Week 2 Review Flashcards by Howard Sanders

What function do cadherins serve? What about integrins? Selectins?

Cadherens are proteins involved in cell-cell junctions.

Integrins are involved in cell-matrix junctions.

Selectins are involved in temporary cell-cell junctions.

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By what mechanism does pemphigus mess up the skin?

Antibodies destroy desmoglein (a cadherin - cell-cell adhesion molecule) that binds intermediate filaments in desmosomes and hemidesmosomes –> blistering.

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Name and briefly describe the steps involved in specimen slide preparation.

Accessioning (receiving, sorting, etc.)
Fixation using formalin preserves the tissue
Processing dehydrates the specimen; uses alcohol and subsequent removal of solvent
Embedding with paraffin wax or epoxy resin
Sectioning (cutting with a microtome)
Staining

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Is hematoxylin basic, or acidic? What charge does it carry? What does it bind to? What color is it? What about eosin?

Hematoxylin is a basic dye and has a (+) charge because it has picked up a proton. It stains negatively charged stuff like nucleic acids blue.

Eosin is an acidic dye and has a (-) charge because it has lost a proton. It stains positively charged stuff like cytoplasmic proteins pink/red.

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How does trichrome stain connective tissue? Is that a distinguishing characteristic of the dye?

It stains connective tissue blue. Yeah its characteristic.

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What is one class of molecules that are stained particularly well with PAS stain?

Carbohydrates/mucus

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Do fluorescent stains use antibodies with dye attached as markers?

Yeah

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Describe the differences of euchromatin, heterochromatin, and the nucleolus regarding histologic staining.

Euchromatin stains light

Heterochromatin is dark

Nucleolus is a dark round spot

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Name two cellular organelles in which enzymes for protein glycosylation are found.

In the RER and the Golgi

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Name five things that happen to a newly synthesized protein in the RER.

Proteolysis of the signal peptide
Protein folding
Disulfide bonding
Glycosylation
Double-checking (quality control)

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COPII secretory vesicles are used for transport from the _______ to the _______.

COP II: from RER to Golgi

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Proinsulin is cleaved to insulin in the…?

secretory vesicle

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What is the little thing called that recognizes N-terminal hydrophobic sequences on proteins undergoing translation and brings the ribosome/polysome over to the RER for docking? What is the thing that it all docks to?

The signal recognition particle (SRP) recognizes the N-terminal hydrophobic sequence.

It all docks on a translocon in the RER membrane.

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What is a COPI vesicle?

A vesicle that is sent back from the Golgi to the RER that helps maintain the size of the Golgi.

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Nascent ER membrane proteins are recognized by SRPs and docked to translocons on the RER in a similar manner to secreted proteins. What is the big difference with ER membrane proteins in the translation process?

As the nascent chain is fed through the translocon, a stop transfer sequence is encountered (a hydrophobic transmembrane sequence) and the translocon opens up to allow the protein to slide laterally into the membrane.

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What happens when there is an accumulation of misfolded proteins in the ER?

The ER stress response happens:

Increased chaperone synthesis and activity
Reduction of protein translation
Increased ub-proteasome activity
Apoptosis if it gets bad

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Outline the steps in carrier vesicle formation and fusion with the plasma membrane.

Coat complexes help form vesicle
Scissioning (budding)
Rab proteins on vesicle bind to tethering factors on the inner PM to bring the vesicle close to the PM
v-SNARE (on vesicle) and t-SNARE (on PM) bind to form a Trans-SNARE complex.
Trans-SNARE complex zippers together to form a cis-SNARE complex

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The terminal compartment of the endocytic system is the _______.

lysosome

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Clathrin coated vesicles are used for _________ at the plasma membrane as well as for secretory vesicle formation at the _______ (sometimes). They use inner adapter proteins to grab hold of _______.

Clathrin coated vesicles are used for endocytosis

also used for some vesicle formation at the Golgi

inner adapter proteins grab hold of cargo

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Explain the mechanism of action of tetanospasmin (tetanus neurotoxin).

Tetanospasmin causes spastic paralysis by cleaving t-SNAREs on inhibitory interneurons that regulate the activity of motor neurons. No regulation of motor neurons = uncontrolled release of Ach at the neuromuscular junction –> spastic paralysis.

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Explain the mechanism of action of botulism toxin.

Botulism toxin cleaves t-SNAREs on the excitatory motor neuron that releases Ach. No Ach release = no muscle contraction (flaccid paralysis)

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F-actin assembly is coupled to the hydrolysis of _____. F-actin’s monomers are globular proteins called _____ that assemble into spiraling rows. The “plus” end is the end that grows _______.

F-actin assembly is coupled to hydrolysis of ATP during assembly.

G-actin is the monomer

Plus end grows faster

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Microtubule assembly is coupled to the hydrolysis of _____, which binds to ______. Microtubules are made from ______ and _______ _______ that assemble into tubes called ________. The “plus” end is the end that grows _______.

Microtubule assembly is coupled to GTP hydrolysis, which binds to B-tubulin.

Microtubules are made from a- and B-tubulin heterodimers that assemble into tubes called protofilaments

Plus end grows faster

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What is one big consequence of not having polarity on intermediate filaments?

They can’t be used as tracks for molecular motors.

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Keratin is an example of a(n)...?

Intermediate filament

What type of cytoskeletal protein is responsible for spindle formation during mitosis?

Microtubules

Adherens junctions can encircle the cell like a belt. They attach to ______ cytoskeletal proteins inside cells.

actin

Tight junctions stop ________ transport and attach to _______ cytoskeletal proteins inside cells.

Tight junctions stop paracellular transport (between cells) and attach to actin cytoskeletal proteins.

Desmosomes and hemidesmosomes attach to which class of cytoskeletal proteins inside cells?

intermediate filaments

What type of cytoskeletal proteins are involved in gap junctions?

Trick question! They don't use cytoskeletal proteins. Connexins are the proteins used.

Pemphigus is an autoimmune disease that attacks desmoglein, a _________ protein involved in what type of cell-cell junction complex?

Desmoglein is a cadherin involved in desmosomes.

Kinesins move towards the ____ end of which which type of cytoskeletal protein? What is the fancy word for movement in the direction away from the microtubule organizing center?

Kinesin moves towards the (+) end of microtubules. Called anterograde movement.

Dyneins usually move towards the _____ end of which type of cytoskeletal protein? What is the fancy word for movement in the direction towards from the microtubule organizing center?

Dynein moves towards the (-) end of microtubules. Called retrograde movement.

The mechanical work of molecular motor proteins are usually coupled with...?

ATP hydrolysis

Define processivity in regards to molecular motors.

The motor's ability to perform many chemo-mechanical cycles without disconnecting from the track.

A 25 year-old presents to your office for infertility. On physical exam you palpate his liver on his left side instead of his right. What is likely causing his infertility? How?

Primary ciliary dyskinesia/Kartagener's - lack of dynein motors in cells so sperm cannot beat flagellum (a ciliary structure) for motility. Patients also have situs inversus.

During microtubule assembly, heterodimers bound to GTP form a _____ _____. When heterodimers within the growing microtubule hydrolyze GTP --> GDP, the microtubule becomes less _______. Catastrophe occurs when the ______ ______ is lost.

GTP-bound heterodimers on the growing end of the MT form a GTP cap. GTP hydrolysis makes the MT less stable. Catastrophe happens when the GTP cap is lost.

What do the drugs colchicine and taxol do, respectively?

Colchicine prevents assembly of the microtubule spindle during mitosis. Taxol freezes the spindle during assembly.

Which germ layer is responsible for formation of the ribs?

Paraxial mesoderm

Which germ layer is responsible for formation of the vertebrae?

Paraxial mesoderm

Which germ layer is responsible for formation of the kidneys?

Intermediate mesoderm KIDS Kidneys Intermediate mesoderm gonaDS

Which germ layer is responsible for formation of skeletal muscle?

Paraxial mesoderm

Which germ layer is responsible for formation of the dermis of the skin?

Paraxial mesoderm

Which germ layer is responsible for formation of the parietal pleura?

Somatic mesoderm

Which germ layer is responsible for formation of the visceral pleura?

Splanchnic mesoderm

Which nerve innervates the diaphragm? In which structure is this nerve located during week 4 of embryonic development?

Phrenic nerve, located in the pleuropericardial folds during formation of the pleural and pericardial cavities in week 4.

Which ends of the neural tube close last? What are these called? What can happen if they don't close?

The caudal and cranial ends close last. These are called the caudal and cranial neuropores. If they don't close, anencephaly or spina bifida may occur.

Sarcoccygeal tumors likely form from a remnant of the ______ _____ that failed to degenerate.

primitive streak

Why might you find all sorts of different tissue in a sacroccygeal tumor?

Because epiblast cells that give rise to all three germ layers were involved in the initial formation of the tumor at the caudal end of the primitive streak.

Describe the three classes of spina bifida.

Spina bifida occulta - asymptomatic; spinal cord and meninges are housed within the vertebral "foramen," although the lamina and spinous processes of the vertebra did not form. Meningocele - meninges and CSF have bulged out of the vertebrae but the spinal cord remains within the vertebrae. Meningomyelocele - both the meninges and spinal cord are bulged out of the vertebrae. Spinal cord usually gets kinked --> paralysis.

What is rachischisis aka myeloschisis?

Failure of the neural folds to close. No spinal cord formed.

Which germ layer is responsible for formation of the heart?

Lateral mesoderm

Which germ layer is responsible for formation of the epidermis and lens of the eye?

surface ectoderm

Which germ layer is responsible for formation of the CNS?

neuroectoderm

The lateral mesoderm is separated into the ________ mesoderm on the dorsal side and the ________ mesoderm on the ventral side after formation of the intraembryonic coelom.

somatic mesoderm on the dorsal side and splanchnic mesoderm on the ventral side

State the amount of exposure to radiation each imaging modality exposes to patients.

In milliSieverts (mSv): ``` MRI: 0 Ultrasound: 0 Chest XR: 0.02 Mammogram: 0.4 Upper GI: 6 CT: 1-7 for modern scanners, 1-15 for old ones Nuclear med: 1-14 ```

The basement membrane is made up of two sub-layers. What are they?

Basal lamina + reticular lamina = basement membrane

The basal lamina is made by _______ cells while the reticular lamina is made by both ________ and _______ cells.

Basal lamina is made by epithelial cells. Reticular lamina is made by CT and epithelial cells.

Name two types of collagen the epithelial cells secrete into the basal lamina.

Type IV and VII collagen

Which collagen type is mainly responsible for securing the reticular lamina to the basal lamina?

Type VII collagen

__________ cells in the CT secrete stuff that makes up the CT.

Fibroblasts

Name the four types of collagen which fibroblasts secrete to make up the CT. What other two substances do they produce that make up "ground substance?"

Collagen Type I, Type III (reticular fibers), Type IV, and Type VII They also make glycoproteins and proteoglycans (core protein+GAGs)

Explain how epithelial cells are renewed.

Stem cells located at the basal lamina divide, as daughter cells move towards the apical surface they mature.

What are the three major types of gland structure?

1. Acinar/alveolar (round) 2. Tubular 3. Tubuloalveolar

Describe the three types of ducts.

1. Simple: single gland empties into a single duct. 2. Simple branched: several glands empty into a single duct. 3. Compound: several simple branched units empty into a large duct.

Define merocrine secretion.

Exocytosis of product

Define apocrine secretion.

Decapitation of a portion of the apical cell with loss of cytoplasm.

Define holocrine secretion.

Whole cell secretion

What is the inheritance pattern of CF? Which chromosome is the CFTR protein-coding gene located on?

Autosomal recessive chromosome 7

G551D is a CF a mutation that switches a glycine for an asparagine at the 551 position in the polypeptide. This type of mutation is called a _______ mutation.

missense

A mutated nucleotide-binding domain on the CFTR protein is considered a class III mutation. This results in...?

Altered REGULATION: Cl- pore won't open for long enough

The deltaF508 CF mutation is considered a class II mutation. Describe what happens to the CFTR protein in this case.

The deltaF508 frameshift mutation causes protein misfolding --> ub-proteasome pathway for destruction

CF mutations with a "X" on the end (G542X, W1282X) denote what type of mutation?

Nonsense

How does CF present in newborns? Why?

Failure to thrive. Blockage of pancreatic duct means no digestive enzymes in duodenum

How does a beta-2 adrenergic receptor agonist help patients with CF?

It dilates the airways

Patients with which specific CF mutation would benefit from a "corrector?" How do these drugs work?

Patients with deltaF508. Correctors stabilize the mutated CFTR protein during folding in the ER lumen.

What do "potentiators" do for CF patients?

These drugs increase the amount of time that the CFTR pore is open (good for G551D and deltaF508 patients)

Ataluren causes read-through of stop codons; it is potentially helpful for CF patients who have a ______ mutation.

nonsense

What is the tail of Spence/axillary tail/axillary process and why is it clinically relevant?

It is the extension of breast tissue into the armpit and should be checked during routine screening.

Describe the retromammary space and why it is clinically relevant.

It is a potential space between the deep fascia of the pectoralis major and the superficial fascia of the dermis. Cancer metastasis can invade this area and prevent free movement between the two fascial layers.

________ ligaments are located within breast tissue and provide structural integrity.

Cooper's/suspensory ligaments

Describe the pathway of breast milk in the duct system of a breast.

Lobules --> terminal duct --> lactiferous duct --> lactiferous sinus

Describe the pathway of lymph drainage to the venous circulation for the lateral half of the breast.

Lateral breast → axillary nodes → supraclavicular nodes → subclavian ducts → right lymphatic duct/thoracic duct → right subclavian vein/left subclavian vein

Describe the pathway of lymph drainage to the venous circulation for the medial half of the breast.

Medial breast → parasternal nodes → bronchomediastinal trunk → right lymphatic duct/thoracic duct

What is a sentinel lymph node?

The first node to receive lymph drainage from a particular area.

Osteogenesis imperfecta is a defect in ______ _______ and is also called "brittle-bone disease"

defect in type I collagen

Weak muscle tone (hypotonia), brittle hair, sagging facial features, seizures, intellectual disability, and developmental delay are some clinical features of Menkes disease. What causes Menkes disease?

Defective GI epithelial cell transport of copper into the bloodstream. Copper is a cofactor for lysyl oxidase in collagen cross-linking.

Patients with Alport syndrome exhibit proteinuria and hematuria because the type ____ collagen in the glomerular basement membrane is mutated and doesn't filter properly.

type IV

Vitamin C is a cofactor for prolyl hydroxylase, the enzyme that converts proline to hydroxyproline during collagen synthesis. What disease can result from prolonged vitamin C deficiency?

Scurvy

Goodpasture syndrome is an autoimmune disease by which type _____ collagen in the lungs and kidneys is destroyed.

type IV

What does the drug Kalydeco do?

It is a "potentiator" that helps correct altered regulation of the CFTR protein's NBD, helping the Cl- pore open for a longer period of time.

What does Lumacaftor (VX-809) do?

It is a "corrector" that acts as a chaperone during CFTR protein folding in the RER. Particularly helpful for patients with deltaF508 mutation.

What does Ataluren (PTC124) do?

It causes read-through of stop codons. May help CF patients with a nonsense mutation (ending in "X")