mduque's blog

Inhibitory interneurons make it harder for action potential to fire. They work by allowing GABA to bind to transmembrane receptors that allow chloride ions into the cell. This binding makes the membrane potential more negative and the threshold for action potential harder to be achieved. If these were changed to excitatory in the stretch reflex, functions to maintain the muscle at a constant length would fail. As soon as the stretched muscle began to contract the antagonist muscle would stretch & both muscles would contract simultaneously.

Optogenetics refers to the biological technique which involves the use of light to control neurons. These neurons are genetically modified to express light-sensitive ion channels. Precise neural control is achieved by using channelrhodopsin, halorhodopsin, and other similar opsins that function as light-gated ion channels. Channelrhodopsins excite neurons while halorhodopsin inhibits them.  This method has to act and operate precisely and quickly in order to allow addition or deletion of specific activity patterns within cells. In order to keep up with optical control, reporter proteins are used, enabling the fused fluorescent proteins to detect the selected neurons. This advancement is now giving humanity the ability to alter the activity of specific types of neurons. Depression, a huge problem in the U.S, for example can be possibly treated with optogenetics. MRI images have suggested parts the brains of people who have depression look different than those without it. Since dopamine and serotonin have shown to be important in cognition, motivation, drug addiction and psychiatric disorders, stimulation by LED light at the wavelength of blue light to activate channelrhodopsin expressed in targeted dopamine neurons in the mid-brain should be extensively studied. That is, it is now technically possible to study what the activation and deactivation of specific neurotransmitters in this part of the brain does.

CD44 is a cell surface adhesion receptor that is highly expressed in many cancers and appears to regulate metastasis. Its recruitment to the cell surface and its interaction with extracellular matrix ligands promote the migration and invasion processes involved in metastases. Therefore, elevated levels of soluble CD44 in the serum of cancer patients can be used as a marker for the existence of tumor cells. The over-expression of this receptor is particularly seen in breast cancer cells. This discovery may allow for specific cancer cells to be detected rather than invading healthy cells through chemotherapy to get rid of defective muted ones.

Cells are normally searching for bacterial invaders and potential tumor cells, if they recognize one, they induce an immune response. However, healthy T-cell “checkpoints” can be muted by other proteins on the cell surface and can in turn weaken immune responses. This phenomenon is often seen in tumor cells where muted T-cell checkpoint molecules are expressed. To overcome this problem without the need of radiation, nontoxic nanoparticles can be used to sensitize the immune system. New antigens can be exposed to T cells which can prime those T cells to target other tumor cells that carry them as well. In order to get past the immune system, they need to be the appropriate size because small particles are more likely to get around macrophages. Prior to inducing them into the body, they have to be coated with polyethylene glycol shell which can help them survive longer in the bloodstream.

The genus canis has showed an interesting phenomenon with the discovery of the “coywolf”; a hybrid canid exhibiting mostly Canis lupus and Canis dirus genes but also Canis lupus familiaris genes. Many have gone as far as to calling the coywolf a new species. However, this assumption might be a bit of a stretch. Genetic tests show this is not the first time intermixing takes place. The eastern coyote for example, is also a mix of the three. In my opinion, that is because coyotes, domestic dogs, and wolves are the same species “that would very much prefer not to breed with each other”. The fact that they have continuously mated with one another throughout history and created viable offspring suggests they are indeed the same species. This has resulted in genetic swapping and gene variations amongst the three. The gene differences may result in sexual “preferences” where wolves would rather mate with a wolf, coyotes with coyotes, and so on. Still, preference is not enough to deem them three separate species. “Gene flow continues in all directions, keeping things mixed up, and leading to continual variation over their range, with no discrete boundaries."  Instead of being called closely related species, it would be more accurate to call them subspecies.

A study I recently analyzed for my sensory neurology course, aimed to find which mechanically-sensitive transducer channels allow hair cells to detect vibrations. The channels are believed to activate as a result of deflection towards the tallest stereociliary row. This is caused by a force applied by extracellular tip-links. Calcium signals in the first, second, and third stereociliar rows of a rat’s cochlear inner hair cells were visualized by using fast confocal imaging of fluorescence changes that reflect calcium entry during stereociliary bundle stimulation. Calcium was the ion of choice because hair cell channels have shown to be highly permeable to it. Individual stereocilia were imaged at the apical portion of the bundle and indicator dyes with a range of affinities were used. The results from these experiments indicated there are no channels in first row stereocilia therefore suggesting channels that detect vibrations of the stereociliary bundle are only present at the bottom of tip-links.

Yesterday I went to a seminar held by Steve Ramirez from Boston University who is studying a way to artificially activate positive and negative memories in healthy and maladaptive states. He explained optogenetic reactivation of hippocampal dentate gyrus neurons activated during fear conditioning were sufficient to induce freezing behaviour.  That is, activating these neurons without actually presenting the mouse with the fear stimulus was sufficient for the mouse to show signs of fear. In a similar proportion of cells, the freezing was not detected upon light-stimulation on ChR2 in non-fear conditioned mice. The freezing, act of fear, was also not detected upon fear-conditioned mice with cells labeled by a different protein instead of ChR2. 

In my Sensory Neurology class I was asked to analyze a paper that paper aimed to demonstrate cadherin-23 and protocadherin-15 interact to form the tip links in sensory hair cells. More specifically that tip links are adhesion complexes consisting of CDH23 and PCDH15 and interact at .1mM Ca2+. What is known about tip links is that they are extracellular filaments that connect stereocilia to one another and allow for mechanotransduction to take place. They connect to cation-selective transduction channels that allow K+ and Ca2+ to enter the hair cell. There they have the ability to be deflected which allows for depolarization to take place. What these tiplinks were made of was unknown until this recent hypothesis. Skeptics say the development of the hair bundle is much more complex. Hearing loss and lack of mechanotransduction in a CDH23 mutant animal does not necessarily prove direct involvement of CDH23 in mechanotransduction. There is a possibility that the hair bundle itself has a different mutation or development issue that does not allow mechanotransduction to take place in the first place or that a particular mutation or change in one of the CDH23 domains affects a particular pathway that has a downstream effect on the actual tiplink.

This hypothesis suggests that living in larger groups promotes cognitive development. This hypothesis is under the idea that maintaining social bonds as well as anticipating the actions of others is the central driver of cognitive evolution. The potential for group-size-dependent cognitive traits to come under selection is not completely understood. However, this theory hypothesizes that social intelligence and social demands were the central force in the developing size of the human brain. This theory is backed up by the fact that key growth periods in human brain size are directly correlated to times where early humans were living in more complex groups which required greater mental capacity that potentially led to the evolution of language. Therefore, social intelligence is not fixed but rather involves complex information-processing that can be acquired and has an adaptive equilibrium directly related to the individual and the environment. 

According to a recent publication, Microorganisms found in dirt can yield antibiotics that can kill pathogens that already have found a way to create drug-resistance to known antibiotics. Soil samples across the country were analyzed, particularly in the search for known genetic sequences used in the production of antibiotics. A sequence was identified and a new possible antibiotic has been tested on the skin of rats which showed signs of sterilization of MRSA. Even if this method initially fails to kill pathogens in human cells, the discovery brings hope as increasing antibiotic resistance is becoming becoming a huge problem all around the world.