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OK, let me start off by saying that the lectures were tough. Zwickey went way too fast for me and her lecture outline is pretty minimal. This first post is a summary of her first 1.5 lectures.

Brons' lectures have been alternately terribly boring and repetitive, or wildly unfamiliar and poorly explained. I often have no idea what his main point was. His power point presentations have many illustrations with huge amounts of information that we are repeatedly told not to worry about. Formulae are given with the caveat that we will not do any math in this class. The professor has said that we are to "learn the song but don't worry about the words". Well, frankly, I already know the song that he is singing. To put it very briefly, the entire first part of his class has been about how gene expression is modified in many ways at many times in the development of an organism starting with the zygote. And about the fact that it is these adjustments to gene expression that cumulatively cause the development of every specialized cell, tissue and organ in the body. So now I am going to embark into learning some of the words of the song. After the test I will provide you with an assessment as to how much my previous knowledge of the song prepared me for his exam.

There are two types of cells, prokaryotes and eukaryotes. We are eukaryotic, meaning that we (generally) have no cell wall, our cells are relatively large, our DNA is contained inside a nuclear envelope, or a nucleus, and is in strand form. Plants, fungi and protists are eukaryotic too. We have organelles which are areas with specialized functions inside membranes inside the cell. We eukaryotic creatures are different from prokaryotes, which don't have organelles. They are smaller, and their DNA is circular (plasmid). They don't have a membrane-bound nucleus, instead they have a "nuclear area". Prokaryotes are bacteria, for the most part. There's also a new kingdom in the categorization of life that is prokaryotic, which is called archaea, which is basically the very archaic bacteria. There are two types of prokaryotes as divided by the gram-positive protein contents of their cell walls, those containing LTA (lipotechoic acid) and LPS (lipopolysaccharide). The cell walls also contain polysaccharides, lipids and other proteins.

Eukaryotic cell membranes are made of a lipid bilayer with lots of proteins in them. The proteins serve functions such as: protein receptor, enzyme, transport, digestion, ion channels and more. Our membranes also are full of cholesterol. Cholesterol gives our membranes rigidity (due to the rings in the molecule), makes the membrane less permeable and more fluid (unable to crystalize). High levels of cholesterol have been shown to be involved in diseases such as alzheimer's, parkinson's and autism.

If a membrane has a lot of proteins in it then there is more transport going on, but if there are more lipids (such as cholesterol) then it's more insulated. Neuron axon membranes are mostly lipid. Mitochondrial membranes (hotbeds of metabolic activity) are have lots of proteins.

A 2004 study showed that increased cholesterol causes alzheimers by causing a mutation in an enzyme known as CYP46, which is a lipoprotein that affects transport across a cell membrane.

A normal eukaryotic membrane of a living cell has phosphatidyl choline and sphingomyelin on the outer "leaflet", ahd phosphatidyl serine and phosphatidyl ethanolamine on the inner leaflet. When the cell dies a "flippase" (enzyme) causes those molecules to trade places. Phagocytes know the cell is dead and needs to be broken down when the inside markers show up on the outside.

Cell membranes also contain carbohydrates, in the form of glycoproteins and glycolipids, which are often blood group antigens.

There are four ways through a cell membrane. Osmosis along a concentration gradient is one. Water can get across even though it is polar. Passive transport, which works for uncharged stuff like O2 and CO2. Facilitated diffusion uses a protein to get things through. And active transport which requires energy to move something against a concentration gradient.

There are three kinds of active transport: uniport, symport, and antiport. Uniport moves one thing one way. Symport moves two things the same way, for example glucose and sodium are moved from the intestinal lumen to a brush border cell together via the glucose-sodium symport protein. Antiport moves things in opposite directions. The sodium potassium pump moves 3 sodium out and 2 potassium in, per cycle. Cardiac muscle moves calcium out and sodium in to decrease the frequency of contractions.

Cystic fibrosis is caused by screwed up transport, specifically a botched chloride channel. The symptom list for CF is terrible, a few of the list: increased mucus in general, rectal prolapse, club fingers and toes, sweaty salty skin because NaCl is coming out of the pores, bowel blockage, thick sputum, cirrhosis, nasal growths, chest and sinus infections...the list goes on.

brush border = A bunch of microvilli lining the small intestine. Brush border enzymes contribute to digestive breakdown (these enzymes are lacking from absorptive cells of the colon). The microvilli are supported by a mesh of microfilaments (the terminal web). At the lateral edges of each cell, the the terminal web reinforces the junctional complex that attaches adjoining cells. This junctional complex was visible as a black dot in histology lab.

Phosphorylation is an important step in the transduction of signals from receptors on the cell membrane to the nucleus.

Energy medicine affects membrane permeability. Sound affects it too.

Tatoos made of are India ink injected into cells where it is then endocytosed by fibroblasts and macrophages in the dermis and subcutis. The ink paralyzes the cell, which just sits there hapless until it dies.

Endocytosis = a cell taking in things through the membrane by sucking in a part of the membrane, keeping the material inside that bubble of membrane until it reaches its destination. Fluid phase endocytosis or pinocytosis is "cell drinking", or taking in water. There is no receptor involved with this kind. Receptor mediated endocytosis on the other hand involves the formation of a clathrin coated pit to pull the endosome into the cell. Clathrin looks like boomerangs. Phagocytosis is the 3rd kind of endocytosis, and only macrophages, dendritic cells and neutrophils do it, with or without receptors.

clathrin = a protein that is the major constituent of the 'coat' of the clathrin coated pits and coated vesicles formed during endocytosis of materials at the surface of cells. Studied by a lady named Catherine. Clathrin molecules are recruited with the aid of adaptor proteins to a membrane segment that is destined to be incorporated into a vesicle. In synaptic vesicle formation one such adaptor protein is AP180. This protein both recruits clathrin to membranes and also promotes its polymerisation in a localized polyhedral lattice on the plasma membrane.

Exocytosis side note:
The toxins Botox (clostridium botulinum, a club shaped bacteria) and Black Widow venom act in opposite ways.
-Botox inhibits the exocytosis of acetylcholine (ACh) at synaptic junctions. ACh is required for communication in autnomic anglia. The result of botulism toxin is reduced muscle tension.
-Black widow venom causes all the ACh to release at once, locking up the muscles in a spasm like a seizure. Something called alpha lactotoxin pokes ion-permeable holes in presynaptic cell membranes, so calcium flows freely across. Calcium flowing in triggers a massive release of presynaptic vesicles.

OK, on to Lecture 2 on Intracellular Organelles::::::

NUCLEUS: very full of stuff. Lots of pores in nuclear envelope, transcription factors and other small proteins can get in via diffusion or transported if they're too large to diffuse. Steroid hormone receptors are transcription factors (TF), so the hormone crosses the plasma membrane into the cell, binds to a receptor on the outside of the nucleus. This binding causes the receptor to "sit down" (thru the envelope) on the DNA and have some effect on transcription.

The nucleus has a double membrane that is thicker than the plasma membrane, and is continuous with the ER (endoplasmic reticulum). Inside the membrane is the nuclear lamina, which is a lattice-like network of proteins that organizes the nucleus, like a scaffolding. It's involved in cell division and connects the chromatin to the nuclear envelope.

The NUCLEOLUS is the regoin in the nucleus where rRNA synthesis happens, ie. ribosomes made here. The darkest parts on an electron microscope are where the ribosomes are being assembled. The lightest parts are where the DNA is not being transcribe. In cells making large amounts of protein, the nucleolus may occupy 20-25% of the total volume of the nucleus. In cells that aren't making protein it can be invisible.

Functions of the nucleus: mitosis. Green tea affects cdcs and cdks, affects when a cell goes into replication cycle. Meiosis (making gametes). DNA replication -- copies galore. Transcription --make RNA of all kinds. Chromatin storage.

DNA---know that purines are adenosine and guanine, pyrimidines are cytosine and thymine.

DNA packaging:

Histones = positively charged proteins with many lysine and arginine residues. The chief protein components of chromatin. They act as spools around which DNA winds, and they play a role in gene regulation. Involved in DNA packaging: the DNA winds around them and makes nucleosomes. There are 150 base pairs in a wrap, with 60 base pairs in the strand between wraps. When the cell dies enzymes chew through these strands.

Solenoid fibers = long strands of nucleosomes packaged by histone H1 insto a helical secondary chromatin structure. Each turn of the solenoid is ~6 nucleosomes. So in order from small to large: DNA, string of nucleosomes, solenoid fiber, loops, chromatin, chromosome. ... In eukaryotes, DNA supercoiling exists on many levels of both plectonemic and solenoidal supercoils, with the solenoidal supercoiling proving most effective in compacting the DNA. Solenoidal supercoiling is achieved with histones to form a 10nm fiber. This fiber is further coiled into a 30nm fiber, and further coiled upon itself numerous times more.

Types of chromatin: Heterochromatin and Euchromatin.
- Heterochromatin is darker, highly condensed, transcriptionally inactive and is about 10% of the total....it resides at the ends and in the middle of a chromosome, to keep enzymes from chewing up the ends, and in the middle where the two parts of the chromosome are attached.
- Euchromatin is more extended, transcriptionally actrive, and is about 90% of the chromatin though maybe 10% is actively transcribed. ... a lightly packed form of chromatin that is rich in gene concentration, and is often (but not always) under active transcription. Unlike heterochromatin, it is found in both eukaryotes and prokaryotes.

This is getting terribly long so I'm cutting to go to a new post.



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