Creative Destruction in the Information Age: The Fallout on America\u27s Latino Communities

The 104th Congress is in the midst of the first wholesale reform of telecommunications regulation in one-half century. The new regulatory framework emerging in the Republican-controlled Congress, if enacted, will usher in a radically deregulated, market-driven telecom environment, one in which the benefits of the emerging national information infrastructure will likely be distributed differentially, based on ethnicity and socio-economic status. Many U.S. residents may actually be charged higher rates for essential telecommunication services after deregulation (just as they did when cable television was deregulated), which may force many vulnerable users off the network. In addition, the concentration of media ownership eschews the viability of greater minority control of telecommunications and media outlets. The irony then is that although advanced, interactive technologies promise empowerment and choice, a laissez-faire approach to reform may exacerbate fault lines in the information society between those who are already advantaged and less affluent ethnic and racial minorities

Paths reunited: initiation of the classical and lectin pathways of complement activation

Understanding the structural organisation and mode of action of the initiating complex of the classical pathway of complement activation (C1) has been a central goal in complement biology since its isolation almost 50 years ago. Nevertheless, knowledge is still incomplete, especially with regard to the interactions between its subcomponents C1q, C1r and C1s that trigger activation upon binding to a microbial target. Recent studies have provided new insights into these interactions, and have revealed unexpected parallels with initiating complexes of the lectin pathway of complement: MBL–MASP and ficolin–MASP. Here, we develop and expand these concepts and delineate their implications towards the key aspects of complement activation via the classical and lectin pathways

Hexamethylhydrindacenes Derived from Isoprene and the Xylenes

Organic Chemistr

Conserved metabolite regulation of stress granule assembly via AdoMet

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Begovich, K., Vu, A. Q., Yeo, G., & Wilhelm, J. E. Conserved metabolite regulation of stress granule assembly via AdoMet. Journal of Cell Biology, 219(8), (2020): e201904141, doi:10.1083/jcb.201904141.Stress granules (SGs) are evolutionarily conserved condensates of ribonucleoproteins that assemble in response to metabolic stresses. Because aberrant SG formation is associated with amyotrophic lateral sclerosis (ALS), understanding the connection between metabolic activity and SG composition can provide therapeutic insights into neurodegeneration. Here, we identify 17 metabolic enzymes recruited to yeast SGs in response to physiological growth stress. Furthermore, the product of one of these enzymes, AdoMet, is a regulator of SG assembly and composition. Decreases in AdoMet levels increase SG formation, while chronic elevation of AdoMet produces SG remnants lacking proteins associated with the 5′ end of transcripts. Interestingly, acute elevation of AdoMet blocks SG formation in yeast and motor neurons. Treatment of ALS-derived motor neurons with AdoMet also suppresses the formation of TDP-43–positive SGs, a hallmark of ALS. Together, these results argue that AdoMet is an evolutionarily conserved regulator of SG composition and assembly with therapeutic potential in neurodegeneration.Work from the Wilhelm laboratory was supported by a grant to J.E. Wilhelm from the Collaborative Innovation Awards program of Howard Hughes Medical Institute and the James Wilhelm Memorial Fund. K. Begovich is a Howard Hughes Medical Institute Gilliam Fellow. Work from the Yeo laboratory was supported by grants to G. Yeo from the National Institutes of Health (HG004659), Target ALS (20193440), and the ALS Association (272 and 438)

Engineering novel complement activity into a pulmonary surfactant protein

Complement neutralizes invading pathogens, stimulates inflammatory and adaptive immune responses, and targets non- or altered-self structures for clearance. In the classical and lectin activation pathways, it is initiated when complexes composed of separate recognition and activation subcomponents bind to a pathogen surface. Despite its apparent complexity, recognition-mediated activation has evolved independently in three separate protein families, C1q, mannose-binding lectins (MBLs), and serum ficolins. Although unrelated, all have bouquet-like architectures and associate with complement-specific serine proteases: MBLs and ficolins with MBL-associated serine protease-2 (MASP-2) and C1q with C1r and C1s. To examine the structural requirements for complement activation, we have created a number of novel recombinant rat MBLs in which the position and orientation of the MASP-binding sites have been changed. We have also engineered MASP binding into a pulmonary surfactant protein (SP-A), which has the same domain structure and architecture as MBL but lacks any intrinsic complement activity. The data reveal that complement activity is remarkably tolerant to changes in the size and orientation of the collagenous stalks of MBL, implying considerable rotational and conformational flexibility in unbound MBL. Furthermore, novel complement activity is introduced concurrently with MASP binding in SP-A but is uncontrolled and occurs even in the absence of a carbohydrate target. Thus, the active rather than the zymogen state is default in lectin·MASP complexes and must be inhibited through additional regions in circulating MBLs until triggered by pathogen recognition

The SEGUE Stellar Parameter Pipeline. IV. Validation with an Extended Sample of Galactic Globular and Open Clusters

Spectroscopic and photometric data for likely member stars of five Galactic globular clusters (M3, M53, M71, M92, and NGC 5053) and three open clusters (M35, NGC 2158, and NGC 6791) are processed by the current version of the SEGUE Stellar Parameter Pipeline (SSPP), in order to determine estimates of metallicities and radial velocities for the clusters. These results are then compared to values from the literature. We find that the mean metallicity () and mean radial velocity () estimates for each cluster are almost all within 2{\sigma} of the adopted literature values; most are within 1{\sigma}. We also demonstrate that the new version of the SSPP achieves small, but noteworthy, improvements in estimates at the extrema of the cluster metallicity range, as compared to a previous version of the pipeline software. These results provide additional confidence in the application of the SSPP for studies of the abundances and kinematics of stellar populations in the Galaxy.Comment: 98 pages, 31 figures; accepted for publication in A

The SEGUE Stellar Parameter Pipeline. II. Validation with Galactic Globular and Open Clusters

We validate the performance and accuracy of the current SEGUE (Sloan Extension for Galactic Understanding and Exploration) Stellar Parameter Pipeline (SSPP), which determines stellar atmospheric parameters (effective temperature, surface gravity, and metallicity) by comparing derived overall metallicities and radial velocities from selected likely members of three globular clusters (M 13, M 15, and M 2) and two open clusters (NGC 2420 and M 67) to the literature values. Spectroscopic and photometric data obtained during the course of the original Sloan Digital Sky Survey (SDSS-I) and its first extension (SDSS-II/SEGUE) are used to determine stellar radial velocities and atmospheric parameter estimates for stars in these clusters. Based on the scatter in the metallicities derived for the members of each cluster, we quantify the typical uncertainty of the SSPP values, sigma([Fe/H]) = 0.13 dex for stars in the range of 4500 K < Teff < 7500 K and 2.0 < log g < 5.0, at least over the metallicity interval spanned by the clusters studied (-2.3 < [Fe/H] < 0). The surface gravities and effective temperatures derived by the SSPP are also compared with those estimated from the comparison of the color-magnitude diagrams with stellar evolution models; we find satisfactory agreement. At present, the SSPP underestimates [Fe/H] for near-solar-metallicity stars, represented by members of M 67 in this study, by about 0.3 dex.Comment: 56 pages, 8 Tables, 15 figures, submitted to the Astronomical Journa