Part Bs (Epithelia, Differentiation, Bone and Skeletal muscle)

Question 1

Tight junctions

Answer 1

Claudins and occludins, create apical and basolateral sealing, selective barrier EG CLDN1 in Bowman’s capsule and restrict rotation around a junction

Question 2

Adherens junctions

Answer 2

Ca2+ dependent cadherins - removed = less rigid, selective recognition (velcro) in homotypic cluster interactions (cardiac contraction) with alpha and beta catenins with recruited actin and myosin filaments

Question 3

Experiment epithelia

Answer 3

N- E cadherin dependent cell sorting - that encode cell surface identity - heavy and light too - important in neural tube development and closing

Question 4

Desmosomes

Answer 4

Mechanical strength dependent on desmogleins and desmocoilins, pemphigus is the result of ABs produced in response to these proteins

Question 5

Gap junctions

Answer 5

Electrical and mechanical coupling - low resistance pathway 6 connexins make up one connexon - dextran tracer determines size - open/ close in response to diff things

Question 6

Classification

Answer 6

Used to be according to visual - but now according to function as secretory, absorptive, protective or for transport

Question 7

Actin Linked cell matrix

Answer 7

Anchors actin filaments to the ECM

Question 8

Hemidesmosomes

Answer 8

Link intermediate filaments to the basal membrane in spot welding ( binding collagen and keratin filaments with an intermediate laminin - by alpha6beta8 integrin - identified by X-Ray crystallography

Thrombin internal signalling cascade result of active integrins

Question 9

Epidermolysis bullosa

Answer 9

Genetic mutation of gene for keratin filaments COL7A1 gene is dystrophic bullosa - dermis and epidermis don’t link

Question 10

Differentiation experiments

Answer 10

Demonstrate what is necessary and sufficient, determined from classical experimental biology (cutting and pasting) eg Transplantation of quail -chick chimera and neural crest cells, and ectopic graft of a dorsal limb onto a blastopore induces a secondary body axis and mice bred to be p53 deficient - Blackburn 2002

Question 11

Morphenogenesis

Answer 11

Morphogenesis - form shaping process
Malformative has primary, deformative has secondary cause

Question 12

3 layered embryo top down

Answer 12

Ecto, meso, endoderm

Question 13

Signalling positions

Answer 13

Autocrine, juxtracrine, paracrine then endocrine

Question 14

Wnt signalling

Answer 14

Binds to frizzled receptors plus LRP4 complex to degrade beta catenin - if not it accumulates and enters nucleus

Question 15

Hedghog

Answer 15

SHH ligand binds to PTCH1 (TM protein) which activates SMO and int. signalling cascade to activate Gli TFs - dysregulated in cancer

Question 16

TGFbeta

Answer 16

Ligand+ receptor + smad = activated transcriptional complex to target gene expression and act on -OH groups - defects in this cause PMDS - persistent Mullerian duct syndrome - internal female genitals and external male genitals

Question 17

Tyrosine Kinase signalling

Answer 17

External PM receptor to ligand cases entry to nucleus and phosphorylation of a TF, faults = Pfeiffer syndrome (early fusion of certain bones) and Apert syndrome (FGFR2 and underdeveloped midfacial features)

Question 18

Notch signalling

Answer 18

Physical interaction between signalling and receiving cell - used in binary lineage decisions for sc maintenence
Mutation in Jagged 1 notch 1 protein = Alagille syndrome and liver damage from too much bile build up

Question 19

Osteoprogenitor cells

Answer 19

osteoblast and osteocyte precursors

Question 20

Osteoblasts

Answer 20

Lay down new bone

Question 21

Osteoclasts

Answer 21

Acidify and degrade bone

Question 22

Osteocytes and recognition

Answer 22

Sclerostin (SOST gene - mutated is sclerosteosis) then activates osteoblasts and recruits osteoclasts - OBs then migrate to model in TF TGFbeta and osteoclasts activate in presence of RANKL and MCSF

Question 23

Howships lacunae

Answer 23

Seal on damaged bone w/ ruffled border - H+ ions secreted from OCs by a proton pump then carbonic anhydrase produces more of these proteins, Cl- ions are exchanged for bicarbonate, HCl produced and degrades the bone, proteases then secreted, Ca2+ and signalling peptidases then released from broken down proteins and peptidases stimulate OB activation

Question 24

OB activation

Answer 24

Stimulated by peptidases, osteocytes, hormones and PTH to release ODF (RANKL) and OPG to inhibit RANKL action by behaving as a decoy receptor = BALANCE

Question 25

MSC to OPG

Answer 25

TF Runx2

Question 26

Achondroplasia

Answer 26

FGF3 gene mutation promoted full chondrocyte differentiation = short long bones

Question 27

TFG alpha

Answer 27

In presence of FGF stimulates MSCs to express T2 collagen and cells become chondroblasts for matrix formation

Question 28

Mineralisation

Answer 28

Maturation of OBs to BLCs and then trapped in matrix network by canniliculi

Question 29

Paget’s disease

Answer 29

The osteoclasts are larger than normal and break down bone faster than normal. The osteoblasts respond to this by depositing new bone at an increased rate

Question 30

Ogen imperfecta

Answer 30

T1 collagen = weak bones

Question 31

Osteoporosis

Answer 31

RankL and OPG imbalance

Question 32

Rickets

Answer 32

Vit D3 deficient - Ca2+ deficience = weak bones

Question 33

Hypercalcemia

Answer 33

Overactive osteoclasts = alters RMP and muscle spasms

Question 34

Cross bridge cycle

Answer 34

Ca2+ dependent on the binding to troponin (TTNC) = conformational change on (TTNT) tropomyosin then. TTNI = Inhibitory subunit. Myosin heads bind to actin then ATP hydrolysis causes angle change from 90 to 45 degrees - breaks crossbridges - then ATPase on myosin head breaks down the new molecule of ATP bound to the myosin head which assists in the active transport of Ca2+ to the SR for the next AP to be received

Question 35

Sarcomere

Answer 35

I band is actin only H band is myosin only, A band is overlap, Z line is boundary and M line is myosin

Question 36

How is skeletal muscle innervated

Answer 36

ACh to nAChR on Sarcolamma

Question 37

AP generation on skeletal muscle

Answer 37

Generated at sodium channel T4 subunit (SCN4A) which travels down the T tubules as the AP depolarises the dihydroxy receptor DHPR on the T tubules - this causes release of CA2+ from SR because of ionotropic change

Question 38

Myasthenia gravis

Answer 38

IG antibodies are produced in response to nAChRs - and affects distribution of LRP4 and MuSK which control distribution of nAChRs (TM peptides)

Question 39

Muscle contraction termination

Answer 39

Major is SERCA, small is the PMCa and the NCX

Question 40

Regulation of active muscle tension

Answer 40

Selective recruitment (spatial summation) and frequency (temporal)

Question 41

RYR1 disorder

Answer 41

Malignant hypothermia and problems w General anaesthetic - Ca2+ flood - RYR1 gene encodes the major sarcoplasmic reticulum calcium release channel of the skeletal muscle

Question 42

Myosin myopathies

Answer 42

Problems w Force regulation - w Myosin binding protein C (cardiac type)

Question 43

Nemaline myopathy

Answer 43

Faulty autosomal gene from each parent = bad tropomyosin

Question 44

SKM structure

Answer 44

Muscle in epimysium to fascicle in perimysium to endomysium to myofibril in sarcolemma to actin/ myosin - all supported by ECM giving tensile strength