Without this wonderfully precise organization, the cell would lapse into chaos.
James E. Rothman was born 1950 in Haverhill, Massachusetts, USA. He received his PhD from Harvard Medical School in 1976, was a postdoctoral fellow at Massachusetts Institute of Technology, and moved in 1978 to Stanford University in California, where he started his research on the vesicles of the cell. Rothman has also worked at Princeton University, Memorial Sloan-Kettering Cancer Institute and Columbia University. In 2008, he joined the faculty of Yale University in New Haven, Connecticut, USA, where he is currently Professor and Chairman in the Department of Cell Biology.
Randy W. Schekman was born 1948 in St Paul, Minnesota, USA, studied at the University of California in Los Angeles and at Stanford University, where he obtained his PhD in 1974 under the supervision of Arthur Kornberg (Nobel Prize 1959) and in the same department that Rothman joined a few years later. In 1976, Schekman joined the faculty of the University of California at Berkeley, where he is currently Professor in the Department of Molecular and Cell biology. Schekman is also an investigator of Howard Hughes Medical Institute.
Thomas C. Südhof was born in 1955 in Göttingen, Germany. He studied at the Georg-August-Universität in Göttingen, where he received an MD in 1982 and a Doctorate in neurochemistry the same year. In 1983, he moved to the University of Texas Southwestern Medical Center in Dallas, Texas, USA, as a postdoctoral fellow with Michael Brown and Joseph Goldstein (who shared the 1985 Nobel Prize in Physiology or Medicine). Südhof became an investigator of Howard Hughes Medical Institute in 1991 and was appointed Professor of Molecular and Cellular Physiology at Stanford University in 2008.

Sunday, June 30, 2013

IAMM AP CHAPTER GUIDELINES SERIES : INTRODUCTION



One scenario :
“What did you see in the smear”
“Gram positive cocci in clusters sir”
“Did you do hanging drop”
“No sir”
“WHY…..?! who told you not to do?....(gives a scornful look at the internals and says,) OK. Name some motile cocci”
********
Another scenario :
“What did you see in the smear”
“Gram positive cocci in clusters sir”
“Did you do hanging drop”
“Yes  sir.. they are nonmotile”
“WHY…..?! who told you to do the hanging drop ? ?....(gives a scornful look at the internals and says,)  you are wasting time and resources. Are there any pathogenic cocci that are motile ? NO. then why did you do. ”

****
Everybody who are attending the PG practical examinations regularly (as a facilitating faculty/internal or as a candidate..!) would have witnessed such conversations. Leave alone the confusions in the diagnostic microbiology.

The already tense exam-going PGs are exposed to several such ambiguities. Ambiguities, right from the Gram staining. And different colleges in the state, different batches in the college, different faculty have different opinions even on simple things (the paradox is, even 12th edition of Cruickshank differs from 14th ed in certain issues.Koneman gives different version from other books in some aspects. Bailey and scott or Monica Cheesbrough adds to variety). Let the ambiguities persist in the science.. that is quiet natural and needed too for testing and trying different variables in varying situations. But, as far as examinations are concerned, the ambiguity may cost the degree and put the candidate in undue or unreasonable stress.



In this context, IAMM AP Chapter publishes certain suggestions regarding the split-up and distribution of marks in the  PG practical examinations, submitted by Dr. P.Sreenivasulu Reddy, Professor of Microbiology, Narayana Medical College, Nellore. These are based on regular NTRUHS exam pattern with further elaboration of the split up of marks.  All are requested to go through the file and please submit your comments and suggestions (either through comments in the blog directly  or through email to iammapchapter@yahoo.co.in).
  
click here to go to the guidelines series published by IAMM AP CHAPTER

****
A comment  that appeared  on the guidelines, for information to visitors of this blog : 
(July 1, 2013 at 3:45 PM)

Dear....I should congratulate you for the concern and admire you for your initiative. Any attempt to set things move in the proper direction is always 'WELCOME' But something puzzles me....

HOW DO YOU RATE THE TRAINING YOU HAVE RECEIVED AS A POST GRADUATE?

IF YOUR ANSWER IS SATISFACTORY .......

THEN WHY ARE WE FEELING THAT THE SAME SYSTEM OF EXAMINATION NEEDS A REVAMP?

THE FAULT IS NOT WITH THE SYSTEM BUT WITH THE ATTITUDE OF THE PEOPLE GOVERNING THE SYSTEM.

CAN WE DO SOMETHING TO ADDRESS THIS FIRST?

Ofcourse YES, if only we have people like you who recognizes the problem! Keep it up
****
My reply :

Thank you for your comments and compliments;
I rate the training I have received as a Postgraduate as 'satisfactory' in the given settings and available facilities in those days.

And, it is not the reason to stop or start any innovative activity. There will always be a scope for improvement even for the so called best circumstances. We can always work on improving the circumstances or the training we give for the students. That is an incessent process...!

And, I dont want to revamp any....I am not that big. I am a tiny creature in the whole big system. My intention is just to throw some light on the existing ambiguities in the examination system.
As you mentioned, the fault may not be with the system. but, it is the system we all passed through...and watching our juniors to pass through. we have to watch the same for several more years to come.

We can not help with the individual attitudes of either the examiners or the students. Nobody can help it. It will be ONLY the individual introspection that brings about change in their attitudes..not any other external force.
A change in the smaller things will gradually reflect in course of time as a major change in the system . I am a strong believer of this concept.

With this, I request you and other seniors to please provide strength to pursue the goal, by providing your valuable suggestions and guidance.

You may be too modest to not to mention your name, but we will be more happy if we could know who are leaving the comments. And even more happy to get your blessings in my endeavours.- with regards- Dr. D.S.Murty  

****

click here to go to the guidelines series published by IAMM AP CHAPTER

Tuesday, April 23, 2013

Love Your Irritations

A piece of interesting collection shared by one of my friend through email . This is a good one, that guides us to have introspection of our weaknesses and a simple way that motivates us to overcome those negative traits. I am just sharing it here with thanks to the original source.
*****
Khalil Gibran, one of the greatest thinkers, once wrote: "I have learned silence from the talkative, tolerance from the intolerant, and kindness from the unkind; yet, strange, I am grateful to those teachers"
***

A psychiatrist was consulted by a man whose marriage and career were both in serious trouble. His problem was his constant irritability and bad temper. He was concerned about this himself, but if any one tried to discuss it with him, he exploded in anger. He constantly told himself that everyone was picking on him and that he had to defend himself against them.
To counter the negative auto suggestion, he advised him to use positive autosuggestion. Several times a day in the morning, noon, and at night prior to sleep he was to repeat to himself.

"From now on, I shall grow more good-humored. Joy, happiness, and cheerfulness are now becoming my natural states of mind.
Every day I am becoming more and more lovable and understanding.
I will be center of cheer and goodwill to all those around me, infecting them with my good spirits.
This happy, joyous, and cheerful mood is now becoming my normal, natural state of mind. I am grateful "

 After a month, his wife and his coworkers remarked on how much easier he was to get along with.

 The things that drive you crazy are actually giant opportunities. The people who press your buttons are actually your greatest teachers. The issues that make you angry are actually your biggest gifts. Be grateful to them. Love them.
The people or circumstances that take you out of your power have extraordinary value: they reveal your limiting beliefs, fears and false assumptions. The celebrated psychologist Carl Jung once said: "Everything that irritates us about others can lead us to an understanding of ourselves." Powerful point. The things that irritate, annoy and anger you are entry points into your evolution and elevation as a human being. They are signposts for what you need to work on and the fears you need to face. They are gifts of growth. You can blame the people who trigger you and make it all about them. Or you can do the wise thing and look deeply into yourself to discover the reason for your negative reaction. Use the challenges to grow self-awareness. Because how can you overcome a fear you are not even aware of? And how can you transcend an insecurity you don't even know you have?
As you begin to shed light on your personal weaknesses and take responsibility for them, you actually begin the very process of shedding them. You become stronger. More powerful. You begin to see the world through a different set of eyes.

Saturday, March 30, 2013

Kindness...timely display..!

One day, a poor boy who was selling goods from door to door to pay his way through school, found he had only one thin dime left, and he was hungry.

He decided he would ask for a meal at the next house.
However, he lost his nerve when a lovely young woman opened the door. Instead of a meal he asked for a drink of water. 

She thought he looked hungry so brought him a large
glass of milk He drank it slowly, and then asked, "How much do I owe you?""You don't owe me anything," she replied "Mother has taught us never to accept payment for a kindness."

He said... "Then I thank you from my heart." 
As Howard Kelly left that house, he not only felt; stronger physically, but his faith in God and man was strong also. He had been ready to give up and quit. Years later that young woman became critically ill. The local doctors were baffled. They finally sent her to the big city, where they called in specialists to study her rare disease. Dr. Howard Kelly was called in for the consultation.
When he heard the name of the town she came from, a strange light filled his eyes. Immediately he rose and went down the hall of the hospital to her room. Dressed in his doctor's gown he went in to see her. 

He recognized her at once. He went back to the consultation
room determined to do his best to save her life. From that day he gave special attention to the case. After a long struggle, the battle was won. Dr. Kelly requested the business office to pass the final bill to him for approval.

He looked at it, then wrote something on the edge and the bill was sent to her room. She feared to open it, for she was sure it would take the rest of her life to pay for it all. Finally, she looked, and something caught her attention on the side as she read these
words...... 

"Paid in full with one glass of milk." (Signed) Dr. Howard Kelly.
Tears of joy flooded her eyes & happy heart.
****


(.....A collection from one of the  mails I got )

Friday, March 15, 2013

Science...Discarding It..?! (Part 2)

In Facebook or other social media, I see some comments on religion and science (mostly making fun of them). But, please understand that... In olden days, science and religion are practiced together. They tried to spread science under the cover of religious respect...which are easy to follow even by those who did not understand them. gradually, the people who knew the actual science became extinct and there is increment of  people who go on  degrade religious customs without properly  understanding them. Some people say growing tulasi at home is for religious symbol. Actually few Western scientists are conducting  large-scale trials to confirm the benefits of tulsi leaves, including its anticancerous effects. If our aurveda says Kakara (bitter gourd) is good for madhu meha, the so-called  pseudo-scientific people will laugh. But,  some  colarado scientists declared recently that kakara(bitter gourd) cures diabetes and  pancreatic cancer.  Is there any name for the present day pseudo- scientists, whose priority agenda is to discard religious values and ancient knowledge without properly understanding them..? It is becoming a fashion to elevate our scientific value by degrading culture and religious values.  True scientists try to explore, understand and experiment  while Pseudo scientists try to project themselves as scientists by constantly criticising and show intolerance towards the religious values and ancient knowledge.
Just to share a recent news clipping about kakara (bitter gourd):
http://archives.eenadu.net/03-14-2013/news/newsitem.aspx?item=story&no=5
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Monday, March 11, 2013

NTR's awesome performance: Praying for Lord Shiva

NTR's awesome performance: Praying for Lord Shiva
in the movie, "Seetarama Kalyanam", produced and directed by him.  After the siva tandava stotram, the performance of rudraveena is even more spectacular.
Part 1 : siva tandava stotram
Part 2 : Rudra veena

Wednesday, February 20, 2013

A Distressing day

A particularly distressing day for me...got into tears after reading the Sri Lanka episode... Let it be any country or race, why people become so brutal towards  fellow human beings...? why should people kill others? couldn't they find ways to resolve the issues with peace? why sadism is ruling the minds? we blame bacteria and viruses for killing the people...and spend millions of dollars to find a cure. who will finance the cure for sadism ? will there be any cure at all....for the greedy, who destroys his own race? What happened to all the rulers who thought that they are immortal? Does anybody has a right to take other's life lawfully or unlawfully? whose life is permanent?! why can't we keep our transient stay on this earth peaceful and cohesive?

Sunday, February 17, 2013

Geeta Makarandam

Listening to the commentaries by sri vidya prakasanandagir swami on Bhagavadgeeta (Geeta Makarandam):


One devotee is praying to Lord Krishna
(in sanscrit : Ksheera sara mapavrutya sankaya sweekrutham yadi palaayanam, mamake mama ghanadha tamase...nanda nandana kadham naleeyase..!) :

క్షీర సార మప వృత్య శంకయా  స్వీకృతం యది పలాయనం ..
మామకే మమ ఘనాన్ధ తామసే  నంద నందన కధం నలీయసే..!

 O Lord Krishna, after stealing butter if you are looking for dark places to hide (to hide from Yashoda), you can happily hide in the darkness of my mind (filled with ignorance).



Wednesday, January 30, 2013

Simple....extraordinary...!

Just listening to a commentary on Bhagavadgeetha by Vidyaprakasandagiri swamy. In a context, he mentions the following quote (author unknown) :
"A great man is not the one who does extraordinary things, but who does ordinary things in an extraordinary way...!"
I remember a similar quote from Mother Theresa : "We need not do great things but little things with great love".
These look simple  but carry a great meaning. And if followed, they bring about a great impact on our woking nature and the result such work brings. 

Saturday, January 12, 2013

Humanity..? where are you..!

Entire nation erupted over brutal rape and murder of  Delhi girl...And will the Nation responds to the painful facts revealed by the friend of the Delhi girl?!
certain things..better not said here...lighting candles..shouting slogans to punish the suspect....propose various forms of punishment...all happen..but, little attention will be paid to modification of human behaviour to help the needy in time (and the law/rules contribute to inaction... it is more important to bring about change in attitude of police and public. ).
Sometimes, help denied in time or delayed, will be more grievous (physically and mentally) than the crime itself. A change in human behavior is needed more importantly than to suggest the law various killing methods or methods to make the criminals impotent...Law will give necessary punishment. No comment here. But, when it comes to change in our behavior to help others, we always think that the other person/others in society are responsible for it... we conveniently ignore our role..we expect somebody else or the system to change..without contributing ourselves anything to the change. we get immense energy to put blame on others or the system. But, we forget that we are also part of the system.
Change in the individual level  is reflected as change in the society.
Humanity...where are you? please come out from the shades of the lighted candles...come out from the silence hiding behind the aggressive slogans...!
And Humanity, please prove that you really exist persistently and not just in the temporary emotional outbursts occurring  episodically...!

Friday, January 4, 2013

Happy new year ...?!

Happy new year...yet it sounds odd to me...what extra happiness we can derive by changing the calendar.. from tomorrow, it will be just the same again..waiting for another new year...another birthday.. or another 'reason' to celebrate....it always surprises me....! anyway, if I comment like this, it may appear cynical........ But, Infact, for me, every day, or every minute is a happy one.... We should be happy to be able to wake up alive each day....thank God for giving another day...to do the things we like..to help others......we should "live" and love every moment. And every moment should be a celebration...towards emotional enhancement...!