Tuesday 24 December 2019

Spilling the guts with the gut-brain axis

The relationship between our guts (intestines) and brains can be seen through the phrases used in our daily conversation from spilling our guts to having the guts to do something. Most people are also familiar with how mental states like nervousness can lead to gastrointestinal (GI) discomfort. It has been recently shown how this connection is much more than just an upset stomach before a major interview or exam.

There is a separate branch of nervous system that is present in the GI tract called as the enteric nervous system (ENS) that can function independent of the brain and the spinal cord (Central Nervous System or CNS). ENS also has connections with the CNS via a specific nerve called as the Vagus nerve. The major function of ENS is to make sure that the GI tract muscles can contract and relax so as to ensure a smooth passage for food along with the timely release of gastric juices and enzymes that aid in digestion. ENS send signals to CNS via Vagus nerve and usually they go unnoticed by us unless they are causing a feeling of nausea or bloating. The intestine is also host to a wide range of microrgansisms that include bacteria and fungi. Surprisingly, our bodies have more bacterial cells than normal body cells, which together constitute the microbiota. The specific types of bacteria that are present in the intestines constitute the gut microbiota. 

The exposure of brain to toxins can affect the ENS and vice versa. Many of the disease causing pathogens can enter the brain via this gut brain connection i.e., the vagus nerve. Besides pathogens, other molecules can enter the brain via this connection. This is also evident in the infectious brain degenreative diseases like Creutzfeldt-Jakob disease and spongiform encephalopathy (brain dissection on autopsy show spongy structure), where the infectious protein particles enter the brain utilizing this very connection.
Recently it has also been shown that the gut bacteria can affect the development of certain other diseases like Depression, Anxiety, neurodevelopmental disorders like Autism and neurodegenerative disorders like Parkinson's Disease (PD). This is a surprising finding because it changes the way we look at many of these CNS diseases. 


But how do diseases like anxiety and depression occur due to the gut microbiota? These bacteria release substances that influences neurons and affects levels of different neurotransmitters in the brain, which have the potential to modulate our mood and behaviour. Although, the exact mechanisms are still not clear. Some of the known mechanisms and proposed hypotheses are:

1. Infectious protein particles enter brain via gut, as described above. Braak hypothesis suggests that infectious pathogens can enter the brain via the gut brain connection (like the Rabies and Polio virus) and can lead to death of neurons as seen in PD and AD. 

2. Leaky gut suggests that the epithelial lining of the GI tract is not intact which can lead to entry of bacteria, and other macromolecules into the brain. This is suggested as a possible mechanism for the development of Autism.

3. Certain bacteria affect stress circuit in brain.
The first study that showed gut microbiota can affect the brain, showed how stress response was affected in rats. It was found that the GF rats, which did not have any bacteria in their gut (called as germ free or GF rats), were more stressed.

4. Infection and inflammation of the gut
Specific bacterial infections of the gut have shown to result in inflammation of the gut followed by increased anxiety. This again was experimentally studied in rats.

So, there are still human studies lacking which would show that these proposed mechanisms would be true for us. Thus, there is a potential for the gut-brain connection to be a diagnosis cum treatment cum prevention site as can be seen by the following examples:

1. Early diagnosis 
For diseases like Autism and PD it has been shown that there are GI symptoms present in many of the patients. For many PD patients such symptoms are present even before the classical CNS related symptoms of PD emerge. Thus the assessment of GI symptoms can help in early detection of neurodegenerative diseases like PD. 

2. Potential treatment
Since, now we know that gut microbiota can influence these diseases, it is possible to use it to our advantage by providing the kind of bacteria that would help in reversing the symptoms. This has been shown by reversing some of the sypmtoms of Autism that were considered to be irreversible. Treatment for anxiety and depression are too looking in this direction for alternatives other than the current drugs in use.

3. Prevention
The most exciting discovery would be if we can prevent some of these CNS diseases from occuring in the first place by altering the gut microbioata of the susceptible individuals.



Does this mean that taking all those probiotics is going to acually save you from developing devastating neurodegenerative diseases in old age? To be honest, there is a lot of research that would go into creating the kind of probiotic that can someday be a cure for all sorts of diseases that we are fighting today. For now, its just a safe precaution to keep your gut healthy (by eating curd and avoiding unnecessary antibiotics) and wait for that day to arrive!

Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5005185/

Sunday 22 December 2019

When Dr. Mann took data fabrication to outworldly levels!

Why do people cheat? What compels them to fabricate data? Guess, both these questions would have to be addressed in separate ways to come to a final conclusion as to what really motivates people to do such deplorable acts.

I'd like to start with Dr. Mann's testimony from outer space. He arrives at this new planet where he was hoping to find life, but to his horror it is uninhabitable. The hero who prepared to embark on this mission to sacrifice his life for a billion others suddenly wants nothing else but to survive and for achieving that he does what no other human or man has done in his lifetime, to fabricate data not from Earth, but from outer space, just because he can breathe once again or get a chance to live. What might have gone through Mann's mind while doing this? He was saving himself. What is more important than that? Survival justifies all that we do, dictating our morals even though we may hide behind the fragile curtains of religion.

Dr. Mann forgot his mission when his life was in danger, but the scientists here on Earth what makes them forget their mission to begin with. I wonder do they even have a goal to begin with. On second thoughts, maybe their goal is to succeed in life without giving any consideration to morals and ethics that are required to be a scientist.



Shouldn't there be an oath just like the Hippocratic oath for scientists? I, would be or current doctor, would take it as my duty to not to get seduced by the easy way of fabricating my own data, but would instead work hard on getting that p<0.05 with proper controls and sample size. Or maybe if we can add a passage or two in Bible, Gita, Quran and the other holy books that thou shall not make your own data and tailor your images unless you want to go to the eighth ring of hell added especially for such evil doers by Dante on special request. Although, we do have our legal system in place working hard to persecute the wrong doers, who might get missed by Karma and Satan.

With these special measures in place would make sure that the future generation of scientists wouldn't fall into the temptation of these acts. But what really is motivating these people to go to these lengths and breadths to do it in first place. Let's look at the different categories these people might fall into.

1. The Victimized. They are being influenced by higher authority, in that case the question turns to this higher authority's purpose.

2. The Ignorant. They don't know what they are doing. Ignorance and innocence aren't equal.

3. The super-smart squad. They think this is smart way to work around the hard work of spending long hours in the lab.

4. The person with influence. No wonder, what had brought them inside was not their own talent, but a phone call. The question then turns towards the entire hiring committee and their morals.

Whichever category they fall into, they have something in common and that is the fear to fail in the job that has been given to them by a supervisor or to a supervisor by the university or by their own minds. And like Yoda says fear drives you to the dark side.

Ethical questions also encompass senior scientists' and the heads mentality to not just harass but also to influence, but those are topics for another post and for another day.

Wednesday 18 December 2019

Why do different people have different voice?




Once upon a time there were two jungles. In one jungle lived birds that all sang the same song, and in another jungle each bird had a unique song. In the first jungle, Coco, the female bird decided to live. It needed a partner to raise a family. So, Coco decided to find the partner by listening to the song that the birds sing. But all the birds sang the same song. Now Coco got confused, how does she find a partner to raise a family. She got so confused that her brain short-circuited, and she died. Only if she visited the second jungle. In this second jungle Coco’s friend Nora had gone. After spending a few days there, Nora heard a song which she liked, she then met the bird who sang this song and she knew she had found the one for her. After Nora sent word around, other female birds started coming to this second jungle. And soon there were new families, new baby birds hatching in this jungle. Now, the father bird took up the responsibility to teach these young birds their unique song so that they could carry on the tradition.



In the caves nearby, lived the early man who still had not learned how to speak. Language with words still had not been discovered. But the early man had learned to make sounds, each person had started keeping birds from the second jungle and they learned from this bird how to make sounds. This was because the birds in the first jungle were all dead. Otherwise each early man would have had the same bird and would have learned to make the same sound.

When the God of sound saw this, she got amused. She made a new plan for man. She was sure that man wouldn’t be able to pet these birds for long, as the birds had their own life to live and they would fly away back to the jungle. She, therefore, made all men of different size, some small and some large, some thin and some fat. She made some men with a long nose and some with a big throat. She made some men have a small nose, and some have a small throat. Deep inside the throat she also made changes to the box that made sound, so that each person now had a different box size.
After a few years the birds flew back to a new jungle, leaving men to live on their own. But the sound god had gifted them with different voice boxes and so now each of the man and woman also had a different voice. They did not need to learn from the birds now. They all had a different voice. This made life easier for them.



As when the man came back to his cave, he would knock three times and make his own special sound. The woman and the children would instantly recognize that it was their man and they would allow him to enter. Now, if all the men had the same voice, would the woman and children recognize their man. No! They would let an unknown man enter their cave, who could take all their wools and fruits. This would starve them to death. This was the biggest advantage of each person having a different voice.

The Science behind it:
Voice is produced by the voice box that is present in the throat of each person. Every person has a different voice box. Now think of a mobile number. Imagine that different numbers are represented by the size of mouth, nose, and throat. Again, each person has a different mouth size, nose size and throat size. Together these different mouth, nose and throats create a different voice number for each person. The voice number decides how a voice would sound, which makes different people have different voices.

This story was written to answer the question of a small kid who wanted to know why do different people have different voice.

Wednesday 11 December 2019

How pain brings depth to our thoughts?

Ever wondered what is it in pain and agony that stirs creativity in humans? Why do most great artists, poets, writers and musicians are the ones that suffered from depression? Why do we better understand songs' lyrics when we are sad? Why do you write or draw better when in pain? What is it in pain that provides extra depth and dimensions to our thoughts and the outcomes that are generated by such a mind are much more asthetic?




To do any task at hand what we require is complete attention towards it. Attention is controlled by specific region of brain called Locus cerulus. As we grow this control becomes all the more absolute, so unless this brain center is engaged we cannot pay attention to a task. What controls this center is the reward pathway, which makes us more attentive towards things that activate our nucleus accumbens (reward center of brain). Thus, there exists a bidding inside our brain for attention, whichever task gives the most  reward would win the attention and the attention center in turn.

Let's see how we behave in different emotional states. Although, each person would behave in a different  manner, but some of the below paths might seem to be possible in majority of individuals.

In say a normal state, which is devoid of any emotions, the basal level of activity is achieved by our minds. We give our best to whatever task we set our attention to.
In a happy or excited state, our minds are a little distracted. We keep on thinking about the stuff that makes us happy, as it is a rewarding and pleasurable state. In excitation, again the mind keeps wandering to the reason behind that excitement.
When sad, and especially when we are lost how to best describe our pain and when direct words fail we look for alternate ways of expression. It is in these times as our minds are fixated on a single task, we do better than even our best.

Although, all the studies that have been performed so far to pinpoint the direct effect of mood on creativity have obtained contradictory results. While some found that positive mood like a state of happiness and elation enhance creativity, others saw similar results for sadness and depression. Amongst these one study stands out, which highlighted the dymanic role of emotions and found how exposure to negtiave mood followed by positive mood lead to extraordinary burst of creativity. Why haven't the researchers found a link between sadness and creativity?

1. Not everyone would be utilizing their mental agony to creative pursuits.

People who use creative outlets to express their emotions can train their mind to create neuronal networks in their brain wherein the sadness can keep their attention to creating stories or paintings or music. It's like their attention is then wholly devoted to creating in the attempt to escape from the real world generated emotions. Most of us use entertainment to escape the reality, but there are people who find an escape in creating and these are the ones that have learnt to use their pain to paint the most stunning of paintings or to weave words in magical stories. So, it all comes down to how you train your mind.

2. The measures of creativity would be realtive for each individual.

Not everyone is as creative to the same extent. And creativity for each person is reflected in different aspects and tasks. The best approach is to measure the level of creativity for the same person under different emotional states. Comparing different individuals and with a reference level of creativity would not show the true effect. It is a generalized effect whose level would be different amongst different individuals.

3. We still do not know the brain pathways and specific brain regions that are involved in generating creativity.

Recent studies have been uncovering secific brain regions and pathways that work together to generate creativity. Maybe we require not to find a neural network with physical location in the brain, but another approach to study the workings of creative thoughts at the cognitive level.

You can read more about factors that affect creativity:
and the anatomical correlates of creativity in the brain:

Friday 6 December 2019

The lost Mo



Mo had never seen the world out there. His curiosity got better of him the other day and he decided to venture out on his own. Leading its way through the wilderness, it came to stop to admire the beauty around. There were such beautiful patterns being created around him by the bushes and tendrils. He had never seen anything so awe inspiring in his life. It was like all the stars of the galaxy had got connected with each other in this small jungle where Mo was born. He kept looking from side to side looking at the thick and thin tendrils, a sense of loneliness entered its mind seeing all the bushes and trees around him connected like that. He longed for a connection too. Thus, he started further on his trail to look around himself with melancholy, which made the entire place even more beautiful to his senses. The shapes of the trees varied, but nonetheless their glory preserved from one tree to another like they were breathing too, just like Mo.

Walking to a stretch and coming to a fork, Mo didn’t know where to move now. A new sensation of a need to get something to let its body feel nourished was arising inside but he couldn’t make sense of it because it had never felt hunger before. It took some time for him to make sense of hunger and its purpose. After a long thought about what to do to satiate this hunger, he thought of taking a bite out of the succulent tendrils around him. That indeed was satisfying, he felt his strength increasing. He moved on through the grasses and bushes, making a new way for himself as it moved. Suddenly, he felt the ground tremble that made him stop. He entered the nearby crevice that it could see and sat there without any movement for long. It lasted for a minute and all went to as before.

Soon, Mo was comfortable in venturing out to nearby area. Each day was a new one as he kept feeling that the paths kept changing, even though he had marked short cuts; he used to get lost each day. His daily losing his way back to his comfortable spot did not deter him from starting each morning to search a nearby path.  But the loneliness remained with him, it made him more determined to search for a mate in this wilderness. His naivety did not let him become hopeless in his search. And soon it paid off.

How extraordinary it is to feel something for the first time! Mo had not known this is what he was looking for, another being just like him. Suddenly, the ground started to tremble again. As he moved on this time without stopping, he saw not one but multiple beings just like him in a clearing. It was the best moment of his life and the worst.

Amidst the thickness of the dense bushes and tendrils there was a creature lost.


Inching towards the depths of the unknown paths that had never been tread upon.
Coming to a destiny that is ever so hard to be predicted, and still worthy to live on.
Nothing can be harder than finding a purpose in this life.
It only gets more harder when it causes the end of the hive.



The ground kept shaking, only it wasn’t the ground but this little girl who was trembling from head to foot again. These seizures had not stopped since the last week and were getting only worse. They were in the hospital now; the little girl being treated for a case of taeniasis and her parents surrounding her with looks of utter shock and concern on their faces for what and how this happened to their child.

Wednesday 4 December 2019

From junk to jumps! How can we make sense of the junk DNA?

DNA is the code that is responsible for storing the information of life. Genes are functional units present in DNA that makes up proteins. It thus can be thought that the more complex an organism, the more number of proteins it would be making and so more the number of genes present in its DNA. The size of DNA does vary amongst different species, but a simple correlation with respect to complexity of an organism and the size of its DNA does not hold true. This brings us to one of the long standing paradoxes of Biology, the C value paradox.



What is C value? C value represents the amount of DNA present inside a single cell. Multicellular organisms have multiple copies of DNA inside their cell, being diploid (2 copies), tetraploid (4 copies) and so on. C value refers to the size of DNA present in a single copy of DNA inside a cell.

What is the C value paradox? The complexity of an organism and the C value do not correlate. Less complex organisms have much more DNA than more complex organisms. An example is the onion that has 5 times more DNA inside its cells than present inside a human cell. 

How can we explain the C value paradox? Although the C value paradox has not still been resolved, but there have been certain revelations that can help us in solving this mystery.

1. Not all of the DNA codes for genes. 
It was found that only 15-20% of human genome codes for proteins. The remaining 80% is composed of what is called as junk DNA, which does not produce proteins. 

2. Junk DNA is not really trash.
There are multiple jumping genes called as transposons present in the junk DNA, which can serve as designers of mutations and lead to diversity that arises amongst different organisms of a species. These transposons can move from one site in the DNA to another, termed as jumps and if they happen to land up in a gene then they change the sequence of that gene. The sole purpose of these jumping genes is to replicate and survive, irrespective of their host DNA and the need of the host.

3. The code is encoded.
The junk DNA also contains elements that can control expression of genes, acting as switches that can switch on and off genes. These include what is called as epigenetic factors and provide an encoding for the expression of genetic code. Recent attempts have found that 80% of the DNA is composed of such functional units. 

Still all these above facts do not explain or resolve the C value paradox, but what can be drawn from this information is the following:

1. The presence of functional units in DNA points out towards the gap in our understanding between genes and how they are expressed. It is thus required to probe for similar units in other species' genomes.

2. The study of evolutionary processes that created the encryption that is provided by epigenetic factors would provide insights into how these evolved and is possible might also resolve the C value paradox.

3. There could be a function of the remaining junk DNA besides jumping genes and functional elements that we still have not figured out yet. One such possible role is in creating structural support to the DNA.

Thus, there is more to DNA than just genes and it is still a mystery that is awaiting to be solved in times to come!



References: