Elongin BC complex prevents degradation of von Hippel-Lindau tumor suppressor gene products

Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene causes the familial cancer syndrome, VHL disease, characterized by a predisposition to renal cell carcinoma and other tumor types. Loss of VHL gene function also is found in a majority of sporadic renal carcinomas. A preponderance of the tumor-disposing inherited missense mutations detected in VHL disease are within the elongin-binding domain of VHL. This region mediates the formation of a multiprotein VHL complex containing elongin B, elongin C, cul-2, and Rbx1. This VHL complex is thought to function as an E3 ubiquitin ligase. Here, we report that VHL proteins harboring mutations which disrupt elongin binding are unstable and rapidly degraded by the proteasome. In contrast, wild-type VHL proteins are directly stabilized by associating with both elongins B and C. In addition, elongins B and C are stabilized through their interactions with each other and VHL. Thus, the entire VHL/elongin complex is resistant to proteasomal degradation. Because the elongin-binding domain of VHL is frequently mutated in cancers, these results suggest that loss of elongin binding causes tumorigenesis by compromising VHL protein stability and/or potential VHL ubiquitination functions.

Neural fate of seen and unseen faces in visuospatial neglect: A combined event-related functional MRI and event-related potential study

To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception.

The Wheat Peptidyl Prolyl cis-trans-Isomerase FKBP77 Is Heat Induced and Developmentally Regulated1

We isolated a cDNA encoding a 568-amino acid, heat-stress-induced peptidyl prolyl isomerase belonging to the FK506-binding-protein (FKBP) family. The open reading frame encodes for a peptidyl prolyl isomerase that possesses three FKBP-12-like domains, a putative tetratricopeptide motif, and a calmodulin-binding domain. Specific antibodies showed that the open reading frame encodes a heat-induced 77-kD protein, the wheat FKBP77 (wFKBP77), which exhibits 84% identity with the wFKBP73 and 42% identity with the human FKBP59. Because of the high similarity in sequence to wFKBP73, wFKBP77 was designated as the heat-induced isoform. The wFKBP77 mRNA steady-state level was 14-fold higher at 37°C than at 25°C. The wFKBP77 transcript abundance was the highest in mature embryos that had imbibed and 2-d-old green shoots exposed to 37°C, and decreased to 6% in 6-d-old green shoots. The transcript level returned to the level detected at 25°C after recovery of the embryos for 90 min at 25°C. We compared wFKBP73 and wFKBP77 with the heat-shock proteins having cognate and heat-stress-induced counterparts.

Characterization of a Maize Tonoplast Aquaporin Expressed in Zones of Cell Division and Elongation1

We studied aquaporins in maize (Zea mays), an important crop in which numerous studies on plant water relations have been carried out. A maize cDNA, ZmTIP1, was isolated by reverse transcription-coupled PCR using conserved motifs from plant aquaporins. The derived amino acid sequence of ZmTIP1 shows 76% sequence identity with the tonoplast aquaporin γ-TIP (tonoplast intrinsic protein) from Arabidopsis. Expression of ZmTIP1 in Xenopus laevis oocytes showed that it increased the osmotic water permeability of oocytes 5-fold; this water transport was inhibited by mercuric chloride. A cross-reacting antiserum made against bean α-TIP was used for immunocytochemical localization of ZmTIP1. These results indicate that this and/or other aquaporins is abundantly present in the small vacuoles of meristematic cells. Northern analysis demonstrated that ZmTIP1 is expressed in all plant organs. In situ hybridization showed a high ZmTIP1 expression in meristems and zones of cell enlargement: tips of primary and lateral roots, leaf primordia, and male and female inflorescence meristems. The high ZmTIP1 expression in meristems and expanding cells suggests that ZmTIP1 is needed (a) for vacuole biogenesis and (b) to support the rapid influx of water into vacuoles during cell expansion.

Payment order for Martha Thayer, 1800 March 26

Handwritten order to John Sale to pay scholarship funds to Martha Thayer for use by her son Andrew Eliot Thayer (Harvard AB 1803), signed by William Emerson, David Tilden, and James Morrill.

Payment order for Martha Thayer, 1800 December 8

Handwritten order to John Sale to pay scholarship funds to Martha Thayer for use by her son Andrew Eliot Thayer (Harvard AB 1803), signed by William Emerson, David Tilden, and James Morrill.

Tutors grants for £77.8.4, 1773

Handwritten receipt signed by Joseph Willard, John Marsh, John Marsh, Andrew Eliot Jr., John Wadsworth, and S. Hall acknowledging money received between August 20th and 23rd, 1773. A handwritten transcription of the Corporation vote on September 7, 1772 that, "the Tutors be allowed in addition to their salary twenty pounds," is signed as a true copy by President Samuel Locke at the beginning of the document.

Cambridge Main St. Subway, walls and well found in 1910 while excavating for Harvard Sq. station, 1912, with Letter from Edward Dana to S.E. Morison, 15 March 1934

Second copy of the previous blueprint. Also includes a 1934 letter from Edward Dana of the Boston Elevated Railway Public Trustees to Samuel Eliot Morison, Editor of The Tercentennial History of Harvard University responding to Morison's request for additional information about discovery of early Harvard building foundations during the subway construction excavation in Harvard Square.

Subjects suggested by Edward Everett, 1823, undated

Four letters in the hand of Edward Everett, the Eliot Professor of Greek Literature from 1815 until 1826, containing suggested subjects and questions for President Kirkland. Three of the documents are undated and one is dated November 5, 1823.

Copy of resolves of the Overseers relative to the Disturbances at the Coll. ye beginning of Apr 1768, 1768 April 12

Handwritten copy of six resolves and one vote passed by the Board of Overseers regarding the behavior of undergraduates, copied by Andrew Eliot, secretary to the Board of Overseers, and entered into the College Book No. 7, page 177. The resolves reflected on the insubordination of Harvard students, declared the support of the Overseers towards the efforts of the College government to maintain order, and proclaimed the expulsion of guilty students a "just punishment." The Overseers voted to have the President read the resolves in the College Chapel, which was done by President Edward Holyoke on April 12, 1768.

"An account of books belonging to the late library wch were in the hands of the senior sophisters when it was consumed by fire," ca. 1764

This list appears to be in the hand of Andrew Eliot, Librarian from 1763 to 1767. Books are listed according to format (folio, quarto, octavo) and entries indicate the surname of the student who checked the book out, its author and title, and whether or not the book had since been "returned and sent down." Some entries indicate unusual locations, including "says he returned it to the Pres[ident]" and "Dr. Marsh has it."

"Continuation of the acco[unt] of books saved from the Fire by being borrow'd," ca. 1764

Lists books borrowed by those with surnames Wyeth, Goodhue, Eliot, Langdon, Adams, Apthorp, Bowdoin, Chardon, and Mayhew. Entries include format, title, author, and volume number. Written in multiple hands.

Notes : manuscript, [16---17--]

Notes on and excerpts of materials used by Harvard undergraduates in the 17th and early 18th cent.; including Prolegomena de arte in genere; William Brattle's A compendium of logick; Alexander Richardson's In dialecticam brevis commentatio; Grammatica hebraea; and other works.