HCC-2, a human chemokine: Gene structure, expression pattern, and biological activity

Cloning and sequencing of the upstream region of the gene of the CC chemokine HCC-1 led to the discovery of an adjacent gene coding for a CC chemokine that was named “HCC-2.” The two genes are separated by 12-kbp and reside in a head-to-tail orientation on chromosome 17. At variance with the genes for HCC-1 and other human CC chemokines, which have a three-exon-two-intron structure, the HCC-2 gene consists of four exons and three introns. Expression of HCC-2 and HCC-1 as studied by Northern analysis revealed, in addition to the regular, monocistronic mRNAs, a common, bicistronic transcript. In contrast to HCC-1, which is expressed constitutively in numerous human tissues, HCC-2 is expressed only in the gut and the liver. HCC-2 shares significant sequence homology with CKβ8 and the murine chemokines C10, CCF18/MRP-2, and macrophage inflammatory protein 1γ, which all contain six instead of four conserved cysteines. The two additional cysteines of HCC-2 form a third disulfide bond, which anchors the COOH-terminal domain to the core of the molecule. Highly purified recombinant HCC-2 was tested on neutrophils, eosinophils, monocytes, and lymphocytes and was found to exhibit marked functional similarities to macrophage inflammatory protein 1α. It is a potent chemoattractant and inducer of enzyme release in monocytes and a moderately active attractant for eosinophils. Desensitization studies indicate that HCC-2 acts mainly via CC chemokine receptor CCR1.

An isolated, surface-expressed I domain of the integrin αLβ2 is sufficient for strong adhesive function when locked in the open conformation with a disulfide bond

We introduced disulfide bonds to lock the integrin αLβ2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing αLβ2 heterodimers containing locked-open but not locked-closed or wild-type I domains constitutively adhered to intercellular adhesion molecule-1 (ICAM-1) substrates. Locking the I domain closed abolished constitutive and activatable adhesion. The isolated locked-open I domain bound as well as the activated αLβ2 heterodimer, and binding was abolished by reduction of the disulfide. Lovastatin, which binds under the conformationally mobile C-terminal α-helix of the I domain, inhibited binding to ICAM-1 by αLβ2 with wild-type, but not locked-open I domains. These data establish the importance of conformational change in the αL I domain for adhesive function and show that this domain is sufficient for full adhesive activity.

Probing of tertiary interactions in RNA: 2'-hydroxyl-base contacts between the RNase P RNA and pre-tRNA.

A general method has been developed to analyze all 2' hydroxyl groups involved in tertiary interactions in RNA in a single experiment. This method involves comparing the activity of populations of circularly permuted RNAs that contain or lack potential hydrogen-bond donors at each position. The 2' hydroxyls of the pre-tRNA substrate identified as potential hydrogen bond donors in intermolecular interactions with the ribozyme from eubacterial RNase P (P RNA) are located in the T stem and T loop, acceptor stem, and 3' CCA regions. To locate the hydrogen-bond acceptors for one of those 2' hydroxyls in the P RNA, a phylogenetically conserved adenosine was mutated to a guanosine. When this mutant P RNA was used, increased cleavage activity of a single circularly permuted substrate within the population was observed. The cleavage efficiency (kcat/Km) of a singly 2'-deoxy-substituted substrate at this position in the T stem was also determined. For the wild-type P RNA, the catalytic efficiency was significantly decreased compared with that of the all-ribo substrate, consistent with the notion that this 2' hydroxyl plays an important role. For the P RNA mutant, no additional effect was found upon 2'-deoxy substitution. We propose that this particular 2' hydroxyl in the pre-tRNA interacts specifically with this adenosine in the P RNA. This method should be useful in examining the role of 2' hydroxyl groups in other RNA-RNA and RNA-protein complexes.

Evidence for DNA phosphate backbone alkylation and cleavage by pyrrolo[1,2-a]benzimidazoles: small molecules capable of causing base-pair-specific phosphodiester bond hydrolysis.

This report presents evidence that a reduced pyrrolo[1,2-a]benzimidazole (PBI) cleaves DNA as a result of phosphate alkylation followed by hydrolysis of the resulting phosphate triester. The base-pair specificity of the phosphate alkylation results from Hoogsteen-type hydrogen bonding of the reduced PBI in the major groove at only A.T and G.C base pairs. Alkylated phosphates were detected by 31P NMR and the cleavage products were detected by 1H NMR and HPLC. Evidence is also presented that a reduced PBI interacts with DNA in the major groove rather than in the minor groove or by intercalation.

Bond, Robert, 2 autographed letters signed to John Winthrop; East Hampton, Conn., 1651 March 8-March 10

Correspondence regarding advice Winthrop had given to Bond's family, and requesting he remit instructions for treating an illness of a neighbor's children.

Sacramento and San Joaquin drainage district refunding act, Reclamation board act and Reclamation board bond act of the state of California, as in effect on and after July 29, 1927, with all amendments to and including those of 1927.

Mode of access: Internet.

The dance music of Scotland; a collection of all the best reels and strathspeys both of the highlands and lowlands, for the pianoforte; arranged and edited by J. T. Surenne. 2. ed.

"Printed collections of ancient and modern Scottish melodies": p. xi-xvi.

Manual of emergency legislation : comprising all the acts of Parliament, proclamations, orders, &c., passed and made in consequence of the war. Supplement no. 2 to December 5th, 1914 /

Incorporating and superseding supplement no. 1.

A dissertation upon the nerves, containing an account : I. Of the nature of man, 2. Of the nature of brutes, 3. Of the nature and connection of soul and body, 4. Of the threefold life of man, 5. Of the symptoms, causes and cure of all nervous diseases /

Mode of access: Internet.

American and foreign stock exchange practice, stock and bond trading, and the business corporation laws of all nations, together with local regulations, laws, fees and taxes affecting American firms and corporations carrying on business in any other states of the U.S.A., or establishing branches or agencies in foreign countries.

"This book is no. B. 105."

Topografia e numismatica dell'antica Imera (e di Terme) : memoria letta all'Accademia di archeologia, lettere e belle arti nella tornata del 2 luglio 1893 /

"Estratto dal vol. XVII degli Atti dell'Accademia di archeologia, lettere e belle arti"--T.p. verso.

The peerage of England, or A genealogical and historical account of all the families of this kingdom, that have born the dignity of peerage, either by tenure, summons to parliament, investiture, or creation, & c. from the conquest to this present year, 1713. Vol. II, [in 2 pt.]

Mode of access: Internet.