IFN consensus sequence binding protein potentiates STAT1-dependent activation of IFNγ-responsive promoters in macrophages

IFNγ, once called the macrophage-activating factor, stimulates many genes in macrophages, ultimately leading to the elicitation of innate immunity. IFNγ's functions depend on the activation of STAT1, which stimulates transcription of IFNγ-inducible genes through the GAS element. The IFN consensus sequence binding protein (icsbγ or IFN regulatory factor 8), encoding a transcription factor of the IFN regulatory factor family, is one of such IFNγ-inducible genes in macrophages. We found that macrophages from ICSBP−/− mice were defective in inducing some IFNγ-responsive genes, even though they were capable of activating STAT1 in response to IFNγ. Accordingly, IFNγ activation of luciferase reporters fused to the GAS element was severely impaired in ICSBP−/− macrophages, but transfection of ICSBP resulted in marked stimulation of these reporters. Consistent with its role in activating IFNγ-responsive promoters, ICSBP stimulated reporter activity in a GAS-specific manner, even in the absence of IFNγ treatment, and in STAT1 negative cells. Indicative of a mechanism for this stimulation, DNA affinity binding assays revealed that endogenous ICSBP was recruited to a multiprotein complex that bound to GAS. These results suggest that ICSBP, when induced by IFNγ through STAT1, in turn generates a second wave of transcription from GAS-containing promoters, thereby contributing to the elicitation of IFNγ's unique activities in immune cells.

Long RNA hairpins that contain inosine are present in Caenorhabditis elegans poly(A)+ RNA

Adenosine deaminases that act on RNA (ADARs) are RNA-editing enzymes that convert adenosine to inosine within double-stranded RNA. In the 12 years since the discovery of ADARs only a few natural substrates have been identified. These substrates were found by chance, when genomically encoded adenosines were identified as guanosines in cDNAs. To advance our understanding of the biological roles of ADARs, we developed a method for systematically identifying ADAR substrates. In our first application of the method, we identified five additional substrates in Caenorhabditis elegans. Four of those substrates are mRNAs edited in untranslated regions, and one is a noncoding RNA edited throughout its length. The edited regions are predicted to form long hairpin structures, and one of the RNAs encodes POP-1, a protein involved in cell fate decisions.

Silicatein α: Cathepsin L-like protein in sponge biosilica

Earth’s biota produces vast quantities of polymerized silica at ambient temperatures and pressures by mechanisms that are not understood. Silica spicules constitute 75% of the dry weight of the sponge Tethya aurantia, making this organism uniquely tractable for analyses of the proteins intimately associated with the biosilica. Each spicule contains a central protein filament, shown by x-ray diffraction to exhibit a highly regular, repeating structure. The protein filaments can be dissociated to yield three similar subunits, named silicatein α, β, and γ. The molecular weights and amino acid compositions of the three silicateins are similar, suggesting that they are members of a single protein family. The cDNA sequence of silicatein α, the most abundant of these subunits, reveals that this protein is highly similar to members of the cathepsin L and papain family of proteases. The cysteine at the active site in the proteases is replaced by serine in silicatein α, although the six cysteines that form disulfide bridges in the proteases are conserved. Silicatein α also contains unique tandem arrays of multiple hydroxyls. These structural features may help explain the mechanism of biosilicification and the recently discovered activity of the silicateins in promoting the condensation of silica and organically modified siloxane polymers (silicones) from the corresponding silicon alkoxides. They suggest the possibility of a dynamic role of the silicateins in silicification of the sponge spicule and offer the prospect of a new synthetic route to silica and siloxane polymers at low temperature and pressure and neutral pH.

Can fractal-like spectra be experimentally observed in aperiodic superlattices?

We numerically investigate the effects of inhomogeneities in the energy spectrum of aperiodic semiconductor superlattices, focusing our attention on Thue-Morse and Fibonacci sequences. In the absence of disorder, the corresponding electronic spectra are self-similar. The presence of a certain degree of randomness, due to imperfections occurring during the growth processes, gives rise to a progressive loss of quantum coherence, smearing out the finer details of the energy spectra predicted for perfect aperiodic superlattices and spurring the onset of electron localization. However, depending on the degree of disorder introduced, a critical size for the system exists, below which peculiar transport properties, related to the pre-fractal nature of the energy spectrum, may be measured.

[Court appointment to inventory the Gannett estate], 1818 April 29

A one-page printed Middlesex County Court of Probate form appointing and authorizing William Hilliard, James P. Chaplin, and Royal Morse to inventory of the estate of Caleb Gannett.

An inventory of all of the estate of Caleb Gannett late of Cambridge in the county of Middlesex, Esquire, deceased, appraised upon oath by us the subscribers, duly appointed to that service by the Hon. James Prescott Esq. Judge of Probate & wills, in said county of Middlesex, viz., 1818 May 21

Eight-page handwritten inventory and appraisal of Caleb Gannett's real estate and personal estate by William Hilliard, James R. Chaplin, and Royal Morse with an attached certification of the Middlesex County Court of Probate signed May 26, 1818.

New England Railroads, 1838 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Sketch of the states of Massachusetts, Connecticut, and Rhode Island, and parts of New Hampshire & New York exhibiting the several rail road routes completed, constructing, chartered & contemplated : published by order of the Legislature of Massachusetts, drawn by A. Kennedy ; engraved by Morse & Tuttle. It was published in 1838. Scale [ca. 1:700,000]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the USA Contiguous Albers Equal Area Conic projection (Meters). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map shows features such as roads, completed, chartered, and contemplated railroads, drainage, state and county boundaries, and more. This layer is part of a selection of digitally scanned and georeferenced historic maps of New England from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

Organic carbon, reduced sulfur, and iron in Miocene to Holocene sediments from the Oman and Beguela upwelling systems

We examined sediments from Neogene and Quaternary sections of the Benguela and Oman upwelling systems (DSDP Site 532, ODP Sites 723 and 722) to determine environmental and geochemical factors which control and limit pyrite formation in organic-carbon-rich marine sediments. Those samples from the upwelling sites, which contained low to moderate concentrations of total organic carbon (0.7%-3%), had C/S ratios typical of normal marine sediments, i.e., around 2.8. In these sediments, TOC availability probably limited pyrite formation. Results that do not conform with accepted models were found for the sediments high in TOC (3^0-12.4%). The organic matter was of marine origin and contained considerable pyrolytic hydrocarbons, a fact that we take as a sign of low degradation, yet significant concentrations of dissolved sulfate coexisted with it (> 5 mmol/L in the case of Sites 532 and 723). Detrital iron was probably not limiting in either case, because the degree of pyritization was always less than 0.65. Therefore, controls on sulfate reduction and pyrite formation in the organic matter-rich sediments do not appear to conform simply to generally accepted diagenetic models. The data from these thermally immature, old, and organic-rich marine sediments imply that (1) the total reduced sulfur content of organic-rich marine upwelling sediments rarely exceeds an approximate boundary of 1.5% by weight, (2) the C/S ratio of these sediments is not constant and usually much higher than the empirical values proposed for marine sediments. We conclude that sedimentary pyrite formation in upwelling sediments is limited by an as yet unknown factor, and that caution is advised in using C/S ratios and C vs. S diagrams in paleoenvironmental reconstructions for organic-rich sediments.

1988 University of Michigan Baseball Team

Top Row: ?, John Ansted, Chris Gagin, Doug Kaiser, Ross Powell, ?, Dan Ruff, Stacy Katlin, Matt Morse, Ass't coach Ted Mahan, trainer Rex Thompson, ?

Middle Row: ?, ass't coach John Young, Kourtney Thompson, Mike Grimes, Greg Haeger, Jeff Tanderys, John Locker?, Tim Lata, Chris Starr, Phil Price, Rich Samplinski, ass't coach Chuck Froning, head coach Bud Middaugh

Front Row: Dave Peralta, Chris Lutz, Mike Gillette, Rick Leonard, Tom Brock, Steve Finken, Mike Ignasiak, Eddie Woolwine, Bill St. Peter, Darrin Campbell, Jim Abbott, Jim Durham

1989 University of Michigan Baseball Team

Top Row: student mngr. John Rutherford, student trainer Steve Fitch, Dave Everly, Dave Julier, Brian Korson, Jason Pfaff, Andy Fairman, Tracy Piehl, Todd Marion, Matt Morse, Steve Buerkel, trainer Kim Hart, student mngr. Mike Gaynor

Middle Row: asst. coach John Young, asst. coach Ted Mahan, Todd Winston, Dan Ruff, Greg Haeger, Kirt Ojala, Rick Leonard, Russell Brock, Jeff Tanderys, Eric Persinger, Mike Matheny, Tim Flanelly, asst. coach Chuck Froning, coach Bud Middaugh

Front Row: John Locker, Greg McMurtry, Tim Lata, Mike Grimes, Doug Kaiser, Dave Peralta, Jim Durham, Kourtney Thompson, mngr. Ed Turek, Phil Price, Ross Powell, Stacey Katlin, Chris Gagin

1990 University of Michigan Baseball Team

Top Row: groundskeeper Erich Keil, Chris Michalek, Scott Winterlee, Matt Copp, Bryan Santo, Ron Buff, Toby Brzoznowski, Eric Persinger, Derek Matthison, Joe Mooney, Pat Maloney, Scott Schorer, Scott Timmerman, student trainer Earl Wenk, student manager Kevin Lewis

Middle Row: trainer Kim Hart, grad. Asst. Ed Turek, asst. coach Ted Mahan, Todd Konuszewski, Mike Matheny, Dave Julier, Steve Buerkel, asst. coach Ace Adams, coach Moby Benedict

Front Row: Russell Brock, Jeff Tanderys, Da ruff, Brian Korson, Stacey Katlin, co-captain Phil Price, coach Bill Freehan, co-captain Kirt Ojala, Rick Leonard, Greg Haeger, Dave Everly, Matt Morse, Jason Pfaff

1914 University of Michigan Football Team

1981 University of Michigan Men's Golf Team

Back Row: Tom Pursel, Ed Frutig, Steve Maddalena, Kip Owen, Ryan Wiezycki, Jim Becker

Front Row: Jim Yaffee, Gary Zenkel?, Mark DeWitt, John Morse, David Koch, Ed Humenik