Uranium exposure can lead to neurobehavioral alterations in particular of the monoaminergic system, even at non-cytotoxic concentrations. However, the mechanisms of uranium neurotoxicity after non-cytotoxic exposure are still poorly understood. In particular, imaging uranium in neurons at low intracellular concentration is still very challenging. We investigated uranium intracellular localization by means of synchrotron X-ray fluorescence imaging with high spatial resolution ( less then 300 nm) and high analytical sensitivity ( less then 1 μg.g-1 per 300 nm pixel). Neuron-like SH-SY5Y human cells differentiated into a dopaminergic phenotype were continuously exposed, for seven days, to a non-cytotoxic concentration (10 μM) of soluble natural uranyl. Cytoplasmic submicron uranium aggregates were observed accounting on average for 62 % of the intracellular uranium content. In some aggregates, uranium and iron were co-localized suggesting common metabolic pathways between uranium and iron storage. Uranium aggregates contained no calcium or phosphorous indicating that detoxification mechanisms in neuron-like cells are different from those described in bone or kidney cells. Uranium intracellular distribution was compared to fluorescently labeled organelles (lysosomes, early and late endosomes) and to fetuin-A, a high affinity uranium-binding protein. A strict correlation could not be evidenced between uranium and the labeled organelles, or with vesicles containing fetuin-A. Our results indicate a new mechanism of uranium cytoplasmic aggregation after non-cytotoxic uranyl exposure that could be involved in neuronal defense through uranium sequestration into less reactive species. The remaining soluble fraction of uranium would be responsible for protein binding and for the resulting neurotoxic effects.Fanconi anemia (FA) is a chromosome instability syndrome with congenital abnormalities, cancer predisposition and bone marrow failure (BMF). Although hematopoietic stem and progenitor cell (HSPC) transplantation is the recommended therapy, new therapies are needed for FA patients without suitable donors. BMF in FA is caused, at least in part, by a hyperactive growth-suppressive transforming growth factor β (TGFβ) pathway, regulated by the TGFβ1, TGFβ2, and TGFβ3 ligands. Accordingly, the TGFβ pathway is an attractive therapeutic target for FA. While inhibition of TGFβ1 and TGFβ3 promotes blood cell expansion, inhibition of TGFβ2 is known to suppress hematopoiesis. Here, we report the effects of AVID200, a potent TGFβ1- and TGFβ3-specific inhibitor, on FA hematopoiesis. AVID200 promoted the survival of murine FA HSPCs in vitro. AVID200 also promoted in vitro the survival of human HSPCs from patients with FA, with the strongest effect in patients progressing to severe aplastic anemia or myelodysplastic syndrome (MDS). Previous studies have indicated that the toxic upregulation of the nonhomologous end-joining (NHEJ) pathway accounts, at least in part, for the poor growth of FA HSPCs. AVID200 downregulated the expression of NHEJ-related genes and reduced DNA damage in primary FA HSPC in vitro and in in vivo models. Collectively, AVID200 exhibits activity in FA mouse and human preclinical models. AVID200 may therefore provide a therapeutic approach to improving BMF in FA.
  We compared the relapse rate at 1 year in patients with vertebral osteomyelitis with or without associated endocarditis.
 
  We conducted a retrospective cohort study.  https://www.selleckchem.com/products/tasquinimod.html  Inclusion criteria were patients hospitalized in the infectious disease, rheumatology, cardiology, cardiovascular surgery and two internal medicine units for vertebral osteomyelitis (blood culture and/or disco-vertebral biopsy) and compatible imaging, between 2014 and 2017. We compared patients with associated endocarditis (VO-EI group) and without endocarditis (VO group) using logistic regression to determine the factors associated with relapse and EI. The main outcome was the relapse rate at 1 year.
 
  Out of the 207 eligible patients, 62 were included (35 in the VO group and 27 in the VO-EI group). Four patients presented with a new VO during follow-up, one (2.86%) patient in VO group and three (11.11%) in VO-EI group (P=0.68). There were more men in the VO-EI group than in the VO group (74.07% vs. 48.57%, P=0.04), valvulopathies (13/27 vs. 8/35, P=0.06), vertebral localization (1.22±0.50 vs. 1.03±0.17, P=0.04) and septic kidney embolism (5/27 vs. 0/35, P=0.01). Control blood cultures were more often positive in the VO-EI group (12/27 vs. 8/35, P=0.04). In 45% of patients, the germ was a staphylococcus, 29% streptococci, 10% enterococci, 10% gram-negative bacillus (GNB). There were more streptococci and enterococci in the VO-EI group than in the VO group (44.44% vs. 17.14% and 18.52% vs. 8.57%, respectively). Antibiotic safety was good and comparable between groups.
 
  In a relatively small population, we did not find significantly more relapse in the endocarditis group.
 In a relatively small population, we did not find significantly more relapse in the endocarditis group.The article is devoted to using the mathematics of multi-dimensional hyperbolic numbers and their matrix representations for modeling of different inherited biosystems, which are parts of the holistic body. The list of considered models includes phyllotaxis sequences; Punnet squares of the Mendelian genetics; the main psychophysical Weber-Fechner law, and some others. This modeling approach reveals hidden structural interconnections among different biosystems and leads a deeper understanding of their commonality related to the commonality of their genetic basis. At the same time, it shows the structural connection of inherited biosystems with formalisms of the theory of resonances of oscillatory systems with many degrees of freedom. This complements works of many authors - from antiquity to the present day - on the importance of coordinated oscillations and resonances in the life of living organisms. The modeling approach based on hyperbolic numbers and their bisymmetric matrices reveals that the structural commonality of different inherited biosystems is related to the harmonic progression 1/n and the harmonic mean, which are long known in arts and culture. They are used in the Pythagorean teaching on the musical harmony and the aesthetics of proportions. Besides, the using - for biosystems modeling - of multi-dimensional hypercomplex numbers, which are one of the main tools in modern mathematical natural sciences, opens a bridge between these sciences and biology for their mutual enrichment.