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CARTILAGE
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Mar 22, 2016

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CARTILAGE

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Features & Functions

The extracellular substance is rich in proteoglycans and gycosaminoglycans

Avascular

Acts as shock absorber

Surrounded by perichondrium Except: ….

It supports soft tissue

It facilitates movement of the bone

It is essential for bone development and growth

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Components of Cartilage

Perichondrium

Outer fibrous

Inner cellular

Cells

Chondroblasts

Chondrocytes

Fibres

Collagen

Elastic

Ground Substance

Proteoglycans

Glycosaminoglycans

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Perichondrium: present in all types of

cartilage except fibrous and articular cartilages.

Outer fibrous: dense regular connective

tissue, fibroblasts and type I collagen fibres.

Inner cellular: contains undifferentiated cells

(chondrogenic), essential for growth.

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Cells of cartilage:

Chondroblasts: situated under the perichondrium, originate

from mesenchymal cell, typical protein synthesizing cells.

Chondrocytes: situated in lacuna, elliptical shape, axis parallel to the

perichondrium. Usually seen in isogenous groups.

Lacuna= space occupied by chondrocyte.

Isogenous group= cells originating from the

mitotic activity of one chondrocyte.

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Types of cartilage

Hyaline Elastic Fibrous

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Distribution of hyaline cartilage

Epiphyseal growth plate

Costal cartilage

Thyroid cartilage

Fetal skeleton

Nose

Trachea and bronchi

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Hyaline Cartilage

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Distribution of elastic cartilage

Ear pinna

External auditory tube

Eustachian tube

Epiglottis

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Growth of Cartilage

Interstitial growth

Appositional growth

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Clinical Problems

Tumors

Chondroma

Chondrosarcoma

Degenerative changes

Herniation of the intervertebral disc

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Herniated Disc

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The Cell Cycle

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Stages of the Cell Cycle

Interphase

Primary growth phase (G1)

Synthesis phase (S)

Secondary growth phase (G2)

Mitosis

Prophase

Metaphase

Anaphase

Telophase

Cytokinesis

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Interphase

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DNA replicated

Organelles replicated

Cell increases in size

cells spend most of their time in this intermediate non-mitotic state

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G1 - Interphase

The time gap between mitosis and RNA replication.

There is active synthesis of RNA and proteins.

Cellular content excluding chromosomes is duplicated.

Cell size grows to the original size.

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S - Interphase

Beginning of centrosome duplication.

Synthesis of DNA and histones.

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G2 - Interphase

Accumulation of proteins needed for mitosis.

Replicated chromosomes become loosely coiled.

Followed by mitosis (M phase).

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Control of the cell cycle

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Mitosis

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Prophase …1

Chromatin begins to coil and condense to form chromosomes

Each chromosome appears to have two strands (each containing a single molecule of DNA), each strand is called a chromatid

Each chromatid is attached to its sister chromatid at the centromere

At this stage, the number of chromosomes (containing a pair of chromatids) is considered to be equal to the number of centromeres .the two chromatids are the result of DNA replication that takes place just before mitosis starts.

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Prophase …2

the two chromatids are the result of DNA replication that takes place just before mitosis starts.

the nuclear envelope disappears

the nucleolus disappears

in cytoplasm, the spindle apparatus forms

eventually the spindle guides the separation of sister chromatids into the two daughter cells

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Metaphase

spindle grows and forms attachments to the chromosomes at the centromeres

chromosomes move to an equatorial plate (metaphase plate) which is formed along the midline of the cell between the poles

chromosomes are at their most condensed state now

metaphase chromosomes can be stained and will show distinctive banding patterns

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Anaphase

centromeres divide to create two chromosomes instead of a pair of attached chromatids

spindle fibers shorten and the sister chromosomes are drawn to the opposite poles of the cell

poles of the spindle apparatus are pushed apart as the cell elongates

anaphase results in the exact division of chromosome, distributing one complete diploid complement of genetic information to each daughter cell

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Telophase

nuclear envelopes reassemble and surround each set of daughter chromosomes

nucleoli reappear inside the newly formed nuclei

in animal cell, a furrow appears around the cell that eventually pinches the cell into two new cells

in plants, a cell plate forms between the two daughter nuclei as the cell wall divides the cell

chromosomes decondense in the daughter cells to become chromatin and the cells are once again in Interphase

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Meiosis

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Mitosis

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Cells produced have the haploid number of chromosomes.

Synapsis = homologous chromosomes of each pair are associated along their length.

• Crossovers occur during the synapsis process, resulting in new combinations.

Chromosomes of cells entering meiosis contain the two identical copies of sister chromatids.

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Unique Features of Meiosis

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At the start of prophase I, the chromosomes have already duplicated. During prophase I, they coil and become shorter and thicker and visible under the light microscope.

The duplicated homologous chromosomes pair, and crossing-over occurs. At this point, each homologous chromosome pair is visible as a bivalent (tetrad

The nucleolus disappears during prophase I.

In the cytoplasm, the meiotic spindle, consisting of microtubules and other proteins, forms between the two pairs of centrioles as they migrate to opposite poles of the cell.

The nuclear envelope disappears at the end of prophase I, allowing the spindle to enter the nucleus.

Prophase I is the longest phase of meiosis, typically consuming 90% of the time for the two divisions.

Prophase I

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Metaphase I

The centrioles are at opposite poles of the cell.

The pairs of homologous chromosomes (the bivalents), now as tightly coiled and condensed as they will be in meiosis, become arranged on a plane equidistant from the poles called the metaphase plate.

Spindle fibers from one pole of the cell attach to one chromosome of each pair (seen as sister chromatids), and spindle fibers from the opposite pole attach to the homologous chromosome (again, seen as sister chromatids).

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Anaphase I

Anaphase I begins when the two chromosomes of each bivalent (tetrad) separate and start moving toward opposite poles of the cell as a result of the action of the spindle.

In anaphase I the sister chromatids remain attached at their centromeres and move together toward the poles. A key difference between mitosis and meiosis is that sister chromatids remain joined after metaphase in meiosis I, whereas in mitosis they separate.

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Telophase I and Interkinesis The homologous chromosome pairs complete

their migration to the two poles as a result of the action of the spindle. Now a haploid set of chromosomes is at each pole, with each chromosome still having two chromatids.

A nuclear envelope reforms around each chromosome set, the spindle disappears, and cytokinesis follows. In animal cells, cytokinesis involves the formation of a cleavage furrow, resulting in the pinching of the cell into two cells. After cytokinesis, each of the two progeny cells has a nucleus with a haploid set of replicated chromosomes.

Many cells that undergo rapid meiosis do not decondense the chromosomes at the end of telophase I. Other cells do exhibit chromosome decondensation at this time; the chromosomes recondense in prophase II.

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Prophase II While chromosome duplication took place prior to meiosis I, no new chromosome replication occurs before meiosis II.

The centrioles duplicate. This occurs by separation of the two members of the pair, and then the formation of a daughter centriole perpendicular to each original centriole. The two pairs of centrioles separate into two centrosomes.

The nuclear envelope breaks down, and the spindle apparatus forms.

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Metaphase II

Each of the daughter cells completes the formation of a spindle apparatus.

Single chromosomes align on the metaphase plate, much as chromosomes do in mitosis. This is in contrast to metaphase I, in which homologous pairs of chromosomes align on the metaphase plate.

For each chromosome, the kinetochores of the sister chromatids face the opposite poles, and each is attached to a kinetochore microtubule coming from that pole.

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Anaphase II

Centromeres of sister chromatids are detached from each other.

The now non-replicated chromosomes are pulled to the poles of the cells.

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Telophase II and Cytokinesis

Each new nucleus formed has half the number of the original chromosomes but each nucleus has one of each type of homologous chromosome.

A total of four new cells will be produced.

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Stages of Meiosis

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Connective Tissue

1

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General Features

Originates from the mesenchyme.

Composed of cells, fibres and extracellular matrix.

Highly vascular.

Variable regenerative power.

2

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Functions of Connective Tissue

Support:

Defense and protection:

Storage:

Medium for exchange:

3

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Cells of the Connective

Tissue

4

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Fixed cells:

• Fibroblasts.

• Adipose cells.

• Pericytes.

• Mast cells.

• Macrophages.

Transient cells:

• Plasma cells.

• White blood cells (Neutrophils, Eosinophils, Basophils, Lymphocytes, Monocytes).

• Macrophages.

5

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Fibroblast

6

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Fibroblasts

The most numerous cells of connective tissue.

Occur in active and inactive forms (fibrocyte).

Originate from undifferentiated mesenchymal cells.

Capable of some movement.

Rarely undergo division.

FGF may influence cell growth and differentiation.

7

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Active fibroblasts

Closely associated with collagen bundles.

Elongated, fusiform, and have many processes.

Cytoplasm is pale and difficult to be differentiated from near by tissue.

Nucleus is large, dark stained and granular.

E.M: prominent Golgi, mitochondria, rER, actin and myosin.

8

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Inactive Fibroblast (Fibrocyte)

Smaller and ovoid with acidophylic cytoplasm.

The nucleus is smaller and darker.

Few processes.

E.M: few rER and many ribosomes.

When stimulated, it may revert to fibroblast.

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Myofibroblast

Has features of both smooth muscles and fibroblasts.

Their contraction is responsible for wound contraction.

12

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Mast Cell

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Mast Cell

Large cell ~ 20-30 m.

Derived from precursors in the bone marrow.

Nucleus: central ovoid.

Cytoplasm highly granular, metachromatic.

Grnules contain:

• Heparin

• Histamin

• Leukotriens

• Eosinophil chemotactic factor.

• Neutrophil chemotactic factor.

• Platelet activating factor.

• Bradykinin.

• Thromboxane A2

14

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Plasma Cell

Derived from B lymphocytes following exposure to an antigen.

Present at portal of entry of organisms and sites of chronic inflammation.

Life span ~ 2-4 weeks.

Large ovoid cells ~ 20 m.

Nucleus: eccentric with clusters of heterochromatin cart-wheel or clock-face nucleus.

15

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Plasma Cell

Cytoplasm:

• Intensely basophilic.

• Well developed supranuclear Golgi apparatus (- ve image).

• Well developed rER.

Functions: secretion of specific antibodies.

16

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Macrophage

Derived from monocyte.

Large cells ~15-30 m.

Surface shows many projections.

Nucleus: eccentric, ovoid, dark, and indented (kidney-shaped).

Cytoplasm: basophilic, well developed Golgi, prominent rER, many lysosomes.

They are part of the MPS.

17

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Pericyte

Derived from undifferentiated mesenchymal cell.

Surrounded by its own basal lamina.

Commonly seen in the walls of capillaries and venules.

They may differentiate into other cells.

18

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Extracellular Matrix

Extracellular Matrix = ground substance + fibres.

• Resists compression and stretching forces.

• The water content allows rapid exchange of metabolites.

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Ground Substance

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Ground Substance

Composed of:

• Glycosaminoglycans:

• Sulfated: keratan sulfate, chondroitin sulfate, dermatan sulfate and heparin.

• Non-sulfated: hylauronic acid

• Proteoglycans:Responsible for the gel state of the extracellular matrix.

• Adhesive glycoproteins: laminin, chondronectin, osteonectin and fibronectin.

21

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Types of GAGs

Distribution GAG

Most connective tissue, cartilage,

dermis, synovial fluid. Hyaluronic acid

Cartilage, cornea, intervertebral disc. Keratan sulfate

Blood vessels, lung, basal lamina Heparan sulfate

Cartilage, bone, blood vessels Chondroitin 4-sulfate

Cartilage, blood vessels, umbilical

cord. Chondroitin 6-sulfate

Skin, heart valves, blood vessels Dermatan sulfate

Mast cell granules, basophils, liver

lung, skin. Heparin

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Functions of Proteoglycans

Resistance of compression.

Retardation of movement of microorganisms.

Act as a filter.

Possess binding sites for growth factors.

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* Connective Tissue Fibres

Collagen

Elastic

Reticular

24

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Connective Tissue Fibres

Fibre Properties

Collagen Undulating course of longitudinally striated bundles,

form meshwork of variable texture, stain pink-red in

H&E. Nonextensible.

Elastic Forms sheets or lamina, Unstained in H & E.

Reversibly extinsible. Stains brown-black in Orcein

or Resorscin Fuchsin.

Reticular Delicate network, Unstained in H & E. Reversibly

extinsible. PAS +ve, stains black in AgNO3

(Argyrophilic).

25

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Collagen Fibers

Gives the extracellular matrix strength to resist tensile forces.

Formed of protein collagen (20% of all proteins of the body).

H & E: long, wavy pink bundles.

E.M: cross banding at 67 nm.

Fibres are formed of aggregation of fibrils.

Fibrils are formed of tropocollagen.

Tropocollagen is formed of 3 helical polypeptide chains.

26

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Collagen bundle

Fibres

Fibrils

Tropocollagen

3 Helical polypeptide chains, α-chains. 27

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α-chains possess 1000 amino acids.

Every 3rd amino acid is glycine.

• Other amino acids: proline, hydroxyproline, hydroxylysine.

The sequence of aminoacids determines the type of collagen.

• There are 16 types of collagen.

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Location Function Synthesizing cell Type

Dermis, tendons,

ligament, capsules,

bone, dentin,

cementum

Resist tension Fibroblast, osteoblast,

odontoblast, cementoblast

I

Hyaline and elastic

cartilage

Resists pressure chondroblasts II

Reticuloendothelia

l system, lung, skin

Form structural

framework of

organs

Fibroblasts, reticular cells,

smooth muscle,

hepatocytes

III

Basal lamina Meshwork of the

lamina densa

Epithelium, muscle,

Schwann cells

IV

As in type I and

placenta

Associated with

type I.

Fibroblasts, mesenchymal

cells

V

Derma-epidermal

junction

Anchoring fibrils

between the lamina

densa and reticularis

Epidermal cells VII

Major Types of Collagen

30

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EXTRA CELLULAR

Cleavage and assembly

Intracellular * Transcription (Nucleus).

* Translation (rER).

* Hydroxylation (rER).

* Glycosylation (rER & Golgi).

* Formation of the triple helix.

* Secretion of procollagen (trans Golgi network

and microtubules).

*** Vit. C is essential

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Clinical Notes:

Progressive Systemic Sclerosis

Keloid

Vitamin C deficiency (Scurvy)

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Elastic Fibers

• Oxytalan: found in the zonule of the eye and upper dermis.

• Not elastic, highly resistant to pulling forces.

• Elaunin: found in deep dermis around sweat glands

• Elastic:

• Elasticity is due to elastin.

• Elastin = glycine + proline + lysine.

• Stability is due to microfibrils (resistant to boiling).

• Digested by pancreatic enzyme elastase

Composed of:

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Reticular Fibres

Consist mainly type III collagen.

Short, thin and branching.

Give PAS +ve reaction.

Stain with Silver Nitrate (Argyrophylic).

Found mainly in RES organs, endometrium and around blood vessels.

36

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Edema الوذمــة

37

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Edema = increase in the intercellular fluid.

• Arterial:

• Venous:

• Lymphatic: Causes:

38

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Forces acting on water in capillaris:

Hydrostatic pressure: favors filtration at the

arterial side of the capillary.

Oncotic pressure: favors absorption at the

venous side of the capillary.

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Classification of Connective Tissue

Connective tissue proper: Loose (areolar): mesentery

Dense regular: tendons and ligaments

Dense irregular: dermis, capsules.

Special connective tissue: Elastic

Reticular

Adipose

Bone

Cartilage

Blood

Embryonic connective tissue: Mesenchymal connective tissue

Mucous connective tissue

41

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Epithelium

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Features and classification of epithelium were discussed in the practical class.

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Discipline is the bridge between goals and accomplishments.

anonymous

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The epithelial cell

Shown to have the following domains:

• Apical

• Baso-lateral

Each domain shows modifications to suit its functions.

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Apical Domain

It is the part of the cell that faces the lumen (the free surface of the cell).

It is rich in ion channels, carrier proteins and hydrolytic enzymes.

The apical modifications are:

• Microvilli.

• Stereocilia.

• Cilia.

• Flagella.

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Microvilli

Present mainly in absorptive cells.

Their number and size vary according to the degree of activity of the cell.

They are usually crowded on the cell apex forming the striate border in the intestine and the brush border in the kidney.

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Structure of the Microvillus

The microvillus is 1- 2µ in length.

Contains a core of 25-30 actin filaments.

Actin filaments are cross-linked with villin.

The actin filaments are inserted into the terminal web.

The terminal web is a network of actin and spectrin supported by myosin, IF, and camodulin in the apical part of the cell.

The microvillus is covered by glcocalyx; it gives PAS +ve reaction

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Stereocilia are long immotile microvilli present in the

epididymis and inner ear. They have special functions in these

places.

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Cilia

Motile cytoplasmic hair like projections capable of moving fluid and particles along epithelial surfaces.

Measurements: length 7-10μ, diameter 0.2 μ.

Number of cilia/cell is variable and ranges 1-300 cilium/cell.

They move rhythmically and rapidly in one direction.

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The core of the cilium is called axoneme.

The axoneme consists of longitudinal microtubules arranged as 9 (doublets) peripheral surrounding 2 (singlets) central (9+2).

The singlets are separated by 13 protofilaments.

The doublets are composed of 2 subunits A & B.

Subunit A is formed of 13 protofilaments.

Subunit B is formed of 10 protofilaments.

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Neighboring doublets are connected by nexin.

Doublets are connected to the singlets by radial spokes.

Dynein radiates form subunit A to subunit B.

Dynein has ATPase activity.

Cilia are attached to basal bodies similar in structure to centrioles.

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Baso-Lateral Domain

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Terminal bars are light microscopic structures at the site of contact of cells.

E.M revealed that the terminal bar is a junctional complex composed of:

• Occluding junctions.

• Anchoring junctions.

• Communicating junctions.

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Cell Junctions

Anchoring (Desmosomes and Macula adherentes) - mediate cell-cell and cell-matrix adhesions; linked to cytoskeleton to transmit and distribute stress

Occluding (Zonula Ocludentes) - form seals between epithelial cells; block or regulate (paracellular) permeability between cells

Channel-forming (Gap Junction) - allow diffusion of small molecules

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Tight Junctions

Occluding junction (encircles epithelial cells)

Barrier to diffusion between cells (paracellular pathway)

Separates apical and basolateral plasma membranes, the outer layers of 2 adjacent plasmalemma fuse together.

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Tight Junctions

Tight junction blocks diffusion of soluble tracer molecules added to either the apical or basolateral compartment.

MBoC5 Fig 19-24

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Tight Junction

TEM: is the most apical junction

Freeze fracture of TJ reveals ridges in membranes that correspond to sites of contact between cells

Ridges are linear arrays of occludin and claudin proteins

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Tight Junction Permeability

Some claudins and occludins have pores (A, B, and C) that allow selective (paracellular) movement of ions or solutes

Side view Top view

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Tight Junction Proteins

Occludins and claudins are transmembrane proteins that interact across the intercellular space to form TJs

ZO (zonula occludens) proteins 1-3 link occludin and claudin to each other, to JAMs, and to actin filaments

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Zonula Adherens

Anchoring junction (encircles the cell)

AKA adhesion belt, belt junction, or belt desmosome

Located "under" tight junction in epithelial cells

Connected to actin microfilaments that join terminal web

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Zonula Adherens

Cadherin proteins attach to crosslinked actin filaments

Mechanical support - ZA and actin filaments transmit and distribute stress throughout cell and to neighboring cells

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Desmosomes

Anchoring junctions

Function as "spot welds" to join cells

Located along lateral plasma membranes of columnar epithelial cells or on processes of squamous cells

Intermediate filaments associate with plaque proteins in cytoplasm

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Desmosomes

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Desmosomes

cadherins interact across intercellular space

Adaptor proteins form a dense plaque that interconnects cadherins and binds them to intermediate filaments

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Desmosomes

Desmoglein and desmocollin are non-classical cadherins

Adaptor proteins such as -catenin (plakoglobin) and desmoplakin link cadherins to intermediate filaments

MBoC5 Fig 19-17

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Gap Junction

Channel-forming junction

Named for gap of regular width between cells visualized by TEM

Water-filled junctions transport molecules <1 kDal such as ions, nucleotides (including cAMP), and metabolites

Ross Fig 5-17

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Connexin - protein subunit, six form a hexameric connexon

Connexons - two align to form the gap junction channel

Regulation - elevated calcium concentrations close channel

Gap Junction

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Hemidesmosomes

Hemidesmosome - "half-desmosome" in appearance only

Mediates attachment to basal lamina (extracellular matrix)

Cytoplasmic plaque is attached to cytoskeletal elements

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Hemidesmosomes

Integrins - membrane protein that "integrates" cell into matrix

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Integrins

Mediate calcium-independent cell-matrix adhesion

Function as dimers of two membrane proteins ( and )

Adaptor proteins link integrins to intermediate filaments in hemidesmosomes or actin filaments in focal adhesions

Integrins bind matrix proteins such as laminin or fibronectin

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Focal Adhesions

Anchoring junction (AKA actin-linked cell-matrix adhesion)

Growing fibroblasts form many focal adhesions (orange) that serve as anchoring points for actin filaments (green)

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Focal Adhesions

Fibroblasts attach to extracellular matrix via focal adhesions

Integrins - membrane proteins link actin filaments and matrix

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Blistering Disease

Many mechanisms underlie blistering disorders of the skin

Pemphigus group - autoimmune disease in which autoantibodies target desmogleins present in desmosomes

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Pemphigus Histology

Acantholysis - separation of epidermal keratinocytes (H&E)

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Basal Laminae & Basement Membrane

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Basal Lamina

Only visible with E.M

Found also in other tissues

Components are secreted by epithelium, connective tissue, muscle, Schwann cell

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Layers of Basal Lamina

Layers of the Basal Lamina

• Lamina Lucida

• Lamina Densa

Lamina Reticularis: not part of the basal lamina

Molecular components are variable but include:

• type IV collagen,

• Glycoproteins (Laminin, entactin…)

• Proteoglycans (Perlecan)

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E.M of Basal Lamina

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Functions of Basal lamina

Support

Selective barrier

Influencing cell polarity

Regulation of proliferation and growth

Affect cellular metabolism

Affect cell-cell interaction

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Clinical Importance of Basal Lamina

Tissue culture

Tumor grading

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Glandular

Epithelium

1 Dr. Darwish Badran 2008/2009

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Glands are divided into:

Endocrine: • Unicellular: DNES • Multicellular: Thyroid, Adrenal

Exocrine: • Unicellular: Goblet cell • Multicellular: Parotid, Submandibular, Sublingual

Mixed: Liver, Pancreas, Ovary, Testis.

2 Dr. Darwish Badran 2008/2009

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GLAND DEVELOPMENT I

Mesenchymal-epithelial

exchange of signals

Cell de-differentiation, &

proliferation Epithelium

Mesenchyme

3 Dr. Darwish Badran 2008/2009

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GLAND DEVELOPMENT II

Cell de-differentiation,

& proliferation

Epithelial downgrowth

into modified

mesenchyme

Mesenchymal-epithelial exchange of signals

4 Dr. Darwish Badran 2008/2009

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GLAND DEVELOPMENT III

Differentiation into

duct & secretory cells

Epithelial downgrowth

into modified

mesenchyme

5 Dr. Darwish Badran 2008/2009

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GLAND DEVELOPMENT IV

Differentiation into

duct & secretory cells

Construction of lumens

Simple alveolar gland

Stroma

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Although cells in covering and lining epithelia secrete, they are limited

in number. To get more secreting power, and sometimes to focus it

differently, e.g. to interact with blood, rather than dump into a principal

tube, epithelial cells can build glands

GLANDULAR EPITHELIA

ENDOCRINE GLAND

Clumps of endocrine cells

hormone

Duct lined by

cuboidal cells

Secretory unit (acinus or tubule) lined

by “cuboidal” cells

EXOCRINE/DUCTED GLAND

Capillary

basal

lamina

Nerve

control

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Exocrine Glands.. 1:

Classified according to the mode of secretion:

•Merocrine (eccrine): •Apocrine: •Holocrine:

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secretion released by

exocytosis, with no loss

of cytoplasm

Sebaceous gland

SEBUM

e.g., by endocrine cells

hormone

secretion released,

filling a dead cell

HOLOCRINE

MODES OF SECRETORY RELEASE

MEROCRINE / ECCRINE

released by exocytosis, with

a little loss of cytoplasm

APOCRINE

Female breast 9 Dr. Darwish Badran 2008/2009

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Exocrine Glands.. 2:

Classified according to nature of

secretion: • Serous: • Mucous: • Mixed:

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Exocrine Glands.. 3:

Classified according to the duct system and the

secretory part:

Duct:

Simple Compound

Secretory part:

Tubular Acinar

(alveolar) Tubulo-

acinar

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SIMPLE GLANDS

COMPOUND GLANDS

alveolar

tubular tubulo-alveolar

DUCT tubular alveolar /

acinar

Classification by shape & duct complexity

straight/coiled

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Glandular Epithelia : Products & Roles

Airway glands, Duodenal & Salivary glands

Extra mucus

Airway glands Extra defense Gastric glands, Pancreas Digestion Liver Blood processing Endocrine glands Hormones Mammary glands Milk

Sweat glands

Sweat

Sebaceous glands

Grease

Special genito-urinary functions Genital glands 13

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MUCOUS TUBULE

MYOEPITHELIAL CELL

SEROUS DEMILUNE

BL

SEROUS ALVEOLUS

MUCOUS TUBULE

with

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muco-ciliary escalator

rids airway of particles

MUCUS-SECRETING

GOBLET CELL

Deliver all along a surface BL

Single cells

exocrine

Deliver all along a surface

Single cells & simple glands

Simple straight tubules,

with - SIMPLE

TUBULAR

Surface goblet cells

Colon cells 15 Dr. Darwish Badran 2008/2009

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GUT PARTS

VILLI covered

with simple

columnar

epithelium

MUSCULARIS smooth muscle

SUBMUCOSA

connective tissue

suspensory MESENTERY

with blood vessels

covering SEROSA

with simple

squamous epithelium

GLANDS

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THIN HAIRY SKIN Hair shaft

D

E

R

M

I

S

Epidermis

H

Y

P

O

D

E

R

M

I

S

Large round/ovoid group

of cells, with no duct

SIMPLE ALVEOLAR

Sebaceous gland

SEBUM

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SWEAT GLAND

Sweat gland

D

E

R

M

I

S

Epidermis

H

Y

P

O

D

E

R

M

I

S

Coiled secretory tubule feeding a coiled thin

wiggly duct - SIMPLE COILED TUBULAR Sweat gland 18 Dr. Darwish Badran 2008/2009

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PANCREAS

Duodenum

Exocrine acini

digestive enzymes

Lobule

}

Endocrine islet

metabolic

hormones

Ducts

alkaline ions

Many secretory acini/alveoli feeding branching

duct system - COMPOUND ALVEOLAR

a mixed

exocrine-

endocrine

gland

Deliver at wide intervals

along a surface BL

Large, elaborate, compound

glands

exocrine

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EXOCRINE PANCREAS Ducts 1 Duodenal

papilla Exocrine acini

Lobule

} Principal duct

Interlobular duct

Intralobular ducts

Intercalated ducts 20 Dr. Darwish Badran 2008/2009

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Stroma Stroma

Stroma

Traumatic loss of

surface epithelium

Duct Cell de-differentiation,

& proliferation

Stromal cell re-activation, &

proliferation

Restitution of basal lamina &

stroma

Epithelial upgrowth and

outgrowth over clot

Fibrin clot

Differentiation into

surface & duct cells

REGENERATION from

ducts 21 Dr. Darwish Badran 2008/2009

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22 Dr. Darwish Badran 2008/2009

Unicellular gland

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Unicellular gland

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Simple tubular glands

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Simple coiled tubular gland

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Simple branched tubular

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Simple alveolar glands

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Compound tubular glands

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Serous gland- parotid

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Seromucous gland

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Mucus gland

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Apocrine gland

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The Nucleus

1

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Nucleus • The nucleus is a

membrane bound

structure that contains the

cell's hereditary

information and controls

the cell's growth and

reproduction.

• It is commonly the most

prominent organelle in the

cell

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Nuclear Envelope

Surrounds the nuclear material.

Consists of two parallel membranes, separated from each other by a narrow perinuclear cisterns.

These membranes fuse at intervals, forming openings in the nuclear envelope called nuclear pores.

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Outer Membrane

The outer membrane 6 nm thick.

It faces the cytoplasm and is continuous at certain sites with the rough endoplasmic reticulum.

A loosely arranged mesh of intermediate filaments (vimentin) surrounds the outer nuclear membrane on its cytoplasmic aspect.

Ribosomes stud the cytoplasmic surface of the outer nuclear membrane.

These ribosomes synthesize proteins that enter the perinuclear cisterna.

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Inner Membrane

6 nm thick.

Faces the nuclear material.

Separated from it and supported on its inner surface by the nuclear lamina, a fibrous lamina that is 80-300 nm thick.

Composed primarily of lamins A, B, and C.

These intermediate filament proteins help organize the nuclear envelope and perinuclear chromatin.

Additionally they are essential during the mitotic events, when they am responsible for the disassembly and reassembly of the nuclear envelope.

Phosphorylation of lamins leads to disassembly, and dephosphorylation results in reassembly of the nuclear envelope.

5

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Perinuclear cisterns

Located between the inner and outer nuclear membranes and is 20-40 nm wide.

Continuous with the cisternae of the RER.

It is perforated by nuclear pores at various locations.

6

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Nuclear pores

Average 80 nm in diameter.

Number from dozens to thousands depending upon the metabolic activity; they are associated with: The nuclear pore complex (NPC).

Formed by fusion of the inner and outer nuclear membranes.

Permit passage of certain molecules in either direction between the nucleus and cytoplasm via a 9-nm chamel opening.

7

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Nuclear pore complex (NPC)

The NPC is composed of nearly 100 proteins, some of which are arranged in eight-fold symmetry around the margin of the pore.

It consists of cytoplasmic ring, nucleoplasmic ring and the middle ring.

The nucleoplasmic side of the pore exhibits a nuclear basket, whereas the cytoplasmic side displays fibers extending into the cytoplasm.

A transporter protein is located in the central core and is believed to be responsible for transporting proteins into and out of the nucleus via receptor-mediated transport.

8

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Functions of the Nuclear Pore Complex (NPC)

The NPC permits passive movement across the nuclear envelope via a 9- to 11-nm open channel fiber simple diffusion.

Most proteins, regardless of size, pass in either direction only by receptor-mediated transport.

These proteins have clusters of certain amino acids known as nuclear localization segments (NLS) that act as signals for transport.

9

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Nucleolus

Nuclear inclusion that is not surrounded by a membrane.

It is present in cells that are actively synthesizing proteins;

More than one nucleolus can be present in the nucleus.

It is generally detectable only when the cell is in interphase.

Contains mostly rRNA and protein as well as a modest amount of DNA.

It possesses nucleolar organizer regions (NORs), portions of those chromosomes (in humans, chromosomes 13,14,15,21, and 22) where rRNA genes are located; these regions are involved

in reconstituting the nucleolus during the GI phase of the cell cycle.

10

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Nucleolus

The nucleolus contains four distinct regions.

• Fibrillar centers are composed of inactive DNA where DNA is not being transcribed.

• Pars fibrosa are composed of 5-nm fibrils surrounding the fibrillar centers and contain transcriptionally active DNA and the rRNA precursors that are being transcribed.

• Pars granulosa are composed of 15-nm maturing ribosomal precursor particles.

• Nucleolar matrix is a fiber network participating in the organization of the nucleolus.

11

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Nucleolus Functions

Synthesis of rRNA and its assembly into ribosome precursors.

sequesters certain nucleolar proteins that function as cell-cycle checkpoint signaling proteins.

Three such cell-cycle regulator proteins have been identified within the nucleolus, where they remain sequestered until their release is required for targets in the nucleus and/or cytoplasm.

12

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Nucleoplasm

Nucleoplasm is the protoplasm within the nuclear envelope.

It consists of a nuclear matrix and various types of particles.

13

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Nuclear matrix

Nuclear matrix acts as a scaffold that aids in organizing the nucleoplasm.

It contains other components:

Structural components include fibrillar elements, nuclear pore, nuclear lamina complex, residual nucleoli, and a residual ribonucleoprotein (RNP) network.

Functional components are involved in the transcription and processing of mRNA and rRNA, steroid receptor-binding sites, carcinogen binding sites, heat-shock proteins, DNA viruses, and viral proteins ('I‘ antigen).

• It may have many more functions which are currently not known. 14

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Nuclear Particles

Heterchromatin granules are clusters of irregularly distributed particles

(20-25 nm in diameter) that contain RNP and various enzymes.

Perichromatin granules are single dense granules (30- 50 nm in diameter) surrounded by a less dense halo.

• Located at the periphery of heterochromatin and exhibit a substructure of 3-nm packed fibrils.

• Contain 4.7s RNA and two peptides similar to those found in heterogeneous nuclear RNPs (hnRNPs ).

• They may represent messenger RNPs (mRNPs).

• The number of granules increases in liver cells exposed to carcinogens or temperatures above 37°C.

15

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Nuclear particles

The hnRNP particles are complexes of precursor mRNA (premRNA) and proteins and are involved in processing of pre-mRNA.

Small nuclear RNPs (snRNPs) are complexes of proteins and small RNAs and are involved in hnRNP splicing or in cleavage reactions.

16

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Chromatin

Chromatin consists of double-stranded DNA complexed with histones and acidic proteins.

It resides within the nucleus as heterochromatin and euchromatin.

The euchromatin-heterochromatin ratio is higher in malignant cells than in normal cells.

17

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Chromatin

Heterochromatin is the condensed inactive chromatin, is concentrated at the periphery of the nucleus and around the nucleolus, as well as scattered throughout the nucleoplasm.

Euchromatin is the trascriptionally active form of chromatin that appears in the LM as a lightly stained region of the nucleus.

The main function of chromatin is the synthesis of RNA and cell division.

18

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19

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Other components of the nucleus

Some of the components which also form a part of the nucleus include the:

• DNA.

• Different classes of RNA (m-RNA, r-RNA and t-RNA).

These are important for cell survival, cell division, and protein synthesis.

20