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    Chapter 11Cellular Signaling

    Cells must signal to each other and interpret the signals they receive

    from other cells and the environment Signals are ussually chemicals

    The same small set of cell signaling mechanisms shows up in diverse

    species and processes (conserved strategies)

    Definitions

    KinaseEnzyme that catalyzes phosphorylation

    LigandA signal molecule

    Secondary MessengerIntracellular signals

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    Local vs Long distance signaling

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    Intercellular receptor

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    Signal Transduction - Phosphorylation cascade

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    Cells can respond to signals differently

    Signalingmolecule

    Receptor

    Relaymole-

    cules

    Response 1 Response 2 Response 3 Response 4 Response 5

    Cell A: Pathway leadsto a single response. Cell B: Pathwaybranches, leading to

    two responses.

    Cell C: Cross-talkoccurs between two

    pathways.

    Cell D: Differentreceptor leads to a

    different response.

    Activation

    or inhibition

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    CAMPBELL

    BIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    2014 Pearson Education, Inc.

    TENTH

    EDITION

    CAMPBELL

    BIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    TENTH

    EDITION

    12The Cell Cycle

    Lecture Presentation by

    Nicole Tunbridge and

    Kathleen Fitzpatrick

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    The Cell Cycle.

    Interphase90% of cell cycle, this is when cell grows- G1& G2 phases are gap phases

    - S phase (synthesis) is when DNA is replicated

    Mitotic phasewhen cell actually divides

    -Mitosisdivision of the nuclear material

    -Cytokinesis is the division of the cytoplasm

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    Figure 12.12-4

    Chromosome

    replication

    begins.

    Two copiesof origin

    E. co li cell

    Origin of

    replication

    Cell wall

    Plasma

    membrane

    Bacterial

    chromosome1

    2 Origin OriginOne copy of the

    origin is now at

    each end of the

    cell.

    3

    Two daughter

    cells result.

    4

    Replication

    finishes.

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    How do we organize information transfer (DNA)

    Eukaryotic chromosomes made of chromatin

    Chromatin iscomplex of DNA and protein Chromatin condenses during cell division into chromosomes

    Number of chromosomes is specific for every species

    Somatic cells(nonreproductive cells) 2 sets of chromosomes

    Gametes(reproductive cells: sperm and eggs) have half as

    many chromosomes as somatic cells

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    Mitosis

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    Cytokinesiscell splitting

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    Do cells just randomly move through these stages?

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    The Cyclin-dependent kinases (Cdk) Cyclins are proteins expressed in G1

    They bind to Cdk proteins

    Cdk proteins are activated

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    CAMPBELL

    BIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    2014 Pearson Education, Inc.

    TENTH

    EDITION

    CAMPBELL

    BIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    TENTH

    EDITION

    13Meiosis and

    Sexual Life

    Cycles

    Lecture Presentation by

    Nicole Tunbridge and

    Kathleen Fitzpatrick

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    Reproduction

    Living organisms distinguished by reproduction

    Hereditytransmitting traits from one generation to the next

    Variationthe differences in appearance between offspring,parents, and siblings

    GeneticsThe scientific study of heredity and variation.

    Genes The fundamental unit of heredity made of DNA segments

    The location of a gene along a chromosome is its locus

    The gene for a trait is usually found on the same locus.

    Below are sister chromatids (identical chromatids)

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    Distribution of genes in biology

    Somatic cellsnon-reproductive/DIPLOID

    Gametesreproductive cells (sperm and egg)/HAPLOID

    Haploid: 1 copy of the chromosome (1n)

    Diploid: 2 copies of each chromosome (2n)

    Human somatic cells have 23 distinct chromosomes for a total

    of 46 (2x23=46)

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    Terminology for chromosomes

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    Determining gender

    The sex chromosomes,determine thesexof the

    Human females have a homologous pair of X chromosomes (XX)

    Human males have one X and one Y chromosome (XY)

    The remaining 22 pairs of chromosomes are the autosomes

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    Asexual reproduction

    Asexual reproductionsingle individual passes genes to

    offspring without fusion of gametes

    Clonesgenetically identical individuals from same parent

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    Sexual reproduction

    Sexual reproductiontwo parents give rise to offspring with unique

    combinations of genes inherited from both parents.

    Genes are passed between generations through gametes

    Gametesreproductive cells (haploid)

    Fertilizationthe union of gametes

    Zygotea fertilized egg with one set of chromosomes from each gamete

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    Meiosis I and IImaking gametes

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    Introduction of genetic diversity

    Crossing over (Recombination)

    Independent assortment

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    Blended InheritanceAn old ideaWhen gametes fuse (fertilization) the traits blend

    together and the original traits are lost.

    Eventually all members of a species would be exactly the same!

    Inheritance would actually work AGAINST speciation (making new species)

    Wh t i th h t d h t i th

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    What is the character and what is the

    trait for each one?

    How are traits passed on to their descendents?

    GeneThe unit of heredity. (carries the information for a

    polypeptide or RNA) responsible for a trait(s).

    AlleleAlternate forms of gene that leads to different traits.

    GeneticsThe study of heredity

    HeredityThe passing of traitsacross generations

    Character (eye color) vs Traits (blue or brown)

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    How can alleles be different?!?!?

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    Gregor MendelFather of Genetics

    Mendel discovered the basic principles of heredity bybreeding garden peas in carefully planned experiments

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    Experimental design/nomenclature Mated 2 contrasting, true-breeding varieties -hybridization

    True-breeding parents - P generation

    Hybrid offspring of P generation - F1generation F1individuals pollinate w/other F1hybrids - F2generation

    Ovulewhere the eggs are stored

    PistilReceptacle for pollen

    StamenWhere pollen is generated and released

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    Traits do not blend.

    Particulate inheritanceGametes fuse (fertilization) and one trait will manifest

    but the other remains intact. Must be physically distinct elements

    D i /R i i

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    Dominant/Recessive traitsMendels Law of Dominance

    One allele is dominant and when present will always be manifested.

    HomozygousOnly one allele (SS or ss)HeterozygousTwo different alleles (Ss or sS)

    PhenotypeWhat is expressed

    GenotypeWhat is stored in the code

    How does a recessive trait ever get unmasked?

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    Mendels Law of Segregation

    During meiosis each gamete

    receives one allele

    H d di i i h b

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    How do you distinguish between

    homozygous dominant and heterozygous?

    What about multiple traits?

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    What about multiple traits?

    Mendels Law of Independent Assortment

    traits sorts independently of one another.

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    I l t d i

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    Incomplete dominance

    M lti l All l

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    Multiple Alleles

    Pl i t 1 lti l ff t

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    Pleiotropy1 gene = multiple effects

    Gene for white eyes in

    Drosophila make flightmuscles defective.

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    ID genetic material Hershey and Chase

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    ID genetic materialHershey and Chase

    Additi l E id Ch ff R l

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    Additional EvidenceChargaffs Rules

    1950 - Erwin Chargaff (Chargaffs rules) reported that:

    In any species the number of A and T bases are equaland the number of G and C bases are equal

    The total number of bases between species may vary.

    Watson and Crick

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    Watson and Crick

    Models for DNA replication

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    Models for DNA replication

    Messelsson and Stahl test the model

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    Messelsson and Stahltest the model

    DNA R li i A Cl L k

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    DNA Replication:A Closer Look

    The copying of DNA is remarkable in speed and accuracy

    ~6 billion base pairs in humans (1400 bio textbooks) Speed is ~50 nucleotides per second

    Accuracy is 1 mistake per 10 billion base pairs

    More than a dozen enzymes and other proteins participate

    in DNA replication

    Figure 16.12

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    Origin of

    replication

    0.5m

    0.2

    5m

    Bacterial

    chromosome

    Two daughter

    DNA molecules

    Replication

    bubble

    Parental (template)

    strandDaughter

    (new) strand

    Replicationfork

    Double-

    stranded

    DNA molecule

    (a) Origin of replication in an E. coli cell (b) Origins of replication in a eukaryoticcell

    Origin of

    replication Eukaryotic chromosome

    Double-stranded

    DNA molecule

    Parental (template)

    strand

    Daughter (new)strand

    Replication

    forkBubble

    Two daughter DNA molecules

    Figure 16.14

    New strand Template strand

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    5 53

    3

    5 5

    New strand Template strand

    SugarPhosphate Base

    OH

    A T

    C

    C

    G

    G

    A

    C

    Nucleotide

    DNApoly-

    merase

    OH

    Pyro-phosphate

    2 P i

    P iP

    3

    3

    A T

    C

    C

    G

    G

    A

    C

    T

    Leading strand synthesis

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    Leading strand synthesis

    Lagging strand synthesis discontinuous

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    Lagging strand synthesis - discontinuous

    Figure 16.17

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    Overview

    5

    3

    Laggingstrand

    Leading

    strand

    Leading

    strand

    Lagging

    strandLeading strand

    Leading strand

    template

    Origin of

    replication

    Overall directions

    of replication

    5

    3

    53

    5

    5

    3

    33

    Single-strand

    binding proteins

    Helicase

    Parental

    DNA

    DNA pol III

    Primer

    Primase

    Lagging

    strand

    Lagging strand

    template

    DNA pol III

    DNA pol I5

    DNA ligase

    123

    4

    5

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    R li ti th E d f DNA M l l

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    Replicating the Ends of DNA Molecules

    Limitations of DNA polymerase create problems for linear DNA of

    eukaryotic chromosomes

    The usual replication machinery provides no way to complete the 5ends,so repeated rounds of replication produce shorter DNA molecules with

    uneven ends

    Not a problem for prokaryotes, most of which have circular chromosomes

    Eukaryotic chromosomal DNA molecules have special nucleotidesequences at their ends called telomeres

    Telomeres postpone the erosion of genes near the ends of DNA molecules

    Shortening of telomeres may be connected to aging

    An enzyme called telomerase catalyzes the lengthening of telomeres ingerm cells

    Chapter 17: From Gene to Protein

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    Chapter 17: From Gene to Protein

    The information content of genes is in the specific nucleotide sequence

    The DNA inherited by an organism leads to specific traits by dictating

    the synthesis of proteins. (ex: enzymes that make flowers purple)

    Proteins are the links between genotype and phenotype

    Gene expression, the process by which DNA directs protein synthesis,

    includes two stages: transcription and translation

    Central dogma: information flows from DNARNAProteins

    Transcription and Translation

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    Transcription and Translation

    DNA

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    A C C A A A C C G A G T

    ACTTTT CGGGGT

    U G G U U U G G C CU A

    SerGlyPheTrp

    Codon

    TRANSLATION

    TRANSCRIPTION

    Protein

    mRNA 5

    5

    3

    Amino acid

    DNAtemplatestrand

    5

    3

    3

    Figure 17.5Second mRNA base

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    Third

    mRNAbase

    (3

    endofcodon)

    FirstmRNAbase

    (5

    endofcodon)

    UUU

    UUC

    UUA

    UUG

    Phe

    Leu

    Leu

    Ile

    Val

    CUU

    CUC

    CUA

    CUG

    AUU

    AUC

    AUA

    AUG

    GUU

    GUC

    GUA

    GUG

    UCU

    UCC

    UCA

    UCG

    CCU

    CCC

    CCA

    CCG

    ACU

    ACC

    ACA

    ACG

    GCU

    GCC

    GCA

    GCG GAG

    GAA

    GAC

    GAU

    AAG

    AAA

    AAC

    AAU

    CAG

    CAA

    CAC

    CAU

    Ser

    Pro

    Thr

    Ala

    Glu

    Asp

    Lys

    Asn

    Gln

    His

    Tyr Cys

    Trp

    Arg

    Ser

    Arg

    Gly

    GGG

    GGA

    GGC

    GGU

    AGG

    AGA

    AGC

    AGU

    CGG

    CGA

    CGC

    CGU

    UGG

    UGA

    UGC

    UGUUAU

    UAC

    UAA

    UAG Stop

    Stop Stop

    Met or

    start

    U

    C

    A

    G

    U

    C

    A

    G

    U

    C

    A

    G

    U

    C

    A

    G

    U C A G

    G

    A

    C

    U

    Transcription overview

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    p. -

    Promoter Transcription unit

    RNA polymeraseStart point

    1

    Template strand of DNARNA

    transcript

    Unwound

    DNA

    RewoundDNA

    RNAtranscript

    Direction of

    transcription(downstream)

    Completed RNA transcript

    Initiation

    Elongation

    Termination

    2

    3

    5

    3

    5

    5

    3

    5

    3

    5

    3

    5

    5

    3

    3

    5

    3

    3

    5

    3

    5

    3

    Termination

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    Termination

    Bacteria: RNA poly. stops transcription at the terminatorand the mRNA

    can be translated without further modification

    In eukaryotes, RNA poly. transcribes thepolyadenylation signal

    sequence; the RNA transcript is released 1035 nucleotides past this

    polyadenylation sequence. This must get processed.

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    Exons, Domains, and Activity.

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    Exons, Domains, and Activity.

    Different domains on a protein can have different roles.

    By swapping domains between proteins you can engineer activity

    The Ribosome

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    Initiation

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    1 2

    P site

    3

    Largeribosomalsubunit

    Translation initiation complex

    Large ribosomal subunitcompletes the initiationcomplex.

    Small ribosomal subunit bindsto mRNA.

    mRNA binding site

    Smallribosomalsubunit

    InitiatortRNA

    Start codon35

    E A

    35

    GTP GDP

    P i+

    3 5

    5

    U A C

    GA U

    mRNA

    Elongation Amino end

    of polypeptide

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    of polypeptideCodon

    recognition1

    3

    5

    E

    P Asitesite

    E

    P A

    mRNA

    GTP

    Pi

    23GTP

    Pi

    GDP +

    GDP +

    Translocation

    E

    P A

    Peptide bond

    formation

    E

    P A

    Ribosome ready fornext aminoacyl tRNA

    Termination of Translation

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    31 2

    Releasefactor

    3

    55

    3

    Stop codon(UAG, UAA, or UGA)

    Ribosome reaches a

    stop codon on mRNA.

    Release factor

    promotes hydrolysis.

    Ribosomal subunits

    and other components

    dissociate.

    Freepolypeptide

    3

    5

    2 GTP

    2 GDP + 2 P i

    How does a ribosome find the ER?

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    Protein

    ER

    membraneSignal

    peptideremoved

    SRP receptor

    protein

    Translocation complex

    ER LUMEN

    CYTOSOL

    SRP

    Signal

    peptide

    mRNA

    Ribosome

    Polypeptide

    synthesisbegins.

    SRP

    binds tosignalpeptide.

    SRP

    binds toreceptorprotein.

    SRP

    detachesandpolypeptidesynthesisresumes.

    Signal-

    cleavingenzyme cutsoff signalpeptide.

    Completed

    polypeptidefolds intofinalconformation.

    1 2 3 4 5 6

    So how do errors in processing lead to mutations?

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    So how do errors in processing lead to mutations?

    Substitutions, additions, or deletions of even one base pair can make a big difference

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    Missense mutationsdifferent codon AND different AA

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    Additions or deletions can result in a frameshift mutation

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    CAMPBELL

    BIOLOGYCAMPBELL

    BIOLOGY

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    BIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    2014 Pearson Education, Inc.

    TENTH

    EDITIONBIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    TENTH

    EDITION

    18Regulation

    of Gene

    Expression

    Lecture Presentation by

    Nicole Tunbridge and

    Kathleen Fitzpatrick

    Regulating the rate of transcription

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    Operator regulation of gene expression

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    A sequence of DNA in promoter (the operator) binds activator or repressor proteins

    The DNA containing the promoter, operator, and gene is called an operon.

    Tryptophan is a corepressor which binds to a repressor protein.

    The trpOperon

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    The trpOperon

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    The lacOperon

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    Alternative splicing

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    CAMPBELL

    BIOLOGYCAMPBELL

    BIOLOGY

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    BIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    2014 Pearson Education, Inc.

    TENTH

    EDITIONBIOLOGYReece Urry Cain Wasserman Minorsky Jackson

    TENTH

    EDITION

    19Viruses

    Lecture Presentation by

    Nicole Tunbridge and

    Kathleen Fitzpatrick

    Virus

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    Virus- an infectious particle consisting of nucleic acids packaged in a

    protein coat (with or without a membrane)

    Cannot reproduce or carry out metabolism outside of a host cell

    Alive? Not alive?

    Genomes

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    Viral genomes may consist of either

    Double- or single-stranded DNA or RNA

    A DNA virus or RNA virus

    The genome is either a single linear orcircular molecule of the nucleic acid

    Viruses have between three and several

    thousand genes in their genome

    Genomes

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    Membranes can be derived from host cells

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    Lytic cycle1 Attachment

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    2 Entry of phageDNA and

    degradationof host DNA

    3 Synthesis of viralgenomes andproteins

    4 Self-assembly

    5 Release

    Phage assembly

    Head Tail Tailfibers

    Prions

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    Slow-acting, virtually indestructible infectious

    proteins that cause brain diseases in mammals

    Scrapie in sheep, mad cow disease, Creutzfeldt-Jakob disease, Kuru, glaucoma, certain diabeties

    all caused by prions