(no subject)
Teaching is all kinds of things that you don't expect.
I have to amplify my C-DNA with PCR and then run the products on agarose to identify how strong or weak the bands are. I haven't done PCR on my own (or at all since Fall 2014 for that matter). Friday I start helping with the model model study. My classes went from 0 to 100 MPH basically and we're covering all kinds of things.
This is like, 1/16th of what I learned today and will be on the written essay exam.
"1,25-dihydroxyvitamin D3 acts as the ligand for the ligand-activated nuclear steroid hormone Vitamin D Receptor, which is 1/2 of the heterodimeric nuclear response element VDRE.* Both hetero- and homozygotic mutations in the form of single nucleotide polymorphisms (SNPs) alter the abilities of VDR including its binding affinity, SNPs occuring in genes that code for zinc finger functional domain of VDR especially so. Individuals who carry a higher number of SNPs and experience deficiency in vitamin D intake may suffer from an increased risk of unfortunate sequelae, as linkage between number of SNPs and chronic disaease has been suggested in many studies. Changes in untranslated regions such as introns that result in silent mutations have also been associated with increased risk.
*RXR is the other half of the dimer.
Known non-genomic mechanisms of action are comprised of cell-membrane signalling cascdes. The interaction of an extracelluar factor (e.g., hormone or growth factor) with its membrane receptor results in the activation of membrane G-protein inducing GTP binding to the alpha-G-protein subunit. (I am assuming these are part of the secretin family of g-protein coupled receptors, which have a much larger amino terminal domain/the factor will fit into the gap between the AT domain and the 7 membrane-spanning alpha-helices). The GTA-alpha subunit stimulates Phospholipase C (PLC) activity (converted from its inactive form to its active form) which can now hydrolyze phosphatidylinositol 4,5-bisphosphate (PIP2) into water-soluble inositol-1,4,5-triphosphate and lipid-soluble diacylglycerol (DG) second messenger. Water-soluble IP3 then travels through the cytosol to the endoplasmic reticulum where it interacts with a receptor, resulting in a release of stored calcium. This initiates a rapid increase of free calcium concentrations within the cytosol. Transient, hormone-mediated changes in intracellular calcium concentration trigger the activation of calcium-responsive molecules, such as an ubiquitous protein called Calmodulin (CaM). CaM is activated by binding Ca+ which in turn activates CaM-dependent enzymes; kinases that phosphorylate to downstream target molecules of the signalling cascade leading to an eventual "physiological response" *can include alzheimer's disease*. It is suggested that calmodulin-dependent kinases also phosphorylate serine residues in zinc regions on VDR which are critical for binding to DNA. Within the plasma membrane, DG in the present of phosphatidylserine (PS) and calcium activates another cellular kinase (protein kinase C [PKC] which catalyses the phosphorylation of other proteins in the signaling pathway, leading to a physiological response."
Next time you have free time, please have a drink for me.