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Understanding the impact of different Candida species on patient outcomes is crucial for effective management and treatment strategies. This study aims to comprehensively analyze the association between Candida species and mortality in documented candidemia. We queried TriNetX, a global research network database, to identify patients diagnosed with candidemia through polymerase chain reaction from 2020 to 2023. The primary outcome was mortality in candidemia patients, categorized by Candida species at 90 days and 1 year. The time to death was assessed using Kaplan-Meier plots. Cox proportional hazard (PH) models were also used for comparative analysis, unadjusted and adjusted for demographic and comorbidity covariates. We captured 1234 candidemia episodes during the study period. The 90-day and 1-year mortality rates for the various Candida species were as follows: C. tropicalis (33.9% and 35.6%), C. glabrata (28.3% and 34%), multispecies (27.7% and 36.4%), C. parapsilosis (25.8% and 31.8%), C. krusei (21.4% and 28.6%), C. albicans (21.1% and 23.9%), and C. auris (13.3% and 15.9%). The unadjusted Kaplan-Meier Survival analysis showed that multispecies candidemia, followed by C. tropicalis, had the lowest survival. The adjusted multivariable Cox PH model found that C.albicans, C. glabrata, C. parapsilosis, C. tropicalis, and multispecies candidemia had significantly higher mortality rates than C. auris. Age and a higher Charlson comorbidity index value emerged as independent predictors of increased mortality. Among patients with candidemia, we found an overall 1-year mortality of 28%. Multispecies candidemia, C. tropicalis, older age, and a higher comorbidity burden were associated with the highest mortality rates., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The rate of invasive pneumococcal disease has markedly declined after the introduction of pneumococcal conjugated vaccines. In spite of the high effectiveness of this vaccine, there are some reports of vaccine failure and vaccine breakthroughs. Data on children with pneumococcal pneumonia in a European tertiary Hospital, from 2012 to 2014, were retrospectively collected before the implementation of pneumococcal conjugated vaccines in our country. We found four cases of pneumococcal serotype 3 vaccine failure and three cases of vaccine breakthroughs (two with serotype 3 and one with serotype 19A). All of these children were previously healthy., (© The Author 2016. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Context: The molecular etiology of cold and benign thyroid nodules (CBTNs) is largely unknown. Increased thyroid epithelial cell proliferation is a hallmark of CBTNs. MicroRNAs (miRNAs) are prominent regulators of cell proliferation., Objective: Our objective was to assess the influence of miRNAs on the increased proliferation and thus the molecular etiology of CBTNs., Design: By using microarrays, we defined the molecular pattern of increased proliferation of CBTNs as a differential expression of cell-cycle-associated genes and miRNAs. In silico integration of differentially expressed miRNAs and mRNAs showed an inverse correlation between the expression of 59 miRNAs and 133 mRNAs. Inverse correlations between cell-cycle-associated genes such as CDKN1C and miR-221, CCND1 and miR-31, GADD45A and miR-130b, or CDKN1A and let-7f suggest a modulation of proliferation in CBTNs by miRNAs. Their expression was validated using quantitative RT-PCR and functionally characterized in cell line models., Results: Comparative quantitative RT-PCR of 20 samples of CBTNs and their surrounding tissue revealed an 11-fold down-regulation of miR-31 with a 2.6-fold up-regulation of CCND1, and a 2.6-fold up-regulation of miR-130b with a 2.3-fold down-regulation of its target GADD45A. Using HTori and FTC-133 cell lines, we analyzed proliferation, cell cycle, and apoptosis after transfection of miRNA-31 and miRNA-130b mimic and inhibitors. Overexpression of miR-31 and the resultant down-regulation of CCND1 led to an arrest in the cell cycle phase G1. Overexpression of miR-130b led to an increase of apoptosis and necrosis within 72 h., Conclusion: miR-31 and miR-130b may have an effect on tumorigenesis of CBTNs by regulating proliferation and apoptosis and the cell cycle through cyclin D1.

Context: Fine-needle aspiration biopsy (FNAB) is the most sensitive and specific tool for the differential diagnosis of thyroid malignancy. Some limitations of FNAB can be overcome by the molecular analysis of FNAB. This review analyzes the current state and problems of the molecular analysis of FNAB as well as possible goals for increasing the diagnostic rate, especially in the indeterminate/follicular lesion cytological group., Evidence Acquisition: Twenty publications were evaluated for the diagnostic material and assay systems used, the type, and the number of mutations screened. Sensitivity, specificity, and false-negative and false-positive rates were calculated for all publications., Evidence Synthesis: Testing for a panel of somatic mutations is most promising to reduce the number of indeterminate FNAB. A mean sensitivity of 63.7% was achieved for indeterminate lesions. However, there is a broad sensitivity range for the investigation of mutations in the indeterminate lesions. Therefore, additional molecular markers should be defined by mRNA and microRNA expression studies and evaluated in FNAB samples of thyroid carcinomas without known somatic mutations, and especially for the many benign nodules in the indeterminate/follicular lesion fine-needle aspiration cytology category. This approach should improve the differential diagnosis of indeterminate/follicular lesion FNAB samples., Conclusion: Testing for a panel of somatic mutations has led to an improvement of sensitivity/specificity for indeterminate/follicular proliferation FNAB samples. Further methodological improvements, standardizations, and further molecular markers should soon lead to a broader application of molecular FNAB cytology for the differential diagnosis of thyroid nodules and to a substantial reduction of diagnostic surgeries.

The complete nucleotide sequence of the mt (mitochondrial) and cp (chloroplast) genomes of the unicellular green alga Ostreococcus tauri has been determined. The mt genome assembles as a circle of 44,237 bp and contains 65 genes. With an overall average length of only 42 bp for the intergenic regions, this is the most gene-dense mt genome of all Chlorophyta. Furthermore, it is characterized by a unique segmental duplication, encompassing 22 genes and covering 44% of the genome. Such a duplication has not been observed before in green algae, although it is also present in the mt genomes of higher plants. The quadripartite cp genome forms a circle of 71,666 bp, containing 86 genes divided over a larger and a smaller single-copy region, separated by 2 inverted repeat sequences. Based on genome size and number of genes, the Ostreococcus cp genome is the smallest known among the green algae. Phylogenetic analyses based on a concatenated alignment of cp, mt, and nuclear genes confirm the position of O. tauri within the Prasinophyceae, an early branch of the Chlorophyta.

The cell cycle has been extensively studied in various organisms, and the recent access to an overwhelming amount of genomic data has given birth to a new integrated approach called comparative genomics. Comparing the cell cycle across species shows that its regulation is evolutionarily conserved; the best-known example is the pivotal role of cyclin-dependent kinases in all the eukaryotic lineages hitherto investigated. Interestingly, the molecular network associated with the activity of the CDK-cyclin complexes is also evolutionarily conserved, thus, defining a core cell cycle set of genes together with lineage-specific adaptations. In this paper, we describe the core cell cycle genes of Ostreococcus tauri, the smallest free-living eukaryotic cell having a minimal cellular organization with a nucleus, a single chloroplast, and only one mitochondrion. This unicellular marine green alga, which has diverged at the base of the green lineage, shows the minimal yet complete set of core cell cycle genes described to date. It has only one homolog of CDKA, CDKB, CDKD, cyclin A, cyclin B, cyclin D, cyclin H, Cks, Rb, E2F, DP, DEL, Cdc25, and Wee1. We have also added the APC and SCF E3 ligases to the core cell cycle gene set. We discuss the potential of genome-wide analysis in the identification of divergent orthologs of cell cycle genes in different lineages by mining the genomes of evolutionarily important and strategic organisms.

We conducted a phylogenetic survey of the endogenous retrovirus Gypsy in the eight species of the Drosophila melanogaster subgroup. A 362-bp fragment from the integrase gene (int) was amplified, cloned, and sequenced. Phylogenetic relationships of the elements isolated from independent clones were compared with the host phylogeny. Our results indicate that two main lineages of Gypsy exist in the melanogaster subgroup and that vertical and horizontal transmission have played a crucial role in the evolution of this insect endogenous retrovirus.

We have used human beta-tropomyosin produced in Escherichia coli and deletion mutants obtained by site-directed mutagenesis to analyse the conformational stability of this molecule under various experimental conditions. Protein engineering has allowed us to answer some questions raised by stability analysis of the wild-type tropomyosin. The complex pattern of denaturation is due neither to heterogeneity of the preparation nor to head-to-tail interactions. The N- and C-termini are not of importance for the thermal stability of the molecule. On the contrary, deletion of the 31 C-terminus amino acids leads to a dramatic decrease of the stability observed in guanidinium chloride. This lowering is interpreted as the participation of one more guanidinium chloride ions to the denaturation equilibrium. Analysis of the stability in presence of organic solvents reveals that acetonitrile and methanol induce opposite effects. Investigation of these effects by three methods (CD, fluorescence and electrophoresis that measure respectively the content in alpha-helix, the contact between the two strands and the strands exchange) leads to the conclusion that strand separation can precede the denaturation of the alpha-helix.

Evolution analysis is used to locate the regions of a protein that are important for its function or structure. The rate of evolution is generally constant for a given family of homologous sequences. From the starting point of this observation, an algorithm is proposed to establish quantitatively the sequence zones where selective pressure is maximal. A program that computes this pressure has been written in PASCAL. Analysis of results on some sequences validate this theoretical approach, and this knowledge can be used as a starting-point for carrying out site-directed mutagenesis.