Glycation-induced inactivation of malate dehydrogenase protection by aspirin and a lens molecular chaperone, α-crystallin

AbstractNon-enzymic glycosylation (glycation) of structural proteins has been widely studied as a possible mechanism in the long-term complications of diabetes. Here we show that glycation inactivates malate dehydrogenase. Aspirin affords some protection against the glycation, but α-crystallin, a lens protein which appears to act as a molecular chaperone in other systems, is much more effective. For example, 5 mM glucose completely inactivates malate dehydrogenase in four days, and 5 μg α-crystallin/ml provides complete protection against this inactivation. Fructose, a superior glycating agent, inactivates the enzyme in 24 hours but even so the same low concentration of α-crystallin is able to protect 80% of the activity. Other proteins provide no protection at the same concentration. The inactivation of malate dehydrogenase and other enzymes by glycation could play a role in diabetic complications, and molecular chaperones like α-crystallin could serve to protect them

Mapping the Galactic Halo. V. Sgr dSph Tidal Debris 60 degrees from the Main Body

As part of the Spaghetti Project Survey (SPS) we have detected a concentration of giant stars well above expectations for a smooth halo model. The position (l~350, b~50) and distance (~50 kpc) of this concentration match those of the Northern over-density detected by SDSS (Yanny et al. 2000, Ivezic et al. 2000). We find additional evidence for structure at ~80 kpc in the same direction. We present radial velocities for many of these stars, including the first published results from the 6.5m Magellan telescope. The radial velocities for stars in these structures are in excellent agreement with models of the dynamical evolution of the Sgr dwarf tidal debris, whose center is 60 degrees away. The metallicity of stars in these streams is lower than that of the main body of the Sgr dwarf, which may indicate a radial metallicity gradient prior to disruption.Comment: 10 pages, 3 figures accepted in Astrophysical Journal Letter

Halo Star Streams in the Solar Neighborhood

We have assembled a sample of halo stars in the solar neighborhood to look for halo substructure in velocity and angular momentum space. Our sample includes red giants, RR Lyrae, and red horizontal branch stars within 2.5 kpc of the Sun with [Fe/H] less than -1.0. It was chosen to include stars with accurate distances, space velocities, and metallicities as well as well-quantified errors. We confirm the existence of the streams found by Helmi and coworkers, which we refer to as the H99 streams. These streams have a double-peaked velocity distribution in the z direction. We use the results of modeling of the H99 streams by Helmi and collaborators to test how one might use v_z velocity information and radial velocity information to detect kinematic substructure in the halo. We find that detecting the H99 streams with radial velocities alone would require a large sample. We use the velocity distribution of the H99 streams to estimate their age. From our model of the progenitor of the H99 streams, we determine that it was accreted between 6 and 9 Gyr ago. The H99 streams have [alpha/Fe] abundances similar to other halo stars in the solar neighborhood, suggesting that the gas that formed these stars were enriched mostly by Type II SNe. We have also discovered in angular momentum space two other possible substructures, which we refer to as the retrograde and prograde outliers. The retrograde outliers are likely to be halo substructure, but the prograde outliers are most likely part of the smooth halo. The retrograde outliers have significant structure in the v_phi direction and show a range of [alpha/Fe]. The methods presented in this paper can be used to exploit the kinematic information present in future large databases like RAVE, SDSSII/SEGUE, and Gaia.Comment: 46 pages, 13 figures, and 9 tables. Minor changes to text to match proofed version of the paper. Low resolution figures. High resolution version at http://www.astro.wisc.edu/~kepley/solar_streams.p

Diffuse Light in the Virgo Cluster

We present deep optical imaging of the inner 1.5 x 1.5 degrees of the Virgo cluster to search for diffuse intracluster light (ICL). Our image reaches a 1 sigma depth of mu_v=28.5 mag/arcsec^2 -- 1.5 mag/arcsec^2 deeper than previous surveys -- and reveals an intricate web of diffuse intracluster light. We see several long (>100 kpc) tidal streamers, as well as a myriad of smaller-scale tidal tails and bridges between galaxies. The diffuse halo of M87 is traced out to nearly 200 kpc, appearing very irregular on these scales, while significant diffuse light is also detected around the M84/M86 pair. Several galaxies in the core are embedded in common envelopes, suggesting they are true physical subgroups. The complex substructure of Virgo's diffuse ICL reflects the hierarchical nature of cluster assembly, rather than being the product of smooth accretion around a central galaxy.Comment: 4 pages, 3 figures, accepted for publication in ApJ Letter

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

A case report and genetic characterization of a massive acinic cell carcinoma of the parotid with delayed distant metastases.

We describe the presentation, management, and clinical outcome of a massive acinic cell carcinoma of the parotid gland. The primary tumor and blood underwent exome sequencing which revealed deletions in CDKN2A as well as PPP1R13B, which induces p53. A damaging nonsynonymous mutation was noted in EP300, a histone acetylase which plays a role in cellular proliferation. This study provides the first insights into the genetic underpinnings of this cancer. Future large-scale efforts will be necessary to define the mutational landscape of salivary gland malignancies to identify therapeutic targets and biomarkers of treatment failure