Before China Beat, There Was China beyond the Headlines

For several years now there has been a close connection between China Beat and China beyond the Headlines. The latter, a series of essay collections edited by myself and Lionel M. Jensen, is designed for a general and classroom audience (Volume One was published in 2000; Volume Two, China’s Transformations, was released in 2007). In addition to some common players who have been involved with both, such as Geremie Barmé, Tim Cheek, Tim Oakes, Jeff Wasserstrom and myself, China Beat and China beyond the Headlines are fortunate to share Susan McEachern of Rowman & Littlefield Publishers as an editor. Each of these ongoing projects strives to create a space for discussion of China that falls between the purely academic and the purely journalistic. Both are committed to accessible and open-ended discussion and to a plurality of subjects and sensibilities. Both are informed by the belief that there’s a strong need for robust, open-minded, and self-reflexive public intellectualism with regard to contemporary China and its rapidly evolving place in the world. Given these close connections and parallel goals, it is fitting to announce an upcoming public outreach workshop that will take place at the University of Colorado this coming weekend. This event will serve as the basis for a third edition of China beyond the Headlines, which will be published in 2011. Workshop Schedule: Panel discussion #1: “China In the Headlines” Friday, April 16, 6:30 – 8:30 PM, CU Boulder campus, Humanities 250 Timothy Cheek, University of British Columbia: intellectuals & intellectual life Alex Wang, Natural Resources Defense Council: environmental issues Zheng Liang, University of Colorado: ethnic relations in Xinjiang David Bandurski, University of Hong Kong: investigative journalism Timothy Weston, University of Colorado: urbanization in Chin

A Cultural Symbol Passes from the Scene: Ji Xianlin, Not Michael Jackson

It’s been moving to watch the response in China to the July 11 death of renowned scholar, Ji Xianlin (1911-2009). While Ji’s unsurprising departure at the ripe old age of 98 has not brought quite the same flood tide of emotion and cultural stock taking in China as Michael Jackson’s completely unexpected death a few weeks earlier at age 50 has in the United States and around the world, the way the venerable scholar is being remembered in Beijing is nevertheless remarkable. Long lines of people wishing to pay their last respects waited for hours to gain entrance to a memorial ceremony held on the Beijing University campus where Ji taught, the press was full of tributes, and Communist Party leaders were very public in the honors they paid to the man from academe. In the United States it is hard to imagine the death of an elderly scholar, of a humanist who worked on the ancient past no less, ever attracting anything approaching the level of attention that Ji’s passing has in China. Ji Xianlin and Michael Jackson shared nothing in common except the coincidence of the timing of their deaths and the fact that in passing both were mourned as departed cultural symbols. Frankly, as the hysteria over Michael Jackson’s death has continued to pulsate through American society I have found it refreshing to follow the treatment that Ji Xianlin’s high-minded life has received in China. I feel this way even though it’s clear that the Chinese Communist Party’s highly public paeans to the deceased scholar have not been free of political considerations and while also acknowledging that Michael Jackson’s life and career certainly merit serious reflection and social commentary. Still, when looking at the way Ji’s death has been treated as compared with Jackson’s, and at what the two cultural symbols meant to their times and places, I find myself more drawn to the values and maturity on display in China than to the self-referential, entertainer-obsessed conversation that Jackson’s death has occasioned in the United States (even if much of that conversation has been about the sadness and oddity of Jackson’s life)

Pressing the Issue: Sino-American Discourse on the Proper Role of the Media, Past and Present

Sino-American discourse on the nature of the press as a social institution is a historical subject in addition to one for our times. This article locates today’s Sino-American discourse on the role of the media in a broad historical context before observing the degree to which the globalization of media technologies has complicated what for a century was typically a confrontational discourse between the two countries over the appropriate role of the press in society. It reveals that China and the United States sparred over that question from the early 20th century forward and that each country has served as a foil for the other insofar as attitudes about the media, as well as media practices, have been articulated and justified

Modulation of Glucagon Receptor Pharmacology by Receptor Activity-modifying Protein-2 (RAMP2).

The glucagon and glucagon-like peptide-1 (GLP-1) receptors play important, opposing roles in regulating blood glucose levels. Consequently, these receptors have been identified as targets for novel diabetes treatments. However, drugs acting at the GLP-1 receptor, although having clinical efficacy, have been associated with severe adverse side-effects, and targeting of the glucagon receptor has yet to be successful. Here we use a combination of yeast reporter assays and mammalian systems to provide a more complete understanding of glucagon receptor signaling, considering the effect of multiple ligands, association with the receptor-interacting protein receptor activity-modifying protein-2 (RAMP2), and the role of individual G protein α-subunits. We demonstrate that RAMP2 alters both ligand selectivity and G protein preference of the glucagon receptor. Importantly, we also uncover novel cross-reactivity of therapeutically used GLP-1 receptor ligands at the glucagon receptor that is abolished by RAMP2 interaction. This study reveals the glucagon receptor as a previously unidentified target for GLP-1 receptor agonists and highlights a role for RAMP2 in regulating its pharmacology. Such previously unrecognized functions of RAMPs highlight the need to consider all receptor-interacting proteins in future drug development.This work was supported by a Warwick Impact Fund (C.W., G.L.), the BBSRC (G.L. - BB/G01227X/1), (T.S., G.R., D.R. - BB/F008392/1), (D.P. - BB/M007529/1 and BB/M000176/1), Warwick Research Development Fund (C.W., G.L.) grant number (RD13301) and the Birmingham Science City Research Alliance (G.L).This is the final version of the article. It first appeared from ASBMB at http://dx.doi.org/10.1074/jbc.M114.62460

The contribution of inherited genotype to breast cancer

The etiology of breast cancer is complex, and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. These inherited genotypes include those that affect the propensity to be exposed to breast carcinogens, and those associated with breast tumorigenesis directly. In addition, inherited genotypes may influence response to breast cancer chemoprevention and treatment. Studies relating inherited genotypes with breast cancer incidence and mortality should consider a broader spectrum of genes and their potential roles in multistage carcinogenesis than have been typically evaluated to date. Understanding the role of inherited genotype at different stages of carcinogenesis could improve our understanding of cancer biology, may identify specific exposures or events that correlate with carcinogenesis, or target relevant biochemical pathways for the development of preventive or therapeutic interventions

Open and closed conformations of a sub-80 kDa Chagas vaccine candidate defined by a cryo-EM led integrative approach

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a significant global public health concern. It affects an estimated eight million individuals worldwide, with the majority remaining undiagnosed. Despite its profound health impact in both endemic and non-endemic areas, no vaccine is available, and the existing therapies are outdated, producing severe side effects.The 80kDa prolyl oligopeptidase of Trypanosoma cruzi (TcPOP) has been recently identified as a leading candidate for Chagas vaccine development. However, its three-dimensional structure has remained elusive for almost two decades since its discovery. We report the first three-dimensional structure of TcPOP in open and closed conformation, at a resolution of 3.0 and 2.5 Angstroms respectively, determined using single-particle cryo-electron microscopy. Multiple conformations were observed and were further characterized, using plasmonic optical tweezers.To assess the immunogenic potential of TcPOP, we immunized mice and evaluated both polyclonal and monoclonal responses against the TcPOP antigen and its homologues. The results revealed unexpected cross-reactivity across prolyl POPs from other closely related parasites, but intriguingly, not towards the human homologue.Altogether, our findings provide critical structural insights necessary to understand the immunogenicity of TcPOP for future Chagas vaccine development and diagnostic applications.Additionally, our integrative approach indicated that stage-tilted acquisition can yield biologically relevant information for challenging sub-80kDa proteins and could adequately resolve the cryoEM structures. Consequently, this comprehensive strategy can significantly enhance the success rate in determining the structures of proteins that present challenges in characterization

Spatial extent and historical context of North Sea oxygen depletion in August 2010

Prompted by recent observations of seasonal low dissolved oxygen from two moorings in the North Sea, a hydrographic survey in August 2010 mapped the spatial extent of summer oxygen depletion. Typical near-bed dissolved oxygen saturations in the stratified regions of the North Sea were 75–80 % while the well-mixed regions of the southern North Sea reached 90 %. Two regions of strong thermal stratification, the area between the Dooley and Central North Sea Currents and the area known as the Oyster Grounds, had oxygen saturations as low as 65 and 70 % (200 and 180 µmol dm-3) respectively. Low dissolved oxygen was apparent in regions characterised by low advection, high stratification, elevated organic matter production from the spring bloom and a deep chlorophyll maximum. Historical data over the last century from the International Council for the Exploration of the Sea oceanographic database highlight an increase in seasonal oxygen depletion and a warming over the past 20 years. The 2010 survey is consistent with, and reinforces, the signal of recent depleted oxygen at key locations seen in the (albeit sparse) historical data

Intramyocellular Lipid and Insulin Resistance: Differential Relationships in European and African Americans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93716/1/oby.2011.45.pd

Molecular properties of CD133+ glioblastoma stem cells derived from treatment-refractory recurrent brain tumors

Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM

Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation

Auditory hair cells spontaneously regenerate following injury in birds but not mammals. A better understanding of the molecular events underlying hair cell regeneration in birds may allow for identification and eventually manipulation of relevant pathways in mammals to stimulate regeneration and restore hearing in deaf patients.Gene expression was profiled in forskolin treated (i.e., proliferating) and quiescent control auditory epithelia of post-hatch chicks using an Affymetrix whole-genome chicken array after 24 (n = 6), 48 (n = 6), and 72 (n = 12) hours in culture. In the forskolin-treated epithelia there was significant (p<0.05; >two-fold change) upregulation of many genes thought to be relevant to cell cycle control and inner ear development. Gene set enrichment analysis was performed on the data and identified myriad microRNAs that are likely to be upregulated in the regenerating tissue, including microRNA181a (miR181a), which is known to mediate proliferation in other systems. Functional experiments showed that miR181a overexpression is sufficient to stimulate proliferation within the basilar papilla, as assayed by BrdU incorporation. Further, some of the newly produced cells express the early hair cell marker myosin VI, suggesting that miR181a transfection can result in the production of new hair cells.These studies have identified a single microRNA, miR181a, that can cause proliferation in the chicken auditory epithelium with production of new hair cells