Identification of a potent serum factor that causes desensitization of the receptor for C-Type natriuretic peptide

BACKGROUND: Guanylyl cyclase-B (GC-B; NPR-B), the receptor for C-type natriuretic peptide (CNP) is rapidly and effectively desensitized by a factor(s) in serum. Given the potential importance of this receptor in remodeling after tissue injury, identification of the serum factor(s) is of significant medical importance. RESULTS: Partial purification of desensitization activity in serum by DEAE-Sepharose and reverse phase C18 chromatography, followed by mass spectroscopy, identified peptide sequences identical to those of apolipoprotein A2 (Apo A2), a known component of high density lipoprotein (HDL). Apo A2, however, could be eliminated as the active desensitization factor. Never the less, substantial desensitization activity was associated with purified preparations of bovine or human HDL. Since HDL is a well-known transporter of various lipids and phospholipids, we extracted either HDL or partially purified serum preparations with butanol and all activity extracted into the solvent. Of various lipophilic signaling molecules known to be associated with HDL, a prominent component is sphingosine-1-phosphate (S1P). We therefore tested authentic S1P as well as other known components of HDL (sphingosylphosphorylcholine; platelet activating factor) for activity; only S1P caused desensitization of GC-B. S1P was relatively potent, causing one-half maximal desensitization of GC-B at concentrations of 5–10 nM. These effects were seen within a few minutes after addition. Lysophosphatidic acid, another component of serum capable of desensitizing GC-B, was only effective at Micromolar concentrations. The pathway by which serum or S1P desensitizes GC-B seems unique in that pertussis toxin failed to inhibit GC-B desensitization, and yet blocked serum or S1P activation of extracellular signal-regulated kinase (ERK) or Akt/protein kinase B (Akt/PKB). CONCLUSION: Since the concentrations of S1P that desensitize GC-B are well within serum physiological ranges, this mitogenic signaling molecule likely functions as a strong adversary of the CNP/GC-B signaling pathway in the regulation of cell proliferation and other growth factor-induced phenotypes. The mechanism by which S1P desensitizes GC-B appears different than the known S1P signaling pathways

Analisis Kinerja Anggaran Belanja pada Badan Pengelola Keuangan dan Barang Milik Daerah Provinsi Sulawesi Utara

Belanja dalam Laporan Realisasi Anggaran Merupakan Komponen penting yang mengundang perhatian publik. Hal itu disebabkan karena masyarakat sebagai pemberi dana melalui pajak daerah yang mereka bayarkan berkepentingan untuk mengetahui apakah dana tersebut telah digunakan dengan semestinya, efisien, efektif, dan berorientasi pada kepentingan publik. Adapun tujuan dari penelitian ini adalah untuk mengetahui dan menganalisis kinerja anggaran belanja dalam laporan realisasi anggaran pada Badan Pengelola Keuangan Dan Barang Milik Daerah Provinsi Sulawesi Utara dari Tahun Anggaran 2009-2012. Data yang digunakan adalah Laporan Realisasi Anggaran Tahun Anggaran 2009-2012. Dari hasil analisis yang terdiri dari analisis varians (selisih) belanja, analisis pertumbuhan belanja, analisis keserasian belanja, rasio efisiensi belanja dan rasio belanja daerah terhadap PDRB. Tahun 2009 terdapat selisih anggaran belanja sebesar Rp. 95.735.271.217,62, tahun 2010 Rp. 61.329.077.260,00, tahun 2011 Rp. 157.837.732.725,00, tahun 2012 Rp. 189.330.495.775,00. Tahun 2010 terjadi pertumbuhan realisasi belanja sebesar 9,96% dibanding tahun sebelumnya, tahun 2011 sebanyak 13,05%, tahun 2012 sebanyak 37,74%. Untuk analisis keserasian belanja, tahun 2012 rasio belanja operasi sebesar 69,013%, rasio belanja modal sebesar 19,795%, rasio belanja tak terduga 0,004%, rasio transfer bagi hasil 11,188%. Tahun 2009 realisasi belanja sebesar 91,53% dari yang dianggarkan, tahun 2010 hanya sebesar 94,88%, tahun 2011 hanya sebesar 89,07%, tahun 2012 hanya sebesar 90,34%

Physical Acoustics

Contains reports on four research projects.U. S. Navy (Office of Naval Research) under Contract Nonr- 1841(42

The influence of depth and velocity on age‐0 Scaphirhynchus sturgeon prey consumption: Implications for aquatic habitat restoration

After the pallid sturgeon (Scaphirhynchus albus) was listed as endangered in 1990, a variety of management actions focusing on early life history needs have been implemented to aid species recovery. Given the scarcity of age‐0 pallid sturgeon, managers and scientists have relied on sympatric congeners to evaluate the effectiveness of management actions in the short term; however, increased understanding of habitat requirements for age‐0 Scaphirhynchus sturgeon is still needed to appropriately focus management efforts. Recently, a lack of food‐producing and foraging habitats were proposed as potential limiting factors for pallid sturgeon, and the purpose of this study was to evaluate the current definition of these habitats at multiple spatial scales using data from age‐0 Scaphirhynchus sturgeon (shovelnose sturgeon [Scaphirhynchus platyrhynchus] or hybrid [shovelnose sturgeon x pallid sturgeon]). Results showed the water depths and velocities that currently define age‐0 pallid sturgeon foraging habitat had little effect on age‐0 Scaphirhynchus sturgeon prey consumption. Similar results occurred when evaluating the relationship between prey consumption and food‐producing habitat present 10, 20, and 30 days before capture. Assuming that individuals captured during this study were a valid surrogate, these results suggest that increasing foraging and food‐producing habitat as defined by the current depth and velocity criteria is unlikely to result in the desired benefits of increased growth and survival of age‐0 pallid sturgeon

A roadmap for China to peak carbon dioxide emissions and achieve a 20% share of non-fossil fuels in primary energy by 2030

As part of its Paris Agreement commitment, China pledged to peak carbon dioxide (CO2) emissions around 2030, striving to peak earlier, and to increase the non-fossil share of primary energy to 20% by 2030. Yet by the end of 2017, China emitted 28% of the world's energy-related CO2 emissions, 76% of which were from coal use. How China can reinvent its energy economy cost-effectively while still achieving its commitments was the focus of a three-year joint research project completed in September 2016. Overall, this analysis found that if China follows a pathway in which it aggressively adopts all cost-effective energy efficiency and CO2 emission reduction technologies while also aggressively moving away from fossil fuels to renewable and other non-fossil resources, it is possible to not only meet its Paris Agreement Nationally Determined Contribution (NDC) commitments, but also to reduce its 2050 CO2 emissions to a level that is 42% below the country's 2010 CO2 emissions. While numerous barriers exist that will need to be addressed through effective policies and programs in order to realize these potential energy use and emissions reductions, there are also significant local environmental (e.g., air quality), national and global environmental (e.g., mitigation of climate change), human health, and other unquantified benefits that will be realized if this pathway is pursued in China

Novel insights into host-fungal pathogen interactions derived from live-cell imaging

Acknowledgments The authors acknowledge funding from the Wellcome Trust (080088, 086827, 075470 and 099215) including a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377 and FP7-2007–2013 grant agreement HEALTH-F2-2010-260338–ALLFUN to NARG.Peer reviewedPublisher PD

Bose-Einstein Correlations of Three Charged Pions in Hadronic Z^0 Decays

Bose-Einstein Correlations (BEC) of three identical charged pions were studied in 4 x 10^6 hadronic Z^0 decays recorded with the OPAL detector at LEP. The genuine three-pion correlations, corrected for the Coulomb effect, were separated from the known two-pion correlations by a new subtraction procedure. A significant genuine three-pion BEC enhancement near threshold was observed having an emitter source radius of r_3 = 0.580 +/- 0.004 (stat.) +/- 0.029 (syst.) fm and a strength of \lambda_3 = 0.504 +/- 0.010 (stat.) +/- 0.041 (syst.). The Coulomb correction was found to increase the \lambda_3 value by \~9% and to reduce r_3 by ~6%. The measured \lambda_3 corresponds to a value of 0.707 +/- 0.014 (stat.) +/- 0.078 (syst.) when one takes into account the three-pion sample purity. A relation between the two-pion and the three-pion source parameters is discussed.Comment: 19 pages, LaTeX, 5 eps figures included, accepted by Eur. Phys. J.

Measurements of Flavour Dependent Fragmentation Functions in Z^0 -> qq(bar) Events

Fragmentation functions for charged particles in Z -> qq(bar) events have been measured for bottom (b), charm (c) and light (uds) quarks as well as for all flavours together. The results are based on data recorded between 1990 and 1995 using the OPAL detector at LEP. Event samples with different flavour compositions were formed using reconstructed D* mesons and secondary vertices. The \xi_p = ln(1/x_E) distributions and the position of their maxima \xi_max are also presented separately for uds, c and b quark events. The fragmentation function for b quarks is significantly softer than for uds quarks.Comment: 29 pages, LaTeX, 5 eps figures (and colour figs) included, submitted to Eur. Phys. J.

Plasma Dynamics

Contains research objectives and summary of research on twenty-one projects split into three sections, with four sub-sections in the second section and reports on twelve research projects.National Science Foundation (Grant ENG75-06242)U.S. Energy Research and Development Administration (Contract E(11-1)-2766)U.S. Energy Research and Development Agency (Contract E(11-1)-3070)U.S. Energy Research and Development Administration (Contract E(11-1)-3070)Research Laboratory of Electronics, M.I.T. Industrial Fellowshi