roebe 0.5.187

data/lib/roebe/www/microbiology/microbiology.rb

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+english('Microbiology') {
+autoextend
+ruby_favicon
+default_template '
+
+a,
+a:link  { text-decoration: none; color: steelblue; font-weight: bold;}
+a:hover { text-decoration: underline; color: royalblue; font-weight: bold;}
+
+p, 
+p.default {
+  margin:   0.3em;
+  padding:  0.6em;
+}
+div.default {
+  margin:   8px;
+  padding: 12px;
+}
+'
+body_css_class 'mar0px s2px padt2px VERDANAs'
+body_css_style 'background-color: #d3d2d1;'
+default_font_size_and_hyperlinks
+
+smaller_width('mar0px pad0px s0_8em') {
+  h1 dot(105, 'marr8px')+
+     'Microbiology',
+     'mart1px marb0_5em'
+  # ========================================================================= #
+  # === Bacterias
+  # ========================================================================= #
+  fancy3 'Bacteria','martb8px'
+  p_default_le('ind0 FW4'){
+    e 'Here is a textbook - everything about microbes.'
+    br
+    a 'http://textbookofbacteriology.net/',
+       content: '→ All about Microbes',
+       css_class: 'BOLD mars1em'
+  }
+  # ========================================================================= #
+  # === Phantom microbes
+  # ========================================================================= #
+  fancy3 'Phantom microbes','martb8px'
+  p_default_le {
+    e "The so-called <b>'phantom microbes'</b> can not be cultured.
+    We know about them because we can <b>use modern genomic techniques
+    to expose their existence</b>."
+  }
+  # ========================================================================= #
+  # === Streptococcus pyogenes
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#streptococcus_pyogenes
+  # ========================================================================= #
+  fancy3 'Streptococcus pyogenes','martb8px'
+  p_default_le(id: 'streptococcus_pyogenes') {
+    e 'The natural environment - or, at the least, a popular environment -
+    for <i>Streptococcus pyogenes</i> is <b>the human oral cavity</b>. Due
+    to this environment, S. pyogenes does not need to synthesize glutamtic
+    acid and alanine. It has thus <b>lost the genes</b> whose protein
+    products synthesize tehse aminoacids.'
+  }
+  # ========================================================================= #
+  # === Spirochete
+  # ========================================================================= #
+  fancy3 'Spirochete','martb8px'
+  p('ind0 FW4'){
+    e '<b>Spirochete</b> have a fairly interesting shape. The following
+    image shows this:'
+    br
+    dimg 'science/microbiology/Spirochete.jpg',
+         'round_black2 mars2em'
+  }
+  # ========================================================================= #
+  # === Die Gramfärbung
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#gramf%C3%A4rbung_schritte
+  # ========================================================================= #
+  fancy3 'Gramfärbung - Schritte:','martb8px'
+  div_default_le('martb8px') {
+    p_default_le {
+      e '- Hitzefixierung'
+      e '- Kristallviolet (Bakterien werden blau)'
+      e '- Safranin-Gegenfärbung'
+    }
+    p_default_le {
+      boldbr 'Examples of gram-positive bacteria:'
+    }
+    p_default_le {
+      counter 'Streptococcus','mars2em BOLD'
+      counter 'Staphylococcus','mars2em BOLD'
+      counter 'Propionibacterium','mars2em BOLD'
+      counter 'Nocardia','mars2em BOLD'
+      counter 'Streptomyces','mars2em BOLD'
+    }
+  }
+  # ========================================================================= #
+  # === Symbionts
+  # ========================================================================= #
+  fancy3 'Symbionts','martb8px'
+  div_default_le('martb5px') {
+    e 'A symbiont is an organism that lives in intimate association with
+    (at the least) a second organism.'
+  }
+  # ========================================================================= #
+  # === Quorum sensing in bacteria
+  # ========================================================================= #
+  fancy3 'Quorum sensing in bacteria','martb8px'
+  div_default_le('martb5px') {
+    e '<b>Quorum sensing</b> allows bacteria to <b>coordinate</b> their
+    behavior, including their motility, antibiotic production, spore
+    formation and sexual conjugation.'
+  }
+  # ========================================================================= #
+  # === E. coli TEMP cell wall
+  # ========================================================================= #
+  fancy3 'E. coli TEM cell wall picture','martb8px'
+  div_default_le('martb5px') {
+    dimg 'science/microbiology/Escherichia_coli_TEM_cell_wall.jpg',
+         'bblack2 mar1em'
+    br
+    e 'The <b>ATP operon</b> in <i>E. coli</i> is organized in the
+    following manner:'
+    br
+    dimg 'science/microbiology/ATP_OPERON_ECOLI.png',
+         'round_black2 mar1em'
+  }
+  # ========================================================================= #
+  # === Natural competence in bacteria                   (transformation tag)
+  #
+  # Natürliche Kompetenz in Bakterien.
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#natural_competence_in_bacteria
+  # ========================================================================= #
+  fancy3 'Natural competence in bacteria','martb8px'
+  div_default_le('martb5px') {
+    p_default_le('ind0 FW4'){
+      e 'The process of taking up extracellular DNA (== naked DNA)
+      from the environment is called transformation.'
+      br
+      e 'Natural competence was discovered by Frederick Griffith
+      in the year <b>1928</b>.'
+      br
+      e 'In 1944 it was discovered (by Oswald Avery and others)
+      that the <b>transforming factor</b> was DNA.'
+      br
+      e 'At the least the following bacteria have been found to
+      use <b>natural competence</b>:'
+      br; reset_the_counter
+      counter 'Bacillus subtilis','marl3em BOLD'
+      counter 'Streptococcus pneumoniae','marl3em BOLD'
+      counter 'Neisseria gonorrhoeae','marl3em BOLD'
+      counter 'Haemophilus influenzae','marl3em BOLD'
+      counter 'members of the Acinetobacter genus','marl3em BOLD'
+      br
+      e 'The first barrier to overcome is - quite logically - 
+      the cell membrane. DNA has to be transported across
+      the cell membrane.'
+      br
+      e 'Once inside the cell, two options are available:'
+      br
+      earrow 'The DNA may be degraded to individual nucleotides.',
+      'marl2em'
+      br
+      e 'or'
+      br
+      earrow "The DNA may recombine into the cell's genome by its DNA
+      repair enzymes. The latter option is the actual 
+      <b>transformation</b>.",'marl2em'
+      br
+      e 'Most naturally competent bacteria components make use
+      of extracellular filaments (the <b>type IV pili</b>,
+      a type of fimbria) to bind extracellular
+      double stranded DNA.'
+      br
+      selfy 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993363/' # === 2014
+    }
+  }
+  # ========================================================================= #
+  # === Bacteria and disease
+  # ========================================================================= #
+  fancy3 'Bacteria and disease','martb8px'
+  div_default_le('martb5px') {
+    e 'The causative agent of syphilis is <i>Treponema pallidum</i>,
+    a <b>spirochaete</b>. The drug <b>Salvarsan</b> was historically
+    used to combat this microorganism.'
+  }
+  # ========================================================================= #
+  # === Flagella in Bacteria
+  # ========================================================================= #
+  div(id: 'flagella') {
+    fancy3 'Flagella in Bacteria'
+    boldbr 'Peritrichous flagella:'
+    dimg 'science/microbiology/peritrichous_flagella.png',
+         'bblack2 mar1em mars3em'
+    br
+    boldbr 'Lophotrichous flagella:'
+    dimg 'science/microbiology/lophotrichous_flagella.png',
+         'bblack2 mar1em mars3em'
+    br
+    boldbr 'Polar flagella:'
+    dimg 'science/microbiology/polar_flagella.png',
+         'bblack2 mar1em mars3em'
+    br
+    e 'The electron microscopy image in gram-negative bacteria
+    looks like this:'
+    br
+    dimg 'science/microbiology/flagellum_in_gram_negative_bacteria.png',
+         'bblack3 mars3em'
+  }
+  # ========================================================================= #
+  # === Bakterien auf den Händen.
+  #
+  # 04.11.2008
+  #
+  # URL: https://science.orf.at/science/news/153184
+  # ========================================================================= #
+  div {
+    datum '04.11.2008','BG_Black pad0_5em gold'
+    fancy2 'Bakterien auf den Händen'
+    e 'Frauen haben mehr Bakterien an den Händen als Männer. Der Grund liegt
+    sehr wahrscheinlich darin begründet, dass der saure Schweiß der Männer
+    für diesen Unterschied verantwortlich ist.'
+    br
+    e 'An unseren Händen tummeln sich pro Quadratzentimeter mehr als zehn 
+    Millionen Bakterien.'
+    br
+    e 'Im <b>PNAS</b> (doi: <b>10.1073/pnas.0807920105</b>)
+    "<i>The influence of sex, handedness, and washing on the
+    diversity of hand surface bacteria</i>" wird berichtet das die
+    Handinnenflächen quasi der "<i>tropische Regenwald der Epidermis</i>"
+    sind: Satte 4.700 verschiedene Bakterienarten fanden sich auf
+    den 102 analysierten Händen.'
+    br
+    e 'Interessanterweise dürfte das <b>bakterielle Profil</b> eine
+    recht individuelle Angelegenheit sein, denn davon kamen nur fünf
+    auf allen Händen vor.'
+    br
+    e 'Selbst zwischen rechter und linker Hand derselben Testperson
+    gab es beträchtliche Unterschiede. Die Übereinstimmung betrug,
+    nach Arten gerechnet, lediglich 17 Prozent - was nicht viel
+    mehr ist als die Deckung zweier zufällig ausgewählter Hände,
+    nämlich 13 Prozent.'
+    br
+    e 'Frauen besitzen <b>mehr Bakterienarten</b> auf ihren
+    Händen als Männer.'
+    br
+    e 'Die Unterschiede im Artenspektrum könnte man mit dem
+    <b>pH-Wert des Schweißes</b> erklären.'
+    br
+    e 'Aus Studien an anderen Ökosystemen weiß man, dass ein
+    niedriger pH-Wert der Bakterienvielfalt eher abträglich ist.'
+    br
+    e 'Händewaschen beeinflusst der Studie zufolge die bakterielle
+    Vielfalt kaum.'
+  }
+  # ========================================================================= #
+  # === Transcription in bacteria
+  # ========================================================================= #
+  fancy2 'Transcription in <i>bacteria</i>'
+  div_default {
+    e 'The σ-factor (sigma-factor) is important to detect
+    promoters. This is also called discrimination, e. g.
+    to discriminate between different DNA sequences. After
+    initiation of transcription the σ-factor dissociates
+    from the complex assembled around the RNA polymerase
+    again.'
+  }
+  # ========================================================================= #
+  # === Kanamycin tag
+  # ========================================================================= #
+  fancy2 'Kanamycin <span class="subtitle">Antibiotikum</span>'
+  div(id: 'kanamycin') {
+    e '<b>Kanamycin</b> ist ein <b class="ud">Aminoglycosid-Antibiotikum</b> 
+    aus <b>Streptomyceten</b> (Streptomyces kanamyceticus).'
+    br
+    e 'Es ist ein basisches, stark polares Oligosaccharid, farblos, gut 
+    wasserlöslich und im pH-Bereich von 2,2 - 10,0 lösungsstabil.'
+    br
+    e 'Kanamycin durchdringt die bakteriellen Zellmembranen durch passive 
+    Diffusion oder durch sauerstoffabhängigen, aktiven Transport. Es lagert 
+    sich an die 30S-Untereinheit membranassoziierter bakterieller Ribosomen 
+    an und hemmt damit die (bakterielle) Proteinsynthese.'
+    br
+    e 'In der <b>Humanmedizin</b> wird es als <b>Sulfatsalz</b> in Form 
+    von Augentropfen/salben eingesetzt. Handelsübliches Kanamycin ist ein 
+    Gemisch aus den Kanamycinen A, B und C.'
+    br
+    e 'Eine typische Infektion des <b>Lidrandes</b> ist beispielsweise 
+    das Gerstenkorn. Dabei handelt es sich um eine akute Infektion der 
+    Schweißdrüsen am Rand des Auges oder an der Talgdrüse im Lid 
+    mit eitererregenden Bakterien (<b>Staphylokokken</b>).'
+  }
+  # ========================================================================= #
+  # === Phosphotransferase
+  # ========================================================================= #
+  div(id: 'phosphotransferase') {
+    h4 'Phosphotransferase'
+    dimg 'science/chemistry/PHOSPHOTRANSFERASESYSTEM.jpg',
+         'bblack3'
+  }
+  # ========================================================================= #
+  # === The trp-operon                                              (trp tag)
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#trp
+  # ========================================================================= #
+  fancy2 'The trp-operon in bacteria'
+  div_default_le(id: 'trp') {
+    e "Let's look at the <b>trp operon</b> in <i>E. coli</i> next."
+    br
+    e 'This operon codes for the necessary biosynthetic enzymes that
+    will ultimately synthesize the amino acid tryptophan.'
+    br
+    e 'The trp operon is turned on - that is, expressed - when tryptophan
+    levels are low. Conversely it is turned off - that is, repressed -
+    when the tryptophan levels are high.'
+    br
+    e 'The trp operon is regulated by the <b>trp repressor</b>.
+    This repressor, when bound to tryptophan, will block
+    the expression of the operon.'
+    br
+    e 'If tryptophan is available in the environment then <i>E. coli</i>
+    will take it up and use it to build proteins. Under this condition
+    tryptophan will not be synthesized by <i>E. coli</i>.'
+    br
+    e 'The <b>trp operon</b> in <i>E. coli</i> consists of <b>five
+    structural genes</b>, called
+    <b>trpE</b> (encodes enzyme Anthranilate synthase I),
+    <b>trpD</b> (encodes the enzyme Anthranilate synthase II),
+    <b>trpC</b>, <b>trpB</b>, and <b>trpA</b>. TrpA and TrpB
+    are the two subunits of the <b>tryptophan synthetase</b>.'
+    br
+    e 'The operon has a so-called <b>leader sequence</b> upstream
+    of the coding region of the trpE structural gene. This leader
+    sequence encodes a 14 amino acid leader peptide containing
+    two tryptophan residues one after the other.'
+    br
+    e 'The repressor is encoded by gene <b>trpR</b>.'
+    br
+    e 'The trp operator region partly overlaps the trp
+    promoter.'
+    br
+    e 'If tryptophan is present then the trpR protein will bind
+    to the operator, which will block transcription of the trp
+    operon by the RNA polymerase.'
+    br
+    e '<b>Tryptophan biosynthesis</b> is additionally regulated by
+    a process called <b>attenuation</b> - a mechanism based on
+    coupling of transcription and translation. This is a second
+    mechanism of negative feedback in the trp operon, interestingly
+    enough. This secondary regulation, via attenuation, responds
+    to the concentration of charged tRNAtrp. Rather than blocking
+    initiation of transcription, <b>attenuation</b> prevents
+    <b>completion</b> of transcription.'
+    br
+    e 'Thus, the trpR repressor decreases gene expression by
+    altering the initiation of transcription, whereas attenuation
+    does so by altering the process of transcription that is
+    already in progress. In this role, tryptophan is said to be
+    a <b>co-repressor</b>. It is called <b>negative control</b>,
+    because <b>the bound repressor prevents transcription</b>.'
+    br
+    e 'While the TrpR repressor decreases transcription by a
+    factor of 70, attenuation can further decrease it by a
+    factor of 10, thus allowing accumulated repression of
+    about <b>700-fold</b>.'
+    br
+    e 'Attenuation is made possible by the fact that in prokaryotes
+    the ribosomes begin translating the mRNA while the RNA polymerase
+    is still transcribing the DNA sequence. This allows the process of
+    translation to affect transcription of the operon directly. The
+    process of attenuation involves the presence of a stop signal
+    that indicates premature termination.'
+    br
+    e "When levels of tryptophan are high, attenuation causes
+    RNA polymerase to stop prematurely when it is transcribing
+    the trp operon. Only a short mRNA is made, not encoding any
+    of the tryptophan biosynthesis enzymes. Attenuation works
+    through a mechanism that depends on coupling (the
+    translation of an mRNA that is still in the process of
+    being transcribed)."
+    br
+    e 'At the beginning of the transcribed genes of the trp
+    operon is a sequence of at least 130 nucleotides termed
+    the leader transcript: <b>trpL</b>,
+    see <a href="https://www.ncbi.nlm.nih.gov/protein/NP_415781.1?report=fasta">
+    NP_415781.1</a>.'
+    br
+    e 'Lee and Yanofsky found that the attenuation efficiency is
+    correlated with the stability of a secondary structure embedded
+    in trpL. Hairpins will form that give rise to a
+    terminator structure, as elucidated by Oxender et al. in 1979.'
+    br
+    e 'This transcript includes four short sequences, designate
+    1, 2, 3 and 4.'
+    br
+    e 'These sequences are partially complementary to the next one.'
+    br
+    e 'Thus, three distinct hairpins, as secondary structures,
+    can form.'
+    br
+    e 'These are:'
+    br
+    cmd '1-2'
+    cmd '2-3 # formed when there is a lack of tryptophan'
+    cmd '3-4 # formed when tryptophan is in abundance; this 
+    is then called the <b>attenuator</b>'
+    br
+    e 'From the above, it can be logically inferred that region
+    3 is complementary to both region 2 and region 4.'
+    br
+    embed_remote_image 'https://textimgs.s3.amazonaws.com/boundless-microbiology/trp-operon-attenuation.svg#fixme',
+                       'mar1em bblack3'
+    br
+    e 'This is all made possible by RNA-to-RNA base pairings -
+    thus <b>hairpin loops</b>.'
+    br
+    e 'Hybridization of sequences 1 and 2 to form the 1-2 structure
+    is rare because the RNA polymerase waits for a ribosome to
+    attach before continuing transcription past sequence 1.
+    If, however, 1-2 hairpin were to form it would prevent the
+    formation of the 2-3 structure (but not 3-4).'
+    br
+    e 'The formation of a hairpin loop between sequences 2-3 prevents
+    the formation of hairpin loops between both 1-2 and 3-4.'
+    br
+    e 'The 3-4 structure is a transcription termination sequence
+    (abundant in G/C and immediately followed by several uracil
+    residues). Once it forms RNA polymerase will disassociate
+    from the DNA and transcription of the structural genes of
+    the operon can not occur.'
+    br
+    e 'Part of the leader transcript codes for a short polypeptide
+    of 14 amino acids, termed the leader peptide. This peptide
+    contains two adjacent tryptophan residues, which is unusual,
+    since tryptophan is a fairly uncommon amino acid (about one
+    in a hundred residues in a typical E. coli protein is
+    tryptophan).'
+    br
+    e 'The strand 1 in trpL encompasses the region encoding the
+    trailing residues of the leader peptide: Trp, Trp, Arg, Thr,
+    Ser.'
+    br
+    dimg 'science/biology/operons/the_trp_operon.png',
+         'bblack3 mar1em mars3em BG_White'
+  }
+  # ========================================================================= #
+  # === Magnet-Bakterien
+  # ========================================================================= #
+  fancy3 'Magnet-Bakterien'
+  div_default {
+    e 'Das klassische Magnet-Bakterium schlechthin ist
+    <b>Magnetospirillum magnetotacticum</b>.'
+    br
+    selfy 'https://de.wikipedia.org/wiki/Magnetospirillum_magnetotacticum'
+  }
+  # ========================================================================= #
+  # === The bacterial SRP - an example for a co-translational process
+  # ========================================================================= #
+  fancy3 'The bacterial SRP - an example for a co-translational process'
+  div_default {
+    e 'The <b>SRP</b> is the signal-recognition particle, a
+    <b>ribonucleoprotein</b>. It is important for the proper localization
+    of newly synthesized proteins and can be found in the <b>cytosol</b>
+    of a cell. It can recognize and bind to the signal peptide of such
+    newly synthesized proteins.'
+    br
+    e 'The SRP will deliver the complex of ribosome and mRNA towards the
+    rough endoplasmic reticulum (RER) and will then bind to the SRP
+    receptor there.'
+    br
+    e 'In bacteria, about 30% of the newly synthesized proteins may be
+    relocated towards the bacterial plasma membrane.'
+    br
+    e 'The SRP is ultimately a <b>protein targeting machine</b>.
+    Its receptor is membrane-bound. The SRP exists in both
+    eukaryotes and prokaryotes - at the least as a homologue.'
+    br
+    e 'The typical composition of the SRP is of the following
+    six polypeptides, named after their molecular weight:'
+    br
+    cmd '  SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72'
+    br
+    e 'In addition to that the 7SL-RNA can be seen here, also
+    known as SRP-RNA. The 7SL RNA is also a precursor of the
+    <b>Alu elements</b> in the human genome.'
+    br
+    e 'In Eukaryotes, SRP-mediated protein targeting is a
+    cotranslational process that begins when a nascent
+    polypeptide destined for the ER or plasma membrane
+    emerges from the ribosome.'
+    br
+    e 'Important here is the N-terminal signal sequence on
+    the nascent polypeptide. This is the signal that
+    allows the cargo to engage the SRP. Through interaction
+    with the SRP receptor it is then delivered to the
+    vicinity of the <b>Sec61p</b> - or <b>SecYEG</b> in
+    prokaryotes translocon at the target membrane.'
+    br
+    e 'Interestingly, the bacterial SRP, though highly simplified
+    compared to those in eukaryotes, can replace their
+    mammalian homologues to mediate efficient targeting
+    of mammalian proteins to the ER. The functional core of
+    the SRP is thus sufficient for protein targeting and it
+    can be represented by the bacterial machinery even in
+    eukaryotic cells. The bacterial FtsY can be found at
+    the plasma membrane.'
+    br
+    e 'The bacterial SRP contains the universally conserved
+    <b>SRP54 protein</b> - called Ffh in bacteria - bound
+    to the 4.5S SRP RNA. Ffh has two primary domains:'
+    br
+    e '- a methionine-rich M-domain. This domain recognizes the
+    signal sequence and binds to the SRP RNA.'
+    e '- a special GTPase (the NG-domain). This one interacts
+    with the NG-domain in the SR.'
+    br
+    e 'The <b>cotranslational SRP pathway</b> minimizes the
+    aggregation or misfolding of nascent proteins before they
+    arrive at their cellular destination.'
+    br
+    e 'Links:'
+    br
+    abr 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805129/',
+        content: 'Signal Recognition Particle: An essential protein targeting machine (Feb 2013)',
+        css_class: 'BOLD mars1em'
+  }
+  # ========================================================================= #
+  # === Infektionen
+  # ========================================================================= #
+  fancy2 'Infektionen'
+  p_default_le {
+    e 'Der häufigste natürliche Verlauf einer Infektionskrankheit ist die
+    akute, ausheilende Infektion.'
+  }
+  # ========================================================================= #
+  # === Topoisomerases in Bacteria
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#topoisomerases_in_bacteria
+  # ========================================================================= #
+  fancy2 'Topoisomerases in Bacteria'
+  p_default_le(id: 'topoisomerases') {
+    e '<b>Topoisomerases</b> are <b>enzymes</b> (group: <b class="italic">
+    isomerases</b>) that <b>catalyze changes in the topological state of
+    DNA</b> - in other words, they can <b>alter DNA topology</b> by
+    interconverting relaxed and supercoiled forms of DNA into one another.
+    (This activity may also be called <b>relaxing supercoiled DNA</b>.'
+    dimg 'science/molecular_biology/topoisomerase.avif',
+         'round_black3 mar0_5em marl3em'
+    br
+    e 'Topological issues in DNA arise due to the intertwined nature
+    of its double-helical structure, such as <b>during DNA replication</b>
+    and transcription. Without the actions of Topoisomerases, 
+    RNA and DNA polymerases could not progress along the DNA.'
+    br
+    e 'The processes of DNA supercoiling and transcription are
+    interdependent because the movement of a transcription
+    elongation complex simultaneously induces under- and overwinding
+    of the DNA duplex.'
+    br
+    e 'The first DNA topoisomerase was <b>discovered</b> in bacteria
+    by James Wang in the year <b>1971</b>. It is now called
+    <b>Escherichia coli (<i>E. coli</i>) topoisomerase I (topo I)</b>.'
+    br
+    e 'DNA topoisomerases are '+sspan('classified','underline')+
+    ' based on whether they create a single- or double-stranded break
+    in the DNA phosphodiester backbone.
+    class I (EC 5.99.1.2) uses single-stranded breaks;
+    class II (EC 5.99.1.3) uses double-stranded breaks.'
+    br
+    e 'class I is further subdivided into IA and IB. Its
+    active site contains the amino acid tyrosine.'
+    br
+    e 'class II can introduce negative supercoils into DNA.'
+    br
+    e 'Topoisomerase II is also called <b>DNA-Gyrase</b>. It
+    contains two subunits: GyrA and GyrB.'
+    br
+    e 'All known <b>eukaryotic topoisomerases</b> <b>can only relax
+    DNA</b>.'
+    br
+    e 'Inserting supercoils into DNA requires energy from ATP,
+    whereas releasing supercoils does not.'
+    br
+    e 'Eukaryotes do not make use of supercoiling, as their genomic
+    DNA is linear rather than circular.'
+    br
+    e '<b>Type I topoisomerases</b> can be inhibited via 
+    <b>Irinotecan</b> and <b>Topotecan</b>.'
+    br
+    e '<b>Type II topoisomerases</b> can be inhibited via
+    <b>Etoposid</b>, <b>Teniposid</b> and
+    <b>Doxorubicin</b>. In general the fluoroquinolones
+    are potent inhibitors of prokaryotic type II
+    topoisomerases.'
+    br
+    boldbr 'Links:'
+    br
+    selfy 'https://academic.oup.com/nar/article/40/20/10432/2414715',
+           css_class: 'mars1em BOLD' # 2012
+    selfy 'https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397423/',
+           css_class: 'mars1em BOLD' # 2013
+    selfy 'https://bmcmolcellbiol.biomedcentral.com/articles/10.1186/s12860-019-0211-6',
+           css_class: 'mars1em BOLD' # 2019
+  }
+  # ========================================================================= #
+  # === Disinfectants
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#disinfectants
+  # ========================================================================= #
+  fancy2 'Disinfectants',
+     id: 'disinfectants'
+  div_default_english {
+    e '<b>Alcohol</b> can be used as a disinfectant against microorganisms.
+    Interestingly enough, the concentration for this is more effective
+    below 100%; typically a concentration of 70% is used. This is because
+    the denaturation of proteins - but also membranes - proceeds more
+    effectively in the presence of water. For similar reasons, alcohol
+    will be more damaging to microbial membranes if there is water
+    available.'
+    br
+    e '<b>Moist heat</b> is also <b>more effective</b> than <b>dry heat</b>
+    for the same reasons.'
+  }
+  # ========================================================================= #
+  # === Das Diphtherietoxin Toxin
+  # ========================================================================= #
+  fancy2 'Das Diphtherietoxin Toxin'
+  div_default_english {
+    e 'Das A-Fragment des Dipthetire-Toxins bewirkt im Zytosol
+    eine ADP-Ribosylierung des Elongationsfaktors EF2.'
+  }
+  # ========================================================================= #
+  # === Aquaporins
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#aquaporins
+  # ========================================================================= #
+  fancy2 'Aquaporins'
+  div_default_english {
+    e 'Aquaporins can increase the rate of diffusion of water and
+    glycerol across cell membranes.'
+    br
+    e 'Not all bacteria contain aquaporins - for instance,
+    <b>aqpZ</b> was found in all four <b>Escherichia coli</b>
+    strains for which whole genome sequences were available
+    (in 2002), as well as in <i>Shigella flexneri</i>. It
+    does, however had, not occur in the closely related
+    bacteria such as <i>Salmonella enterica serovar Typhimurium</i>
+    or in <i>Yersinia pestis</i>.'
+    br 
+    selfy 'https://journals.asm.org/doi/10.1128/JB.184.15.4304-4307.2002' # 01.08.2002
+  }
+  # ========================================================================= #
+  # === The two-component regulatory system in prokaryotes
+  # ========================================================================= #
+  # http://localhost/programming/ruby/src/roebe/lib/roebe/www/microbiology/microbiology.cgi#the_two-component_regulatory_system_in_prokaryotes
+  # ========================================================================= #
+  fancy2 'The two-component regulatory system in prokaryotes'
+  div_default_english {
+    e '<i>Bacteria</i> must be able to sense their environment.'
+    br
+    e 'One sensor-system widespread among them is the
+    <b>two-component regulatory system</b>.'
+    br
+    e 'Here, the so-called <b>sensor kinase</b> (a <b>histidine kinase</b>)
+    will auto-phosphorylate itself, at a histidine.'
+    br
+    e 'The activity of the response regulator in the <b>two-component
+    systems</b> depends on the level of phosphorylation. The phosphate
+    group is passed to the response regulator, which typically has a
+    slow phosphatase activity to remove that phosphate group again.
+    Alternatively another protein will remove that phosphate group
+    and thus reset the system to its default state.'
+    br
+    e '<i>E. coli</i> has about 50 different two-component systems. One of
+    these is the OmpC / OmpF systems (two porines). They will regulate
+    the osmotic pressure in <i>E. coli</i>.'
+    br
+    selfy 'https://en.wikipedia.org/wiki/EnvZ/OmpR_two-component_system'
+  }
+  # ========================================================================= #
+  # === Cell division in bacteria
+  # ========================================================================= #
+  fancy2 'Cell division in bacteria'
+  p_default_le {
+    e '<b>FtsA</b> and <b>ZipA</b> anchor the Z-ring into the cytoplasmic
+    membrane.'
+  }
+  # ========================================================================= #
+  # === Flechten
+  # ========================================================================= #
+  fancy2 'Flechten'
+  p_default_le {
+    e 'Flechten treten oft als Erstbesiedler auf neu entstandenen
+    kahlen Felsflächen auf.'
+  }
+  # ========================================================================= #
+  # === Aufbau und Funktion des Zwei-Komponenten System.
+  # ========================================================================= #
+  fancy2 'Aufbau und Funktion des Zwei-Komponenten-System BvgSA'
+  div_default {
+  	lembre '- membranständige Histidinkinase BvgS'
+  	lembre '- zytoplasmatischer Transkriptionsfaktor BvgA'
+  	br
+    e '<b>BvgS</b> ist das Sensorprotein, das Umweltreize mittels einer
+    Serie von Phosphorylierungsreaktionen, die letztlich zur Aktivierung
+    von BvgA führen, in ein zelluläres Signal umwandelt. BvgA bindet 
+    daraufhin an die Promotoren der Virulenzgene und induziert deren 
+    Transkription.'
+    br
+    e 'BvgAS gehört zur kleinen Gruppe der unorthodoxen Systeme, die
+    eine komplexere Domänenstruktur besitzen als die typischen
+    Zwei-Komponenten-Systeme:'
+    br
+    e 'So besitzt das BvgS Protein C-terminal zusätzliche 
+    Domänen, die in klassischen Sensorproteinen nicht vorkommen. 
+    Bei diesen unorthodoxen Systemen erfolgt ein über mehrere Domänen 
+    ablaufender zwischen Histidin- und Aspartatresten alternierender 
+    Phosphorelay.'
+    br
+    e 'Durch Mutations- und Komplementationsanalysen kann gezeigt 
+    werden, daß die zusätzlichen BvgS Domänen für die Funktion von 
+    BvgS essentiell sind und der Phosphorelay obligat ist. Durch den 
+    Vergleich mit dem strukturell ähnlich gebauten EvgAS 
+    Zwei-Komponenten-Systems von E. coli kann auch die der 
+    C-terminalen BvgS Domäne bei der Spezifität der Signalübertragung 
+    auf das Regulatorprotein BvgA belegt werden.'
+    br
+    e 'Die Expression dieser Faktoren wird durch Umweltfaktoren wie
+    zum Beispiel die Temperatur gesteuert.'
+  }
+  # ========================================================================= #
+  # === Slogans tag
+  # ========================================================================= #
+  h1 'Slogans'
+  p('mars2em') {
+    e 'The science of microbiology is all about <b>microorganisms</b>.'
+    br
+    e 'Microbiology is the study of the dominant form of life on Earth.'
+    br
+    e 'Microscopy is foundational to microbiology.'
+    br
+    e 'In microbiology the word <b>growth</b> refer to the increase in cell
+    number as a result of cell division.'
+    br
+    e 'The ability to grow microorganisms rapidly under controlled conditions
+    makes them highly useful for experiments that probe the fundamental
+    processes of life.'
+    br
+    e 'In nature, microbial cells typically live in groups called microbial
+    communities.'
+    br
+    e 'Microorganisms have the ability to sense and respond to
+    changes in their local environment.'
+    br
+    e "Cyanobacteria began the slow process of oxygenating Earth's
+    atmosphere."
+    br
+    e 'There are an estimated 2 * 10³⁰ microbial cells on Earth.'
+    br
+    e "The total amount of carbon present in all microbial cells
+    is a significant fraction of Earth’s biomass."
+    br
+    e 'Microbes represent <b>a major fraction of the total DNA in
+    the biosphere</b> - about <b>31%</b>.'
+    br
+    e 'Extremophiles and their properties define the physiochemical
+    limits to life as we know it.'
+    br
+    e 'Most microorganisms are not harmful to humans but instead are
+    beneficial. In many cases they are even essential to human 
+    welfare and the functioning of the planet.'
+    br
+    e 'Microbes are intimately associated with the foods we eat.'
+    br
+    e 'Fermentation products affect the flavor and taste of foods.'
+    br
+    e 'Biofilms are of great importance in medicine, as biofilms
+    that form on implanted medical devices can cause infections
+    that are extremely difficult to treat.'
+    br
+    e 'Microbial diversity in the human colon is quite high.'
+    br
+    e 'Microorganisms in wastewater treatment are essential to 
+    sanitation and human health. Waterborne diseases such as 
+    cholera or typhoid can proliferate in the absence of proper
+    wastewater treatment, which reinforces the notion that this
+    is vital to human health.'
+    br
+    e 'The goal of bioremediation is to accelerate the cleanup 
+    process and degrade the pollutants in the environment.'
+    br
+    e 'Microscopes provide an essential portal though which
+    microbiologists can gaze into the world of microbes.'
+    br
+    e 'Although staining is widely used in light microscopy,
+    staining often kills cells and can distort their
+    features.'
+    br
+    e 'Dark-field microscopy is a particularly good way to
+    observe microbial motility, as bundles of flagella are
+    often resolvable with this technique.'
+    br
+    e 'Fluorescence microscopy using DAPI is widely used in
+    clinical diagnostic microbiology. It is also used in
+    microbial ecology for enumerating bacteria in a natural
+    environment or in a cell suspension.'
+    br
+    e 'Sterile means "without the presence of living organisms".
+    Aseptic techniques are essential for the isolation and 
+    maintenance of pure cultures of bacteria.'
+    br
+    e 'Pasteur discovered that microorganisms could
+    discriminate between optical isomers.'
+    br
+    e 'Proof that some microorganisms can cause disease
+    provided the greatest impetus for the development
+    of microbiology as an independent biological science.'
+    br
+    e "Kochs postulates link cause and effect in an infectious
+    disease."
+    br
+    e 'Richard Petri developed the transparent double-sided 
+    "Petri dish" in 1887, which became the standard tool
+    for obtaining pure cultures.'
+    br
+    e "Koch's crowning scientific accomplishment was his
+    <b>discovery of the causative agent of tuberculosis</b>."
+    br
+    e 'The bacterium that causes tuberculosis, Mycobacterium 
+    ­tuberculosis, is very difficult to stain because M. 
+    tuberculosis cells contain large amounts of a waxlike
+    lipid in their cell walls.'
+    br
+    e 'Beijerinck devised a precise chemically defined medium to 
+    isolate rhizobia and prove that they are responsible for the
+    formation of the root nodules of legumes.'
+    br
+    e 'Chemolithotrophy is the oxidation of inorganic compounds
+    to yield energy.'
+    br
+    e 'Chemolithotrophic bacteria obtain their carbon from CO₂.'
+    br
+    e 'Microbiologists realized that the ability to grow bacteria
+    rapidly and in controlled laboratory conditions made them
+    excellent model systems in which to explore the fundamental
+    nature of life.'
+    br
+    e 'The use of microbes as metabolic model systems led to the
+    important discovery that certain macromolecules and biochemical
+    reactions are universal. If one is to understand their function
+    in one cell one may be able to understand their function in
+    all cells (to some extent).'
+    br
+    e "Griffith's experiment showed that bacteria can transfer
+    genetic information."
+    br
+    e 'The term "Monera" is an antiquated term used to refer to
+    prokaryotic cells.'
+    br
+    e 'The ability of microbiologists to culture the microbial
+    diversity that abounds in nature has lagged behind the
+    ability to detect this diversity in the lab, via molecular
+    techniques.'
+    br
+    e 'Bacteria typically have a length that ranges from 1
+    to 10 μm.'
+    br
+    e 'More than 90% of bacteria in cultivation belong to one of
+    only four phyla: <b>Actinobacteria</b>, <b>Firmicutes</b>,
+    <b>Proteobacteria</b>, and <b>Bacteroidetes</b>.'
+    br
+    e "- Prokaryotes catalyze unique and indispensable
+    transformations in the biogeochemical cycles of the
+    biosphere, produce important components of the earth's
+    atmosphere, and represent a large portion of life's
+    genetic diversity."
+    br
+    e 'The bacterium <b>Epulopiscium</b> reaches a length of
+    700 μm.'
+    br
+    e 'Bacterial phyla are billions of years old and this
+    time has allowed for extensive diversification.'
+    br
+    e 'While Archaea are quite diverse in their physiology,
+    cultured isolates have less morphological diversity than
+    Bacteria.'
+    br
+    e 'Methanogens (<i>Archaea</i>) are common in the guts of
+    animals - including humans.'
+    br
+    e '<i>Thaumarchaeota</i> are important contributors to the
+    global nitrogen cycle.'
+    br
+    e 'The <b class="italic">nanoflagellates</b> are microbial
+    predators that can be as small as 2 μm long.'
+    br
+    e 'The bacterial flagellum rotates like a propeller and is
+    powered not by ATP but by the proton motive
+    force (PMF).'
+    br
+    e 'Genomic studies of motile Archaea revealed that the
+    archaellum does have a structural counterpart in
+    Bacteria: the <b>type IV pilus</b>.'
+    br
+    e 'Cell morphologies in bacteria form a continuum, with some
+    shapes, such as rods and cocci, being very common, whereas
+    others, such as spiral, budding, and filamentous shapes,
+    being less common.'
+    br
+    e 'Bacteria may have evolved an optimal cell shape in order
+    to maximize nutrient uptake for survival in nutrient-limiting
+    environments. This is in particular important for the
+    consideration of a high surface-to-volume ratio.'
+    br
+    e 'Thiomargarita namibiensis (a large sulfur chemolithotroph)
+    is presently the largest known of all prokaryotic cells.'
+    br
+    e 'How fast a prokaryotic cell can grow depends in part on
+    the rate at which it can exchange nutrients and waste
+    products with its environment.'
+    br
+    e 'Amoebae use phagocytosis to ingest their prey via
+    phagocytosis.'
+    br
+    e 'The lipids of Archaea contain <i>ether</i>.'
+    br
+    e 'The cytoplasmic membrane of Bacteria and Archaea plays
+    a major role in energy conservation.'
+    br
+    e 'The normal microflora is highly dependent on the
+    conditions to which an individual is exposed to.'
+    br
+    e 'The cell wall of Bacteria and Archaea functions
+    to prevent osmotic lysis and gives the cell its shape.'
+    br
+    e 'The cytoplasm of prokaryotic cells maintains a
+    high pressure that is comparable to the pressure of
+    an automobile tire.'
+    br
+    e 'The cell wall confers shape and rigidity onto the
+    bacterial cell.'
+    br
+    e 'Antibiotics such as the penicillins and cephalosporins,
+    target bacterial cell wall synthesis, leaving the cell
+    susceptible to osmotic lysis.'
+    br
+    e 'As much as 90% of the cell wall of a gram-positive
+    bacterium can consist of peptidoglycan.'
+    br
+    e 'Many gram-positive bacteria produce acidic molecules
+    called teichoic acids embedded in their cell wall.'
+    br
+    e 'Some <b>teichoic acids</b> are covalently bonded to membrane
+    lipids rather than to peptidoglycan, and these are called 
+    <b>lipoteichoic acids</b>.'
+    br
+    e 'Many antibiotics that are clinically useful against
+    gram-positive bacterial pathogens show little to no
+    activity against gram-negative pathogens because
+    of their outer membrane.'
+    br
+    e 'Endotoxins can cause violent symptoms in humans. The
+    endotoxins produced by Salmonella and enteropathogenic
+    strains of E. coli transmitted in contaminated foods are a 
+    classic example of this.'
+    br
+    e 'Bacterial chemoreceptors are proteins that govern the
+    <b>chemotaxis response</b>.'
+    br
+    e 'An example for a slime-forming species is the lactic acid
+    bacterium called <b>Leuconostoc</b>.'
+    br
+    e 'Surface polysaccharides assist in the attachment of
+    microorganisms to solid surfaces.'
+    br
+    e 'Prokaryotic cells often contain inclusions of one sort or another.
+    These inclusions function as energy reserves and may functiona as 
+    carbon reservoirs or have other special functions.'
+    br
+    e 'The microbiological process of forming minerals is called
+    <b>biomineralization</b>.'
+    br
+    e 'Endospores function as survival structures.'
+    br
+    e 'Pentosen entstehen aus Hexosen unter Abspaltung eines
+    CO₂ Moleküls.'
+    br
+    e 'The ABC transporter uses a periplasmic binding protein
+    which has high affinity for the substrate.'
+    br
+    e 'Hopanoids strengthen (some) bacterial cell walls.'
+    br
+    e 'Many bacteria are capable of producing several different
+    sigma factors, each of which recognizes a different
+    promoter sequence.'
+    br
+    e 'Phototrophic purple bacteria make use of <b>scotophobotaxis</b>
+    in order to avoid entering darkened habitats.'
+    br
+    e 'Algae can trigger chemotactic movements of bacteria toward
+    the algal cell via the substances that they produce.'
+    br
+    e 'Upon a nutrient downshift, rRNA, tRNA and protein synthesis
+    temporarily cease in bacteria.'
+    br
+    e 'Mitochondria are of bacterial dimensions.'
+    br
+    e 'Alarmones rapidly accumulate during a shift down
+    from amino acid excess to amino acid starvation.'
+    br
+    e 'Endospores function as survival structures and enable
+    the microorganism to endure unfavorable growth
+    condition.'
+    br
+    e 'Microbial eukaryotes that contain hydrogenosomes
+    carry out a strictly fermentative metabolism.'
+    br
+    e 'The M. tuberculosis cell envelope provides a
+    formidable protective barrier against drugs, host
+    defence mechanism and antibiotics.'
+    br
+    e 'The best carbon source is used first by bacteria.'
+    br
+    e 'The cytoplasmic membrane acts as <b>a selective
+    permeability barrier</b>.'
+    br
+    e "A 'selective medium' used in microbiology will
+    contain compounds that inhibit the growth of
+    some microorganisms, but not others."
+    br
+    e 'In regards to natural transformation of bacteria: DNA
+    from closely related species has a much higher chance to
+    be incorporated and integrated into the bacterial 
+    chromosome than unrelated DNA.'
+    br
+    e 'Phosphatase activity is typically slower than
+    phosphorylation activity - in chemotaxis at the least.'
+    br
+    e 'The energy stored in ATP can drive membrane transport
+    of nutrients.'
+    br
+    e '<b>Periplasmic binding proteins</b> display a
+    very high binding affinity for their respective
+    substrates.'
+    br
+    e 'Das Verändern eines Faktors in einer Kultur von 
+    Bakterien kann die Wirkung eines anderen Faktors
+    für das Wachstum dieser Bakterien beeinflussen.'
+    br
+    e 'Gene expression changes in bacteria follow a "shift
+    down" or a "shift up" in regards to the nutrient
+    state.'
+    br
+    e 'Sterilization eliminates all microorganisms -
+    including endospores.'
+    br
+    e 'The metabolic capacities of microbes differ.'
+    br
+    e 'The microbiome can be defined as the community
+    of microorganisms that live in a particular environment.'
+    br
+    e 'High GC contents are characteristic for microbes living
+    under extreme temperature conditions.'
+    br
+    e 'The Calvin cycle is the major biochemical pathway by which phototrophic
+    organisms incorporate CO₂ into cell material.'
+    br
+    e "Bacteria called Clostridium perfringens and Vibrio natriegens are 
+    among the world's fastest doublers, reproducing in seven to ten 
+    minutes respectively."
+    br
+    e 'The bacterium <i>Staphylococcus aureus</i> kills an average of about 
+    100,000 Americans per year, more than any other single microorganism.'
+    br
+    e 'Even bacteria suffer infection, aka phages that infect them
+    and inject their DNA/RNA into these bacteria.'
+    br
+    e 'The genome size of <b>Mesorhizobium loti</b> is more than
+    7 million bp.'
+    br
+    e 'The war with bacteria will never end.'
+    br
+    e 'Auf besondere Situationen wie einen Hitzeschock oder
+    Nahrungsstress reagiert ein Bakterium, indem es mittels
+    anderer σ-Faktoren andere Promotoren erkennt und die
+    Gene selektiv anschaltet.'
+    br
+    e 'Nitrogen is an essential component of proteins, nucleic
+    acids and other cellular constituents, and as such it
+    is required in large amounts by living organisms.'
+    br
+    e '<b>Transport systems</b> move nutrients across phospholipid
+    bilayer membranes.'
+    br
+    e 'The survival and metabolism of any one group of organisms depends
+    on the survival and metabolism of other groups of organisms. For instance,
+    <b>metazoa</b> rely on microbial metabolism in order to survive.'
+    br
+    e 'We can assume a bacterium to contain information inside
+    (its genome) while being able to respond to external information
+    (e. g. signaling molecules or other information originating
+    from outside that bacterium).'
+    br
+    e '<b>Bacteria</b> are <b>extremely adaptable</b>.'
+    br
+    e 'Plasmide bieten Selektionsvorteile für ihre Wirte in ihren
+    Lebensräumen.'
+    br
+    e '<i>Rickettsia prowazekii</i> is the causative agent of epidemic
+    typhus.'
+    br
+    e 'The core proteome that defines the species.'
+    br
+    e 'Phenotypic diversity in prokaryotes (which refers primarily to 
+    metabolic and ecological versatility) is achieved by varying the 
+    proteome.'
+    br
+    e 'Almost any given environment has a huge, mixed population of 
+    prokaryotes.'
+    br
+    e 'Bacterial cells do not possess pre-mRNA.'
+    br
+    e 'Microbes are like little chemical factories.'
+  }
+  # ========================================================================= #
+  # === Links
+  # ========================================================================= #
+  fancy2 dot108?+
+     'Links'
+  p('mars1em') {
+    selfy :local_genetics
+    selfy :local_biotechnology
+    selfy :local_cellbiology
+    selfy :local_cyanobacteria
+    selfy :local_synthetic_biology
+  }
+}}