B&B Cell Bio

Question 1

Which cell cycle checkpoint is blocked by p53?<div><br></br></div><div>{{c1::G1 to S}}</div>

Answer 1

“<div><i>Hence a mutation can cause uncontrolled cell division</i><br></br></div><div><i>Also blocked by hypophosphorylated Rb <br></br></i><div><img></img></div></div>”

Question 2

Which cell cycle checkpoint is blocked by hypophosphorylated Rb?<div><br></br></div><div>{{c1::G1 to S}}</div>

Answer 2

“<div><i>Hence a mutation can cause uncontrolled cell division</i><br></br></div><div><img></img></div>”

Question 3

<div><b>Rhabdomyoblasts</b> are characterized by positive IHC staining for <b>{{c1::desmin}}</b> and <b>{{c1::myogenin}}</b> </div>

Answer 3

“<i>desmin is an intermediate filament of muscles cells; </i><i>malignant rhabdomyoblasts cause embryonal </i><b><i>rhabdomyosarcoma</i></b><div><b><i><br></br></i></b></div><div><i>myogenin<b> </b>is a transcription factor present in immature muscle cells</i></div>”

Question 4

<div>What process is used by <b>mismatch repair enzymes</b> to distinguish between <u>old</u> and <u>new</u> <b>DNA strands</b> in prokaryotes?</div>

<div><br></br></div>

<div>{{c1::DNA methylation}}</div>

Answer 4

template strand <b>cytosine</b> and <b>adenine</b> are methylated for this very purpose

Question 5

<div>What process takes <b>DNA</b> and makes more <b>DNA</b>? </div>

<div><br></br></div>

<div>{{c1::Replication}}</div>

Answer 5

“<img></img>”

Question 6

<div><div>What process takes <b>DNA</b> and makes <b>RNA</b>? </div><div><br></br></div><div>{{c1::transcription}}</div></div>

Answer 6

“<img></img>”

Question 7

<div><div>What process takes <b>RNA</b> and makes <b>protein</b>? </div><div><br></br></div><div>{{c1::translation}}</div></div>

Answer 7

“<img></img>”

Question 8

<div><div><div>DNA & RNA are made of <b>{{c1::nucleotide monophosphates}}</b> connected via a(n) {{c2::<b>phosphodiester</b>}} bond</div></div></div>

Answer 8

“<img></img>”

Question 9

<div>One feature of the <b>genetic code</b> is that it is {{c1::degenerate/redundant}}: most amino acids are coded by <i>multiple</i> codons </div>

Answer 9

<i><u>exceptions</u>: methionine and tryptophan are encoded by only 1 codon (AUG and UGG, respectively)</i>

Question 10

<div>One feature of the <b>genetic code</b> is that it is {{c1::commaless, nonoverlapping}}: it is read from a fixed starting point as a continuous sequence of bases</div>

Answer 10

<i><u>exceptions</u>: some viruses</i>

Question 11

<div>One feature of the <b>genetic code</b> is that it is {{c1::universal}}: genetic code is conserved throughout evolution</div>

Answer 11

<i>exceptions: mitochondria (in humans)</i>

Question 12

<div>What does <b>AUG</b> encode for in <i>eukaryotes</i>?</div>

<div><br></br></div>

<div>{{c1::Methionine (start codon)}}</div>

Answer 12

<i>rarely GUG is a start codon as well</i>

Question 13

<div><div>What does <b>AUG</b> encode for in <i>prokaryotes</i>?</div><div><br></br></div><div>{{c1::N-formylmethionine, or fMet (start codon)}}</div></div>

Answer 13

<i>fMet also stimulates neutrophil chemotaxis</i>

Question 14

<div>Which <u>three</u> sequences of bases are mRNA <b>stop codons</b>? </div>

<div><br></br></div>

<div>{{c1::<b>UGA</b>, <b>UAA</b>, <b>UAG</b>}}</div>

Answer 14

“<i>”“<b>U G</b>o <b>A</b>way, <b>U</b> <b>A</b>re <b>A</b>way, <b>U</b> <b>A</b>re <b>G</b>one””</i> “

Question 15

<div>The {{c1::origin of replication}} is a particular consensus sequence of base pairs in a genome where <b>DNA replication begins</b> </div>

Answer 15

“<div><i>may be <u>single</u> (prokaryotes) or <u>multiple</u> (eukaryotes)</i> </div><div><img></img></div>”

Question 16

<div>{{c1::AT}}-rich sequences are found in <b>promoters</b> and <b>origins</b> <b>of replication</b></div>

Answer 16

AT has 2 bonds vs 3 in GC-easier to break apart

Question 17

<div>The {{c1::replication fork}} is a Y-shaped region along the DNA template where <b>leading</b> and <b>lagging strands are synthesized</b> </div>

Answer 17

“<img></img>”

Question 18

<div>Which enzyme is responsible for <b>unwinding the DNA template</b> at the replication fork? </div>

<div><br></br></div>

<div>{{c1::Helicase}} </div>

Answer 18

“<img></img>”

Question 19

<div>{{c1::Single-stranded binding}} proteins <u>prevent</u><b> DNA strands from reannealing</b> during replication </div>

Answer 19

“<img></img>”

Question 20

<div>Which enzyme is responsible for <b>relaxing the DNA strand</b> by creating single- or double-stranded breaks in the DNA helix to add/remove supercoils? </div>

<div><br></br></div>

<div>{{c1::Topoisomerase}} </div>

Answer 20

“<div><img></img></div>”

Question 21

<div>Which enzyme is responsible for <b>making an RNA primer</b> on which DNA polymerase III can initiate replication (<u>prokaryotes</u>)? </div>

<div><br></br></div>

<div>{{c1::Primase}}</div>

Answer 21

“<img></img>”

Question 22

<div>Which enzyme is responsible for <b>elongating the DNA strand</b>? </div>

<div><br></br></div>

<div>{{c1::DNA polymerase (specifically, DNA polymerase III in <u>prokaryotes</u>)}}</div>

Answer 22

“<div><i>DNA polymerase uses <b>dNTP</b> substrates to add <b>monophosphates</b>; In the process, inorganic pyrophosphate (PPi) is given off</i></div><div><i><img></img></i></div>”

Question 23

<div><div><div><b>{{c2::DNA}} polymerase</b> <i>must</i> see a(n) {{c1::<b>RNA primer</b>}} to bind, which is <b>complementary</b> and <b>antiparallel</b> to the polymerase</div></div></div>

Answer 23

“Technically it doesn’t need to be an <u>RNA</u> primer, just any primer with a 3’-OH group (i.e. PCR)<div><img></img></div>”

Question 24

“<div><div><div><b>DNA polymerase </b>pauses and checks (““<b>proof-reads</b>””) via {{c1::3’ -> 5’ exonuclease}} activity</div><div></div></div></div>”

Answer 24

“<img></img>”

Question 25

<div>Which enzymes are responsible for <b>removing the RNA primer</b> in <i><u>eukaryotes</u></i>? </div>

<div><br></br></div>

<div>{{c1::RNase H and FEN-1::2}}</div>

Answer 25

“<div>*<i>note: this is probably pretty low yield for step 1</i></div><div><br></br></div><div>Removal of primers</div><div>Prokaryotes: RNase H and DNA polymerase I (5’→3’ exonuclease activity)</div><div>Eukaryotes: RNase H and FEN-1 (flap endonuclease-1)</div><div><br></br></div><div>Gaps between fragments are filled after primer removal</div><div>Prokaryotes : DNA polymerase I</div><div>Eukaryotes : Polymerase δ</div><div><img></img></div>”

Question 26

<div>Which enzyme catalyzes the formation of a phosphodiester bond between <b>Okazaki</b> <b>fragments</b>?</div>

<div><br></br></div>

<div>{{c1::DNA ligase}}</div>

Answer 26

“<div><i>this is the <b>lagging strand</b> and is synthesized in the direction <u>away</u> from the replication fork</i> </div><div><img></img></div>”

Question 27

“<div>The enzyme which adds {{c2::<u>TTAGGG</u>::sequence}} to 3’ ends of chromosomes to <b>avoid loss of genetic material</b> with every duplication is known as {{c1::<b>Telomerase</b>}}</div>”

Answer 27

<i>- eukaryotes only; prokaryotes have circular DNA</i> <div><br></br></div><div>- critically shortening in telomere length –> signal for programmed cell death (TP53 becomes activated –> apoptosis)</div>

Question 28

<div><div>Which replication enzyme is a <b>RNA-dependent</b> <b>DNA</b> <b>polymerase</b>, and thus a major example of reverse transcriptase activity, in humans? </div><div><br></br></div><div>{{c1::Telomerase}} </div></div>

Answer 28

• endogenously expressed in cells that need to divide regularly(ex. <b>germ cells, </b>certain adult <b>stem cells</b>), allowing them to proliferate indefinitely in a controlled manner

Question 29

<div><div><div>Telomerase is a rare example where <b>{{c1::reverse transcriptase::enzyme}}</b> activity occurs <i>endogenously</i> in humans </div></div></div>

Answer 29

This is found in <b>eukaryotes only</b>

Question 30

<div><div><div>What pathology is associated with <u>increased</u> telomerase activity?</div><div><br></br></div><div>{{c1::Cancer}}</div></div></div>

Answer 30

> 90% of cancer cells contain increased telomerase activity, allowing for continued proliferation without apoptosis

Question 31

“<div><div><div><div><b>{{c1::RNA}} polymerase</b> <u>doesn't have to</u> see a <b>RNA primer</b> to bind</div><div></div></div></div></div>”

Answer 31

“binds to promoter regions and requires transcription factors<div><img></img></div>”

Question 32

<div>Which type of <b>DNA</b> <b>mutation</b> causes the <u>least</u> severe damage? </div>

<div><br></br></div>

<div>{{c1::Silent mutations}}</div>

Answer 32

<i>silent &laquo_space;missense < nonsense < frameshift</i>

Question 33

<div><div>Which type of <b>DNA</b> <b>mutation</b> causes the <u>most</u> severe damage? </div><div><br></br></div><div>{{c1::frameshift mutations}}</div></div>

Answer 33

<i>silent &laquo_space;missense < nonsense < frameshift</i>

Question 34

<div>A(n)<b>{{c1::silent}} mutation</b> occurs when a nucleotide substitution codes for the <u>same</u> amino acid</div>

Answer 34

“<div><i>often a base change in 3rd position of codon (tRNA wobble)</i></div><div><i><img></img></i></div>”

Question 35

<div>A(n)<b>{{c1::missense}} mutation</b> occurs when a nucleotide substitution codes for a <u>different</u> amino acid</div>

Answer 35

“<div><i>e.g. sickle cell disease (substitution of glutamic acid with valine)</i></div><div><i><img></img></i></div>”

Question 36

<div>A(n)<b>{{c1::nonsense}} mutation</b> occurs when a nucleotide substitution codes for a <b>stop</b> codon</div>

Answer 36

“<div><i>usually results in a nonfunctional protein</i></div><div><img></img> </div>”

Question 37

<div>A(n)<b>{{c1::frameshift}} mutation</b> occurs when there is a <u>deletion</u> or <u>insertion</u> of a number of nucleotides <b>not divisible by {{c2::3}}</b>, resulting in misreading of all nucleotides downstream</div>

Answer 37

“<div><i>protein may be shorter or longer, and its function may be disrupted or altered; examples include </i><b>duchenne muscular dystrophy</b><i> and </i><b>Tay-sachs disease</b> </div><div><br></br></div><div><img></img></div><div><br></br></div><div><img></img></div>”

Question 38

<div><div>A mutation at a(n) {{c1::splice site}} results in a <b>retained intron</b> in the mRNA, leading to a protein with impaired or altered function</div></div>

Answer 38

“<i>rare cause of cancers, dementia, epilepsy, and some types of </i><b>β-thalassemia</b> “

Question 39

<div><div>The enzyme that <u>recognizes</u> and <u>excises</u> <b>pyrimidine dimer</b> mutations is {{c1::excision endonuclease}}</div></div>

Answer 39

<i>nucleotide excision repair</i>

Question 40

<div><div>What phase of the cell cycle do <b><u>nucleotide</u> excision repairs</b> occur?</div><div><br></br></div><div>{{c1::G₁}}</div></div>

Answer 40

“In contrast, BER occurs in all phases of the cell cycle and Mismatch Repair occurs predominantly in S<br></br><div><br></br></div><div><img></img></div>”

Question 41

<b>Xeroderma Pigmentosum</b> is an inherited pathology due to a defective {{c1::Nucleotide Excision Repair}} pathway

Answer 41

“<div><div><i>- This is inherited in an <b>autosomal recessive </b>manner </i></div><div><i><br></br></i></div><div><i>- can diagnose by measurement of repair mechanisms in WBCs</i></div></div><div><i><br></br></i></div><div><i><img></img></i></div>”

Question 42

<div><div><div>What form of <b>DNA repair</b> fixes mutations due to DNA replication errors?</div><div><br></br></div><div>{{c1::Mismatch repair}}</div></div></div>

Answer 42

very important for maintaining <b>microsatellite stability</b> (DNA slippage can occur easily at these sites). Problems with this can lead to <u>colon cancer</u>

Question 43

<div><div><u>Recognition</u> and <u>facilitation of excision</u> of <b>{{c2::mismatched nucleotides}}</b> occur via enzymes found on <b>two</b> genes: {{c1::<b>MSH2 (MutS)</b>}} or {{c1::<b>MLH1 (MutL)</b>}} </div></div>

Answer 43

<i>- <b>MutS</b> recognizes the mismatch on the newly created daughter strand (distinguished from parent strand by occasional nicks in the daughter strand phosphodiester bonds), <b>MutL</b> is then recruited and the complex slides along the DNA until 1 of daughter strand nicks is encountered</i><div><i><br></br></i></div><div><i>- <b>exonuclease 1 </b>is then loaded onto the repair complex and activated, which then excises the mismatch<br></br></i><div><i><br></br></i></div><div><i>Mutations in these genes account for 90% of cases of Lynch syndrome</i></div></div>

Question 44

<div><div>What pathology is characterized by a deficiency of the <u>enzymes</u> used in <b>mismatch base repair</b>? </div><div><br></br></div><div>{{c1::Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC])}}</div></div>

Answer 44

leads to colon cancer with <b>microsatellite instability</b> (DNA slippage can occur easily at these sites). Problems with this can lead to <u>colon cancer</u>

Question 45

<div><div>What phase of the cell cycle do <b>mismatch base repairs</b> <u>predominantly</u> occur?</div><div><br></br></div><div>{{c1::S}}</div></div>

Answer 45

”- <b>some also occur in G2</b>; whereas NER occurs in G1 and BER occurs throughout cell cycle<div><br></br></div><div><img></img></div>”

Question 46

<div><div><div>What form of <b>DNA repair</b> fixes mutations due to spontaneous/toxic deamination?</div><div><br></br></div><div>{{c1::Base excision repair}}</div></div></div>

Answer 46

i.e. deamination, oxidation, etc

Question 47

<div><div>In <b>base excision repair</b>, base-specific {{c1::glycosylases}} <u>remove</u> the altered base and create a(n) {{c2::AP (apurinic/apyrimidinic)}} site </div></div>

Answer 47

“<i>ex. cytosine deamination is repaired with uracil glycosylase</i><div><div><i><img></img></i></div><div><i><br></br></i></div><div><i><img></img></i></div></div>”

Question 48

“<div><div>Which <b>base excision repair </b>enzyme is responsible for <u>removing nucleotides</u> at the <b>5’ end</b>?</div><div><br></br></div><div>{{c1::AP-endonuclease}} </div></div>”

Answer 48

“<img></img><div><img></img></div>”

Question 49

“<div><div><div>Which <b>base excision repair </b>enzyme is responsible for <u>removing nucleotides</u> at the <b>3’ end</b>?</div><div><br></br></div><div>{{c1::Lyase}} </div></div></div>”

Answer 49

“<img></img><div><img></img></div>”

Question 50

<div><div>What phase of the cell cycle do <b><u>base</u> excision repairs</b> occur?</div><div><br></br></div><div>{{c1::Throughout the cell cycle}}</div></div>

Answer 50

“Whereas NER occurs in G1, and mismatch occurs predominantly in S<br></br><div><br></br></div><div><img></img></div>”

Question 51

<div><div>Which forms of <b>DNA repair</b> repairs double-stranded breaks (due to <u>ionizing radiation)</u>?</div><div><br></br></div><div>{{c1::Nonhomologous end joining}} and {{c2::homologous recombination}}</div></div>

Answer 51

“<div><i>Nonhomologous End Joining depicted below</i></div><div><i><br></br></i></div><div><i><img></img></i></div><div><i>Homologous Recombination depicted below</i></div><div><i><img></img></i></div>”

Question 52

<div>Mechanisms to repair {{c1::dsDNA}} breaks are defective in Ataxia telangiectasia, Fanconi anemia, and SCID</div>

Answer 52

<i>- Due to defects in the ATM protein, FANC enzymes, and Artemis enzyme respectively</i>

Question 53

<div>The {{c1::template}} strand is the dsDNA strand used for transcription; it is <b>complementary</b> and <b>antiparallel</b> to mRNA</div>

Answer 53

“<img></img>”

Question 54

<div>The {{c1::coding}} strand is the strand of dsDNA that is <u>NOT</u> used during transcription, but is <b>identical to mRNA</b> (substitute T/U)</div>

Answer 54

“<img></img>”

Question 55

<div><div><u>Practice</u>: If a DNA template sequence is TAGC, what is the mRNA sequence?</div><div><br></br></div><div>{{c1::GCUA}}</div></div>

Answer 55

“<i>AUCG is wrong because the strand is <u>built</u> in the 5’ to 3’ direction</i> “

Question 56

<div>The {{c1::untranslated region (UTR)}} of m<b>RNA </b>is the portion of mRNA which contains no protein information</div>

Answer 56

“<div><div><i>every RNA contains a <b>5’ </b>and <b>3’ UTR</b></i></div></div><div><i><img></img></i></div>”

Question 57

“<div><div>In <i>eukaryotes</i>, each gene has it’s <i>own</i> {{c1::promoter}}, to which RNA polymerase II may bind </div></div>”

Answer 57

<i>in prokaryotes, there may be one promoter for many genes (<u>operons</u>)</i>

Question 58

<div>The <b>promoter</b> is an AT-rich upstream sequence with {{c1::TATA}} and {{c1::CAAT}} boxes </div>

Answer 58

“<div>- TATA (Hogness) is located approximately 25 bases upstream, CAAT is located 70-80 bases upstream</div><div><br></br></div><div>- these regions of weak A:T bonds are where RNA polymerase binds (easy to open up vs stronger G:C bonds)</div><div><br></br></div><div><img></img></div>”

Question 59

<div><div><b>Promoters</b> serve as binding sites for {{c1::general::general/specific}} transcription factors</div></div>

Answer 59

“<div><i>they are present in <u>all cells with a nucleus</u> and are involved in basal transcription</i></div><div><br></br></div><div><img></img></div>”

Question 60

<div><div>{{c1::Enhancers}}<b> </b>are stretches of DNA that <b>increase</b> <b>gene</b> <b>expression</b> by binding <i>specific </i>transcription factors</div></div>

Answer 60

“These bind regulatory activator proteins which stabilize RNA polymerase<div><br></br></div><div><img></img></div>”

Question 61

<div><div>{{c1::Silencers}} are sites where <b>negative</b> <b>regulators</b> (repressors) bind to DNA</div></div>

Answer 61

<div>These <b>decrease</b> expression of a gene on the same chromosome by preventing RNA polymerase from binding</div>

Question 62

<div><div><b>Enhancers</b> increase transcription via enhanced activity of the enzyme {{c1::RNA polymerase II}}</div></div>

Answer 62

”- enhancers bind regulatory Activator proteins that stabilize transcription factors / RNA pol<div><br></br></div><div><img></img></div>”

Question 63

<div><div><b>Enhancers</b> serve as binding sites for {{c1::specific::specific/general}} transcription factors</div><div></div></div>

Answer 63

“<img></img>”

Question 64

<div><div>Are <b>enhancers</b>/<b>silencers</b> <i>close</i> or <i>far</i> from the gene it regulates?</div><div><br></br></div><div>{{c1::May be close to, far from, or within the gene (in an intron)}}</div></div>

Answer 64

“<div>- Because of DNA coiling, many are geometrically close but many nucleotides away from gene</div><div><br></br></div><div>- enhancer sequences can also bind activator proteins that facilitate bending of DNA</div><div><br></br></div><div><img></img></div>”

Question 65

<div><div><div>How can <b>enhancers</b> be far away from the gene it regulates?</div><div><u><br></br></u></div><div>{{c1::DNA will bend to bring enhancer to promoter}} </div></div></div>

Answer 65

“<img></img>”

Question 66

<div>RNA polymerase {{c1::I}} makes {{c2::r}}RNA </div>

Answer 66

“<i>rRNA is the <u>most numerous</u> RNA; this is restricted to the <b>Nucleolus </b>and thus in Cancer, malignant cells with high mitotic activity have a large # of active rRNA and <b>prominent nucleoli</b></i><div><br></br><div><img></img></div></div>”

Question 67

<div>RNA polymerase {{c1::II}} makes {{c2::m}}RNA </div>

Answer 67

“<i>mRNA is the <u>largest</u> RNA; this enzyme is inhibited by the <b>amanita phalloides (death cap mushroom) amatoxin</b></i><div><b><i><br></br></i></b><div> <img></img></div></div>”

Question 68

<div>RNA polymerase {{c1::III}} makes {{c2::t}}RNA and 5S rRNA </div>

<div></div>

Answer 68

“<i>tRNA is the <u>smallest</u> RNA</i><div><img></img></div>”

Question 69

<div>In <i>eukaryotes</i>, <b>{{c2::RNA polymerase II}}</b> may be <u>inhibited</u> by {{c1::<b>α-amanitin</b>}}</div>

Answer 69

<i><div></div></i><i>- absorbed into GI tract, amatoxins are transported to liver by portal circulation whereby active transport by organic anion transporting polypeptide (OATP) and sodium taurocholate cotransporter (NTCP) concentrate toxin within liver cells</i><div><i><br></br></i></div>- found in Amanita phalloides (<b>death cap mushrooms</b>); causes severe <u>hepatotoxicity</u> if ingested (6-24 hours post ingestion, abdominal pain, vomiting, and cholera like diarrhea)

Question 70

<div>What drug is an <u>inhibitor</u> of <i>prokaryotic</i> <b>RNA polymerase</b>? </div>

<div><br></br></div>

<div>{{c1::Rifampin}}</div>

Answer 70

<i>therefore, rifampin blocks prokaryotic transcription</i>

Question 71

“<div><div><div>One <i>co-transcriptional modification</i> is the addition of a(n)<b>{{c1::7-methylguanosine cap}}</b> at the <b>{{c2::5}}’ end</b> </div></div></div>”

Answer 71

“<img></img><div>- occurs in 2 stages, adding GTP, then methylation</div><div><br></br></div><div>- capping occurs in the nucleus as RNA is being transcribed; functions as protection against cellular degradation / allow escape from nucleus</div>”

Question 72

“<div><div><div>One <i>post-transcriptional modification</i> is the addition of a(n)<b>{{c1::poly-A tail}}</b> at the <b>3’ end</b> </div></div></div>”

Answer 72

“<div><i>- synthesized by poly-A polymerase in the nucleus</i></div><div><i><br></br></i></div><div><i>- <b>protects mRNA from degradation within the cytoplasm</b> after it exits the nucleus</i> </div><img></img>”

Question 73

<div><div><div>What sequence of bases represents a <b>polyadenylation signal</b>?</div><div><br></br></div><div>{{c1::AAUAAA::6}}</div></div></div>

Answer 73

telomeres are TTAGGG

Question 74

<div><div><div>mRNA <b>quality control</b> occurs at {{c1::cytoplasmic processing bodies (P-bodies)}}, which contain exonucleases, decapping enzymes, and microRNAs</div></div></div>

Answer 74

• these are involved in regulation and turnover of mRNA; particularly in translation repression and mRNA decay<div><br></br></div><div>- additionally, certain constituents are involved in microRNA induced mRNA silence</div>

Question 75

<div><div><div>mRNAs may be <b>stored</b> in {{c1::P-bodies}} for future translation</div></div></div>

Answer 75

• typically mRNA once entering cytosol associates with ribosomes, certain mRNA associated with proteins found in P bodies<div><br></br></div><div>- P bodies can partake in mRNA quality control, but also act to store mRNA to later release for further translation</div>

Question 76

<div><div><div><div><div>In the <i>first</i> step of <b>alternative</b> <b>splicing</b>, the primary transcript (hnRNA) combines with {{c1::<b>small nuclear ribonucleoproteins</b> (snRNPS)}} and other proteins to form the <b>{{c2::spliceosome}}</b> </div></div></div></div></div>

Answer 76

“<div><i><b>Anti-snRNP antibodies are known as anti-Smith antibodies (SLE)</b></i></div><br></br><div><img></img></div>”

Question 77

<div><div><div><div><div>After the <b>spliceosome</b> has been formed in <u>alternative splicing</u>, a(n) {{c1::lariat-shaped (looped)}} intermediate is generated</div></div></div></div></div>

Answer 77

“<img></img>”

Question 78

<div><div><div><div><div>In the <i>final</i> step of <b>alternative splicing</b>, the {{c2::lariat}} is released to precisely remove the {{c1::intron}} and join <u>two</u> {{c1::exons}}</div></div></div></div></div>

Answer 78

“<img></img><div>Spliceosomes remove introns containing <b>GU </b>at the 5’ splice site and <b>AG</b> at the 3’ splice site</div><div><br></br></div>”

Question 79

<div><div><div><div><div>Antibodies to <b>spliceosomal snRNPs</b>, also known as <b>{{c2::anti-Smith}} antibodies</b>, are highly specific for {{c1::<b>SLE</b>}}</div></div></div></div></div>

Answer 79

Lupus

Question 80

<div><div><div><div>Different <i>exons</i> are frequently combined by {{c1::alternative splicing}} to produce a larger number of <u>unique</u> proteins </div></div></div></div>

Answer 80

“<div><i>allows for </i><b>multiple</b><i>, </i><b>different</b><i> </i><b>proteins</b><i> to be generated from a </i><b>single</b><i> </i><b>gene</b> </div><div><img></img></div>”

Question 81

<div><div><div><div><div>One <u>hematological pathology</u> that is due to <b>abnormal splicing variants</b> is {{c1::β-thalassemia}}</div></div></div></div></div>

Answer 81

“<i>mutation in 5’ splice donor site of intron 1, therefore intron 1 is not removed</i><div><i><br></br></i></div><div><i>others include; Gaucher disease, Tay-Sachs Disease, Marfan syndrome</i></div>”

Question 82

<div><div>{{c1::microRNAs}} are small, <i>noncoding</i> <b>RNA</b> <b>molecules</b> that <i>post-transcriptionally</i> regulate <b>protein</b> expression</div></div>

Answer 82

“<i><b>introns</b> can contain microRNA (miRNA) genes</i><div><div><img></img></div></div>”

Question 83

<div><b>microRNA</b> often leads to the {{c1::silencing/inactivation}} of <i>target</i> <i>mRNA</i>, thus causing {{c1::<u>decreased</u>}} translation into protein</div>

Answer 83

<div><i>can have multiple mRNA targets, typically</i></div>

<div><i>related to complementary base pairing</i> </div>

Question 84

<div><div>{{c1::tRNAs}} are the <i>smallest</i> RNAs and have a <u>clover-leaf structure</u> </div></div>

Answer 84

“<img></img>”

Question 85

<div><div>At the <u>base</u> of a <b>tRNA molecule</b> is a(n)<b>{{c1::anti-codon loop}}</b>, which base pairs with a codon of mRNA in a <i>complementary</i>, <i>antiparallel</i> fashion</div></div>

Answer 85

“<img></img>”

Question 86

“<div>At the <b>{{c2::3}}’ end</b> of a <b>tRNA molecule</b> is a(n)<b>{{c1::5’-CCA-3’}} sequence</b>, which<i> </i>is the amino acid <i>acceptor stem</i></div>”

Answer 86

“<div><i>CCA = <b>C</b>an <b>C</b>arry <b>A</b>mino acids</i> </div><div><br></br></div><div>The -OH of A links to the amino acid</div><div><br></br></div><div><img></img></div>”

Question 87

<div><div>The <b>{{c1::T-arm}}</b> of <b>tRNA</b> contains the <u><b>TΨC</b> </u><u><b>sequence</b></u> (<b>ribothymidine</b>, <b>pseudouridine</b>, <b>cytidine</b>) necessary for tRNA-ribosome binding</div></div>

Answer 87

“<img></img>”

Question 88

<div><div>What is the function of the <b>T-arm</b> of <b>tRNA</b>? </div><div><br></br></div><div>{{c1::tRNA-ribosome binding}}</div></div>

Answer 88

“<img></img>”

Question 89

<div><div>The <b>{{c1::D-arm}}</b> of <b>tRNA</b> contains <u>dihydrouridine</u> residues necessary for tRNA recognition by the correct aminoacyl-tRNA synthetase</div></div>

Answer 89

“<img></img>”

Question 90

<div><div><div><b>Aminoacyl-tRNA synthetase</b> requires {{c1::ATP}} and releases inorganic PP_i</div></div></div>

Answer 90

“<div><i>scrutinizes an amino acid before and after it binds to tRNA; if incorrect, bond is hydrolyzed</i></div><div><img></img></div>”

Question 91

“<div><div>Accurate base pairing is usually required only in the first <b>two</b> nucleotide positions of a <u>mRNA codon</u> because codons differing in the <b>3rd</b> “”{{c1::wobble}}”” position may code for the same amino acid</div></div>”

Answer 91

“<img></img>”

Question 92

<div><b>Peptide bond formation</b> is facilitated by the <b>ribozyme</b> <i>{{c1::peptidyl transferase}}</i></div>

Answer 92

“<div><i>a <b>ribozyme </b>is RNA carrying out a catalytic reaction (enzyme is a protein)</i></div><div><img></img></div>”

Question 93

<div><div><div>What is the <u>smaller</u> <b>ribosomal subunit</b> used in <i>prokaryotic</i> translation? </div><div><br></br></div><div>{{c1::30s}}</div></div></div>

Answer 93

<i>this subunit recognizes the shine dalgarno sequence</i>

Question 94

<div><div><div>What is the <u>total</u> size of the <b>ribosome</b> used in <i>prokaryotic </i>translation?</div><div><br></br></div><div>{{c1::70s}}</div></div></div>

Answer 94

“<img></img>”

Question 95

<div><div><div>What is the <u>smaller</u> <b>ribosomal subunit</b> used in <i>eukaryotic</i> translation? </div><div><br></br></div><div>{{c1::40s}}</div></div></div>

Answer 95

“<i>this subunit recognizes the 5’-7-Methyl-G-cap</i> “

Question 96

<div><div><div><div>What is the <u>larger</u> <b>ribosomal subunit</b> used in <i>eukaryotic</i> translation? </div><div><br></br></div><div>{{c1::60s}}</div></div></div></div>

Answer 96

“<i>this is the target of </i><b>shiga</b><i> </i><b>toxins</b><i> and </i><i>verotoxin</i> “

Question 97

<div><div><div><div>What is the <u>total</u> size of the <b>ribosome</b> used in <i>eukaryotic </i>translation?</div><div><br></br></div><div>{{c1::80s}}</div></div></div></div>

Answer 97

“<img></img>”

Question 98

<div><div><i>Eukaryotic</i> {{c1::Initiation Factors}} help <u>assemble</u> the <b>40s</b> <b>ribosomal subunit</b> with the initiator tRNA</div></div>

Answer 98

“<i><div></div></i><i>- IF’s identify either the 5’ cap or an internal ribosome entry site (IRES - often located in 5’-UTR); Uses GTP to assemble the structure</i><div><br></br></div>- initiation factors are released when the mRNA and the ribosomal 60S subunit assemble with the complex <div><br></br></div><div><br></br></div><div><img></img></div><div><img></img></div>”

Question 99

<div><div><b>Translation</b> is initiated by {{c1::GTP}} hydrolysis </div></div>

Answer 99

“<img></img>”

Question 100

<div><div>At what <u>site</u> of the <i>ribosome</i> does tRNA bind to for translation <b>initiation</b>? </div><div><br></br></div><div>{{c1::P site}}</div></div>

Answer 100

”"”prepare”” site- the ““peptidyl”” site<div><img></img></div>”

Question 101

<div><div>In the <u>first</u> step of strand <b>elongation</b>, a(n) {{c1::aminoacyl-tRNA}} binds to the <b>A</b> site </div></div>

Answer 101

“<img></img>”

Question 102

<div><div>After aminoacyl-tRNA binds to the A site of the ribosome, {{c1::peptidyl transferase}}, a <b>ribozyme</b>, catalyzes peptide bond formation (translation)</div></div>

Answer 102

“<img></img>”

Question 103

“<div><div>In the final step of translation <b>elongation</b>, {{c1::translocation}} of the ribosome occurs, advancing the ribosome 3 nucleotides towards the 3’ end of mRNA</div></div>”

Answer 103

“<div><i>requires GTP and elongation factors</i></div><div><i><br></br></i></div><img></img>”

Question 104

<div><div>In addition to GTP, <b>translocation</b> of the ribosome during <i>translation</i> also requires eukaryotic {{c1::elongation factor 2 (eEF-2)}}</div></div>

Answer 104

“<div><i>- pseudomonas exotoxin A and diphtheria toxin act via inhibition of eukaryotic enlongation factor 2 </i><i>via <b>ADP ribosylation</b></i></div><div><br></br></div><div>- translocation occurs when Ribosome advances 3 nucleotides towards 3’ end, moving the peptidyl tRNA to the P site (A site is now empty)</div><div><img></img></div><div><br></br></div><div><img></img></div>”

Question 105

<div><div>In the <i>final</i> step of <b>translation</b>, a stop codon is recognized by {{c1::release factor}} and the completed polypeptide is released from the ribosome</div><div><div><div></div></div></div></div>

Answer 105

“<img></img>”

Question 106

<div>A(n)<b>{{c1::chaperone}} protein</b>, is an intracellular protein involved in facilitating and/or maintaining <b>protein</b> <b>{{c2::folding}}</b> </div>

Answer 106

<i>in yeast, <b>heat shock proteins (e.g. Hsp60)</b> are expressed at high temperatures to prevent protein denaturing/misfolding</i>

Question 107

<div><div><div><div><div>What is the <u>shortest</u> phase of the <b>cell cycle</b>?</div><div><br></br></div><div>{{c1::M phase (mitosis + cytokinesis)}}</div></div></div></div></div>

Answer 107

“<img></img>”

Question 108

<div><div><div><div><div>Which <b>cell cycle phase</b> is characterized by resting, non-dividing cells?</div><div><br></br></div><div>{{c1::G₀}} </div></div></div></div></div>

Answer 108

“<img></img>”

Question 109

<div><div><div><div><div>What <u>cell type</u> remains in G₀ and can only regenerate from stem cells?</div><div><br></br></div><div>{{c1::Permanent}}</div></div></div></div></div>

Answer 109

<i>examples include neurons, skeletal/cardiac muscle, and RBCs</i>

Question 110

<div><div><div><div><div><div>What <u>cell type</u> enters G₁ from G₀ when stimulated?</div><div><br></br></div><div>{{c1::Stable (quiescent)}}</div></div></div></div></div></div>

Answer 110

<i>examples include hepatocytes, lymphocytes, renal tubular cells, periosteal cells</i>

Question 111

<div><div><div><div><div><div>What <u>cell type</u> <i>never</i> enters G₀ and divides rapidly with a short G₁?</div><div><br></br></div><div>{{c1::Labile}}</div><div></div></div></div></div></div></div>

Answer 111

<i>examples include bone marrow, gut epithelium, skin, hair follicles, and germ cells</i>

Question 112

<div><div><div><div><div><div>Which <b>cell cycle phase</b> is characterized by DNA synthesis and replication?</div><div><br></br></div><div>{{c1::S}} </div></div></div></div></div></div>

Answer 112

<i><u>46</u> chromosomes/chromosomes per cell before S phase; <u>92</u> <b>chromatids </b>per cell after S phase (still 46 chromosomes)</i>

Question 113

<div><div><div><div><div>Which <b>cell cycle phase(s)</b> are part of <b>interphase</b>? </div><div><br></br></div><div>{{c1::G₁, S, G₂}}</div></div></div></div></div>

Answer 113

“<div>- G1 - cells in this phase prepare building blocks for DNA synthesis (synthesis of RNA, protein, lipid, and carbs)</div><div><br></br></div><div>- S - DNA replication occurs during this phase</div><div><br></br></div><div>- G2 - DNA is checked for errors and corrections are made if possible, if corrections cannot be made, then apoptosis will result; ATP synthesis occurs here</div><div><br></br></div><div><img></img></div>”

Question 114

<div><div><div><div><div><div>Which <b>cell cycle phase(s)</b> are <u>NOT</u> part of <b>interphase</b>? </div><div><br></br></div><div>{{c1::M}}</div></div></div></div></div></div>

Answer 114

“<img></img>”

Question 115

<div>{{c1::<b>Free</b>}} <b>ribosomes</b> are unattached to any membrane and are the site of <u>synthesis</u> for <b>cytosolic</b> and <b>organellar </b><b>proteins</b></div>

Answer 115

“<img></img>”

Question 116

<div>What part of the cell is the site of <b>steroid synthesis</b> and <b>detoxification </b>of drugs and poisons?</div>

<div><br></br></div>

<div>{{c1::Smooth endoplasmic reticulum}}</div>

Answer 116

<i>liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and gonads are rich in SER</i>

Question 117

<div>When proteins are <b>misfolded</b>, multiple {{c1::ubiquitins}} are added, which aids in trafficking to the <i>proteasome</i></div>

Answer 117

“<img></img>”

Question 118

<div>The {{c1::proteasome}} is a barrel-shaped protein complex that degrades damaged or <b>ubiquitin-tagged</b> proteins</div>

Answer 118

“<img></img>”

Question 119

<u>Defects</u> in the <b>ubiquitin-proteasome system </b>have been implicated in some cases of {{c1::Parkinson}} disease

Answer 119

<i>defects in the <b>Parkin</b>, <b>PINK1</b>, and <b>DJ-1</b> genes specifically</i>

Question 120

<div><div>On the <b>N terminal side</b> of <i>newly synthesized protein</i>, a stretch of 10-15 <b>hydrophobic</b> <b>amino acids</b> forms the {{c1::<b>N-terminal signa</b>l}} <b>sequence</b></div></div>

Answer 120

“<img></img>”

Question 121

<div><div>The <b>N-terminal signal</b> <b>sequence</b> of a newly synthesized protein is bound by a(n) {{c1::<b>signal recognition particle (SRP</b>)}}, which attaches the complex to the {{c2::ER}} membrane </div></div>

Answer 121

“<div><i>once the <u>SRP-protein complex</u> is bound to the ER, the signal sequence is removed and the protein enters the ER (co-translational)</i> </div><div><img></img></div>”

Question 122

<div><div>Which enzyme <b>phosphorylates</b> <b>mannose</b> in the <u>Golgi apparatus</u>, facilitating protein trafficking? </div><div><br></br></div><div>{{c1::Phosphotransferase}}</div></div>

Answer 122

<i>specifically, N-acetylglucosaminyl-1-phosphotransferase</i>

Question 123

“<div><div><div>What pathology is associated with a defect in the enzyme <i>N-acetylglucosaminyl-1-phosphotransferase</i>?</div><div><br></br></div><div>{{c1::I-cell disease (inclusion cell disease/mucolipidosis type II)}}</div></div></div>”

Answer 123

<i>failure of the Golgi to phosphorylate mannose residues (i.e. mannose-6-phosphate) on glycoproteins</i>

Question 124

<div><div><div><b>{{c1::Endosomes}}</b> are <b>sorting</b> <b>centers</b> for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use</div></div></div>

Answer 124

“<img></img>”

Question 125

<div><div><div>Which inherited <u>lysosomal storage disorder</u> is characterized by <b>coarse facial features</b>, <b>clouded</b> <b>corneas</b>, and restricted joint movement with <u>high</u> serum levels of <i>multiple</i> lysosomal enzymes? </div><div><br></br></div><div>{{c1::I-cell disease}}</div></div></div>

Answer 125

“<i><div><i>- often fatal in childhood (typically due to <u>severe dilated cardiomyopathy)</u></i><br></br></div></i><div><i><u><br></br></u></i></div><div><i><u><img></img></u></i></div>”

Question 126

<div><div><div><b>I-cell disease</b> is characterized by high plasma levels of {{c1::lysosomal}} enzymes</div></div></div>

Answer 126

<i>proteins are secreted extracellularly rather than delivered to lysosomes</i>

Question 127

<div>Which <b>vesicular trafficking protein</b> is responsible for <i><u>retrograde</u> Golgi transport</i> (<i>cis-</i><i>Golgi and ER) and intra-Golgi transport</i>? </div>

<div><br></br></div>

<div>{{c1::COPI}}</div>

Answer 127

“<div>Normally, Proteins are made at the ER, packaged / modified in the Golgi, and then routed to different locations (lysosomes, secretory vesicles, plasma membrane)</div><div><br></br></div><div>COPI aids in taking proteins that are packaged / modified in the golgi and sending them back to the ER for use there, or to another spot on the golgi apparatus</div><div><div><br></br></div></div><div><img></img></div>”

Question 128

<div><div>Which <b>vesicular trafficking protein</b> is responsible for <i><u>anterograde</u> Golgi transport</i> (ER to cis Golgi)?</div><div><br></br></div><div>{{c1::COPII}}</div></div>

Answer 128

“<img></img>”

Question 129

<div><div>Which <b>vesicular trafficking protein</b> is responsible for transport between the <i>trans-Golgi</i> and <i>lysosomes</i>? </div><div><br></br></div><div>{{c1::Clathrin}}</div></div>

Answer 129

“<img></img>”

Question 130

<div><div>Which <b>vesicular trafficking protein</b> is responsible for transport between the <i>plasma membrane</i> and <i>endosomes</i> (receptor-mediated endocytosis)?</div><div><br></br></div><div>{{c1::Clathrin}}</div></div>

Answer 130

“<img></img>”

Question 131

<div><div>Which type of <u>filament</u> is predominantly involved in <b>maintainence of cell structure</b>? </div><div><br></br></div><div>{{c1::Intermediate filaments (e.g. desmin, cytokeratin)}}</div></div>

Answer 131

<i>other examples include vimentin, lamins, glial fibrillary acid proteins (GFAP), and neurofilaments</i>

Question 132

<div><div>Which type of <u>filament</u> is predominantly involved in <b>movement</b> and <b>cell division</b>? </div><div><br></br></div><div>{{c1::Microtubules (e.g. cilia, flagella)}}</div></div>

Answer 132

<i>other examples include <b>mitotic</b> <b>spindles</b>, <b>axonal</b> <b>trafficking</b>, and centrioles</i>

Question 133

<div><div>What type of <u>filament</u> are <b>cilia</b> and <b>flagella</b>?</div><div><br></br></div><div>{{c1::Microtubule}}</div></div>

Answer 133

“In contrast, villi are actin filaments<div><br></br></div><div><img></img></div>”

Question 134

<div><b>{{c1::Microtubules}}</b> are a cylindrical outer structure composed of a helical array of polymerized heterodimers of <b>{{c2::α-}}</b> and <b>{{c2::β-tubulin}}</b></div>

Answer 134

“<img></img>”

Question 135

<div>Each <b>α-</b> and <b>β-tubulin</b> heterodimer of a <u>microtubule</u> has 2 {{c1::GTP}} bound</div>

Answer 135

GDP bound tubulin will dissociate

Question 136

<div>Which <b>molecular motor</b> <b>protein</b> is responsible for <i>retrograde</i> transport to the microtubule (+ to -)?</div>

<div><br></br></div>

<div>{{c1::Dynein}} </div>

Answer 136

“<img></img>”

Question 137

<div><div>Which <b>molecular motor</b> <b>protein</b> is responsible for <i>anterograde</i> transport to the microtubule (- to +)?</div><div><br></br></div><div>{{c1::Kinesin}} </div></div>

Answer 137

“<img></img>”

Question 138

<div><b>{{c1::Cilia}}</b> are organized in a(n)<b>{{c2::9+2}} arrangement</b> of microtubule doublets</div>

<div></div>

Answer 138

“<div>Flagella as well; </div><div><br></br></div><div><img></img></div><div><br></br></div><div><img></img></div>”

Question 139

<div>The base of a <b>cilium</b> below the cell membrane, called the {{c1::basal body}}, consists of 9 microtubule triplets with no central microtubules</div>

Answer 139

“<img></img>”

Question 140

<div><b>Axonemal</b> <b>{{c2::dynein}}</b> is a(n)<b>{{c1::ATPase}}</b> that links peripheral 9 doublets and causes <u>bending of cilium</u> (movement)</div>

Answer 140

“Coordinated ciliary beating is facilitated by <b><span>gap junctions</span></b> <br></br> <div> <br></br> </div> <div><img></img></div> <div> <br></br> </div> <div><img></img></div> “

Question 141

<div><b>{{c1::Kartagener}} syndrome</b> is a(n) {{c3::autosomal recessive::inheritance}} disease characterized by <u>immotile cilia</u> due to a(n)<b>{{c2::dynein arm}} defect</b></div>

Answer 141

<i>also known as primary ciliary dyskinesia; dynein is important for cilia function, thus anything that requires cilia will be dysfunctional (organogenesis, mucociliary tract, fallopian tubes)</i>

Question 142

<div><b>Kartagener syndrome</b> results in <u>decreased</u> male and female {{c1::fertility}}</div>

Answer 142

<i>due to <b>immotile sperm</b> and dysfunctional fallopian tube cilia, respectively</i>

Question 143

<div>Which developmental pathology is characterized by <b>bronchiectasis</b>, <b>recurrent sinusitis</b>, and <b>situs inversus</b>? </div>

<div><br></br></div>

<div>{{c1::Kartagener syndrome}}</div>

Answer 143

“<div><i>an example of situs inversus is <b>dextrocardia</b> on CXR</i> </div><div><img></img></div>”

Question 144

<div>What is the <b>most abundant protein</b> in the human body?</div>

<div><br></br></div>

<div>{{c1::Collagen}}</div>

Answer 144

<i>extensively modified by post-translational modification</i>

Question 145

<div>What <u>type</u> of <b>collagen</b> is the most common (90%)? </div>

<div><br></br></div>

<div>{{c1::Type I}}</div>

Answer 145

• Found in <b>Bone</b>, <b>Skin</b>, <b>Tendon</b>, <b>Ligaments</b>, Dentin, Fascia

Question 146

<div>What <u>type</u> of <b>collagen</b> makes up <b>bone</b>, <b>skin</b>, and <b>tendon</b>? </div>

<div><br></br></div>

<div>{{c1::Type I}}</div>

Answer 146

<i>also makes up <b>dentin</b>, fascia, cornea, and is part of <u>late</u> wound repair</i> <div><br></br></div><div>this is defective in <b>Osteogenia Imperfecta</b></div>

Question 147

<div>What <u>type</u> of <b>collagen</b> makes up <b>cartilage</b>? </div>

<div><br></br></div>

<div>{{c1::Type II}}</div>

Answer 147

<i>also makes up the vitreous body, pubic symphysis, nucleus pulposus</i> <div><br></br></div><div>Autoantibodies to type II collagen can be seen in patients with <b>relapsing polychondritis</b></div>

Question 148

<div>What <u>type</u> of <b>collagen</b> makes up <b>skin</b> and <b>blood vessels</b>? </div>

<div><br></br></div>

<div>{{c1::Type III}}</div>

Answer 148

<i><div></div></i><i>- Also makes up <u>uterus</u>, <u>fetal tissue</u> (growing fetus need to be able to stretch), <u>granulation tissue</u></i><div><i><u><br></br></u></i></div><div><i>- defective in Vascular Ehlers Danlos</i></div>

Question 149

<div>What <u>type</u> of <b>collagen</b> makes up <b>reticulin fibers</b>?</div>

<div><br></br></div>

<div>{{c1::Type III}}</div>

Answer 149

This is a very pliable structure

Question 150

<div>What <u>type</u> of <b>collagen</b> makes up the <b>basement membrane</b>?</div>

<div><br></br></div>

<div>{{c1::Type IV}}</div>

Answer 150

<i>also makes up the basal lamina and lens</i>

Question 151

<div>The <u>{{c3::vascular}}</u> type of Ehlers-Danlos Syndrome that is caused by a <u>deficiency</u> of <b>type {{c4::III}} collagen</b> can lead to:</div>

<div><br></br></div>

<div>- the formation and rupture of {{c1::<u>aneurysms</u>}} </div>

<div>- rupture of <u>organs</u> (ex. in women the {{c2::uterus::specific organ}} during birth)</div>

Answer 151

<i>- Both <u>Berry</u> and <u>Aortic</u> Aneurysms</i><div><i><br></br></i><div><i>- Pregnant patients with vascular Ehlers-Danlos can rupture their <u>Uterus</u></i></div></div>

Question 152

<div>What <u>type</u> of collagen is <i>decreased</i> in <b>osteogenesis imperfecta type I</b>?</div>

<div><br></br></div>

<div>{{c1::Type I}}</div>

Answer 152

<i>- collagen is <u>normal</u> but production is decreased</i><div><i><br></br></i></div><div><i>- type I collagen is the predominant collagen in <b>osteoid </b>(organic portion of bone matrix)</i></div>

Question 153

<div><div>What pathology is characterized by a <u>defective</u> <b>type IV collagen</b>? </div><div><br></br></div><div>{{c1::Alport syndrome}}</div></div>

Answer 153

• Cant See (Lens)<div>- Cant Pee (Basement membrane of the Glomerulus)<br></br><div>- Cant Hear a Bee (Cochlea)</div></div>

Question 154

<div><b>Type {{c1::IV}} collagen</b> is targeted by <u>autoantibodies</u> in <b>{{c2::Goodpasture}} syndrome</b> </div>

Answer 154

<i>specifically, the <b>alpha 3 chain</b> of <b>type IV collagen</b> is targeted</i> <div>- found in lungs (hemoptysis) and glomeruli (GBM)</div>

Question 155

<div><div><div><div><div><b>Collagen</b> is a repeat of a <i>tripeptide</i> following the pattern {{c1::Gly-X-Y}}, made by <b>fibroblasts</b></div></div></div></div></div>

Answer 155

<i>- X and Y are usually proline or lysine</i><div>- also have signal molecules </div>

Question 156

<div><div><div><div><div>One third of the <b>collagen</b> <b>strand</b> is made of the amino acid {{c1::glycine}}</div></div></div></div></div>

Answer 156

<i>glycine has the smallest side chain, therefore easy to form a triple helix (very little <b>steric hindrance</b>)</i>

Question 157

<div><div><div><div><div>In the first step of <u>collagen synthesis</u>, translation of <b>collagen</b> <b>alpha chains</b> forms {{c1::preprocollagen}}</div></div></div></div></div>

Answer 157

“<div>- Collagen mRNA is first translated in the RER to preprocollagen</div><div>- Signal molecules direct it into the ER lumen, and the structure is now the ““Pro-Alpha chain””</div><div><br></br></div><div><img></img></div>”

Question 158

<div><div><div><div><u>Collagen Synthesis</u>: After the collagen alpha chains are synthesized, specific residues of the amino acids <b>{{c1::proline}}</b> and <b>{{c1::lysine}}</b> are <b>{{c2::hydroxylated}}</b> </div></div></div></div>

Answer 158

“This step requires <b>Vitamin C </b>(deficient in <u>Scurvy</u>)<br></br><div><br></br></div><div><img></img></div>”

Question 159

<div><div><div><div><u>Collagen Synthesis</u>: <b>Hydroxylation</b> of selected <u>prolines</u> and <u>lysines</u> during collagen synthesis requires vitamin {{c1::C}}</div></div></div></div>

Answer 159

“<i>deficiency of vitamin C causes </i><b>scurvy</b> as these patients will have <u>defective pro-alpha chains</u> that can’t form a triple helix, resulting in collagen being degraded instead of secreted”

Question 160

<div><div><div><div><u>Collagen Synthesis</u>: Following hydroxylation of proline and lysine, there is {{c1::<b>glycosylation</b>}} of pro-α-chain {{c2::<b>hydroxylysine</b>}} residues </div></div></div></div>

Answer 160

“<img></img>”

Question 161

<div><div><div><div><u>Collagen Synthesis</u>: After <i>hydroxylation</i> and <i>glycosylation</i>, <b><u>hydrogen</u></b> and <b><u>disulfide</u></b> <b>bonds</b> help form a(n) {{c1::<b>triple</b> <b>helix</b>}} of <b>collagen α chains</b> (<b>procollagen</b>) </div></div></div></div>

Answer 161

“<div><i>problems forming the triple helix may be indicative of <b>osteogenesis imperfecta</b></i><b> </b>- glycine is swapped out with a bulkier amino acid causing steric hindrance that makes a faulty triple helix structure for type I collagen</div><div><b><br></br></b></div><div><img></img></div>”

Question 162

<div><div><div><div><u>Collagen Synthesis</u>: <i>After</i> the <b>triple helix</b> is formed, the procollagen is {{c1::exocytosed}} into the extracellular space</div></div></div></div>

Answer 162

“<div><img></img><br></br></div>”

Question 163

<div><div><div><div>Where in the cell does <b>synthesis</b>, <b>hydroxylation</b>, and <b>glycosylation</b> of <u>preprocollagen</u> occur?</div><div><br></br></div><div>{{c1::Rough endoplasmic reticulum}}</div></div></div></div>

Answer 163

“<img></img>”

Question 164

<div><div><div><div><u>Collagen Synthesis</u>: Once in the extracellular space, <u>cleavage</u> of disulfide-rich terminal regions of <b>procollagen</b> by {{c2::<u>procollagen peptidase</u>}} forms the <i>insoluble</i> <b>{{c1::tropocollagen}}</b> </div></div></div></div>

Answer 164

“<div>These are individual triple helix alpha chain molecules that haven’t been crosslinked at this point </div><div><br></br></div><div>problems with cleavage of procollagen to tropocollagen due to defects in procollagen peptidase result in <b>Ehlers-Danlos</b></div><div><br></br></div><div><img></img></div>”

Question 165

<div><div><div><div><u>Collagen Synthesis</u>: Staggered <b>tropocollagen</b> molecules are reinforced by covalent {{c1::lysine-hydroxylysine}} {{c2::cross-linkages}} to make <b>collagen fibrils</b> </div></div></div></div>

Answer 165

“<div><b>- </b>this step is catalyzed by Lysyl oxidase and is deficient in Menkes disease</div><b><div><b><br></br></b></div>- Collagen fibrils</b> self assemble to form <b>Collagen Fibers</b><br></br><div><br></br></div><div><img></img></div>”

Question 166

<div><div><div><div>Formation of <b>lysine-hydroxylysine cross-linkages</b> (collagen synthesis) requires both {{c1::copper}} and the enzyme <i>{{c1::lysyl oxidase}}</i></div></div></div></div>

Answer 166

“<i>copper deficiency leads to <b>Menkes</b> <b>disease</b></i><div><i><b><br></br></b></i></div><div><i><b><img></img></b></i></div><div><i><b><br></br></b></i></div><div><i><b><img></img></b></i></div>”

Question 167

<div>Where in the cell does the <b>synthesis</b> and <b>formation</b> of<u>tropocollagen</u> and <u>collagen fibrils</u> occur?</div>

<div><br></br></div>

<div>{{c1::Extracellular space}}</div>

Answer 167

“<img></img>”

Question 168

<div>Which <u>collagen synthesis</u> pathologies are associated with <b>problems with cross-linking</b>?</div>

<div><br></br></div>

<div>{{c1::Ehlers-Danlos syndrome, Menkes disease::2}}</div>

Answer 168

• Ehlers-Danlos is problems with proteolytic cleavage (deficiency in procollagen propeptidase) to generate the insoluble tropocollagen substrate from procollagen<div><br></br></div><div>- Menkes Disease results in copper deficiency (resulting in a dysfunctional Lysyl Oxidase), making it impossible to cross link tropocollagens into collagen fibrils</div>

Question 169

<div>Which <u>collagen synthesis</u> pathologies are associated with <b>problems forming the triple helix</b>?</div>

<div><br></br></div>

<div>{{c1::Osteogenesis imperfecta and Scurvy}}</div>

Answer 169

“<div>-in osteogenesis imperfecta; Deficient Type 1 Collagen replaces Glycine with a bulky amino acid, creating steric hindrance that prevents 3 pro-alpha chains from properly linking into the triple helix procollagen; This improper collagen structure is either destroyed in the fibroblast, or is faultily incorporated into bone with hydroxyapatite causing brittleness</div><div><br></br></div><div>In scurvy, These patients can’t hydroxylate pro-alpha chains (hydroxylation of proline or lysine requires vit C), thus they can’t form the triple helix and the nascent collagen is degraded in the cell without being secreted</div>”

Question 170

<div><b>Osteogenesis imperfecta</b> is most commonly caused by gene defects in <i>{{c1::COL1A1}}</i> and <i>{{c1::COL1A2}}</i></div>

Answer 170

• <u>COL1</u> = type 1 collagen, type 1 collagen is the predominant collagen in <b>osteoid</b>, which allows the bone to be somewhat flexible while maintaining strength

Question 171

<div>What is the<i> inheritance</i> of <b>osteogenesis imperfecta</b> (most common)? </div>

<div><br></br></div>

<div>{{c1::Autosomal dominant}}</div>

Answer 171

<i>with decreased production of otherwise normal type 1 collagen</i>

Question 172

<div><b>Osteogenesis imperfecta</b> is characterized by multiple recurrent {{c1::fractures}} with <u>minimal</u> trauma </div>

Answer 172

“<div><i>treat with <b>bisphosphonates</b> to <u>reduce fracture risk</u></i></div><div><i><br></br></i></div><div><i>may occur during the birth process; can mimic child abuse, but bruising is <u>absent</u></i> </div><div><img></img></div>”

Question 173

<div><b>{{c2::Osteogenesis imperfecta}}</b> may present with {{c1::<b>blue</b> <b>sclerae</b>}} due to <i>translucent</i> connective tissue over <u>choroidal</u> veins</div>

Answer 173

“<img></img>”

Question 174

<div><b>Osteogenesis imperfecta</b> may present with {{c1::hearing loss}} due to abnormal ossicles</div>

Answer 174

<i>bones of the middle ear fracture easily</i>

Question 175

<div>Some forms of <i>osteogenesis</i> <i>imperfecta</i> have <b>tooth</b><b>abnormalities</b>, including <u>opalescent teeth</u> that wear easily due to lack of {{c1::dentin}}</div>

Answer 175

“<div><i>this is known as </i><b><i>dentinogenesis imperfecta</i> </b></div><div><b><img></img></b></div>”

Question 176

<div>The <b>{{c1::classical}} type</b> of <b>Ehlers-Danlos syndrome</b> (joint and skin symptoms) is caused by a mutation in <b>type {{c2::V}} collagen</b></div>

Answer 176

<i>the classical type includes Ehlers-Danlos types 1 & 2</i>

Question 177

<div>What type of <b>Ehlers-Danlos syndrome</b> is the most common type?</div>

<div><br></br></div>

<div>{{c1::Hypermobility type (joint instability)}}</div>

Answer 177

<i>this is also known as Ehlers-Danlos type 3</i>

Question 178

<div><b>Ehlers-Danlos syndrome</b> is characterized by <u>faulty collagen synthesis</u> causing {{c1::hyperextensible}} skin</div>

Answer 178

“<img></img>”

Question 179

<div><b>Ehlers-Danlos syndrome</b> is characterized by <u>faulty collagen synthesis</u> causing {{c1::hypermobile}} joints</div>

Answer 179

“<img></img>”

Question 180

<div>The classical and vascular forms of <b>Ehlers-Danlos syndrome</b> are inherited in a(n) {{c1::autosomal dominant}} manner</div>

Answer 180

However, other types of Ehlers-Danlos can be inherited in Autosomal Recessive manner; remember the classical and vascular forms involve structural proteins

Question 181

<div>What is the <i>inheritance</i> of <b>Menkes disease</b>? </div>

<div><br></br></div>

<div>{{c1::X-linked recessive}}</div>

Answer 181

<u>Men</u>kes. Men are more likely to get it

Question 182

<div>What gene is defective in <b>Menkes disease</b>? </div>

<div><br></br></div>

<div>{{c1::ATP7A}} </div>

Answer 182

<i>not to be confused with ATP7B (Wilson disease)</i>

Question 183

“<div><b>{{c2::Menkes}} disease</b> results in {{c1::brittle, ““kinky””}} hair, growth retardation, and hypotonia</div><div></div>”

Answer 183

“<img></img>”

Question 184

<div>{{c1::Elastin}} is a <b>stretchy protein</b> within skin, lungs, large arteries, elastic ligaments, vocal cords, and ligamentum flava</div>

Answer 184

”- dominant elastic protein in the arteries, makes up 50% of aortic tissue <br></br><div><br></br></div><div>- Ligamentum flava has lots of elastin, allowing it to connect vertebrae to allow relaxed and stretched conformations</div><div><br></br></div><div><img></img></div><div><img></img></div>”

Question 185

<div><b>Elastin</b> is rich in <i>non-hydroxylated</i> {{c1::proline}}, {{c1::glycine}}, and {{c1::lysine}} residues (amino acids)</div>

Answer 185

“In comparison to collagen<div><br></br><div>- mostly non-hydroxylated amino acids (some hydroxyproline, no hydroxylysine)</div><div><br></br></div><div>- no glycosylation (surrounding network of fibrillin microfibrils)</div><div><br></br></div><div>- elastin is secreted as <b>tropoelastin</b>, whose unique polypeptide backbone when cross linked causes random coiling (giving it its elastic property)</div></div><div><br></br></div><div><img></img></div>”

Question 186

<div><b>Elastin</b> is <i>tropoelastin</i> with {{c1::fibrillin}} scaffolding</div>

Answer 186

”- Elastin has an unusual polypeptide backbone that causes random coiling when crosslinked - giving it it’s elastic properties<div><br></br><div>- central core of tropoelastin has two unique amino acids that crosslink and provide stability<br></br><div><br></br></div><div><img></img></div></div></div>”

Question 187

“<div>What gives <b>elastin</b> its elastic ““rubber-like”” properties?</div><div><br></br></div><div>{{c1::Cross-linking}}</div>”

Answer 187

“<div><i>- mediated by <b>lysyl oxidase </b>which <u>deaminates</u> <b>lysine residues</b> of tropoelastin, facilitating formation of <b>desmosine cross-links </b></i></div><div><i><b><br></br></b></i></div><div><i>- allows for elastin fibers to be stretched to several times original length and then recoil once stretching forces are withdrawn</i></div><img></img><div><img></img></div>”

Question 188

<div>Where in the cell does <u>cross-linking</u> of <b>elastin</b> take place? </div>

<div><br></br></div>

<div>{{c1::Extracellular space}}</div>

Answer 188

“<div><img></img></div>”

Question 189

{{c1::<b>Wrinkles</b>}}<b> of</b> <b>aging</b> are due to <u>decreased</u> <b>{{c2::collagen}}</b> and <b>elastin</b> production

Answer 189

“<i>decreased collagen production and increased collagenases secondary to UV-A radiation induced inflammatory damage</i> <div><img></img></div>”

Question 190

<div><div><b>Gel electrophoresis </b>separates fragments on the basis of {{c1::size}} </div></div>

Answer 190

<i>all DNA/RNA/protein fragments used are negatively charged</i>

Question 191

<div><div>When using <b>blotting procedures</b>, the {{c1::probe}} determines what sequences are detected </div></div>

Answer 191

“<div><div><i>the probe is complementary to the gene sequence of interest</i></div></div><div><i><b><img></img></b></i></div>”

Question 192

<div>A(n)<b>{{c2::Southern}} blot</b> is used to analyze {{c1::DNA}}</div>

Answer 192

“<i>Used in genetic testing of diseases, forensics (DNA identification - microsatellite analysis can also be used here)</i><div><i><br></br></i></div><div><i>Can use to observe inheritance of <b>RFLP </b>markers</i></div><div><i><br></br></i></div><div><i><img></img></i></div>”

Question 193

<div>A(n)<b>{{c2::Northern}} blot</b> is used to analyze {{c1::RNA}}</div>

Answer 193

<i>measure mRNA levels (<b>gene</b> <b>expression</b>)</i>

Question 194

<div><div>Does a <b>Southern blot</b> require <u>gel electrophoresis</u> before analysis? </div><div><br></br></div><div>{{c1::Yes}}</div></div>

Answer 194

“<img></img>”

Question 195

<div><div>What type of <i>probe</i> is used to bind <u>protein</u> when using a <b>Western blot</b>? </div><div><br></br></div><div>{{c1::Labeled antibody}}</div></div>

Answer 195

“<div><i>binds protein that has been separated by gel electrophoresis and transferred to a membrane</i></div><div><img></img></div>”

Question 196

<div><div><div>What type of <i>probe</i> is used to bind <u>DNA/RNA</u> when using a<b>Southern/Northern blot</b>? </div><div><br></br></div><div>{{c1::Labeled single stranded DNA / RNA oligonucleotide}}</div></div></div>

Answer 196

“This can be radioactive or fluorescently labeled<div><br></br></div><div><img></img></div>”

Question 197

<div><div>The <b>{{c1::Western}} blot</b>*used to be* the confirmatory test for HIV after a positive ELISA</div></div>

Answer 197

“FA 2019: Western blot tests are no longer recommended by the CDC for confirmatory testing. Presumptive diagnosis is made with HIV-1/2 Ag/Ab immunoassays. These assays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2.”

Question 198

<div><div>Does a <b>Dot (slot) blot</b> require <u>gel electrophoresis</u> before analysis?</div><div><br></br></div><div>{{c1::No!}}</div></div>

Answer 198

“<div><i>useful for analyzing DNA, RNA, or protein but must know the <u>specific</u> mutation being looked for; e.g. <b>Hemochromatosis</b> (person #3 is homozygous mutant for the C282Y mutation) </i> </div><div><img></img></div><div><br></br></div>”

Question 199

<div>A(n)<b>{{c1::Southwestern}} blot</b> is used to identify <b>{{c2::DNA-binding}} proteins</b> using labeled oligonucleotide probes</div>

Answer 199

“<i>useful for identifying </i><u>transcription factors</u> “

Question 200

<div><div><div>In the <u>first</u> step of <b>PCR</b>, DNA is {{c1::denatured}} by using {{c2::heat}} to separate the strands</div></div></div>

Answer 200

“<div><i>temperature is approximately 95° C</i> </div><div><img></img></div>”

Question 201

<div><div><div>In the <u>second</u> step of <b>PCR</b>, {{c2::<u>DNA</u> primers}} <b>{{c1::anneal}}</b> to <i>specific sequences</i> on each DNA strand to be amplified</div></div></div>

Answer 201

“<div><i>temperature is approximately 55° C</i> </div><div><img></img></div>”

Question 202

<div><div><div>In the <u>final</u> step of <b>PCR</b>, heat-stable {{c2::Taq DNA polymerase}} <b>{{c1::elongates}}</b> the DNA sequence following each primer </div></div></div>

Answer 202

“<div><i>temperature is approximately 72° C</i> </div><div><img></img></div>”

Question 203

<div><div><div>What <u>type</u> of <b>primer</b> is used in a polymerase chain reaction (PCR)?</div><div><br></br></div><div>{{c1::DNA primer}}</div></div></div>

Answer 203

“<div><i>in the body, RNA primers are used; in the test tube, DNA primers are used</i> </div><div><img></img></div>”

Question 204

“<div><div><div>Which end of the DNA strand does the <b>DNA primer</b> bind to during PCR?</div><div><br></br></div><div>{{c1::3’ end}}</div></div></div>”

Answer 204

“<img></img>”

Question 205

<div><div><div><b>PCR</b> requires the addition of all <u>four</u> {{c1::deoxynucleotide triphosphates (dNTPs)}} for DNA synthesis</div></div></div>

Answer 205

“<div><div><i>also requires DNA polymerase and primers</i> ; PCR is repeated until DNA sample size is sufficient</div></div><div><img></img></div>”

Question 206

<div><div><b>{{c1::Flow cytometry}}</b> is a laboratory technique used to assess size, granularity, and protein expression of <u>individual</u> cells in a sample</div></div>

Answer 206

“<div><i>commonly used in the workup of <b>hematologic</b> <b>abnormalities</b> and <b>immunodeficiencies</b></i> </div><div><img></img></div>”

Question 207

<div><div>In <b>flow cytometry</b>, cells are tagged with {{c1::antibodies}} specific to surface or intracellular proteins </div></div>

Answer 207

“<img></img>”

Question 208

<div><div>In <b>flow cytometry</b>, <u>antibodies</u> are tagged with a unique {{c1::fluorescent dye}}, which is detected and counted during analysis </div></div>

Answer 208

“<img></img>”

Question 209

“<div><div><div><u>Flow Cytometry Example</u>: Cells in the <b>right lower quadrant</b> are CD3{{c1::-}} and CD8{{c1::+}} </div><div><br></br></div><div><img></img></div></div></div>”

Answer 209

<i>all CD8 expressing cells also express CD3, hence why this quadrant is empty</i>

Question 210

<div><div><div><b>{{c1::Microarrays}}</b> analyze <u>thousands</u> of nucleic acid sequences arranged in <i>grids</i> on glass or silicon</div></div></div>

Answer 210

“<div><i>useful for genotyping, clinical genetic testing, forensic analysis, cancer mutations, and genetic linkage analysis</i></div><div><img></img> </div>”

Question 211

<div><div><div><div><b>{{c1::Microarrays}}</b> are a laboratory technique used to profile <b>gene expression</b> levels of <u>thousands</u> of genes <i>simultaneously</i> to study certain diseases and treatments</div></div></div></div>

Answer 211

“<img></img>”

Question 212

<div><div><div><b>Microarrays</b> use a(n) {{c1::labeled DNA/RNA}} probe, which is hybridized to the chip, and a scanner detects the relative amounts of complementary binding</div><div></div></div></div>

Answer 212

“<img></img>”

Question 213

<div><div><div>What <u>two</u> types of variations in DNA are detected when using <b>microarrays</b>? (DNA markers)</div><div><br></br></div><div>{{c1::<div> - Single nucleotide polymorphisms (SNPs)</div><div> - Copy number variations (CNVs)</div>}}</div></div></div>

Answer 213

disadvantage: cannot detect translocation or inversions, only can detect <u>gain or loss</u> of material

Question 214

“<div>{{c1::Enzyme-linked immunosorbent assay (ELISA)::not Coombs}} is an <u>immunologic test</u> used to detect the presence of either a <i>specific</i> <b>antigen</b> or <b>antibody</b> in a patient’s blood sample</div>”

Answer 214

<i>major ELISA variations include direct, sandwich, and competitive; can have high sensitivity and specificity</i>

Question 215

<div>When using <b>ELISA</b>, detection involves the use of a(n) {{c1::antibody}} linked to a(n) {{c2::enzyme}} </div>

Answer 215

“<div><i>added <b>substrate</b> then reacts with enzyme, producing a detectable signal (e.g. color change)</i></div><div><br></br></div><div><img></img></div>”

Question 216

<div>{{c1::Fluorescence in situ hybridization (FISH)}} uses a <b>fluorescent DNA/RNA probe</b> to bind to a specific gene of interest on chromosomes</div>

Answer 216

“<img></img>”

Question 217

<div>{{c1::Fluoresence in situ hybridization (FISH)}} is a laboratory technique used for specific <u>localization</u> of genes and direct <u>visualization</u> of chromosomal anomalies</div>

Answer 217

**vs Karyotyping it is <u>higher resolution</u> and can be done in <u>interphase</u>

Question 218

<div>A(n) {{c1::microdeletion}} is detected with <b>FISH</b> as <u>no fluorescence</u> on a chromosome compared to fluorescence at the same locus on the second copy of that chromosome</div>

Answer 218

“<img></img>”

Question 219

<div>A(n) {{c1::translocation}} is detected with <b>FISH</b> as fluorescence <u>outside</u> the original chromosome</div>

Answer 219

“white arrows in image [A] show fragments of chromosome 17 that have been translocated to chromosome 19<div><br></br><div><img></img></div><div><img></img></div></div>”

Question 220

<div>A(n) {{c1::duplication}} is detected with <b>FISH</b> as an <u>extra site</u> of fluorescence on one chromosome relative to its homologous chromosome</div>

Answer 220

“Can result in a <b>trisomy</b> or <b>tetrasomy</b> (blue arrows in image [A])<br></br><div><br></br></div><div><img></img></div><div><br></br></div><div><img></img></div>”

Question 221

<div>What protein is defective in <b>Marfan syndrome</b>?</div>

<div><br></br></div>

<div>{{c1::Fibrillin (scaffold for elastin)}}</div>

Answer 221

“<i>connective tissue disorder affecting skeleton, heart, and eyes</i> <div><img></img><div><i><img></img></i></div></div>”

Question 222

<div>What pathology is associated with <b>long, tapering fingers and toes </b>(arachnodactyly) and <b>subluxation</b> <b>of lenses</b>?</div>

<div><br></br></div>

<div>{{c1::Marfan syndrome}}</div>

Answer 222

“<i>other findings include tall with long extremities, pectus carinatum or excavatum, hypermobile joints, and cystic medial necrosis of the aorta</i> <div><img></img></div>”

Question 223

<div><b>Marfan syndrome</b> typically presents with subluxation of the lenses {{c1::upward::direction}} and {{c1::temporally::direction}}</div>

Answer 223

<i>versus homocystinuria which is usually downward and inward</i>

Question 224

<div><b>Marfan syndrome</b> is associated with a floppy {{c1::mitral}} valve</div>

Answer 224

<i>also associated with aortic incompetence and dissecting aortic aneurysms </i>

Question 225

<div>What is the <u>mode of inheritance</u> of <b>Marfan syndrome</b>?</div>

<div><br></br></div>

<div>{{c1::Autosomal dominant}}</div>

Answer 225

chromosome 15<div>missense=dominant</div>

Question 226

<div><div>What <i>class</i> of diseases is <b>Huntington disease</b> a part of?</div><div><br></br></div><div>{{c1::Trinucleotide repeat expansion diseases}}</div></div>

Answer 226

<i><b>Try</b> (trinucleotide) <b>hunting</b> for <b>my</b> <b>fried</b> <b>eggs</b> (X)</i>

Question 227

<div><div>What <i>class</i> of diseases is <b>Friedreich ataxia</b> a part of?</div><div><br></br></div><div>{{c1::Trinucleotide repeat expansion diseases}}</div></div>

Answer 227

<i><b>Try</b> (trinucleotide) <b>hunting</b> for <b>my</b> <b>fried</b> <b>eggs</b> (X)</i>

Question 228

<div>The influx of calcium during the<b> plateau phase</b> of a <u>myocardial action potential</u> triggers release of Ca²⁺ from the {{c1::sarcoplasmic reticulum}}, causing<b> myocyte {{c2::contraction}}</b></div>

Answer 228

<i>Ca²⁺-induced Ca²⁺ release</i>

Question 229

<div>A defect in <b>left-right dynein</b> during <u>heart morphogenesis</u> can result in {{c1::dextrocardia}}</div>

Answer 229

<i>e.g. Kartagener syndrome (primary ciliary dyskinesia)</i>

Question 230

<div>In the <b>{{c1::peroxisome}}</b>, <u>ethanol</u> may be converted to <u>acetaldehyde</u> via the enzyme <b>{{c2::catalase}}</b></div>

Answer 230

“<img></img>”

Question 231

<div><b>Cystic fibrosis </b>most commonly occurs due to a(n) {{c2::<u>in-frame</u>}} <u>deletion</u> of {{c1::Phe508}}</div>

Answer 231

”- This results in a <b>impaired post translational processing: </b>improper folding and glycolyslation of CFTR results in misfolded protein that gets retained in the RER and marked for proteasomal degradation<div><br></br><div>- thus there is decreased CFTR transported to the cell membrane; decreased Cl secreted at mucosal epithelium, decrease Cl reabsorbed at sweat glands</div></div><div><br></br></div><div><img></img></div><div><img></img></div>”

Question 232

<div><div><div>Following binding of <b>LDL </b>to its <b>LDL receptor</b>, the ligand-receptor complex is <u>endocytosed</u> in <b>{{c1::clathrin}}-coated pits</b></div></div></div>

Answer 232

“<img></img>”

Question 233

<div><div><div>The <b>LDL-containing</b> <u>clathrin-coated pits</u> fuse with <b>{{c1::lysosomes}}</b>, which break down <b>cholesterol ester</b> into <b>cholesterol</b> </div></div></div>

Answer 233

“<div><i>via the enzyme lysosomal esterase</i></div><div><img></img> </div>”

Question 234

<div><b>Sickle cell anemia</b> occurs due to a<i> </i><u>point mutation</u> that substitutes <b>{{c1::glutamic acid}} </b>(hydrophilic) with <b>{{c1::valine}}</b> (hydrophobic) </div>

Answer 234

“<b>glutamic acid</b><i> (HbA) is </i><u>negatively</u><i> charged; </i><b>valine</b><i> (HbS) is </i><u>neutral</u><i> </i>”

Question 235

<div><b>{{c1::Paroxysmal nocturnal hemoglobinuria}}</b> may be confirmed via {{c3::<u>flow cytometry</u>}}, which detects a <u>lack</u> of <b>CD-{{c2::55}}</b> and <b>CD-{{c2::59}}</b></div>

Answer 235

“DAF and MIRL<div><img></img></div>”

Question 236

<div><b>Aplastic anemia</b> may be caused by <b>{{c2::Fanconi}} anemia</b>, which occurs due to a(n) {{c1::<u>dsDNA repair</u>}}<u> defect</u>, resulting in bone marrow failure</div>

Answer 236

“<i>- defect in <b>homologous recombination </b>(double stranded break repair)</i><div><i><br></br></i></div><div><div><i>- dsDNA breaks can be detected by the FA Core Complex, acting as a nidus to recruit BRCA repair enzymes</i></div><div><i><br></br></i></div><div><i><img></img></i></div></div>”

Question 237

<div>The <b>{{c3::cell body}}</b> and <b>{{c3::dendrites}}</b> of a <u>neuron</u> can be seen histologically with <b>{{c1::Nissl}} staining</b>, which stains {{c2::RER}} </div>

Answer 237

“<div><i>RER is not present in the axon</i> </div><div><img></img></div>”

Question 238

<div><b>Lynch syndrome</b> and <i>some</i> <u>sporadic</u><b> colorectal carcinomas</b> arise via the {{c1::microsatellite}} instability pathway </div>

Answer 238

<i>i.e. the serrated polyp pathway</i>

Question 239

<div><div>The <b>{{c2::microsatellite}} instability pathway</b> of <u>colorectal cancer</u> is characterized by <i>mutations</i> or <i>methylation</i> of {{c1::<b>mismatch</b> <b>repair</b>}} <b>genes</b> </div></div>

Answer 239

<i>e.g. MLH1, MSH2</i>

Question 240

<div><b>Free radicals</b> cause cellular injury via {{c1::<u>peroxidation</u>}} of <b>lipids</b> and {{c2::<u>oxidation</u>}} of <b>DNA</b> and <b>proteins</b></div>

Answer 240

<i><b>DNA</b> <b>damage</b> is implicated in <b>aging</b> and <b>oncogenesis</b></i>

Question 241

<div>During phagocytosis, <b>pseudopods</b> extend from <u>leukocytes</u> to form <b>{{c1::phagosomes}}</b>, which are <i>internalized</i> and merged with <b>{{c2::lysosomes}}</b> </div>

Answer 241

“<div><i>thus producing a </i><b>phagolysosome</b> </div><div><img></img></div>”

Question 242

<div><b>{{c2::Ataxia-Telangiectasia}}</b> is due to <u>defects</u> in the <b><i>{{c1::ATM}} </i>gene</b></div>

Answer 242

failure in <b>nonhomologous end joining</b>

Question 243

<div>Which <u>immunodeficiency</u> is caused by <b>failure to repair DNA double strand breaks</b>? </div>

<div><br></br></div>

<div>{{c1::Ataxia-telangiectasia}}</div>

Answer 243

<i>results in <b>unrestricted cell cycle progression</b> (resulting in mutations accumulating) </i> and <b>DNA hypersensitivity </b>to <u>ionizing radiation</u><div><u><br></br></u></div><div>VDJ recombination requires double strand breaks to occur, without ATM these are hard to repair (resulting in a weakened immune system)</div>

Question 244

“<div><b>Ataxia-TelangiectasiA</b> presents with a <u>triad</u> of:</div><div>- {{c1::cerebellar defects (<b>A</b>taxia)}}</div><div>- {{c2::spider angiomas (<b>T</b>elangiectasia)}}</div><div>- {{c3::Ig<b>A</b> deficiency}} </div>”

Answer 244

<i>lymphopenia and cerebellar atrophy</i> <div><br></br></div><div><div>- Toddlers wobble and sway when walking (almost appear drunk)</div><div><br></br></div><div>- patients present also with slurred distorted speech, swallowing, dysarthria, and oculomotor apraxia</div><div><br></br></div><div>- Telangiectasias erupt on skin and eye, early aging (premature greying of hair)</div></div>

Question 245

<div>What <i>type</i> of tissue is comprised of <b>stem cells</b> that can <u>continuously cycle</u> to <b>regenerate tissue</b>? </div>

<div><br></br></div>

<div>{{c1::Labile}}</div>

Answer 245

<i>e.g. small and large bowel, skin, bone marrow</i>

Question 246

<div><b>{{c1::Duchenne}} muscular dystrophy</b> is typically due to <u>frameshift</u> or <u>non-sense</u> mutations, resulting in a <b>truncated</b> or <b>absent dystrophin protein</b> </div>

Answer 246

“<i>”“<b>D</b>uchenne = <b>D</b>eleted <b>D</b>ystrophin”” (vs. Becker, where dystrophin is mutated)</i> “

Question 247

<div><b>{{c1::Liposarcoma}}</b> is a <u>malignant</u> tumor of <b>adipose tissue</b> </div>

Answer 247

<i>characterized histologically by nuclear indentations and <b>scalloping</b> of the nuclear membrane</i>

Question 248

<div>{{c1::<b>Ubiquitin</b>}}-ation of proteins recruits the {{c2::<b>proteasome</b>}} to degrade them</div>

Answer 248

“<img></img>”

Question 249

<div><b>Irinotecan, </b>a(n) {{c2::<b>Topoisomerase I</b>}} <b>inhibitor</b>, is used to treat {{c1::<b>Colon</b>}} <b>Cancer</b></div>

Answer 249

“<img></img>”

Question 250

<div><div><b>Vinca Alkaloids</b> are antineoplastics that prevent cell cycle progression at the {{c2::<b>M</b>}} <b>phase</b></div></div>

Answer 250

“<i>ex. include <b>Vinblastine </b>and <b>Vincristine</b></i><div><i><img></img></i></div>”

Question 251

<div><div><div>A general rule of chemotherapeutic side effects is that they will affect all {{c1::rapidly}} dividing cells</div></div></div>

Answer 251

These are known as <b>Labile </b>cells; thus side affects at the skin, GI tract, bone marrow

Question 252

<b>Growth Factors </b>induce cellular {{c1::growth}}<div><br></br></div><div><i>vs mitogen</i></div>

Answer 252

<div>- Examples include EGF, IGF-1, NGF</div>

<div><br></br></div>

• Note, <b>mitogens</b> induce cellular division, compounds can be growth factors and mitogens

Question 253

<div>The <b>Cell Cycle</b> is regulated by <u>Cyclins</u> and<u>Cyclin-Dependent Kinases (CDKs)</u> which when {{c2::<b>complexed</b>}} allow cells to bypass {{c1::<u>restriction points</u> (checkpoints)}}</div>

Answer 253

”- Thus, these proteins are an important point of regulation by the cell in order to avoid tumorigenesis<br></br><div><br></br></div><div>- restriction points occur near the end of <b>G1</b>, near the end of G2, and within M metaphase</div><div><br></br></div><div><img></img></div>”

Question 254

The <b>G₁ restriction point</b> of the cell cycle is regulated by the <u>tumor suppressors</u> {{c1::<b>p53</b>}} and {{c1::<b>Rb</b>}}

Answer 254

“<div>This allows the cell to verify:</div><div>- should I be going into S phase?</div><div>- would I be carrying any mutations into S phase?</div><div><br></br></div><div><img></img></div>”

Question 255

p53 restricts the cell cycle to <b>G1</b> by engendering the inhibition of {{c2::<b>CDK4</b>}}, maintaining the <u>{{c1::hypo}}phosphorylated</u> state of Rb

Answer 255

“However when stimulated, CDK4 binds Cyclin D1 to initiate the hyperphosphorylation of Rb (**this leads to Rb leaving and E2F acting as a transcription factor for things needed in S phase)<br></br><div><br></br></div><div><img></img></div>”

Question 256

In response to <b>DNA damage</b>, p53 initially attempts to {{c1::<u>halt</u>}}<u> the cell cycle</u> and <u>facilitates the activity of {{c2::DNA repair}} enzymes</u><div><u><br></br></u></div><div>*<i>bonus-what does it <u>induce</u> that inhibits the cell cycle?</i></div>

Answer 256

”- <u>induces P21</u> which inhibits CDK complexes important for release of E2F from RB<div><br></br></div><div>- facilitates NER, BER, Mismatch Repair, dsDNA repair pathways<br></br><div><br></br></div><div><img></img></div></div>”

Question 257

If <b>DNA repair</b> is not possible, p53 induces {{c1::apoptosis}}

Answer 257

“<img></img>”

Question 258

<b>Growth Factors </b>stimulate G₁ phase by increasing the levels of the {{c1::Cyclins}}

Answer 258

”- Once cyclins (ex <b>Cyclin D1</b>) reach a sufficient level, these activate <b>CDKs</b> to stimulate progression past the G₁ restriction point<div><br></br></div><div>- growth factors include EGF, PDGF, EPO</div><div><br></br></div><div><img></img></div>”

Question 259

Once levels of <b>Cyclins</b> reach an appropriate level, these complex with {{c1::Cyclin-Dependent Kinases}} to hyperphosphorylate <u>Rb</u>

Answer 259

”- <u>Cyclin D / CDK4</u> monophosphorylate Rb, which is followed by hyperphosphorylation by <u>Cyclin E / CDK2</u><div><br></br></div><div>- this causes a conformational change that releases sequestered E2F from Rb<br></br><div><div><br></br></div><div><img></img></div></div></div>”

Question 260

<b>Tumor suppressor </b>genes {{c1::regulate}} cell growth

Answer 260

”- These <u>decrease</u> (““suppress””) risk of tumor formation (ex. p53 / Rb)<div><br></br></div><div>- as opposed to proto-oncogenes which promote cell growth</div>”

Question 261

<div>When performing <b>Immunohistochemistry</b>; a(n) {{c1::Cytokeratin}} stain can be used to identify <u>Epithelial tumors (ex Squamous Cell Carcinoma)</u></div>

Answer 261

“<div><div>- ex. SCC of the head and neck, cervical cancer, lung, skin, esophagus</div><div><br></br></div><div><u><img></img></u></div></div>”

Question 262

<div>When performing <b>Immunohistochemistry</b>; a(n) {{c1::Vimentin}} stain can be used to identify <u>Sarcomas, Endometrial Carcinoma, RCC, Meningioma</u></div>

Answer 262

“These are tumors of <u>mesenchymal tissue</u><div><u><br></br></u><div><img></img></div></div>”

Question 263

<div>When performing <b>Immunohistochemistry</b>; a(n) {{c1::Desmin}} stain can be used to identify <u>Rhabdomyosarcomas, Leiomyomas, Leiomyosarcomas</u></div>

Answer 263

“These are tumors of <u>muscle tissue</u> <div><u><br></br></u><div><img></img></div></div>”

Question 264

<div>When performing <b>Immunohistochemistry</b>; a(n) {{c1::Glial Fibrillary Acidic Protein (GFAP)}} stain can be used to identify <u>Astrocytomas, Glioblastomas, Oligodendrogliomas, Ependymomas</u></div>

Answer 264

“<div>These are tumors of <u>neuroglia</u> <div><u><br></br></u><div><img></img></div></div></div>”

Question 265

<div>When performing <b>Immunohistochemistry</b>; a(n) {{c1::Neurofilament}} stain can be used to identify <u>neuroblastomas, medulloblastomas, retinoblastomas</u></div>

Answer 265

“These are tumors of <u>neurons</u> <div><u><br></br></u><div><img></img></div></div>”

Question 266

<div><b>Colchicine</b> works by inhibiting intracellular {{c1::<b>microtubule</b>}} polymerization through binding and stabilizing {{c1::<b>tubulin</b>}}</div>

<div><br></br></div>

Answer 266

“<div>- this prevents <u>polymerization</u> of microtubules, thus cells that rely on microtubule polymerization (ex <b>Neutrophils</b>) will be strongly affected</div><div><br></br><div><img></img></div></div>”

Question 267

The exotoxin <b>Diphtheria</b> toxin causes {{c2::<u>ADP-ribosylation</u> (and therefore inhibition)}} of <u>{{c2::elongation factor-2 (EF2)}}</u>

Answer 267

“EF2 is needed for protein synthesis, therefore protein synthesis is inhibited by the exotoxin<div><img></img></div>”

Question 268

<u>Diagnosis of HIV</u>previouslywas made initially with {{c1::<b>ELISA</b>}}; <i>positive results</i> are <u>confirmed</u> with a(n)<b>{{c2::Western}} blot</b>

Answer 268

“FA 2019: <span>Western blot</span> tests are no longer recommended by the <span>CDC</span> for <span>confirmatory testing</span>. <b>Presumptive diagnosis is made with <span>HIV</span>-1/2 Ag/Ab immunoassays</b>. These assays detect viral <span>p24</span> Ag <span>capsid</span> protein and <span>IgG</span> Abs to <span>HIV</span>-1/2. <br></br> <div><img></img><img></img></div> “

Question 269

{{c1::PCR}} is the gold standard used in the diagnosis of <b>Herpes Simplex Virus</b>

Answer 269

“<img></img>”

Question 270

<b>Colchicine</b> binds {{c1::<b>tubulin</b>}}, preventing <i>polymerization</i> of <u>{{c2::microtubules}}</u>

Answer 270

“<img></img>”

Question 271

Which <b>gout drug</b> binds <u>tubulin</u> and inhibits intracellular <u>microtubule polymerization</u>?<div><br></br></div><div>{{c1::Colchicine}}</div>

Answer 271

“<div><i>thus inhibiting neutrophil entry and inflammation due to MSU crystal deposition</i></div><div><br></br></div><img></img>”

Question 272

What used to be the <b>rule out</b> test for <u>HIV</u>?<div><br></br></div><div>{{c1::ELISA}}</div>

Answer 272

“<div>FA 2019: Western blot tests are no longer recommended by the CDC for confirmatory testing. Presumptive diagnosis is made with HIV-1/2 Ag/Ab immunoassays. These assays detect viral p24 Ag capsid protein and IgG Abs to HIV-1/2.</div><div><br></br></div><div>sensitive (SNout)</div><img></img>”

Question 273

<b>{{c2::Ionizing}} radiation</b> results in the formation of <u>double-stranded</u> <b>breaks</b> in DNA and <u>{{c1::hydroxyl free radicals}}</u> which <b>damage DNA</b>

Answer 273

“H₂O in tissues hit with ionizing radiation -> *OH free radicals generated<div><br></br></div><div>associated with AML, CML, and papillary thyroid carcinoma</div><div><img></img><br></br></div>”

Question 274

{{c1::Xeroderma pigmentosum}} results from lack of <b>excision endonuclease</b> activity to remove <u>pyrimidine dimers</u>

Answer 274

“<div>defective nucleotide excision repair</div><img></img>”

Question 275

{{c1::<b>Sarcoma</b>}} implies the cancer is of <u>mesenchymal</u> origin

Answer 275

soft tissues (e.g. fat, musle, bone, etc)

Question 276

<b>Li-Fraumeni syndrome</b> is characterized by <u>multiple malignancies</u> at a(n) {{c1::early}} age

Answer 276

“<img></img>”

Question 277

Which enzyme is inhibited by <b>topotecan</b>?<div><br></br></div><div>{{c1::topoisomerase I}}</div>

Answer 277

“<img></img>”

Question 278

Which enzyme is inhibited by <b>irinotecan</b>?<div><br></br></div><div>{{c1::topoisomerase I}}</div>

Answer 278

“<img></img>”

Question 279

Which of the cytotoxic microtubule inhibitors <u>bind</u> <b>β-tubulin</b> and <u>inhibit</u><b> polymerization</b>?<div><br></br></div><div>{{c1::Vincristine; Vinblastine::2}}</div>

Answer 279

“<div>thus preventing mitotic spindle formation</div><img></img>”

Question 280

Which of the cytotoxic microtubule inhibitors <u>prevent</u> <b>mitotic spindle formation</b>?<div><br></br></div><div>{{c1::Vincristine; Vinblastine}}</div>

Answer 280

“<div>via binding to <b>β</b>-tubulin and inhibit its<b> </b>polymerization</div><img></img>”

Question 281

Which phase of the <u>cell cycle</u> do <b>vincristine</b> and <b>vinblastine</b> act at?<div><br></br></div><div>{{c1::M phase}}</div>

Answer 281

“<div>prevent mitotic spindle formation (specifically the <u>prophase</u> of mitosis)</div><img></img>”

Question 282

Which of the cytotoxic microtubule inhibitors <u>bind</u> <b>microtubules</b> and <u>inhibit</u> their<b> depolymerization</b>?<div><br></br></div><div>{{c1::Paclitaxel (taxanes)}}</div>

Answer 282

“<img></img>”

Question 283

Which of the cytotoxic microtubule inhibitors <u>enhance</u> <b>mitotic spindle formation</b>?<br></br><div><br></br></div><div>{{c1::Paclitaxel (taxanes)}}</div>

Answer 283

“<img></img>”

Question 284

Which phase of the <u>cell cycle</u> does <b>paclitaxel</b> (taxanes) act at?<div><br></br></div><div>{{c1::M phase}}</div>

Answer 284

“<img></img>”

Question 285

Which <u>antifungal</u> works by <i>disrupting</i> <b>mitotic spindles</b>?<div><br></br></div><div>{{c1::Griseofulvin}}</div>

Answer 285

“<div><br></br></div><div><br></br></div><img></img>”

Question 286

<b>{{c1::Mesenchyme}} </b>is the embryonic connective tissue

Answer 286

• not found in adults except for mesenchymal stem cells<div><br></br><div>- <b>mostly</b> derives from <u>mesoderm</u></div></div>

Question 287

The <b>Mesenchyme </b>gives rise to <i>most</i> <b>{{c1::connective tissue}}</b>

Answer 287

• bones, cartilage, lymphatic, and circulatory systems<div><br></br><div>- cells of the mesenchyme are surrounded by protein and fluid</div></div>

Question 288

Patients with <b>Xeroderma Pigmentosum</b> often present with <u>freckled and dry</u> skin, <u>extreme</u> <b>{{c1::sunlight}} sensitivity, </b>and {{c2::<b>corneal</b>}} <b>ulcers</b>

Answer 288

”- patients will typically be light skinned<div><br></br></div><div><i><img></img></i></div>”

Question 289

Patients with <b>xerodermapigmentosum</b>are at risk for which type/s of skin cancer?<div><br></br></div><div>{{c1::All :)}}</div>

Answer 289

• Melanoma, Basal Cell Carcinoma, Squamous Carcinoma

Question 290

Patients with <b>Xeroderma Pigmentosum</b> cannot repair {{c1::Thymidine Dimers}} formed as a result of <u>UV-B</u> exposure

Answer 290

“<div>These patients either have a defective enzyme that recognizes <u>helix distortions</u> (XPC / XPA) or have a defective <u>excision endonuclease</u> (XPB, XPD-XPG)</div><div><br></br></div><div><img></img></div><div><img></img></div>”

Question 291

<b>Nonhomologous End Joining (NHEJ)</b> occurs {{c1::before::before/after?}} S phase of the cell cycle

Answer 291

”- There is NO requirement for homology<div><br></br></div><div><img></img></div>”

Question 292

Is <b>Nonhomologous End Joining </b><u>error prone</u>?<div><br></br></div><div>{{c1::Yes}}</div>

Answer 292

HIGHLY error prone; this has no template strand to compare to

Question 293

<u>Nonhomologous End Joining</u> is defective in {{c1::<b>SCID</b>}} and {{c2::<b>Ataxia Telangiectasia</b>}}

Answer 293

”- Ex. defect in the <u>Artemis</u> protein or <u>ATM</u><br></br><div><br></br></div><div><img></img></div>”

Question 294

The <u>intermediate filament</u> <b>Cytokeratin</b> is found in {{c1::Epithelial}} cells

Answer 294

”- Thus IHC stains can be developed for tumors of epithelial cells<div><br></br></div><div>- Keratin proteins are highly abundant in exposed stratified squamous epithelium (such as epidermis, oral mucosa) and are less abundant but still present in simple epithelium (such as liver, gut, pancreas)</div><div><br></br></div><div><img></img></div>”

Question 295

The <u>intermediate filament</u> <b>Vimentin</b> is found in {{c1::mesenchymal}} tissue

Answer 295

“<div>(ex fibroblasts, endothelial cells, macrophages)</div><div>- Thus IHC stains can be developed for tumors of mesenchymal origin</div><div><br></br></div><div>- endogenously, Vimentin’s role is to maintain cell structure in mesenchymal cells</div><div><br></br></div><div><img></img></div>”

Question 296

The <u>intermediate filament</u> <b>Desmin</b> is found in {{c1::muscle}} cells

Answer 296

”- Thus IHC stains can be developed for tumors of muscle cells<div><br></br></div><div>- endogenously, Desmins role is to maintain cell structure in muscle cells (Smooth, cardiac, skeletal)</div><div><br></br></div><div><img></img></div>”

Question 297

The <u>intermediate filament</u> <b>Glial Fibrillary Acidic Protein (GFAP)</b> is found in {{c1::neuroglial}} cells (ex. astrocytes, Schwann cells, oligodendrocytes)

Answer 297

”- Thus IHC stains can be developed for tumors of neuroglial cells; do not rely on this for schwannoma as it also has S-100<div><br></br></div><div>- endogenously, GFAPs role is to maintain cell structure in Neuroglia</div><div><br></br></div><div><img></img></div>”

Question 298

The <u>intermediate filament</u> <b>Neurofilament</b> is found in {{c1::neurons}}

Answer 298

• Thus IHC stains can be developed for tumors of neurons (ex. Neuroblastoma)<div><br></br></div><div>- endogenously, Neurofilaments role is to maintain cell structure in neurons</div>

Question 299

The <b>Peroxisome</b> is a cytosolic membrane involved in the β-oxidation of {{c1::Very-long-chain fatty acids (VLCFA)}}

Answer 299

<div>- this is defective in <b>Adrenoleukodystrophy</b> - VLCFA build up and cause pathology</div>

Question 300

Which cellular organelle is responsible for catabolism of <u>branched-chain fatty acids</u>, <u>amino acids</u>, and <u>ethanol</u>?<div><br></br></div><div>{{c1::Peroxisome}}</div>

Answer 300

An example of a branched-chain fatty acid = Phytanic Acid

Question 301

A <u>germline P53 mutation</u> predisposes you to what tumor <i>syndrome</i>?<div><br></br></div><div><b>{{c1::Li-Fraumeni (SBLA) Syndrome}}</b></div>

Answer 301

When patients develop a somatic hit of the normal P53, the absence of both alleles of this tumor suppressor results in pathology

Question 302

“<b>Li-Fraumeni Syndrome</b> is also known as ““<b>SBLA</b>”” Syndrome, which stands for:<div style=""><div class=""><div><br></br></div><div><b>S</b> - {{c1::Sarcoma}}</div><div><b>B </b>- {{c2::Breast Cancer}}</div><div><b>L </b>- {{c3::Leukemia}}</div><div><b>A </b>- {{c4::Adrenal Gland tumor}}</div></div></div>”

Answer 302

Loss of the P53 tumor suppressor results in a constellation of tumors due to absence of G1-S checkpoint regulation

Question 303

In regards to <b>wrinkles of aging</b>, there is <u>{{c1::decreased}}</u> synthesis of collagen fibrils and <u>{{c2::increased}}</u> crosslinking of collagen

Answer 303

“<div>In contrast to FA2018, UWORLD says there is increased cross linking of collagen</div><div>- in aging, the atrophic dermis and increased collagen cross linking + dessication of stratum corneum produce the characteristic wrinkling of photoaged skin</div><div><br></br></div><div><img></img></div>”

Question 304

A <b>direct ELISA</b> tests for a(n) {{c1::antigen}}, whereas the <b>indirect ELISA</b> tests for a(n) {{c2::antibody against an antigen}}

Answer 304

The antibodies for an indirect ELISA are easier to acquire

Question 305

Patients with <b>ataxia-telangiectasia</b> have vitiligo, granulomas, and a high recurrence of {{c1::sinopulmonary}} infections

Answer 305

recurrent sinopulmonary infections can lead to bronchiectasis; due to being IgA, IgG, and IgE deficient

Question 306

<b>Anthracyclines</b> (-rubicin) bind {{c1::topoisomerase II}} to cause <b>cleavage</b> of DNA

Answer 306

“<div>in addition to binding Fe -> free radical formation</div><img></img>”

Question 307

<b>Depurination</b> results in the loss of {{c1::purine}} bases

Answer 307

occurs thousands of times per day- sugar phosphate stays in the backbone