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1
Q

prepares cell for replicating DNA; cell is busy doubling its contents in preparation for an eventual cell division

A

G1

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2
Q

DNA replication

A

S

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3
Q

prepares cell for segregation/division of genome and cytoplasma

A

G2

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4
Q

chromosome segregation (mitosis) and separation of daughter cells (cytokinesis)

A

M

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5
Q

after mitosis cells enter

A

G1 phase

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6
Q

time between mitosis and G1 phase

A

R point

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7
Q

R-point

A

cells require external signals, such as growth factors and hormones, to continue cell cycle progression

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8
Q

R point occurs when?

A

a few hours before the onset of DNA synthesis

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9
Q

when cells get to the R-point they make a decision as to whether they have enough nutrients to sustain them through DNA replications or they need to enter

A

G0 phase, the resting phase

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10
Q

growth factors stimulate synthesis of

A

cyclins D and E

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11
Q

Cyclin D partners with

A

cdk4 or cdk6

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12
Q

Cyclin E partners with

A

cdk2

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13
Q

99.9% of cell are in the _____

A

Go phase reason why it is so important to go through the R-point

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14
Q

in nearly all cancers the

A

R- point is defective

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15
Q

when enough of cyclin D/cdk4-6 and cyclin E/cdk2 complexes are activated, they

A

phosphorylate Rb protein

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16
Q

normally the Rb protein is

A

hypophosphorylated

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17
Q

when RB is hyposhorylated they complex with ______ needed for cell proliferation and ______ them from binding to DNA

A

when Rb is hypophosporylated they complex with transcription factors needed for cell proliferation and prevents them from binding to DNA

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18
Q

phosphorylation by the cyclin D/cdk4-6 and cyclin E/cdk2 complexes causes a

A

conformational change that releases the TFs

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19
Q

what do the TFs bind once acted by the cyclins?

A

bind to DNA and activate transcription that encodes proteins which push cells through R-point and S-phase

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20
Q

once DNA synthesis commences, a _______ is activated that destroys the cyclin D/cdk4-6 and cyclin E/cdk2 , thus _________ the complex

A

once DNA synthesis commences, a protease is activated that destroys the cyclin D/cdk4-6 and cyclin E/cdk2 , thus inactivating the complex

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21
Q

new cancer chemotherapies are now in use and in clinical trials that

A

block Cdk2 and Cdk4 function

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22
Q

MFP

A

cylin B/cdk1

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23
Q

consequences of MFP activation (2)

A

(1) phosphorylation of lamins, leading to nuclear membrane disassembly
(2) phosphorylation of histones, initiating chromatin condensation

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24
Q

altered proliferative states of cells that are reversible/stoppable: proliferation stops when the stimulus that provoked it is removed (4)

A

(1) regeneration
(2) hyperplesia
(3) metaplasia
(4) dysplasia

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25
Q

irreversible proliferation: proliferation continues in the absence of an external stimulus

A

neoplasia

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26
Q

1-for-1 replacement of lost cells by the same cell type

A

regeneration

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27
Q

endothelial cell ________ following vascular surgery or liver-cell _______ following partial hepatectomy or live-donor liver transplants

A

regeneration

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28
Q

hyperplasia

A

increase in the number of cells in a tissue; cells are truly differentiated. Can be helpful or hramful

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29
Q

metaplasia

A

adaptive substitution of one cell type for another

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30
Q

dysplasia

A

activated metabolic pathways for proliferation; loss of orientation in a tissue

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31
Q

neoplasia (2)

A
  • benign

- malignant

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32
Q

benign

A

loss of proliferation control only

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33
Q

example of a benign tumor

A

fibroids

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34
Q

malignant

A

loss of both proliferation and positional controls

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35
Q

example of malignant

A

metastatic tumors in cancer

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36
Q

hyperplaisa: helpful or harmful

hematopoietic cells in bone marrow following severe blood loss or changes in altitude

A

helpful

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37
Q

hyperplaisa: helpful or harmful

thyroid cells in Graves diseases

A

harmful

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38
Q

hyperplaisa: helpful or harmful

smooth muscle cells in the arterial wall in atherosclerosis or following vascular surgery. What is this?

A

harmful and it is called restenosis

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39
Q

replacement of ciliated columnar epithelium by stratified squamous epithelium in response to chronic inflammation

A

metaplasia

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40
Q

abnormal appearance of cells such as pleiotropy, disorientation within tissue and high mitotic rate is indicative of

A

dysplasia

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41
Q

cervical ______as seen in on a Pap smear in women and _______ moles removed from skin

A

dysplasia

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42
Q

the position of a cell within a tissue can determine its

A

proliferation rate

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43
Q

why does the position within a cell determine proliferation rate?

A

information in the extracellular matrix helps regulate cell proliferation

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44
Q

Why have apoptosis?

A

you need a balance between cell death and cell proliferation

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45
Q

leads to inflammation

A

necrosis

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46
Q

leads to phagocytosis

A

apoptosis

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47
Q

How is necrosis triggered?

A

by sustained ischemia, physical or chemical trauma

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48
Q

How is apoptosis triggered?

A

by specific signals that activate specific genes

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49
Q

What happens at the start of necrosis?

A

Cells swell, organelles damaged, chromatin randomly degraded

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50
Q

What happens to cells and organelles in necrosis?

A

cells lyse and organelles destroyed

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51
Q

What happens at the start of apoptosis?

A

cells shrink, organelles intact, chromatin degraded systematically

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52
Q

What happens to cells and organelles in apoptosis?

A

membrane blebs, cell contents retained

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53
Q

the three basic steps of apoptosis

A

(1) induction
(2) modulation
(3) execution

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54
Q

Inducers of apoptosis (3)

A

(1) physiological activators
(2) Damage-related activators
(3) therapy-associated

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55
Q

physiological activators

A

TNF-alpha,
FasL,
growth/ survival factor withdrawal,
glucocorticoids

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56
Q

Damage-related activators

A 
viral infection, 
heat schock, 
toxins, 
tumor suppressors, 
oxidants/free radicals
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57
Q

Therapy-associated

A

UV/gamma radiation

chemotherapeutic drugs

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58
Q

“death signals”

A

inducers

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59
Q

“death effectors”

A

effectors

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60
Q

effectors

A

caspases

endonucleases

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61
Q

mitochondrial pathway

A

intrinsic

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62
Q

death-receptor- initiated pathway

A

extrinsic

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63
Q

what happens if we go through the intrinsic pathway?

A

the process may be modulated (either enhanced or dampened) by members of the Bcl family

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64
Q

modulators

A

Bcl-2 family

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65
Q

key feature of the intrinsic pathway

A

mitochondrial leakage of cytochrome C activating the caspase cascade

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66
Q

key feature of te extrinsic pathway

A

death receptors activating the caspase cascade

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67
Q

How is the intrinsic pathway activated?

A

by growth factors/survival factor withdrawal, glucocorticoids, viruses, DNA damage-causing events, toxins, oxidized compounds and ischemia

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68
Q

How is the extrinsic pathway activated?

A

by TNF-alpha or Fas ligand binding to their receptors on the cell surface

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69
Q

the intrinsic pathway works by creating ______ through the ______ membrane tat cause ________ leakage into the cytoplasm that initiates the ______ cascade

A

The intrinsic pathway works by creating channels through the mitochondrial membrane that cause cytochrome C leakage into the cytoplasm that initiates the caspase cascade

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70
Q

in the extrinsic pathway, the cytoplasmic tail of the ______ or _________ receptor directly initiates the _____ cascade when the _________________.

A

in the extrinsic pathway, the cytoplasmic tail of the TNF-alpha or FasL receptor directly initiates the caspase cascade when the receptor is occupied by its ligand

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71
Q

Both extrinsic and intrinsic, result in massive amounts of ________ activity

A

caspase 3

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72
Q

Caspase-3

A

chief executioner of the cell in both extrinsic and intrinsic pathways for apoptosis

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73
Q

The caspases activate specific ________ that cleave DNA in the linker regions between the _____ and also cleave ______ proteins resulting in the formation blebs

A

The caspases activate specific endonucleases that cleave DNA in the linker regions between the nucleosomes and also cleave cytoskeletal proteins resulting in the formation of blebs

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74
Q

the blebs formed by the pathway apoptosis are

A

taken in via phagocytosis

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75
Q

inhibitors of apoptosis might be useful in limiting the damage caused by

A

strokes and heart attacks

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76
Q

goal of therapeutic solution with apoptosis in cancer and restenosis

A

increase apoptosis of the tumor cells or hyper-proliferating smooth muscles

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77
Q

goal of therapeutic solution with apoptosis in Hashimoto

A

decrease apoptosis in the thyroid cells

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78
Q

Major ECM molecules (8)

A

(1) collagens
(2) elastin
(3) proteoglycans
(4) Matricellular proteins
(5) integrins
(6) Matrix metalloproteinases
(7) cell adhesion molecules
(8) cadherins

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79
Q

provide structural integrity for bone and cartilage and major component of the Basement membrane

A

collagens

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80
Q

Collagen Type I found

A

almost everywhere

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81
Q

Collagen type II found

A

almost exclusively in cartilage

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82
Q

Collagen type IV found and role

A

best remembered for its role in basement membranes (basal lamina)

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83
Q

Type I and II are

A

fibril forming collagens

84
Q

Type IV is a

A

network (sheet) forming collagen.

-think lamina

85
Q

Type I is like a

A

CT collagen

86
Q

Type II is like a

A

cartilage collagen

87
Q

Type IV is like the

A

epithelial basement membrane/basal lamina collagen

88
Q

Type XVIII is important because

A

it is blood vessel-specific and contains an internal peptide sequence

89
Q

endostatin is cleaved by an ______ from ______

A

endostatin is cleaved by an MMP from Collagen XVIII

90
Q

What is endostatin?

A

powerful anti-angiogenesis protein

91
Q

Elastin is cross-linked with

A

fibrillin

92
Q

elastin

A

major component of the elastic laminae of large artery wall

93
Q

Proteoglycans and Hyaluronan are _______ and provide ______ and ______ for cells and cartilage

A

Proteoglycans and Hyaluronan are ubiquitous and provide hydration and structural support for cells and cartilage

94
Q

acts as reservoirs for growth factors and cytokines

A

Proteoglycans and Hyaluronan

95
Q

Shock-absorber

A

Proteoglycans and Hyaluronan

96
Q

Matricellular proteins

A

secreted and bind tightly to the cell surface through their interactions with integrins

97
Q

Matricellular protein examples (2)

A

(1) fibronectin

(2) lamina

98
Q

help attach cells to each other and to the ECM via multiple binding sites for cells, proteoglycans, and collagen

A

Matricellular proeins

99
Q

found in CT/mesenchymal matrices

A

fibronectin

100
Q

found in basement membranes

A

laminin

101
Q

A relative nwcomer in the matricellular protein field are the ______

A

CCN family of proteins

102
Q

Matricellular proteins are connected to the cytoskeleton and signaling pathways via their interactions with _____ and _______ and thus help regulate important cell functions like ______, _______ and _______

A

via their interactions with integrins and growth factors and thus help regulate important cell functions like proliferation, motility and differentiation

103
Q

receptors for fibronectin, laminins, CCN proteins as well as other molecules

A

Integrins

104
Q

Integrins often connect to ___________ and ________ machinery via tightly complexed proteins on ________ side of membranes

A

Integrins often connected to cell signaling and cytoskeletal machinery via tightly complexed proteins on cytoplasmic side of membranes

105
Q

Cadherins are _____-requiring cell adhesion molecules important in maintaining tissue _____ by connecting the _______ of adjacent cells.

A

Cadherins are calcium-requiring cell adhesion molecules important in maintaining tissue integrity by connecting the desmosomes of adjacent cells

106
Q

Defects in cadherins cause

A

blistering

107
Q

also critical in embryonic development; required for compaction of the embryo

A

cadherins

108
Q

ICAM-1

A

1st cell adhesion molecules discovered

109
Q

P-selectin

A

matricellular protein

110
Q

_______ “rolling” along the vascular endothelium is due to weak ________ interactions between _____ on the endothelial cell and a ______ ligand on the _______

A

Leukocyte “rolling” along the vascular endothelium is due to weak on-off interactions between P-selectin on the endothelial cell and a carbohydrate ligand on the leukocyte.

111
Q

If a tissue is inflamed, the ECs in that area express ___________, which binds to the _____ receptor on the leukocyte. This activates a specific _____ that binds tightly to ______ on the EC membrane, causing the leukocyte to _____. This initiates __________ of the _____.

A

If a tissue is inflamed, the ECs in that area express Platelet Activating Factor, which binds to the PAF receptor on the leukocyte. This activates a specific integrin that binds tightly to ICAM-1 on the EC membrane, causing the leukocyte to stick. This initiates extravasation of the leukocyte

112
Q

This initiates extravasation of the leukocyte

A

migration between EC to enter the inflamed area

113
Q

MMPs

A

metal-requiring enzymes

114
Q

MMPs degrade

A

matrix molecules including collagens, proteoglycans and other proteins

115
Q

MMPs are required for

A
  • cancer cell metastasis
  • tissue remodeling
  • wound healing
  • angiogenesis
116
Q

a major structural protein that is present in the elastic laminae in the wall of large arteries

A

elastin

117
Q

elastin

A

long, rod-like protein which is cross-linked

118
Q

cross-links in elastin mediated by

A

fibrillin

119
Q

defective fibrillin leads to

A

stretching of the artery–> aneurysm

120
Q

Axis in women

A

HPO

121
Q

Axis in men

A

HPT

122
Q

Gonadotropin releasing hormone:

source

A

hypothalamus (brain)

123
Q

Gonadotropin releasing hormone:

target

A

anterior pituitary

124
Q

Gonadotropin releasing hormone:

action

A

synthesis and secretion of FSH and LH

125
Q

Follicle Stimulating Hormone:

source

A

anterior pituitary

126
Q

Follicle Stimulating Hormone:

target

A

ovary

127
Q

Follicle Stimulating Hormone:

action

A

stimulates ovarian follicle growth, differentiation and steroidogenesis

128
Q

Luteinizing hormone:

source

A

anterior pituitary

129
Q

Luteinizing hormone:

target

A

ovary

130
Q

Luteinizing hormone:

action

A

stimulates ovulation, corpus luteum formation and steroidogenesis

131
Q

Estrogens:

source

A

ovary; follicle cells

132
Q

Estrogens:

target

A

uterus, vagina oviduct, mammary glands

133
Q

Estrogens:

action

A

growth and differentiation of targets

134
Q

Progestins:

source

A

corpus luteum

135
Q

progestins:

target

A

uterus, vagina, oviduct, mammary glands

136
Q

Progestins:

action

A

growth and differentiation of targets

137
Q

1/? couples experience fertility issues

A

1/8

138
Q

Males major cause of infertility (4)

A

(1) varicocele
(2) sperm motility problems
(3) hormonal imbalances in HPT axis
(4) congenital absence of the vas deference

139
Q

Females major cause of infertility (4)

A

(1) PCOS
(2) hormonal imbalances in the HPO
(3) insufficient progesterone production
(4) anatomic problems like Asherman syndrome

140
Q

PCOS

A

not enough FSH

141
Q

Asherman syndrome

A

scarring from either surgeries, fibroids, endometriosis…

142
Q

when oocytes are fertilized what is the arrested state?

A

metaphase of meiosis II

143
Q

once fertilization happens what happens?

A

oocyte goes through the rest of Meiosis II and in an hour the zygote will have two pronucli

144
Q

why does the pronucli have two eggs?

A

one from the oocyte and the other from the sperm

145
Q

The pronuclei fuse and go through a round of _____ to double the number of chromosomes, and then undergo the first ________ which is a mitotic division that produces ____ equal daughter cells each with a full complement of chromosomes

A

The pronuclei fuse and go through a round of DNA replication to double the number of chromosomes, and then undergo the first zygotic cleavage which is a mitotic division that produces 2 equal daughter cells each with a full complement of chromosomes

146
Q

to produce ___ diploid blastomeres it has to have the ____ DNA/chromosome content before it divides

A

to produce 2 diploid blastomeres it has to have the 4n DNA/chromosome content before it divides

147
Q

how long does it take for a fertilized egg to go through the first cleavage

A

24-30hr

148
Q

after 3 days of fertilization how many cells should there be?

A

8

149
Q

blastomeres

A

cells are identical

150
Q

can 2 of the 8 of the blastomerse can be plucked up for genetic diagnosis

A

YES!

151
Q

what is the current best method for PGD uses

A

trophoblast cells from an early (day 5 or 6) blastocyst

152
Q

The ______ is formed around Day 3-4 by a _________ called compaction and it is the first time that we see _____ (differences between cells) in the embryo

A

The morula is formed around Day 3-4 by a cadherin-dependent process called compaction and it is the first time that we see polarity (differences between cells) in the embryo

153
Q

until when the zona pellucida remains around the embryo

A

until the early blastocyst stage

154
Q

fluid expansion of the blastocoel puts enough hydrodynamic pressure on the zona pellucida to break it open and allow blastocyst hatching

A

ZP shedding

155
Q

the blastocyst consist of (3)

A

(1) inner cell mass
(2) trohoblasts
(3) blastocoel

156
Q

fluid-filled space

A

blastocoel

157
Q

will give rise to the placenta

A

trophoblasts

158
Q

will give rise to the embryo and is the best source of stem cells

A

inner cell mass

159
Q

where does the blastocyst implant?

A

uterine wall

160
Q

represents the first real 3-D embryonic structure

A

gastrulation

161
Q

rise from the epiblast

A

germ layers

162
Q

germ layers present at which stage

A

gastrulation

163
Q

contains the epiblast and hypoblasts

A

blastocyst

164
Q

gastrulation occurs after

A

blastocyst formation

165
Q

all the embryonic cells and critical structures and systems are pretty much in place by the end of

A

week 8

166
Q

high spontaneous abortion rate (3)

A

(1) major chromosmal abnormalities
(2) early cleavage problems
(3) progesterone insufficiency

167
Q

where does fertilization occurs?

A

fallopian tube

168
Q

supports the first 20 weeks of gestation by secreting progesterone that helps maintain a functional endometrial layer in the uterus

A

corpus luteum

169
Q

what keeps the corpus luteum in top progesterone-secreting shape

A

LH and later hCG

170
Q

Sperm transport

A

mostly propelled by contraction of uterine smooth muscle cells and ciliary

171
Q

critical to fertility because it enable sperm to swim well and prepares them for acrosome rxn. if it does not go well sperm is useless and infertility results

A

capacitation

172
Q

how is capacitation mimicked in IVF clinic?

A

washing the sperm before IUI or IVF

173
Q

When the sperm come into contact with the follicular cells surroundings the oocyte the _____ membrane perforates and realeases enzymes that can chew up the matrix and ______ thus allowing sperm to penetrate the ZP and fuse with the ___________

A

When the sperm come into contact with the follicular cells surroundings the oocyte the acrsome membrane perforates and realeases enzymes that can chew up the matrix and Zona pellucida thus allowing sperm to penetrate the ZP and fuse with the oocyte plasma membrane

174
Q

polyspermy leads to

A

triploid embryos… lethal

175
Q

provides the block of polyspermy

A

cortical rxn

176
Q

Fusion of the sperm and oocyte plasma membrane causes _____ pulses in the oocyte and triggers the ____ granules to exocytose their contents,which are enzymes that cross-link the proteins in the _____ preventing any additional sperm penetration

A

Fusion of the sperm and oocyte plasma membrane causes calcium pulses in the oocyte and triggers the corticol granules to exocytose their contents, which are enzymes that cross-link the proteins in the Zona pellucida preventing any additional sperm penetration

177
Q

Ejaculation is followed by rapid ____, then comes the _______ rxn, followed by fusion of the sperm and oocytes, which initiates the ______ reaction via waves of ________ pulses across the cell

A

Ejaculation is followed by rapid capacitation, then comes the acrosome rxn, followed by fusion of the sperm and oocytes, which initiates the cortical reaction via waves of calcium pulses across the cell

178
Q

age-dependent loss of oocytes

A

oocyte atreasia

179
Q

absence of viable oocytes that can mature into secondary oocytes capable of being ovulated causes the onset of

A

menopause/fertility

180
Q

did teratogenic drugs like thalidomide and diseases like Rubella have allowed embryologists to determine the precise timing of developmental events in humans?

A

Yes!!

181
Q

when are complete gametes produced in males?

A

from puberty until death

182
Q

in females the vast majority of oocytes in the ovary are arrested

A

prophase of Meiosis 1

183
Q

gametes are ____ in chromosome number

A

haploid

184
Q

gametes are

A

germ cells

185
Q

in meiosis the parent cell is ____ and the progeny are ____

A

parent is diploid and progeny haploid

186
Q

parent and progeny cells are genetically

A

different

187
Q

liver, vascular enodothelium after surgery

A

regeneration

188
Q

graves, restenosiss

A

hyperplasia

189
Q

CPID smokers

A

Metaplasia

190
Q

cervix, precursor to cancer

A

dysplasia

191
Q

tissue/organs that are enlarging then it mush have more

A

proliferation than apoptosis

192
Q

tissue/organs that are shrinking then it mush have more

A

apoptosis than proliferation

193
Q

express the Fas receptor

A

lymphocytes

194
Q

express the Fas ligand

A

endothelial cell

195
Q

rolling

A

P-selectin- matricellular protein

196
Q

Day:

pronuclei fuse- fertilization

A

0

197
Q

Day:

2-cell embryo/first embryonic cleavage

A

1

198
Q

Day:

4-cell mebryon

A

2

199
Q

Day:

8 cell embryo/embryo biopsy stage

A

2.5-3

200
Q

Morula- compaction/first differentiated cells

A

3-4

201
Q

Day:

Blastocyst- implantation period/embryo biopsy day 5-6

A

4-14

202
Q

Day:

Gastrula/3 germ layers form from epiblast

A

15-17

203
Q

invovled in contraction of thecal cells to expel the oocyte

A

PGE2

204
Q

blocks activation of both T-cells and Natural Killer cells so that the mother does not immunologically reject an embryo or fetus

A

PGE2

205
Q

stimulates the contraction of uterine myometrial smooth muscle cells during labor

A

PGE2

Cell Bio 2 (11 decks)

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