Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type β signaling

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by endocrine tumors of parathyroids, pancreatic islets, and anterior pituitary. The MEN1 gene encodes a nuclear protein called menin. In MEN1 carriers inactivating mutations give rise to a truncated product consistent with menin acting as a tumor suppressor gene. However, the role of menin in tumorigenesis and its physiological functions are not known. Here, we show that menin inactivation by antisense RNA antagonizes transforming growth factor type β-mediated cell growth inhibition. Menin interacts with Smad3, and antisense menin suppresses transforming growth factor type β-induced and Smad3-induced transcriptional activity by inhibiting Smad3/4-DNA binding at specific transcriptional regulatory sites. These results implicate a mechanism of tumorigenesis by menin inactivation.

Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt– Jakob disease: Implications for human health

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt–Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

Traité des champignons, ouvrage dans lequel, on trouve après l'histoire analytique & chronologique des découvertes & des travaux sur ces plantes ...

2

Letters from Daniel Bates to William Jenks, May 1795-September 1798

Daniel Bates wrote these five letters to his friend and classmate, William Jenks, between May 1795 and September 1798. In a letter written May 12, 1795, Bates informs Jenks, who was then employed as an usher at Mr. Webb's school, of his studies of Euclid, the meeting of several undergraduate societies, and various sightings of birds, gardens and trees. In a letter written in November 1795 from Princeton, where he was apparently on vacation with the family of classmate Leonard Jarvis, he describes playing the game "break the Pope's neck" and tells Jenks what he was reading (Nicholson, Paley?, and Thompson) and what his friend's father was reading (Mirabeau and Neckar).

Atlantic 231Pa/230Th and biogenic opal compilation of the Holocene and the LGM

The strength and geometry of the Atlantic meridional overturning circulation is tightly coupled to climate on glacial-interglacial and millennial timescales, but has proved difficult to reconstruct, particularly for the Last Glacial Maximum. Today, the return flow from the northern North Atlantic to lower latitudes associated with the Atlantic meridional overturning circulation reaches down to approximately 4,000 m. In contrast, during the Last Glacial Maximum this return flow is thought to have occurred primarily at shallower depths. Measurements of sedimentary 231Pa/230Th have been used to reconstruct the strength of circulation in the North Atlantic Ocean, but the effects of biogenic silica on 231Pa/230Th-based estimates remain controversial. Here we use measurements of 231Pa/230Th ratios and biogenic silica in Holocene-aged Atlantic sediments and simulations with a two-dimensional scavenging model to demonstrate that the geometry and strength of the Atlantic meridional overturning circulation are the primary controls of 231Pa/230Th ratios in modern Atlantic sediments. For the glacial maximum, a simulation of Atlantic overturning with a shallow, but vigorous circulation and bulk water transport at around 2,000 m depth best matched observed glacial Atlantic 231Pa/230Th values. We estimate that the transport of intermediate water during the Last Glacial Maximum was at least as strong as deep water transport today.

Three revolutionary architects : Boullée, Ledoux, and Lequeu.

Includes bibliographical references.

Tractatus posthumus Jani Jacobi Boissardi Vesuntini De divinatione & magicis praestigiis : quarum veritas ac vanitas solidè exponitur per descriptionem deorum fatidicorum qui olim responsa dederunt : eorundemque prophetarum, sacerdotum, phoebadum, sybyllarum & divinorum, qui priscis temporibus celebres oraculis exstiterunt ; adjunctis simul omnium effigiebus, ab ipso autore e gemmis, marmoribus, tabulisq[ue] antiquis ad vivum delineatus : jam modo eleganter aeri incisis per Joh. Theodor. de Bry ...

Includes errata, last p.

De l'Isthme de Suez et du canal maritime à ouvrir de la Méditerranée à̀ la Mer-Rouge /

"Extrait de la Revue des deux mondes, livraison du 15 mars 1855."

Discours qui a eu la mention honorable, sur cette question proposée par l'Institut de France: quelle a été l'influence de la reformation de Luther, sur les lumières et la situation politique des différens états de l'Europe? ...

Mode of access: Internet.