Otoconin-90, the mammalian otoconial matrix protein, contains two domains of homology to secretory phospholipase A2

The ability to sense orientation relative to gravity requires dense particles, called otoconia, which are localized in the vestibular macular organs. In mammals, otoconia are composed of proteins (otoconins) and calcium carbonate crystals in a calcite lattice. Little is known about the mechanisms that regulate otoconial biosynthesis. To begin to elucidate these mechanisms, we have partially sequenced and cloned the major protein component of murine otoconia, otoconin-90 (OC90). The amino acid sequence identified an orphan chimeric human cDNA. Because of its similarity to secretory phospholipase A2 (sPLA2), this gene was referred to as PLA2-like (PLA2L) and enabled the identification of human Oc90. Partial murine cDNA and genomic clones were isolated and shown to be specifically expressed in the developing mouse otocyst. The mature mouse OC90 is composed of 453 residues and contains two domains homologous to sPLA2. The cloning of Oc90 will allow an examination of the role of this protein in otoconial biosynthesis and in diseases that affect the vestibular system.

Unwinding of nucleic acids by HCV NS3 helicase is sensitive to the structure of the duplex

Hepatitis C virus (HCV) helicase, non-structural protein 3 (NS3), is proposed to aid in HCV genome replication and is considered a target for inhibition of HCV. In order to investigate the substrate requirements for nucleic acid unwinding by NS3, substrates were prepared by annealing a 30mer oligonucleotide to a 15mer. The resulting 15 bp duplex contained a single-stranded DNA overhang of 15 nt referred to as the bound strand. Other substrates were prepared in which the 15mer DNA was replaced by a strand of peptide nucleic acid (PNA). The PNA–DNA substrate was unwound by NS3, but the observed rate of strand separation was at least 25-fold slower than for the equivalent DNA–DNA substrate. Binding of NS3 to the PNA–DNA substrate was similar to the DNA–DNA substrate, due to the fact that NS3 initially binds to the single-stranded overhang, which was identical in each substrate. A PNA–RNA substrate was not unwound by NS3 under similar conditions. In contrast, morpholino–DNA and phosphorothioate–DNA substrates were utilized as efficiently by NS3 as DNA–DNA substrates. These results indicate that the PNA–DNA and PNA–RNA heteroduplexes adopt structures that are unfavorable for unwinding by NS3, suggesting that the unwinding activity of NS3 is sensitive to the structure of the duplex.

Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions.

Macromolecular interactions define many biological phenomena. Although genetic methods are available to identify novel protein-protein and DNA-protein interactions, no genetic system has thus far been described to identify molecules or mutations that dissociate known interactions. Herein, we describe genetic systems that detect such events in the yeast Saccharomyces cerevisiae. We have engineered yeast strains in which the interaction of two proteins expressed in the context of the two-hybrid system or the interaction between a DNA-binding protein and its binding site in the context of the one-hybrid system is deleterious to growth. Under these conditions, dissociation of the interaction provides a selective growth advantage, thereby facilitating detection. These methods referred to as the "reverse two-hybrid system" and "reverse one-hybrid system" facilitate the study of the structure-function relationships and regulation of protein-protein and DNA-protein interactions. They should also facilitate the selection of dissociator molecules that could be used as therapeutic agents.

The C-proteinase that processes procollagens to fibrillar collagens is identical to the protein previously identified as bone morphogenic protein-1.

Bone morphogenic protein-1 (BMP-1) was originally identified as one of several BMPs that induced new bone formation when implanted into ectopic sites in rodents. BMP-1, however, differed from other BMPs in that it its structure was not similar to transforming growth factor beta. Instead, it had a large domain homologous to a metalloendopeptidase isolated from crayfish, an epidermal growth-factor-like domain, and three regions of internal sequence homology referred to as CUB domains. Therefore, BMP-1 was a member of the "astacin families" of zinc-requiring endopeptidases. Many astacins have been shown to play critical roles in embryonic hatching, dorsal/ventral patterning, and early developmental decisions. Here, we have obtained amino acid sequences and isolated cDNA clones for procollagen C-proteinase (EC 3.4.24.19), an enzyme that is essential for the processing of procollagens to fibrillar collagens. The results demonstrate that procollagen C-proteinase is identical to BMP-1.

An introduction to alysidal algebra (V): phenomenological components

Purpose – This paper aims to refer to a subjective approach to a type of complex system: human ecosystems, referred to as deontical impure systems (DIS) to capture a set of properties fundamental to the distinction between human and natural ecosystems. There are four main phenomenological components: directionality, intensity, connection energy and volume. The paper establishes thermodynamics of deontical systems based on the Law of Zipf and the temperature of information. Design/methodology/approach – Mathematical and logical development of human society structure. Findings – A fundamental question in this approach to DIS is the intensity or forces of a relation. Concepts are introduced as the system volume and propose a system thermodynamic theory. It hints at the possibility of adapting the fractal theory by introducing the fractal dimension of the system. Originality/value – This paper is a continuation of other previous papers and developing the theory of DIS.

Request to parents of students, 1809 March 21

This brief handwritten note requests a meeting with the parents of Croswell's students in order to continue the school.

Petition to the General Court (photostat copy), 1646 May 15

Photostat copy of a petition from ferrymen James Heyden and Francis Hudson requesting compensation for unpaid fares of "magistrates & deputyes" using the ferry.

Petition to the General Court (photostat copy), 1662

Photostat copy of a petition from ferrymen Francis Hudson and John Burrage requesting the General Court coin twopenny and fourpenny pieces for change so the ferrymen could accommodate customers attempting to pay with larger currency denominations.

Draft of a petition to the General Court from the Corporation, 1743 October 26-27

Two-page handwritten draft of a petition to the General Court signed by President Edward Holyoke, and a half-page letter that accompanied the draft from President Holyoke to Tutor Flynt, a member of the Committee to draft the petition.

Letter to the Selectmen of Charlestown, 1785 January 13

Three-and-a-half-page handwritten letter from "FM Dana by order &c," to the Selectmen of Charlestown. Dana is presumably speaking on behalf of the Selectmen of Cambridge and provides an extensive response to the Charlestown Selectmen about increased ferry fares that is critical of the demands of the Harvard Corporation.

Letter from Charles Stearns to Edward Wigglesworth, 1781 November 8, and receipt signed by Stephen Sewall, 1781 November 16

In a letter to Wigglesworth, acting president of Harvard and Hollis Professor of Divinity, Stearns resigns his tutorship and writes that he will return an unnamed silver tankard and various books to the College. The folder also includes as a receipt for those objects upon their return, signed by Harvard Professor Stephen Sewall.

Letter from Oliver Wendell to John Thornton Kirkland, 1817

One letter offering Harvard President Kirkland a donation of 100 dollars to acquire a "handsome Christening Cup or Baptismal Basin" for the new College Church, which held services in University Hall.

The sovereign debt crisis that isn't: Or, How to turn a lending crisis into a spending crisis and pocket the spread. ACES Cases No. 2014.1

It’s a testament to the power of ideas in politics that the ongoing policy disaster in Europe is still referred to, by academic as well as popular commentators, as the European Sovereign Debt Crisis. That there was a crisis in European sovereign debt markets in 2010 through the middle of 2012 is not in doubt. That is was a crisis of European sovereign debt markets generated by ‘too much spending’ should be very much in doubt. The ongoing European economic crisis is in fact a transmuted private sector banking crisis first exacerbated and then calmed by central bank policy, the costs of which have been asymmetrically distributed across European mass publics.

Fourth International conference of American states. Message from the President of the United States transmitting a letter from the secretary of state inclosing a report, with accompanying papers, relative to the fourth International conference of American states, held at Buenos Aires from July 12 to August 30, 1910 ...

Henry White, chairman of the delegation.

Message from the president of the United States relative to civil rights.

"February 28, 1963.--Referred to the Committee on the Judiciary and ordered to be printed."