Cooperation of Gq, Gi, and G12/13 in Protein Kinase D Activation and Phosphorylation Induced by Lysophosphatidic Acid

To examine the contribution of different G-protein pathways to lysophosphatidic acid (LPA)-induced protein kinase D (PKD) activation, we tested the effect of LPA on PKD activity in murine embryonic cell lines deficient in Galpha q/11 (Galpha q/11 KO cells) or Galpha 12/13 (Galpha 12/13 KO cells) and used cells lacking rhodopsin kinase (RK cells) as a control. In RK and Galpha 12/13 KO cells, LPA induced PKD activation through a phospholipase C/protein kinase C pathway in a concentration-dependent fashion with maximal stimulation (6-fold for RK cells and 4-fold for Galpha 12/13 KO cells in autophosphorylation activity) achieved at 3 µM. In contrast, LPA did not induce any significant increase in PKD activity in Galpha q/11 KO cells. However, LPA induced a significantly increased PKD activity when Galpha q/11 KO cells were transfected with Galpha q. LPA-induced PKD activation was modestly attenuated by prior exposure of RK cells to pertussis toxin (PTx) but abolished by the combination treatments of PTx and Clostridium difficile toxin B. Surprisingly, PTx alone strikingly inhibited LPA-induced PKD activation in a concentration-dependent fashion in Galpha 12/13 KO cells. Similar results were obtained when activation loop phosphorylation at Ser-744 was determined using an antibody that detects the phosphorylated state of this residue. Our results indicate that Gq is necessary but not sufficient to mediate LPA-induced PKD activation. In addition to Gq, LPA requires additional G-protein pathways to elicit a maximal response with Gi playing a critical role in Galpha 12/13 KO cells. We conclude that LPA induces PKD activation through Gq, Gi, and G12 and propose that PKD activation is a point of convergence in the action of multiple G-protein pathways

Electroweak symmetry breaking and cold dark matter from hidden sector technicolor

We consider models with a vectorlike confining gauge theory in the hidden sector, and demonstrate that the origin of the electroweak symmetry breaking (EWSB) is due to the dimensional transmutation in the hidden sector gauge theory, and the lightest mesons in the hidden sector could be a good cold dark matter (CDM) candidate. There would be more than one neutral Higgs-like scalar bosons, and they could decay mainly into the CDM pair, if that decay channel is kinemtically allowed.Comment: To appear in the proceeding of the 4th International Conference on Flavor Physic

Figure S6: Silencing Mmp14

Membrane-anchored matrix metalloproteinase 14 (MMP14) is involved broadly in organ development through both its proteolytic and signal-transducing functions. Knockout of Mmp14 (KO) in mice results in a dramatic reduction of body size and wasting followed by premature death, the mechanism of which is poorly understood. Since the mammary gland develops after birth and is thus dependent for its functional progression on systemic and local cues, we chose it as an organ model for understanding why KO mice fail to thrive. A global analysis of the mammary glands’ proteome in the wild type (WT) and KO mice provided insight into an unexpected role of MMP14 in maintaining metabolism and homeostasis. We performed mass spectrometry and quantitative proteomics to determine the protein signatures of mammary glands from 7 to 11 days old WT and KO mice and found that KO rudiments had a significantly higher level of rate-limiting enzymes involved in catabolic pathways. Glycogen and lipid levels in KO rudiments were reduced, and the circulating levels of triglycerides and glucose were lower. Analysis of the ultrastructure of mammary glands imaged by electron microscopy revealed a significant increase in autophagy signatures in KO mice. Finally, Mmp14 silenced mammary epithelial cells displayed enhanced autophagy. Applied to a systemic level, these findings indicate that MMP14 is a crucial regulator of tissue homeostasis. If operative on a systemic level, these findings could explain how Mmp14KO litter fail to thrive due to disorder in metabolism

Poetry in motion : Ko Un and Korean democratisation

This essay focuses on the poet and intellectual Ko Un, a prominent nationalist and critic of successive authoritarian regimes in Korea. Ashis Nandy gleaned insights into colonial India by investigating the lives of individuals who were emblematic of British colonialism. For instance Nandy focused on Rudyard Kipling to explain how colonialism damaged both Indians and the English who were complicit to it. Similarly, I intend to use the life and literary output of Ko Un to glean insights into Korea&rsquo;s fight for democracy in the context of the onset of modernisation. Through his political activism and writing Ko celebrated the lives of ordinary Koreans, including his one-time prison mate Kim Dae-jung and numerous political activists, workers, and farmers. He linked their struggle for democracy to a much longer quest to preserve what he considered to be the unique and invaluable aspects of the Korean national character.<br /

Knockout of Pannexin-1 Induces Hearing Loss

Mutations of gap junction connexin genes induce a high incidence of nonsyndromic hearing loss. Pannexin genes also encode gap junctional proteins in vertebrates. Recent studies demonstrated that Pannexin-1 (Panx1) deficiency in mice and mutation in humans are also associated with hearing loss. So far, several Panx1 knockout (KO) mouse lines were established. In general, these Panx1 KO mouse lines demonstrate consistent phenotypes in most aspects, including hearing loss. However, a recent study reported that a Panx1 KO mouse line, which was created by Genentech Inc., had no hearing loss as measured by the auditory brainstem response (ABR) threshold at low-frequency range (\u3c 24 kHz). Here, we used multiple auditory function tests and re-examined hearing function in the Genentech Panx1 (Gen-Panx1) KO mouse. We found that ABR thresholds in the Gen-Panx1 KO mouse were significantly increased, in particular, in the high-frequency region. Moreover, consistent with the increase in ABR threshold, distortion product otoacoustic emission (DPOAE) and cochlear microphonics (CM), which reflect active cochlear amplification and auditory receptor current, respectively, were significantly reduced. These data demonstrated that the Gen-Panx1 KO mouse has hearing loss and further confirmed that Panx1 deficiency can cause deafness

The Taiwanese Perspective in Investigating Korean Confucianism: Lee Ming-huei's Interpretation of Han Wonjin (1682–1750)

Numerous representatives of the contemporary Confucian revival from Taiwan are increasingly demonstrating the fact that the development of Confucian philosophy has to be viewed in a broader cultural context, especially in the context of different East Asian regions. While the development of the Japanese Confucian studies has been elaborated to a great extent during the last decades, studies in Korean Confucianism are still rare. Hence, the present article aims to offer a report on a pioneer contribution in this regard. It introduces Lee Ming-huei’s investigation into the work of one of the most influential Korean Confucians of the Joseon period; on the basis of Huang Chun-chieh’s methodology which exposes the contextualization paradigm, the article explains the main hypotheses and offers a theoretical reflection of the main issues discussed in this research work.      Številni predstavniki sodobnega konfucijanskega preporoda na Tajvanu izpostavljajo dejstvo, da je razvoj konfucijanske filozofije potrebno obravnavati iz širšega kulturnega konteksta, zlasti ko govorimo o različnih regijah Vzhodne Azije. Medtem ko je bil ravoj japonskih konfucijanskih študij v veliki meri izdelan v zadnjih desetletjih, so študije korejskega konfucianizma še vedno maloštevilne. Zato je cilj tega članka predstaviti pionirsko raziskavo iz tega področja. Članek predstavi raziskavo profesorja Lee Ming-hueija s področja del enega izmed najbolj vplivnih korejskih konfucijancev obdobja Joseon. Na podlagi Huang Chun-chieh-jeve metodologije, ki izpostavi kontekstualno paradigmo, razloži poglavitne hipoteze in ponudi kritičen razmislek o poglavitnih vprašanjih obravnavanih v tem raziskovalnem delu.

Excited Heavy Baryon Masses from the 1/N_c Expansion of HQET

The mass spectra of the L=1 orbitally excited heavy baryons with light quarks in both the spin-flavor symmetric and the mixed representations are studied by the $1/N_c$ expansion method in the framework of the heavy quark effective theory. The mixing effect between the baryons in the two representations is also considered. The general pattern of the spectrum is predicted which will be verified by the experiments in the near future.Comment: 9 pages, latex, no figure, uses sprocl.sty (included). Talk by Chun Liu at the workshop on Non-Perturbative Methods and Lattice QCD (Guangzhou, May 15-21, 2000

Ko Un and the poetics of postcolonial identity

Ko Un is one of South Korea\u27s most important writers of the past 50 years, and a poet whose work provides important insights into crucial linkages between language, identity and community. He lived through, chronicled and critically engaged most of the traumatic events his nation faced during the last century: a brutal colonial occupation by Japan; the division of the peninsula into communist North and capitalist South; an unusually devastating fraternal war; the integration of the divided peninsula into global Cold War politics; periods of authoritarian rule on both sides; and the more recent challenge to promote reconciliation. Some of these episodes challenged the very existence of Korea as a people, nation and state. Ko Un\u27s poetry was part of a larger effort to regain a sense of being and national identity in the face of turmoil, war and globalisation. We argue that by engaging with these highly political issues Ko Un\u27s work provides important clues about how to articulate notions of identity and community in a way that empathetically portrays other people and their identities. In doing so he offers an alternative to the prevailing inside/outside logic that often leads to problematic forms of nationalism. <br /