Mutant

"Most miscarriages (about 60%) occur randomly when an embryo receives an abnormal number of chromosomes during fertilization. This type of genetic problem happens by chance; there is no medical condition that causes it. However, it becomes more common in women of increased reproductive age. Are there other genetic problems associated with repeated miscarriages? In a small number of couples who have repeated miscarriages, one partner has a chromosome in which a piece is transferred to another chromosome. This is called a translocation. People who have a translocation usually do not have any physical signs or symptoms, but some of their eggs or sperm will have abnormal chromosomes. If an embryo gets too much or too little genetic material, it often leads to a miscarriage."

"Early miscarriages usually happen because the embryo is not developing as it should. Chromosome problems are thought to be the most common cause. These problems usually happen for no reason and are unlikely to happen again. To develop properly, a baby needs the right number of normal chromosomes. He’ll need 23 from his mum and 23 from his dad. Chromosomal abnormalities can prevent a baby from developing. These abnormalities may happen because there are too many chromosomes or not enough chromosomes, or because there are changes to a chromosome’s structure. In that case, the pregnancy will come to an end at the embryo stage. It’s thought that up to 95 per cent of pregnancies with chromosomal abnormalities end in miscarriage."

"It is agreed that most, if not all, new mutations are deleterious. In plants, much fewer than 1% of radiation-induced mutants are found to be useful. In insects, a few induced mutations confer some advantage, but only to completely inbred populations - a situation quite in contrast with the human condition (NEWCOMBE 1960). According to DOBZHANSKY (1957) : ‘if anything, radiation-induced mutants are more destructive than the spontaneous ones. As far as genetic effects are concerned, the only safe dose of high-energy radiation is no radiation’. As observed in mammals, mostly the mouse, the effects of radiation-induced mutations may be : (1) Dominant: lethals, seen as reduced litter size, or non-lethals, evidenced as offspring which are malformed or diminished in vitality or life-span; semi-sterility, resulting from translocation, is seen one generation later as a reduction of litters by one-half and is handed down to subsequent generations (PAULA HERTWIG 1940). (2) Recessive mutations are demonstrated by mating the offspring of exposed males to females known to be (heterozygous) carriers of certain traits (W. L. RUSSELL 1954; CARTER et coll. 1956). (3) Mutations involving sex-chromosomes may be reflected by a change in the sex ratio of the offspring (sex-linked lethals, see Fig. 1)"

"In point of fact, as MULLER (1955) notes, the less harmful a mutant, the greater the number of individuals it affects, inasmuch as reproduction remains possible. Thus the total measure of mutational harm is the number of mutations produced, of whatever degree of harmfulness, rather than the damage to any one individual or generation. In a population which, like the human, is not inbred, the generation showing the greatest effect of a mutation should be the first filial one; but the total effect in the posterity, over an indefinite number of generations, is still greater (CROW 1958). This point shall be illustrated in relation to the foreseeable effects of radiation upon descendants of man (see Part 11)."

"There are a number of studies that show radiation can cause heritable mutations in the offspring of irradiated organisms. These “germ-line mutations” have been shown to occur in unique sequences of DNA called “minisatellite loci”. The high frequencies of spontaneous and induced mutations at minisatellite loci allow mutation induction to be measured at low doses of exposure in a small population, making minisatellite mutation a powerful tool to investigate radiation-induced heritable mutations. However, the biological significance of these mutations is uncertain, and their relationship to health risk or population fitness is unknown. We have adopted this mutation assay to study the role of adaptive response in protecting mice against radiation-induced heritable defects. We have shown that male mice, adapted to radiation with a low dose priming exposure, do not pass on mutations to their offspring caused by a subsequent large radiation exposure to the adapted males."

"Lola the six-clawed lobster has escaped the fate that would face most of her kind, thanks to her genetic mutation, and will be served up in an exhibit case at the Maine Maine State Aquarium rather than on a dinner table."

"Two assumptions are commonly made in the estimation of genetic risk: (1) that the seven specific loci in the mouse constitute a suitable basis for extrapolation to genetic disease in humans, and (2) that mutations are induced by radiation damage (energy-loss events leading to double-stranded damage) occurring within the gene and are induced linearly with dose, at least at low doses. Recent evidence on the mutability of repeat sequences is reviewed that suggests that neither of these assumptions is as well founded as we like to think."

"Last night I encountered a dream cat with a very long neck and a body like a human fetus, gray and transluscent. I don't know what it needs or how to provide for it. Another dream years ago of a human child with eyes on stalks. It is very small, but can walk and talk "Don't you want me?" Again, I don't know how to care for the child. But I am dedicated to protecting and nurturing him at any cost! It is the function of the Guardian to protect hybrids and mutants in the vulnerable stage of infancy."

"When the frequency of a gene in the general population exceeds 1%, is not considered a random mutation but a mutation that has been positively selected during evolution."

"It is possible that the presence of altered gene combinations, as in ADHD, can bring concrete benefits to society but are detrimental to the individual."

"Charles Xavier's dream — where all Earth's children, mutant or otherwise, live together in peace and harmony! Where people are judged for who they are — not what they look like or how they're born. That's why he created the X-men, to exemplify that dream."

"Mutants; the Children of the Atom. Men and women granted power beyond measure. Mankind not understanding these gifts of evolution have chosen to meet them with persecution and death. There are those mutants that agree with the humans that this world is too small for both species and that one shall by necessity forever stricken from the face of the Earth. I believe in an alternative. A world wherein man and mutant coexist in peace. They’re providing a much needed balance to an all too fragile world. To that end, I have assembled those men and women willing to fight for that peace. To defend the world that fear is optional. To that end, I, Professor Charles Xavier, have assembled the X-Men."

"Mutants are all around us. They could be your neighbors. They could be your co-workers. They could be related to you. Gifted with extraordinary powers, they are the next step on the evolutionary ladder. Some use their powers for good; some, for unspeakable evil. One group had dedicated its wondrous abilities to protect mankind, even those who hate and fear them. Known to the world at large as outlaws, they are the X-Men."

"Unique events are unrepeatable and cannot be subjected to any sort of experimental investigation. … His general theory, that all life on earth had originated and evolved by a gradual successive accumulation of fortuitous mutations, is still, as it was in Darwin’s time, a highly speculative hypothesis entirely without direct factual support and very far from that self-evident axiom some of its more aggressive advocates would have us believe."

"Here I am saying that mutants are dangerous to us ordinaries, a view which John W. Campbell, Jr. deplored. We were supposed to view them as our leaders. But I always felt uneasy as to how they would view us. I mean, maybe they wouldn't want to lead us. Maybe from their superevolved lofty level we wouldn't seem worth leading. Anyhow, even if they agreed to lead us, I felt uneasy as where we would wind up going. It might have something to do with buildings marked SHOWERS but which really weren't."

"We were always afraid a mutant with superior intellectual powers would come along," Baines said reflectively. "A deeve who would be to us what we are to the great apes. Something with a bulging cranium, telepathic ability, a perfect semantic system, ultimate powers of symbolization and calculation. A development along our own path. A better human being." "He acts by reflex," Anita said wonderingly. She had the analysis and was sitting at one of the desks studying it intently. "Reflex — like a lion. A golden lion." She pushed the tape aside, a strange expression on her face. "The lion god." "Beast," Wisdom corrected tartly. "Blond beast, you mean." "He runs fast," Baines said, "and that's all. No tools. He doesn't build anything or utilize anything outside himself. He just stands and waits for the right opportunity and then he runs like hell." "This is worse than anything we've anticipated," Wisdom said. His beefy face was lead-gray. He sagged like an old man, his blunt hands trembling and uncertain. "To be replaced by an animal! Something that runs and hides. Something without a language!" He spat savagely. "That's why they weren't able to communicate with it. We wondered what kind of semantic system it had. It hasn't got any! No more ability to talk and think than a — dog."

"According to Goldschmidt, all that evolution by the usual mutations—dubbed "micromutations"—can accomplish is to bring about "diversification strictly within species, usually, if not exclusively, for the sake of adaptation of the species to specific conditions within the area which it is able to occupy." New species, genera, and higher groups arise at once, by cataclysmic saltations—termed macromutations or systematic mutations—which bring about in one step a basic reconstruction of the whole organism. The role of natural selection in this process becomes "reduced to the simple alternative: immediate acceptance or rejection." A new form of life having been thus catapulted into being, the details of its structures and functions are subsequently adjusted by micromutation and selection. It is unnecessary to stress here that this theory virtually rejects evolution as this term is usually understood (to evolve means to unfold or to develop gradually), and that the systematic mutations it postulates have never been observed. It is possible to imagine a mutation so drastic that its product becomes a monster hurling itself beyond the confines of species, genus, family, or class. But in what Goldschmidt has called the "hopeful monster" the harmonious system, which any organism must necessarily possess, must be transformed at once into a radically different, but still sufficiently coherent, system to enable the monster to survive. The assumption that such a prodigy may, however rarely, walk the earth overtaxes one's credulity, even though it may be right that the existence of life in the cosmos is in itself an extremely improbable event."

"Mutants. Since the discovery of their existence they have been regarded with fear, suspicion, often hatred. Across the planet, debate rages. Are mutants the next link in the evolutionary chain or simply a new species of humanity fighting for their share of the world? Either way it is a historical fact: Sharing the world has never been humanity's defining attribute."

"For randomized controlled trials of treatments, it is essential to have a clear classification of pregnancy loss type for both fetal and very early loss events. In addition, there is a strong argument for mandatory karyotyping of all pregnancy losses to exclude a lethal trisomy karyotype or triploidy. This is because, irrespective of treatment intervention, pregnancy loss has occurred and may have been described as a ‘false’ treatment failure. Recent papers testify to the high rate of abnormal chromosome type when pregnancy loss has occurred (Bricker and Farquharson, 2002; Levine et al., 2002; Stephenson et al., 2002; Philip et al., 2003; Morikawa et al., 2004)."

"The young watch television twenty-four hours a day, they don't read and they rarely listen. This incessant bombardment of images has developed a hypertrophied eye condition that's turning them into a race of mutants."

"The most common cause of miscarriage is chromosomal/genetic abnormalities, leading to ~50% of spontaneous miscarriages. Genetic abnormalities most frequently occur due to aneuploidy—when the chromosomes fail to separate properly during cell division—meaning that some cells have extra copies of a particular chromosome while others have none. The exact causes of aneuploidy are not well understood, although increased maternal age (>35 yrs) is the greatest risk factor."

"Numerous authors have looked at the role of chromosomal abnormalities in these embryonic losses. One study looked at 144 spontaneous miscarriages by obtaining direct preperations of chorionic villi. Seventy per cent had abnormal chromosomes of which 64% were autosomal trisomies, 9% polyploidy, 7% monosomy X ad 6% structural rearrangements. Errors of gonadogenesis during meiosis will result in autosomal trisomies. Errors of fertilization can result in triploidy from dispermy. Errors of the first division of the zygote result result in tetraploidy or mosaicism. None of these would be expected to be a repetitive event except in the very rare instances of balances translocations or inversions in one parent"

"We applaud the burgeoning emphasis on change in regulatory genes as the stuff of morphological evolution... if only because one of us had written a book to argue that the classical, and widely ignored data on evolution by heterochrony should be exhumed and valued as a primary demonstration of regulatory change. We do not see how point mutations in structural genes can lead, even by gradual accumulations, to new morphological designs. Regulatory changes in the timing of complex ontogenetic programs seem far more promising—and potentially rapid, in conformity with our punctuational predilections. The near identity of humans and chimps for structural genes, and the evidence of major regulatory change indicated by human neoteny provides an important confirmation."

"Mutation: it is the key to our evolution. It is how we have evolved from a single-celled organism into the dominant species on the planet. This process is slow, and normally taking thousands and thousands of years. But every few hundred millennia, evolution leaps forward."

"Anything can happen. How absolutely true. You're exactly the mutant I'm looking for! You're hired."

"Aside from inheriting half of the genome of each of our parents, we are born with a small number of novel mutations that occurred during gametogenesis and postzygotically. Recent genome and exome sequencing studies of parent–offspring trios have provided the first insights into the number and distribution of these de novo mutations in health and disease, pointing to risk factors that increase their number in the offspring. De novo mutations have been shown to be a major cause of severe early-onset genetic disorders such as intellectual disability, autism spectrum disorder, and other developmental diseases. In fact, the occurrence of novel mutations in each generation explains why these reproductively lethal disorders continue to occur in our population. Recent studies have also shown that de novo mutations are predominantly of paternal origin and that their number increases with advanced paternal age."

"The prevalence of chromosome abnormalities in women facing a single sporadic miscarriage is to be 45%. Approximately 50% to 60% of early spontaneous miscarriages are associated with a chromosomal anomaly of conceptus. Most common abnormality is aneuploidy, with autosomal trisomy accounting for more than 50% of chromosomally abnormal abortuses. A strong family history of recurrent miscarriage or genetic anomaly suggests a parental karyotypic abnormality, and a chromosomal analysis of the affected partner is appropriate in the primary evaluation. Chromosomal analysis of the miscarriage offers an explanation in at least 50% of cases. Parental karyotyping is not predictive of a subsequent miscarriage. Routine karyotyping of couples with recurrent miscarriage is not recommended. Cytogenetic analysis may be performed on products of conception to avoid unnecessary evaluation and treatment and because an aneuploid conceptus indicates a somewhat greater likelihood of success with a subsequent pregnancy (Evidence Level III)."

"What would you do with mutants who were just plain boys and girls and certainly not dangerous? You school them. You develop their skills. So I gave them a teacher, Professor X. Of course, it was the natural thing to do, instead of disorienting or alienating people who were different from us, I made the X-Men part of the human race, which they were. Possibly, radiation, if it is beneficial, may create mutants that’ll save us instead of doing us harm. I felt that if we train the mutants our way, they’ll help us - and not only help us, but achieve a measure of growth in their own sense. And so, we could all live together."

"This was a period when we were experimenting with the atom bomb. People were wondering what the effects would be. Everybody worried ‘Would we all become mutants? We played around with this ‘mutation thing’ and I came up with the X-Men, who were associated with radiation and its effects on humanity."

"Mutants and humans. They have long struggled to coexist. While some try to unite the world, others try to dominate it. Neither strategy has prevailed. But when conflicts reach an impasse, inevitably something happens to shift the balance forever."

"When an individual acquires great power, the use or misuse of that power is everything. Will it be used for the greater good or will it be used for personal or destructive ends? Now this is a question we must all ask ourselves. Why? Because we are mutants."

"They wish to "cure" us. But I say to you we are the cure! The cure for that infirm, imperfect condition called "Homo sapiens!" They have their weapons... We have ours. We will strike with a vengeance and a fury that this world has never witnessed!"

"It was things like the Teenage Mutant Ninja Turtles, he thought, that made you believe the world was maybe just as well off destroyed."

"I'm either a mutant or a cripple, and I refuse to be a cripple. People pity cripples, but they're afraid of mutants … Fear implies respect."

"It is a generally accepted assumption that sporadic pregnancy losses occurring before an embryo has developed represent a ‘physiological’ phenomenon, which prevents conceptions affected by serious structural malformations or chromosomal aberrations incompatible with life from progressing to viability. This concept is supported by clinical studies in which embryoscopy was used to assess fetal morphology prior to removal by uterine evacuation. Fetal malformations were observed in 85% of cases presenting with early clinical miscarriage. The same study also demonstrated that 75% of the fetuses had an abnormal karyotype. Fetal chromosomal aneuploidies arising from non-inherited and non-disjunctional events are common. Indeed, in a recent study using comparative genomic hybridization to study the chromosomal complement of all blastomeres in preimplantation human embryos, more than 90% were found to have at least one chromosomal abnormality in one or more cells. The clinical implications of minor, mosaic and possibly ‘transient’ aneuploidies remain unclear. However, while most fetuses with severe developmental defects will die in utero some aneuploidies can be compatible with survival to term. The most commonly encountered is trisomy 21, although 80% of affected embryos perish in utero or in the neonatal period. In most cases, the extra chromosome is of maternal origin and caused by a malsegregation event in the first meiotic division. The risk of this increases with maternal age and may be considered to be a biological rather than pathological phenomenon. Although fetal chromosomal aberrations may be identified in 29% to 60% of cases in women with RM, the incidence decreases as the number of miscarriages increases suggesting other mechanisms as a cause of the miscarriage in RM couples with multiple losses."

"I declare that The Beatles are mutants. Prototypes of evolutionary agents sent by God, endowed with a mysterious power to create a new human species, a young race of laughing freemen."

"The X-Men, created by Jewish American comics legends Stan Lee and Jack Kirby in 1963, is a team of mutants, a class of human being first introduced as people that “possess an extrapower…one which ordinary humans do not!!” (EUX1 #1: 8ii). Especially after the introduction of the mutant-hunting robot Sentinels in X-Men #14 (Nov. 1965, EUX1), Marvel Comics’ mutants have been increasingly inscribed with allegorical Otherness. They have been subject to many of the prejudices that have historically plagued marginalized minorities, including, among other things, forced and voluntary segregation, slurs, persecution, and genocidal campaigns, and, conspiracy theories about their aims as a group."

"Most miscarriages occur because the fetus isn't developing as expected. About 50 percent of miscarriages are associated with extra or missing chromosomes. Most often, chromosome problems result from errors that occur by chance as the embryo divides and grows — not problems inherited from the parents."

"It's 1987, do you know what your children are? Paid for by citizens in support of the Mutant Registration Act."

"Sometimes something can go wrong at the point of conception and the foetus receives too many or not enough chromosomes. The reasons for this are often unclear, but it means the foetus will not be able to develop normally, resulting in a miscarriage. This is very unlikely to recur. It does not necessarily mean there's any problem with you or your partner."

"The most common cause of pregnancy loss is a problem with the chromosomes that would make it impossible for the fetus to develop normally."

"We conclude — unexpectedly — that there is little evidence for the neo-Darwinian view: its theoretical foundations and the experimental evidence supporting it are weak, and there is no doubt that mutations of large effect are sometimes important in adaptation. We hasten to add, however, that we are not "macromutationists" who believe that adaptations are nearly always based on major genes. The neo-Darwinian view could well be correct. … We hope to encourage evolutionists to reexamine this neglected question and to provide evidence to settle it."

"But, be that as it may, is this variation, or variations, beneficial to humanity in their environment? According to Lois Gresh and Robert Weinberg, the X-men do have “helpful mutations..." This point is demonstrated numerous times in the adventures of the X-Men, where team members use their mutant powers to help them survive dangerous situations where normal humans would be killed instantly” (Gresh and Weinberg 2002, 135). What Gresh and Weinberg have overlooked, however, is that these “dangerous situations” came after the genetic variation, not before. Most of the battles the X-Men fight are either against other mutants-- such as Magneto and the Brotherhood of Evil Mutants, who have a more violent response to human oppression of mutants-- or against anti-mutant hate groups, such as the Sentinels or Friends of Humanity, whose only goal is to wipe out all mutants. All of these “dangerous situations” come up in response to the X-Men’s genetic variation, meaning that this variation cannot be an adaptive response to an environment. Of course, under the theory of evolution by natural selection, every mutation need not necessarily be useful."

"Family entertainment? Bollocks. What they want is filth: people doing things to each other with chainsaws during tupperware parties, babysitters being stabbed with knitting needles by gay presidential candidates, vigilante groups strangling chickens, armed bands of theatre critics exterminating mutant goats. Where's the fun in pictures? Oh, well, there we are. Here's the theme music. Goodnight."

"One way to further improve the estimate of the abortion rate is to account for at least some of the occult abortions that are not detected by high-sensitivity comes from studies comparing aneuploidy in very young embryos (cleavage stage and blastocysts) to conceptuses that spontaneously aborted after a pregnancy had been clinically detected. At the early embryo stages, monosomy (missing one homolog from one or more of the 23 pairs of homologous chromosomes) and trisomies (a extra chromosome at one or more of the 23 pairs of homologous chromosomes) were found to be equally common. But among conceptuses that survive to clinical detection, and then abort, essentially no autosomal monosomies were observed (<<1%). This repeated finding demonstrates that all autosomal monosomic conceptuses spontaneously abort before a pregnancy can be detected by elevated levels of hCG, i.e., prior to implantation. As a consequence, for every observed aborted conceptus that carried one or more trisomies after clinical detection, there must have been one occult aborted conceptus due to one or more monosomies. At least 50% of aborted fetuses are karyotypically abnormal and at least 60% of these carry one or more trisomies. There are therefore at least 0.5*0.6* = 0.3 occult abortions due to monosomy for every detected post-implantation abortion. In Fig. 3, I have added these additional occult abortions to the total."

"6.2 Genetic factors The finding of an abnormal parental karyotype should prompt referral to a clinical geneticist. Genetic counselling offers the couple a prognosis for the risk of future pregnancies with an unbalanced chromosome complement and the opportunity for familial chromosome studies. Reproductive options in couples with chromosomal rearrangements include proceeding to a further natural pregnancy with or without a prenatal diagnosis test, gamete donation and adoption. Preimplantation genetic diagnosis has been proposed as a treatment option for translocation carriers. Since preimplantation genetic diagnosis necessitates that the couple undergo in vitro fertilisation to produce embryos, couples with proven fertility need to be aware of the financial cost as well as implantation and live birth rates per cycle following in vitro fertilisation/preimplantation genetic diagnosis. Furthermore, they should be informed that they have a higher (50–70%) chance of a healthy live birth in future untreated pregnancies following natural conception than is currently achieved after preimplantation genetic diagnosis/in vitro fertilisation (approximately 30%). Preimplantation genetic screening with in vitro fertilisation treatment in women with unexplained recurrent miscarriage does not improve live birth rates. Preimplantation genetic screening in conjunction with in vitro fertilisation has been advocated as a treatment option for women with recurrent miscarriage, the rationale being that the identification and transfer of what are thought to be genetically normal embryos will lead to a live birth. The live birth rate of women with unexplained recurrent miscarriage who conceive naturally is significantly higher than currently achieved after preimplantation genetic screening/in vitro fertilisation (20–30%)."

"I'm telling you, with everything we know, about science, about the makeup of the human body, what happened in that classroom is impossible. That kid attracted an arc of electricity from thirty feet away, and not just from the Jacob's Ladder, I mean, after a second it was like it was coming out of the whole… building."

"We're stumbling around in a very dark age basically trying not to kill each other. So it hurts me when you say "So what?" Because you are not just different, Jeremy, I think you have a mind that we won't evolve to for like thousands of years — you're maybe the man of the future right here and now."

"People love a nice shot of an orange sunrise over the islands in Casco Bay, of waves crashing on the rocks in front of Portland Head Light, or of seagulls fighting over rotten bait. But the time tested crowd favorite is a picture of a mutant lobster. They’re actually a lot more common than one might think, sometimes they come up with multiple claws, sometimes they’re different colors, and sometimes they’re so riddled with shell disease that they’re almost unrecognizable."

"We hypothesize that the increased risk of spontaneous abortion with male age is a consequence of an increasing frequency of chromosomal anomalies in the spermatozoa with male age, which in turn increases the risk of spontaneous abortion. The influence of male age on the proportion of spermatozoa carrying a chromosomal anomaly or with damaged DNA has been documented in several groups of men. It may well result, in part, from the continuous replication of stem cell chromosomes from puberty onward; indeed, male stem cells have undergone about 150 chromosomal replications at the age of 20 years and about 600 by the age of 40 years. The chromosomal anomalies found in spontaneous abortions include autosomal trisomies, present in about 50 percent of abortuses with chromosomal anomalies, monosomy X (present in about 20 percent), and triploidy (16 percent). The remaining 12 percent correspond mainly to tetraploidy and structural anomalies of the chromosomes. The two most frequent anomalies sometimes have a paternal origin: Autosomal trisomies stem from nondisjunction during spermatogenesis in 10–20 percent or more of cases and, in monosomy X, the missing chromosome is most often the paternal one. Moreover, sperm chromosome aneuploidy may play a role in the etiology of recurrent pregnancy loss."

"There was a world of mutants, men and women who were more than normal men and women, persons who had certain human talents and certain human understandings which the normal men and women of the world had never known, or having known, could not utilize in their entirety, unable to use intelligently all the mighty powers which lay dormant in their brains."

"The people finally know. They've been told about the mutants. And they hated the mutants. Of course, they hated them. They hated them because the existence of the mutants makes them second-class humans, because they are Neanderthalers suddenly invaded by a bow and arrow people."

"Genetic bases of defective chromosome content or structure In a biological sense, genetic defects leading to abortion may originate from two partners: The conceptus and the uterus. From the conceptus side, it is well established that chromosomal anomalies lead to implantation defects. However, they occur mostly stochastically; to be the genetic cause of a recurrent loss, a genetic defect leading to systematic chromosome anomalies has to be found, as nicely reviewed recently by Kurahashi and coworkers. Abnormal chromosome structure may originate from defects in the checkpoint mechanisms that constitute a quality control factory of the cell, which is able to detect meiosis anomalies and is called Spindle Assembly Checkpoint (SAC), constituted by pro teins such as Mad1, Mad2, Bub1, Bub3, BubR1, and Mps1. A very recent study addressed this question on the general issue of defective reproduction performance, by screening two candidate genes, aurora kinase B (AURKB) and synaptonemal complex protein 3 (SYCP3). In the AURKB gene, the authors identified low frequency (0.5%) non synonymous variants (c. 155C.T, c. 236T.C, and c. 880G.A) inducing the changes p.A52V, p.I79T, and p.A294T in the polypeptidic chain, respectively. 236T >C and 880G >A were associated with antecedents of pregnancy losses. This preliminary study is one of those that pave the way toward evaluating genes playing a role in the quality of the meiotic progression. Two other genes have been investigated to this respect in miscarriage, BUB1 and MAD2. The authors showed firstly that as generally assumed, half the embryos from spontaneous miscarriages have an abnormal karyotype. By western blotting, the authors quantified the two proteins and estimated that they were under expressed in pathological cases. The authors also isolated chorionic villi where they targeted BUB1 and MAD2 expression by short hairpin RNA (shRNA) and showed that this induces an abnormal karyotype at a ~ sixfold increased frequency, compared to controls (indicating that mitotic defects can also be induced when these genes are dysfunctional). The role of MAD2 in such defects was independently confirmed by another study on trisomic abortuses. Clearly, therefore, anomalies in spindle assembly can lead to aneuploidies, and infertilities in the most severe cases, such as in the case of the recently identified mutation of the cohesin STAG3, leading to premature ovarian failure, but less severe mutations in the SAC genes could lead to variants that have more subtle effects. There is clearly space for studying this aspect of spindle stability on a wider basis than what has been performed up to now in the context of recurrent miscarriage."

"Robert Anton Wilson is the unacknowledged elephant in our cultural living room: a direct and indirect influence on popular books, movies, TV shows, music, games, comics, and commentary. … Wilson is a primary source for the ironic style of conspiracism, a sensibility that treats alleged cabals not as intrigues to be exposed or lies to be debunked but as a bizarre mutant mythos to be mined for laughs, metaphors, and social insights."

"Of all creatures, only the Binder had bested the Lord of Hellwell. Then the gods had come to challenge his power. They had been puny in the early days, struggling to discipline their mutant powers with drugs, hypnosis, meditation, neurosurgery — forging them into Attributes — and across the ages, those powers had grown. Four of them had entered Hellwell, only four, and his legions had not been able to repel them."