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Biology Park

The bodacious cop – Constance Kopp

I am a big fan of books featuring strong female leads. Of late, I have been excitedly following the life of Constance Kopp, a reluctant farmer turned cop from Wyckoff, New Jersey.  She and her sisters more or less live a quiet life on the outskirts of Paterson, NJ with no close neighbors until their buggy gets hit by a motor car driven by a rich thug. When Constance repeatedly but politely demands in writing that he reimburse her family for the loss of their only mode of transport, he chooses not to. She finally decides to ask him in person but when he refuses again and threatens to harm her little sister, Constance does not hesitate to take him by the collar and threaten him back!  This only enrages him more so he along with his friends start intimidating the sisters. I could imagine how difficult it must have been for women in the early 1900s to live by themselves as everyone is always wondering why, judging the prudence of the decision and thinking that anything that happens to them is because they deserved it. While reading the challenges they face, I kept thinking that for many women around the world, the situation still remains the same almost a century later!

Due to their troubles, the sisters get introduced to the sympathetic and emphatically duty bound town sheriff who offers them protection. He takes it upon himself to teach Constance how to use a gun, encourages her to press charges against the culprit-in-chief and helps her doggedly pursue him. The first book titled “Girl waits with Gun” is amazingly written and although the situation for the ladies is difficult, there is plenty of humor and Constance is a super cool woman. In pursuing this rich thug, she discovers her knack for detective work and is really good at it too. She takes lead, makes smarter choices and thinks to look where others don’t and succeeds (Yes!!). A well-built woman, she is not afraid to chase after wrongdoers and catch them – all while wearing a corset, long flowing skirts and uncomfortable shoes :). All this work gets her the job of a ‘deputy sheriff’.

In the equally colorful and adventurous sequel “Lady cop makes trouble”, as the sheriff works to get her a deputy badge, Constance works as the jail matron. She is very good at that job too but yearns to get her badge soon and officially do detective work. Back in 1915, she was one of the few women working in law enforcement that were actually paid a salary, allowing her to support her family. It would be no easy task for the sheriff to convince the county officials (referred to as freeholders in New Jersey) that a woman deserves to serve in the police department much less as the deputy to a sheriff, a job considered totally inappropriate for a woman (although many men in the department were less than capable and did not have much training). The 37year old Constance often gets referred to as the ‘girl’ in the press. Even when she catches a culprit after a chase and a fierce fight (see image below), some of the papers of the day take it upon themselves to make her actions read lady like. Take for instance the headline “Girl deputy sheriff “pinches” a minister!”. The report goes further to completely change what really occurs and publishes that “she stepped up to a husky well-dressed man in front of Borough Hall and tapped him on the shoulder”. Constance takes these in her stride and continues being a totally bodacious cop!

lady-cop-drawing-of-constance-fighting-von-matthesius

Last year, I was looking at NPR’s book recommendations and chanced upon Amy Stewart’s “Girl waits with Gun”. Amy Stewart’s descriptions of Brooklyn and the suburban areas in the early 20th century and the factual notes of Constance’s life and times, are all a treat for the reader. Both the novels she has penned in this series are absolutely delightful. Constance Kopp is one cop you want to read about 🙂

For more fun details:

Amy stewart’s website on the characters featured in the books- http://www.amystewart.com/characters/

What could possibly be common between killer whales and humans ? Menopause!

Female killer whales apparently live for about 60 years after the end of their reproductive life (totally about 90-95 yrs). Why do they stop reproducing in the first place? That is a central question in this new study (1). In many mammalian groups, once a male reaches reproductive age, they mate within the group and then leave. In the case of apes, the females leave instead of the males.  But Killer whales have unique kinship dynamics or group architecture. Here neither male nor female killer whale babies (brothers and sisters) leave their group after reaching reproductive age and about 2-3 generations of them continue to live together led by the original mom whale. The males however mate outside of their group.

In this study they looked at two groups of whales (n= 200) and find that the relatedness between males and a female in a group increases up until she reached reproductive age (as predicted by a previous study). But after that, it declines steadily because the males, although they live in the same group, die around 30 years of age! The relatedness between females remains constant throughout their life span as they are born in the group and do not leave it and also as mentioned above, live twice as long as the males after they stop reproducing. Based on the unique group dynamics of whales compared to mammals and apes, the authors make predictions about why menopause might occur in females. According to this, if females were to increase their reproductive capacity (fecundity) with age, then they would be competing with the younger females in the group for food (foraging and sharing of salmon), contributing to conflicts over collective movement and not able to effectively assist their male progeny in successfully mating outside of their group. Very interestingly and seen in many human cultures around the world, the mom likes to share food with her male progeny preferentially as she wants to ensure his reproductive success. So with increase in fecundity, the female will also be required to invest more of her energies in competitive efforts and this will indirectly affect the well-being of the entire group for the above mentioned reasons.

They test this prediction by observing the intergenerational conflict in the two groups of 525 killer whale calves from Washington state, US and British Columbia, Canada. They define intergenerational conflict as when mom whale gives birth to a calf within 2 years either side of the birth of a grand-offspring. Pregnant mothers require more food and resources during gestation and lactation and so their definition of intergenerational conflict is supposed to represent these periods of highest conflict for food and resources. As predicted, they found that when mom and daughter are in intergeneration conflict, the mom’s calf (sibling of the daughter) has about 1.7 fold lesser chances of survival compared to her grand offspring. They explain that this could be primarily due to food and resource sharing in which the younger mothers might be at an advantage in competing than the older mother who has to share not only with the new born but also with her male offspring from before if any.

inter_generational

Among the calves that are born in intergenerational conflict, they found that the first born calf has a slightly higher chance of mortality than the later born calves. These second born calves take advantage of having two lactating females around while that benefit is unavailable to the first born calf in intergenerational conflict. Another study previously showed that grandmother killer whales provide leadership in times of food scarcity and also salmon foraging knowledge to their offspring and these might be additional benefits that the group gains (2). However, the authors of this study believe that this knowledge-sharing benefit alone has been insufficient to explain why other mammals like elephants that do the same thing continue to reproduce till the end of their lives. Based on their findings, they suggest that given their unique kinship dynamics, and as a result the intergenerational conflicts that arise in food and resource sharing, killer whales could have been selected to experience menopause.

I cannot imagine how exhausting and difficult such a prolonged study following hundreds of whales would have been but the results are interesting simply because killer whales are among the very few (3 including humans) animals that undergo menopause and live long lives after. Why were we selected to go through with this? This study presents a glimpse of one possible reason ‘why’ in killer whales but leaves us wanting to explore more, especially in humans.

References

1. Reproductive Conflict and the Evolution of Menopause in Killer Whales

2. Ecological Knowledge, Leadership, and the Evolution of Menopause in Killer Whales

Pregnant? Get ready to lose a bit of your brain!

Two and half years ago, as I was getting ready for labor, I asked my attending nurse how long she thought it would take for the baby to finally make an appearance. She said she has seen a baby pop out in 20 mins or sometimes take 3 hours or more! I had hoped and prayed that I would be the 20 min lucky mom. After 3 hours of pushing and finally going through an emergency caesarian section, the upper limit of my nurse’s experience turned out to be mine as well. I was relieved, physically drained and thought is there any part of my body that is not bloated beyond recognition now? So when I recently read an article in the Science magazine about a new paper that for the first time shows how women’s gray matter is significantly reduced after pregnancy (1), I was very intrigued.

The authors preface this study by sharing that other studies have already shown that significant physiological changes in the female brain result from changes in the sex steroid hormone levels upon attaining puberty.  The focus of this study is the second time such hormonal changes occur in a woman – Pregnancy. What they measure here is Gray Matter (GM) volume using a Magnetic Resonance Image (MRI) scanner. So what is gray matter? Very simply, it includes various types of cells and cell bodies that make sure the brain is able to function well. Basically they are measuring any changes in the density of cells in the various regions of the cerebral cortex of the brain (see Fig.1).

cortex

Fig. 1

In 25 first time mothers they tested, they saw a significant reduction in GM volume post pregnancy compared to their pre pregnancy measurements, and that of women who never became pregnant during the course of this study (5.25 yrs). Their study included women who naturally conceived as well as those that underwent fertility treatment to become pregnant. The GM volume changes however were consistent among the women who became pregnant, no matter the method of conception. The consistency in GM volume reduction was so high (95%) that they claim they could predict whether a women had undergone pregnancy or not between MRI sessions just by observing that measurement alone. Interestingly, changes in GM volume were only seen in the mothers and not their spouses. So even though fathers have the knowledge of an upcoming child, their brain does not undergo the same physical changes. As mentioned above, GM consists of various different types of cells that perform different functions and as the authors point out, MRI data cannot provide information on which constituents of gray matter are undergoing a reduction as a result of pregnancy.

So what if the GM volume decreases? The areas in which they saw a decrease in GM volume overlapped with the same areas that fired when tasks defined as “theory of mind tasks” are performed (as defined by two other independent studies). Theory of mind tasks include a whole array of tasks that require the brain to assess the mental states of other people (2). In this study, the subjects were asked to look at their baby’s picture and a picture of an unrelated baby, and the areas that fired were within the regions that showed GM volume reduction, especially when the mother looked at pictures of her own baby. They also made mothers fill out Maternal Attachment Scale questionnaires for the first 6 months after birth and found that they could closely predict the quality of attachment between mom and baby based on the reduction in GM volume. Overall, they suggest that their experiments provide a peak into how the mom’s brain is altered possibly in preparation for motherhood and better interaction with her baby.

Mothers often joke that one of the side effects of childbirth is a reduction in memory. Going back to my job as a post-doctoral researcher was therapeutic for me and I felt that my mind worked more efficiently. In this study the moms were made to take various cognitive tests and to my relief, the authors found no significant change in the moms’ performance on the memory tests before and after pregnancy 🙂 . So ladies, yes our brains change but according to this paper, most likely to prepare better for our role as mothers and not to make us forgetful and absent minded!

Changes in the GM volume in almost all of the regions persisted two years after the birth of the baby in the mothers they were able to follow up with. Although there were no further reductions or increases in these areas, this was an interesting finding that these changes sustain long after birth of a baby. Some of the mothers that participated in this study had another child within the two years of their last MRI session. Although they did not participate in the follow up session, it would have been interesting to see if the GM volume changes were any different in these mothers.

From the results observed in the fathers who participated in this study, it might seem that the brain transformations are dependent on the biological hormonal changes associated with pregnancy.  But what kind of changes occur in adoptive mothers? This paper does not touch on that. Since menopause is the third time that a woman’s body is subjected to big hormonal changes, it would be very interesting to learn more about how and if brain undergoes another physical transformation in preparation for that phase of life.

References

  1. Pregnancy leads to long-lasting changes in human brain structure (http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.4458.html)
  2.  Fractionating theory of mind: A meta-analysis of functional brain imaging studies –  (http://www.sciencedirect.com/science/article/pii/S0149763414000128)
  3. http://brainmadesimple.com/cortex-and-lobes-of-the-brain.html

Lab Girl : The journey of a Tree and Hope

Lab girl by Geobiologist Hope Jahren is one of the best books I have read recently. There are many reasons I enjoyed the book and I will discuss some of them in the review below.

Jahren starts off her own journey side by side with the journey of a tree starting from the seed stage. These are some of the best parts of the book. Fascinating and rich with wonderful details, these chapters are beautifully written.

A seed knows how to wait. Most seeds wait for at least a year before starting to grow; a cherry seed can wait for hundred years with no problem. What exactly the seed is waiting for is known only to that seed. Some unique trigger-combination of temperature-moisture-light and many other things is required to convince a seed to jump off the deep end and take its chance – to take its one and only chance to grow.”

She writes about this lotus seed that waited for 2000 years to take its chance! There are many more really interesting nuggets she discusses as the seed takes each important step in its growth period. As I read these chapters and followed the seed’s journey from germination to sprouting roots, forming the first leaves, making food, fighting enemies, looking out for its friends all while blossoming into a whole tree, I painted such a vivid picture in my mind. This picture continues to stay with me and has made my mind go back to the book every time I stop to look at a tree. I think that is a great achievement as a writer to make readers think of the book and what it has to say for a long time after you close it!

Hope Jahren is a remarkable person and while reading her travails and successes navigating the research world, I found myself often recalling a similar instance(s) while doing my own research work.  For instance, she describes how she felt when she used X ray diffraction to identify the mineral in the hackberry pit that she was studying and the feelings she experienced upon discovering it.

“Until I phoned someone, the concrete knowledge that opal was the mineral that fortified each seed on each hackberry tree was mine alone. Whether or not this was something worth knowing seemed another problem for another day. I stood and absorbed this revelation as my life turned a page, and my first scientific discovery shone, as even the cheapest plastic toy does when it is new.”

This feeling was my own drive to do research with all its ups and downs. Even if the discovery from an everyday experiment may not be entirely new, aspects of it are still yours and that is a special feeling. It was my feel good drug and kept me going especially when many other experiments would routinely fail!

Jahren’s struggle with Bipolar disorder was hard to read. Of late, I have been reading a lot about the disorder and watched a few movies where I could see how difficult life can be for people suffering from it. She writes this chapter as just another part of her life and I deeply admired the courage it takes to do that, to make peace with it and accept it.

I enjoyed reading about everything that she went through with Bill, her friend, partner in research and also in every other crazy adventure. Bill is an extremely intelligent, skilled and eccentric researcher. I had mixed feelings while reading the many colorful episodes Bill and Hope go through together. At times I was rooting for them and during others I was baffled! Although there are many things I felt I would do differently from Hope Jahren, I found plenty to admire about her. I have come to realize that women should and must find qualities that we can appreciate in each other. I find that we are often our first and harshest critics (including yours truly).  It may be hard but if we don’t find it in us to see the good in other women, even those we disagree with, then it is going to be even more hard to crack any glass ceiling!

In summary, the book is beautifully structured and the juxtaposition of a tree’s life with Jahren’s own was a very interesting idea and it works here. Of course there are things I still wanted to know more about. For instance, although she does touch on her work-life balance, I wanted to learn more about her struggles of having a flourishing and demanding career and having a young child at the same time. She does say “I will not be this child’s mother. Instead, I will be his father”. I loved that statement! I have always felt that women including myself carry around a guilt basket about not being good enough mothers to our children. Jahren carries it too. However, just reading that statement in the book was oddly relieving. I also wanted to understand why she drifted away from her family, especially her mother to whom she dedicates the book and everything else she writes. Oh well, may be in the next book!

I encourage everyone to borrow/buy “Lab Girl” and hope you enjoy it as much as I did. Write me your thoughts!

A time to write!

I am Lakshmi. I am a researcher and an instructor. I am also an avid reader, love music and cooking. As a researcher, I wrote a lot of technical stuff and it was an enjoyable exercise. I love to learn about new topics and write about interesting and complex science and make it accessible to everyone.

If you are visiting, hope you check out some of the posts and leave a comment.

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Of genes and humans : Tracing the history of the Gene world

In “The Gene”, Siddharth Mukherjee begins with a personal history of his family’s struggles with bipolar disorder/manic depression and he embarks on a quest to make sense of it by unravelling the story of genes and their profound influence on human life. From Pythagoras’s  theory of ‘spermism’ according to which, man provided the potion that magically formed a baby in the woman’s womb whose role was merely to nourish and give birth, we get treated to the various theories that were formulated, disproved and rediscovered. The first chapters trace out the history of ground breaking discoveries before and after what we now know as “Genes” (I think of these times as BG and AG!).  Siddharth Mukherjee’s writing style is very engaging and it is remarkable to rediscover the history behind these discoveries that I read about in text books. It describes in good detail the struggles, disappointments and the ridicule faced by many scientists who made great strides in giving shape and structure to genes. I particularly enjoyed these parts that are peppered throughout the book.

Once scientists knew the structure of genes, it was tantalizing to think of ways to manipulate them.  Gene cloning allows one to cut and paste two completely unrelated pieces of DNA and make multiple copies of this new DNA. This is a procedure I have done countless number of times as a researcher and it works beautifully. However, when gene cloning was a new thing in the 1960s, crucial parts of this process were being worked on by different investigators asking different questions and they needed to come together to allow for successful manipulation of genes. Of course once you know how to manipulate genes, what next? These questions were highly debated by scientists and members of the larger society at the Asilomar Conferences (1973 and 1975) held in California. The debates that ensued in these meetings were contentious. There were doubts expressed, accusations hurled and potential for lawsuits discussed. But somehow at the end of it all, self-imposed regulations were formulated  by a small group of scientists that surprisingly most attendees agreed to adhere to. Gene cloning gave birth to the Biotech industry and transformed human lives forever. Siddharth Mukherjee revisits few of these raging biotech successes by writing an exciting account of the race to make human insulin for diabetic patients and recounting the painful reasons that motivated scientists to manufacture Clotting factor VIII protein for Haemophilic patients.  Many discoveries since then have allowed us to manipulate genetic information in various interesting ways helping us unlock and decipher the entire genetic information contained in an organism.

The ‘Gene’ presents us not only with these amazing scientific advancements that helped shape our understanding of genes and the science behind trait inheritance but also devotes significant time to exploring the larger consequences and impacts of these on society, pushing the reader to pause and think. Back in the 1920s, the knowledge that your genes make you the way you are unleashed a spectrum of interpretations. It led to the idea of “Eugenics” the basis of which was to have a society devoid of ‘genetically unfit and inferior’ humans.  The proponents of Eugenics defined vaguely what constituted ‘unfit and inferior’ and proceeded to categorize men and women, isolate and banish them into colonies and force sterilize women while selecting for ‘fittest’ humans. They believed they were merely applying genetic principles and ‘accelerating the betterment of human race’. Eugenics motivated Hitler and his advisers to pronounce superiority of the Aryan race and to order one of the worst ethnic cleansings in history.

A whole range of ethical questions will continue to be posed to scientists and the larger society as genetic information continues to be unraveled and modified with new technologies. Knowledge of your genetic make-up is powerful information. What if we could use this knowledge to alleviate the suffering of patients who are normal except for one defective gene? What about most diseases where more than one gene is generally involved – like bipolar disorder that Siddharth Mukherjee starts off the book with? What if we can make small edits to genes with just a small concoction? Can these edits be made even before a baby is born? These are realities that are upon us already and the book offers plenty to learn and reflect on.

“The Gene” is not just Siddharth Mukherjee’s quest. It should be all of ours too.

You are what and WHEN you eat!

Since we are in the season of making and breaking resolutions, one of the most broken resolutions appears to be – ‘lose weight’. As we approach the new year, I wanted to share research findings by Amanda Chaix and others from Salk Institute’s Satchindananda Panda’s lab. This paper, published timely in December 2014 explores ‘Time Restricted Feeding or TRF’ and its possible use in obesity therapy (1). A previous paper by this same lab was published in The Cell two years earlier and showed that in mice, if feeding was restricted to 8 hours of their active phase (i.e in the night), even if they ate high fat food, they were protected from weight gain and other obesity induced metabolic disorders. Recently, it has also come to light that many metabolic pathways and even drug targets designed to deal with metabolic disorders have diurnal rhythms (2). In light of these observations, in this study the authors extend their previous findings and undertake a more comprehensive study to include different diets and feeding patterns that might possibly mimic human food consumption patterns.

In this paper they investigate the beneficial effect of Time Restricted Feeding (TRF) under different diets, the legacy effect of TRF on different time-scales and the possible therapeutic effect of TRF on diet induced obesity and overall metabolism.

For the experiments, two feeding patterns were followed

1) Adlibitum Feeding (ALF) – food is available at all times with the quantity and frequency of consumption being the free choice of the animal and 2) Time Restricted Feeding (TRF) –  food is available only during their active time i.e in the night (9 hours)

In both cases the food provided was isocaloric (same amount of calories) in content but varied in the percentage of energy the mice get from each of the macronutrients (fats, carbs and protein). Just as a reference, regular chow that is fed to lab mice is composed of agricultural byproducts, such as ground wheat, corn, or oats, alfalfa and soybean meals, a protein source such as fish, and vegetable oil and is supplemented with minerals and vitamins. Chow is inexpensive to manufacture and is palatable to rodents.

So let me dive into what they tested one by one. First, what is/are the beneficial effects of Time Restricted Feeding (TRF) and is it irrespective of diet composition. They take 10 week old mice and feed them with normal chow for two weeks adlibitum. Then they start the experiment. The experiment is carried out for 12 weeks and the gain in weight is measured. So at the start of the experiment, they gave mice different types of diets either adlibitum (ALF) or time restricted for 9 hours (TRF). The types of diets included sucrose + fat, high fructose, normal chow feed and high fat diet. For the high fat diet alone, they also tested the effects of increasing TRF times – 9 hours, 12 hours and 15 hours.

In every case, irrespective of the diet composition, mice fed by TRF gained less weight compared to ALF. Secondly, mice on a fatty diet showed increasing weight gain with increase in the time of feeding (9hrs, 12hrs and 15 hrs) but it was still much lower compared to mice on fat diet adlibitum. An important side note, mice on normal chow diet whether on ALF or TRF regiments did not show any significant difference in the amount of weight gained during the course of the experiment. So they suggest that overall TRF does restrict weight gain irrespective of the composition of the diet (some diets are slightly better than others).

Coming to the second question – What happens if you give TRF a break and do ALF for whatever reason? They liken this to a human consuming TRF(9hrs) 5 days a week and going ALF in the weekend! True to their expectations, they found that even if there is a break in TRF when the mice were feeding ad libitum in the weekend, the weight gain was similar to the ones that were on TRF the whole time for 9 hours. So we can take comfort in the fact that at least in the short term, it is ok to occasionally binge :).  They also wanted to test the long term effect on changing feeding regimens (they call this legacy effect). For this 25 week long experiment, mice began by eating high fat food TRF(9hrs) for 12 weeks and then half of them continued in the TRF regimen and half were shifted to ALF for the reminder of the experiment.  They also tested the converse regimen (Start with ALF, half continued in ALF and half were shifted to TRF).

Obviously, the animals that started out on an ALF regimen of high fat diet and continued in the same regimen for the entire period of the experiment (25 weeks) showed the maximum weight gain, a whopping 111% increase. However, among the other half that were switched to TRF mid way (after the 12th week), the weight gain was much more reduced compared to the mice on ALF for 25 weeks. Conversely, the animals that were on TRF throughout showed the lowest weight gain. But among the TRF mice that were switched to ALF, weight gain was rapid. They control the experiments with a normal chow diet and show that irrespective of the feeding regimen and any changes midway, the animals gained about the same weight. So of course a balanced diet is the best 🙂

Thirdly and not surprisingly, the metabolic effects usually associated with obesity and Type II diabetes were seen in mice on a high fat ALF regimen (fat accumulation in liver, serum glucose level accumulation, glucose tolerance). However, these effects were less pronounced in mice that were on the TRF regimen throughout and were reversed to a significant extent when the feeding regimen was changed from ALF to TRF. They suggest that switching to the TRF regimen improves the motor coordination ability of the high fat diet consuming mice by measuring their rotarod and treadmill performance. They find that overall, TRF improves metabolic rhythms (making proteins, burning carbs and fat) and the metabolic capacity irrespective of diet.

Based on this study, you are not just what you eat but also when you eat. Obese mice that consume high fat diet in a time restricted manner are obese but fit and better protected from metabolic pathway perturbations and obesity associated outcomes. One important suggestion of this study based on their short term and long term cross over studies is that the earlier obese mice were switched to TRF, the better the outcome. When I presented this paper at Carnegie, some of the experts working on metabolism shared how different the metabolisms of humans were from mice; especially lab mice. For us, practicing TRF by restricting eating to 8-9 hrs in 24 hours might be a little hard although recent studies are showing that it is beneficial in humans as well (4). More research is needed to understand how TRF can be effectively translated to humans and tweaked to be truly beneficial. It is an exciting paper though!

References

1.http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00498-7

2http://www.cell.com/cell-metabolism/abstract/S1550-4131(14)00005

3. http://www.salk.edu/news-release/another-case-against-the-midnight-snack/

4.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0136240

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