Shiga toxin is a dangerous by-product of certain infectious bacteria, such as strains of Shigella and E. coli, which causes symptoms ranging from intestinal pain to kidney failure and even death. Over 150 million people are afflicted with Shiga toxicosis every year, mostly in developing countries where waterborne diseases are prevalent. It is estimated that Shiga toxins kill more than one million people annually, and is particularly lethal to children. Even in developed countries, Shiga toxicosis remains a threat via foodborne outbreaks.
While exploring the inner workings of the cell, scientists at Carnegie Mellon discovered that Shiga toxin exploits the GPP130 protein found in the Golgi apparatus. As described in their article for the January 20th issue of Science, when a harmful substance enters the cell, it is normally packaged by the Golgi apparatus and sent to the lysosome for degradation. GPP130, however, is an unusual protein that cycles from the Golgi apparatus to endosomes and back without crossing paths with the lysosome. This feature of the GPP130 is utilized by the Shiga toxin which binds to the protein to avoid detection allowing it to remain in the cell where it can cause harm.
However, when high levels of manganese infiltrate the cell, GPP130 alters its pathway to go directly to the lysosome. Beyond a certain point, manganese is also toxic to humans, but the concentrations and methods of administration are already well-documented.
“Manganese is inexpensive. While Shiga toxin affects people in the developed world, it affects far more people in the developing world. An inexpensive, accessible treatment– not a designer drug — is the ideal solution,” says Adam Linstedt, professor of biological sciences at Carnegie Mellon. “While further testing is needed to determine if manganese is a suitable treatment for humans, I’m optimistic that trials should move forward quickly.
Current treatment methods utilize antibiotics to kill the Shiga-excreting bacteria, which actually causes them to lyse (or break apart) and release the toxin in higher concentrations to the detriment of the host. The researchers propose using manganese in conjunction with the antibiotics to neutralize the toxin as well as the bacteria simultaneously. If the scientists are successful in balancing the manganese dosage and the proper supply chain avenues are set up, millions of lives could be saved.
Oxytocin is the hormone present during child birth which results in the mother-child bond, and is responsible for feelings of connection and trust in social relationships. It is thought to have developed to prevent abandonment of an infant by its mother.
Researchers at Duke University have conducted a study on macaque monkeys to determine the effect of oxytocin on the social behavior of primates. The monkeys were administered oxytocin spray through a respirator, and then presented with an option to keep, share, or waste a drink of fruit juice (a reward). The options were presented symbolically to one monkey with another monkey present, and consisted of two choices in three scenarios: in the first scenario, the monkey chose between rewarding itself vs. not rewarding itself, in the second, between rewarding itself vs. rewarding the other monkey, and in the third, between rewarding the other monkey vs. wasting the drink.
Monkeys treated with oxytocin showed an increase in prosocial behavior, choosing the “reward other” option more often, especially in scenario three, where the alternative was to waste the drink. Eye tracking cameras also showed increased eye contact between oxytocin treated monkeys, especially while making a “reward other” choice, suggesting the monkeys were more aware of each other. However, it took about 30 minutes for the increased prosocial behavior to manifest, suggesting that the hormone has a 30 minute delay period before coming into effect.
This study has shone light on the neurological effect of oxytocin within an animal model which is physiologically similar to humans. Researchers hope to use this knowledge to create hormone therapies for autism, schizophrenia, and other social disorders which involve a dis-interest in other humans.
Researchers at the Washington University School of Medicine in St. Louis have discovered that variations in the CD36 gene can alter a human’s sensitivity to the taste of fat in foods. Prior investigation of the CD36 gene in rodent models showed that rats and mice engineered without the CD36 gene no longer had a preference for fatty foods and were not able to digest fat properly. The preference for high-fat foods with higher energy yields is a vital part of the diet.
As noted in their article for the Journal of Lipid Research, not only can people who produce more CD36 protein more easily detect fat, it is estimated that 20% of people have a variant of the CD36 gene associated with making less CD36 protein. 21 participants, all with body mass indexes of 30 or more (within the range of “obese”), and varying degrees of CD36 protein production, were asked to taste and identify three different solutions. One solution contained fatty oil, while the other two were fat-free, but similar in consistency. To avoid cheating by scent and visual cues, the subjects wore nose clips and were tested in a room lit by red lamps. As expected, it was found that participants with genotypes conducive of higher CD36 production were better able to detect the solution containing fat than participants with genotypes less conducive of CD36 production.
“We did the same three-cup test several times with each subject to learn the thresholds at which individuals could identify fat in the solution,” explains Marta Yanina Pepino, PhD, research assistant professor of medicine. “If we had asked, ‘does it taste like fat to you?’ that could be very subjective. So we tried to objectively measure the lowest concentration of fat at which someone could detect a difference… We have to learn what the signal means. It could be how much fat they need to absorb to get the signal of satiety. This is just the tip of the iceberg, the beginning of the story.”
The ultimate goal is to understand how the CD36 gene works in humans, it’s relation to satiety, and how it may play a role in obesity. With such knowledge, researchers may be able to devise new measures and methods aimed at tackling obesity.
It seems obvious that to move comfortably at a fast speed, it is necessary to run rather than walk very quickly. Until recently, however, it was widely unknown as to what exactly makes it easier to run than to walk quickly.
Biomedical Engineers at North Carolina State University, after some experimentation, have determined the reason. These engineers work in a lab with a pressure sensitive tread mill, eight infrared cameras, and ultrasonic imaging devices to quantify human motion in hopes of developing robotic limbs to assist people in rehabilitation and therapy (see video below).
By recording the movement of the medial gastrocnemius muscle in the calf during walking and jogging, these researchers have discovered a mechanism which greatly increases efficiency while running. The medial gastrocnemius is the muscle which helps the all-important Achilles tendon function, working opposite the tendon as a ballast. As the stride is initiated, the muscle contracts, locking the Achilles tendon in place at the top, causing the tendon to stretch as the leg moves forward. A stretched tendon contains potential energy, which is released as the stride finishes, pushing the person forward.
Now consider the speed of gait in a power walk as compared to a jog. Power walking requires a much faster gait than running, where the stride is much larger, reducing the speed of the gait. This elevated walking gait causes the medical gastrocnemius to contract faster and change its length more quickly, resulting in less power and less efficient muscle use. When switching to a jogging gait (usually around 2 meters per second), the muscle returns to a slower contraction, storing more energy in the tendon and resulting in a more efficient stride.
This information is not only interesting to runners and joggers, but could also be critical in designing prosthetic or robotic limbs for disabled patients and in injury rehabilitation. The engineers involved in this study discuss their work and lab below:
Describing their achievement in an article titled “Generation of Chimeric Rhesus Monkeys” for the latest issue of Cell, scientists from Oregon Health & Science University engineered the first successful birth of chimeric Rhesus monkeys. Roku and Hex (shown right) are twins born to the same mother, while Chimero (a singleton) was born to a different surrogate mother at the Oregon National Primate Research Center (ONPRC). All three chimeras are male, though Roku was shown to contain both male and female cells.
A chimera is an organism composed of two or more differing populations of genetically distinct cells and tissues. Chimeric animals are formed from at least four parent cells, (i.e. two fused early embryos). In laboratory research, chimeric animals are valuable tools for investigating questions of genetics and cell lineage.
To conduct the study, surrogate Rhesus monkey females were implanted with in-vitro fertilized blastocysts, which were previously injected by a mix of tagged and untagged embryonic stem cells (ESCs) from multiple donors. After some time, an analysis of mid-term fetuses showed that chimeric tissues were not present. Due to this, further steps were taken to investigate whether the ESCs or the blastocysts were at fault for the lack of chimeric presence. The results showed that monkey blastocysts do not readily incorporate foreign inner cell masses or ESCs. In order to successfully create a chimeric Rhesus monkey, the scientists had to synthesize blastocysts from cells at an even earlier stage of development (totipotent rather than pluripotent cells) for implantation.
Totipotency describes cells that can potentially divide into all cell types, including the placental and fetal cells required for a viable organism (as opposed to pluripotent cells, such as ESCs, which cannot form placental cells). Thus, with the trial and error creation of chimeric Rhesus monkeys, the researchers discovered that higher primate chimeras can only develop from totipotent cells, unlike rodent chimeras, which can develop from a range of donor cell types (including ESCs).
Ultimately, medical applications for human stem cell technology may improve with these findings.
“This is an important development… it points out a key distinction between species and between different kind(s) of stem cells that will impact our understanding of stem cells and their future potential in regenerative medicine,” explains the Cell article co-author and associate scientist of ONPRC’s Division of Reproductive and Developmental Sciences, Shoukhrat Mitalipov, Ph.D.
Proteins regulate the expression of genes in order to maintain physiological balance within the body. Improper protein concentrations can lead to over or under expression of certain genes, resulting in pathological or psychological disorders. One such protein, MeCP2, has been shown to affect genes which regulate anxiety and social interaction.
Scientists at the Neurological Research Institute of Texas Children’s Hospital have recently isolated two genes (Crh and Oprm-1), regulated by MeCP2, which have a direct effect on symptoms of anxiety and autism spectrum disorders. The researchers found overexpression of these genes in an animal model of anxiety, leading them to investigate human patients suffering from anxiety for similarities. When they found elevated MeCP2 levels in many patients suffering from anxiety, they returned to the animal model to demonstrate that elevated MeCP2 protein levels caused overexpression of the Crh and Oprm-1 genes. Thus, the researchers successfully demonstrated a link between elevated levels of MeCP2 and overexpression of Crh and Oprm-1, and overexpression of Crh and Oprm-1 to anxiety disorders.
The protein MeCP2 regulates many genes in addition to Crh and Oprm-1, making it difficult to control levels of MeCP2 without compromising other systems in the body. The researchers, therefore, chose to block activation of the Crh and Oprm-1 genes in mice (through drug induced chemical blockades) rather than directly affecting MeCP2 levels. They found that reduced expression of Crh decreased symptoms of anxiety in mice, while reduced expression of Oprm-1 decreased the severity of social disorder symptoms. With this knowledge, developing genetic therapies for the treatment of anxiety and social disorders such as autism may one day become possible.
