The newest in artificial enzymes

For our last week of class, I have decided to write about an interesting topic that may have molecular biology applications in the future, but is not quite there yet. An upcoming technology technology involves using carbon nanodots and quantum carbon nanodots to replicate the active sites of enzymes. This allows a manufactured structure to replicate the function of naturally produced enzymes.

 I found the concept behind this to be a little incredulous, but after reading the review I found online (link below) it looks like the results have been replicated by different research groups and the use of this technology is expanding. To create the carbon nanodots there are two approaches. In a top-down approach carbon from a bulk material, like a mass of graphene, is broken down into the shapes necessary through the application of laser irradiation, arc discharges, electrochemical carbonization, and plasma treatment to form appropriately sized and shaped carbon dots. In the bottom up approach carbon is added to an organic molecule that forms a sort of base from which the carbon can assemble into the correct shape. The nanodots, once created, can be modified to more closely replicate enzyme active sites. The nanodots have shown to have a low toxicity and high specificity when used in experiments. This makes them ideal for later research in drug delivery.

I am interested to see how advanced they can make this technology. Being able to create enzymes for specific tasks sounds like a great help in elucidating biochemical mechanisms and a variety of other applications. For now, though most of the research is focused on carbon nanodots that act like peroxidases, not particularly exciting, but still a proof of concept that the carbon nanodot research is working. Let me know what you think below!

An overview of carbon nanodots and their applications:

http://www.mdpi.com/1420-3049/21/12/1653/htm

Nature’s Farmers: The Honey Bee

As some of you may know there are certain animal species that are commonly considered vital to human survival. Protecting these species is necessary to avoid food insecurity or large environmental disasters. One of the species that is often talked about is the honey bee.

Honey bee colonies not only make delicious natural honey, but they also help to pollinate crops. While honey is a great product the pollination powers of a honey bee colony help a farm be successful. In this past couple of decades, a decrease in bee populations, both feral and commercial, have been noticed. These deaths have led farms to be less productive. Under certain conditions bee colonies can collapse without the necessary workers to sustain a hive.

 Research has been done to find out what has been killing the honey bees and much of it originally focused on pesticides. Increased use of certain pesticides has been linked to decreased bee populations, however that is not the whole story. Bee colonies have also been tested and it has been found that certain viruses have become prevalent in bee colonies before they begin to die off. One such virus is the Deformed Wing Virus (DWV). This virus causes malformation and paralysis in the wings and legs of honey adult honey bees. DWV is an RNA virus that is transmitted from the Varroa mite to honey bees. It can then be passed orally by honey bee secretions or from queen and worker bee sex cells to offspring.

Until recently working with this virus was difficult but isolating the virus and synthetically replicating it has been done. The research team that did this used many processes that may sound familiar to us such as PCR, Western blotting, and immunohistochemical staining. Having the ability to replicate the virus in vitro is important to research groups trying to stop viral transmission among honey bee colonies. Finding cures and treatments to stop the spread of DWV in conjunction with safe pesticide use is vital to recovering our honey bee population.

Let me know what you think about this research in the comments below!

A research paper about the subject:
Construction and Rescue of a Molecular Clone of Deformed Wing Virus (DWV)

By: Benjamin Lamp, Angelika Url et al.

 

A news article from Science Daily:

New findings about the deformed wing virus, a major factor in honey bee colony mortality https://www.sciencedaily.com/releases/2016/11/161111120731.htm

 

Sneaky Snakes!

The article listed below details some of the research being on the Venezuelan mapanare, or Bothrops columbiensis. Specifically, this research group was running experiments to identify the different compounds in snake venom. The Venezuelan mapanare is a common snake that is responsible for 70% of snake bites in Venezuela. The proteome of the venom has been identified in other research, but due to the high density of proteins in venom glands it is hard to identify and research each protein using standard methods. In particular, the group pointed out that proteome research may miss proteins that are expressed in extremely low quantities. During this research the venom glands of the snake were used to make a transcriptome, or list of all the DNA that is currently being transcribed into RNA in a cell group. The cells making up the venom gland should have mRNA for each protein in the venom, allowing researchers to identify proteins differently than the methods used to make a proteome.

When constructing the transcriptome, the research group identified expressed sequence tags (ESTs). These are the mRNA products from the cDNA being translated into mRNA. The transcriptome identified 729 unique sequences. Of these 47.2% matched known snake toxins, 22% were regular products found in most cells, 11.9% were identified as proteins with unknown functions, 18.9% did not match anything in GenBank.  These sequences will likely be the subject of further research.

The results from this analysis can be used for a variety of things. The mapanare venom can be better compared to other snakes, and the evolutionary history of different snakes can be elucidated with the information. Better antibodies can be made since the venom is more fully understood. There is also some research being done to isolate specific proteins that can be used in medicine for a variety of things. Different proteins can coagulate or thin blood. Some proteins can cause specific inflammatory responses that may also have some use in trauma medicine.

What do you think about this research? Let me know below.


http://bmcmolbiol.biomedcentral.com/articles/10.1186/s12867-016-0059-7
Gene expression profiling of the venom gland from the Venezuelan mapanare (Bothrops colombiensis) using expressed sequence tags (ESTs)
By: Montamas Suntravat, Néstor L. Uzcategui, Chairat Atphaisit, Thomas J. Helmke, Sara E. Lucena, Elda E. Sánchez1 and Alexis Rodríguez Acosta

Microbial Fuel Cells

Currently most energy production is fueled by a variety of fossil fuels such as natural gas, coal, and oil. There are some obvious problems with burning fossil fuels to create energy. The pollutants produced during energy production cannot be properly stored forever and the CO₂ levels have a variety of effects on the environment, including ocean acidification. With the obvious drawbacks of fossil fuels research is being done in a variety replacement energy sources. These sources include gasoline producing bacteria, nuclear power, solar energy, wind energy, hydroelectric power production, and geothermal energy. While some of these solutions are more environmentally friendly than others, they all have their drawbacks. Most of them need large boosts in efficiently to make them viable replacements to fossil fuels in the market place. A combination of multiple sources will be needed to sustain the amount of energy we will need to meet the power requirements of future populations.

One source of energy production that I stumbled across while looking for interesting articles to write about is the use of microbial fuel cells to produce electricity. In microbial fuel cells bacteria are used to perform reactions that generate electricity. In one case researchers developed a fuel cell to take the wastewater from a brewery and convert it into power and clean water for future brewing. A link to that is down below. The article I chose to focus on is a group of researchers using simple E. coli to make power. Originally they researched the mechanisms behind the production of energy using E. Coli. They found that while energy production of the bacteria when biomass was added was measurable there were ways to improve on the process. The bacteria were not conductive and it was expensive to harvest the energy. The bacteria secreted Indole, a benzene ring fused to a five membered ring with a nitrogen on it. Indole can be oxidized by oxygenases from other bacteria, one of which was subsequently transplanted via plasmid into the bacteria. The indole and modified E. Coli made nine times more power than the control microbial fuel cells. This was an interesting result and shows that bacteria can be designed to perform specific reactions and produce significantly different amounts of electricity. While the MFCs are not at all efficient, in the brewery case it led to major savings on wastewater treatment. This means they can also be designed to purify water after certain industrial uses. This make them cost efficient for water purification while also being able to produce power as an added benefit.

Being able to purify waste products and produce power seems like something the future needs. Let me know what you thing in the comments below.

For more reading:                

Basics on a microbial fuel cell:

https://en.wikipedia.org/wiki/Microbial_fuel_cell

Energy from beer article:

https://www.beeradvocate.com/mag/1394/fosters-australian-for-electricity/

A scholarly article on optimizing fuel cells:

Indole oxidation enhances electricity production in an E-coli-catalyzed microbial fuel cell.

By: Han, TH; Cho, MH; Lee, J.

Is diabetes medication the cure for cancer?

The CDC estimates that in 2014 29.1 million people had diabetes, with 8.2 million people living without a diagnosis of their condition. One of the most popular medications to help those with diabetes is Metformin. One popular brand name of metformin is Glucophage, although it is marketed as part of a variety of diabetes medications. It is an oral medication given to diabetics and people that are pre-diabetic in order to help control glucose levels and increase insulin sensitivity. Some studies in the past have found diabetes medications can also help with other problems, such as preventing cardiovascular disease and polycystic ovary syndrome. While interesting these studies have limited impact on treatment options besides diabetes.

New studies, like the one linked below, are starting to test and see if metformin can help to treat cancer and decrease tumor growth. It has long been known that controlling glucose levels in diabetics is key to lower the incidence of other diseases, even some that at first do not seem related to glucose levels. The exact mechanism of metformin is unknown, and the extent of biochemical pathways it interacts with has been increased as more research has been done. This has been researched since the 1950s and things are still being discovered about the mechanisms of action exhibited in the body. One thing that has been found is that metformin activates the AMPK pathway, leading to increased glucose uptake in cells.

The AMPK pathway has also been linked antineoplastic properties, since the AMPK pathway will upregulate mRNA that degrades a long noncoding RNA called H19. H19 serves to stop methylation of some genes by inactivating an enzyme called SAHH. With H19 knocked down by the addition of metformin, SAHH will help a methyltransferase methylate many oncogenes, leading to decreased growth in cancer cells. It is hypothesized that this reaction will also serve to keep healthy cells from becoming cancerous as well.

Since metformin is near side effect free it is safe for use by people without diabetes and is much less destructive than many current cancer treatments. Hopefully, after further testing and better elucidation of all of the pathways metformin interacts with, metformin can be used to create better cancer treatments. 

Want to see articles? Check it out below:

Metformin alters DNA methylation genome wide via the H10/SAHHH axis

By: T. Zhong, Y. men, L. Lu, et al. http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016391a.html

Cellular and molecular mechanisms of metformin: an overview

By: B Viollet, B Guigas

Diabetes Stats:

http://www.cdc.gov/diabetes/data/statistics/2014statisticsreport.html

 

Miracle Berries and how we can use them

There is a particularly unique plant in west Africa that I find interesting. The Synsepalum dulcificum is a plant that grows a berry containing the aptly named glycoprotein call miraculin. When consumed miraculin makes sour foods taste sweet. While eating the berry this effect can last from thirty minutes to an hour.  The actually name miracle fruit or miracle berry can be used to describe a few different plants, but all the plants share the same characteristic of altering the perception of taste.

While the exact mechanism of miraculin is unknown it is known that it binds to taste receptors on the tongue. When miraculin is exposed to lower pH, which is typical for acidic sour foods, it will change the binding to the taste receptors, activating the sweet receptors, causing any sour foods to seem sweet. Miracle berries are safe to eat and have been consumed in west Africa for some time without any reported side effects. The properties of miraculin have led to it being tested as a food additive. The only minor drawback is that miraculin can be denatured by heat, however it is still being tested and in some places used to sweeten diet sodas.

It has not been approved in the U.S., however with no negative outcomes being linked to consumption and with additional benefits coming to light that may be subject to change. Recent studies have tested miraculin as a supplement to control uric acid, a category known as anti-hyperuricaemia agents. High uric acid levels can cause gout and kidney stones. These problems occur more often among overweight populations, and finding a way to control uric acid levels could be beneficial to many people with chronic uric acid related problems. In the study I linked below miraculin lowered uric acid levels in mice as effectively as allopurinol, a commonly used drug for gout sufferers. The name miracle berry was given long before these benefits were known, however with these new benefits coming to life it makes the name even more appropriate.

The use of natural subsatnces to make modern medical treatments is a common occurrence. Many medicines have similar origin stories. Let me know what you think in the comments below.

For more reading on how miraculin decreases uric acid levels: 

Miracle Fruit (Synsepalum dulcificum) Exhibits as a Novel Anti-Hyperuricaemia Agent

Authors: Yeu-Ching Shi

Molecules. 2016, Vol. 21 Issue 2, p1-13.

ISSN: 1420-3049

DOI: 10.3390/molecules21020140

Autophagy: The Newest Nobel Prize

The newest Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi for his work on understanding and elucidating the mechanisms of autophagy. He has a doctorate of science from the University of Tokyo and has had professorships at multiple colleges in Japan. Much of his work has been on the vacuole of simple yeast. His decades of research have led to wide ranging advances in the understanding of autophagy and its relation to bodily processes. He also characterized many of the genes that code for the proteins involved in autophagy, as well as some mutations of the same genes.

Autophagy is the mechanism by which cells degrade and reuse cellular components that are no longer necessary. It involves the sequestration, transport, degradation, and recycling of material.  The body recycles components through the use of lysosomes, one part of the autophagy process. Autophagy is an important part of many biochemical processes and has been linked to many different causes and outcomes in cells from a variety of species. There are three types of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy is commonly triggered in response to physical stresses on the body, that forces it to efficiently clean and reuse cell materials. Some of these physical stresses include starvation and disease.

The degradation caused by autophagy helps power the cell in these trying times and it can also protect against infection and viruses. It has a role in a multitude of disease responses and can cause programmed cell death. Having said that there are many diseases that occur because of malfunctions in the autophagy process. When the mechanism malfunctions because of mutations in the genes that code for proteins involved in the process there has been linked to osteoarthritis, cancer, and Parkinson disease.

I highly recommend reading the interview of Yoshinori Ohsumi that I linked below. He talks about how he followed his interests to continue his research and at the end he shares some advice to younger scientists.

For more reading:

An interesting interview of Professor Ohsumi where he talks about the progression of his work:

Yoshinori Ohsumi: Autophagy from beginning to end

By: Caitlin Sedwick

J Cell Biol. 2012 Apr 16; 197(2): 164–165

http://jcb.rupress.org/content/197/2/164

Some more in depth information on autophagy:

Autophagy: process and function

By: Noboru Mizushima

http://genesdev.cshlp.org/content/21/22/2861.long

Developments in HIV Research

As a little introduction to the topic I will explain how Human Immunodeficiency Virus (HIV) works. HIV is a retrovirus, meaning that it infects cells and uses reverse transcriptase to infect normal cells with the genetic material of the virus. HIV creates RNA then uses a reverse transcriptase protein to integrate a complimentary DNA strand into the DNA of the host cell. HIV is particularly deadly because it attacks macrophages, dendritic cells, and CD4 helper T-cells, an integral part of the immune system. It can be spread through the transfer of many bodily fluids such as blood, semen, breast milk, or vaginal secretions. The virus has a long incubation period and is also known as a lentivirus. It infects CD4 cells, using them to replicate and over time it lowers the amount of CD4 cells in the blood to levels too low to stop infections. People with the lowest CD4 count are diagnosed as having stage 4 HIV infection, often called AIDS, or Acquired Immune Deficiency Syndrome.  

HIV is a relatively new disease, only being discovered in 1983. There is not a cure widely available and most treatments are a combination of drugs designed to limit the viral load in fluids to undetectable levels, which reduces transmission rates and increases the life span. If treatment is stopped the virus will begin replicating back to pre-treatment levels. Only one man has been cured of HIV, by being giving a bone marrow transplant from someone with natural immunity to the disease. It was a rare circumstance that cannot be replicated readily since bone marrow transplants are expensive and matches are hard to find, particularly since immunity to HIV is rare.  A few days ago a new series of treatments also produced a patient with no viral load, although further observation is needed to if this was a permanent solution.  

This research paper focuses on some of the inner workings of the cells that have been infected by HIV. It was thought that when a cell was infected with HIV it did not realize it was infected and the cell did not attempt to fight the infection. In reality this paper shows that the cells recognize HIV replication products and produce type 1 interferon. This would normally fight off many types of infections, however HIV produces accessory proteins that regulate interferon production. In many cases interferon is ineffective at fighting HIV and causes inflammation that is detrimental to the patient.  

Finding new things about HIV infections opens up new avenues of research. This research could lead to effective cures that work quicker and cheaper than those being researched now. It also shows that the understanding of this disease is not complete. What do you think about this ongoing research? Do you think HIV will be effectively cured sometime in the future?  

For more reading on research about HIV here is the journal article I started on:  

HIV Triggers a cGAS-Dependent, Vpu- and Vpr- Regulated Type I Interferon Response in CD4+ T Cells 

By: Jolien Vermeire, Bruno Verhasselt, et. al

GMO’s: Harder, Better, Faster, Stronger

As the world’s population increases the demand for sustainable and efficient agriculture has grown and many companies are competing to make ever better genetically modified crops.

 

Many genetically modified organisms (GMOs) are being improved in ways that have just been discovered. Older GMOs exist and have for some time, but the methods used to make the older generation of GMOs had many limits on what advantaged could be added to crops. Research has found programmable DNA binding proteins such as ZFP, TALEN, and CRISPR/Cas that allow for the input of specific DNA sequences in specific spots on chromosomes. These new techniques allow scientist to create widely improved crops and even add in totally new attributes that do not belong to those crops.

 

These newer crops can be changed in ways that were impossible by the older methods, creating crops that are disease resistant, protected from pests, and do not require as much sun. These are just three of many attributes that are closely targeted by scientist. There have also been some sensational news reports about odd but useful modifications being made in some places, and not all are related to this research. In Japan watermelons are being grown in square shaped containers, originally to decrease later shipping costs of the fruit. These watermelons are now highly prized and sold for more than regular watermelons because of this new shape. It is possible that the future holds GMOs created to not only be better for growing but also more ascetically pleasing.

 

The advantage to these techniques is that they are some of the only methods that have real potential to raise food production to the levels needed to meet demand. Crops will not spoil as fast and are better in every way than tradition crops, or even older GMOs.

 

Some of the disadvantages include patent protection on GMOs by the companies that make them, which are used to artificially increase seed prices for farmers and stop these great crops from ruining company profit margins. But while good for the company the prices can have negative impact on medium sized farms that have a hard time selling their produce at higher prices. There has also been some concern about lack of diversity in the crops. The lack of diversity is both in types of crops grown and the diversity among a single crop. With natural breeding no longer being a factor crops do not have the range of immunity to diseases that are seen in the wild nor the lucky mutations that prove advantageous in the face of adversity. As certain crops are more heavily modified and profitable than others the diversity of what is grown to meet the food supply will decrease. We have already seen evidence of this by the decreasing numbers of apple varieties available at super markets. Having diverse food sources helps grow food security since it is unlikely that that any one mishap will be able to ruin every type of crop. Decreased diversity will allow one type of mold, bacteria, or natural disaster to disproportionally affect the food supply if there are only a few types of crops being grown.

 

Let me know what you think about GMO’s. Are they good, great, or horrible for the future? Are the conspiracy theorists right about them being unhealthy?

 

Precision genetic modifications: a new era in molecular biology and crop improvement

By: Franziska Fichtner, Reynel Urrea Castellanos, Bekir Ülker

DOI 10.1007/s00425-014-2029-y

 

Nanotechnology vs. HIV: The fight of the future

Most HIV treatments focus on the use of anti-retroviral drugs to decrease the amount of virus in the body to almost undetectable levels. These drugs frequently target the enzymes that HIV needs to replicate itself inside of cells in order to slow replication and decrease viral load.

HIV has a high rate of mutation compared to a mammal such as ourselves, and it will often mutate in enough to develop resistance to certain anti-retroviral drugs. Mutations in viral RNA that change the proteins produced in cells or mutations that change how HIV enter the cell can lead to drug resistance. In order to slow down the development of drug resistance many patients are put on combination therapies, which use multiple medications to keep the viral load in a person low and stop virus replication at many steps.

With combination therapies the development rate of resistance is slowed, however there are worries that viruses will still mutate fast enough to outpace our ability to develop new drugs. As HIV drug resistance becomes more common it is likely that this will eventually be the case. New treatments that attack HIV in radically different ways are being developed to hopefully find a long lasting and safe treatment for HIV. One such treatment involves the use of RNAi or RNA interference. This involves using microRNA and siRNA to target conserved genes in HIV with little mutation, binding and destroying the viral mRNA to stop production of the virus effectively and efficiently. The only problem with this research is delivering the RNA necessary for interference to every cell that needs it.

Attempts have been made to create viral vectors to do this, however the results were often underwhelming and at times dangerous. This brings me to nanotechnology. The latest research is delving into multiple types of nanotechnology to safely deliver RNA to targeted cells. This technology includes artificial liposomes, polymeric nanoparticles, dendrimers, and inorganic nanoparticles. Finding something that can deliver the RNA will allow for advances in many medications and may help to put a major dent in the spread of HIV worldwide.

Let me know what you think. Will nanotechnology be able to advance fast enough to find a transport system for RNAi? If you want to do more research on this topic you can start on the article below.

Nanotechnology Approaches for the Delivery of Exogenous siRNA for HIV Therapy

Simeon K. Adesina and Emmanuel O. Akala

Mol. Pharmaceutics

DOI: 10.1021/acs.molpharmaceut.5b00335

http://pubs.acs.org.ezproxy.shsu.edu/doi/10.1021/acs.molpharmaceut.5b00335

The evolution of disease

Some diseases are caused by a person’s genetics. In many cases diseases can be predicted by looking at DNA for specific genes that predispose someone to a disease. Having said that DNA is also connected to evolution, in that genomes that confer an advantage to a person will increase the probability of that person reproducing. Over time well adapted and healthy genomes will become prominent in a species.

            Why is it that so many diseases can be passed genetically when the theory of evolution claims that only the fittest will survive? Would that not mean that genetic based diseases should have died out long before the modern day? In truth it is much more complicated than that and there are many factors at play. Genetic diseases could always occur in a later generation through mutation in reproductive cells, being passed in that way. Or a series of other advantages will allow someone to still be fit enough to pass along a disease. Some diseases hide as recessive traits, only appearing when two carriers of the recessive trait mate.

            Then there are some diseases that are relics of a different time. Some diseases are still prevalent because they conferred an advantage in the past, and even with the significant side effects of a disease the advantage proved invaluable. Once this advantage was selected for it became prevalent in certain populations over time. Fast forward generations later and people still have these diseases in different circumstances that no longer provide a benefit, yet medical science has advanced enough that even without the advantage the disease will still be a permanent part of the population.

            One interesting example is Type 1 diabetes. People born with Type 1 diabetes have an autoimmune response that prevents them from producing enough insulin. Without insulin the person will have unusually high amounts of glucose in the blood. It has been found that Type 1 diabetes is most prevalent in northern Europeans, occurring at a frequency that is more common than random chance would suggest possible, showing signs of having been selected for in that area in the past. What advantage would that give? As it turns out high amounts of glucose in blood will depress the freezing point, increasing the tolerance for cold in humans. In the past minor ice ages and unseasonably cold weather would kill those unprepared for it, selecting those with Type 1 diabetes because of their tolerance for the cold. Trading a healthy amount of insulin for this advantage proved invaluable in the past and modern northern Europeans still suffer today as a result.

This leaves an interesting new avenue for understanding the epidemiology of disease. People with sickle cell trait have a higher resistance to malaria because of their malformed hemoglobin. Iron deficiency improves the chances of surviving infection by Yersinia Pestis, the bacteria that causes the plague, better known as the Black Death.

Finding how many diseases conferred an advantage in the past would also lead to better understanding of what diseases may give advantages in the modern day. A more holistic view of disease could also lead to new treatment ideas as well.

Want to learn more? I have an article about the prevalence of Type 1 diabetes listed below. A well written book on the subject of advantageous diseases that I have read in the past is also below. The book is much more interesting than any textbook and I highly recommend it for some casual reading.

For further reading please see:

The sweet thing about Type 1 diabetes: A cryoprotective evolutionary adaptation

By: S. Moalema, K.B. Storeyb, M.E. Percyc, M.C. Perose, D.P. Perl

http://www.sciencedirect.com.ezproxy.shsu.edu/science/article/pii/S030698770500054X

A more in depth novel on the subject:

Survival of the sickest: A medical maverick discovers why we need disease

By: Sharon Moelem

Why Questions in Science are so Important: Studies on Adaptive Sex Ratios

For the first addition to my blog I would like to talk about the importance of peer review. Though it is not strictly speaking molecular biology, it is important to every field of science and is gives people a good reason to blog and read about scientific discovery. I have provided an example of how peer review can help to evolve research on a subject.

For some time, scientists have provided evidence for or against the idea that malnutrition and stress lead to a change in the sex ratio at birth. For those of you not so familiar with the subject humans naturally have slightly more male births, usually around 106 male births for every 100 female births. It had been postulated in 1973 by biologist Robert Trivers and computer scientist Dan Willard that females in good condition, whether it was in regards to physical hunger or economic class, would always have a sex ratio skewed in favor of males. This of course meant that females that suffered from hunger or were in a disadvantaged economic class would have a more balanced sex ratio at birth, or in extreme cases even more female than male births.

This was controversial and many people disagreed with them, however scientific studies could not definitively prove or disprove the theory. The debate on this idea has persisted to this current day, with many researchers publishing on both sides of an argument, often citing papers of the opposing side in order to point out some flaw in a previous method. I have provided four such papers at the end of this post if you would like to read more on the subject. The first, “Maternal undernutrition and the sex ratio at birth in Ethiopia: evidence from a national sample” finds that there is a slight correlation between hunger and birth but it is not definitive and to points out that previous papers that say otherwise were statistical aberrations. The next two actually study the same famine, from the Great Leap Forward in China, in order to disprove then prove the connection between hunger and sex ratio. The last is a paper detailing how poor experimentation, observation, and calculation has allowed the debate on the subject to persist when it should be long over.

Most articles published now accept the connection as fact. Without a peer review process would the debate have even occurred? Or would Willard and Trivers been dismissed as crackpot theorists in 1973? My challenge to you is to review the literature and let me know what you think. Is there enough evidence to definitely say starvation can cause more female births? Is it appropriate to call out past researchers on flawed methodology?

·       Maternal undernutrition and the sex ratio at birth in Ethiopia: evidence from a national sample

By: Aryeh D. Stein, Paul G. Barnett, Daniel W. Sellen (2004)

http://rspb.royalsocietypublishing.org.ezproxy.shsu.edu/content/271/Suppl_3/S37

·       Could changes in reported sex ratios at birth during and after China’s 1958-1961 famine support the adaptive sex ratio adjustment hypothesis?

By: Zhongwei Zhao, Yuan Zhu, Anna Reimondos (2013)

http://search.proquest.com.ezproxy.shsu.edu/docview/1501334626?pq-origsite=gscholar

·       Malnutrition, Sex Ratio, and Selection A Study Based on the Great Leap Forward Famine

By: Shige Song (2014)

http://eds.a.ebscohost.com.ezproxy.shsu.edu/eds/pdfviewer/pdfviewer?sid=7be5eac1-8c2e-4a12-b235-2c56e4e06a83%40sessionmgr4006&vid=6&hid=4211

·       Privation, stress, and human sex ratio at birth

By: Shige Song (2015)

http://www.sciencedirect.com.ezproxy.shsu.edu/science/article/pii/S0378378215002133?