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The antifungal agent 5-fluorocytosine (5-FC) is used for the treatment of several mycoses, but is unsuitable for monotherapy due to the rapid development of resistance. Here, we show that cryptococci develop resistance to 5-FC at a high frequency when exposed to concentrations several fold above the minimal inhibitory concentration. The genomes of resistant clones contain alterations in genes relevant as well as irrelevant for 5-FC resistance, suggesting that 5-FC may be mutagenic at moderate concentrations. Mutations in FCY2 (encoding a known permease for 5-FC uptake), FCY1, FUR1, UXS1 (encoding an enzyme that converts UDP-glucuronic acid to UDP-xylose) and URA6 contribute to 5-FC resistance. The uxs1 mutants accumulate UDP-glucuronic acid, which appears to down-regulate expression of permease FCY2 and reduce cellular uptake of the drug. Additional mutations in genes known to be required for UDP-glucuronic acid synthesis (UGD1) or a transcriptional factor NRG1 suppress UDP-glucuronic acid accumulation and 5-FC resistance in the uxs1 mutants., Pathogenic fungi rapidly develop resistance to the antifungal agent 5-fluorocytosine (5-FC). Here, Chang et al. explore the mechanisms by which Cryptococcus develops 5-FC resistance at a high frequency, including mutations in several genes and altered levels of key metabolites.

In vitro antifungal susceptibility profiling of 32 clinical and environmental Talaromyces marneffei isolates recovered from southern China was performed against olorofim and 7 other systemic antifungals, including amphotericin B, 5-flucytosine, posaconazole, voriconazole, caspofungin, and terbinafine, using CLSI methodology. In comparison, olorofim was the most active antifungal agent against both mold and yeast phases of all tested Talaromyces marneffei isolates, exhibiting an MIC range, MIC 50 , and MIC 90 of 0.0005 to 0.002 μg/ml, 0.0005 μg/ml, and 0.0005 μg/ml, respectively.

T lymphocytes play an important role in cellular and adaptive immunity in vertebrates. The mechanisms of the fish immune system are little studied because of the lack of population-specific antibodies. This study examined the expression of two T lymphocyte markers, TCRα (PoTCRα) and CD8α (PoCD8α) in the Japanese flounder (Paralichthys olivaceus). The expression of PoTCRα and PoCD8α was mainly detected in immune/mucosal tissues. Recombinant PoTCRα and PoCD8α were expressed in pET32a and pET259, respectively. Then, rabbit anti-PoTCRα serum and rat anti-PoCD8α serum were prepared. Using serum, the characteristics of TCR+ and CD8+ head kidney leucocytes (HKLs) were investigated. The results of laser scanning confocal microscopy (LSCM) demonstrated that TCRα and CD8α were transmembrane proteins localized on the cell surface. The populations of CD8α

In vitro antifungal susceptibility profiling of 32 clinical and environmental Talaromyces marneffei isolates recovered from southern China was performed against olorofim and 7 other systemic antifungals, including amphotericin B, 5-flucytosine, posaconazole, voriconazole, caspofungin, and terbinafine, using CLSI methodology. In comparison, olorofim was the most active antifungal agent against both mold and yeast phases of all tested Talaromyces marneffei isolates, exhibiting an MIC range, MIC(50), and MIC(90) of 0.0005 to 0.002 μg/ml, 0.0005 μg/ml, and 0.0005 μg/ml, respectively.

OBJECTIVES: Critically ill children are often malnourished and require nutrition support (NS). Early enteral nutrition (EEN) seems to be safe in critically ill patients. However, there is a scarcity of data about the management of EEN in sick pediatric patients. The aim of this study was to analyze the nutritional status, NS characteristics, macronutrient supply, and associations between NS and outcomes in critically ill children in Spain. METHODS: This was a multicentric, prospective, cross-sectional study involving critically ill children who received NS and with an expected length of stay (LOS) in the pediatric intensive care unit of =3 d. Anthropometric variables, characteristics of NS, EEN, nutrient supply, and complications were recorded. RESULTS: We enrolled 86 children. Undernutrition and overweight were more prevalent in children =2 y of age than in older children (undernutrition: 40 versus 19%, respectively; overweight: 22.2 versus 14.3%, respectively). Being overweight was associated with a shorter PICU LOS (5.8 ± 2 versus 9.8 ± 6.5; P = 0.005). EN was the preferred method for nutrient delivery. EEN was administered to 58.1% of patients and was more common in children >2 y of age than in younger patients (73.1 versus 44.4%; P = 0.015). EEN was safe and was associated with a higher caloric intake (81.6 ± 35.3 versus 59.6 ± 36.6; P = 0.019). There was a negative correlation between mean time to EN initiation and maximum energy supply (r = -0.32; P = 0.07). CONCLUSIONS: Malnutrition was prevalent among critically ill children in Spain. Being overweight was associated with a shorter PICU LOS. EEN was safe and was associated with a higher caloric intake; however, it is rarely used in PICUs in Spain.

Magnetoelectric systems could be used to develop magnetoelectric random access memory and microsensor devices. One promising system is the two-phase 3-1-type multiferroic nanocomposite in which a one-dimensional magnetic column is embedded in a three-dimensional ferroelectric matrix. However, it suffers from a number of limitations including unwanted leakage currents and the need for biasing with a magnetic field. Here we show that the addition of an antiferromagnet to a 3-1-type multiferroic nanocomposite can lead to a large, self-biased magnetoelectric effect at room temperature. Our three-phase system is composed of a ferroelectric Na0.5Bi0.5TiO3 matrix in which ferrimagnetic NiFe2O4 nanocolumns coated with antiferromagnetic p-type NiO are embedded. This system, which is self-assembled, exhibits a magnetoelectric coefficient of up to 1.38 × 10–9sm–1, which is large enough to switch the magnetic anisotropy from the easy axis (Keff=0.91×104Jm–3) to the easy plane (Keff=–1.65×104Jm–3).