紫外線発光ダイオード照射は宿主細胞内でのウイルスRNAの複製と転写を抑制することでA型インフルエンザウイルスを不活化する

Influenza A viruses (IAVs) pose a serious global threat to humans and their livestock, especially poultry and pigs. This study aimed to investigate how to inactivate IAVs by using different ultraviolet-light-emitting diodes (UV-LEDs). We developed sterilization equipment with light-emitting diodes (LEDs) those peak wavelengths were 365 nm (UVA-LED), 310 nm (UVB-LED), and 280 nm (UVC-LED). These UV-LED irradiations decreased dose fluence-dependent plaque-forming units of IAV H1N1 subtype (A/Puerto Rico/8/1934) infected Madin-Darby canine kidney (MDCK) cells, but the inactivation efficiency of UVA-LED was significantly lower than UVB- and UVC-LED. UV-LED irradiations did not alter hemagglutination titer, but decreased accumulation of intracellular total viral RNA in infected MDCK cells was observed. Additionally, UV-LED irradiations suppressed the accumulation of intracellular mRNA (messenger RNA), vRNA (viral RNA), and cRNA (complementary RNA), as measured by strand-specific RT-PCR. These results suggest that UV-LEDs inhibit host cell replication and transcription of viral RNA. Both UVB- and UVC-LED irradiation decreased focus-forming unit (FFU) of H5N1 subtype (A/Crow/Kyoto/53/2004), a highly pathogenic avian IAV (HPAI), in infected MDCK cells, and the amount of FFU were lower than the H1N1 subtype. From these results, it appears that IAVs may have different sensitivity among the subtypes, and UVB- and UVC-LED may be suitable for HPAI virus inactivation

Functional characterization of the regulators of calcineurin in Candida glabrata

The serine-threonine-specific protein phosphatase calcineurin is a key mediator of various stress responses in fungi. Herein, we characterized functions of the endogenous regulators of calcineurin (RCNs), Rcn1 and Rcn2, in the pathogenic fungus Candida glabrata. Rcn1 exerted both inhibitory and stimulatory effects on calcineurin signaling, but Rcn2 displayed only inhibitory activity. Phenotypic analyses of C. glabrata strains lacking either RCNs, calcineurin, or both revealed that calcineurin requires Rcn1, but not Rcn2, for antifungal tolerance in C. glabrata

The glycosylphosphatidylinositol-linked aspartyl protease Yps1 is transcriptionally regulated by the calcineurin-Crz1 and Slt2 MAPK pathways in Candida glabrata.

In the pathogenic fungus Candida glabrata, the YPS1 gene, which encodes a glycosylphosphatidylinositol-linked aspartyl protease, is required for cell wall integrity and virulence. Although the expression of YPS1 has been studied in Saccharomyces cerevisiae, the transcriptional regulation of this gene in C. glabrata is not well understood. Here, we report that C. glabrata Yps1 is required for cell growth at elevated temperatures, and that the heat-induced expression of YPS1 is regulated predominantly by the calcineurin-Crz1 pathway and partially by the Slt2 MAPK pathway. Although a total of 11 YPS genes are present in the C. glabrata genome, the loss of transcriptional induction in a calcineurin mutant was observed only for YPS1. The results of a YPS1 promoter-lacZ reporter assay using a series of constructs with mutated promoter elements indicated that the transcription factor Crz1 binds to multiple sites in the promoter region of YPS1. To date, as none of the putative Crz1 targets in C. glabrata have been characterized using a Δcrz1 mutant, monitoring the expression of YPS1 represents an effective method for measuring the activity of the calcineurin-Crz1 signaling pathway in this fungus

Macroscopic and microscopic hydrodynamic mixing of stratified suspensions

We conducted numerical experiments to investigate the mixing of stratified suspensions containing different types of particles. We used a point-force two-way coupling method. We studied the mixing behavior of stratified suspensions and we discovered two types of mixing: microscopic (individual-particle-level) and macroscopic (vessel-scale) collective mixing. In addition, we examined the vertical mixing speed of the stratified suspension. We used a simple theoretical model to analyze the fingering settling velocity. Then we introduced a nondimensional number representing the difference in collectivities of the upper and lower suspensions while accounting for particle terminal velocities. We discovered that the proposed nondimensional parameter has a negative sign that distinguishes the mixing form of only microscopic individual-particle-level mixing and a positive value that predicts the speed of macroscopic collective mixing of stratified suspensions

Application of a chiral copper-1,1-bis{2-[(4S)-tert-butyloxazolinyl]} cyclopropane catalyst for asymmetric cyclopropanation of styrene

The structural effects of the bridge moiety and 5-position on bisoxazoline ligands were studied for the copper-catalyzed asymmetric cyclopropanation of styrene with ethyl diazoacetate. The 1,1-bis{2-[(4S)-tert-butyloxazolinyl]}cyclopropane ligand showed a remarkable enhancement in the stereoselectivities (trans/cis = 84/16, >99.9 1.466888e-268e for the trans product) compared with the previously reported best ligand, 2,2-bis{2-[(4S)-tert-butyloxazolinyl]}propane (trans/cis=75/25, 99.0 0.000000e+00e for the trans product)

Synthesis and characterization of hexacoordinate cobalt(III) complexes bearing three C,O-bidentate ligands

Hexacoordinated Co(III) complexes bearing three C,O-bidentate ligands (9a and 9b) were prepared from 1-bromo-2-(p-tolyloxymethyl)benzene (8a) and 1-bromo-2,6-bis(p-tolyloxymethyl)benzene (8b), respectively. Both complexes were stable in air at room temperature. X-ray analyses revealed that the structures of both complexes were essentially the same. According to variable temperature 1H NMR study, it was found that the two oxygen ligands on the same aromatic ring of 9b interchanged with each other

Synthesis and characterization of hexacoordinate cobalt(III) complexes bearing three C,O-bidentate ligands

Hexacoordinated Co(III) complexes bearing three C,O-bidentate ligands (9a and 9b) were prepared from 1-bromo-2-(p-tolyloxymethyl)benzene (8a) and 1-bromo-2,6-bis(p-tolyloxymethyl)benzene (8b), respectively. Both complexes were stable in air at room temperature. X-ray analyses revealed that the structures of both complexes were essentially the same. According to variable temperature 1H NMR study, it was found that the two oxygen ligands on the same aromatic ring of 9b interchanged with each other

Demethylation of an Allene Bearing Two Dimethoxythioxanthene Groups by Oxidation via a Vinyl Cation Intermediate

With the objective of preparing an isolable triplet carbene, we have carried out the oxidation of an allenic compound bearing two thioxanthene moieties (5). Relatively weak oxidants such as Ph3C+BF4 – gave 8, which is the conjugate acid of 5, as a result of a one-electron oxidation followed by hydrogen abstraction, whereas relatively strong oxidants such as SbCl5 furnished a dicationic ketal (9) as a consequence of oxidation and demethylation. Computations on the supposed dicationic intermediate suggest that the singlet state is more stable than the triplet state by 6.7 kcal mol–1 and that the reason for this peculiarity is because the singlet state is essentially a vinyl cation stabilized by a coordinating methoxy group

Cancer immunity and therapy using hyperthermia with immunotherapy, radiotherapy, chemotherapy, and surgery

Hyperthermia is a type of medical modality for cancer treatment using the biological effect of artificially induced heat. Even though the intrinsic effects of elevated body temperature in cancer tissues are poorly understood, increasing the temperature of the body has been recognized as a popular therapeutic method for tumorous lesions as well as infectious diseases since ancient times. Recently accumulated evidence has shown that hyperthermia amplifies immune responses in the body against cancer while decreasing the immune suppression and immune escape of cancer. It also shows that hyperthermia inhibits the repair of damaged cancer cells after chemotherapy or radiotherapy. These perceptions indicate that hyperthermia has potential for cancer therapy in conjunction with immunotherapy, chemotherapy, radiotherapy, and surgery. Paradoxically, the anticancer effect of hyperthermia alone has not yet been adequately exploited because deep heating techniques and devices to aggregate heat effects only in cancer tissues are difficult in practical terms. This review article focuses on the current understanding concerning cancer immunity and involvement of hyperthermia and the innate and adoptive immune system. The potential for combination therapy with hyperthermia and chemotherapy, radiotherapy, and surgery is also discussed