Introduction
Eve K. Boyle, Vondel S. E. Mahon, Rui Diogo in Handbook of Muscle Variations and Anomalies in Humans, 2022
When Charles Darwin wanted to convince a highly skeptical scientific community and general public that we evolved from other primates in The Descent of Man (1871), he started by discussing human anatomical variations and anomalies. Why? Because he knew that a strong way to show that we descend from other animals is to highlight the commonalities we share with them and particularly, the commonalities that are only present in some humans, as a reminder of the nonhuman ancestors we had several millions of years ago. Our anatomical variations and anomalies, in particular those that are related to the presence of evolutionary reversions, are indeed the most direct, strong evidence of our evolutionary past. This is because there are features that are present in adults of other species that are typically absent in humans, but for some reason can still be found in some human adults. The most likely scientific explanation, Darwin argued, is that such features were present in our adult ancestors and then were evolutionary lost but evolutionarily “re-acquired.” Not only that: even for some anatomical features that appear in humans that have nothing to do with traits typically present in other animals, these usually also show that we share evolutionary and developmental commonalities with them because such variations and anomalies are also present in some cases within other species. For instance, one of the more severe malformations in humans is cyclopia, the presence of a single eye. We never had an ancestor that was truly a cyclops, but many other mammals also have cyclopic malformations.
Growth of the Orbit
D. Dixon Andrew, A.N. Hoyte David, Ronning Olli in Fundamentals of Craniofacial Growth, 2017
Some of the grossest orbital malformations occur in holoprosencephaly. “In alobar prosencephaly, the embryonic forebrain fails to cleave sagittally into cerebral hemispheres, transversely into telencephalon and diencephalon, and horizontally into olfactory and optic bulbs” (Cohen, 1986). There may result the single median orbit of cyclopia, with or without a tubular proboscis above, with eye development varying from anophthalmia, or monophthalmia to synophthalmia; ethmocephaly with hypotelorism and absent nose; or premaxillary agenesis, again with hypotelorism, which also occurs in cebocephaly where there is a single nostril nose (Cohen et al. in Bergsma, 1971; Cohen and Sulik, 1992). Currarino and Silverman (1960) and Silverman (1965) described hypotelorism in association with trigonocephaly and arrhinen-cephaly (part of the spectrum of holoprosencephaly). McGrath (1989, 1992) and McGrath and Sperber (1990) gave detailed descriptions of the structure and contents of the median orbit in human cyclopia. In the absence of some nasal structures — mesethmoid (crista galli, perpendicular plate of the ethmoid and adjacent portion of the cribriform plate), nasal septum, and vomer — and parts of the medial walls of the orbits, the frontais approach each other above the single cavity, and the maxillae fuse below to form a floor, which also incorporates the lacrimal and palatine bones, and which extends further backwards than normal because the presphenoid is absent. The ectethmoid conchae do develop.
Small-Molecule Targeted Therapies
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Aberrant activation of the Hedgehog pathway has been implicated in the genesis and progression of a number of cancer types including basal cell carcinoma and medulloblastoma, making it a potential target for therapeutic intervention. Cyclopamine (11-deoxojervine), a steroidal alkaloid, is a naturally occurring SMO antagonist and is a teratogen isolated from the corn lily (Veratrum californicum) that causes fatal birth defects. It prevents the embryonic brain from separating into two lobes which causes the development of a single eye (cyclopia), a phenomenon first observed in sheep in the 1950s due to grazing on the corn lily.
Protective effects of fermented honeybush (Cyclopia intermedia) extract (HU-018) against skin aging: a randomized, double-blinded, placebo-controlled study
Published in Journal of Cosmetic and Laser Therapy, 2018
Sun Young Choi, Ji Yeon Hong, Eun Jung Ko, Beom Joon Kim, Sung-Woon Hong, Mi Hyoung Lim, Sung Hum Yeon, Rak Ho Son
Cyclopia intermedia, also referred to as honeybush, is a popular traditional herbal tea in its native South Africa and has a growing worldwide market. Cyclopia plants are rich in polyphenols including xanthones, flavones, isoflavones, flavanones, and soumestans (16–18). Of these various polyphenols, hesperidin has been shown to be an active marker compound of fermented C. intermedia extracts. Hesperidin is a bioactive flavonoid characterized by its antioxidant and antimutagenic properties. Many studies have demonstrated that hesperidin exerts diverse positive effects including antimicrobial activity, anti-carcinogenic activity, anti-melanogenic activity, and UV protective activity (19–22). Based on its biological effects, hesperidin is a popular active cosmetic ingredient of various anti-wrinkle and whitening products(23). Therefore, we focused on the potential of C. intermedia, a source of hesperidin, as an effective anti-aging dietary supplement.
Screening drugs for myocardial disease in vivo with zebrafish: an expert update
Published in Expert Opinion on Drug Discovery, 2019
Yanbin Zhao, Kun Zhang, Patrick Sips, Calum A. MacRae
A phenotype-based approach is designed to study biologically active small molecules based on their interactions with whole organisms. Before in vitro approaches made possible by advances in molecular biology, many biologically active molecules were empirically discovered based on their unexpected phenotypes resulting from their effects on whole organisms. For instance, the anticoagulant dicoumarol and its derivatives were first discovered when cattle fed on rotting sweet clover died of internal bleeding, while the Hedgehog signaling antagonist cyclopamine was discovered because of a fetal deformity, cyclopia, which was observed in offspring from sheep grazing on veratrum californicum [18,19]. Some attempts were also made to accelerate the discovery of bioactive small molecules by systematic chemical screening, albeit in costly screens in modest numbers of rodents [20,21].
Fetal hydrops – a review and a clinical approach to identifying the cause
Published in Expert Opinion on Orphan Drugs, 2020
Esther Dempsey, Tessa Homfray, John M Simpson, Steve Jeffery, Sahar Mansour, Pia Ostergaard
Trisomy 18 (Edward Syndrome) and Trisomy 13 (Patau Syndrome) are also relatively frequently diagnosed in the context of fetal hydrops. Both are multisystem disorders with Edward syndrome characteristically recognized by the ultrasound demonstration of clenched hands and ‘rocker-bottom feet’. Midline defects are prominent in Patau syndrome with holoprosencephaly and cyclopia seen in addition to multisystem abnormalities. Fetal hydrops develops in 14% of fetuses with trisomy 18 and 3% of those with trisomy 13 [102].
Related Knowledge Centers
- Birth Defect
- Childbirth
- Cyclopamine
- Forebrain
- Holoprosencephaly
- Teratology
- Miscarriage
- Orbit
- Proboscis
- Stillbirth