Lions, and Tigers, and Vampires! Oh My!

Vampires. No not the Edward Cullen type of vampire who sparkles when he gets in the sun and he only drinks the blood of animals because he is "vegan." I am talking about Dracula-type, who only can come out at night because the sun will kill them and they have to drink blood of humans to survive. These living-dead creatures are immortal with characteristically sharp teeth that help them penetrate the jugular of their midnight snacks. The sun basically turns them into a walking fireball that first starts out as small patches of burning that within seconds engulfs them in flame. In reality these beings do not exist (don't go to New Orleans or they will tell you otherwise), but there is a disease that mimics the vampire's sensitivity to light, fang-like appearance, and need for blood. Congenital erythropoietic porphyria (CEP) or Gunther's disease is marked with hypersensitivity to light, anemia, passing of dark colored urine. in some cases the gums recede making the teeth look fang-like.

CEP is an autosomal recessive disease that occurs when both parents have a copy of the mutated/abnormal gene and the baby inherits both abnormal version of it. The chance of passing CEP is higher in individuals who are closely related. According to Congenital erythropoietic porphyria: Insight into the molecular basis of the disease, having molecular conformation is crucial to the treatment of this disease. This disease is caused by the deficiency of uroporphyrinogen III cosynthase enzyme, expressed by the UROS gene. This enzyme is important in creating heme, which is the factor that allows your blood to bind to oxygen. Sequencing of this gene has found about  39 different mutations that could be the basis of this disease, although data on the mutations is limited. All of the mutations are either missense mutations, nonsense mutations, or frameshift mutations. In most cases, the genotype determines the different aspects of the disease and the severity of each. For example, patients who had the C73R/C73R mutations on exon 4 of the UROS gene showed very severe manifestations of the disease, while individuals with the T228M/C73R mutations showed a more milder form of the disease. However, what makes this disease hard to understand is that sometimes the genotype-phenotype is not present. Two individuals with the same mutations, P248Q/P248Q, showed a different clinical profile. (If you are not familiar with the way each of these mutations are set up (C73R/C73R), it is basically one mutation that is found on one chromatid and the other mutation is found on the other chromatid.)

Since the molecular basis of the disease is vague and confusing, only symptomatic treatment is being administered until scientist can figure out a way to treat it by gene therapy. Like vampires, individuals with this disease need blood to survive, frequent blood transfusions are given to those individuals that present with severe anemia. Bone marrow transplants are another, more beneficial, way to virtually cure the disease with the hope that the new bone marrow has a functional copy of the UROS gene.

For Further Reading:
http://eds.b.ebscohost.com.ezproxy.shsu.edu/eds/pdfviewer/pdfviewer?vid=14&sid=4a683f92-0d69-44d0-887b-5b95858acb25%40sessionmgr105&hid=127

http://www.porphyriafoundation.com/about-porphyria/types-of-porphyria/CEP

Nature's Deadpool

I know many of you are looking at the above picture and questioning what the heck this adorable creature is. It is called an axolotl and it is a Mexican salamander. These little guys are unique because they do not undergo metamorphosis at maturation. This means that these little amphibians stay in water for the entirety of their lives since they never grow lungs and keep their cute gills. They are also particularly interesting because they can regrow almost every one of their limbs, similar to the starfish or the lizard. Scientists believe that this could be in relation to gene expression of homeobox genes.

Hox genes, or homeobox genes, are responsible for pattern development of limbs. Since urodele amphibians, like the axolotl, have a really remarkable ability to regenerate their limbs scientists at the University of California, Irvine's Developmental Biology Center wanted to see the role Hox genes, in particular the play HoxA complex, in this ability.

These genes essentially get turned off after limbs are developed in the embryo and in humans they do not get turned on again, which is unfortunate. Within the HoxA complex, Hox9  and Hox13 are both reexpressed early within the regeneration of the axolotl limbs. Not only does the axolotl express these Hox genes, these scientists isolated 17 different genes that are similar. Along with Hox, these 17 genes are responsible for the complex regeneration system. These genes are usually expressed with temporal and spatial colinearity during embryo development, meaning that the genes at one end of the chromosome are expressed at the head while the genes at the other end of the chromosome are expressed at the tail end. This is not the case for limb regeneration. Once signaled, these genes express the same way no matter where the limb loss is located (the cells do not differentiate). It is not until the later process does the cells start to differentiate depending what place along the proximal-distal axis they are being grown from. Basically, all of the limbs and tail start out as a stump and then once they reach a certain point, they will differentiate into the correct limb.

Could we potentially use this knowledge to help amputees regrow limbs or would that be pushing science a little too far? Humans do express both the HoxA13 and the HoxA9 genes.

LSD Causes Schizophrenia???

Schizophrenia is a mental disorder that is classified by its symptoms of abnormal social behavior and the inability to discern what is real from what is not. Many symptoms are circled around having false beliefs, unclear thinking, hearing voices, and reduced social engagement. If you know anyone with schizophrenia you know that this disorder can have a detrimental effect on the individual's life. With that said, no one really knows the absolute causes of this disease. It is believed that environmental factors along with brain chemistry and genetics play a huge role in the progression of the disorder. In research regarding this topic, scientists have discovered that aromatic l-amino acid decarboxylase (AADC) concentrations in blood serum is increased. AADC is the rate limiting step in the production of 2-phenylethylamine (2PE), which is a known psychotogenic (causes the individual to experience psychosis) and dopamine agonist. This is particularly useful knowledge because it is also known that schizophrenia is a highly dopaminergic system. 

To play off the knowledge of the knowns about schizophrenia, scientists at the University of Wales College of Medicine, tested to see what two psychotogenic drugs, LSD and PCP, do to the levels of AADC  mRNA levels in rats. LSD and PCP are two known hallucinogenic drugs but they are considered non-dopaminergic, as LSD affects serotonin levels and PCP affect many neurotransmitters but mainly glutamate. The reason why these two drugs were chosen is because they are used as schizophrenia models in animals but they both have different structures and different pharmacologies.

In this study, however, it was shown that both LCD and PCP have small effects on AADC gene expression, with LCD acting as a probe for exon 8. The mechanism of the up-regulation of AADC mRNA is unclear for both of these drugs but the mRNA change patterns for both of the drugs is really similar. This study does further prove that using these drugs could cause the expression of the gene that codes for AADC and in turn produces 2PE, but the evidence in this study was not statistically significant. In humans there are two alternative exons at the 5' non-coding region of the gene one being predominate and lacks exon 3 causing it to be short 38 amino acids and does not catalyse the conversion of DOPA into dopamine. This shorter form could be the cause of phenylalanine converting to 2PE. Since rats do not experience schizophrenia then this primary version of the gene might not exist or exist in such small quantities that caused the statistical insignificance. There might have to be other types of studies that would have to be tested on individuals that actually use these drugs or other animals that experience schizophrenia to get statistically important results. 

Genes Associated with Human Interaction in Dogs

We have all heard the phrase that says dogs are a man's best friend. In many people's opinion dogs are the superior pet because they have the ability to be trained, while cats know what you are saying but they honestly do not care. Over their evolution, domestic dogs have developed social skills that allow them to communicate and cooperate with humans and even pick up on when "their" human is emotional. Even puppies seem to have this cognitive ability to process human communication; this makes scientists question that this might have a genetic basis. Persson et al. used this concept and a genome wide association study in beagles to map the genes that are responsible for their superior social skills.




One hundred and ninety laboratory beagels' genomes were mapped using an HD Canine SNP-chip and then given a device that they could manipulate to get treats. The first two were fairly easy to get but the third was one difficult and this made them seek out a human for assistance. Five possible genes on chromosome 26 were then identified that were associated with their social skills with humans. These genes are the first possible genes that corroborate that there is a genetic basis in human socializing in dogs meaning that this socialization happened over the course of their domestication and evolution.




Another interesting finding is that one of the possible genes, SEZ6L, is the same gene that has been recently found to be associated with autism spectrum disorder and polymorphisms are responsible with bipolar disorder in humans. The polymorphism of the gene COMT is also known to be the cause of susceptibility to develop schizophrenia in humans. This same polymorphism in varying degrees was found in other dog breeds suggesting that this could be the gene responsible for regulating behaviors.


While the purpose of this research is to map the genes associated with behavioral traits in dogs, the also paper cites other studies suggesting that there are breed-dependent diseases, like heart disease and epilepsy, that suggest that dogs could be used as a model organism for human disorders. This brings me to question, how would these scientists use dogs as a model for understanding disease progression and mental health disorders? Would they induce the disease process by genetic modification like they do for mice, who have shorter gestation periods and life spans? What do you think about this new information?


Reference: http://www.nature.com/articles/srep33439