Near-infrared spectroscopy and multivariate analysis as effective, fast, and cost-effective methods to discriminate Candida auris from Candida haemulonii.

Candida auris and Candida haemulonii are two emerging opportunistic pathogens that have caused an increase in clinical cases in the recent years worldwide. The differentiation of some Candida species is highly laborious, difficult, costly, and time-consuming depending on the similarity between the species. Thus, this study aimed to develop a new, faster, and less expensive methodology for differentiating between C. auris and C. haemulonii based on near-infrared (NIR) spectroscopy and multivariate analysis. C. auris CBS10913 and C. haemulonii CH02 were separated in 15 plates per species, and three isolated colonies of each plate were selected for Fourier transform near-infrared (FT-NIR) analysis, totaling 90 spectra. Subsequently, principal component analysis (PCA) and variable selection algorithms, including the successive projections algorithm (SPA) and genetic algorithm (GA) coupled with linear discriminant analysis (LDA), were employed to discern distinctive patterns among the samples. The use of PCA, SPA, and GA algorithms associated with LDA achieved 100% sensitivity and specificity for the discriminations. The SPA-LDA and GA-LDA algorithms were essential in selecting the variables (infrared wavelengths) of most importance for the models, which could be attributed to binding of cell wall structures such as polysaccharides, peptides, proteins, or molecules resulting from yeasts' metabolism. These results show the high potential of combined FT-NIR and multivariate analysis techniques for the classification of Candida-like fungi, which can contribute to faster and more effective diagnosis and treatment of patients affected by these microorganisms.

Subgroup-specific structural variation across 1,000 medulloblastoma genomes.

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-ß signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy.

Binding of nitrite and its reductive activation to nitric oxide at biomimetic copper centers.

The reactivity of nitrite towards the copper(II) and copper(I) centers of a series of complexes with tridentate nitrogen donor ligands has been investigated. The ligands are bis[(1-methylbenzimidazol-2-yl)methyl]amine (1-bb), bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-bb), and bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (ddah) and carry two terminal benzimidazole (1-bb, 2-bb) or pyrazole (ddah) rings and a central amine donor residue. While 2-bb and ddah form two adjacent six-membered chelate rings on metal coordination, 1-bb forms two smaller rings of five members. The binding affinity of nitrite and azide to the Cu(II) complexes (ClO4- as counterion) has been determined in solution. The association constants for the two ligands are similar, but nitrite is a slightly stronger ligand than azide when it binds as a bidentate donor. The X-ray crystal structure of the nitrite complex [Cu(ddah)(NO2)]ClO4 (final R=0.056) has been determined: triclinic P1space group, a=8.200(2) A, b=9.582(3) A, c=15.541(4) A. It may be described as a perchlorate salt of a "supramolecular" species resulting from the assembly of two complex cations and one sodium perchlorate unit. The copper stereochemistry in the complex is intermediate between SPY and TBP, and nitrite binds to Cu(II) asymmetrically, with Cu-O distances of 2.037(2) and 2.390(3) A and a nearly planar CuO2N cycle. On standing, solutions of [Cu(ddah)(NO2)]ClO4 in methanol produce the dinuclear complex [Cu(ddah)(OMe)]2(ClO4)2, containing dibridging methoxy groups. In fact the crystal structure analysis (final R=0.083) showed that the crystals are built up by dinuclear cations, arranged on a crystallographic symmetry center, and perchlorate anions. Electrochemical analysis shows that binding of nitrite to the Cu(II) complexes of 2-bb and ddah shifts the reduction potential of the Cu(II)/Cu(I) couple towards negative values by about 0.3 V. The thermodynamic parameters of the Cu(II)/Cu(I) electron transfer have also been analyzed. The mechanism of reductive activation of nitrite to nitric oxide by the Cu(I) complexes of 1-bb, 2-bb, and ddah has been studied. The reaction requires two protons per molecule of nitrite and Cu(I). Kinetic experiments show that the reaction is first order in [Cu(I)] and [H+] and exhibits saturation behavior with respect to nitrite concentration. The kinetic data show that [Cu(2-bb)]+ is more efficient than [Cu(1-bb)]+ and [Cu(ddah)]+ in reducing nitrite.