Dimerization of Translationally Controlled Tumor Protein Is Essential For Its Cytokine-Like Activity

BACKGROUND:Translationally Controlled Tumor Protein (TCTP) found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF). Human recombinant HRF (HrHRF) has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn). METHODS AND FINDINGS:We found that only NH(2)-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH(2)-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP) was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP). Allergenic activity of Del-N11TCTP prompted us to see whether the NH(2)-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. CONCLUSIONS:Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development

Polar middle atmospheric responses to medium energy electron (MEE) precipitation using numerical model simulations

Abstract Energetic particle precipitation (EPP) is known to be an important source of chemical changes in the polar middle atmosphere in winter. Recent modeling studies further suggest that chemical changes induced by EPP can also cause dynamic changes in the middle atmosphere. In this study, we investigated the atmospheric responses to the precipitation of medium-to-high energy electrons (MEEs) over the period 2005–2013 using the Specific Dynamics Whole Atmosphere Community Climate Model (SD-WACCM). Our results show that the MEE precipitation significantly increases the amounts of NOₓ and HOₓ, resulting in mesospheric and stratospheric ozone losses by up to 60% and 25% respectively during polar winter. The MEE-induced ozone loss generally increases the temperature in the lower mesosphere but decreases the temperature in the upper mesosphere with large year-to-year variability, not only by radiative effects but also by adiabatic effects. The adiabatic effects by meridional circulation changes may be dominant for the mesospheric temperature changes. In particular, the meridional circulation changes occasionally act in opposite ways to vary the temperature in terms of height variations, especially at around the solar minimum period with low geomagnetic activity, which cancels out the temperature changes to make the average small in the polar mesosphere for the 9-year period

Responses of nitrogen oxide to high‐speed solar wind stream in the polar middle atmosphere

Abstract During high‐speed solar wind stream (HSS) events, energetic electrons from the Earth’s inner magnetosphere transfer solar wind energy to the high‐latitude upper atmosphere, which may affect chemical compositions in the region. We conduct a study on the production of nitrogen oxides (NOₓ) in the polar middle atmosphere by energetic electron precipitation (EEP) during HSS events in the period of international polar year 2007–2008 northern winter. During this period, the geomagnetic activity was generally quiet and there were no major solar events, which indicates that the EEPs were mostly associated with HSS events. The electron flux immediately increases with the onset of HSS events and remains elevated during the passage of the events. The estimation of the directly produced NOx by EEPs was attempted by using the correlation between NOₓ and dynamic tracers such as CO and CH₄. It was found that the direct effect of EEPs on NOₓ reaches down to about 55‐km altitude and the amount is estimated to be about 2 ppbv. This result indicates that the variations of polar stratospheric NOₓ in winter are mostly associated with dynamical processes such as vertical transport and horizontal mixing. We also found that the middle atmospheric O₃ depletion during HSS events seems to be related to the EEP‐induced NOₓ at least in the uppermost stratosphere in the polar region

Compact variant-rich customized sequence database and a fast and sensitive database search for efficient proteogenomic analyses

In proteogenomic analysis, construction of a compact, customized database from mRNA-seq data and a sensitive search of both reference and customized databases are essential to accurately determine protein abundances and structural variations at the protein level. However, these tasks have not been systematically explored, but rather performed in an ad-hoc fashion. Here, we present an effective method for constructing a compact database containing comprehensive sequences of sample-specific variants-single nucleotide variants, insertions/deletions, and stop-codon mutations derived from Exome-seq and RNA-seq data. It, however, occupies less space by storing variant peptides, not variant proteins. We also present an efficient search method for both customized and reference databases. The separate searches of the two databases increase the search time, and a unified search is less sensitive to identify variant peptides due to the smaller size of the customized database, compared to the reference database, in the target-decoy setting. Our method searches the unified database once, but performs target-decoy validations separately. Experimental results show that our approach is as fast as the unified search and as sensitive as the separate searches. Our customized database includes mutation information in the headers of variant peptides, thereby facilitating the inspection of peptide-spectrum matches. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.