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Week 10 - From beginning to end
w10
136
Pharmacology
Undergraduate 1
01/18/2016

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Cards

Term
Define a nucleosome
Definition
8 histone proteins wrapped by 2 winds of the DN double helix
Term
How large is the diameter of a double helix
Definition
2nm
Term
What are the 3 phases of interphase?
Definition
G1
S
G2
Term
What occurs in G1 and how long does is take?
Definition
normal cell functions and cell growth
organelle duplication
protein synthesis
8-12hours
Term
What occurs in S and how long does is take?
Definition
Duplicates chromosomes
DNA replication
Synthesis of histones
6-8hours
Term
What occurs in G2 and how long does is take?
Definition
Protein synthesis
Further cell growth
Enzymes synthesised
2-5hours
Term
Which are the checkpoints?
Definition
G1 (restriction point)
G2 checkpoint
Term
What is the final stage of the cell cycle?
Definition
Mitosis: prophase, mataphase, anaphase, telophase
cytokinesis
Term
What did Meselon and Stahl's experiment prove?
Definition
DNA replication is semi-conservative
2nd generation makes 1 hybrid and 1 light double heilx from one hydrid
Term
Describe DNA replication
Definition
1.helicase enzymes unwind strands and disrupt H bonds between bases
2.dna polymerase bind to exposed bases
3.dna polymerase can only move in 1 direction (w/ leading strand)
4.lagging strand moves in other direction
5.dna ligase splice two dna segments together
6.cell is ready for mitosis
Term
what is mitosis
Definition
the division of the replicated dna into 2 daughter cells.
Term
Describe the events of early prophase
Definition
chromosomes coil tightly
microtubules called spindle fibres extend between centrioles
nucleoli disappear
Term
Describe the events of late prophase
Definition
nuclear envelope disappears
kinetochores (on centromere) attach to spindle fibres forming
chromosomal microtubules
Term
Describe the events of mataphase
Definition
chromatids move towards and align at metaphase plate
centrosomes at opposite ends of cell
Term
Describe the events of anaphase
Definition
centromeres split and separate the chromatids
mitotic spindle pulls the V shaped chromosomes to opposite ends of cell
Term
Describe the events of telophase
Definition
nuclear envelope reforms
nuclei enlarge
chromosomes uncoil
2 identical nuclei in the cell
mitotic spindle will now break down
Term
Describe the events of cytokinesis
Definition
division of cytoplasm into 2 daughter cells
cleavage furrow forms to pinch cytoplasm
not distinct from telophase, begins at anaphase
Term
What triggers a cell to divide?
Definition
cell size
chemical signals
cyclins and cyclin dependent kinases
Term
how does cell size cause a cell to divide?
Definition
as a cell grows, the surface area to volume ratio doesnt work in favour of diffusion. the nucleus needs more nutrients plus more waste removed.
therefore cell splits into 2.
Term
how does chemical signal/growth factor cause a cell to divide?
Definition
external signals can stimulate cell growth if there arent enough cells to fill our their roles
Term
What is required at G1 for the cell to progress
Definition
requires sufficient nutrients and signalling molecules present in extracellular environment.
Term
What happens if this isn't there?
Definition
they move to G0 where they can rest of leave cycle and terminally differentiate.
Term
What is required at G2 for the cell to progress
Definition
ensures all dna has been replicated and not damaged, otherwise mitosis will not be able to occur successfully.
Term
What are cyclins
Definition
regulatory proteins
fluctuating levels
increase during interphase
destroyed by proteases after miitosis
Term
What are CDKs
Definition
catalytic subunit
constant concentration in cells
inactive when cyclins not present
phosphorylate proteins responsible for cell division
Term
What role do cyclins and CDKs play?
Definition
they combine to form an activated heterodimer which is responsible for activating proteins that are required for cell division.
Term
Define cranial and caudal
Definition
cranial = head
caudal = tail
Term
What are the 3 embryological planes?
Definition
transverse
coronal
sagittal
Term
What are the two ways of dating pregnancy?
Definition
menstural
fertilisation
Term
What is menstural age dating?
Definition
dates pregnancy from the woman's last menstural period
done by obstertricians and clinicians
pregnancy is divided into 3 equal trimesters
Term
What is fertilisation age dating?
Definition
dates pregnancy from time of fertilisation
done by emryologists
pregnancy divided into 3 unequal parts
Term
How is the pregnancy divided in fertilisation age dating
Definition
2 week: early development (cell division, pre-embryonic) period
3-9 weeks: embryonic (organogenesis) period
9+ weeks: foetal period
Term
When does ovulation occur?
Definition
14 days into the menstural cycle
Term
What is the difference between menstural and fertilisation age?
Definition
menstural age is 2 weeks greater than the fertilisation age
Term
What causes Down's syndrome?
Definition
Trisomy 21
abnormal number of chromosomes
21st pair are triplet
Term
What is Down's syndrome associated with?
Definition
growth retardation
intellectual retardation
craniofacial abnormalities
congenital heart defects
Term
What are teratogens
Definition
environmental factors that cause birth defects.
sensitivity varies with the developmental stage at time of exposure.
Term
When is the highest risk of birth defect induced?
Definition
5th week (embryonic)
Term
How do infectious agents enter and what are the most common?
Definition
across the placenta
TORCH:
toxoplasmosis
other (hep B, syphilis)
rubella (german measles)
cytomegalovirus (CMV)
Herpes complex virus (HDV)
Term
What is thialidomide
Definition
drug used for morning sickness in 50's
shorted/absent limbs
now used to treat leprosy/HIV
Term
What is foetal alcohol syndrome
Definition
clear relationship between alcohol consumption and congenital abnormalities
eg growth retardation and in severe cases intellectual disability
Term
Define fertilisation
Definition
the fusion of male and female gamete (23 chromosomes) fuse to form a zygote.
Term
What are the 3 layers of the uterus (out to in)
Definition
perimetrium
myometrium
endometrium
Term
Where does fertilisation usually occur
Definition
ampulla of the uterine tube
Term
What is the fimbrae and what is its role
Definition
finger like projections from the infundibulum that sweep oocyte (egg) into uterine tube
Term
Where do sperm under capacitation (maturation)
Definition
female reproductive tract
Term
What is the acrosome reaction
Definition
sperm bind to zona pellucida and release enzymes to break down the zona.
Term
What is the zona reaction
Definition
zona pellucida secrete an enzyme to prevent further sperm from entering
Term
What happens to the zygote after fertilisation
Definition
zygote undergoes a series of cell divisions (cleavage) where the zygote remains the same size but the cells (blastomeres) get smaller
Term
How many cells are there at day 0, 1, 2, 3, 4 and 5?
Definition
1, 2, 4, 8, Merula, Blastocyst
Term
What is a merula
Definition
16-32 cell stage
inner cell mass: embryo proper (embryoblast)
outer cell mass: placenta (trophoblast)
Term
What is a blastocyst
Definition
whena merula forms a fluid filled cavity
Term
What is an ectopic pregnancy
Definition
when implant occurs somewhere other than in the uterus
Term
Describe implantation
Definition
When a blastocyst is fully formed it contacts the endometrium and attaches
Term
how do trophoblasts develop?
Definition
-trophoblast cells divide rapidly and layer becomes thick
-plasma membranes disappear and are replaced with a multinucleated cytoplasm (called syncytical trophoblast)
-remaining trophoblasts become cytotrophoblasts
Term
How is the amniotic cavity formed?
Definition
=syncytical trophoblast continues to spread
-Eroded uterine glands release nutrients absorbed by synctical trophoblast providing energy for early embryo formatio-
Term
What do embryoblasts differentiate into
Definition
epiblasts and hyperblasts
Term
What is hCG?
Definition
hormone secreted by syncytitrophoblasts that helps maintain endometrium and maternal immunotolerance. Pregnancy indicator
Term
Define gastrulation
Definition
formation of a third layer of cells between the superficial and deep layers of the inner cell mass. Forms 3 germ layers.
Term
What makes up the bilaminar disc?
Definition
consists of hypoblast and epiblast cells
Term
When does the groove form? and what is its role
Definition
15 days
primitive streak defines major body axis
Term
What happens once the groove has formed?
Definition
cells of the epiblast migrate inwards towards the streak. They detach from the epiblast and slip beneath it.
Term
What is the hypoblast replaced by?
Definition
a new layer (definitive endoderm)
Term
What happens after endoderm is formed?
Definition
epiblast cells move down and form middle mesoderm layer.
Term
What happens after mesoderm is formed?
Definition
Mesoderm becomes highly organised:
-lateral plate mesoderm
-intermediate mesoderm
-paraxial mesoderm
and then a notochodal process
Remaining epiblast becomes ectoderm.
Term
What does the embryonic ectoderm surround?
Definition
amniotic cavity with the primitive groove
Term
What does the embryonic endoderm surround?
Definition
yolk sac
Term
What cell produces the 3 germ layers and what are they
Definition
Epiblast produces ectoderm, mesoderm and endoderm
Term
What does the ectoderm eventually develop into
Definition
outer layer of skin, hair, lining of nose and mouth and nervous system
Term
What does the mesoderm eventually develop into
Definition
muscle and skeleton
Term
What does the endoderm eventually develop into
Definition
digestive tract, respiratory tract, liver and pancreas
Term
In which direction does development occur
Definition
cranial region before caudal
Term
What are the two consequences of abnormal gastrulation?
Definition
sirenomelia and SCT
Term
Describe sirenomelia
Definition
'mermaid syndrome' occurs when insufficient mesoderm is formed in the caudal region of the embryo.
Causes abnormalities of urogenital system and lower limbs
Term
Describe SCT
Definition
remnants of primitive streak may persist and give rise to a tumour (sacrococcygeal teratoma). Most common newborn tumour (1/40000 and 80% female). Most neonates diagnosed are fine.
Term
What is neurolation
Definition
first event in CNS development
initiated by signals from the notochord that cause induction
overlying ectoderm thickens and forms neural plate
Term
What is the neural plate
Definition
thickened area of cells formed at cranial end of embryo
Term
Describe the formation of the neural tube
Definition
lateral edges of the neural plate elevate and fuse to form neural tube. Fusion beings in neck of embryo and continues cranially and caudally.
Term
What do neural crest cells contribute to
Definition
formation of the peripheral nervous system
Term
What does the notochord do
Definition
initiates and organises the formation of vertebrae from somites
Term
What does paraxial mesoderm divide into?
Definition
segments called somites which the notochord induces differentation of
Term
What are the somites and what they become
Definition
sclerotome > bone and cartilage
myotome > skeletal muscle
dermatome > dermis
Term
How is the vertebral body and vertebral arch formed?
Definition
sclerotome cells surround the notochord to form the vertebral body and the neural tube to form the vertebral arch.
Term
What do abnormal inductions of the sclerotomes result in?
Definition
spinal defects
Term
What is spina bifida?
Definition
spine does not close causing a gap and dimpling of skin, hair sometimes sprouts
Term
What is meningocele?
Definition
protusion of the meninges through a gap in the spine
Term
What is myelomeningoecele
Definition
spinal cord and meninges protude from childs back there is no skin covering it so high infection chance.
Term
When is neuralation complete
Definition
-when anterior (day 25) and posterior (day 28) neuropores fuse
-cranial end of the neural tube forms the brain and caudal end forms the spinal cord
Term
What is the result of failure of the anterior neuropore to fuse?
Definition
-anencephaly
-forebrain does not form
-brainstem present
-still birth/short life
Term
What is the result of failure of the posterior neuropore to fuse?
Definition
-Rachischisis
-spinal cord does not fuse properly > paralysis
-open neural tube prevents formation of vertebrae
-flat plate of neural tissue is exposed at birth
Term
Name 3 neural tube defects and how they can be reduced
Definition
Rachischisis
Anencephaly
Spina bifida
FOLIC ACID
Term
what is the '4th germ layer' and what does it do
Definition
neural crest cells separate from the neural tube and migrate and disperse widely and differentiate into a variety of structures throughout the body
Term
What are neural crest cells derivatives
Definition
-sensory ganglia
-autonomic ganglia
-meninges of the brain and spinal cord
-Schwann cells
-satelite cells
-melanoblasts
-suprarenal medulla
-several skeletal and muscular components in the head
Term
What is neurofibromatosis
Definition
genetic disorder caused by mutation of neurofibromin 1 (NF1 gene)
Term
What is NF1
Definition
tumour suppressor gene that is 'switched off' in neurofibromatosis leading to increased cell division
Term
What occurs in the 4th week of development
Definition
the embryo undergoes a rapid development in size and shape
trilaminar disc undergoes folding craniocaudally and laterally
Term
What causes embryonic folding
Definition
differential growth of the amniotic sac and yolk sac
amniotic sac grows much more
Term
Describe lateral folding
Definition
-amniotic sac expands and pushes down left and right edges of the embryonic disc
-lateral plate mesoderm splits into a visceral layer and a parietal layer
-starts to pinch the endoderm and pinches yolk sac
-left and right sac fuses and surrounds embryo
Term
Describe cranial folding
Definition
pushes head and tail together as amniotic cavity expands
Term
Describe ectopia cardis
Definition
lateral folding fails to fuse in thoracic region leaving the heart outside the body 1/5million
Term
Describe gastrosdusis
Definition
lateral folding fails to fuse in abdominal region leaving intestines outside the body wall (not covered by a membrane)
Term
What is senescence
Definition
biological aging where cells stop diviing/proliferating and become more susceptable to death
Term
What are the 3 causes of ageing
Definition
Increased production of free radicals
Replicative cell senescence (Hayflick phenomenon)
Telomere shortening
Term
What are free radicals and the role they play
Definition
reactive oxygen species
highly damaging to DNA, proteins etc
scavenged by antioxidants
reducing ROS production increases lifespan
Term
how many times can one cell divide
Definition
50
Term
What are telomeres and their signifigance
Definition
telomeres form the ends of human chromosomes and synthesised by telomere
telomeres shorten with each round of cell division
exposed chromosome ends activate p53 dependent cell arrest (halts cell cycle)
Term
define necrosis
Definition
the death of cells/tissues from disease/injury.
uncontrolled and triggers inflamatory response
Term
define apoptosis
Definition
'programmed cell death'
tightly controlled and does not elicit inflammatory response
Term
Describe the stages of apoptosis
Definition
cell shrinks and chromatin condenses (ATP dependent)
forms apoptotic bodies with functioning organelles
adjoining healthy cells phagocytose apoptotic bodies
Term
Describe the stages of necrosis
Definition
cell, organelles swell. Chromatin in nucleus clump. ATP independent.
loss of membrane integrity
nucleus swells
LEAKS
Term
What is apoptosis mediated by
Definition
caspases
there are 12 in humans
two types: initiator and executioner
Term
How is apoptosis triggered?
Definition
1.apoptotic stimuli
2.causes cleavage of initiator procaspases
3.converting them into active initiator caspases
4.which cleave exectuitioner procaspases
5.converting them into active executioner caspases
6.which cleave specific cellular targets within the cell to trigger apoptosis
Term
Describe the extrinsic plasma membrane apoptosis
Definition
1.pro-apoptotic receptor activated by pro-apoptotic ligand
2.ligand binding causes receptors to cluster and form a complex
3.when a complex is activated, pathway works as intrinsic
Term
Describe the extrinsic mitochondria apoptosis
Definition
1.stimulus causes release of cytochrome C from mitochondria
2.cytochrome c activates Apaf 1 and converts dATP to dADP
3.leads to Apaf 1 assembling into a heptamer called apoptosome
4.apoptosome recruits and activates the initiator caspase 9, resulting in activation of execuitioner caspases and apoptotis.
Term
What regulates the release of cytochrome c
Definition
Bcl proteins
Term
What do Bcl-2 family proteins do?
Definition
regulate the mitochondrial pathway for apoptosis
Term
What do BH123 proteins do and give examples
Definition
form a pore to release cytochrome c =. this occurs when bh123 proteins are activated after a death signal within a cell.

bax and bak
Term
What do bh3 proteins do and give examples
Definition
BH3 proteins stimulated bh123 homo-dimerisation (direct activators)
BH3 proteins can repress the pro-survival function of Bcl-2 proteins.
Term
What is p53
Definition
tumour supressor protein
encoded by tp53 gene
promotes apoptosis
malfunction or loss promotes cancer
Term
Relate p53 and apoptosis
Definition
1.dna damage
2.rise of p53 in cell
3.trigger Bax channel in mitochondria
4.release of cytochrome c
5.induce production of caspase 9
6.induced apoptosis
7.damaged dna cell does not divide
Term
What diseases are caused by excessive apoptosis
Definition
stroke
heart attack
neuronal diseases
Alzheimers and parkinsons
Term
What diseases are caused by reduced cell death
Definition
cancer
-Fas mutation
-BCl2 mutations
-p53 mutations
Term
What does cancer result from
Definition
abnormal proliferation of cells and decreased apoptosis
Term
What tissue is affected by carcinoma
Definition
epithelial
Term
What tissue is affected by sarcoma
Definition
connective tissue and muscle
Term
What tissue is affected by myeloma
Definition
b lymph
Term
What tissue is affected by lymphoma
Definition
other: wbc's nervous system cells etc
Term
how can mutations cause cancer
Definition
1.mutations that activate proto-oncogenes to oncogenes
2.inactive tumour suppressor genes
Term
What environmental factors cause cancer
Definition
1.uv light/radiation
2.chemicals (cigarette smoke)
3.viral infections (papilloma virus, hep B&C)
Term
What are oncogenes
Definition
promotes abnormal proliferation of cells
present in retroviruses (as proto-oncogenes acquired from eukaryotes and mutated to oncogenes)
result from mutations of proto-oncogenes
Term
what are proto-oncogenes
Definition
-encode proteins that regulate cell growth and differentation
-involved in signal transductions
-examples: growth factors, g proteins, protein kinases
-become oncogenes when mutated
Term
what happens when proto-oncogene RAS is mutated
Definition
goes from G->C switches this protein on to become permenantly
active, resulting in uncontrolled cell proliferation
Term
How is cancer diagnosed?
Definition
physical examination
mammography
bood markers
faecal occult in blood test
mri
main: biopsy
stages 1-4
Term
how is cancer treated?
Definition
surgery
radiotherapy
chemotherapy
Term
what does radiotherapy do
Definition
kills cells that have spread to adjacent local/regional tissues:
ionising radiation kills cancer cells
damages healthy tissue
more localised than chemo
Term
what does chemotherapy do
Definition
kills cancer cells through the body:
anti-cancer or cytotoxic drugs
targets all cells
unpleasant side effects
high does chemo often proceeds stem cell transplantation for haemotological cancers
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