bsi
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Connective tissue | most diverse and abundant form of tissue
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fibrocyte | connective tissue proper
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cartilage | chondrocyte
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bone tissue | osteocyte
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basil lamina | a non-cellular supporting sheet between the epithelium and the connective tissue.
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basil lamina | consists of proteins secretedby epithelial cells
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basil lamina | acts as a selective filler and scaffolding
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tight junctions | interlocking junctions of proteins
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desmosome | intermediate filaments that form linker proteins
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gap junction | form channels between cells
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cyclin CDK inhibitor | P21 (S CDK)
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cyclin CDK inhibitor | P27 (G1/S CDK)
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transcription factors | myc
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transcription factors | e2F
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transcription factors | p53
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inhibitors involved with cell cycle | Rb
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inhibitors involved with cell cycle | Wee1
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inhibitors involved with cell cycle | securin
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UBQ ligases in cell cycle control | MDM2
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UBQ ligases in cell cycle control | APC
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UBQ ligases in cell cycle control | SCF
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anaphase | the APC triggers separation of chromatids the spindles draw the chromatids to opposite poles
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telophase | nuclear envelope reassembles around each set of separated chromatids. the chromasomes start to decondense
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cytokinesis | division of cytoplasm. begins in anaphase and ends in telo phase
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prophase | the replicated chromosomes condense. the centrosomes move to opposite sides of the nucleus
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prometaphase | nuclear envelope breaks down. the spindles attach to kinetochores on chromatids.
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kinetochores | protein complexes on chromosomes
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metaphase | mitotic spindle aligns the chromosomes at the equator
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S-CdK | triggers DNA replication in S phase
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How does the cell prevent entry into S phase if there is DNA damage? | 1)DNA damage leads to phosphorylation and increased stability of 2)p53 increases the transcription of p21 3)p21 binds to G1/S-CdK and S-CdK inhibiting their activity
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Potential candidates for knocking gene out will it lead to increased cell proliferation. | Rb P27 P21 Wee1 ATM Securin P53
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Which enzyme replicates DNA? | DNA polymerase
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How many chromosomes are copied? | 46
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What are the phases of mitosis? | PPMAT
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In what phase do the sister chromatids separate? | Anaphase
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How does APC trigger anaphase? | Ubiquitinates securing
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MAPK activates G-CDK and G1?S-CDK by phosphorylating them? (T/F) | False
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G1-CDK and G1/S CDK activate S-CDK by phosphorylating it. (T/F) | False
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P 27Inhibits: | G1/S CDK
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P21 Inhibits | G1/S CDK S-CDK
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How does S-CDK activate M-CDK? | It phosphorylates cdc-25
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In mammals an external cellular signal is required to initiate the cell cycle | mitogen
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The mitogen stimulated activity of G1-CdK and G1/S-CdK | leads to transition into S-phase and activation of S-CdK
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M-CdK activity | is responsible for transition through the M-phase
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Mitogen signaling | leads to increased activity of G1-CdK and G1/-CdK
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Rb phosphorylation | leads to increased activity of E2F and entry into S phase
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E2F | a transcription factor that increases expression of proteins needed for s-phase
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S-CdK | triggers DNA replication in S phase
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CdKs | phosphorylate key proteins involved in the cell cycle
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CdKs must be bound to | cyclins inorder to be active
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When cyclins are degraded | the CdK becomes inactive
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Cyclins degraded by the | ubiquitin-proteasome system
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There are a variety of CdKs and cyclins that regulate the different phases of the cell cycle. | The cyclin-CdK complexes are called G1-CdK, G1/S-CdK, S-CdK, M-CdK.
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Aside form cyclin binding, CdKs also require | phosphorylation/dephosphorylation to be fully active
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Necrosis | Death due to injury or severe insult
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Physical characteristics of necrosis | 1.Cell and organelles swell and rupture releasing intracellular contents 2. Induces an inflammatory response a. Infiltration of immune cells (white blood cells) 3. Damage and/or death to surrounding tissue
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Apoptosis | Death is tightly regulated and Cell suicide is executed via specific signaling pathways
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physical characteristics of apoptosis | 1.Cell shrinks 2.Condense nucleus 3.DNA fragments into oligonucleosomes 4. Membrane blebbing and formation of apoptotic bodies ingested by neighboring cells or macrophages 5.No inflammatory response 6. Death of single cell
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Signal for phagocytosis of apoptotic bodies | exposure of phosphatidylserine on outer layer of plasma membrane
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External stimuli (triggers of apoptosis) | 1. Withdrawal of growth factors/survival signals 2. Detachment from extracellular matrix 3. Cytokines a. Produced by cells of immune system b. Example: tumor necrosis factor alpha (TNF-alpha) 4. Cytotoxic T cells 5. Toxins
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Internal stimuli (triggers of apoptosis) | 1. DNA damage 2. Mitochondrial dysfunction a. Decreased ATP production b. Excessive free radical production and damage
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Variations in cell type (triggers of apoptosis) | 1. Stimuli that induce apoptosis 2. Resistance to apoptosis
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Caspases | Executioners of Apoptosis, Proteases that cleave proteins
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Capases | Synthesized as proenzymes-inactive precursors
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Cleavage forms large and small subunit which forms | the active caspase
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Caspases cleave | specific substrates
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number of capases | 14 caspases
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Intrinsic Apototic signaling pathways | 1. Mitochondrial-mediated apoptosis 2. p53/Nuclear-mediated apoptosis
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Extrinsic Apototic signaling pathways | 1. Receptor-mediated apoptosis a. Fas/FasL signaling
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mitochondrial-mediated apoptotic signaling is triggered by | mitochondrial function and apoptotic signaling pathway
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mitochondrial functions that trigger mitochondrial-mediated apototic signaling | a. Deficient ATP production b. Oxidative stress/ROS production
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apoptotic signaling pathway apototic signaling | p53/Nuclear-mediated which is Receptor-mediated
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mitocondrial-mediated signaling event | 1. Cytochrome c release 2. Formation of apoptosome (Procaspase-9, Apaf-1, cytochrome c, dATP) 3. Activation of caspase cascade
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Formation of apoptosome | Procaspase-9, Apaf-1, cytochrome c, dATP
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Caspases | proteases which cleave other proteins
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Procaspases | also known as proenzyme cleaved to active caspases
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Procaspase-9 → active caspase-9 | auto cleaves itself cleaves procaspase-3 this leads to → Apoptosis
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Regulators of apoptosis | Bcl-2 family, Inhibitors of Apoptosis Proteins (IAPs)and Repressors of IAPs
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Anti-apoptotic: prevents cytochrome c release | Bcl-2, (Other: Bcl-XL)
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Pro-apoptotic: favors cytochrome c release | Bax, tBid (truncated Bid) (Other: Bak, Bim, Bad, Bok, etc)
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Inhibitors of Apoptosis Proteins (IAPs) | XIAP, (Others: cIAP1, cIAP2, survivin, Binds to cleaved caspases and inhibits activity
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XIAP inhibits activity of | caspase-9 and caspase-3
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Repressors of IAPs | Smac/Diablo and Omi/Htra2
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Smac/Diablo and Omi/Htra2 | i. Released from mitochondria upon stimulation ii. Binds to IAPs and represses their inhibition on caspases allowing caspases to exhibit their activity to execute apoptosis
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In cells not undergoing apoptosis ICAD (I =inhibitor) binds to | CAD and inhibits its activity
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When cells are undergoing apoptosis | caspase-3 cleaves and degrades ICAD
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CAD is free and active to fragment DNA into mono-and oligonucleosomes after | ICAD binds to CAD and inhibits its activity or when capase-3 cleavs and degrades ICAD
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Proteins that caspase-3 inactivates by cleavage | ICAD,Cleavage of proteins involved in DNA repair, Cytoskeleton, Anti-apoptotic BCL-2 family proteins
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Tumor <0.5mm can receive O2 and nutrients by | diffusion from blood vessel
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Tumor >0.5mm requires | proliferation & morphogenesis of vascular endothelial cells to form new blood vessels
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The Onset of angiogenesis is due to | the imbalance between pro- and anti-angiogenic factors (upregulation of pro-angiogenic proteins/downregulation of anti-angiogenic proteins)
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In adults, active angiogenesis is required only for | wound healing, endometrial proliferation, and during pregnancy
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Angiogenesis required for progression & metastasis of | cancer
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The most potent stimulus for angiogenesis is | VEGF
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VEGF stands for | Vascular endothelial growth factor
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The most potent stimulus for VEGF production by tumor | Hypoxia
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HIF- binds to VEGF gene and induces transcription | Hypoxia-inducible transcription factor-
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HIF- binds to | VEGF gene and induces transcription
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overexpression of VEGF can result from | Mutations in p53 and Activation of ras
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Step 1 of angiogenesis | pericytes detach, blood vessels dilate
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Step 2 angiogenesis | basement membrabe and extracellular matrix are degraded by MMP's creating a tunnel toward VEGF for tumor cells to crawl through
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Step 3 angiogenesis | endothelial cells migrate towards angiogenic stimuli (VEGF) produced by tumor cells
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Step 4 angiogenesis | endothelial cells proliferate
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step 5 angiogenesis | endothelial cells adhere to each other and create a lumen
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step 6 of angiogenesis | formation of basement membrane and pericyte re-attachment
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lumen | tunnel/opening formed by endothelial cells during angiogenesis
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MMP stands for | matrix metalloproteinase
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Agents targeting the VEGF pathway | 1)Antibody for vegf (binds to vegf in general) 2)Anti vegf receptor antibody 3)Small molecule vegf receptor inhibitors (binds to the intracellular domain of the receptor)
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Invasion is | the migration of cells into deeper tissues—cancer cells break through the barrier that keeps them localized
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a tumor is malignant if it has | The invasive phenotype
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Metastasis is | the spread of cancer cells from a primary tumor to distant sites in the body
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the major causes of cancer treatment failure | Invasiveness and metastasis
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Steps in matastasis | T.AS.AP.SC.EGSS.AST.EIR. (Tri AskedShelley AboutPookie SeeCar EGSS, AshleySlapsTri ExtremelyIrriatableReaction)
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To be able to invade a tumor must | 1)Increase MMPs, 2)turn on cell motility systems, 3)Decrease expression of adhesion molecules to detach and crawl away to blood supply
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Tumor cells can induce apoptosis of | cytotoxic T cells
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Cytotoxic T cells express | FasL & Fas
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Tumor cells express | Fas L (normal cells usually do not) and downregulate Fas receptor
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Tumor cells can upregulate | cFLIP (will block caspase 8)
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Consequences of Tumor cells can induce apoptosis of cytotoxic T cells | 1)Tumor cells (with low Fas) resistant to apoptosis by cytotoxic T cells 2)Tumor cells (due to FasL expression) induce apoptosis in cytotoxic T cells
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HPV | is a virus that causes cancer and inactivates p53 and Rb
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Interphase consists of what 3 phases | G1, S, G2
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G1 phase | Cell growth (Some cells remain in this phase permanently then called G0)
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S phase | 1)Replication of genome (DNA synthesis) 2)DNA is copied by DNA polymerase 3)The duplicate chromosomes remain bound together by proteins called cohesions (until M-phase when the chromosomes will be separated)
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G2 | cell growth, again
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MPhase consists of | Mitosis and cytokinesis
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Mitosis consists of | Prophase, prometaphase, metaphase, anaphase, telophase
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Prophase | i. The replicated chromosomes condense ii. Centrosomes (which replicated during S phase) start to move to opposite sides of the nucleus and the mitotic spindle begins to assemble outside the nucleus
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prometaphase | i. Nuclear envelope breaks down ii. This allows the spindle microtubules to contact the condensed chromosomes iii. The microtubules bind to kinetochores located at centromeres of sister chromatids
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kinetochores | protein complexes which assemble on the condensed chromosomes
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metaphase | Mitotic spindle gathers all the chromosomes to the center (equator) of the spindle
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anaphase | i.sister chromatids split apart 2.Spindle draws them to opposite poles 3. Anaphase begins with the release of linker of sister chromatids iv. chromatids are pulled to the spindle pole v.sets of chromosomes to opposite ends of the spindle
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Activation of anaphase promoting complex (APC) | triggers the separation of sister chromatids
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telophase | 1.Nuclear envelope reassembles around each of the two sets of separated chromosomes to form two nuclei 2.Nucleus expands and chromosomes decondense to interphase state 3. Assembly of contractile ring necessary for cytokinesis
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Cytokinesis | a. Division of the cytoplasm (including all organelles) 2. Begins in anaphase and is complete by the end of telophase
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epithelial tissues basic function | covering
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connective tissue basic function | suport
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muscle tissue basic function | movement
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nervous tissue basic function | control
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epithelial tissue | covers a body surface or lines cavities forms glands protects absorbtion, secretion and ion transport filtration slippery
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squamous | cells wider than tall (squished flat)
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cuboidal | cells are as wide as tall (cube like)
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columnar | cells taller than wider (columns, usually have cilia)
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ducts carry what? | products of exocrine glands to surface
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simple ducts | ducts that branch
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compound duct | ducts that branch
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simple tubular ducts | found in intestinal glands
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simple branched tubular ducts | found in gastric glands
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compound tubular ducts | found in duodenal glands of small intestine
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coumpound alveolar ducts | found in mamary glands
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simple alveolar ducts | not found in humans
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simple branched alveolar ducts | found sebaceous (oil) glands
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compound tubuloalveolar ducts | found in salivary glands
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endocrine glands | ductless glands, secrete sunstances diretly into clood and produce hormones
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basil lamina | noncellular supporting sheet between epithelium and connective tissue and consists of proteind secreted bu the epithelial cells
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functions of the basil lamina | acts as a selective filter to the epithelium,, acts as scaffolding where epithelial cells can migrate
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basement membrane consists of | the basil lamina and reticular layers of connective tissue
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tight junction | forming a virtually impermeable barrier to fluid between cells
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desmosome junctions | form cell-cell adhesions and help to resist shearing forces and are found in simple and stratified squamous epithelium.
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gap junctions | directly connects the cytoplasm of two cells, which allows various molecules and ions to pass freely between cells
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Connective tissue | Most diverse and abundant tissue Cells separated by large amount of extracellular matrix Common embryonic origin – mesenchyme
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main types of connective tissue | Connective tissue proper Cartilage Bone tissue Blood
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types of loose connective tissue | aerolar, adipose, reticular
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types of dense connective tissue | regular, irregular, eliasic
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types of cartilage | hyaline, fibro, and elastic
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types of bone | spongy (callceous), and compact
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areolar connective tissue | gel like matrix with all three fiber types, wraps and cushions organs
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areolar connective tissue is found | under epithelium, forms lamina prpria of mucous membranes, packages organs, surrounds capillaries
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adipose tissue | matrix of adipocytes that have nucleus pushed to the side , provides reserve food fuel, insulates, supports and protects organs
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adipose tissue is found | under the skin; around kidneys and eyeballs, within abdomen; in breasts
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Reticular tissue | network of reticular fibers in a lose ground substance, form soft internal skeleton that supports other types of cell types (blood, mast, macrophages)
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reticular tissue is found | lymphoid organs (lymph nodes, bone marrow, and sleen)
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Dense Irregular connective tissue | irregulary arranged collagen and some elasic fibers, able to withstand tension exerted in many directions, provides structural strength
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Dense Irregular connective tissue is found | dermis of the skin, submucosa of digestive tract, fibrous capsules of organs and joints.
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Dense regular connective tissue | parallel collagen and a few elastin fibers attaches muscles to bones, withstands stress when pulling in one direction
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Dense regular connective tissue is found | tendons, most ligaments, aponeuroses
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Hyaline cartilage | amorphous but firm matrix made of collagen fibers, chondroblasts produce the matrix and can lie in lacunae when mature; supports and reinforces
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Hyaline cartilage is found | embryonic skeleton, covers ends of long bone, forms costal cartilages of the ribs, nose trachea and larynx
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Elastic cartilage | firm matrix made of elastin fibers; maintains shape whicle allowing flexibility
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elastic cartilage location | external ear(pinna) epiglottis
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fibrocartilage | less firm matrix with thich collagen fibers; tensile strength with the ability to absorb shock
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fibrocartilage is found | intervetebral discs, pubic symphysis, discs of knee joint
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Bone tissue | hard calcified matrix containing many collagen fibers osteocytes lie in lacunae, very well vascularized; supports and protects stores calcium, minerals and fat, blood cell formation
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blood tissue | red and white blood cells in a fluid matrix (plasma) transport of respiratory gases, nutrients, wastes and other substances
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thoracic cavity | heart and lungs
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major organs or tissues of circulatory system | heart, blood vessels
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major organs or tissues of respiratory | nose, larynx, trachea, bronchi, and lungs
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major organs or tissues of digestive | mouth, pharynx, esophagus, stomach, intestines, salivary glands, pancreas, liver, gallbladder
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major organs or tissues of urinary | kidneys, ureters, bladder, urethra
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major organs or tissues of musculoskeletal | cartilage, bone, ligaments, tendons, joints, skeletal muscle
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major organs or tissues of immune | white blood cells, lymph vessels and nodes, spleen, thymus, and other lymphoid tissues
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major organs or tissues of nervous | brain, spinal cord, peripheral nerves and ganglia, special sense organs
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major organs or tissues of endocrine | all glands secreting hormones, pancreas, testes, ovaries, hypothalamus, kidneys, pituitary, thyrois, parathyroid, adrenal, intestinal, thymus, heart, and pineal
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Most control systems operate by | negative feedback which basically means that the change in a sensed body parameter initiates a response that opposes that change in an attempt to maintain homeostasis.
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negative feedback | which basically means that the change in a sensed body parameter initiates a response that opposes that change in an attempt to maintain homeostasis
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Positive feedback is | usually inappropriate as it tends to increase the stimulus that was monitored as a deviation from homeostasis
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4 main cell types of the integumetory system | keratinocytes, melanocytes, Merkel cells and Langerhans cells (can act as APC antigen presenting cells).
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Keratinocytes are | the most common and are constantly formed from the germinal layer on the underlying basement membrane.
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keratinocytes produce | tough, fibrous protein keratin, some antibodies and enzymes (for protection: see Immunology). As they ascend from the basement membrane to the surface, they die and form an outer physical barrier (toughened by the keratin).
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The deepest layer of the epidermis is | the stratum basale which is attached to the underlying dermis and contains, as well as actively dividing keratinocytes, Merkel cells (sensory function) and melanocytes (produce the pigment melanin for UV protection).
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the most superficial layer is | the stratum corneum which is composed of dead keratinocytes with thickened cell membranes.
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the next layer superficially from the stratum basale | is the stratum spinosum where keratin is forming and Langerhans cells are found.
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Langerhans cells | immune cells that present antigenic fragments of pathogens to special T-lymphocytes to activate them and produce a specific immune response. They are part of a very important group of cells known collectively as Antigen Presenting Cells (APCs)
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the third layer of skin is | stratum granulosum which is primarily made up of maturing keratinocytes containing keratin filaments (tonofilaments) plus a waterproofing glycolipid. And stops water loss as well
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In thick skin there is an extra layer known as the | stratum lucidum which is composed of now flattening, dead keratinocytes.
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what 2 layers is the dermis composed of | papillary and reticular (deepest)
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the reticular layer is composed of | dense, irregular connective tissue
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Hair is composed of | flexible strands of dead, keratinized cells: there are 3 concentric rings starting with the inner medulla → cortex → cuticle.
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Sebaceous glands produce | an oily secretion called sebum which helps trap dirt and softens and lubricates both skin and hair (this is holocrine secretion meaning that the entire cell breaks down to release the sebum (and is replaced by new cells).
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