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• 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


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


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.


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


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


Epimutation

1 One example of an epigenetic change in eukaryotic biology is the process of cellular differentiation


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.


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.


Epimutation - MicroRNAs

1 MicroRNAs (miRNAs) are members of non-coding RNAs that range in size from 17 to 25

nucleotides


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)


Epimutation - sRNAs

1 Bacterial small RNA|sRNAs are small (50-250 nucleotides), highly-structured, non-coding RNA fragments found in bacteria


Epimutation - Prions

1 Prions are Infection|infectious forms of

proteins


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


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.


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


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.


Epimutation - Medicine

1 Epigenetics has many and varied potential medical applications as it

tends to be multidimensional in nature


Epimutation - Evolution

1 Epigenetics can impact evolution when

epigenetic changes are heritable


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


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


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


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



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.



1 Current front-runner candidates for new drug targets are Histone

methyltransferase|histone lysine methyltransferases (KMT) and

protein arginine methyltransferases (PRMT).


Epimutation - Twin studies

1 Recent studies involving both dizygotic and monozygotic twins have produced some evidence of epigenetic influence in humans.



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



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



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


Epimetheus (mythology)

1 While Prometheus is characterized as ingenious and clever, Epimetheus is depicted

as foolish.


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.



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.



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.



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.


Epimetheus (mythology) - In modern culture

1 Carl Schmitt, in his book Ex captivitate salus describes himself as a Christian Epimetheus.


Epimetheus (mythology) - In modern culture

1 Les Amis, in his book Commemorating Epimetheus (2009), reinstates the value of

Epimetheus


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.


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.


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.


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.


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.


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


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


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:



1 * Dysmorphic features



1 * Sensorineural hearing loss



1 * Depletion of cerebellar Purkinje

cells



1 * Ovarian failure (POI) and hypertrophic hypergonadism



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

model.https://store.theartofservice.com/itil-2011-foundation-complete-certification-kit-fourth-edition-study-guide-ebook-and-online-course.html

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


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


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.


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.


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

represents MIC susceptibility data for a few medically significant

microorganisms.https://store.theartofservice.com/itil-2011-foundation-complete-certification-kit-fourth-edition-study-guide-ebook-and-online-course.html


1 * Pseudomonas aeruginosa: 0.06 -

256 μg/ml



1 * Streptococcus pneumoniae: ≤0.007 - 8 μg/ml



1 http://www.toku-e.com/Assets/MIC/Cefepime.pdf


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.


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


Epimenides

1 Epimenides was also said to have prophesied at Sparta on

military matters.


Epimenides

1 Epimenides is also reckoned with Melampus and Onomacritus as one

of the founders of Orphism (religion)|Orphism.


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.


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).



1 In the poem, Minos addresses Zeus

thus:



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.



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.



1 Chrysostom ([http://www.newadvent.org/fathers/23083.htm Homily 3 on Titus]) gives

an alternative fragment:



1 :For even a tomb, King, of you



1 :They made, who never died, but ever shall be.


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.


Planetary nomenclature - Epimetheus (moon)|Epimetheus

1 People from myth of Castor and Pollux

(twins)


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


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


Centipede - Anamorphy vs. epimorphy

1 Centipedes grow their legs at

different points in their development



1 The Craterostigmomorpha only have one phase of anamorphis, with embryos having 12 pairs, and

moultees 15.



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


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.


Epimer

1 Doxorubicin and epirubicin are two

closely related drugs and epimers.


Epimer - Examples

1 The two molecules pictured are both epimers and anomers (as indicated

by the 'α'-glucose and 'β' designation).


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)


Epimer - Examples

1 Other closely related compounds are epi-inositol and inositol and lipoxin and epilipoxin.


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.


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.


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


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.


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.



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


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


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.


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


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.


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



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.



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.


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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