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When stressed, cells synthesize di-adenosine polyphosphates (Ap n A), and cellular organisms also express proteins that degrade these compounds to release ATP. Most of these proteins are members of the nudix hydrolase superfamily, and several are involved in bacterial pathogenesis, neurodevelopment, and cancer. The goal of this project is to assist in the discovery of inhibitors of these enzymes that could be used to study Ap n A function and the cellular role of these nudix enzymes. Because these enzymes cleave Ap 4 A and Ap 5 A to produce ATP, two standard ATP detection techniques were optimized and compared here for their suitability for high throughput screening. In the first assay, cleavage is monitored by coupling to a reaction catalyzed by firefly luciferase. In the second assay, cleavage is detected by coupling to hexokinase, glucose 6-phosphate dehydrogenase, and diaphorase. Although the former assay was more sensitive, the latter was more reproducible, linear, and suitable for screening and kinetic analyses. The assays were used to characterize the kinetics of reactions catalyzed by various nudix enzymes isolated from E. coli, humans, and Mycobacterium tuberculosis, the bacterium that causes tuberculosis. Results reveal subtle differences between the proteins that might be exploited to identify specific small molecule inhibitors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

For many years, the potential pathogenic of non-diphtheriae corynebacteria were underestimated. Nowadays, a growing number of Corynebacterium species are recognized as opportunistic agents of human infections, mainly in hospital settings. In addition, multidrug-resistant Corynebacterium isolates from clinical specimens, have been reported and the role of Corynebacterium spp. in urinary tract infections (UTIs) has been highlighted. Several studies have reported Corynebacterium species as the agent of UTIs especially in patients with risk factors. Thus, the present work aimed to report the first isolation of Corynebacterium mycetoides from human urine and an initial study on its virulence properties. The isolate, initially characterized by phenotypical tests as a multidrug-resistant Corynebacterium sp., was recovered from the urine of a female transplant patient. Mass spectrometry and 16S rRNA and rpoB genes sequencing identified the isolate as C. mycetoides. The isolate was found able to adhere to and survive into epithelial cells (Vero cells), and its pathogenic potential was confirmed when tested against Caenorhabditis elegans nematode. The results obtained suggest that C. mycetoides is a potential pathogen for the urinary tract in humans and for a better understanding of the multifactorial mechanisms of virulence, studies about this species should be continued., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Diseases involving cilia dysfunction, such as Usher Syndrome (USH), often involve visual and auditory loss. Psychophysical evidence has suggested that this may also hold true for the peripheral olfactory domain. Here we aimed to go a step further by attempting to establish relations between the integrity of cortical structures and olfactory function in this condition. We investigated olfactory function for USH types 1 (USH1) and 2 (USH2). Bilateral olfactory bulb (OB) volume and olfactory sulcus (OS) depth were also analysed. Thirty-three controls with no previous olfactory deficits were age, sex and handedness-matched to 32 USH patients (11 USH1, 21 USH2). A butanol detection threshold test was performed to measure olfactory function. For OB volume and OS depth, morphometric measurements were performed using magnetic resonance imaging (MRI) based on detailed segmentation by three independent operators. Averaged values across these were used for the statistical analyses. Total intracranial volume was estimated using Freesurfer to account for head size variability. Olfactory threshold was significantly lower in controls when compared to USH, USH1, and USH2. OS depth was found to be shallower in both hemispheres in USH patients when compared with the control group. OB volume was not significantly different between control and USH groups, or respective subgroups. Nevertheless, butanol threshold was negatively correlated with the left OB volume for the USH type 1 subgroup. The main effect of OS depth reduction was found to be mainly due to the comparison between USH2 and controls. Our results provide evidence for morphometric changes and olfactory dysfunction in patients with USH. This correlated with a reduction in left OB volume in the USH1 subgroup, the most severe USH phenotype. The main effect of reduced OS depth was found to stem mainly from USH2 raising questions regarding a possible complex interaction between sensory olfactory loss and central cortical changes in this disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Coagulation and fibrinolysis tests were performed in 14 patients with hydatidiform mole before any significant therapy was given and again, after evacuation of the mole, in eight instances. The results were compared with those found in a group of ten volunteers with normal pregnancies. The most frequent abnormalities in the problem cases were a shortening of the partial thromboplastin time and a prolongation of the thrombin time. From a total of seven cases with complete hematologic profiles before and shortly after evacuation of the mole, first showed important drops in platelets and fibrinogen. The most altered profiles occurred after expulsion of the mole in cases with important previous uterine activity. The findings suggested a latent state of hypercoagulability with higher turn over rate of fibrinogen and increased levels of fibrinogen-fibrin degradation products, that may exist even before the mechanism of expulsion begins. It was concluded that the alterations in coagulation and fibrinolysis seen in molar pregnancies most likely have a multifactorial pathogenesis, but the initiating causes must depend on several events taking place in the trophoblast itself and their consequences upon a very distorted intervillous blood circulation.