Mapping of the local environmental changes in proteins by cysteine scanning

Protein conformational changes, which regulate the activity of proteins, are induced by the alternation of intramolecular interactions. Therefore, the detection of the local environmental changes around the key amino acid residues is essential to understand the activation mechanisms of functional proteins. Here we developed the methods to scan the local environmental changes using the vibrational band of cysteine S-H group. We validated the sensitivity of this method using bathorhodopsin, a photoproduct of rhodopsin trapped at liquid nitrogen temperature, which undergoes little conformational changes from the dark state as shown by the X-ray crystallography. The cysteine residues were individually introduced into 15 positions of Helix III, which contains several key amino acid residues for the light-induced conformational changes of rhodopsin. The shifts of S-H stretching modes of these cysteine residues and native cysteine residues upon the formation of bathorhodopsin were measured by Fourier transform infrared spectroscopy. While most of cysteine residues demonstrated no shift of S-H stretching mode, cysteine residues introduced at positions 117, 118, and 122, which are in the vicinity of the chromophore, demonstrated the significant changes. The current results are consistent with the crystal structure of bathorhodopsin, implying that the cysteine scanning is sensitive enough to detect the tiny conformational changes

Perchloric acid-soluble protein regulates cell proliferation and differentiation in the spinal cord of chick embryos

AbstractThe role of perchloric acid-soluble protein (PSP) was investigated in chick embryos. Fluorescently labeled anti-chick liver (CL)-PSP IgG was injected into the yolk sac in ovo at embryonic day 3, and became localized in neuroepithelial cells. Within 12h, morphological changes were observed in 37.5% of anti-CL-PSP IgG-injected embryos, and the neuroepithelial cells formed a wavy line. No significant changes were observed in embryos injected with non-immune IgG or PBS. Increased expression of PCNA and decreased expression of neuronal class III β-tubulin were observed in the spinal cord after anti-CL-PSP IgG injection. These results suggest that PSP controls the proliferation and differentiation of neuroepithelial cells in chick embryos

Generation of novel cationic antimicrobial peptides from natural non-antimicrobial sequences by acid-amide substitution

<p>Abstract</p> <p>Background</p> <p>Cationic antimicrobial peptides (CAMPs) are well recognized to be promising as novel antimicrobial and antitumor agents. To obtain novel skeletons of CAMPs, we propose a simple strategy using acid-amide substitution (i.e. Glu→Gln, Asp→Asn) to confer net positive charge to natural non-antimicrobial sequences that have structures distinct from known CAMPs. The potential of this strategy was verified by a trial study.</p> <p>Methods</p> <p>The pro-regions of nematode cecropin P1-P3 (P1P-P3P) were selected as parent sequences. P1P-P3P and their acid-amide-substituted mutants (NP1P-NP3P) were chemically synthesized. Bactericidal and membrane-disruptive activities of these peptides were evaluated. Conformational changes were estimated from far-ultraviolet circular dichroism (CD) spectra.</p> <p>Results</p> <p>NP1P-NP3P acquired potent bactericidal activities via membrane-disruption although P1P-P3P were not antimicrobial. Far-ultraviolet CD spectra of NP1P-NP3P were similar to those of their parent peptides P1P-P3P, suggesting that NP1P-NP3P acquire microbicidal activity without remarkable conformational changes. NP1P-NP3P killed bacteria in almost parallel fashion with their membrane-disruptive activities, suggesting that the mode of action of those peptides was membrane-disruption. Interestingly, membrane-disruptive activity of NP1P-NP3P were highly diversified against acidic liposomes, indicating that the acid-amide-substituted nematode cecropin pro-region was expected to be a unique and promising skeleton for novel synthetic CAMPs with diversified membrane-discriminative properties.</p> <p>Conclusions</p> <p>The acid-amide substitution successfully generated some novel CAMPs in our trial study. These novel CAMPs were derived from natural non-antimicrobial sequences, and their sequences were completely distinct from any categories of known CAMPs, suggesting that such mutated natural sequences could be a promising source of novel skeletons of CAMPs.</p

Health impact assessment of PM2.5-related mitigation scenarios using local risk coefficient estimates in 9 Japanese cities

Previous studies have highlighted the negative effects of PM2.5 on mortality, expressed in terms of attributable deaths and life years lost. However, there are very few studies assessing the health impacts of air pollution in terms of economic burden/benefits. This study assessed the health impact of two hypothetical interventions among sex- and age-specific risk populations using a robust risk estimation and economic valuation process. We utilized the sex- and age-stratified daily all-cause mortality together with the daily PM2.5 of the 9 Japanese cities from 2002 to 2008 in estimating the relative risks. The estimated risks were then utilized for the economic valuation of co-benefits/burden with respect to the two hypothetical PM2.5-related mitigation scenarios, in comparison to status quo, namely: i) decrease to Japanese standards, and ii) decrease to WHO standards. Impact of these interventions on health were assessed using the following HIA metrics: attributable mortality, attributable years life lost, and environmental health impact. A 10-μg/m3 increase in PM2.5 would increase the risk by 0.52% (95% CI: −0.91% to 1.99%) for all-cause mortality, with varying risk estimates per subgroup. High economic burdens were estimated at status quo, with particularly distinct burden difference for age-specific mortality; 0.40 trillion yen (0–64 y.o.) and 1.50 trillion yen (>64 y.o.). If stricter standards, relative to status quo, were to be enforced, i.e. WHO standard, there is a potential to yield economic benefits in the same risk population; 0.26 trillion yen (0–64 y.o.) and 0.98 trillion yen (>64 y.o.). We did not observe any substantial difference with the burden and benefit related to sex-specific mortality. Using the estimated local risk coefficients complemented with the valuation of the risks, policymaking entities will have the opportunity to operate their own HIA to assess the relevant air pollution-related health impacts

ACO-Inspired Energy-Aware Routing Algorithm for Wireless Sensor Networks, Journal of Telecommunications and Information Technology, 2019, nr 1

Multi-hop networks, such as WSNs, become an object of increasing attention as an emerging technology which plays an important role for practical IoT applications. These multi-hop networks generally consist of mobile and small terminals with limited resources, which makes them vulnerable to various network status changes. Moreover, the limited nature of terminal resources available, especially in terms of battery capacity, is one of the most important issues to be addressed in order to prolong their operating time. In order to ensure efficient communications in such networks, much research has already been conducted, especially in the field of routing and transmission technologies. However, conventional approaches adopted in the routing field still suffer from the so-called energy hole problem, usually caused by unbalanced communication loads existing due to difficulties in adaptive route management. To address this issue, the present paper proposes a novel routing algorithm that utilizes ACO-inspired routing based on residual energy of terminals. Operational evaluation reveals its potential to ensure balanced energy consumption and to boost network performance

High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123) for Extraskeletal Ewing's Sarcoma: A Case Report

Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123) contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment