May 2012
53 posts
Structure of the First Sphingosine 1-Phosphate Receptor →
stke.sciencemag.org
The sphingosine 1-phosphate receptor 1 (S1P1) and its ligand, sphingosine 1-phosphate (S1P), have now emerged as critical regulators of lymphocyte trafficking, vascular development and integrity, and immunity. S1P1 is targeted by the phosphorylation product of fingolimod, which has been approved for the treatment of multiple sclerosis. The recent progress in the structural biology of heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors has now enabled the elucidation of the structure of S1P1. Analysis of the structure, along with structure activity and mutagenesis analysis, highlighted key interactions associated with the binding of S1P and agonists and suggested that the ligand may gain access to the binding pocket by lateral diffusion within the plasma membrane. The S1P1 crystal structure will be helpful for designing ligands that specifically target S1P1.
Announcement: Name Change and More
Due to this blog’s formerly controversial title, I’ve decided to change the name to “The Biology Lair” with a URL of http://www.biologylair.tumblr.com. The former name may have been off-putting for some, and I’m hoping that this new name reflects the fact that biology is for everyone. Feel free to provide feedback on the change!
With that said, I would like to also announce that today, we’ve reached over 100 followers. That may not sound like much, but I am ecstatic considering that this blog was created less than two weeks ago. It’s nice to know that there are so many people who appreciate biology!
This is kind of random but I’d also like to acknowledge Tumblr user apoptotica (http://apoptotica.tumblr.com), whose fantastic biology blog in part inspired the creation of this one. Follow him if you aren’t already!
The Evolutionary Complications of Human Teeth
The various dental and orthodontic complications of human teeth today can be attributed to their evolutionary origins. Human teeth evolved to mechanically digest coarse seeds, nuts, fruits, etc, not digest the high-sugar, processed foods of today’s post-industrialized societies. An article in Science Magazine provides an interesting theory as to why humans during the Neolithic era had such amazing teeth.
Necrosis: Programmed Cell Death?
Necrosis is widely considered a “premature” death of cells and tissues. However, it is possible that the process can in fact occur as a type of programmed cell death, similarly to apoptosis.
…Recent data indicate that, in contrast to necrosis caused by very extreme conditions, there are many examples when this form of cell death may be a normal physiological and regulated (programmed) event. Various stimuli (e.g., cytokines, ischemia, heat, irradiation, pathogens) can cause both apoptosis and necrosis in the same cell population. Furthermore, signaling pathways, such as death receptors, kinase cascades, and mitochondria, participate in both processes, and by modulating these pathways, it is possible to switch between apoptosis and necrosis. Moreover, antiapoptotic mechanisms (e.g., Bcl-2/Bcl-x proteins, heat shock proteins) are equally effective in protection against apoptosis and necrosis. Therefore, necrosis, along with apoptosis, appears to be a specific form of execution phase of programmed cell death, and there are several examples of necrosis during embryogenesis, a normal tissue renewal, and immune response. However, the consequences of necrotic and apoptotic cell death for a whole organism are quite different. In the case of necrosis, cytosolic constituents that spill into extracellular space through damaged plasma membrane may provoke inflammatory response; during apoptosis these products are safely isolated by membranes and then are consumed by macrophages. The inflammatory response caused by necrosis, however, may have obvious adaptive significance (i.e., emergence of a strong immune response) under some pathological conditions (such as cancer and infection). On the other hand, disturbance of a fine balance between necrosis and apoptosis may be a key element in development of some diseases.
From the abstract of “Necrosis: a specific form of programmed cell death?”
The research suggests that necrosis, from an evolutionary perspective, is not entirely detrimental. The benefit of the immune response it triggers, in some cases, may outweigh its complications.
