Covalent Modification of p53 by ()-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one.

is commonly mutated in cancer, giving rise to loss of wild-type tumor suppressor function and increases in gain-of-function oncogenic roles. Thus, inhibition of mutant p53 and reactivation of wild-type function represents a potential means to target diverse tumor types. ()-1-(4-Methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one (NSC59984), first identified from a high-throughput screen, induces wild-type p53 signaling and antiproliferative effects while inhibiting mutant p53 gain-of-function activities.

Did Michelangelo paint a young adult woman with breast cancer in "The Flood" (Sistine Chapel, Rome)?

The Flood is the first pictorial scene that Michelangelo Buonarroti painted on the ceiling of the Sistine Chapel in the Vatican. On the right side of the fresco a woman with abnormal breast morphology is presented and the nature of her disease is considered using the Guidelines for Iconodiagnosis. A team of experts covering art history, art expertise, medicine, genetics, and pathology undertook the process and concluded that the pathology shown is probably breast cancer, most likely linked to the symbolic significance of an inevitable death as expressed in the Book of Genesis.

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species.

Although few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability of these methyltransferases to methylate thiol-based HDACis is conserved across different species.

The Methyltransferases METTL7A and METTL7B Confer Resistance to Thiol-Based Histone Deacetylase Inhibitors.

Histone deacetylase inhibitors (HDACi) are part of a growing class of epigenetic therapies used for the treatment of cancer. Although HDACis are effective in the treatment of T-cell lymphomas, treatment of solid tumors with this class of drugs has not been successful. Overexpression of the multidrug resistance protein P-glycoprotein (P-gp), encoded by ABCB1, is known to confer resistance to the HDACi romidepsin in vitro, yet increased ABCB1 expression has not been associated with resistance in patients, suggesting that other mechanisms of resistance arise in the clinic.

The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species.

Although few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability of these methyltransferases to methylate thiol-based HDACis is conserved across different species.

The Evolution of Pituitary Gland Surgery from the Ancients to the Millennials.

Located at the base of the skull, the pituitary gland has a long and controversial history, not only in terms of its anatomy, but especially in the functions it performs and in the attempt to approach it surgically. Considered by Galen of Pergamon to have a role in releasing waste products of the brain, a theory accepted until the 17th century, the pituitary gland became a separate entity once with the anatomical descriptions of the famous Andreas Vesalius. At the beginning of the 18th century, researches of the time began to be more and more interested in this gland, trying to identify its functions, and at the same time correcting the traditional theories that were wrong or incomplete.

Chronic Gastro-Duodenal Ulcerative Disease and the Death of Father Stephan Schätzl from Viechtwang (Austria).

Stephan Schätzl was the parish priest of Viechtwang, Upper Austria. He lived in the aftermath of the Peace of Augsburg in a period of schism between Roman Catholics and Lutherans. His portrait, depicted only 6 days before his demise in 1590, shows that he had extreme ante mortem cachexia.

A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma.

Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pyrimidine biosynthesis pathway.

Votive Offerings from Floresti Orthodox Monastery in Romania: An Ophthalmological Lesson from the Eighteenth and Nineteenth Centuries CE.

Since Antiquity, votive offerings were deposited in temples dedicated to deities in order to fulfil a special request of a supplicant. Later, in Orthodox churches, votive offerings entered in the form of anatomical ex-voto or tamata, metallic effigies that realistically represented the disease-affected portion of the body. In this paper, we show four tamata from eighteenth-nineteenth century identified in the museum of the Orthodox monastery of Floresti (Romania); votive offerings that represent ocular pathologies.

Unilateral Facial Asymmetry in a 40 BCE Roman Carved Head.

We describe the peculiar facial morphology of a carved head dating to the end of the Roman Republican period (40 BCE) which displays evident unilateral asymmetry. A comprehensive discussion of the different etiologies is provided and a contextualization of this condition in the broader frame of Roman artistic verism is offered. This case study contributes to the knowledge of disease presentation in the ancient world, with a special focus on the anatomy of soft tissue pathology.