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Introduction During tumor initiation and progression, cancer cells undergo various forms of intra- and extracellular stresses, resulting in significant proteostasis perturbations (1, 2). How do cancer cells survive and proliferate [...], The unfolded protein response (UPR) is a cellular homeostatic mechanism that is activated in many human cancers and plays pivotal roles in tumor progression and therapy resistance. However, the molecular mechanisms for UPR activation and regulation in cancer cells remain elusive. Here, we show that oncogenic MYC regulates the inositol-requiring enzyme 1 (IRE1)/ X-box binding protein 1 (XBP1) branch of the UPR in breast cancer via multiple mechanisms. We found that MYC directly controls IRE1 transcription by binding to its promoter and enhancer. Furthermore, MYC forms a transcriptional complex with XBP1, a target of IRE1, and enhances its transcriptional activity. Importantly, we demonstrate that XBP1 is a synthetic lethal partner of MYC. Silencing of XBP1 selectively blocked the growth of MYC- hyperactivated cells. Pharmacological inhibition of IRE1 RNase activity with small molecule inhibitor 8866 selectively restrained the MYC-overexpressing tumor growth in vivo in a cohort of preclinical patient-derived xenograft models and genetically engineered mouse models. Strikingly, 8866 substantially enhanced the efficacy of docetaxel chemotherapy, resulting in rapid regression of MYC-overexpressing tumors. Collectively, these data establish the synthetic lethal interaction of the IRE1/XBP1 pathway with MYC hyperactivation and provide a potential therapy for MYC-driven human breast cancers.

Namuka Reef is a broad fringing reef flat situated immediately adjacent to the populous and heavily industrialized areas surrounding Suva Harbor, Fiji Islands. Reef flat sediments are mainly very poorly to moderately sorted carbonate gravels and sands with occasional boulders and very little silt' with terrigenous sediments limited to a narrow' nearshore strip. Bulk sediment geochemical analyses show that trace metal concentrations are generally very low across the reef flat and closely similar to pristine reef areas offshore rather than to the nearby contaminated areas within Suva Lagoon. Exceptions occur close to villages, however, where sediments are enriched in Pb, As, and other trace metals, and possibly near wreck sites on the reef where Fe increases locally. These data together with those for major and minor oxides show that there is little or no movement of sediments from the rivers and deeper lagoon onto the carbonate reef flat even though extreme events such as tsunamis or cyclones affect the area. This indicates that the geomorphic separation of reef flats from adjacent contaminated environments is sufficient to prevent the introduction of solid contaminants. Reef flats may thus retain healthy ecosystems and provide resources to the community even though close to heavily contaminated areas., Many coastal areas around the world have been increasingly impacted during the past century by anthropogenic contaminants that affect both water quality and the health of marine ecosystems (e.g., Wade [...]

ALESSANDRO DELFINO. Forum Iulium: L'area del Foro di Cesare alla luce delle campagne di scavo 2005-2008. Le fasi arcaica, repubblicana e cesariano-augustea. (British Archaeological Reports International series 2607). vii+296 pages, [...]

Several species of mycobacteria express abundant glycopeptidolipids (GPLs) on the surfaces of their cells. The GPLs are glycolipids that contain modified sugars including acetylated 6-deoxy-talose and methylated rhamnose. Four methyltransferases have been implicated in the synthesis of the GPLs of Mycobacterium smegmatis and Mycobacterium avium. A rhamnosyl 3-O-methytransferase and a fatty acid methyltransferase of M. smegmatis have been previously characterized. In this paper, we characterize the methyltransferases that are responsible for modifying the hydroxyl groups at positions 2 and 4 of rhamnose and propose the biosynthetic sequence of GPL trimethylrhamnose formation. The analysis of M. avium genes through the creation of specific mutants is technically difficult; therefore, an alternative approach to determine the function of putative methyltransferases of M. avium was undertaken. Complementation of M. smegmatis methyltransferase mutants with M. avium genes revealed that MtfC and MtfB of the latter species have 4-O-methyltransferase activity and that MtfD is a 3-O-methyltransferase which can modify rhamnose of GPLs in M. smegmatis.

Research has been conducted on Mycobacterium smegmatis glycopeptidolipids. The biosynthetic gene cluster of these glycopeptidolipids and the methyltransferase catalyzing the fatty acid conversion to the 3-methoxy form have been investigate and are discussed.

The continuous respiration olfactometer (CRO) was designed as a respiration-synchronous method for derivering odorants during recordings of brain electrical activity, providing control and monitoring of the timing of the delivery as well as the quantities of odorant involved. The CRO incorporates a purpose-built electronic system designed with very specific temporal and quantitative chracteristics, and is composed of four main parts: the respiratory monitoring apparatus, the odorant/air delivery system, the serial interface device and the respiratory monitoring software. Tests were undertaken to determine the performance of the system with reference to the accuracy and precision of timing and control of odorant delivery. Tests were also undertaken to determine the effects of variations in natural respiration between subjects on the capability of the respiratory monitoring system, using a group Of 50 Subjects, to test the success of a variable gain control to optimize the range of the digitized respiratory output. The delivery system wits able to provide information concerning quantities of air or odorant delivered, and the stimulus timing information required for integration with neurophysiological recording techniques. Index Terms--Brain topography, delivery apparatus, olfactometry, olfactory, respiratory monitoring.

An effort to use a CD46 transgenic mouse model to study measles virus (MV) pathogenesis and its effects on the central nervous and immune systems is discussed. Expression of the MV receptor CD46 closely mimicked the location and amount of CD46 found in humans. A small animal model is now available for MV pathogenesis analysis. Lack of such a model has inhibited progress in the study of how MV causes disease and in the development of novel therapies better vaccines.

When federal agents showed up at the front door of Governor Rod Blagojevich's Chicago bungalow to arrest him on conspiracy charges early one morning last December, they handed Illinois lawmakers [...]

At the heart of Maori philosophy is the concept of Mauri, a life force which unites all creatures and enables them to flourish. Respect for Mauri necessarily leads to a [...]

Byline: John M. Patterson, Harold H. Zakon Abstract: Transdifferentiation is the conversion of one differentiated cell type into another. The electric organ of fishes transdifferentiates from muscle but little is known about how this occurs. To begin to address this question, we studied the expression of muscle- and electrocyte-specific proteins with immunohistochemistry during regeneration of the electric organ. In the early stages of regeneration, a blastema forms. Blastemal cells cluster, express desmin, fuse into myotubes, and then express [alpha]-actinin, tropomyosin, and myosin. Myotubes in the periphery of the blastema continue to-differentiate as muscle; those in the center grow in size, probably by fusing with each other, and lose their sarcomeres as they become electrocytes. Tropomyosin is rapidly down-regulated while desmin, [alpha]-actinin, and myosin continue to be diffusely expressed in newly formed electrocytes despite the absence of organized sarcomeres. During this time an isoform of keratin that is a marker for mature electrocytes is expressed. One week later, the immunoreactivities of myosin disappears and [alpha]-actinin weakens, while that of desmin and keratin remain strong. Since nerve fibers grow into the blastema preceding the appearance of any differentiated cells, we tested whether the highly rhythmic nerve activity associated with electromotor input plays a role in transdifferentiation and found that electrocytes develop normally in the absence of electromotor neuron activity. Author Affiliation: Department of Zoology and Center for Developmental Biology, University of Texas at Austin, Austin, Texas 78712, USA Article History: Received 3 February 1997; Accepted 31 March 1997

Mycophenolic acid is generated when 2,4-dihydroxybenzoic acid suffers three essential substitutions regioselectively. A fast, uncatalyzed substitution of the bromide by methyllithium at low temperature leads to incorporation of the methyl substituent at site 5 of the 2,4-dihydroxybenzoic acid. Many intermediates come from these reactions, in a process suited to lab use with few chromatographic separations.

The Alder-Rickert reaction of activated acetylenes with 1-chloro-3-(trimethylsiloxy)1-3-cyclohexadienes produces highly substituted m-chlorophenols. Use of methyl propiolate as the dienophile increases the regioselectivity of the reaction. Synthesis of 4-chloromycophenolic acid involves the use of this Alder-Rickert reactions.

The standard sources for Maori ethics are the traditional narratives. These depict all things in the environment as sharing a common ancestry, and as thereby required, ideally, to exhibit certain virtues of respect and responsibility for each other. These environmental virtues are expressed in terms of distinctively Maori concepts: respect for mauri and tapu, kaitiakitanga, whanaungatanga, manaakitanga, and environmental balance. I briefly explore these Maori environmental virtues, and draw from them some messages for the world at large.

The nutritional and temperature requirements for extracellular polysaccharide (EP) production by Butyrivibrio fibrisolvens nix was determined. Strain nyx was grown anaerobically using different carbon and nitrogen sources. Results showed that EP poduction was similar at temperatures 35-40 degrees C. In addition, glucose was found to be the most efficient carbon source resulting in the fastest growth and highest EP production. The different nitrogen sources supported the same rates of growth and EP production. The resuls also showed that EP production was exponential during exponential growth but no EP was produced during the lar or stationary phases.

Archeological, topographical and scholarly research on Rome's ancient monuments progressed markedly between 1980 and 1990. This research centered on six main subjects: the Forum Romanum built under the Republic; the Campus Martius where the patricians vied for power; upper-class homes; the Palatine hill where the emperors dwelt; the Imperial Fora; and the circuses, amphitheaters and baths with which the emperors sought to amuse and placate the people. Research on these monuments will improve understanding of the aristocratic disunity and other causes of the shift from Republic to Empire.

Edited by Neil V. Rosenberg. Foreword by Alan Jabbour. Folklore and Society. Music in American Life. A Publication of the American Folklore Society. New Series [unnumbered]. Urbana: University of Illinois [...]