epim
TRANSCRIPT
• EPIM
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Strategies for Engineered Negligible Senescence - Cancer-causing nuclear mutations/epimutations—OncoSENS
1 For the purposes of SENS, the effect of mutations and epimutations that
really matters is cancer, this is because if even one cell turns into a
cancer cell it might spread and become deadly
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DNA repair - Frequencies of epimutations in DNA repair genes
1 Deficiencies in DNA repair enzymes are occasionally caused by a newly arising somatic mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes
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Heparin sulfate - Epimerisation and 2-O-sulfation
1 Epimerisation is catalysed by one enzyme, the GlcA C5 epimerase or heparosan-N-sulfate-glucuronate 5-
epimerase (). This enzyme epimerises GlcA to iduronic acid (IdoA). Substrate
recognition requires that the GlcN residue linked to the non-reducing side of
a potential GlcA target be N-sulfated. Uronosyl-2-O-sulfotransferase (2OST) sulfates the resulting IdoA residues.
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Epimutation
1 In biology, and specifically genetics, 'epigenetics' is the study of heritable changes in gene activity that are not
caused by changes in the DNA sequence; it also can be used to
describe the study of stable, long-term alterations in the transcriptional
potential of a cell that are not necessarily heritable
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Epimutation
1 The term also refers to the changes themselves: functionally relevant
changes to the genome that do not involve a change in the nucleotide
sequence
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Epimutation
1 One example of an epigenetic change in eukaryotic biology is the process of cellular differentiation
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Epimutation
1 In 2011, it was demonstrated that the methylation of messenger RNA|mRNA plays a critical role in human
energy balance (biology)|energy homeostasis. The obesity-associated
FTO gene is shown to be able to demethylate N6-methyladenosine in
RNA. This discovery launched the subfield of RNA epigenetics.
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Epimutation - Mechanisms
1 Several types of epigenetic inheritance systems may play a role in what has become known as cell
memory, note however that not all of these are universally accepted to be
examples of epigenetics.
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Epimutation - MicroRNAs
1 MicroRNAs (miRNAs) are members of non-coding RNAs that range in size from 17 to 25
nucleotides
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Epimutation - MicroRNAs
1 It appears that about 60% of human protein coding genes are regulated by miRNAs.Friedman RC, Farh KK,
Burge CB, Bartel DP (2009)
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Epimutation - sRNAs
1 Bacterial small RNA|sRNAs are small (50-250 nucleotides), highly-structured, non-coding RNA fragments found in bacteria
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Epimutation - Prions
1 Prions are Infection|infectious forms of
proteins
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Epimutation - Prions
1 Fungal prions are considered by some to be epigenetic because the infectious phenotype caused by the
prion can be inherited without modification of the genome
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Epimutation - Structural inheritance systems
1 In ciliates such as Tetrahymena and Paramecium, genetically identical cells show heritable differences in the patterns of ciliary
rows on their cell surface. Experimentally altered patterns can be transmitted to
daughter cells. It seems existing structures act as templates for new structures. The
mechanisms of such inheritance are unclear, but reasons exist to assume that
multicellular organisms also use existing cell structures to assemble new ones.
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Epimutation - Development
1 Somatic epigenetic inheritance through epigenetic modifications,
particularly through DNA methylation and chromatin remodeling, is very important in the development of
multicellular eukaryotic organisms
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Epimutation - Development
1 Epigenetics can be divided into predetermined and probabilistic epigenesis. Predetermined epigenesis is a unidirectional movement from structural development in DNA to the functional maturation of the protein. Predetermined here means that development is scripted and predictable.
Probabilistic epigenesis on the other hand is a bidirectional structure-function
development with experiences and external molding development.
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Epimutation - Medicine
1 Epigenetics has many and varied potential medical applications as it
tends to be multidimensional in nature
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Epimutation - Evolution
1 Epigenetics can impact evolution when
epigenetic changes are heritable
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Epimutation - Evolution
1 Two important ways in which epigenetic inheritance can be
different from traditional genetic inheritance, with important
consequences for evolution, are that rates of epimutation can be much
faster than rates of mutation and the epimutations are more easily
reversible
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Epimutation - Genomic imprinting and related disorders
1 Some human disorders are associated with genomic imprinting, a phenomenon in mammals where the father and mother contribute different epigenetic patterns for
specific genomic loci in their germ cells
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Epimutation - Variant histones H2A in cancer
1 The histone variants of the H2A family are highly conserved in
mammals, playing critical roles in regulating many nuclear processes
by altering chromatin structure
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Epimutation - Cancer treatment
1 Current research has shown that epigenetic pharmaceuticals could be a putative replacement or adjuvant
therapy for currently accepted treatment methods such as radiation therapy|radiation and chemotherapy, or could enhance the effects of these
current treatments
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Epimutation - Cancer treatment
1 Drug development has focused mainly on histone acetyltransferase
(HAT) and histone deacetylase (HDAC), and has included the
introduction to the market of the new pharmaceutical vorinostat, an HDAC inhibitor. HDAC has been shown to
play an integral role in the progression of oral squamous cancer.
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Epimutation - Cancer treatment
1 Current front-runner candidates for new drug targets are Histone
methyltransferase|histone lysine methyltransferases (KMT) and
protein arginine methyltransferases (PRMT).
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Epimutation - Twin studies
1 Recent studies involving both dizygotic and monozygotic twins have produced some evidence of epigenetic influence in humans.
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Epimutation - Twin studies
1 Direct comparisons between identical twins constitute the ideal
experimental model for testing environmental epigenetics, because
DNA sequence differences that would be abundant in a singleton-based
study do not interfere with the analysis
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Epimutation - Twin studies
1 One of the first high-throughput studies of epigenetic differences
between monozygotic twins focused in comparing global and locus-
specific changes in DNA methylation and histone modifications in a sample of 40 monozygotic twin
pairs.Fraga MF, Ballestar E, Paz MF et al (2005) Epigenetic differences arise
during the lifetime of monozygotic twins
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Epimutation - Twin studies
1 A more recent study, where 114 monozygotic twins and 80 dizygotic
twins were analyzed for the DNA methylation status of around 6000 unique genomic regions, concluded that epigenetic similarity at the time
of blastocyst splitting may also contribute to phenotypic similarities
in monozygotic co-twins
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Epimetheus (mythology)
1 While Prometheus is characterized as ingenious and clever, Epimetheus is depicted
as foolish.
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Epimetheus (mythology) - Mythology
1 According to Plato's use of the old myth in his Protagoras (dialogue)|Protagoras (320d–322a), the twin Titans were entrusted with
distributing the traits among the newly created animals. Epimetheus was
responsible for giving a positive trait to every animal, but when it was time to give man a positive trait, lacking foresight he
found that there was nothing left.Leo Strauss, Natural Right and History, p. 117.
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Epimetheus (mythology) - Mythology
1 Prometheus decided that mankind's attributes would be the civilizing arts and
fire, which he stole from Zeus. Prometheus later stood trial for his crime. In the context of Plato's dialogue, Epimetheus, the being in whom thought follows production, represents nature in the sense of materialism, according
to which thought comes later than thoughtless bodies and their thoughtless motions.Leo Strauss, Natural Right and
History, p. 117.
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Epimetheus (mythology) - Mythology
1 According to Hesiod, who related the tale twice (Theogony, 527ff; Works
and Days 57ff), Epimetheus was the one who accepted the gift of Pandora from the gods. Their marriage may
be inferred (and was by later authors), but it is not made explicit in
either text.
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Epimetheus (mythology) - Mythology
1 In later myths, the daughter of Epimetheus and Pandora was Pyrrha, who married Deucalion and was one of the two who survived the Deluge
(mythology)|deluge.
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Epimetheus (mythology) - In modern culture
1 Carl Schmitt, in his book Ex captivitate salus describes himself as a Christian Epimetheus.
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Epimetheus (mythology) - In modern culture
1 Les Amis, in his book Commemorating Epimetheus (2009), reinstates the value of
Epimetheus
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Self-refuting idea - Epimenides paradox
1 The first notable self-refuting idea is the Epimenides paradox, a statement
attributed to Epimenides, a Cretan philosopher, that All Cretans are
liars. If interpreted as meaning no Cretan ever speaks the truth, this
cannot be true if uttered by a Cretan.
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Self-refuting idea - Epimenides paradox
1 A more common example is the self-refuting statement I am lying
(because the first statement allows the possibility some Cretans do not speak the truth, the speaker being
one of them). The second statement has no third alternative—the
speaker's statement is either true or false.
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Galactose epimerase deficiency
1 'Galactose epimerase deficiency', also known as 'GALE deficiency',
'Galactosemia III' and 'UDP-galactose-4-epimerase deficiency', is
a rare, autosome|autosomal dominance (genetics)|recessive form
of galactosemia associated with a deficiency of the enzyme galactose
epimerase.
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Galactose epimerase deficiency - Genetics
1 Galactose epimerase deficiency is an autosomal recessive disorder, which means
the defective gene is located on an autosome, and two copies of the defective gene - one from each parent - are required to inherit the disorder. The parents of an individual with an autosomal recessive
disorder both carry one copy of the defective gene, but usually do not
experience any signs or symptoms of the disorder.
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Galactose epimerase deficiency - Genetic basis
1 Various human GALE mutations resulting in Type III galactosemia have been identified. Functional analysis of these mutant GALE isoforms suggests that reduced
catalytic efficiency and increased likelihood of proteolytic digestion act causatively in Type III galactosemia.
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Galactose epimerase deficiency - Biochemical basis
1 GALE deficiency inhibits UDP-glucose regeneration, preventing the
formation of glucose-1-phosphate and leading to the accumulation of
galactose and galactose-1-phosphate
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Galactose epimerase deficiency - Biochemical basis
1 Blockage of the Leloir pathway by GALE deficiency or dysfunction activates alternate pathways of
glucose metabolism and leads to galactitol and galactonate formation
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Galactose epimerase deficiency - Symptoms
1 Symptoms of congenital Type III Galactosemia are apparent from
birth, but vary in severity depending on whether the peripheral or
generalized disease form is present. Symptoms may include:
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Galactose epimerase deficiency - Symptoms
1 * Dysmorphic features
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Galactose epimerase deficiency - Symptoms
1 * Sensorineural hearing loss
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Galactose epimerase deficiency - Symptoms
1 * Depletion of cerebellar Purkinje
cells
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Galactose epimerase deficiency - Symptoms
1 * Ovarian failure (POI) and hypertrophic hypergonadism
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Galactose epimerase deficiency - Symptoms
1 Studies of Type III galactosemia symptoms are mostly descriptive,
and precise pathogenic mechanisms remain unknown. This is largely due to a lack of functional animal models of classic galactosemia. The recent
development of a Drosophila melanogaster GALE mutant
exhibiting galactosemic symptoms may yield a promising future animal
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Galactose epimerase deficiency - Detection and treatment
1 Screening for elevated galactose levels may detect GALE deficiency or dysfunction in infants, and mutation
studies for GALE are clinically available
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Cefepime
1 A 2007 meta-analysis suggested when data of trials were combined,
Mortality rate|mortality was increased in patients treated with cefepime compared with other β-
lactam antibiotics
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Cefepime - Clinical use
1 Cefepime is usually reserved to treat moderate to severe nosocomial
pneumonia, infections caused by multiple drug-resistant
microorganisms (e.g. Pseudomonas aeruginosa) and empirical treatment
of febrile neutropenia.
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Cefepime - Clinical use
1 Cefepime has good activity against important pathogens including Pseudomonas
aeruginosa, Staphylococcus aureus, and multiple drug-resistant Streptococcus
pneumoniae. A particular strength is its activity against Enterobacteriaceae. Whereas other cephalosporins are degraded by many plasmid- and chromosome-mediated beta-
lactamases, cefepime is stable and is a front-line agent when infection with
Enterobacteriaceae is known or suspected.
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Cefepime - Spectrum of bacterial susceptibility
1 Cefepime is a broad-spectrum cephalosporin antibiotic and has
been used to treat bacteria responsible for causing pneumonia
and infections of the skin and urinary tract. Some of these bacteria include
Pseudomonas, Escherichia, and Streptoccus species. The following
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Cefepime - Spectrum of bacterial susceptibility
1 * Pseudomonas aeruginosa: 0.06 -
256 μg/ml
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Cefepime - Spectrum of bacterial susceptibility
1 * Streptococcus pneumoniae: ≤0.007 - 8 μg/ml
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Cefepime - Spectrum of bacterial susceptibility
1 http://www.toku-e.com/Assets/MIC/Cefepime.pdf
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Cefepime - Chemistry
1 The combination of the syn-configuration of the methoxyimino Moiety (chemistry)|moiety and the aminothiazolyl moiety confers extra stability to beta lactamase|beta;-lactamase
enzymes produced by many bacteria. The N-methylpyrrolidine moiety increases
penetration into Gram-negative bacteria. These factors increase the activity of cefepime against otherwise resistant organisms including Pseudomonas
aeruginosa and Staphylococcus aureus.
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Epimenides
1 Plutarch writes that Epimenides purified Athens after the pollution brought by the Alcmeonidae, and
that the seer's expertise in sacrifices and reform of funeral practices were of great help to Solon in his reform of
the Athenian state
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Epimenides
1 Epimenides was also said to have prophesied at Sparta on
military matters.
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Epimenides
1 Epimenides is also reckoned with Melampus and Onomacritus as one
of the founders of Orphism (religion)|Orphism.
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Epimenides - Works
1 Several prose and poetic works, now lost, were attributed to Epimenides, including a theogony, an epic poem
on the Argonauts|Argonautic expedition, prose works on
purifications and sacrifices, a cosmogony, oracles, a work on the
laws of Crete, and a treatise on Minos and Rhadymanthus.
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Epimenides - Cretica
1 Epimenides' Cretica (Κρητικά) is quoted twice in the New Testament.
Its only source is a 9th-century Syriac commentary by Isho'dad of Merv on the Acts of the Apostles, discovered, edited and translated (into Greek) by
Prof. J. Rendel Harris in a series of articles in the Expositor (Oct. 1906,
305–17; [http://books.google.com/books?
id=facQAAAAYAAJpg=PA336#v=onepageqf=false Apr. 1907, 332–37];
Apr. 1912, 348–353).
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Epimenides - Cretica
1 In the poem, Minos addresses Zeus
thus:
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Epimenides - Cretica
1 The lie of the Cretans is that Zeus was mortal; Epimenides considered
Zeus immortal. Cretans, always liars, with the same theological intent as
Epimenides, also appears in the Hymn to Zeus of Callimachus. The
fourth line is quoted (with a reference to one of your own poets) in Acts of the Apostles, s:Bible (King
James)/Acts#17:28|chapter 17, verse 28.
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Epimenides - Cretica
1 The second line is quoted, with a veiled attribution (a prophet of their own), in the Epistle to Titus, s:Bible (King James)/Titus#1:12|chapter 1, verse 12, to warn Titus about the
Cretans. The prophet in Titus 1:12 is identified by Clement of Alexandria
as Epimenides (Stromata, [http://www.newadvent.org/fathers/0
2101.htm i. 14]). In this passage, Clement mentions that some say Epimenides should be counted
among the seven wisest philosophers.
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Epimenides - Cretica
1 Chrysostom ([http://www.newadvent.org/fathers/23083.htm Homily 3 on Titus]) gives
an alternative fragment:
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Epimenides - Cretica
1 :For even a tomb, King, of you
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Epimenides - Cretica
1 :They made, who never died, but ever shall be.
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Epimenides - Epimenides paradox
1 In the Middle Ages, many forms of the liar paradox were studied under the heading of insolubilia, but these
were not associated with Epimenides.
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Planetary nomenclature - Epimetheus (moon)|Epimetheus
1 People from myth of Castor and Pollux
(twins)
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Isomerase - Racemases, epimerases
1 Isomerization at one chiral carbon of several yields epimers, which differ
from one another in absolute configuration at just one chiral
carbon
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Isomerase - Epimerization
1 An example of epimerization is found in the Calvin cycle when D-ribulose-
5-phosphate is converted into D-xylulose-5-phosphate by ribulose-
phosphate 3-epimerase
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Centipede - Anamorphy vs. epimorphy
1 Centipedes grow their legs at
different points in their development
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Centipede - Anamorphy vs. epimorphy
1 The Craterostigmomorpha only have one phase of anamorphis, with embryos having 12 pairs, and
moultees 15.
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Centipede - Anamorphy vs. epimorphy
1 The clade Epimorpha, consisting of orders Geophilomorpha and Scolopendromorpha, exhibits
epimorphy: all pairs of legs are developed in the embryonic stages, and offspring do not develop more
legs between moults
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Epimer
1 In stereochemistry, 'epimer' refers to one of a pair of
Stereoisomerism|stereoisomers. The two isomers differ in configuration at only one stereogenic center. All other
stereocenters in the molecules, if any, are the same in each.
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Epimer
1 Doxorubicin and epirubicin are two
closely related drugs and epimers.
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Epimer - Examples
1 The two molecules pictured are both epimers and anomers (as indicated
by the 'α'-glucose and 'β' designation).
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Epimer - Examples
1 These two molecules are epimers but, because not mirror images of
each other, are also not enantiomers (enantiomers have the same name
but differ in 'D' and 'L' classification)
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Epimer - Examples
1 Other closely related compounds are epi-inositol and inositol and lipoxin and epilipoxin.
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Epimer - Epimerisation
1 Epimerisation is a chemical process where an epimer is transformed into its chiral
counterpart. It can happen in condensed tannins depolymerisation reactions. Epimerisation can be spontaneous
(generally a slow process), or catalyzed by enzymes, e.g. the epimerization between the sugars N-acetylglucosamine and N-
acetylmannosamine, which is catalyzed by RENBP|Renin-Binding Protein.
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Lobry-de Bruyn-van Ekenstein transformation - Epimerization
1 The carbon atom at which the initial deprotonation takes place is a stereocenter.
If, for example, D-glucose (an Aldose) rearranges to D-fructose, the ketose, the stereochemical configuration is lost in the
enol form. In the chemical reaction the enol can be protonated from two faces, resulting
in the backformation of glucose or the formation of the epimer mannose|D-
mannose. The final product is a mix of D-glucose, D-fructose and D-mannose.
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Methylmalonyl CoA epimerase - Role in Fatty Acid Catabolism
1 Methylmalonyl CoA epimerase then catalyzes the rearrangement of (R)-
methylmalonyl-CoA to the (S) form in a reaction that uses a vitamin B12
cofactor (biochemistry)|cofactor and a resonance-stabilized carbanion
Reactive intermediate|intermediate
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Methylmalonyl CoA epimerase - Reaction Mechanism
1 Acting as a Enzyme catalysis|general base, the enzyme abstracts a proton
from the β-carbon of (R)-methylmalonyl-CoA. This results in
the formation of a carbanion intermediate in which the α-carbon is stabilized by resonance. The enzyme
then acts as a general acid to protonate the β-carbon, resulting in the formation of (S)-methylmalonyl-
CoA.https://store.theartofservice.com/itil-2011-foundation-complete-certification-kit-fourth-edition-study-guide-ebook-and-online-course.html
Epimetheus (moon)
1 'Epimetheus' is an inner satellite of Saturn. It is also known as 'SaturnXI'.
It is named after the mythological Epimetheus (mythology)|Epimetheus,
brother of Prometheus.
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Epimetheus (moon) - Discovery
1 Epimetheus occupies essentially the same orbit as the moon Janus
(moon)|Janus. Astronomers assumed that there was only one body in that orbit, and accordingly had difficulty
determining their orbital characteristics. Observations were photographic and spaced widely apart in time, so that while the
presence of two objects was not obvious, the observations were
difficult to reconcile with a reasonable orbit.
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Epimetheus (moon) - Discovery
1 Audouin Dollfus observed a moon on December 15, 1966, which he
proposed to be named Janus. On December 18, Richard Walker
(astronomer)|Richard Walker made a similar observation which is now
credited as the discovery of Epimetheus. However, at the time, it was believed that there was only one moon, unofficially known as Janus, in
the given orbit.https://store.theartofservice.com/itil-2011-foundation-complete-certification-kit-fourth-edition-study-guide-ebook-and-online-course.html
Epimetheus (moon) - Discovery
1 Twelve years later, in October 1978, Stephen M. Larson and John W. Fountain realised that the 1966
observations were best explained by two distinct objects (Janus and
Epimetheus) sharing very similar orbits. This was confirmed in 1980 by
Voyager 1, and so Larson and Fountain officially share the
discovery of Epimetheus with Walker.https://store.theartofservice.com/itil-2011-foundation-complete-certification-kit-fourth-edition-study-guide-ebook-and-online-course.html
Epimetheus (moon) - Discovery
1 Epimetheus received its name in 1983. The name Janus was approved
by the International Astronomical Union|IAU at the same time, although the name had been used informally
since Dollfus proposed it shortly after the 1966 discovery.
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Epimetheus (moon) - Orbital relationship between Epimetheus and Janus
1 The exchange takes place about once every four years; the last close approaches occurred on January 21,
2006, and in 2010, when Janus's orbital radius increased by ~20km, while Epimetheus's decreased by
~80km; Janus's orbit is less affected because it is four times more
massive than Epimetheus
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Epimetheus (moon) - Orbital relationship between Epimetheus and Janus
1 The orbital relationship between Janus and Epimetheus can be
understood in terms of the Three-body problem#Circular restricted
three-body problem|circular restricted three-body problem, as a case in which the two moons (the
third body being Saturn) are similar in size to each other.
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Epimetheus (moon) - Physical characteristics
1 From its very low density and relatively high albedo, it seems likely that Epimetheus is a very porous icy
body
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Epimetheus (moon) - Physical characteristics
1 The south pole shows what might be the remains of a large impact crater
covering most of this face of the moon, and which could be
responsible for the somewhat flattened shape of the southern part
of Epimetheus.
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Epimetheus (moon) - Physical characteristics
1 There appear to be two terrain types: darker, smoother areas, and brighter,
slightly more yellowish, fractured terrain. One interpretation is that the
darker material evidently moves down slopes, and probably has a
lower ice content than the brighter material, which appears more like bedrock. Nonetheless, materials in both terrains are likely to be rich in
water ice.https://store.theartofservice.com/itil-2011-foundation-complete-certification-kit-fourth-edition-study-guide-ebook-and-online-course.html
Epimetheus (moon) - Ring
1 A Rings of Saturn#Janus/Epimetheus Ring|faint dust ring is present around the region occupied by the orbits of Epimetheus and
Janus, as revealed by images taken in forward-scattered light by the Cassini–
Huygens|Cassini spacecraft in 2006. The ring has a radial extent of about 5000km. Its
source are particles blasted off their surfaces by meteoroid impacts, which then
form a diffuse ring around their orbital paths.
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Epistle to Titus - Epimenides paradox
1 One of the secular peculiarities of the Epistle to Titus is the inclusion of text which
has become known as the Epimenides paradox. According to the World English Bible translation, Titus 1:12–13 reads (in
part) One of them, a prophet of their own, said, 'Cretans are always liars, evil beasts, and idle gluttons.' This testimony is true.
The statement by a member of a group that all members are liars is now a famous logic
problem.https://store.theartofservice.com/itil-2011-foundation-complete-certification-kit-fourth-edition-study-guide-ebook-and-online-course.html
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