John Hopkins University researchers believe they’ve found a nerve cell that may serve as a “switch” that tells the brain it’s time to put down the fork and walk away from that second helping of chocolate cake.
The nerve cell, discovered in mice, could be a useful tool in the fight against obesity… if you don’t mind becoming a genetically modified human.
The scientists found that when the cells “fired,” sending other signals to the brain, the mice ate 25% less in the course of a day. Switching off those cells caused the mice to eat more, and double their weight in 3 weeks.
The cells were located in a small region of the brain called the para-ventricular nucleus, which was already known to send signals and receive signals related to appetite and food intake. 
Richard Huganir, Ph.D., director of the Department of Neuroscience at the Johns Hopkins University School of Medicine and graduate student Olof Lagerlöf, M.D., honed in on an enzyme known as OGT, a biological catalyst that is involved in several bodily functions, including sugar chemistry and the body’s use of insulin.
When the researchers deleted the gene from the primary nerve cells located in the hippocampus and cortex of the adult mice, that’s when researchers noticed the mice’s rapid weight gain. 
The missing gene caused the rodents to binge on their food more, and consume more calories in the process. When the team removed the mice’s food, they stopped gaining weight, which suggested the mice were incapable of telling when they were full, which made them overeat. And the weight they gained was pure fat, not muscle.
“When the type of brain cell we discovered fires and sends off signals, our laboratory mice stop eating soon after. The signals seem to tell the mice they’ve had enough.” 
“These mice don’t understand that they’ve had enough food, so they keep eating. We believe we have found a new receiver of information that directly affects brain activity and feeding behavior, and if our findings bear out in other animals, including people, they may advance the search for drugs or other means of controlling appetites.”
There are a lot of reasons why people overeat. There is big money in trying to find the magic cure, but I’m not sure deleting or shutting off a gene is a safe bet. And any drug created based on the findings would surely have unpleasant side effects.
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A team of researchers from Copenhagen University have located a single mutation that causes the mysterious phenomenon of blue eyes. And all blue eyed people are genetically related to a person who lived in the Black Sea region sometime between 6 – 10,000 years ago.
The research was published in the Journal of Human Genetics. A mutation in a gene called OCA2 came into being nearly 8,000 years ago. It can be definitively traced back to an ancestor from the Black Sea.
Dr. Hans Eiberg claims that before this time, every human being had brown eyes. “A genetic mutation affecting the OCA2 gene in our chromosomes resulted in the creation of a ‘switch,’ which literally ‘turned off’ the ability to produce brown eyes,” Eiberg said.
The brown melanin pigment is still dominant. However, following the last Ice Age, Europeans developed this rare mutation that differentiated them from the rest of the human race.
Ninety-five percent of Europeans in Scandinavian countries have blue eyes. They are also found to have a greater range of hair and skin color.
Comparatively, Europe has a wider variety of hair color and skin pigment than is found in any other continent in the world. These mutations are recent as Europe was colonized only a few thousand years ago, say mainstream scientists.
Through interbreeding, the brunette with blue eyes was evidenced about 25,000 years ago. Researchers attribute this to ancient interbreeding with Neanderthals.
Although no Neanderthal DNA has been found in modern Homo Sapien-Sapien, mainstream science clings to this theory as fact because they haven’t come up with anything better.
“The question really is, ‘Why did we go from having nobody on Earth with blue eyes 10,000 years ago to having 20 or 40 percent of Europeans having blue eyes now?” John Hawks of the University of Wisconsin-Madison said. “This gene does something good for people. It makes them have more kids.”
This world map shows the frequencies of Neandertal-like TLR DNA in a 1000 Genomes dataset. The size of each pie is proportional to the number of individuals within a population. Credit: Dannemann et al./American Journal of Human Genetics 2016
When modern humans met Neanderthals in Europe and the two species began interbreeding many thousands of years ago, the exchange left humans with gene variations that have increased the ability of those who carry them to ward off infection. This inheritance from Neanderthals may have also left some people more prone to allergies.
The discoveries reported in two independent studies in theAmerican Journal of Human Genetics on January 7 add to evidence for an important role for interspecies relations in human evolution and specifically in the evolution of the innate immune system, which serves as the body’s first line of defense against infection.
“We found that interbreeding with archaic humans–the Neanderthals and Denisovans–has influenced the genetic diversity in present-day genomes at three innate immunity genes belonging to the human Toll-like-receptor family,” says Janet Kelso of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
“These, and other, innate immunity genes present higher levels of Neanderthal ancestry than the remainder of the coding genome,” adds Lluis Quintana-Murci of the Institut Pasteur and the CNRS in Paris. “This highlights how important introgression events [the movement of genes across species] may have been in the evolution of the innate immunity system in humans.”
Earlier studies have shown that one to six percent of modern Eurasian genomes were inherited from ancient hominins, such as Neanderthal or Denisovans. Both new studies highlight the functional importance of this inheritance on Toll-like receptor (TLR) genes–TLR1, TLR6, and TLR10. These TLR genes are expressed on the cell surface, where they detect and respond to components of bacteria, fungi, and parasites. These immune receptors are essential for eliciting inflammatory and anti-microbial responses and for activating an adaptive immune response.
Quintana-Murci and his colleagues set out to explore the evolution of the innate immune system over time. They relied on vast amounts of data available on present-day people from the 1000 Genomes Project together with the genome sequences of ancient hominins. Quintana-Murci’s team focused on a list of 1,500 genes known to play a role in the innate immune system. They then examined patterns of genetic variation and evolutionary change in those regions relative to the rest of the genome at an unprecedented level of detail. Finally, they estimated the timing of the changes in innate immunity and the extent to which variation in those genes had been passed down from Neanderthals.
These investigations revealed little change over long periods of time for some innate-immunity genes, providing evidence of strong constraints. Other genes have undergone selective sweeps in which a new variant came along and quickly rose to prominence, perhaps because of a shift in the environment or as a result of a disease epidemic. Most adaptations in protein-coding genes occurred in the last 6,000 to 13,000 years, as human populations shifted from hunting and gathering to farming, they report.
But, Quintana-Murci says, the biggest surprise for them “was to find that the TLR1-6-10 cluster is among the genes presenting the highest Neanderthal ancestry in both Europeans and Asians.”
Kelso and her colleagues came to the same conclusion, but they didn’t set out to study the immune system. Their interest was in understanding the functional importance of genes inherited from archaic humans more broadly. They screened present-day human genomes for evidence of extended regions with high similarity to the Neanderthal and Denisovan genomes,then examined the prevalence of those regions in people from around the world. Those analyses led them to the same three TLR genes.
Two of those gene variants are most similar to the Neanderthal genome, whereas the third is most similar to the Denisovan genome, Kelso’s group reports. Her team also provides evidence that these gene variants offered a selective advantage. The archaic-like variants are associated with an increase in the activity of the TLR genes and with greater reactivity to pathogens. Although this greater sensitivity might protect against infection, it might also increase the susceptibility of modern-day people to allergies.
“What has emerged from our study as well as from other work on introgression is that interbreeding with archaic humans does indeed have functional implications for modern humans, and that the most obvious consequences have been in shaping our adaptation to our environment — improving how we resist pathogens and metabolize novel foods,” Kelso says.
As surprising as it may seem, it does make a lot of sense, she adds. “Neanderthals, for example, had lived in Europe and Western Asia for around 200,000 years before the arrival of modern humans. They were likely well adapted to the local climate, foods, and pathogens. By interbreeding with these archaic humans, we modern humans gained these advantageous adaptations.”
The above post is reprinted from materials provided by Cell Press. Note: Materials may be edited for content and length
Immunotherapies have been gaining in popularity in the last few years as a potential treatment for cancer. The idea is to use a patient’s own immune system to reject tumorous growth, either by vaccination, injection of substances that stimulate immunity, or cell transfer.
T cells are a subset of white blood cells, which can specifically recognise and destroy virally infected or cancerous cells. This recognition is done via their T cell receptor. This receptor is designed to interact at the molecular level with proteins on the surface of all cells. If the T cell receptor is compatible with a given protein, binding occurs, which means the two cells become attached. The T cell receptor can recognise proteins on target cells with sharp discrimination. If the protein is of the “self”, binding does not occur and the T cell does not react. If the protein is a viral protein, or a modified self protein in a cancerous cell, strong binding induces the T cell to destroy the abnormal cell.
Adoptive cell transfer
T cells’ importance in tumour control was recently highlighted, when it was observed than patients whose tumours were highly infiltrated with T cells had a better prognosis. But how can we increase the amount of T cells in tumours of patients with poor prognosis?
Since T cells circulate in the blood, it was imagined that T cells could be extracted from the blood and transfused into cancer patients, as a cellular therapy. However, for an efficient anti-tumour effect via transfer of immune cells, one needs to select the right cells.
Since a T cell receptor can bind proteins on the surface of other cells with high specificity, it can discriminate between billions of proteins. This means that there are only a very small percentage of cells that bear the correct receptor for a given protein. To try to find such a specific immune cell in the blood to target a specific cancer would be as hard as finding a needle in a haystack.
To solve this problem, researchers have found a way to extract T cells from tumours excised by surgery and then to expand them in vitro in the lab. Liberated from the deleterious tumour environment, and carefully looked after in their petri dishes, the T cells are able to expand to numbers more favourable for making an efficient therapy.
They can then be transfused back into the patient together with a T cell growth factors (which stimulate cellular growth). This technique has shown great promise in metastatic melanoma where patients, having failed all standard lines of treatment, showed remarkable responses to cell transfer therapy: 50% of those treated had an improvement in their disease, while 20% showed long-term remission (five years or more).
So far so straightforward. Unfortunately, retrieving immune cells from tumour tissue is not a trivial process and, clearly, is impossible for cancers that are not accessible by surgery. Moreover, T cells which recognise cancer cells are typically less potent than, for example, virus-specific T cells, because they have low-affinity T cell receptors. This is because cancer cells are non-foreign self-cells and the immune system has evolved to avoid reacting strongly against this kind of tissue to avoid autoimmunity – essentially to prevent it from attacking itself.
Hence, it was proposed to genetically modify T cells from the blood of cancer patients, to confer potent but highly specific recognition of cancer proteins. This is feasible, since stable genetic modification of many cell types can be efficiently and safely achieved through modern genetics technology. It is possible to mutate naturally-occurring T cell receptors to achieve a higher protein-binding ability, and even to be more creative and design new receptors that are superior to those found in nature.
The chimeric antigen receptor (CAR) is an example of this. It is a synthetic protein which contains components of both an antibody and a T cell receptor. Expression of CARs in T cells results in a strong recognition of tumour proteins, just like an antibody, and highly specific destruction of tumour cells. CARs have proven extremely effective in the treatment of blood-borne cancer. For example, in treatment-resistant leukaemia patients, CAR therapy can induce durable remission, as published by the laboratory of Carl June in 2011. Numerous similar studies have since followed, with very promising results. However, leukaemias are relatively easily and safely targeted based on their location in the body (the blood), but this is not the case for most solid tumours such as melanoma (skin) and carcinoma (tissue) cancers.
The main problem with T cells and their exquisite specificity is that one has to be aware of the appropriate tumour protein to target. Additionally, tumours evolve rapidly and often stop expressing proteins which are targeted by the immune system. However, this might not be a problem if the therapy acts fast enough, or targets an antigen that is necessary for tumour survival.
Finally, there could be dramatic consequences if the antigen is expressed in other parts of the body. For example, a recent report described a patient who lost his life after adoptively transferred T cells that were specific for a tumour antigen started attacking tissue cells in the lung, where low levels of the targeted protein were expressed. Such adverse events are difficult to predict since antigens may be expressed by normal tissue cells at certain times or under certain conditions.
To address this safety issue, scientists have created so called “suicide genes”. These genes can be added to the T cell at the same time as it is genetically modified to express the tumour-specific receptor. Consequently, it is possible to induce rapid T cell destruction upon treatment, in the event of a dangerous autoimmune response.
Immunotherapies in general, and adoptive cell transfer specifically, hold many promises for the future of cancer treatment. The field is developing at breakneck speed, and many studies are currently being made to identify new cancer-associated proteins to target and additional safety mechanisms to prevent autoimmunity upon transfer of T cells. In cancer science, this is certainly one field to watch closely.
Previous work by the research teamfrom the Walter and Eliza Hall Institute showed that the protein MOZ could relay external ‘messages’ to the developing embryo, revealing a mechanism for how the environment could affect development in very early pregnancy.
Dr Bilal Sheikh, Associate Professor Tim Thomas, Associate Professor Anne Voss and colleagues have now discovered that MOZ and the protein BMI1 play opposing roles in giving developing embryos the set of instructions needed to ensure that body segments including the spine, nerves and blood vessels develop correctly and in the right place.
Associate Professor Voss said the study revealed that the proteins tightly regulatedHox gene expression in early embryonic development. “In very early development, when the embryo is still just a cluster of dividing cells, the embryo must become ‘organised’ so that the body tissues and organs develop correctly, with everything in its right place,” Associate Professor Voss said.
“The embryo is organised along an ‘axis’ from head to tail, and a standard pattern of development is established that subdivides the body into segments, with each segment responsible for producing specific aspects of tissues and organs, including the vertebral column, spinal cord and nerves.
“We showed that the proteins MOZ and BMI1 were important for initiating activation of the Hox genes – section by section – providing the blueprint the developing organism needs for proper development.”
Associate Professor Voss said that, though they worked together, MOZ and BMI1 played opposing roles. “We discovered that MOZ and BMI1 were important for initiating and correctly timing Hox gene expression, ensuring the genes were activated at the right time and in the right place,” she said.
MOZ was responsible for activating the genes, while BMI1 prevented Hox genes being switched on prematurely, Associate Professor Voss said.
She said the research also showed that significantly reducing Hox gene expression still allowed normal development, as long as the timing and location of expression were correct.
“We found that if the Hox genes were activated too early or late, it had significant repercussions for the developing embryo, such as malformations of the spine,” Associate Professor Voss said. “Interestingly, we also found that producing an ‘accurate’ amount of MOZ or BMI1 in developing embryos was not nearly as important for correct development as when and where Hox genes were activated.”
Importantly, MOZ and BMI1 could provide a mechanism to transmit signals from the environment to the developing embryo, with potentially devastating consequences.
“We know that Hox genes can be directly affected by too much vitamin A, which can cause severe deformities in the embryo,” Associate Professor Voss said. “Substances or environmental challenges that impact MOZ or BMI1 expression could affect when and where Hox genes are expressed, causing defects in the developing embryo.”
Dr Anne Voss said the research team’s discovery overturned a decades-old belief about embryonic development. “A lot of what we know about embryonic development and how it is controlled was learned from studies of fruit flies,” Associate Professor Voss said. “In this study we showed a key difference; two molecules that have only a maintenance role in fruit flies are indispensible for initiating the blueprint in mammalian development.”