Choice A bc there is more Na excretion

Block Na reabsorption -- triggers ADH release

Loop diuretic bc too much ADH so by blocking the thick ascending limb, the water can't be absorbed as well

ENac

Thiazide

Use loop diuretics bc they are potent and fast acting (thick asending limb of Henle where 25% of Na is reabsorbed)

Need a lot of treatment for proximal RTA, distal RTA severe acidosis, hyperkalemic has high K+ and requires mineralocorticoid tx

Blood cancer that affects plasma cells

Fanconi's is not limited to bicarbonate, other disorderly absorption is involved

Retain Cl- to maintain anion gap

Less efficient bc it doesn't retain Na, so the H2O distributes across all compartments instead of just ECF where it is needed to maintain ECV. Only a small fraction reaches intravascular space (most needed to restore blood volume)

5% dextrose is considered just free water since it is metabolized quickly. -Na will become more dilute. Helps in H2O balance but oesn't correct volume deficits

To treat hyponatremia, use normal or half normal saline to correct hypovolemia (restore volume and Na) Use D5 to address water imbalance.

There can be a disconnect in the Na status and H2O status

Dec BV so less bloo can be redistributed to upper body when standing

Hypotonic hyponatremia-- Na is a good indicator of osmotic state (evaluate hyponatremia)

Hypertonic hyponatremia (serum osmolarity is higher than suggested by serum concentration)-- another osmolite is doing this

Pseudo hyponatremia (serum osmolarity is normal, but Na conc is low)-- protein or triglycerides artifically lower the measured Na - Solid make up a larger portion of the volume, "diluting the liquid portion" - Na in liquid is normal but larger volume of solids make it look like there's too little Na

When ADH is released innapropriately, it can retain too much water

Too little Na, too much H2O

This will lead to a dec in K so the body reabsorbs via adjusting Na/K ATPase pump and ROM-K.

Aldosterone inc the Na reabsorption and K excretion

Too much H+, so this excretes it

Too little K, alpha intercalated exchanges K/H

Downregulates AQP2 expression

Enteric removal: exchanges Na for K to remove it in GI

Raises threshold potential for cardiac myocyte. does NOT lower serum K

Breakdown of skeletal muscle

Inhibits glutamine metabolism

Significantly inc K+ secretion at high flow rates

Aldosterone trying to get rid of K+

Diuretics inc distal flow-> inc K+ loss -> hypokalemia

Treatment as usual

Technique

A stretch

Embodiment saves energy-> more energy for survival and reproduction

View emerging that biology and cognition are separate. Another view says that behavior must be viewed as embedded in the environment

They don't know to go against the opinion of the scientists.

intervening variable interpretation terms are exhaustively defined relative to observable measures hypothetical construct interpretation terms are partially defined relative to observable measures - Both work but need to be consistent in that usage

Logical positivism favors partial definitions - A negative attitude can influence many behaviors, so it needs more broad, partial solutions

Exhaustive definition: fully defined by refering to observable things (habit strength) Partially defined: some things are observable (superego) - Thought exhaustive was better initially then switched to partial bc it was applicable across situations

Operationalism

SOR where O is the main factor to be observed. It mediates between stimulus and response.

Classical behaviorism (S-R) needed to be modified bc behavior sometimes 1.) was spontaneous 2.) had variation - R is response, which is the thing being studied

People had studied senses and reflexes, but Wundt was responsible for turning it into a more experimentally determined branch of work - Took a physiological approach

Threat

Same underlying principles, with slight shifts in priorities

Making a connection between aggressive presentation and T2/FLAIR hyperintensity. Then seeing the relationship between CVD and how it is incorporated.

Presence of CVD= risk factor for neurological risk

T2/FLAIR hyperintensity is a sign that there are still symptoms-> especially prevalent with CVD

• Going from G to S, in addition to DNA damage being repaired, many diseases are associated with mutations here

• Repressor binds (prevents transcription)
• Under UV light, RecA Coprotease is activated and cleaves the repressor, so the genes are induced-> umuC and umuD (code for DNA polymerased)
• Repair thymine dimers, but it is error prone, so we don't want it normally
• Lots of mutations, but preventing death

Recognition * MRN complex: prepare for invasion of other strand * Exonuclease chews it down, so there is a primer that is rready for attachment * ssBP come in and Rad51 create a holiday junction that can result in high fidelity * Recognize, process using exonuclease, then, strand migration can occur, and polymerases with hih fidelity copy information and resolve everything

Error-prone * Glue pieces of DNA together * If there is a break, some information will be lost bc the polymerase causes them to be blunt ends * When ligated, insertions and deletions are common -> shifts the reading frrame * CRISPR works by hopefully doing NHEJ to KO genes * Recognition step, ligase

Base: alkylation, oxidation, deamination, x-linking Breaks: ssDNA, dsDNA * Homologous: can only do it when the two chromosomes are paired during the cell cycle (low error! but, can only happen very infrequently)

• Damage is in the leading strand; lagging strand is fine
• Copied across the damage, have not repaired the damage
• But, Y family DNA polymerases are error prone
• Low fidelity!

New okazaki fragment gets stuck, lagging strand is not fine, leading strand IS * Leading strand is transfered so that it is exchanged with the daughter strand. * Gap in old parent strand so then the error can be bypassed, so the replication is no longer stuck * Exchanging the stuck strand and unstuck one, so it bypasses the halting error

In eukaryotes, they don't use the methylation trick

• Endonuclease scans and looks for hemimethylated site, so it can identify the new strand and excises it past the problem.
• DNA polymerase III and ligase close the gap
• Endonuclease: cleaves and forms nick, exonucleuse breaks further

• Know which strand the parent vs daughter is to cleave the correct base.
• In E. coli, there are methyl groups that get added to a particular motif
• Hemimethylation: daughter strand is unmethylated, so it can be targeted for excision
• Methylation takes time to occur after replication

If damage is caught in time, then the glycosylase sees it and removes it. BUT, image, it could not recognize it in time, so replication occurs * Remove A and do DNA synthesis across oG and incorporates the correct base, however, if it adds the wrong one again, there are far more problems to worry about

• Abasic site-> 2 options: AP endonuclease (cleaves phosphodiester bond upstream of the abasic site, so 3'OH is exposed, so a primer is generated)
• Endonuclease can cleave one nucleotide only, and it can be corrected and resealed, or multiple nucleotides -> flap formed (only one is damaged, but excise the entire region)
• Another pathway, instead of endonuclease, uses AP lyase, where it cleaves downstream instead of upstream, so it can't do DNA synthesis, so it must cleave the base before continuing

• Enzyme has an active site that only takes out Uracil-> allows for cleavage
• Nucleotide excision repair doesn't care which base it is, knows that it doesn't look right, but here, it is specific

• Need enzyme that recognizes the incorrect base
• Ex: Uracil, it should not be there
• Get rid of the unincorporated dUTP, cleansing enzymes convert it to dUMP, which can't be used by the polymerase
• Glycosylase: cleaves the base off so an abasic site is formed

• Sensing differs, but after that, it is all the same
• Good at recognizing large adducts.

Don't need to know name of enzymes, but need to know fxn * Recognize, excise up and downstream, remove by helicase, polymerization, then ligation

Repair bulky adducts, which will have an effect on the B helix formation

Enzymes become inactivated in the process * Transfer methyl group from O6 into themselves * Cysteine attacks guanine, but the enzyme becomes inactive. * Once methylated in bacteria, become transcription factors-> activates adaptive response, which allows it to make more of the enzyme itself * Work on all alkylation, but some are repaired rather through excision repair

Becomes a free radical and goes through a rearrangement that corrects the thymine dimer, which allows FADH to return to ground state * Driven by sunlight, don't need to know mechanism, but know what it is * Chromophore is excited, which donates to FADH, which can repair thymine dimers

Why is DNA so good at being repaired? Especially in comparison with RNA? * Information in other strands and chromosomes * Geometry of helix * Only 4 bases

Depurination can cause a deletion

UV A and B can cause damage * Cyclobutane dimerization * 6'4' photoproduct (binds with C 4 instead of 6)

Adduct: modifying agent

React with almost every base, especially guanine * Guanine is the most reactive with these species * When oxidized, it becomes mutagenic * Does not react with WC face, causes the base to switch from anti to syn

Alkylation of O6 is VERY mutagenic * Special suicide enzymes to get rid of it * Even methylation of a non-pairing region can disrupt polymerase binding

Universal methyl donor in cells, don't need to know structure SAM + lys <=> Lys-CH3 Intentional reactions to methylate SAM is highly reactive and can react in an uncatalyzed reaction * ROS can react, creating a profound effect on replication

Water is not reactive with bases, but since it is at such a high [ ], it will react -> depurination * Lose base and have an abasic site Deamination-> instead of amine, have carbonyl * Water driven

• Changing the amine group to a carbonyl, which will have drastic effects
• Acceptor to donor, will base pair with new base
• C -> U is the most problematic, b/c the machinery can't tell if U or G is the problem. If it fixes the G, it will be incorrect-> mutation. If it fixes U, it will also be a mutation

• Water attacks 1'C -> depurinated

Why are biological molecules susceptible to damage? Want DNA to be accessible. * Phosphodiester bond breakage and losing the base are both labile (-dG) * Spontaneous: react with water, itself, etc.

• Refer to drawing

• Not all polymerases are equivalent (either nuclear or mitochondrial DNA replication)
• Delta and epsilon replicate nuclear; gamma replicate mitochondrial DNA
• Look for high fidelity
• Why can alpha have a lower fidelity? Okazaki fragments , polymerizing short fragments
• All others are involved in DNA repair
• Don't need to memorize names, just know fxn

Reduced error rate

• Base pairing between nucleotides and geometry around that addition need to be correct
• Mistakes-> the editing site checks for mistakes and corrects them
• Going to proofreading site is driven by incorrect base pairing

• 1/10,000,000 - error rate
• Checks for geometry of the bases and the helix itself (if helix deviates from typical B-DNA structure)

DNA damage: damage from exogenous or endogenous agents. Some DNA pathways are specific, but others can heal different damages Cell response happens when you overwhelm their DNA repair pathways-> induce signals or death

Prioritize which pathway to activate and which to not-> limited resources

Past: Focus on the replication fork and the roles of the specific components of the replication fork. Don't need to know the names exactly, bc they differ between types of organisms

FALASE Category of noun expression

Only C is true, linguistic expressions can't stand alone

1-5

1, 3, 5

1-5 only

Don't need to read this section