Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals

We recently developed a novel tumor-targeted gene delivery system responding to hyperactivated intracellular signals. Polymeric carrier for gene delivery consists of hydrophilic neutral polymer as main chains and cationic peptide substrate for target enzyme as side chains, and was named polymer-peptide conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor-medicated endocytosis, into polymers mainly with a high cationic charge density such as polyethylenimine can increase tumor-targeted gene delivery. In the present study, we examined whether introduction of CS into PPC containing five cationic amino acids can increase gene expression in tumor cells. Size and zeta potential of plasmid DNA (pDNA)/PPC/CS complex were <200 nm and between -10 and -15 mV, respectively. In tumor cell experiments, pDNA/PPC/CS complex showed lower stability and gene regulation, compared with that of pDNA/PPC. Moreover, no difference in gene expression was identified between positive and negative polymer. These results were caused by fast disintegration of pDNA/PPC/CS complexes in the presence of serum. Thus, we suggest that introduction of negatively charged CS into polymers with a low charge density may lead to low stability and gene regulation of complexes

Laser-driven phase transitions in aqueous colloidal gold nanoparticles under high pressure : picosecond pump–probe study

Pump-probe transient extinction spectroscopy was applied to analyze 355-nm picosecond laser heating-induced phenomena of 60-nm-diameter aqueous gold nanoparticles (AuNPs) under a high pressure of 60 MPa. Kinetic spectroscopy revealed that a supercritical layer surrounding the AuNP nucleated with a lifetime of approximately 1 ns in its dynamic expansion and decay behavior for a fluence of 19.6 mJ cm−2. Moreover, we observed in the post-mortem transmission electron micrographs a number of fragments, a small percentage of size-reduced cores, and erupted particles, among the intact particles after 60 shots, suggesting that evaporation occurs under laser illumination. The particle temperature calculation indicated that evaporation begins with a liquid droplet AuNP surrounded by a supercritical layer at temperatures below the boiling point of gold. By applying high pressure, we are able to obtain a clear picture of the evaporation event, which was not possible at ambient pressure because the forming bubble caused particle temperatures to rise uncontrollably. In this study, we shed light on the critical role of the supercritical layer formed around the AuNP under high pressure during laser-induced evaporation.Pulsed-laser illumination of aqueous gold colloids under high pressure enables the evaporation from liquid droplets surrounded by supercritical water layer

Two-photon excitable boron complex based on tridentate imidazo[1,5-a]pyridine ligand for heavy-atom-free mitochondria-targeted photodynamic therapy

We have synthesized a cyan fluorescent boron complex based on a tridentate imidazo[1,5-a]pyridine ligand. The boron complex was found to have potential applications as not only a chiroptical material but also a heavy-atom-free mitochondria-targeted photosensitizer for cancer treatment

Telephone triage service use is associated with better outcomes among patients with cerebrovascular diseases: a propensity score analysis using population-based data

IntroductionThe telephone triage service is an emergency medical system through which citizens consult telephone triage nurses regarding illness, and the nurses determine the urgency and need for an ambulance. Despite being introduced in several countries, its impact on emergency patients has not been reported. We aimed to determine the effect of the telephone triage service on the outcomes of hospitalized patients diagnosed with cerebrovascular disease upon arrival after being transported by an ambulance.MethodsThis retrospective study included patients with cerebrovascular disease who were transported by ambulance between January 2016 and December 2019. The primary outcome was discharge to home by day 21 of hospitalization. A total of 344 patients who used the telephone triage service were propensity score-matched to 344 patients who directly called for an ambulance.ResultsTelephone triage service use was associated with discharge to home by hospital day 21 (crude odd ratio: 1.8; 95% confidence interval: 1.3–2.4) and was not significantly associated with survival on hospital day 21 in multivariate regression analysis.ConclusionThe prognoses of cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage depend on the time from symptom onset to treatment. Telephone triage services may allow patients to receive treatment more rapidly than traditional ambulance requests, resulting in improved patient outcomes. The findings of this study suggest that the use of telephone triage services is associated with improved outcomes in patients with cerebrovascular disease and indicate that the costs for medical expenses and disability may be greatly reduced in an aging society

The characteristic response of domestic cats to plant iridoids allows them to gain chemical defense against mosquitoes

ネコのマタタビ反応の謎を解明 --マタタビ反応はネコが蚊を忌避するための行動だった--. 京都大学プレスリリース. 2021-01-21.Domestic cats and other felids rub their faces and heads against catnip (Nepeta cataria) and silver vine (Actinidia polygama) and roll on the ground as a characteristic response. While this response is well known, its biological function and underlying mechanism remain undetermined. Here, we uncover the neurophysiological mechanism and functional outcome of this feline response. We found that the iridoid nepetalactol is the major component of silver vine that elicits this potent response in cats and other felids. Nepetalactol increased plasma β-endorphin levels in cats, while pharmacological inhibition of μ-opioid receptors suppressed the classic rubbing response. Rubbing behavior transfers nepetalactol onto the faces and heads of respondents where it repels the mosquito, Aedes albopictus. Thus, self-anointing behavior helps to protect cats against mosquito bites. The characteristic response of cats to nepetalactol via the μ-opioid system provides an important example of chemical pest defense using plant metabolites in nonhuman mammals

Gateways to the FANTOM5 promoter level mammalian expression atlas

The FANTOM5 project investigates transcription initiation activities in more than 1,000 human and mouse primary cells, cell lines and tissues using CAGE. Based on manual curation of sample information and development of an ontology for sample classification, we assemble the resulting data into a centralized data resource (http://fantom.gsc.riken.jp/5/). This resource contains web-based tools and data-access points for the research community to search and extract data related to samples, genes, promoter activities, transcription factors and enhancers across the FANTOM5 atlas. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0560-6) contains supplementary material, which is available to authorized users

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution