Quasiparticle Trapping at Vortices Producing Josephson Supercurrent Enhancement.

The Josephson junction of a strong spin-orbit material under a magnetic field is a promising Majorana fermion candidate. Supercurrent enhancement by a magnetic field has been observed in the InAs nanowire Josephson junctions and assigned to a topological transition. In this work we observe a similar phenomenon but discuss the nontopological origin by considering the trapping of quasiparticles by vortices that penetrate the superconductor under a finite magnetic field. This assignment is supported by the observed hysteresis of the switching current when sweeping up and down the magnetic field. Our experiment shows the importance of quasiparticles in superconducting devices with a magnetic field, which can provide important insights for the design of qubits using superconductors.

Isolation of antifungal-resistant yeasts from bulk milk in Japan.

We isolated ascomycetous yeasts including Candida species, that originally belonged to the genus Candida, from bulk milk in the Aichi area of Japan, and determined the minimum inhibitory concentrations (MICs) of antifungal drugs on these isolates by conducting E-tests. We isolated 7 human pathogenic species (14 isolates) from 14 bulk milk samples: 5 Candida species of yeasts, and 2 Candida-related species. Two isolates of C. albicans and C. inconspicua were resistant to fluconazole (MIC >32 mg/l). One isolate of C. krusei was resistant to both azoles (fluconazole: >256 mg/ml and itraconazole: 4 mg/l). One isolate of C. catenulata might be resistant to amphotericin B (>32 mg/l).

Trichophyton indotineae sp. nov.: A New Highly Terbinafine-Resistant Anthropophilic Dermatophyte Species.

In this report, we describe the first isolation of two highly terbinafine (TRF)-resistant Trichophyton interdigitale-like strains from a Nepali patient and an Indian patient with tinea corporis in Japan. These strains (designated NUBS19006 and NUBS19007) exhibited a TRF minimal inhibitory concentration (MIC) of > 32 mg/L and contained a missense mutation (Phe397Leu) in squalene epoxidase (SQLE) gene. The internal transcribed spacer (ITS) region sequences amplified from the isolates (NUBS19006 and NUBS19007) were 99.5% identical to Japanese isolates of T. interdigitale and T. interdigitale strain CBS 428.63. The homology of region sequences were also 97.6% identical to T. mentagrophytes strain CBS 318.56. Moreover, the ITS sequences amplified from the isolates were 100% identical to highly TRF-resistant strains of T. interdigitale, which were isolated in Delhi, India, and harbored mutations in SQLE. The urease test on Christensen's urease agar was positive for T. mentagrophytes and T. interdigitale after 7 days of incubation. On the other hand, the type strain of T. rubrum CBS 100081 T and highly TRF-resistant strains (NUBS19006 and NUBS19007) were negative on Christensen urease agar after 7 and 14 days of incubation. Moreover, NUBS19006 and NUBS19007 were also negative reaction on the hair perforation test. To avoid confusion in the taxonomy of the T. mentagrophytes/T. interdigitale complex, we suggest that the highly TRF-resistant Indian strains be considered a new species independent of T. interdigitale, according to clinical and mycological features.

Dynamical Separation of Bulk and Edge Transport in HgTe-Based 2D Topological Insulators.

Topological effects in edge states are clearly visible on short lengths only, thus largely impeding their studies. On larger distances, one may be able to dynamically enhance topological signatures by exploiting the high mobility of edge states with respect to bulk carriers. Our work on microwave spectroscopy highlights the response of the edges which host very mobile carriers, while bulk carriers are drastically slowed down in the gap. Though the edges are denser than expected, we establish that charge relaxation occurs on short timescales and suggest that edge states can be addressed selectively on timescales over which bulk carriers are frozen.

Antifungal Susceptibility of Clinical Isolates and Artificially Produced Multi-azole-resistant Strains of Cryptococcus neoformans (formerly: Cryptococcus grubii) to Ravuconazole.

Ravuconazole (RVCZ) is a newly available human azole drug in Japan since 2018 and is a broad-spectrum antifungal agent that exhibits excellent activity against Candida albicans and Cryptococcus neoformans (formerly: Cryptococcus grubii). The drug is also highly active against isolates that are resistant to fluconazole (FLCZ). In the present study, the in vitro susceptibility to ravuconazole (RVCZ) of Japanese clinical isolates and multi-azole-resistant strains of C. neoformans was investigated using the Clinical & Laboratory Standards Institute (CLSI) M27-A3 test. The minimum inhibitory concentrations for the 14 clinical isolates and the multi-azole-resistant strains were 0.003125-0.125 mg/L and 0.25-0.5 mg/L for RVCZ, respectively. RVCZ is as effective as ITCZ and VRCZ for treating clinical isolates from cats and humans. Moreover, RVCZ is highly effective against multi-azole-resistant strains that encode a protein with a G344S substitution in ERG11. Consequently, RVCZ has considerable potential for use as a therapeutic agent for multi-azole resistant cryptococcosis.

High multi-azole-resistant Malassezia pachydermatis clinical isolates from canine Malassezia dermatitis.

Malassezia pachydermatis, a lipophilic and aerobic yeast, is a causative agent of Malassezia dermatitis, a common skin mycosis in dogs and cats. This fungus is also responsible for zoonotic fungal infections in human neonates. Ravuconazole (RVZ) is an antifungal azole compound and the active metabolite of fosravuconazole, which was approved for use in humans in Japan in 2018. In the present study, in vitro RVZ susceptibility and multi-azole resistance of 13 clinical M. pachydermatis strains was investigated using the modified Clinical and Laboratory Standards Institute M27-A3 test. The minimum inhibitory concentrations (MICs) for the 13 isolates ranged from 0.094 to >32 mg/L for itraconazole (ITZ) and from 0.5 to >32 mg/l for RVZ. Similarly, MICs for ITZ- or RVZ-resistant strains (MICs >32 mg/l) were also >32 mg/l for clotrimazole (CTZ), >32 mg/l for miconazole (MCZ), and 0.25 to >32 mg/L for voriconazole (VRZ). BLAST analysis using the NCBI database showed that ERG11 cDNA of the RVZ-resistant strain encoded Gly at codon 461 and Asp in cytochrome p450 encoded by M. pachydermatis ERG11 mRNA. This work is the first report to describe that an RVZ-resistant M. pachydermatis strain contains ERG11 mutations. The affinity of the protein encoded by ERG11 for RVZ may differ from that of ITZ. Therefore, RVZ has considerable therapeutic potential for treating ITZ-resistant canine Malassezia dermatitis. However, RVZ-resistant strains already exist in canine Malassezia dermatitis in Japan.

In Vitro Ravuconazole Susceptibility of Anthropophilic Dermatophyte Strains Isolated from Japanese Patients.

Ravuconazole (RVCZ) is a new human anti-fungal azole drug available in Japan since 2018 and is a broad-spectrum agent that exhibits excellent activity against dermatophytes. In the present study, the in vitro RVCZ susceptibility of clinical isolates of anthropophilic dermatophytes, including Trichophyton interdigitale strains with either low susceptibility to itraconazole (ITCZ) or resistance to terbinafine (TEBR), was investigated using the Clinical & Laboratory Standards Institute M38-A2 test. The MICs of RCVZ for 20 clinical isolates of T. interdigitale were < 0.03125-0.125 mg/L; for 4 clinical isolates of T. rubrum, < 0.03125-0.0625 mg/L; and for 20 clinical isolates of T. tonsurans, < 0.03125 mg/L. Similarly, the MICs of RCVZ for the T. interdigitale strains with either low susceptibility to ITCZ or resistance to TEBR were also < 0.03125 mg/L. To our knowledge, this is first study to investigate the in vitro RVCZ susceptibility of T. interdigitale strains with either low susceptibility to ITCZ or resistance to TEBR. Our results indicated that RVCZ was the most effective drug against these strains.

In vitro algaecid effect of itraconazole and ravuconazole on Prototheca species.

Protothecosis is a rare infection in humans, dogs, and cats, and its causative agent is Prototheca species, which consists of achlorophyllic algae that are ubiquitous in natural environments and hosts intestinal flora. Ravuconazole (RVZ) is a new available human azole drug in Japan since 2018 and broad-spectrum antifungal agent. In the present study, the in vitro susceptibility of clinical and environmental isolates of P. wickerhamii, P. zopfii, and P. blaschkeae to itraconazole (ITZ) voriconazole (VRZ), posaconazole (PCZ), and RVZ. RVZ was more potent than the other azoles against Protheca species and has considerable potential for use as a therapeutic agent for human and animal protothecosis.

Miconazole-tolerant strains of Malassezia pachydermatis generated by culture in medium containing miconazole.

BACKGROUND: Tolerance of Malassezia pachydermatis to azole drugs has been reported worldwide, from strains isolated from dogs. Canine Malassezia dermatitis often is treated with shampoos containing 2% miconazole (MCZ) or other topical MCZ products. OBJECTIVES: In the in vitro study herein, it was investigated whether MCZ-induced amino acid substitutions in the lanosterol 14-alpha-demethylase (ERG11) gene 1 lead to azole tolerance in M. pachydermatis. METHODS AND MATERIALS: Toleranced to MCZ was induced in an azole-susceptible strain of M. pachydermatis (CBS1879T ) by culture in medium containing MCZ. Antifungal susceptibility to MCZ, clotrimazole (CTZ) and itraconazole (ITZ) was assessed using the modified broth microdilution (BM) method. To assess the potential mechanism of tolerance in the three MCZ-resistant strains, ERG11 was sequenced. The interaction between the calcineurin inhibitor tacrolimus and MCZ in the azole-tolerant isolates also was examined. RESULTS: Three strains (NUBS19001 to NUBS19003) from CBS1879T cultured in medium containing MCZ exhibited minimum inhibitory concentrations (MICs) of 40 mg/L to MCZ, 5 mg/L to ITZ and >32 mg/L to CTZ, meaning that the isolates were tolerant. The combination of MCZ and tacrolimus exerted an indifferent effect against the MCZ-tolerant strain. BLAST analysis using the NCBI database showed mutations in the cytochrome p450 encoded by ERG11 in the MCZ-tolerant strains. CONCLUSIONS: In the present in vitro study, it was shown that MCZ exposure can induce amino acid substitutions in ERG11 and subsequent tolerance of M. pachydermatis to several azoles. Whether topical therapy with azole-containing products can exert a similar effect in vivo is a question that requires further research.

Dominant nonlocal superconducting proximity effect due to electron-electron interaction in a ballistic double nanowire.

Cooper pair splitting (CPS) can induce nonlocal correlation between two normal conductors that are coupled to a superconductor. CPS in a double one-dimensional electron gas is an appropriate platform for extracting a large number of entangled electron pairs and is one of the key ingredients for engineering Majorana fermions with no magnetic field. In this study, we investigated CPS by using a Josephson junction of a gate-tunable ballistic InAs double nanowire. The measured switching current into the two nanowires is significantly larger than the sum of the switching current into the respective nanowires, indicating that interwire superconductivity is dominant compared with intrawire superconductivity. From its dependence on the number of propagating channels in the nanowires, the observed CPS is assigned to one-dimensional electron-electron interaction. Our results will pave the way for the utilization of one-dimensional electron-electron interaction to reveal the physics of high-efficiency CPS and to engineer Majorana fermions in double nanowire systems via CPS.

Next-generation sequencing analysis of bacterial flora in bovine protothecal mastitic milk and feces.

The aim of the present study was to evaluate the bacterial flora in the udder and intestinal environments in cows with and without protothecal mastitis. We used next-generation sequencing (NGS) analysis to identify 16S rRNA genes from bacterial flora present in 13 milk and 13 fecal samples from protothecal mastitic and healthy dairy cows in the Aichi region of Japan. Sequences associated with 5 species (Calothrix desertica, Corynebacterium simulans, Corynebacterium striatum, Empedobacter falsenii, and Rothia endophytica) showed the highest prevalence in samples of milk and feces from animals with protothecal mastitis. This range of species differed from those detected in the milk and feces from healthy cows.

Antifungal Susceptibility of Japanese Isolates of Nannizia fulva (Formerly Microsporum fulvum).

Human and animal dermatophytoses are most commonly treated with systemic antifungal drugs such as itraconazole (ITZ) and terbinafine (TRF). The antifungal susceptibility of Nannizia fulva, however, remains poorly documented. In the present study, we investigated the in vitro susceptibility of N. fulva to ITZ and TRF using the CLSI M38-A2 test. The mean MICs for the 12 tested strains were 0.6542 mg/L (range: 0.0625-1 mg/L) for ITZ and 0.15625 mg/L (range: <0.003125-0.5 mg/L) for TRF. These results indicate that ITZ and TRF at standard veterinary doses should be efficacious against N. fulva.

Terbinafine-resistant strain of Trichophyton interdigitale strain isolated from a tinea pedis patient.

Trichophyton interdigitale is an anthropophilic species that is frequently isolated from tinea unguium and tinea pedis throughout the world. In the present study, antifungal susceptibility testing was performed on T. interdigitale isolates from Japanese patients (isolated in 2017-2018; 24 strains) to assess itraconazole (ITZ) and terbinafine (TRF) susceptibility of these strains. E-test determinations revealed that the mean ITZ minimum inhibitory concentration (MIC) of the 24 strains was 0.023 mg/L (range, 0.064-1). Clinical Laboratory Standards Institute M38-A2 determinations revealed that the mean TRF MIC of 23 of the 24 strains was less than 0.03125 mg/L. Among these strains, one (NUBS18016) had a TRF MIC of 2 mg/L, confirming its resistance to TRF. The predicted amino acid sequences of the squalene epoxidase (SQLE) gene from the TRF-resistant strain (NUBS18016) was 100% identical to the SQLE gene sequence of the reference strain T. interdigitale, indicating that no gene mutations were present in NUBS18016. Therefore, the TRF-resistance mechanism of our TRF-resistant strain NUBS18016 has not been defined. Dermatologists should be cautious about the prevalence of foot dermatophytosis due to antifungal drug-resistant strains.

Multi-azole-resistant strain of Malassezia pachydermatis isolated from a canine Malassezia dermatitis.

In the case presented here, we describe the isolation of an azole-resistant strain of M. pachydermatis from a canine Malassezia dermatitis. The isolate (NUBS18001) from this case exhibited a minimum inhibitory concentration (MIC) of 320 µg/ml to itraconazole (ITZ) by broth microdilution (BM) assay, >32 µg/ml to ITZ by E-test, and >32 µg/ml to KTZ by E-test. Synergistic effects between FK506 and ITZ in the azole-resistant strain was evaluated using the microdilution checker-board method. The ITZ-resistant strain exhibited MICs of 320 µg/mL of ITZ alone and 5 µg/ml of FK506 alone; the addition of FK506 attenuated the ITZ MIC to 2.5 µg/ml, yielding an ITZ FICI value of 0.507. This result suggested that the combination of ITZ and FK506 exerted an additive effect against the ITZ-resistant strain. To understand the other mechanism inferred to be present in our multi-azole-resistant strain, we sequenced the ERG11 gene from this isolate, and detected missense mutations (A412G and C905T) in the sequence of the ERG11 open reading frame (ORF). To the best of our knowledge, this work is the first report that a multi-azole-resistant M. pacydermatis strain contains mutations in ERG11.

[Next-generation Sequencing Analysis of Bacterial Flora in Bovine Prototheca Mastitic Milk].

Prototheca zopfii is an achlorophyllic algae that causes bovine mastitis, resulting in a reduction in milk production and the secretion of thin, watery milk with white flakes. The aim of the present study was to evaluate the bacterial flora in the udder environment in protothecal mastitis. We used metagenomic next-generation sequencing (NGS) analysis to identify 16S rRNA genes from bacterial flora present in milk samples from protothecal mastitic dairy cows.Seven clinical strains of P. zopfii genotype 2 were isolated from 7 milk samples from 7 cases (Holstein cow) of protothecal mastitis; another 9 milk samples were obtained from 9 normal Holstein cows. The samples were collected in 2017 from cows in one dairy located in the Kushiro region in Hokkaido, Japan, which had a history of protothecal mastitis infection.The NGS produced 10,000 to 15,000 sequences in each DNA sample. To facilitate comparison, we grouped the sequencing results according to the culture-based protothecal mastitis diagnosis; sequences derived from the milk samples obtained from healthy cows were grouped separately.Sequences classified as Streptococcus spp., Pseudomonas spp. and Sphingomonas spp., Caulobacter segnis, Macrococcus caseolyticus, Methylobacterium tarhaniae, and Sphingomonas leidyi were the main sequences detected in the groups of samples from cows characterized by culture as having protothecal mastitis. Notably, Calothrix desertica (a cyanobacterium) sequences showed higher prevalence in these samples.To our knowledge, this is the first study to report that C. desertica sequences, effectively absent in the samples derived from healthy cows, are detected at high prevalence in samples from protothecal mastitic animals.

Is bovine protothecal mastitis related to persistent infection in intestine?

Prototheca zopfii is associated with bovine mastitis, which causes a reduction in milk production and secretion of thin, watery milk with white flakes. However, the source of infection and an infection route of mastitis have not been clarified. In this study, we evaluated the prevalence of P. zopfii genotype 2 in fecal samples from Japanese dairies with or without a history of protothecal mastitis in 2017. P. zopfii genotype 2 was detected in 23 of 60 (38%) fecal samples in only the herd with a history of protothecal mastitis. These results suggest that occurrence of bovine protothecal mastitis is related to persistent infection in intestine and the source of infection is feces.

Equal-Spin Andreev Reflection on Junctions of Spin-Resolved Quantum Hall Bulk State and Spin-Singlet Superconductor.

The recent development of superconducting spintronics has revealed the spin-triplet superconducting proximity effect from a spin-singlet superconductor into a spin-polarized normal metal. In addition recently superconducting junctions using semiconductors are in demand for highly controlled experiments to engineer topological superconductivity. Here we report experimental observation of Andreev reflection in junctions of spin-resolved quantum Hall (QH) states in an InAs quantum well and the spin-singlet superconductor NbTi. The measured conductance indicates a sub-gap feature and two peaks on the outer side of the sub-gap feature in the QH plateau-transition regime increases. The observed structures can be explained by considering transport with Andreev reflection from two channels, one originating from equal-spin Andreev reflection intermediated by spin-flip processes and second arising from normal Andreev reflection. This result indicates the possibility to induce the superconducting proximity gap in the the QH bulk state, and the possibility for the development of superconducting spintronics in semiconductor devices.

Resistance Mechanism in a Terbinafine-Resistant Strain of Microsporum canis.

To clarify the terbinafine (TRF) resistance mechanism in a TRF-resistant strain of Microsporum canis, the expression of the pleiotropic drug resistance (PDR1), multidrug resistance (MDR1), MDR2 and MDR4 genes were investigated by real-time quantitative PCR (RT-qPCR) analysis, given the known interaction of the corresponding proteins with antifungals and with the efflux blocker FK506. The expression of the PDR1, MDR1, MDR2 and MDR4 genes was 2-4 times higher in the TRF-resistant strain grown in the presence of 0.14 µg/mL of TRF than in TRF-susceptible strains cultured in the absence of TRF. The TRF-resistant strain exhibited MICs of > 32 µg/mL for TRF alone; this resistance was attenuated to an MIC of 8 µg/mL in the presence of FK506, indicating that the TRF inhibitory concentration index value was < 0.75. The additive effect of the efflux blocker FK506 on TRF resistance was detected in the TRF-resistant strain. These results indicated that the TRF resistance in this strain reflects overexpression of genes encoding ABC transporter proteins.

Correction to: Resistance Mechanism in a Terbinafine-Resistant Strain of Microsporum canis.

In the initial online publication, the name of author Hock Siew Han was given incorrectly as Han Hock Siew. The original article has been corrected.